Amyloid isn’t Alzheimer’s – How NOT to Study a Disease

by Patrick Holford

Alzheimer’s disease has, for decades, been framed primarily as a problem of amyloid plaques building up in the brain.

It is a compelling idea. It is measurable, visible on brain scans, and has shaped billions in research funding and drug development. There’s just one problem.

It doesn’t adequately explain what we see in people.

Many individuals with significant amyloid in their brains remain cognitively normal. Others develop clear dementia with little or no amyloid present (1). Treatments that successfully reduce amyloid have, at best, produced only modest effects on slowing decline, with no meaningful reversal of symptoms (2).

Amyloid is associated with Alzheimer’s disease, but association is not the same as causation.

And that distinction changes everything.

This growing tension between theory and evidence is explored in depth by neurobiologist Karl Herrup in How Not to Study a Disease, where he challenges how the field has come to define and pursue Alzheimer’s.

Some people develop increasingly severe cognitive decline as they age. This affects roughly one in ten older adults. We call this dementia. In some cases, brain scans show clear shrinkage in key regions, particularly the medial temporal lobe, which is then used to diagnose Alzheimer’s disease. So we have two observable features: a decline in cognitive function and measurable loss of brain tissue.

The question that follows is simple, but critical.

What is actually causing this process?

What causes Alzheimer’s?

Amyloid has long been positioned as the answer. Yet the evidence tells a more complicated story.

A significant proportion of older adults have amyloid plaques in their brains and remain cognitively normal. At the same time, some individuals with clear dementia show little or no amyloid pathology. Amyloid is associated with Alzheimer’s, but that is not the same as being the cause.

If amyloid were the primary driver, then reducing it should meaningfully change the course of the disease. However, interventions designed to reduce amyloid have consistently lowered amyloid burden in the brain, yet produced, at best, modest effects on slowing decline, often measured as very small changes on cognitive scales. There has been no meaningful reversal of symptoms. In some cases, safety concerns have emerged, including brain bleeding and swelling.

Recent large-scale evidence (6) now reinforces this point. A 2026 Cochrane review concluded that although anti-amyloid monoclonal antibodies can remove amyloid from the brain, this does not appear to translate into clinically meaningful effects for people with mild cognitive impairment or mild dementia due to Alzheimer’s disease, while increasing the risk of amyloid-related imaging abnormalities.

From a scientific perspective, this adds to an already substantial body of evidence suggesting that amyloid accumulation, on its own, does not explain the disease process. It may be part of the picture, but it is not the engine driving it.

And yet, the field has remained heavily focused on this single pathway.

When a hypothesis becomes a lens

Research tends to follow what is measurable, fundable, and already established. Over time, this can narrow the lens rather than expand it.

Amyloid has become that lens. As Karl Herrup argues in his book, once a hypothesis becomes dominant, it can begin to shape not just what is studied, but how results are interpreted and what gets funded next.

The result is that vast resources have been invested in understanding and modifying amyloid biology, while other avenues have received comparatively less attention. We have learned a great deal about amyloid itself, but we are not significantly closer to preventing or reversing the condition that matters most to patients, which is cognitive decline.

This is not unusual in science. Once a model becomes dominant, it shapes the direction of funding, research questions, and even how people interpret results.

A similar pattern is now emerging with another biomarker, p-tau.

Tau is a normal protein that, under certain conditions, becomes altered and associated with the tangles seen in Alzheimer’s pathology. Higher levels of p-tau are linked with increased risk, but again, association does not establish causation. Many individuals have elevated levels without clinical symptoms.

As with amyloid, the risk is that a marker becomes mistaken for the mechanism.

What does influence the disease process?

This is where the picture becomes more interesting.

There are factors that sit upstream of both amyloid and tau, influencing the environment in which brain cells function or fail. One of the most studied is homocysteine, a marker of methylation and B vitamin status.

Unlike amyloid, intervention trials have shown that homocysteine influences outcomes. In the VITACOG study, lowering elevated homocysteine with targeted B vitamins significantly slowed the rate of brain atrophy in individuals with mild cognitive impairment, with corresponding effects on cognitive decline. This is much closer to what we would describe as a disease-modifying effect (3,4). It also raises questions explored in Apparently healthy but diagnosed with Alzheimer’s about whether current diagnostic models are identifying true disease drivers or simply biomarkers.

That does not mean homocysteine is the only cause. It is one piece of a larger system. But it illustrates an important point. When you influence the underlying biology of the brain, rather than a downstream marker, you begin to see meaningful change.

For more on this approach, see our article on early diagnosis of Alzheimer’s: amyloid protein vs homocysteine testing.

A systems problem, not a single cause

Alzheimer’s does not behave like a single-cause disease.

It is better understood as the result of multiple interacting processes. These include inflammation, oxidative stress, insulin resistance, mitochondrial dysfunction, and impaired methylation, among many others (5). Each of these affects how brain cells are built, maintained, and powered.

Individually, they may not be sufficient to cause disease. Together, they can create the conditions in which the brain becomes vulnerable.

This is closer to how we understand most chronic conditions. Not as a single fault, but as a convergence of pressures that eventually exceed the system’s ability to compensate. A more useful way to think about it is not as one switch flipping, but as several dials turning in the wrong direction at the same time.

Why this matters

If we continue to focus primarily on downstream markers such as amyloid or p-tau, we risk missing the broader picture.

If instead we look at the upstream drivers, the factors that influence brain structure, function, and energy supply, we open up a different set of possibilities. Not just for treatment, but for prevention.

These are not fringe ideas. They are part of a growing shift in how Alzheimer’s is being understood, questioned, and re-examined. Researchers like Karl Herrup are helping to bring that conversation into the open, challenging long-held assumptions and asking more useful questions about what truly drives the disease.

It’s a conversation that is only just beginning to reach wider audiences.

This is exactly what we’ll be exploring at Alzheimer’s Prevention: New Frontiers conference, where leading researchers and clinicians will come together to look beyond single-cause models and towards a more complete understanding of brain health and cognitive decline.

Is prevention the real solution?

The prevailing model in medicine has been to identify a single cause and target it with a treatment. That works well for some conditions. It is less suited to complex, multifactorial diseases like Alzheimer’s.

A systems-based approach asks a different question.
What combination of factors leads to decline, and how do we shift that combination in the opposite direction?

This is the approach we take at Food for the Brain. By combining cognitive testing with blood testing and lifestyle information, it becomes possible to see patterns, not just isolated variables. Over time, this allows us to understand what drives resilience as well as risk.

It is likely that we will not find a single primary cause of Alzheimer’s. What we may find is something more useful: a set of modifiable factors that, together, determine whether the brain maintains function or begins to decline.

In that sense, prevention may not just be part of the solution.

It’s the solution.

Find out more with Alzheimer’s: Prevention is the Cure book here

Learn more about our Alzheimer’s Prevention: New Frontiers Conference here.

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Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

Related reading

Apparently Healthy, but Diagnosed with Alzheimerʼs? 
Why “Normal” Vitamin D Levels May Not Be Protective for Women’s Brains
Early Diagnosis of Alzheimer’s – Amyloid Protein vs Homocysteine Testing
‘My Relative Has Memory Problems, Possibly Dementia. What Do You Recommend?’
Homocysteine & Alzheimer’s Disease (2002)

New Study: Is Red Meat Bad for Your Brain?

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In a culture where the average plate still leans heavily towards meat – often processed, often excessive – it’s time to reassess the impact of our protein choices not just on our waistlines, but on our brains. A recent study in Neurology (2025) has added fresh weight to decades of evidence linking red and processed meat consumption to an increased risk of dementia and cognitive decline (1). Meanwhile, fish – particularly oily fish – continues to top the charts as the most protective food for your brain (2,3).

So, what does this mean practically for those of us trying to upgrade our brains and reduce our risk of cognitive decline? The answer may be as simple as this: eat more fish and fewer sausages.

Red Meat, Processed Meat and the Rising Risk to Brain Health

A new US cohort study, which followed over 77,000 adults across 30 years, found that:

Processed red meats (bacon, hot dogs, sausages, salami, bologna and other processed meat products) were clearly problematic. Consuming just 0.25 servings per day or more was associated with a 13% higher risk of developing dementia compared with those eating less than 0.1 serving (1).

Unprocessed red meat (e.g. beef or lamb) was linked to a 16% increased risk of subjective cognitive decline – that is people reporting that their memory or mental sharpness was worsening – when consuming more than one serving daily compared to less than half a serving per day. However, the researchers noted that this link did not reach statistical significance for diagnosed dementia overall (1).

More encouragingly, replacing one daily serving of processed red meat with a serving of nuts, lentils, or beans was associated with a 19% lower risk of dementia (1).

These findings are consistent with a large UK Biobank analysis of almost half a million adults, which found that each additional 25 g/day of processed meat (bacon, ham, sausages, meat pies, kebabs, burgers, chicken nuggets) was associated with a 44% higher risk of all-cause dementia and a 52% higher risk of Alzheimer’s disease. In contrast, each 50 g/day of unprocessed red meat was linked to a 19% lower risk of all-cause dementia and a 30% lower risk of Alzheimer’s disease (4).  This reinforces the idea that it is the processing – not necessarily the meat itself – that may be most harmful.

These associations were observed regardless of whether participants carried the APOE ε4 gene variant – further evidence that dietary choices have a significant impact and that Alzheimer’s is ‘not in the genes’. (4).

The Global Pattern

The irrelevance of genetics in these findings is further supported by global evidence. An ecological analysis across 204 countries found that higher national per-capita total meat supply – including both red and white meats – was significantly associated with higher dementia incidence, even after adjusting for ageing, economic development and genetic risk, including APOE ε4 prevalence where available (5). In other words, the meat-dementia link is not confined to particular genetic subgroups but is observable across populations worldwide, suggesting that the way we produce and consume meat may be influencing brain health trends on a global scale. 

What we put on our plate is powerful when it comes to reducing dementia risk – more so than any genetic variations that attract attention in the media.

Why Fish is Brain Food

The answer is not to go hungry, but to swap for something else – and when it comes to brain health, marine foods are your answer.

Unlike red meat, fish – especially oily varieties like salmon, sardines or mackerel – continue to show a strong protective effect.

A comprehensive 2024 meta-analysis found that:

Eating one to two servings of fish per day (roughly 150 g) is associated with a 20% reduced risk of Alzheimer’s disease and up to 30% slower cognitive decline (2).

Another study found that people who ate fish at least once a week had a one-third lower risk of Alzheimer’s compared with those eating fish less than weekly (3).

Why? Omega-3 fats, especially DHA, are critical for brain function and structure. They reduce inflammation, support synaptic plasticity and help clear beta-amyloid – a protein associated with Alzheimer’s disease.

As explained in the COGNITION™ 6-month programme, omega-3 fats from fish oil play a pivotal role in building and repairing the brain, particularly in mid-life, when early signs of cognitive decline can start to emerge.

That’s why we offer omega-3 at-home blood tests – so you can check whether you’re getting enough through your diet or if it’s time to add a supplement. You can test omega-3 on its own here, or as part of our 5-in-1 DRIfT test where you can also check your homocysteine and glutathione status at the same time.

A Simple Swap with Profound Impact

From a cognitive health perspective, the data is now hard to ignore: if you’re regularly eating red or processed meat – especially more than once a day – your brain may be paying the price. But shifting even one of those servings towards fish, eggs or plant-based proteins could make a meaningful difference.

Interestingly, the main culprit in the latest studies was processed meat. This supports a key principle in brain-friendly eating: most natural whole foods – whether meat, fish, fruit, nuts, legumes, wholegrains or dairy – are not the problem. It’s when we distort them into ultra-processed, factory-made food that health is undermined.

This isn’t about becoming vegan or pescatarian. It’s simply more evidence to reduce processed foods and ensure optimal omega-3 intake. 

So next time you’re at the supermarket make a cow happy and buy a fish.

Resources:

Need help knowing what to eat? Get inspired with over 125 brain-friendly recipes in the Upgrade Your Brain Cook App.

Order your omega-3 test today to find out if you are eating enough of these essential fatty acids. You can test omega-3 on its own here, or as part of our 5-in-1 DRIfT test. Available globally.

Food for the Brain is a not-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References:

You J, Zhang L, Zhou Y, et al. Total meat supply and incidence of dementia: an ecological study of 204 countries. Front Public Health. 2025;13:1589936. doi:10.3389/fpubh.2025.1589936.

Li Y, Li Y, Gu X, Liu Y, Dong D, Kang JH, Wang M, Eliassen H, Willett WC, Stampfer MJ, Wang D. Long-Term Intake of Red Meat in Relation to Dementia Risk and Cognitive Function in US Adults. Neurology. 2025;104(3):e210286. doi:10.1212/WNL.0000000000210286.

Godos J, Micek A, Currenti W, Franchi C, Poli A, Battino M, Dolci A, Ricci C, Ungvari Z, Grosso G. Fish consumption, cognitive impairment and dementia: an updated dose-response meta-analysis of observational studies. Aging Clin Exp Res. 2024;36(1):171-182. doi:10.1007/s40520-024-02823-6.

Beydoun MA, Beydoun HA, Gamaldo AA, Teel A, Zonderman AB, Wang Y. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 2014;14:643. doi:10.1186/1471-2458-14-643.

Zhang Z, He P, Liu M, et al. Meat consumption and risk of incident dementia: cohort study of UK Biobank participants. Am J Clin Nutr. 2021;113(5):1228-1236. doi:10.1093/ajcn/nqaa343.

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Imagine if a simple, well-researched nutrient protocol could prevent cognitive decline in millions of people worldwide. Imagine further that this protocol has been known for years, supported by multiple clinical trials and global experts, yet systematically ignored by the very institutions meant to protect public health. That is precisely the case when it comes to homocysteine, B vitamins, and dementia.

Last year, the UK-based Lancet Commission on Dementia Prevention, Intervention and Care released its third major report, once again omitting any mention of homocysteine as a modifiable risk factor. This was despite direct submissions of evidence and letters from leading scientists demonstrating that lowering homocysteine with B vitamins can slow brain shrinkage and cognitive decline.

Now, in response to this silence, six of the leading dementia researchers, Professors Joshua Miller (Rutgers), David Smith (Oxford), Helga Refsum (Oslo), Jin-Tai Yu (Fudan), Babak Hooshmand (Karolinska), and Andrew McCaddon (Wrexham), have published a powerful rebuttal in the Journal of Alzheimer’s Disease. Many of these experts serve in the Alzheimer’s Prevention Expert Group (APEG) at Food for the Brain.

They wrote:

“In 2018, we published an ‘International Consensus Statement on Homocysteine and Dementia’ in this journal, in which we concluded that elevated plasma total homocysteine is a modifiable risk factor for the development of cognitive decline, dementia, and Alzheimer’s disease (AD) in older persons. (1)

We further stated that intervention trials in elderly people with cognitive impairment show that homocysteine-lowering treatment with B vitamins markedly slows the rate of both wholeand regional brain atrophy, and also slows cognitive decline. We were therefore puzzled as to why the Lancet Commission on Dementia Prevention, Intervention and Care, failed to discuss the possible role of homocysteine and B vitamins in any of their three reports, including the most recent one.” (2)

A Systematic Omission

The UK-based Lancet Commission on Dementia Prevention is meant to objectively consider the evidence on dementia prevention. Yet each edition, despite being sent the relevant papers, has ignored the evidence concerning homocysteine.

Furthermore, it’s expected to uphold the standards for critical debate which allows for experts to question Published findings. That is exactly what these experts did – yet it declined to publish their letter, instead printing a rebuttal from its own Commission while refusing to let readers see the original letter. (3, 4)

The experts wrote to The Lancet again to respond to the Commission’s letter, but their second letter was also rejected. 

Thatetter has now been published in the leading Alzheimer’s journal where the authors finally have their rightful say. It includes the following:

“We wish to reply to the Commission and continue the debate with the aim of reaching a common view on homocysteine, B vitamins and dementia. This is an important matter of public health.”

In other words, The Lancet published the ‘case for the defence’ for the exclusion of homocysteine without allowing readers to even read the ‘case for the prosecution’. (5)

So, what was The Lancet’s case against B vitamins? It rested on three criticisms – each of which these leading dementia researchers refute with scientific precision in their recent journal paper.

Criticism 1: Misunderstanding Who Benefited in the VITACOG Trial

The Lancet Commission questioned the relevance of the VITACOG trial, arguing that the results “do not show benefits in populations already consuming B vitamins in their food or through supplements.” But this fundamentally misrepresents the study population.

In the VITACOG trial, participants with mild cognitive impairment were given high doses of B6, B12, and folic acid for two years. The result was a 31% reduction in whole brain shrinkage and significantly slower rate of cognitive decline in those with raised homocysteine (6). In participants with levels above 11.3 μmol/L – the median – both cognitive and clinical improvements were observed. Importantly, key Alzheimer’s-related brain regions shrank seven times more slowly in these individuals (7, 8).

The Lancet Commission implied that participants were already supplementing, but that is incorrect. The study excluded anyone taking more than 300 mcg of folic acid, 3 mg of vitamin B6, or 1.5 mcg of vitamin B12 – doses lower  than those found in many common multivitamins. Only 16 to 20 percent were taking low-dose supplements, while the majority were not.. No one was excluded based on their dietary intake of B vitamins.

The experts respond:“The Commission authors’ comment is analogous to expecting additional drug treatment to provide benefits over and above the benefits being obtained in people already taking a high dose of the drug, which is why it puzzles us.”

Criticism 2: No Benefit in the Hong Kong Trial?

The Commission’s response also cited a Hong Kong trial that reported no benefit of B vitamins over two years in people with mild cognitive impairment (MCI) (9). However, this overlooks several important confounders.

Firstly, 22% of participants were taking aspirin, which the study authors themselves found to impair the effect of B vitamins. This interference has since been confirmed in further research (10).

Secondly, the authors of The Lancet response failed to consider another critical factor: omega-3 status. Numerous studies show that B vitamins only deliver cognitive benefits when omega-3 fatty acid levels are sufficient. The Hong Kong study did not measure or control for omega-3 status, which likely explains the lack of consistent benefit over the two-year period.

Thus, the absence of effect in this trial does not disprove the role of B vitamins.  The experts go on to demonstrate in their article the overwhelming body of evidence –  reported by us – that homocysteine-lowering B vitamins do not work optimally in individuals with low omega-3 status.

Criticism 3: No Benefit in the VITAL Trial in Alzheimer’s Patients?

The Lancet authors also referenced the VITAL trial, which reported no overall cognitive benefit from B vitamins in patients already diagnosed with Alzheimer’s disease (11). But again, this conclusion overlooks key details.

In a subgroup analysis, those in the early stages of Alzheimer’s disease did show significant benefit (12). The authors of the VITAL trial themselves highlighted this in their paper, suggesting that earlier intervention is more effective. This finding aligns with multiple other studies showing that B vitamin treatment is most effective in the pre-dementia stages (13).

Furthermore, participants in the VITAL trial began with an average homocysteine level of 9 μmol/L, which is below the threshold (>10–11 μmol/L) associated with brain atrophy.  It is extremely rare to find a group of people with Alzheimer’s disease that start with such a low homocysteine level.  While the B vitamins did reduce homocysteine further to 7μmol/L, there was no overall cognitive benefit observed. But this is akin to giving painkillers to people who are not in pain and then reporting no change in pain levels. At Food for the Brain, we consider a homocysteine level above 10μmol/L as in need of correction with B vitamins.

There are also concerns about conflicts of interest. The lead author, Paul Aisen, is described as “a consultant to the following pharmaceutical companies involved in the development of potential treatments for Alzheimer’s disease”. with more than a dozen firms listed. These companies would certainly favour a trial designed to fail – especially if it were widely publicised.

Additionally, when an anti-amyloid drug trial for lecanemab was published – now licensed in the US and UK – the names of Paul Aisen and Christopher Van Dyck appeared once again as lead authors. In other words, the paid pharmaceutical consultants, responsible for running the drug trial were also tasked with overseeing a trial – designed to fail – on a competing approach: lowering homocysteine with B vitamins. The conflict of interest here is both clear and concerning.

What Does the Evidence Really Say?

You can read the full expert response published in the Journal of Alzheimer’s Disease here. 

Their conclusion is clear:

“We hope that the Lancet Commission will consider the substantial existing evidence of raised homocysteine as an important risk factor for dementia and the possibility of modifying its harm by supplementation with B vitamins.”

They emphasise that the evidence for B vitamin intervention is as strong – or stronger than –  many of the risk factors the Commission did include in its 2024 report. To continue ignoring the proven impact of homocysteine, and the benefits of lowering it through B vitamins is not merely a scientific oversight –  it is a missed opportunity with major implications for medicine and public health.

Remember, prevention is better than cure, and there is so much you can do to protect your brain health

The perfect time to start? Today.

What Can You Do?

Test your homocysteine (and omega-3 status) TODAY –  especially if you’re over 50 or at risk of cognitive decline. At Food for the Brain, we offer an accurate at-home test kit that reliably measures plasma homocysteine reliably. 

You can order your single Homocysteine test here or save money and test both omega-3 index and homocysteine (plus other markers) as part of our DRIfT tests here. International shipping available.

Act on your results –  if your level is above 10 μmol/L, supplementation with vitamin B6 (20 mg), methylfolate (400 µg), and vitamin B12 (500 µg) is recommended.
Read more on supplements and homocysteine here.

Support our mission – become a FRIEND of Food for the Brain! Your donation helps us advance prevention-focused brain health research and education.

As a Friend, you’ll also gain access to:
• Monthly group coaching
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Share the knowledge – public awareness can change public health.
We need a paradigm shift, and it starts with us.

By Patrick Holford

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The reason we advocate natural, nutritional, and lifestyle-based approaches to mental health is simple – because they work, and they’re safe.

The next big challenge is to discover which combination of changes has the most impact. This is what our research is focused on.

From depression to dementia, the typical approach is still, all too often, medication While it’s valid to compare a nutrient or diet to a pharmaceutical – take omega-3s, for example, which have been shown to be as effective as antidepressants – the real concern is how rarely we hear about the risks of psychiatric drugs. For many, by the time those dangers become clear, it’s already too late.

A classic example of this is the well-known increased risk of suicide particularly in young people prescribed antidepressants. Not only did this take more than ten years to ‘come out’, even now, despite on-the-box warnings, many remain unaware of this well-established risk.

A similar situation is emerging with the new anti-amyloid antibody treatments being proposed for dementia sufferers. Reported deaths are often downplayed or not fully disclosed.. In trials of the two drugs Lecanemab and Donanemab, eight deaths were reported. Eight deaths were reported during the trials, which involved 1,785 participants – a rate of one in every 219 – though not all were officially attributed to the drug. That’s quite a risk. But it is also the nature of these deaths, caused by brain bleeding and swelling, that is even more concerning. 

Investigative journalist Charles Piller, in his book ‘Doctored’, interviewed the pathologist for the first Lecanemab death who said it was like “her brain exploded”. Another Lecanemab associated death was a 65 year-old woman, who had a blood clot induced stroke and was given a common, often lifesaving intervention (tPA) which went badly wrong. “As soon as they put it in her, it was like her body was on fire,” the woman’s husband told me, he said. “She was screaming, and it took, like, eight people to hold her down. It was horrific. Everybody’s running in and (asking) ‘What the hell is going on?’” His wife was sedated and recovered to intensive care, he said. Soon the woman suffered seizures and was placed on a ventilator. After a few days the family approved disconnecting the device and she died. In his book Piller also reports another case in which a participant ‘died after hideous brain swelling and bleeding, and violent seizures.’

The UK has licensed the use of Lecanemab. The EU has not. The UK has licensed Donanemab, but NICE hasn’t approved it for NHS use.

Safer, Evidence-Based Alternatives

Despite more effective and safer alternatives being available, Alzheimer’s charities continue to advocate for NHS access to these drugs. This raises an important question: why? The combination of homocysteine-lowering B vitamins and omega-3 already has stronger evidence of efficacy – with no adverse effects – and certainly no risk of death (Read Alzheimer’s: Prevention is the Cure for the evidence and the comparison).

We invited Dr Peter Gøtzsche – co-founder of the Cochrane Collaboration, originally established to evaluate health treatments without bias – to speak about the risks of psychiatric drugs and their link to mortality. When the Cochrane Collaboration became corrupted, which he later criticised for being influenced by commercial interests, he founded the Institute for Scientific Freedom.

 “Overtreatment with drugs kills many people, and the death rate is increasing. It is therefore strange that we have allowed this long-lasting drug pandemic to continue, and even more so because most of the drug deaths are easily preventable.” he says.

“In 2013, I estimated that our prescription drugs are the third leading cause of death after heart disease and cancer,(1) and in 2015, that psychiatric drugs alone are also the third leading cause of death”.(2)^”

Read on to understand how he arrived at the conclusion that psychiatric drugs may be the third leading cause of death.

How many people are killed by psychiatric drugs?

If we want to estimate the death toll of psychiatric drugs, the most reliable source of data comes from placebo-controlled randomised trials. However, we need to consider their limitations.

First, these trials typically last just a few weeks, despite the fact that most patients take psychiatric medications for many years.(3, 4) 

Second, polypharmacy – the use of multiple medications –  is common in psychiatry, and this significantly increases the risk of mortality.. As an example, the Danish Health Authority has warned that adding a benzodiazepine to a neuroleptic increases mortality by 50-65% (5).

Third, up to half of all deaths go unreported in published clinical trial data.(6)  For dementia, published data shows that for every 100 people treated with a newer neuroleptic for ten weeks, one patient dies as a result. (7) This represents a high mortality rate for a pharmaceutical intervention, but FDA data on the same trials show it is double this number, equivalent to two deaths per 100 people over ten weeks. (8) And if we extend the observation period, the death toll becomes even higher.  A Finnish study of 70,718 community-dwellers newly diagnosed with Alzheimer’s disease reported that neuroleptics kill 4-5 people per 100 annually, compared to patients who were not treated.(9)

Fourth, the design of psychiatric drug trials is biased. In almost all cases, patients were already in treatment with psychiatric medication before they entered the trial, (1, 2)^, and some of those randomised to placebo will therefore experience withdrawal effects that will increase their risk of dying, due to withdrawal symptoms such as akathisia. Placebo-controlled trials in schizophrenia cannot be reliably used to assess the effect of neuroleptics on mortality because of the drug withdrawal design. The suicide rate in these unethical trials was 2-5 times higher than the norm. (10,11) Among those enrolled in trials of risperidone, olanzapine, quetiapine, and sertindole, one in every 145 patients died. However, none of these deaths were mentioned in the published scientific literature, and the FDA did not require their inclusion in trial reporting.

Fifth, events occurring after the trial period are often ignored. In Pfizer’s trials of sertraline in adults, the risk ratio for suicides and suicide attempts was 0.52 when follow-up lasted only 24 hours, but increased to 1.47 when follow-up was extended to 30 days — indicating a rise in suicidal events. (12) Furthermore, when researchers reanalysed the FDA trial data on depression drugs and included harms occurring during follow-up, they found that antidepressants were associated with twice the number of suicides in adults compared to placebo (13, 14)

Estimating the True Death Toll of Mental-Health Medications

In 2013, I estimated that, in people aged 65 and above, neuroleptics, benzodiazepines or similar, and antidepressants kill 209,000 people annually in the United States.(2) I used relatively conservative estimates, however, and usage data from Denmark, which is far lower than those in USA. I have therefore updated the analysis based on US usage data, again focusing on older age groups.

For neuroleptics, I used the estimate of 2% mortality from the FDA data.(8)

For benzodiazepines and similar drugs, a matched cohort study showed that the drugs doubled the death rate, although the average age of the patients was only 55.(15)  The excess death rate was about 1% per year. In another large, matched cohort study, the appendix to the study report shows that hypnotics quadrupled the death rate (hazard ratio 4.5). The study authors estimated that sleeping pills kill between 320,000 and 507,000 Americans every year. (16)  A reasonable estimate of the annual death rate would therefore be 2%.

For SSRIs, a UK cohort study of 60,746 depressed patients older than 65 showed that they led to falls and a 3.6% annual mortality rate among those treated.(17) The study was well-designed, in that the patients were their own control in one of the analyses, which helps control for confounding variables. Nonetheless, the reported death rate is notably high.

Another cohort study, of 136,293 American postmenopausal women (age 50-79) participating in the Women’s Health Initiative study, found that depression drugs were associated with a 32% increase in all-cause mortality after adjustment for confounding factors, which corresponding to an estimated 0.5% annual mortality rate among women treated with SSRIs.(18). The authors noted that the mortality rate was likely underestimated. The authors warned that their results should be interpreted with great caution due to a high risk of exposure misclassification, which would make it more difficult to find an increase in mortality. Further, the patients were much younger than in the UK study, and the death rate increased markedly with age and was 1.4% for those aged 70-79. Finally, the exposed and unexposed women were different for many important risk factors for early death, whereas the people in the UK cohort were their own control.

For these reasons, I decided to use the average of the two estimates, a 2% annual death rate.

These are my results for USA for these three drug groups for people at least 65 years of age (58.2 million; usage is in outpatients only): (19, 20, 21, 22)

—

A limitation in these estimates is that you can only die once, and many people receive polypharmacy. It is not clear how we should adjust for this. In the UK cohort study of depressed patients, 9% also took neuroleptics, and 24% took hypnotics/anxiolytics. (17)

On the other hand, the data on death rates come from studies where many patients were also on several psychiatric drugs in the comparison group, so this is not likely to be a major limitation considering also that polypharmacy increases mortality beyond what the individual drugs cause.

Statistics from the Centers for Disease Control and Prevention list these four top causes of death: (23) 

Heart disease: 695,547
Cancer: 605,213
COVID-19: 416,893
Accidents: 224,935

COVID-19 deaths are rapidly declining, and many of such deaths are not caused by the virus but merely occurred in people who tested positive for it because the WHO advised that all deaths in people who tested positive should be called COVID deaths.

Young people have a much smaller death risk than the elderly, as they rarely fall and break their hip, which is why I have focused on the elderly. I have tried to be conservative. My estimate misses many drug deaths in those younger than 65 years; it only included three classes of psychiatric drugs; and it did not include hospital deaths.

I therefore do not doubt that psychiatric drugs are the third leading cause of death after heart disease and cancer.

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Learn more and begin your brain upgrade journey today:

Complete the free online brain assessment – the Cognitive Function Test – to get personalised feedback on your brain health
Order the Upgrade Your Brain book here
Order Alzheimer’s: Prevention is the Cure book here
Contribute to our research and order your accurate, at home, blood tests here.
If you are looking for personalised one to one support, visit the Brain Bio Centre here.

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Food for the Brain is a not-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References:
1 Gøtzsche PC. Deadly medicines and organised crime: How big pharma has corrupted health care. London: Radcliffe Publishing; 2013.

2 Gøtzsche PC. Deadly psychiatry and organised denial. Copenhagen: People’s Press; 2015.. US News 2016; Sept 27. 

2. Gøtzsche PC. Mental health survival kit and withdrawal from psychiatric drugs. Ann Arbor: L H Press; 2022.

 3 Gøtzsche PC. Long-term use of antipsychotics and antidepressants is not evidence-based. Int J Risk Saf Med 2020;31:37-42. 

4 Gøtzsche PC. Long-term use of benzodiazepines, stimulants and lithium is not evidence-based. Clin Neuropsychiatry 2020;17:281-3.

5 Forbruget af antipsykotika blandt 18-64 årige patienter, med skizofreni, mani eller bipolar affektiv sindslidelse. København: Sundhedsstyrelsen; 2006.

6 Hughes S, Cohen D, Jaggi R. Differences in reporting serious adverse events in industry sponsored clinical trial registries and journal articles on antidepressant and antipsychotic drugs: a cross-sectional study. BMJ Open 2014;4:e005535. 

7 Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005;294:1934–43.

8 FDA package insert for Risperdal (risperidone). Accessed 30 May 2022. 

9 Koponen M, Taipale H, Lavikainen P, et al. Risk of mortality associated with antipsychotic monotherapy and polypharmacy among community-dwelling persons with Alzheimer’s disease. J Alzheimers Dis 2017;56:107-18.

10 Whitaker R. Lure of riches fuels testing. Boston Globe 1998;Nov 17.

11 Whitaker R. Mad in America: bad science, bad medicine, and the enduring mistreatment of the mentally ill. Cambridge: Perseus Books Group; 2002:page 269.

12 Vanderburg DG, Batzar E, Fogel I, et al. A pooled analysis of suicidality in double-blind, placebo-controlled studies of sertraline in adults. J Clin Psychiatry 2009;70:674-83.

13 Hengartner MP, Plöderl M. Newer-generation antidepressants and suicide risk in randomized controlled trials: a re-analysis of the FDA database. Psychother Psychosom 2019;88:247-8.

14 Hengartner MP, Plöderl M. Reply to the Letter to the Editor: “Newer-Generation Antidepressants and Suicide Risk: Thoughts on Hengartner and Plöderl’s ReAnalysis.” Psychother Psychosom 2019;88:373-4.

15 Weich S, Pearce HL, Croft P, et al. Effect of anxiolytic and hypnotic drug prescriptions on mortality hazards: retrospective cohort study. BMJ 2014;348:g1996.

16 Kripke DF, Langer RD, Kline LE. Hypnotics’ association with mortality or cancer: a matched cohort study. BMJ Open 2012;2:e000850.

17 Coupland C, Dhiman P, Morriss R, et al. Antidepressant use and risk of adverse outcomes in older people: population based cohort study. BMJ 2011;343:d4551.

18 Smoller JW, Allison M, Cochrane BB, et al. Antidepressant use and risk of incident cardiovascular morbidity and mortality among postmenopausal women in the Women’s Health Initiative study. Arch Intern Med 2009;169:2128-39.

19 O’Neill A. Age distribution in the United States from 2012 to 2022. Statista 2024;Jan 25.

20 Olfson M, King M, Schoenbaum M. Antipsychotic treatment of adults in the United States. Psychiatrist.com 2015;Oct 21.

21 Maust DT, Lin LA, Blow FC. Benzodiazepine use and misuse among adults in the United States. Psychiatr Serv 2019;70:97-106.

22 Brody DJ, Gu Q. Antidepressant use among adults: United States, 2015-2018. CDC 2020;Sept.

23 Centers for Disease Control and Prevention. Leading Causes of Death. 2024;Jan 17.

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There is no doubt that autism diagnoses, both across the UK and US are escalating at a worrying rate.

A clear illustration of this is the recently published Scottish Schools Census, showing a year by year steady increase in the percentage of Scottish schoolchildren with a diagnosis. Last year, one in 21 schoolchildren had an autism diagnosis, of which one in 14 are boys. This represents a 43-fold increase in 20 years.

As discussed at Food for the Brain’s Smart Kids conference, research is consistently showing that serum homocysteine, which you can test with us at home here, is a reliable indicator of both folate and B12 status and with each unit increase in homocysteine pre-conceptually, the core symptoms required for an autism diagnosis go up. (1)

The majority of studies show that lack of pre-natal folic acid supplementation or low folate, increase the risk of aspects of neurodivergence. Studies on B12 are less clear however. Further studies are under way which will help determine both the optimal level of folate and B12 and whether they are synergistic, as has been found in Alzheimer’s prevention. Our view is that homocysteine should be measured and high levels lowered with appropriate diet and supplementation.

A recent study of 3,000 EU children reported that one third had B12 levels below 200pg/ml, (2) with deficiency more prevalent in vegan children. Another EU survey reports than only one in ten overweight women supplement folic acid in pregnancy. This is really concerning.

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It’s the total load – not just one thing

The over-arching theme of this excellent conference was that of ‘total load’ and the interaction between predisposing genes and a nutritional deficient diet and/or toxic overload. It stressed the need to think in terms of the ‘total load’ on a child at critical stages of development, starting in pregnancy. A study of 192 twin pairs, published in the Archives of General Psychiatry, concluded that environmental factors were a greater contributor than heritability, contributing 55% of risk (3). 

Additionally, there are many gene variations which don’t cause, but do increase the risk of neurodivergence. An example is a methylation gene variant MTHFR677TT, which increases risk for both autism and Alzheimer’s. Healthy methylation requires B vitamins, especially vitamin B12 and folate, found in ‘foliage’ – vegetables and greens. A study in China in the journal ‘Frontiers in Paediatrics’(4), comparing several thousand with or without this gene variation found that having it “… was associated with the increased risk of autism. For those mothers and children who are generally susceptible to autism, prenatal folate and vitamin B12 may reduce the risk that children suffer from autism.” This is just one example of the gene-environment interplay.

The results of a survey by the Autism Research Institute of over 27,000 parents who rated different nutritional interventions they tried, rating whether their child got better or worse, reported some clear winners of diet changes and supplements. The following had 10:1 or better ratings. 

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‘Life-changing’ improvement through dietary changes…

Another parent-reporting survey conducted by the UK charity Thinking Autism in 2014 (5), involving similar dietary guidance, and written up into a report by academics at Queen Mary, University of London in 2016, found that, out of 237 families who reported using various dietary interventions with their children with autism, 170 families reported either ‘life-changing’ or ‘significant’ improvements, while only 12 children were reported as having  no noticeable change.

If you are a practitioner and would like a deep dive into the Smart Kids conference, recordings are now available.

If you are a parent or are neurodivergent yourself and would like to hear from clinicians who have considerable experience in helping those with symptoms get better, the Optimising Neurodivergence webinar is now available.

But first, do complete the COGNITION for Smart Kids test (or the COGNITION test if you are a parent or practitioner) to help both our research and help yourself at the same time. 

Here’s an example report.

Food for the Brain is a not-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References:

1 Roigé-Castellví J, Murphy M, Fernández-Ballart J, Canals J. Moderately elevated preconception fasting plasma total homocysteine is a risk factor for psychological problems in childhood. Public Health Nutr. 2019 Jun;22(9):1615-1623. doi: 10.1017/S1368980018003610. Epub 2019 Jan 14. PMID: 30636652; PMCID: PMC10261079.
2 Kara İS, Peker NA, Dolğun İ, Mertoğlu C. Vitamin B12 Level in Children. J Curr Pediatr. 2023 Aug;21(2):127-134. doi:10.4274/jcp.2023.75688.
3 https://pmc.ncbi.nlm.nih.gov/articles/PMC4440679/
4 https://pmc.ncbi.nlm.nih.gov/articles/PMC7987783/
5 https://www.thinkingautism.org.uk/taking-action/resources-and-publications/health-and-service-provision-for-people-with-autism/

By Patrick Holford

Recently, the Telegraph reported: “Statins can reduce the risk of dementia among those who already have low cholesterol.” The article claimed that those on statins were less likely to develop dementia – even Alzheimer’s – and that low LDL cholesterol was somehow protective.

Frankly, this is dangerous misinformation.

Why? Because it contradicts robust scientific evidence that low cholesterol – particularly below 4 mmol/l – increases the risk for dementia. That’s hardly surprising when you consider that 25% of the cholesterol in your body is in your brain. Cholesterol is a vital component of neuronal membranes – it’s not just blood fat, it’s brain fuel.

And as for statins? There’s no credible evidence that they prevent dementia. Quite the opposite: the evidence points to statins lowering brain-essential cholesterol and raising dementia risk. So I asked cholesterol expert Dr Malcolm Kendrick for his take on the study in question.

His response was blunt but justified: “This study is horseshit. Here’s why…”

Dr Kendrick Key Critiques:

LDL measurement was vague. It’s unclear if they even measured LDL directly- most studies use the Friedewald formula, known to be wildly inaccurate, especially with high triglycerides or low HDL.

Only one measurement. LDL was recorded once at the study’s start – never again. That’s like measuring someone’s blood pressure once and claiming to predict their lifetime stroke risk.

Bizarre cohort overlap. Somehow, 170,174 participants were in both high and low LDL groups? That’s statistically and biologically nonsensical.

Alzheimer’s exclusion unexplained. Those with pre-existing Alzheimer’s were removed, but with no breakdown of their LDL levels – crucial missing data.

Propensity score manipulation. This “retrospective matching” excluded over 350,000 people, distorting the natural associations. Diabetes and hyperlipidaemia were artificially balanced between groups, masking real-world relationships.

Key confounder: statin timing. Participants were only included after being prescribed statins, meaning LDL levels were already artificially lowered. So “low LDL” here is post-drug, not natural. The entire premise collapses.

This study, like too many others published today, exemplifies what Drummond Rennie famously criticised:

“There is no study too fragmented, no hypothesis too trivial, no design too warped, no analysis too self-serving for it to be published.”

So what do we actually know? Here is an extract from Patrick’s new book – Alzheimers: Prevention is the Cure.

Cholesterol and the Brain – The Real Story

Your brain needs cholesterol. Low cholesterol (<4 mmol/l) is a clear risk factor for dementia. One biomarker study found that high homocysteine and low cholesterol were the best predictors of dementia risk【1】.

And what’s a common cause of low cholesterol in the elderly? Statins. These drugs have consistently failed to show benefits in preventing cognitive decline【2】.

This fits what we know genetically. The ApoE gene governs how cholesterol gets into neurons. Those with ApoE4 are less efficient at this – that’s why they’re more prone to cognitive decline.

It’s not high cholesterol itself that’s dangerous – it’s cholesterol mismanagement in the brain.

Yes, very high cholesterol (above 6.5 mmol/l) is statistically linked to increased dementia risk – but modest elevations, particularly with a healthy lifestyle, are not a problem【3】. And even that data is shaky. One meta-analysis of over a million people showed only a 14% increased dementia risk with “high” cholesterol. But the thresholds varied – some studies defined “high” as anything over 6.2 mmol/l【3】.

More importantly, people with higher cholesterol often eat more sugar, processed foods, and trans fats – all factors known to fuel inflammation and oxidative stress in the brain.

The Lancet Commission, which makes the anti-cholesterol case, even acknowledged this diet–dementia link: in a cohort of 94,184 Danes, poor diet predicted both high LDL and dementia risk【4】.

So maybe it’s not the cholesterol – it’s what comes with it.

Statins and the Hope for Vascular Dementia 

Originally, statins were hyped for vascular dementia – about 20% of all dementia cases – because of their supposed blood vessel–protective effects. But that theory has fallen flat. A Cochrane review found no benefit from statins for dementia prevention【6】.

And the best independent trial – not funded by drug companies – also found no cardiovascular benefit for statins in older adults【5】.

There’s no data supporting the notion that statins protect the brain. Yet the Lancet Commission listed “high cholesterol” as contributing 7% to dementia risk, which will no doubt spur even more statin prescriptions【4】.

The Optimum Nutrition Perspective

From an optimum nutrition standpoint, we view cholesterol differently.

If your total cholesterol is up to 6.5 mmol/l – but you have high HDL, low triglycerides, low homocysteine, and a healthy diet low in sugar and refined carbs – you’re not at risk. In fact, you’re likely protected.

One recent study showed that higher HDL in midlife predicted significantly lower future dementia risk【7】. Low HDL, not high total cholesterol, is a hallmark of metabolic syndrome – the precursor to diabetes, heart disease, and yes, dementia.

The evidence is clear: cholesterol is essential for brain health. Statins do not prevent dementia – and may contribute to cognitive decline by pushing cholesterol levels too low.

Instead of dumbing down the brain with unnecessary statins, we need to smarten up with nutrients that build brain health: omega-3 fats, phospholipids, B vitamins, and a low-sugar diet.

Doctors prescribing statins as dementia prevention are not only missing the mark – they may be making things worse.

Let’s change the narrative. Let’s put nutrition – not cholesterol fear – at the top of the brain health agenda. Find out more in Patrick’s new book – Alzheimer’s: Prevention is the Cure.

Food for the Brain is a not-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References

1  Gong, Q., Xie, L., Bi, M., & Yu, L. (2021). A probability formula derived from serum indicators, age, and comorbidities as an early predictor of dementia in elderly Chinese people. Brain and Behavior 11, e2236. https://doi.org/10.1002/brb3.2236

2 Peters, R, Breitner, J, James, S, et al. Dementia risk reduction, why haven’t the pharmacological risk reduction trials worked? An in-depth exploration of seven established risk factors. Alzheimer’s Dement. 2021; 7:e12202. https://doi.org/10.1002/trc2.12202 

3 Wee J, Sukudom S, Bhat S, Marklund M, Peiris NJ, Hoyos CM, Patel S, Naismith SL, Dwivedi G, Misra A. The relationship between midlife dyslipidemia and lifetime incidence of dementia: A systematic review and meta-analysis of cohort studies. Alzheimers Dement (Amst). 2023 Mar 8;15(1):e12395. doi: 10.1002/dad2.12395. PMID: 36911359; PMCID: PMC9993469.

4  Kjeldsen EW, Thomassen JQ, Rasmussen KL, Nordestgaard BG, Tybjærg-Hansen A, Frikke-Schmidt R. Adherence to dietary guidelines and risk of dementia: a prospective cohort study of 94 184 individuals. Epidemiol Psychiatr Sci 2022; 31: e71. 

5  Han BH, Sutin D, Williamson JD, Davis BR, Piller LB, Pervin H, Pressel SL, Blaum CS; ALLHAT Collaborative Research Group. Effect of Statin Treatment vs Usual Care on Primary Cardiovascular Prevention Among Older Adults: The ALLHAT-LLT Randomized Clinical Trial. JAMA Intern Med. 2017 Jul 1;177(7):955-965. doi: 10.1001/jamainternmed.2017.1442. PMID: 28531241; PMCID: PMC5543335.

6  McGuinness B, Craig D, Bullock R, Passmore P. Statins for the prevention of dementia. Cochrane Database Syst Rev 2016;1: CD003160. 

7 Zhang X, Tong T, Chang A, Ang TFA, Tao Q, Auerbach S, Devine S, Qiu WQ, Mez J, Massaro J, Lunetta KL, Au R, Farrer LA. Midlife lipid and glucose levels are associated with Alzheimer’s disease. Alzheimers Dement. 2023 Jan;19(1):181-193. doi: 10.1002/alz.12641. Epub 2022 Mar 23. PMID: 35319157; PMCID: PMC10078665.

By Patrick Holford

Something concerning is happening to our children – an increasing number are experiencing psychological and behavioural challenges, often diagnosed as autism. 

These challenges range from reduced eye contact and language delays to social difficulties, cognitive struggles, emotional meltdowns, aggression, and in some cases, depression. But what is driving this surge?

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Is it down to genetics & better diagnosis?

While mainstream medicine largely attributes autism to genetics, explaining the rise as improved diagnostic recognition, a growing body of independent researchers and clinicians in the US and UK suggests otherwise. The rapid increase in cases across multiple countries cannot be solely explained by genetics, as genes do not change so quickly. In the US, autism rates have skyrocketed from 2 in 10,000 to 1 in 36 over 50 years. In the UK, official government data estimates 1 in 62 children are classified as autistic; an eightfold increase in 20 years.  Meanwhile, school census data from Scotland and Northern Ireland report even higher rates, with 1 in 20 children diagnosed. These numbers strongly indicate that environmental factors, including diet, play a key role. This also suggests that proactive steps could help reduce risk.

That is why we are launching COGNITION for Smart Kids &Teens in April with the online ‘Smart Kids’ conference. We are bringing together leading experts to examine ways to prevent and potentially mitigate the impact of autism through environmental and nutritional interventions. In addition, we also have our ‘Optimising Neurodivergence public webinar for parents, caregivers or any non-practitioners who want to learn how to support our children to reach their full potential.

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New Approaches Show Encouraging Results

Dr. Chris D’Adamo, Assistant Professor at the University of Maryland School of Medicine and Director of the Centre for Integrative Medicine, has been at the forefront of research into environmental influences on autism. His recent paper, published in Personalized Medicine, estimates a 300% rise in autism cases since 2000. The study also documents a case where early intervention reversed autism symptoms by addressing modifiable lifestyle and environmental factors.

The case involved twin toddler girls exhibiting classic autistic traits;limited communication, repetitive behaviours, resistance to change and severe gastrointestinal issues. Under a comprehensive programme, led by a team of physicians, they implemented tailored interventions focused on diet, environment and lifestyle. The results were striking; within months, both girls showed dramatic improvements. Their autism severity scores dropped significantly, with one twin’s score reducing from 76 to 32 and the other from 43 to just 4. (Read more on this case here)

In the UK, Dr. Lorene Amet, a functional nutritionist and founder of The Lauriston Centre, has been applying similar integrative approaches. She has worked with hundreds of families, with remarkable success. A survey conducted with the charity Thinking Autism, assessed 220 children who followed her recommendations. 169 families reported either ‘life-changing’ or ‘very beneficial’ improvements, while only 11 children saw no noticeable change. 

Yet, despite such promising results, the NHS maintains that autism has no cure and advises against interventions such as vitamins, minerals, and dietary modifications.  The NICE guidelines currently offer no targeted nutritional strategies for autism management, leaving many parents with limited options. 

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Can Autism Risk Be Reduced Before Birth?

Another key topic at the Smart Kids Conference is prevention; reducing the likelihood of autism before birth. Research led by Associate Professor Michelle Murphy of the Universitat Rovira I Virgili in Spain, has revealed a crucial link between B vitamin deficiencies in early pregnancy and a child’s likelihood of developing autism-related traits. Her studies show that children of mothers who were low in B vitamins before conception were significantly more likely to display withdrawn behaviour, anxiety, depression or aggression by age six. 

The connection between maternal nutrition and neurological development is well established. For decades, pregnant women have been advised to take folic acid to prevent neural tube defects; a policy delayed by 25 years, resulting in hundreds of thousands of avoidable birth defects. Children with autism are six times more likely to have neural tube defects, further linking B vitamin deficiencies to neurodevelopmental issues.

This aligns with earlier research from Oxford University’s Professor David Smith, one of our scientific advisors.  His work demonstrated that B vitamins lower homocysteine, a toxic amino acid linked to autism, depression, cognitive impairments in children and Alzheimer’s in adults.  Professor Murphy’s research further suggests that even mildly elevated homocysteine levels before pregnancy strongly predict neurodivergent traits in children. This underscores the importance of nutritional screening and intervention before conception.

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There Is So Much That Parents Can Do…

We are inviting parents to take part in a free online assessment of their child’s cognitive, emotional, and behavioural function, alongside a diet and lifestyle questionnaire to help optimise brain health. Parents can also access a home test kit for homocysteine levels, providing valuable insight into potential nutritional deficiencies that may affect brain function.

The Smart Kids conference will provide further guidance on evidence-based interventions, bringing together researchers, clinicians, and parents seeking practical solutions to support children’s cognitive development.

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“People come in assorted shapes and sizes, with brains that are unique,” says Dr Rona Tutt, OBE, a trustee of Food for the Brain and past President of the National Association of Head Teachers. “A significant minority who are neurodivergent need to be recognised, valued, and supported to maximise their strengths and overcome challenges. Understanding the factors driving the rise in neurodivergence is key to ensuring the best outcomes for future generations.”

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For more information on all the events relating to Smart Kids – visit foodforthebrain.org/smartkids.

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Food for the Brain is a not-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References:

¹ https://www.cdc.gov/mmwr/volumes/72/ss/ss7202a1.htm?s_cid=ss7202a1_w

² https://researchbriefings.files.parliament.uk/documents/POST-PN-0612/POST-PN-0612.pdf; see also Russell G, Stapley S, Newlove-Delgado T, Salmon A, White R, Warren F, Pearson A, Ford T. Time trends in autism diagnosis over 20 years: a UK population-based cohort study. J Child Psychol Psychiatry. 2022 Jun;63(6):674-682. doi: 10.1111/jcpp.13505

³ https://www.gov.scot/publications/pupil-census-supplementary-statistics/

⁴ https://www.health-ni.gov.uk/news/publication-prevalence-autism-including-aspergers-syndrome-school-age-children-northern-ireland-a nnual-report-2023

⁵ D’Adamo C et al., Reversal of Autism Symptoms among Dizygotic Twins through a Personalized Lifestyle and Environmental Modification Approach: A Case Report and Review of the Literature. J Pers Med. 2024 Jun 15;14(6):641. doi: 10.3390/jpm14060641

⁶ Survey conducted in collaboration with the charity Thinking Autism. The full survey results will be shown at the Smart Kids conference, April 24^th 20025.

⁷ https://www.nhs.uk/conditions/autism/autism-and-everyday-life/treatments-that-are-not-recommended-for-autism/

⁸  https://www.nice.org.uk/guidance/cg142/chapter/Recommendations#interventions-for-autism-2

⁹ Roigé-Castellví J, Murphy M, Fernández-Ballart J, Canals J. Moderately elevated preconception fasting plasma total homocysteine is a risk factor for psychological problems in childhood. Public Health Nutr. 2019 Jun;22(9):1615-1623. doi: 10.1017/S1368980018003610; see also Murphy MM, Fernandez-Ballart JD, Molloy AM, Canals J. Moderately elevated maternal homocysteine at preconception is inversely associated with cognitive performance in children 4 months and 6 years after birth. Matern Child Nutr 2017;13,e12289 . doi: 10.1111/mcn.12289

¹0 Hasler M, Fideli ÜS, Susi A, Hisle-Gorman E. Examining the relationship between autism spectrum disorder and neural tube defects. Congenit Anom (Kyoto). 2023 Jul;63(4):100-108. doi: 10.1111/cga.12516. Epub 2023 Apr 18. PMID: 37073427.¹1 Smith AD, Refsum H. Homocysteine – from disease biomarker to disease prevention. J Intern Med. 2021 Oct;290(4):826-854. doi: 10.1111/joim.13279

by Cath Verner

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A landmark study from the Centre for Healthy Brain Ageing (CHeBA) at the University of New South Wales (Sydney, Australia) has provided compelling evidence that targeted diet and lifestyle changes can improve cognitive function in older adults. 

Or put simply, what we teach and promote at Food for the Brain works when it comes to promoting brain health.

Raising awareness and providing tools to support the critical role of diet and lifestyle in long-term cognitive health is both essential and part of the solution.

This recent study affirms our approach: sustained step-by-step adjustments to diet, exercise, sleep, and social engagement significantly reduces the risk of dementia as well as maintaining – and even enhancing – cognitive function.

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Study shows a holistic approach to brain health works

The CHeBA study recruited over 6000 adults aged 55 to 77, dividing them into two groups, one participating in an online lifestyle intervention programme and the other serving as a control group.

Physical activity (strength and balance training), 
Brain training (three weekly cognitive training sessions), 
Mediterranean diet (rich in plant foods and healthy fats with limited meat and dairy), 
Mental well-being (a digital anxiety and depression reduction program).

While both groups showed some cognitive improvements, those in the intervention group experienced significantly greater gains, demonstrating the added value of a structured, multi-domain approach.

Professor Brodaty, one of the study’s research team, stated:

“Participants aged 55-65 showed greater improvement than those aged 66-77, suggesting that prevention programmes should start earlier.”

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Why a Multi-Domain Approach Works!

Unlike traditional approaches that focus on just one or two factors, the COGNITION® Programme, which you get access to when you become a FRIEND of Food for the Brain, is similarly built on eight interwoven pillars—including diet, physical exercise, sleep, social involvement, and even the gut microbiome—to provide a comprehensive brain health plan.

The study’s ‘Maintain Your Brain’ trial further supports this, showing that targeting multiple lifestyle domains simultaneously – including physical activity, nutrition, brain training, and mental well-being – leads to greater cognitive benefits, rather than focusing on a single risk factor.

And, as we always say, the earlier you start, the better!

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Your Roadmap to the 8 Pillars of Cognitive Health

In line with this study, we focus on 8 key domains that influence brain health. These areas provide strategies to help individuals reduce their risk of cognitive decline and support long-term brain health:

Domain 1: Low Glycemic Load (GL) Diet – Managing blood sugar levels is crucial for brain function. High-sugar diets contribute to inflammation and insulin resistance, impairing cognitive performance. A low-GL diet helps stabilise energy levels and protects brain cells from damage

Domain 2: B Vitamins & Homocysteine Levels – High homocysteine levels, a by-product of metabolism, are linked to cognitive decline. Ensuring adequate B vitamins (B6, B12, and folate) supports brain function and lowers homocysteine levels.

Domain 3: Brain-Boosting Fats – Healthy fats like omega-3s (found in fish, flaxseeds, and walnuts) are essential for brain cell structure and function. They help reduce inflammation, enhance memory, and support cognition.

Domain 4: Antioxidants & Polyphenols – Free radicals damage brain cells, but antioxidants (from colourful fruits, vegetables, green tea, and dark chocolate) help combat oxidative stress and keep your brain young.

Domain 5: Healthy Gut & Microbiome – The gut-brain connection is vital for mental clarity and mood. A diverse microbiome (supported by fibre-rich foods, fermented foods, and probiotics) can reduce inflammation and improve neurotransmitter function, supporting memory and mental health.

Domain 6: Active Body (Exercise & Movement) – Regular physical activity boosts blood flow to the brain, supports neuroplasticity, and reduces the risk of dementia. Both aerobic exercise (like walking and cycling) and strength training play a role in maintaining cognitive health.

Domain 7: Active Mind – The brain thrives on challenge! Lifelong learning, problem-solving activities, and hobbies stimulate new neural connections and help build cognitive resilience.

Domain 8: Sleep & Stress Resilience Management – Poor sleep and chronic stress are major contributors to cognitive decline. Deep, restorative sleep allows the brain to clear toxins, while mindfulness, relaxation techniques, and breathing exercises help reduce stress hormones that damage brain cells.

__

We know that these 8 domains can help you protect your brain and prevent cognitive decline – but most of us need support, accountability, motivation and structure to be able to implement the necessary changes consistently.

That is why the  COGNITION® Programme exists.

It’s designed to make implementing the above easier and simpler, one step at a time. By providing tailored advice and guidance on all eight areas, the programme offers tangible, practical steps that members can take to enhance brain function, reduce dementia risk, and improve overall cognitive well-being.

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Real-Life Results…

As a research charity with a stellar scientific advisory board, we care about excellent research being carried out. 

Yet the most important thing is that ‘the science’ helps to transform lives, families and communities. Citizen science in action!

Here is what can happen when you join COGNITION. One participant told us:

“I have taken the CFT for at least seven years now and find it very worthwhile.
By monitoring sensibly what I eat, as you advise and exercising within my limitations, I have found that despite being 84, my results have improved.”

This experience is echoed by another participant who found benefit in making small, sustainable lifestyle changes every day:

“I’ve taken on board your recommendations and I’ve increased my vitamin B intake and started doing puzzle books every day to keep my brain active in different ways from before. I also do more exercise and yoga daily. I love the fact that I can make these small changes myself and hopefully reduce my chances of getting dementia.”

Another participant shared how working with Food for the Brain and starting with the COGNITION® Programme was a wake-up call that led to lasting changes:

“Since starting with Food for the Brain, I’ve completely reshaped my lifestyle. I now attend a weekly Pilates class, work on my allotment, swim regularly, and take longer evening walks. I’ve also cut down on alcohol and meat, increased my vitamin B intake, and started doing daily puzzles to challenge my brain in new ways. My sleep has improved and I feel more energetic with fewer foggy days.”

These testimonials show how small, targeted lifestyle changes can significantly enhance cognitive resilience and well-being. The COGNITION® Programme equips individuals with the necessary tools to take charge of their brain health, which leads to improved cognitive test scores, better mental clarity, and a greater sense of control over their future.

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Join the COGNITION® Programme today!

As a non-profit charity we aim to make resources affordable and accessible to all, while covering essential staff and research costs. Membership of the 8-domain COGNITION® Programme is just £50 per year or £5 per month, ensuring that everyone can benefit from the programme.

You get access to the programme when you become a FRIEND of Food for the Brain.

Members receive:

Guidance on which domains to target based on their test results.
Ongoing cognitive assessments to track progress.
Access to expert-backed articles for long-term brain health.
Access to regular group coaching and Q&A sessions.

How it works:

Become a FRIEND here
Complete the FREE Cognitive Function Test* to get personalised insights and The COGNITION Programme.
Pick one domain to work on each month for six months, attend live coaching calls and watch as your brain health improves!

*You do not need to be a FRIEND to do this test.

Start today!

Your brain health is in your hands.

Become a FRIEND from just  £5 per month or  £50 a year to get access to the COGNITION® Programme

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Food for the Brain is a not-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

By Patrick Holford, in response to the New York Times essay here.

Recently, investigator Charles Piller exposed the fraudulent claims behind the amyloid theory of Alzheimer’s, that has caused heads to roll.

The article, based on his new book Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer’s, presents evidence of fraud. It reveals that Dr Masliah, the Head of the National Institute on Ageing (a division of the US National Institutes of Health) and responsible for billions in funding, had for decades included improperly manipulated images of brain tissue and other technical visuals in his research. 

With roughly 800 papers to his name, many of them considered highly influential, Dr. Masliah seemed a natural choice to steer the funding for Alzheimer’s research. He hailed the moment as the dawning of “the golden era of Alzheimer’s disease research”. The National Institutes of Health announced that it had found that Dr. Masliah engaged in research misconduct and that he no longer held his leadership position.

Marc Tessier-Lavigne, the former president of Stanford University, was known as a global leader in research on the brain’s circuitry in Alzheimer’s and other neurological conditions. He resigned in 2023 after an intrepid student journalist revealed numerous altered images in the research of his lab, in papers he co-authored. A Stanford University investigation, however, didn’t find evidence to conclude that he personally engaged in research misconduct. They did note that at various times when concerns with his papers emerged— between 2001 and 2021—Dr. Tessier-Lavigne failed to decisively and forthrightly correct mistakes in the scientific record.

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Amyloid exaggerations

What isn’t being fully exposed, is just how bad the results of the anti-amyloid drug treatments are and how the drug companies who run these trials manage to squeeze a result, just enough to get a medical licence for their treatment. Everyone is aware of this exaggeration by bigging up the results. 

For example, the Alzheimer’s Society described the miniscule difference in effect of the anti-amyloid drug as follows:  ‘Lecanemab slowed down the speed at which memory and thinking skills got worse by 27%’. 

This is economical with the truth.

The British Medical Journal Editorial on the trial, in relation to a clinically meaningful effect, said it ‘fell well short, representing only around a third of what a minimum clinically important difference might look like’. Those on the drug just hit the same rock bottom about 3 months later than those on the placebo and the difference was so small that no-one is likely to notice.

No-one got better. They all got worse. Quite a few had adverse effects, with brain bleeding and swelling. More than a quarter had adverse reactions. A few died as a consequence. 

Is three months of ‘slightly less worse’ symptoms worth the suffering of adverse events by one in four participants including death (about one in 500) – and all this at vast expense? 

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Expensive, ineffective and rejected by NICE

If such treatment was started before a person was put into care, at best it could mean putting them in a care home three months later, potentially saving £3,000. If treatment were given whilst in a care home it would mean three months more time in a care home, potentially costing £3,000 more. Either way, at a treatment cost likely to be in the region of £50,000 per year this is clearly not cost effective for the NHS, which is why the National Institute for Health and Care Excellence (NICE) quite rightly rejected it.

The greatest missed opportunity is that we already know how to reduce Alzheimer’s risk – through targeted diet, lifestyle and nutrient optimisation – yet far less funding and attention goes toward implementing these strategies at scale.

The power is in your hands and it’s never too late or too early to start.

Prevention is key and you can start today – so please encourage everyone you know to take the Cognitive Function test here.

Read the full NYT article here

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Get started today:

Take the Cognitive Function Test: Assess your brain health today and gain personalised insights. 
Get personalised data on your body and join our research by ordering your DRIfT 5 in 1 test here so you can join our research and find out what your unique body needs.
Become a Friend & join the COGNITION Programme: Support our mission with a small monthly donation and receive tailored steps to improve your brain resilience and track your progress.

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Food for the Brain is a not-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

by Patrick Holford

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What has homocysteine got to do with autism?

Homocysteine, a toxic amino acid commonly associated with disorders of the brain and circulation, is an indicator of a lack of B vitamins resulting in faulty methylation, a process critical for brain function.

So are there links between autism and homocysteine and could this help us to optimise neurodivergence in our children?

(At Food for the Brain we are on a mission to help upgrade and support ALL brains. That is why we are creating the Smart Kids & Teens COGNITION programme. Click here to find out more.)

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Homocysteine Levels in Autistic Children: A Significant Risk Factor

Recent studies have drawn attention to the elevated presence of homocysteine in autistic children. In a well-controlled study involving 119 autistic children compared to age and sex-matched neurotypical children, 13.4% of the autistic group exhibited homocysteine levels above 15 mcmol/L. This contrasts sharply with only 3.4% of typically developing children who showed such elevations (1).  This means that an autistic child is three and a half times more likely to have raised homocysteine. These findings also suggest that approximately one in six autistic children have a significant methylation problem, a process critical to DNA repair and neurotransmitter production.

Previous studies have reported similar findings. A study in 2022 (2) reported that ‘Overall, an increased homocysteine level was associated with autistic spectrum disorder (ASD) in a linear manner and is thus a novel diagnostic biomarker for ASD. Decreased concentrations of folate and vitamin B12 were associated with poor clinical profiles of children with ASD. These findings suggest that homocysteine-lowering interventions or folate and vitamin B12 supplementation might be a viable treatment strategy for ASD.’

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The Role of B Vitamins in mother & child

Homocysteine-lowering interventions, particularly through the supplementation of the most important B vitamins –  B12, B6, and methylfolate, that are required for healthy methylation – have demonstrated effectiveness in clinical settings (3). These vitamins play a vital role in the metabolism of homocysteine, converting it back into methionine, thereby reducing its toxic buildup in the bloodstream.

Research also indicates that maternal homocysteine levels during pregnancy can influence child development. A study found that women with homocysteine levels above 9 mcmol/L during pregnancy were more likely to have children exhibiting behavioural problems by age 6, including withdrawal, anxiety, depression and social or aggressive behaviours (4).

This suggests that early intervention targeting homocysteine levels in expectant mothers or women planning a pregnancy may have long-term benefits for child development.

Autistic children often experience a range of developmental delays and behavioural symptoms, many of which have been linked to elevated homocysteine. These include delayed language and movement skills, cognitive challenges, and abnormal emotional responses. Given the substantial overlap between symptoms of ASD and the effects of high homocysteine, it is logical to explore and implement further research into this biomarker as a target for therapeutic intervention. (As we plan to do in our Smart Kids & Teens COGNITION Programme.)

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The Case for Homocysteine Testing in Autistic Children

Given the evidence linking elevated homocysteine with autism, it makes sense to test homocysteine in all children classified as ASD. A subset will likely have raised homocysteine and benefit from B vitamin supplementation. 

We offer at home testing of homocysteine which can be done from age 2+  and is available globally here.

Given the growing interest in homocysteine as a marker of brain health, it is worth understanding its wider role in cognition and neurological function. You can read more in our guide to homocysteine and brain health: .

Actions

Further reading –  ‘Is Autism Genetic?‘ – read here
Further reading – ‘Autism Reversed: A case study‘ – read here
Order your homocysteine test here
Find out more about our Smart Kids & Teens COGNITION Program here

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Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References

​​1 Gulati S, Narayan CL, Mahesan A, Kamila G, Kapoor S, Chaturvedi PK, Scaria V, Velpandian, T, Jauhari P, Chakrabarty B, Datta SKR, Pandey RM. Transmethylation and Oxidative Biomarkers in Children with Autism Spectrum Disorder: A Cross Sectional Study. J Autism Dev Disord. 2024 Sep 4. doi: 10.1007/s10803-024-06542-9. Epub ahead of print. PMID: 39230783.

2 Li B, Xu Y, Pang D, Zhao Q, Zhang L, Li M, Li W, Duan G and Zhu C (2022) Interrelation between homocysteine metabolism and the development of autism spectrum disorder in children. Front. Mol. Neurosci. 15:947513. doi: 10.3389/fnmol.2022.947513

3 Adams JB, Audhya T, Geis E, Gehn E, Fimbres V, Pollard EL, Mitchell J, Ingram J, Hellmers R, Laake D, Matthews JS, Li K, Naviaux JC, Naviaux RK, Adams RL, Coleman DM, Quig DW. Comprehensive Nutritional and Dietary Intervention for Autism Spectrum Disorder-A Randomized, Controlled 12-Month Trial. Nutrients. 2018 Mar 17;10(3):369. doi: 10.3390/nu10030369. PMID: 29562612; PMCID: PMC5872787.

4 Roigé-Castellví J, Murphy M, Fernández-Ballart J, Canals J. Moderately elevated preconception fasting plasma total homocysteine is a risk factor for psychological problems in childhood. Public Health Nutr. 2019 Jun;22(9):1615-1623. doi: 10.1017/S1368980018003610. Epub 2019 Jan 14. PMID: 30636652; PMCID: PMC10261079.

by Patrick Holford

There is a reason why we don’t just talk about the benefits of omega-3, or encourage people to only focus on vitamin D – many of these nutrients work synergistically and are all needed to work together to maximise the reduction in dementia risk.

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A few months ago, a study looked at three blood tests – homocysteine, vitamin D and omega-3 index and assigned a score of 1 = bad or 0 = good to each result. A person scoring 3 (three ‘bad’ results) had 4.6 times the risk of having dementia compared to a score of 0 (three ‘good’ results). This confirms the synergistic effect of two of our four ‘biological horsemen of the mental health apocalypse’ – brain fats (omega-3 and vitamin D) together with homocysteine-lowering B vitamins. 

The researchers, led by Dr Annike van Soest in Holland say: 

“The effect size we observed was substantial; a four-fold increased risk of developing dementia in individuals with combined suboptimal status of omega-3, vitamin D, and homocysteine (three ‘bad’ results). This effect size is large in comparison with other risk factors of dementia. In our sample, being a current smoker or having diabetes doubled the risk, and being a carrier of at least one APOE ε4 allele (gene variant) tripled the risk of dementia (1).”

In this study, which is the third of its kind, if homocysteine was above 8mcmol/l, that was ‘high risk’ (scoring 1) and if below this, ‘low risk’ (scoring 0). Similarly, if vitamin D was below 15 ng/ml (37.5 nmol/l) that was classified as high risk and if the omega-3 index was below 5%, then that was classified as high risk. 

Interestingly, this was based on the research of risk according to blood levels. So, while it is already known that if homocysteine is above 11mcmol/l the brain is shrinking at an accelerated rate, in this study, even levels above 8 are associated with increased risk of dementia! 

At Food for the Brain, we set the optimal level for homocysteine at 7 or less.

According to Professor David Smith from Oxford University whose group carried out the original study of this kind, homocysteine-lowering B vitamins slowed the rate of brain shrinkage by 73%. They also slowed the rate of cognitive decline, arresting it in a third of trial participants.  

He stated: 

“For too long nutrition has been relatively discounted as a factor in the causation of dementia. This study corrects that misconception and lays the foundation for prevention based upon multiple nutrients.”

A study in France (2), which didn’t include homocysteine but did include a measure of carotenoids as an indicator of ‘oxidation’ reported a fourfold increased risk if all blood tests were in the ‘high-risk’ category.

We offer a similar range of tests in our Dementia Risk Index functional Test (DRIfT) but with more sensitivity, plus adding in HbA1c as a measure of blood sugar resilience. We have also recently added a Glutathione Index test as a measure of antioxidant status. 

In other words, we are looking at ‘four horsemen of the mental health apocalypse’, not just two. Additionally, instead of only having a good/bad, 0/1 scale we have a four-point scale, from 0 to 3 for each test. So, our 4 in 1 test can score within a range of 0 to 12.

On a practical level, your goal is to have all blood test levels in ‘the green’ zone, which we have set as:

– homocysteine below 7
– omega-3 index above 8%
– vitamin D above 40 ng/ml or 100 nmol/l
– HBA1c below 5.5%;
– Glutathione Index above 800.

Tracking changes in these markers against changes in cognitive function would provide further evidence for a systems-based approach to preventing age-related cognitive decline. Whilst it might sound technical, when you test with us (and support our charity and research in the process), we help by making it clear and easy to understand.

We hope to have substantial test results soon, and to plug into NHS patient data to import more test results for vitamin D and HbA1c, along with future dementia diagnoses. This will help further develop and research the perfect DRIfT score and enhance our guidance for your future protection against cognitive decline.

Exciting, isn’t it?

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What can you do?

Online test. Find out more about your own brain health and unique risk factors by completing the FREE Cognitive Function Test here
Blood Tests. Order one of your at-home pin-prick blood tests here.
You can find out your homocysteine, vitamin D, HbA1c, Omega-3 and Glutathione index results from your own home worldwide and also contribute to our Citizen Science Research
Become a FRIEND and support our charity and get access to COGNITION – your personalised online program to help you reclaim your brain. Become a FRIEND here
Get the book! Order the latest Upgrade Your Brain book here if you are in the UK 

—

Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References

1.  van Soest APM, de Groot LCPGM, Witkamp RF, van Lent DM, Seshadri S, van de Rest O. Concurrent nutrient deficiencies are associated with dementia incidence. Alzheimers Dement. 2024 Jun 12. doi: 10.1002/alz.13884. Epub ahead of print. PMID: 38865433.

2.  Neuffer J, Gourru M, Thomas A, Lefèvre-Arbogast S, Foubert-Samier A, Helmer C, Delcourt C, Féart C, Samieri C. A Biological Index to Screen Multi-Micronutrient Deficiencies Associated with the Risk to Develop Dementia in Older Persons from the Community. J Alzheimers Dis. 2022;85(1):331-342. doi: 10.3233/JAD-215011. PMID: 34806604.

The Lancet Report Omission! World Experts Criticise Latest Alzheimer Report

The recent Lancet dementia commission has ignored the best nutrition prevention evidence. (See the Lancet Commission Report here)

The Alzheimer’s Prevention Expert Group has accused the Lancet Commission of bad science for knowingly ignoring two highly effective and firmly evidence-based ways to reduce risk factors for dementia – high dose supplements of B vitamins and omega-3 fish oils as well as the impact of a low sugar diet. 

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We support this group of eleven leading scientists and have called on the Lancet to revise their report, which hit the headlines in the past weeks, minimising the effectiveness of nutrition and lifestyle interventions.

(Click here to read the three letters sent to The Lancet asking for a revision in this report.)

The major benefit of B vitamins is their ability to lower levels of the damaging amino acid homocysteine, found in the brain of Alzheimer’s patients. A comprehensive Chinese review of Alzheimer’s prevention research in 2020, described homocysteine lowering as ‘the most promising intervention for Alzheimer’s disease prevention’ (1).

Last month, a review in the Journal of Prevention of Alzheimer’s Disease, listed reducing homocysteine among the top five evidence-based actions (2).  A US National Institutes of Health review attributes almost a quarter (22%) of the risk of Alzheimer’s to raised homocysteine and a further 22% to lack of seafood and omega-3 fish oils (3). 

The combination of high homocysteine, low omega-3 and vitamin D is present in the majority of those over 50 and quadruples dementia risk, according to research in Holland earlier this year, led by Professor Annick van Soest at Wageningen University (4). 

“Remarkably, a suboptimal status of all three nutrients was associated with a four-fold increased risk of dementia,” she says.  These common combined deficiencies, so easily corrected, could have a bigger impact on dementia risk than any of the 14 risk factors listed in the Lancet Commission’s report.

Yet, for the third time since the first Lancet Commission report in 2017, and despite being sent all the evidence, the report’s scientists, headed by Professor Gill Livingston, have ignored it. 

Instead, two far less significant risk factors have been added – cholesterol and cataracts. The report claims cataract surgery would eliminate a very modest 2% of overall risk. In stark contrast, reducing high homocysteine, which affects one in two of over 65 ‘s could potentially eliminate a quarter of all risk, “saving the UK economy approximately £60 million per year,” says Oxford University health economist, Professor Apostolos Tsiachristas.

Why has important science been missed out?

Asked why she continued to deny any benefit from homocysteine lowering, Professor Gill Livingston commented: “high homocysteine only affects a small number of people and there are no trials that show that lowering it has any benefit.” 

This is simply not true.

Studies in Holland (5), Norway (6), the UK (7) and China (8), have additionally reported a synergistic effect between B vitamins and omega-3, with several times better clinical benefit than any dementia drug. A study at Oxford University showed two thirds less brain shrinkage in those with mild cognitive impairment given B vitamins with sufficient omega-3 compared to placebo and one third of trial participants were clinically dementia-free at the end of one year (9). These studies were sent to Professor Gill Livingston in 2023.

The commission has also ignored studies showing a benefit from improving omega-3 status by eating fish or taking supplements. The Lancet Report cited only one study linking higher blood levels of omega-3 fatty acids with risk for dementia which concluded that this study provided “compelling evidence for a relationship between long-chain omega-3 fatty acids levels and lower risks for dementia and related outcomes .” 

Essentially, the same conclusions were reached by at least eight other similar studies. “Why were these studies ignored?” asked Professor William Harris of the Fatty Acid Research Institute, a leading omega-3 expert in the US. “The vast majority of adults in the western world have suboptimal blood omega-3 fatty acid levels. Increased consumption of marine omega-3 is safe, simple, cheap and effective.”   

By ignoring these well established, easy to change risk factors the Lancet Commission was able to reduce the claimed preventable risk to 45%. Something that China’s leading prevention expert Professor Jin-Tai Yu of Fudan University in Shanghai strongly disputes. “It may be possible to prevent up to 80% of dementia cases if all known risk factors, including homocysteine lowering B vitamins and omega-3, found in oily fish, were targeted.” he says. 

He was co-author of a study in the journal Nature, together with Oxford University’s leading prevention expert Professor David Smith, analysing data from the UK BioBank which concluded that ‘up to 73% of dementia cases can be prevented.” However, even this may be an under-estimate as this study excluded blood test measures, says Professor David Smith. “This figure could be higher if a person’s omega-3 and B vitamin status, measured by a blood test for homocysteine, were taken into account.”

Homocysteine, omega-3 and vitamin D blood levels attribute 45% of modifiable risk to a deficiency of B vitamins and brain fats. 

The Lancet Omission – what can we do?

That is why we offer our free online Cognitive Function Test. In addition, our accurate, at home pin prick blood tests are available internationally, helping you understand your future dementia risk and what you can do to lower it.

We are ‘citizen science’ in action and gathering independent research on the effectiveness of diet, supplements and lifestyle change that anyone can join. 

Simply put – the cultural bias against nutrition, demonstrated by the Lancet Commission’s omissions, isn’t science-based. 

And it certainly isn’t helping those at risk take easy, positive actions to reduce it.

Action steps

The next steps you need to take to reduce your risk:

Complete the FREE Cognitive Function Test here
Order one of your at-home pin-prick blood tests here
Become a FRIEND and support our charity and get access to COGNITION – your personalised online program to help you reclaim your brain. Become a FRIEND here
Get the book! Order the latest Upgrade Your Brain book here if you are in the UK 

Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References:

1 Yu JT, et al. J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1201-1209
2 He S.-Y, et al. Prev Alzheimers Dis. 2024 Aug;11:917–927
3 Beydoun MA, et al. BMC Public Health. 2014 Jun 24;14:643
4 van Soest APM, et al. Am J Clin Nutr. 2021 Apr 6;113(4):801-809
5 van Soest APM, et al. Eur J Nutr. 2022 Jun;15:61 3731–3739
6 Jernerén F, et al. J Azheimers Dis. 2019;69(1):189-197
7 Oulhaj A, et al. J Alzheimers Dis. 2016;50(2):547-57
8 Li M, et al. Eur J Nutr. 2021 Jun;60(4):1795-1808
9 Jernerén F, et al. Am J Clin Nutr. 2015 Jul;102(1):215-21
10 Zhang Y, et al. Nature Human Behaviour. 2023;7:1185–1195

Can Autism Be Reversed? A Published Case Study

At Food for the Brain, we are committed to exploring the factors that influence brain development, cognitive function and mental wellbeing throughout life. While much of our work today focuses on protecting brain health as we age, we also support research and education on children’s brain development through initiatives such as Smart Kids & Teens.

The question of whether autism can be reversed remains one of the most debated topics in developmental medicine. In this guest article, Simon Martin examines a published case study describing two children with autism spectrum disorder who experienced substantial improvements following a comprehensive programme of nutritional, lifestyle and therapeutic interventions. As a single case study, its findings cannot be generalised to all children with autism, but they raise important questions about the potential role of nutrition, metabolism and environmental factors in influencing symptoms and development, and highlight areas where further research is warranted.

Autism: “reversed” in twins with personalised nutrition, supplements and therapeutic approaches

By Simon Martin – this article was originally shared by IHCAN – shared and edited with permission. 

It’s “kind of a miracle”, says one of the paediatricians consulted in a newly-published case study, as twin girls recover – one, so completely it’s as if she never had autism. 

Research charity Documenting Hope, has published a case study detailing the reversal of severe Autism Spectrum Disorder symptoms in fraternal female twin toddlers.

Diagnosed at 20 months with severe (Level 3) ASD and requiring substantial support, the twins exhibited limited communication, repetitive behaviours, and significant gastrointestinal issues. Realising that conventional approaches were unlikely to help, the parents assembled an intervention focusing on environmental and lifestyle factors. 

In a paper published in the journal Personalised Medicine by a multi-disciplinary team, Dr Chris D’Adamo PhD, (who will be speaking at our Smart Kids & Teens Event in 2025) the charity’s Scientific Director and Principal Investigator and Director of the Centre for Integrative Medicine at the University of Maryland School of Medicine, and his colleagues reported the following stunning results: 

“Both twins showed dramatic improvements on the Autism Treatment Evaluation Checklist (ATEC) . The ATEC measures the effectiveness of autism treatment by assessing  communication, social skills, sensory awareness and more. Autism Treatment Evaluation Checklist (ATEC) scores dropped from 76 to 32 and 43 to 4 (scores below 43 indicate neurotypical), respectively, with stability over six months. The progress of Twin P, whose score dropped to 4 from March 2022 to October 2023, was described as “a kind of miracle” by one of the paediatricians. Dr D’Adamo told the Telegraph, “This twin’s functions are comparable to those who have never had an autism diagnosis”.  

Twin L, who had more severe autism at 20 months, scoring 76 initially, reduced this to 32 a year and a half later. D’Adamo said she “improved dramatically, but not quite as much”.

They also highlighted “the clear environmental and lifestyle influences on ASD that these findings help establish, building upon previous studies revealing the comparatively greater impact of these types of factors than genetics”.

D’Adamo and colleagues do not use the word “cure” in their report, but say the symptoms are unlikely to come back; “Because autism is a developmental condition, one can safely say that once they have overcome the developmental aspects of autism and returned to a typical developmental trajectory, they are very unlikely to exhibit the common symptoms of autism again. Symptoms that could return might be more along the lines of things like anxiety, gastrointestinal issues and sensory issues, but not necessarily the behavioural aspects of autism”.

The team from the University of Maryland and Hope concluded: 

“This case revealed a reversal of the Level 3 Autism Spectrum Disorder diagnoses among toddler twin girls that was achieved primarily through environmental and lifestyle modifications over a two-year period. The twins’ dramatic improvements and diagnosis reversal have persisted for over six months with no signs of regression”.

“What’s more”, says Documenting Hope, “we have learned from the parents that the twins’ ATEC scores have continued to drop below those that were originally published in this paper. This is very exciting news for this family and for the promise of symptom reversal in autism as a viable clinical outcome”.

This is not the first report of a reversal/cure of autism, but certainly the first case where researchers have documented treatment initiated and led by parents. The published paper includes a review of the literature, in which D’Adamo and colleagues detail the many “alternative” approaches that have succeeded, but have been ignored by orthodox medicine, even when published, possibly due to lack of blinding, which is challenging for such interventions. Additionally, they say, a degree of expectation bias is possible and more studies are needed for conclusive results regarding any such interventions, particularly in light of both the diversity of possible causes of ASD and the presentation of symptoms.

The nutritional, supplements & therapeutic approaches

Citing almost 50 previous studies, the Hope team write: “There are limited FDA-approved pharmacological options at present to treat ASD. Accordingly, there have been a number of non-pharmacological interventions tailored to address the underlying environmental and lifestyle risk factors that have demonstrated promising, though not conclusive, improvements in ASD symptoms“. 

These include: 

Dietary interventions such as gluten and casein-free, GAPS (Gut & Psychology / Physiology Syndrome), a specific carbohydrate diet, low glutamate and ketogenic.
Targeted or personalised dietary supplements such as vitamin D, methylfolate, carnitine, vitamin B12 and other micronutrient supplementation, mitochondrial support, or supplements thought to be relevant to a child’s functional genomic situation. 
Addressing other modifiable lifestyle factors and environmental interventions, such as more time in nature, a reduction in exposure to artificial light, and improving indoor air quality, have demonstrated promise.
Therapeutic interventions addressing a child’s physical structure and function, such as cranial osteopathy, retained reflex integration, physical therapy, and occupational therapy, have also been associated with improved outcomes among ASD patients.

“While reversal of ASD diagnosis is relatively rare, there have been documented cases in the literature of complete recovery with a multi-modal intervention. One such case achieved reversal of ASD diagnosis through a combination of dietary modifications, probiotics and micronutrient supplementation, and antimicrobials that were personalised to the child’s risk factors, clinical presentation and a variety of laboratory tests”.

The approaches taken for this intervention

The parents gathered support and resources from many places.  They worked with an autism parenting coach, utilising the Child Health Inventory for Resilience and Prevention (CHIRP) survey of the Documenting Hope Project, in addition to resources at Epidemic Answers. They also used Applied Behaviour Analysis (ABA, which is typically recommended for new ASD diagnoses –  find out more here) and speech therapy with the twins.  Additionally, the twins’ parents implemented a rigorous diet and nutrition intervention around the time of diagnosis.

First to go was glutamate – aka MSG – following the principles of the Reduced Excitatory Inflammatory Diet (REID – references can be found here ) developed by PhD biochemist Dr Katherine Reid. Dr Reid is a mother of a daughter “no longer considered on the autism spectrum, which is managed 100% through diet”.

Dr Reid is also the author of Fat, Stressed, and Sick: MSG, Processed Food, and America’s Health. She says: “The Reduced Excitatory Inflammatory Diet (REID) is a food lifestyle focused on reducing excitatory and inhibitory signalling imbalances (ie improving neurotransmitter balance) and reducing inflammation through a balanced whole food approach. Some of the most prevalent excitatory and inflammatory foods are gluten, casein (a class of proteins found in dairy), soy, corn (to a lesser extent) and ready-to-eat or commercially processed foods with various food additives, particularly those containing free glutamate and aspartate. These foods can be problematic because of their high concentration of unbound/free glutamate (glutamic acid). Unbound or free glutamate (aka MSG) is most commonly found in processed foods as a food additive or created as a by-product of commercial food manufacturing processes”. The book is available in our Food for the Brain bookstore: here.

The parents put the girls on a strictly gluten-free, casein-free diet that was low in sugar and had no exposure to artificial colours, dyes, or ultra-processed foods. They emphasised organic, unprocessed, freshly prepared, and home-cooked food from local sources when possible.

The twins took a number of dietary supplements, including omega-3 fatty acids, a multivitamin, vitamin D, carnitine and 5-methyltetrahydrofolate, plus individualised homoeopathic remedies. They also used lab tests and genomic information to select nutritional supplements based on the twins’ DNA.

There were some common findings, such as impaired serotonin metabolism and a recommendation that the girls be fed a diet rich in tryptophan to upregulate serotonin production, as well as consume foods rich in vitamins B12, B6 and folate. Both twins had several genetic variants associated with a higher risk of systemic inflammation.

The mother was advised to feed the children foods that are high in betaine and choline, as well as to supplement with Lion’s mane and resolvins (found in fatty fish). However, each girl also had unique needs. P had variants that suggested an increased need for vitamin D. L had several variants associated with neuroinflammation, oxidative stress and compromised detoxification. Advice was provided to support glutathione production.

Both girls had the most sessions of any intervention with an occupational therapist who focused on the specialised technique of neuro-sensory motor reflex integration developed by Dr Svetlana Masgutova, PhD.

Eventually the parents’ research led them to check their home for air quality, mould and moisture. 

In October of 2022, they brought in a Building Biology Environmental Consultant. The consultant tested the home’s indoor air quality, evaluated possible signs of moisture intrusion, and identified other potential sources of toxicants. Air tests for mould were reported to be “very clean”. However, thermal imaging and moisture metre readings suggested the family was encouraged to further evaluate several areas of the home, which suggested water damage. A window in the twins’ bedroom was one area needing more evaluation.

Both girls were seen by a cranial osteopath. The family decided to pursue osteopathic care for L and not for P. L visited an osteopath at regular intervals in 2023 and saw notable benefits.

Outcomes

Twin L’s ATEC (Autism Treatment Evaluation Checklist) scores improved dramatically, from 76 in March 2022 to 32 in October 2023, and then remained relatively stable at 34 in March 2024. Twin P’s ATEC scores also improved dramatically, from 43 in March 2022 to 4 in October 2023, remaining stable at 4 in March 2024.

“In addition to the twins’ improved ATEC scores, numerous other behavioural and social improvements were noted after the implementation of the interventions”, the paper reports. Both L and P’s eye contact, language, and attention had all improved noticeably by autumn 2022. “This was accompanied by participation in a toddler play group three days per week and ultimately attending pre-school three days per week in Fall 2023″. 

Conclusions & future progress

The University of Maryland team give full credit to the parents’ commitment and drive in achieving these results for their twins. They also acknowledge that this level of complex and sustained treatment may be impossible for many families to take on.

“For instance, the cost of the healthy lifestyle modifications and out-of-pocket costs of care of the numerous practitioners and laboratory assessments in this case would be financially prohibitive to many families. Access to healthy foods and the types of practitioners contributing to this therapeutic approach may also be limited for many families”.

However, they conclude: “It has become increasingly clear that ASD treatment is not one-size-fits-all, and that personalised, multi-modality treatment approaches to help address the total load of stressors are likely required to achieve optimal outcomes”.

This case study does not suggest that all autism has the same underlying causes, nor that every autistic individual requires treatment or wishes to change who they are. Autism is a broad spectrum, and experiences vary considerably from person to person. As a single published case study, its findings cannot be generalised. However, it highlights the possibility that, for some children with complex medical and nutritional needs, identifying and addressing underlying biological factors may contribute to meaningful improvements in health, functioning, communication and quality of life. Further research is needed to determine which approaches may be beneficial, for whom, and under what circumstances.

Through initiatives such as Smart Kids & Teens, alongside our wider work in dementia prevention and lifelong brain health, Food for the Brain continues to explore the evidence on how nutrition and lifestyle may support optimal brain function at every stage of life.

Food for the Brain is a charity dedicated to helping people protect and optimise their brain health throughout life. By becoming a FRIEND for just £50 a year, you’ll support this mission while gaining access to our COGNITION Brain Upgrade Programme, live expert-led webinars, monthly coaching workshops, and practical tools designed to help you put the science of brain health into action.

Other resources:

Save 25% off ICHAN magazine
Want to read more about Autism? Read our ‘Is Autism Genetic?’
Can the Symptoms of Autism be Reversed?
Can the Symptoms of Autism be Reversed? Conference report.
Autistic Children are Three and a Half Times More Likely to Have High Homocysteine

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By Patrick Holford

In terms of a cost-benefit ratio, Lecanemab has to be one of the worst in history.

Reported in the media this week as a ‘breakthrough Alzheimer’s medication’ – is this really the case?

On the benefit side those in the drug company’s own trial got statistically slightly less worse after 18 months of treatment versus placebo. No-one got better. The scale of improvement was not enough to be clinically significant and “does not necessarily reflect a meaningful improvement for patients or their families” according to the British Medical Journal editorial [1]. Given that almost all drug company’s own trial perform better than independent research this is likely to be an over-estimate of benefit not an under-estimate. At best it means delaying the progress of the disease by a few months.

The worst cost is that a quarter of those on the drug got either brain swelling or bleeding.
Three participants in the trial died as a consequence. Also there was accelerated brain shrinkage compared to placebo. Due to these horrendous risks patients getting the twice monthly IV infusions will need to have brain scans to check for brain bleeding and swelling.

The drug itself will cost about £25,000 a year but, with the medical costs, it may actually cost the patients or the NHS as much as double this. That is why the NHS’s watchdog NICE have rejected it “Lecanemab provides on average four to six months’ slowing in the rate of progression from mild to moderate Alzheimer’s disease, but this is just not enough benefit to justify the additional cost to the NHS,” said Helen Knight, director of medicines evaluation at NICE. The Telegraph have stated that an inside source says other anti-amyloid drug treatments would be similarly blocked for NHS use due to bad cost benefit ratio.

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The biggest problem…

The biggest lie reported in the papers is that ‘this is the first treatment that has been found to curb the condition’, says the Mail and ‘the first drug to slow down Alzheimer’s”, says the Telegraph.

It isn’t.

Inexpensive and safe B vitamins given to those with raised homocysteine (about half of all over age 65) have produced far greater clinical improvements to those with pre-dementia. In fact, a third had no clinical dementia rating at the end of the year – in other words were no longer diagnosable with dementia.

Similarly encouraging benefits have been shown when omega-3 fish oil supplements have been given to those with already low homocysteine (due to insufficient levels of B vitamins) – up to three times that of Lecanemab.[2] In addition, the omega-3 and B vitamin combo reported up to 73% less brain shrinkage, not more shrinkage reported with this drug. This gold-standard evidence, from studies at the University of Oxford by Professor of Pharmacology David Smith, is simply being ignored.

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The choice: safe supplementation or risk of brain bleed…

So, that’s the choice for dementia sufferers.

Safe supplements that might cost you £100 a year, reduce the rate of brain shrinkage and deliver clear clinical improvements. Or Lecanemab, that carries a small risk of death, a considerable risk of brain swelling or bleeding, has not shown improvement in a single patient, but is likely to deliver a small, clinically meaningless slowing down of worsening symptoms. NICE has not approved it for the NHS because it costs £50,000 a year and as it only slows down dementia progression by a couple of months (as reported by the BBC).

The caveat for the drug is that the risks for those with the ApoE4 gene variant – about a quarter of people are deemed too high. The caveat for the B vitamins is that those with normal homocysteine levels (below 10 mcmol/l), which is less than half those over 65, may not benefit from the B vitamin treatment. Homocysteine is a simple test any GP can do. Similarly, omega-3 fish oils may not benefit those with an omega-3 index above 8% (and highly likely to benefit those with an omega-3 index of 4% or less.)

That is why we recommend those wishing to prevent dementia test both omega-3 index and homocysteine and why we offer accurate, at-home test kits to help you reclaim your brain. When you support our charity by buying a test kit you become one of our Citizen Scientists and take part in our essential prevention-focused research and includes a free online Cognitive Function Test and the COGNITION questionnaire which calculates your future Dementia Risk Index, then advising you how to lower it.

Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References
[1] BMJ 2022;379:o3010 http://dx.doi.org/10.1136/bmj.o3010
[2] https://brainhealthcheck.foodforthebrain.org/campaigns/alzheimers-prevention/omega-3-
and-b-vitamins/

by Patrick Holford

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Drugs won’t prevent dementia.

Last week’s Lancet Commission on dementia prevention is facing mounting criticism, for favouring targets for drugs including lowering cholesterol and amyloid and completely ignoring quick and easy wins such as supplementing omega-3, homocysteine lowering B vitamins and reducing sugar intake. A very recent report from Cambridge University scientists says that the benefits of new anti-amyloid treatments may be outweighed by the costs and risk of side-effects such as shrinking brain matter.

US National Institutes of Ageing researcher Dr Madhav Thambisetty warned that trial participants lost up to three teaspoons of brain volume. ‘It is far from clear these drugs can ever significantly reduce dementia morbidity at scale’ report the scientists in the journal Alzheimer’s and Dementia and reported in the Telegraph this week.

The Lancet Commission completely ignored, for the third time since 2017, the indisputable evidence that inexpensive B vitamins, given to those with raised homocysteine (half the older population) reduced brain shrinkage in a year by up to 73%, the highest effect being in those with sufficient omega-3 DHA, as well as the substantial evidence in favour of omega-3.

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Our scientists in the Alzheimer’s Prevention Expert Group are actively preparing response letters to the Lancet – and once done, we will give a full report. Against this backdrop of minuscule effect that ‘is so small it would not be recognisable by doctor or patient’ and the need for specialist brain scans with each injection due to one in four getting brain bleeding or swelling we see press-mongering dressing up drugs as prevention; press reports ‘big up’ these unethical drug approaches, as yet unlicensed in the UK, in the guise of prevention – ‘UK needs Covid-style push on dementia drugs’  reports the guardian.

Prevention does not mean drugs, it means tackling the root causes of cognitive decline and brain shrinkage, which is what we are doing at Food for the Brain through our FREE Cognitive Function Test.

“We sent them the indisputable evidence and they ignored it.” Here’s how the Lancet Commission halved the true impact of dementia prevention, says our Founder, Patrick Holford.

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Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

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Do supplements really help when it comes to cognitive decline or are they money wasted down the toilet?!

We believe that the science supports the use of correct supplementation in order to reduce risk of dementia and Alzheimer’s – so what is going on and what does the research really say?

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The WHO report saying supplements are ‘not recommended’

A 2018 report by the WHO states: ‘Vitamins B and E, PUFA and multi-complex supplementation should not be recommended to reduce the risk of cognitive decline and/or dementia.’ 

This 2018 WHO review makes no reference at all to the effect of B vitamins in slowing brain atrophy (1) and in improving cognition (2) in the rather large sub-group, estimated to be up to half of those over 65, with raised homocysteine. After all, why would B vitamins be expected to have an effect in those not deficient?

On closer inspection, three of the four cited studies in the WHO document are actually one meta-analysis (which is a statistical process of analysing and combining results from several similar studies). It cites only one paper which considered B vitamins (the one part-funded by Alzheimer’s Research UK) which showed a clear effect of B vitamins improving cognition in those with raised homocysteine, and one study on omega-3 DHA, which also shows clear benefit as stated in the studies summaries. Thus, it misrepresented the study that ARUK part funded on B vitamins as negative, when they had a clearly positive effect. 

The only cited B vitamin study (2) states, “The mean plasma total homocysteine was 30% lower in those treated with B vitamins relative to placebo. B vitamins stabilised executive function (CLOX) relative to placebo. There was significant benefit of B-vitamin treatment among participants with baseline homocysteine above the median in global cognition, episodic memory and semantic memory. Clinical benefit occurred in the B-vitamin group for those in the upper quartile of homocysteine at baseline in global clinical dementia rating score… In this small intervention trial, B vitamins appear to slow cognitive and clinical decline in people with mild cognitive impairment (MCI), in particular in those with elevated homocysteine.”

The only cited study on omega-3 fish oils (3) states, “The fish oil group showed significant improvement in short-term and working memory.” The 12-month change in memory was significantly better in the fish oil group. This study suggested the potential role of fish oil to improve memory function in MCI subjects.

So, even based on its own cited evidence, the benefit of both B vitamins and omega-3 fish oils is supported.

How the WHO statement then recommends the opposite, ‘Vitamins B and E, PUFA and multi-complex supplementation should not be recommended to reduce the risk of cognitive decline and/or dementia.’ beggars belief. But the real problem is not the shoddy research, from 2015, used to produce this report but that it is out of date. The WHO ‘rules’ for this report was to ignore any study that was more than 5 years old, yet the WHO authors republished this same report, with the same conclusions, in 2022, by then redundant according to its own rules!

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What we’ve learned since 2018

Also, much has been learnt, and published, since 2018. There is now evidence that homocysteine lowering B vitamins are most effective in those with sufficient omega-3 status and omega-3 fish oils are most effective in those with low homocysteine. This is clinical confirmation of the known mechanism of co-dependence and illustrates why the WHO document is now out of date. We prefer published, peer-reviewed reviews such as the editorial in the American Journal of Clinical Nutrition in 2021 (4) and a meta-analysis in 2023 (5).

Additionally, since 2018, there have been at least 17 studies (6-22), including both randomised controlled trials and cohort studies which show benefit of either omega-3 fish oil supplementation, or higher intake from seafood with resultant higher omega-3 blood levels, in reducing risk for and incidence of dementia or cognitive decline.

This is another example showing why the WHO document is no longer current and relevant. Yet leading Alzheimer’s charities such as the Alzheimer’s Society and Alzheimer’s Research UK (ARUK – who part funded the highly effective B vitamin trial) still refer to this redundant report.

With regard to multivitamins, the latest meta-analysis states (7), “The meta-analysis of COSMOS substudies showed clear evidence of multivitamin-mineral benefits on global cognition and episodic memory; the magnitude of effect on global cognition was equivalent to reducing cognitive ageing by 2 years”. B vitamins, given to those with raised homocysteine, are much more effective than multivitamins given to all – and more effecctive in those with sufficient omega-3 status.

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Summary

In conclusion, the 2018 WHO report is so sloppy, and out of date – by its own rules. It would be wise for WHO to withdraw this misleading report and certainly for both ARUK and the Alzheimer’s Society and any other Alzheimer’s or dementia organisations to stop referring to it in the context of omega-3, B vitamins or multivitamins, if they are to maintain credibility in being science-based.

Note: Many people are not aware that the WHO is no longer only funded by donations from the countries that it is supposed to serve but is now also privately funded, with the second largest funder being the Bill Gates Foundation, which accounts for 10% of its budget, leading to questions over influences on its agenda. 

Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References

1. Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PloS one 2010;5(9):e12244.

2. de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. International journal of geriatric psychiatry 2012;27(6):592-600.

3. Lee et al 2013 – https://pubmed.ncbi.nlm.nih.gov/22932777/

4. Smith AD, Jernerén F, Refsum H. ω-3 fatty acids and their interactions. Am J Clin Nutr 2021;113(4):775-8.

5. Fairbairn P, Dyall SC, Tsofliou F. The effects of multi-nutrient formulas containing a combination of n-3 PUFA and B vitamins on cognition in the older adult: a systematic review and meta-analysis. The British journal of nutrition 2023;129(3):428-41.

6. Liu X, Zhuang P, Li Y, Wu F, Wan X, Zhang Y, et al. Association of fish oil supplementation with risk of incident dementia: A prospective study of 215,083 older adults. Clinical nutrition (Edinburgh, Scotland) 2022;41(3):589-98.

7. Vyas CM, Manson JE, Sesso HD, Cook NR, Rist PM, Weinberg A, et al. Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial and meta-analysis of 3 cognitive studies within COSMOS. Am J Clin Nutr 2024;119(3):692-701.

8. Jerneren F, Cederholm T, Refsum H, Smith AD, Turner C, Palmblad J, et al. Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer’s Disease: The OmegAD Study. Journal of Alzheimer’s disease : JAD 2019.

9. Rouch L, Virecoulon Giudici K, Cantet C, Guyonnet S, Delrieu J, Legrand P, et al. Associations of erythrocyte omega-3 fatty acids with cognition, brain imaging and biomarkers in the Alzheimer’s disease neuroimaging initiative: cross-sectional and longitudinal retrospective analyses. Am J Clin Nutr 2022;116(6):1492-506.

10. He X, Yu H, Fang J, Qi Z, Pei S, Yan B, et al. The effect of n-3 polyunsaturated fatty acid supplementation on cognitive function outcomes in the elderly depends on the baseline omega-3 index. Food & function 2023;14(21):9506-17.

11. Doughty KN, Blazek J, Leonard D, Barlow CE, DeFina LF, Omree S, et al. Omega-3 index, cardiorespiratory fitness, and cognitive function in mid-age and older adults. Prev Med Rep 2023;35:102364.

12. Loong S, Barnes S, Gatto NM, Chowdhury S, Lee GJ. Omega-3 Fatty Acids, Cognition, and Brain Volume in Older Adults. Brain Sci 2023;13(9).

13. Maltais M, Lorrain D, Léveillé P, Viens I, Vachon A, Houeto A, et al. Long-chain Omega-3 fatty acids supplementation and cognitive performance throughout adulthood: A 6-month randomized controlled trial. Prostaglandins, leukotrienes, and essential fatty acids 2022;178:102415.

14. Andriambelo B, Stiffel M, Roke K, Plourde M. New perspectives on randomized controlled trials with omega-3 fatty acid supplements and cognition: A scoping review. Ageing Res Rev 2023;85:101835.

15. Wei BZ, Li L, Dong CW, Tan CC, Xu W. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers. Am J Clin Nutr 2023;117(6):1096-109.

16. Grande de França NA, Díaz G, Lengelé L, Soriano G, Caspar-Bauguil S, Saint-Aubert L, et al. Associations Between Blood Nutritional Biomarkers and Cerebral Amyloid-β: Insights From the COGFRAIL Cohort Study. The journals of gerontology Series A, Biological sciences and medical sciences 2024;79(1).

17. Sasaki N, Jones LE, Carpenter DO. Fish consumption and omega-3 polyunsaturated fatty acids from diet are positively associated with cognitive function in older adults even in the presence of exposure to lead, cadmium, selenium, and methylmercury: a cross-sectional study using NHANES 2011-2014 data. Am J Clin Nutr 2024;119(2):283-93.

18. van Soest APM, van de Rest O, Witkamp RF, Cederholm T, de Groot L. DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial. European journal of nutrition 2022;61(7):3731-9.

19. Gao J, Fan H, Wang X, Cheng Y, Hao J, Han S, et al. Association between serum omega-3 PUFAs levels and cognitive impairment in never medically treated first-episode patients with geriatric depression: A cross-sectional study. J Affect Disord 2024;346:1-6.

20. He Y, Huang SY, Wang HF, Zhang W, Deng YT, Zhang YR, et al. Circulating polyunsaturated fatty acids, fish oil supplementation, and risk of incident dementia: a prospective cohort study of 440,750 participants. GeroScience 2023.

21. Chedid G, Malik A, Amangurbanova M, Khraishah H, Welty FK. Docosahexaenoic Acid Levels and Omega-3 Index, but Not Eicosapentaenoic Acid Levels, Are Associated With Improved Cognition in Cognitively Healthy Subjects With Coronary Artery Disease. Arteriosclerosis, thrombosis, and vascular biology 2022.

22. Duchaine CS, Fiocco AJ, Carmichael P-H, Cunnane SC, Plourde M, Lampuré A, et al. Serum ω-3 Fatty Acids and Cognitive Domains in Community-Dwelling Older Adults from the NuAge Study: Exploring the Associations with Other Fatty Acids and Sex. The Journal of nutrition 2022;152(9):2117-24.

By the Alzheimer’s Prevention Expert Group

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You may have heard of a search for new tests to find those most likely to get Alzheimer’s disease? But is this misdirected?

Perhaps so, according to the Alzheimer’s Prevention Expert Group (APEG) –  a collaboration of top UK, American and Chinese academics (which we are a part of – find out more here) who consider this to be “..a misguided waste of money”. 

Controversially, their stance challenges the major thrust of charities such as Alzheimer’s Research (ARUK), which strongly supports search for a reliable test for the disease.

APEG explains that there is already a widely used way to spot failing memory and thinking skills  – hallmarks for dementia and Alzheimer’s. These include a neuropsychological test battery (NTB) and a validated Cognitive Function Test (CFT) similar to the one we provide free. Both are routinely used in memory clinics to diagnose mild cognitive impairment and support the diagnosis of dementia.

Over the last decade the charity Food for the Brain has used the Cognitive Function Test to find people at risk and advise them how to reduce their risk with simple dietary and lifestyle changes. 

Nearly half a million people to date have been tested, with someone taking the test every 2 minutes!

When does Cognitive Decline begin?

Cognitive function declines steadily from the age of 18. This means that it is possible to spot individuals whose cognitive function is dropping off faster than the average, giving time to encourage preventative actions with personalised advice on their diet and lifestyle changes.

Alzheimer’s, which makes up two-thirds of dementia cases, involves the shrinking of certain areas of the brain as neurons die off. It can be detected with a specialised brain scan several years before a diagnosis. These ‘PET’ scans can be used to diagnose Alzheimer’s and/or vascular dementia.  The trouble is that such scans are expensive and not likely performed early enough to discover those ‘at risk’. 

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What about p-tau?

As well as shrinkage, another marker for Alzheimer’s is a toxic protein called p-tau. This creates clumps of tangled nerves in the brain. These can be found in the fluid that bathes the brain but again there is a problem. Detecting it can be done with a lumbar puncture, but this is a risky and expensive process and certainly not suitable to test tens of thousands of people. 

At first sight, if a blood test could identify those heading towards Alzheimer’s earlier this could be a cheaper and less invasive alternative to such scans. However, the search is likely driven by a quite different ulterior motive – to create and sell drugs – much like cholesterol and statins. What’s more it’s unlikely to be an improvement!

A recent New York Times article pointed out that such a test would result in people being diagnosed with ‘pre’ Alzheimer’s, even if they have no obvious symptoms. That’s because having the marker would be considered enough to justify a diagnosis of the disease or, at least, the prescription of a drug.

This is what happens with amyloid protein. Amyloid forms plaque in the brains of those with Alzheimer’s. The latest drugs, such as lecanemab and aducanumab, remove this. But not all those with Alzheimer’s have plaque, and people can develop dementia without plaque. What’s more none of these drugs have a clinically significant effect, and they come with the risk of severe adverse effects, including death from brain bleeding and swelling, especially in those with a history of stroke.

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A very cheap and safe alternative…

Perhaps the most convincing reason why the new blood marker hunt is “misguided” is that there is something very cheap and very safe that can prevent the accumulation of p-tau tangles in the brain – B vitamins.

Suppose you are not taking in enough B6, folate or B12, which becomes harder to absorb as you get older, blood levels of a toxic amino acid called homocysteine rise. This increases the level of p-tau and inhibits the brain from clearing it. According to pharmacology professor David Smith, a member of APEG and our Scientific Advisory Board: “Homocysteine is not a diagnostic marker for dementia but it is a modifiable risk factor. Raised levels of homocysteine account for some 20% of dementia cases and homocysteine testing is relatively inexpensive and available.”

Smith, who was second in charge at Oxford University’s School of Medical Sciences, ran the VITACOG trial which found that high doses of B vitamins given to people with Mild Cognitive Impairment (MCI) and high homocysteine, not only slowed the rate of brain cell death by up to 73% but also arrested cognitive decline.

He, and his APEG colleagues, favour using a Cognitive Function Test, to identify those at risk. Then, testing risk factors and biomarkers such as homocysteine to be included in the research, with funds being made available for testing blood biomarkers because this is one thing you can actually do something about. 

Other useful tests for risk factors include omega-3 and vitamin D levels, since low levels of these nutrients also increase risk; also HbA1c, the standard measure used to diagnose diabetes, since lower levels help protect the brain and high levels indicate those who need to reduce their intake of sugar and processed foods. These tests are corroborative rather than diagnostic but importantly identify prevention actions that people can take. 

We offer at home, accurate pin prick testing for Vitamin D, HbA1c, Omega-3 and Homocysteine (available in US, EU & UK) – order here to be a part of our research and to support our charitable work 

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The new paradigm.

This two-step paradigm of:

1. Testing cognitive function early – you can do so here.

2. Then do further blood tests such as homocysteine, omega-3, vitamin D and HBA1c for glucose control that help guide diet and lifestyle prevention, which is available right now. Order your DRIfT test here

So keep things simple and start today!

Complete our validated Cognitive Function Test, then order your blood tests and be a part of our Citizen Science research and movement.

Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References

The VITACOG trials, evidence for homocysteine as causal and lowering it with B vitamins as disease modifying and a consensus statement regarding this evidence, in the Journal of Alzheimer’s Disease, is here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836397/

The validation of foodforthebrain.org’s Cognitive Function Test in the International Journal of Geriatric Psychiatry is here: https://onlinelibrary.wiley.com/doi/abs/10.1002/gps.3993

The evidence in relation to p-tau and homocysteine is here: https://brainhealthcheck.foodforthebrain.org/the-p-tau-delusion/

Widespread omega-3 deficiency is cranking up aggression.

Children flying off the handle, fighting at school, increasing rates of ADHD, depression and violent offences, perhaps even more global conflicts – a new study suggests that something very simple could be cranking up aggression. 

Less omega-3 from seafood. 

A study of 4,000 participants over 28 years, has found a clear reduction in aggression when children and adults are given either omega-3 supplements or eat more fish. According to advisor to the US National Institutes of Health, Dr Joseph Hibbeln, a country’s incidence of homicide, depression and suicide ‘tracks’ their seafood consumption. In Australia, a prisoner’s omega-3 index, measured in a pin prick blood test predicts anger, aggression and AHDH. A study in UK prisons found that giving omega-3 supplements to prison inmates, compared to placebos, reduced violent offences by more than a third.

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Omega-3 support in community, clinics and our criminal justice system

“Based on this evidence our considered opinion is that there is now sufficient evidence to begin to implement omega-3 supplementation to reduce aggression in children and adults, whether the setting is community, the clinic or criminal justice system” say the study authors Adrian Raine and Lia Brodrick from the University of Pennsylvania.

“There is now clear evidence that not only are low blood omega-3 levels associated with increased aggressive behaviour but supplementation with fish oil can reduce aggressive tendencies in adults and children.” says Professor William Harris from the Fatty Acid Research Institute in the US, one of our scientific advisors. 

This is why we now offer an easy, pin prick home test for omega-3 to go alongside our free online Cognitive Function Test and diet and lifestyle questionnaire that assesses omega-3 status and other factors that are important to your brain function and development.

We need to treat it the same as vitamin D

“Less than 5% of children in the UK achieve the basic recommended levels of omega-3” says Dr Simon Dyall, clinical neuroscientist at the University of Roehampton who also advises the charity “Even these recommendations are too low, according to the evidence regarding brain function. Many children eat no fish at all and don’t supplement omega-3. The evidence is more than sufficient to recommend that we take action now to protect our children’s brains.”

In the same way that GPs test vitamin D we need to test both children and adults presenting with ADHD, depression, anxiety and aggression for their omega-3 index. 

In Japan, where a lot of seafood is eaten, the level is 10% and rates of violence, depression, suicide and Alzheimer’s are a fraction of those in the UK. People in the UK and US average 4% on the pinprick omega-3 index. You need over 8% for a healthy brain. Many offenders test as low as 2%.

You can’t build a healthy brain without omega-3. Our children are suffering. There is more than enough evidence of this.

Yet there is no government recommendation in the UK of how much omega-3 we need. The advice to eat fish twice a week is neither enough, nor heeded. 

That is why we are helping people help themselves by testing their omega-3 index and advising them accordingly. But we need this done on a national scale, especially in poorer communities.

If doctors can test and prescribe vitamin D, why can’t they test and prescribe omega-3?

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Actions:

Find out your omega-3 status (or your child’s, partner or entire family) with the accurate, simple at home blood test. Order here to be a part of our research and support our charity.
Find out more about our Smart Kids & Teen programme we are developing (and need funding for!)
Complete the Cognitive Function Test to get personalised information on how you can upgrade your brain.

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Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References

A. Raine, L. Brodrick ‘Omega-3 supplementation reduces aggressive behavior: A meta-analytic review of randomized controlled trials’Aggression and Violent Behavior, 2024, 101956 doi.org/10.1016/j.avb.2024.101956.

Hibbeln JR. Depression, suicide and deficiencies of omega-3 essential fatty acids in modern diets. World Rev Nutr Diet. 2009;99:17-30. doi: 10.1159/000192992.

Meyer BJ, Byrne MK, Collier C, Parletta N, Crawford D, Winberg PC, et al. (2015) Baseline Omega-3 Index Correlates with Aggressive and Attention Deficit Disorder Behaviours in Adult Prisoners. PLoS ONE 10(3): e0120220. doi:10.1371/ journal.pone.0120220 

Gesch CB, Hammond SM, Hampson SE, Eves A, Crowder MJ. Influence of supplementary vitamins, minerals and essential fatty acids on the antisocial behaviour of young adult prisoners. Randomised, placebo-controlled trial. Br J Psychiatry. 2002 Jul;181:22-8. doi: 10.1192/bjp.181.1.22.

Yesterday’s announcement by the Alzheimer’s Society that dementia will cost the UK almost £91bn a year by 2040 highlights why prevention has to be the way forward. (See the Guardian Article here) 

“Dementia’s devastating impact is colossal – on the lives of those it affects, on the healthcare system and on the economy”, said Kate Lee, the Alzheimer’s Society’s chief executive who is calling for the ‘urgent need to prioritise early diagnosis.’ We know here at Food for the Brain, that these costs, could easily be halved by focussing on prevention. A recent study from the UK Biobank data and conducted by two of the charity’s scientific advisors, China’s leading dementia prevention Professor Jin-Tai Yu from Fudan University, and by former deputy head of Oxford University’s school of medical science, Professor David Smith, concluded that “up to 73% of dementia can be prevented” right now by focussing on prevention. (1) The Biobank research, however, didn’t measure homocysteine and thus excluded one of the most easily actioned prevention steps – lowering homocysteine with B vitamins – which the US National Institutes of Health says accounts for 22% of the risk for Alzheimer’s. (2)

Patrick Holford our CEO says “the reality is that over 80 percent of dementia could be prevented right now if we took prevention seriously. The quickest wins are testing people, for free, for cognitive function then identifying those at risk and why they are at risk. Dementia is diagnosed with a cognitive function test and changes occur at least thirty years before a diagnosis. This is doable right now with no cost at all.” We have tested 425,000 people to date with 200 taking the free, validated test every day. This is followed by a ‘cognition’ questionnaire that shows the person exactly what is driving their future risk. 

The quick wins are increasing omega-3 fats from seafood and supplements, and lowering high homocysteine with B vitamins. The higher a person’s omega-3 level the better their cognition and the more brain density they have, according to research from Loma Linda University in California. (3) “Half of those over 65 have raised blood homocysteine which is easily lowered with a 10p a day B vitamin supplement.” says Holford “The health economist at Oxford University costed the saving just from this one prevention step as £50 million a year. (4) B vitamins with omega-3 have already been shown to reduce the annual rate of brain shrinkage by 73% in those at risk.” (5) The other big driver, he says, is sugar and ultra-processed foods. “Diabetes doubles dementia risk and accelerates brain shrinkage (6) but we can pick up those with the beginnings of blood sugar problems in mid-life with high but ‘normal’ levels of blood sugar which has been shown to increase Alzheimer’s risk by 14.5%. (7)” he says.

We also offer a ‘home-test kit that those at risk can use to measure homocysteine, omega-3, vitamin D and sugar balance (HbA1c – the test used by GPs to diagnose diabetes) then tells the individual what actions to take to protect their brain and improve their cognition. Research shows that having a low vitamin D level increases triples risk for Alzheimer’s (8) and those who supplement vitamin D cut Alzheimer’s risk by a third. (9)

“None of the major charities are taking prevention and the role of nutrition in brain health seriously.” says Holford, author of a new book Upgrade Your Brain which explains how to dementia-proof your diet and lifestyle. “Kate Lee of the Alzheimer’s Society told me they spend nothing on prevention. Alzheimer’s Research UK told us they spend 4.3% of all research money on non-drug prevention. When 80 percent is preventable surely at least half of research funds should be spent on non-drug prevention? We do not need to wait for more research. Dementia is diagnosed using a cognitive function test done in memory clinics. But by the time a GP refers a patient, it is often too late. We offer exactly this cognitive function test for free, online at foodforthebrain.org. There is no need to wait for a mythical blood test to ‘diagnose early’. 

This is like having a blood test to diagnose how unfit you are.” says Holford. “Even if this existed, the critical question for those at risk is how to reduce it. All that is needed is to take prevention seriously. It is not difficult. The government have pledged £166 million for dementia a year but no-one can tell us if any of this is actually to be spent on prevention research or putting prevention into action.”

We are supporting World Alzheimer’s Prevention Day – see alzheimersprevention.info – on Wednesday (May 15^th), with the support of thirty of the world’s leading dementia prevention experts.

Where to start in reducing your risk:

Take the FREE Cognitive Function Test here
Order your at-home blood tests here
Support our research and become a FRIEND here
Participate in Alzheimer’s Prevention Day

—

Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References

1 Zhang, Y., Chen, SD., Deng, YT. et al. Identifying modifiable factors and their joint effect on dementia risk in the UK Biobank. Nat Hum Behav 7, 1185–1195 (2023).
2 Beydoun MA, Beydoun HA, Gamaldo AA, Teel A, Zonderman AB, Wang Y. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 2014 Jun 24;14:643. doi: 10.1186/1471-2458-14-643. PMID: 24962204; PMCID: PMC4099157.
3 Loong, S.; Barnes, S.; Gatto, N.M.; Chowdhury, S.; Lee, G.J. Omega-3 Fatty Acids, Cognition, and Brain Volume in Older Adults. Brain Sci.2023,13,1278. https://doi.org/ 10.3390/brainsci13091278.
4 https://doi.org/10.1016/j.trci.2016.07.0
5 Jernerén F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H, Smith AD (2015). Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. Am J Clin Nutr. 2015 Jul;102(1):215-21
6 Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. 2004 May;61(5):661-6. doi: 10.1001/archneur.61.5.661. PMID: 15148141; see alsoYaffe K, Blackwell T, Kanaya AM, Davidowitz N, Barrett-Connor E, Krueger K. Diabetes, impaired fasting glucose, and development of cognitive impairment in older women. Neurology [Internet]. 2004 Aug 24 [cited 2022 Mar 16];63(4):658–63. Available from: https://n.neurology.org/content/63/4/658; see also Tiehuis AM, van der Graaf Y, Visseren FL, Vincken KL, Biessels GJ, Appelman APA, et al. Diabetes Increases Atrophy and Vascular Lesions on Brain MRI in Patients With Symptomatic Arterial Disease. Stroke. 2008 May;39(5):1600–3; see also Samaras K, Lutgers HL, Kochan NA, Crawford JD, Campbell LV, Wen W, et al. The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study. AGE [Internet]. 2014 Jan 9 [cited 2022 Aug 5];36(2):977–93. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039246/
7 Zhang X, Tong T, Chang A, Ang TFA, Tao Q, Auerbach S, Devine S, Qiu WQ, Mez J, Massaro J, Lunetta KL, Au R, Farrer LA. Midlife lipid and glucose levels are associated with Alzheimer’s disease. Alzheimers Dement. 2023 Jan;19(1):181-193. doi: 10.1002/alz.12641. Epub 2022 Mar 23. PMID: 35319157; PMCID: PMC10078665.
8 Vitamin D deficiency increases the risk of Alzheimer’s.112 In a study in France involving 912 elderly patients followed for 12 years, a total of 177 dementia cases occurred. Those with low vitamin D levels had a nearly three-fold increased risk of Alzheimer’s.113
9 Ghahremani M, Smith EE, Chen HY, Creese B, Goodarzi Z, Ismail Z. Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status. Alzheimers Dement (Amst). 2023 Mar 1;15(1):e12404. doi: 10.1002/dad2.12404. PMID: 36874594; PMCID: PMC9976297.

Everybody wants a cure for Alzheimer’s. 

The medical industry has spent around $100 billion searching for one and so far, come up relatively empty-handed with over thirty failed drug trials. The focus has been on drugs that lower two of the chemical compounds associated with Alzheimer’s and dementia in general – amyloid and p-tau, a pair of messed up proteins that can lead to plaques in the brain and tangled nerves. There is a third compound – an amino acid called homocysteine – that becomes toxic if you have too much, that the drug industry and the Alzheimer charities don’t talk about, for reasons that will become clear.

The actual clinical measures that are used to diagnose Alzheimer’s are a decline in cognitive function and shrinkage of the central area of the brain called the medial temporal lobe. Both changes in cognitive function and brain shrinkage can be picked up thirty years before a diagnosis of Alzheimer’s is made.  

So now a £10 million study is underway to see if a blood test for p-tau, or amyloid, will ‘predict’ if you are more likely to develop the disease and there are plans for a major programme to identify those at risk so they can be treated as early as possible.  This sounds sensible but there are serious drawbacks. To begin with not everyone with raised p-tau or amyloid go on to develop Alzheimer’s. 

This means, as a recent article in the New York Times entitled, ‘Apparently healthy but diagnosed with Alzheimer’s,’ pointed out, people without a diagnosis or no brain scan showing shrinkage, could well be offered new drug treatments that are so far, only marginally better than placebos but can have awful adverse effects. 

These include brain bleeding or swelling which has occurred in more than one in four in the last two drug trials and resulted in seven deaths. Medical agencies in the US, EU and UK are reluctant to licence their use but are under a lot of pressure to do so. 

So thousands of desperate people with early stage Alzheimer’s or cognitive decline, hoping for a cure, are queuing up to join these drug trials because they perceive these drugs, that so far come with little or no benefit plus highly unpalatable side effects, are a better alternative than doing nothing.

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There are alternatives – you just haven’t been told about them!

But are there really no alternatives? Well, none that patients are routinely told about. They involve changes in diet and lifestyle that are very likely to improve your overall health, including that of your brain, and very unlikely to cause damaging side effects. 

Almost all money for research, pledged by governments and raised by Alzheimer’s charities, is going in the direction of drug treatments. Alzheimer’s Research UK’s (ARUK) website says “we exist for a cure”. Most of the money is going toward amyloid and p-tau related research, neither of which have been established as causal. In other words, high levels may just be a consequence of the disease process.

The same is not true for raised blood levels of homocysteine. If levels rise in the brain, it shrinks faster and cognitive abilities decline. If it goes down, they improve, and brain shrinkage slows. This means that it is causing the damage and so would logically be a target for treatment. The only way to do it, however, is with high dose B vitamins (B6, B12 and folate). Several gold standard, placebo-controlled trials have found this to be very safe and effective. But this approach is not patentable and so yields nothing like a drug profit.

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This is a much better biomarker than p-tau

But the benefits of treating homocysteine don’t stop there. It is a much better biomarker of risk for Alzheimer’s than plaque and p-tau both because it is more easily measured and more safely lowered. And when it is lowered, unlike those two, it actually improves cognitive function and slows brain shrinkage by as much as two thirds. It also helps to stop p-tau formation.

Routinely checking homocysteine levels could prevent thousands of cases. Just doing this “could save costs to the UK economy of approximately £60 million per year,” says Dr Apostolos Tsiachristas, Associate Professor in Health Economics at the University of Oxford. His research also estimated it would promote healthy longevity, adding 14 years to life expectancy. 

About half of people over 65 have a homocysteine level above 11 mcmol/l, which is where it starts to become damaging. In one study a third of those treated ended the study with no clinical dementia rating, meaning they could no longer be diagnosed with cognitive impairment. Those with sufficient omega-3 DHA, which is the most important structural fat in the brain, had 73% less brain shrinkage compared to placebo when given the B vitamin treatment. In contrast, in the last anti-amyloid treatment trial, brain shrinkage accelerated by about a fifth in those getting the drug, compared to placebo and not one person achieved a clinical dementia rating of zero.

It should be clear by now, after decades of scientific research that amyloid plaque is not a cause of Alzheimer’s, but a consequence. The same is likely to be true for p-tau tangles.

As an analogy, consider your teeth. Is plaque the cause of tooth decay?  Sure, flossing your teeth and getting the plaque scraped off by the dental hygienist helps, but what causes the plaque? The answer is a bad diet – in this case, one high in sugar and low in fibre. Despite fifty years of research, there is no ‘cure’ for tooth decay, but it can be prevented. The same concept applies to Alzheimer’s, which is as preventable as tooth decay with the right diet and nutrition and lifestyle – which also happens to include less sugar and more fibre.

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Alzheimer’s Prevention

How preventable is Alzheimer’s? It accounts for two thirds of dementia cases. The most conservative figure is 40% . More optimistic estimates say around 80%. Since only one in a hundred cases is caused by genes Alzheimer’s may be entirely preventable in those 99% who do not have the rare causative genes and act early enough to optimise all diet and lifestyle factors. It is not an inevitable consequence of the ageing process as evidenced by the fact that the majority of people don’t get it.

Why the difference in figures? It’s all to do with what is or isn’t included in prevention studies. The most widely used review for dementia prevention in the UK is the 2020 report of the Lancet Commission, authored by Professor Gill Livingston. Both this and the first edition in 2017 failed to even mention homocysteine, despite being repeatedly sent all the evidence of the undeniable beneficial effects of homocysteine-lowering B vitamins by the Oxford Project to Investigate Memory and Ageing (OPTIMA) at the University, headed by former Deputy Head of Medical Science, Professor David Smith.

This is a major and damaging error and has led to the widespread belief that B vitamin supplements are not part of the usual list of preventive actions. But it should be corrected, especially considering that a US National Institutes of Health study attributes 22% of the risk of Alzheimer’s to raised homocysteine. Also, the best study of all, looking at 396 studies in total, published in 2020, concluded: ‘Homocysteine-lowering treatment seems the most promising intervention for Alzheimer’s disease prevention.’

Other prevention studies you may have read are possibly based on data from the UK Biobank. This major research data bank also ignores homocysteine, not for any malevolent reason but simply because it wasn’t measured when it was enrolling people. So, one of the single biggest risk factors and arguably the simplest to change, is repeatedly ignored.

Given that a conservative half of Alzheimer’s cases could be prevented, shouldn’t half the available research money be spent on prevention? 

This certainly doesn’t happen at the moment. Of the three leading charities, two spend nothing on prevention. ARUK claims to spend 5% but none of this goes towards B vitamins or other brain-friendly nutrients such as omega-3 or vitamin D. They, too, ignore homocysteine, and the beneficial effects of lowering it with B vitamins, as first shown in a 2010 Oxford University study they actually helped fund!

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1+1=3

Prevention studies are almost always going to underestimate (never overestimate) the power of prevention due to excluding risk factors, but also because they largely ignore the ‘1+1=3’ compounding impact of interactive risk factors. B vitamins, for example, don’t work without sufficient omega-3 and omega-3 fish oils don’t work in people with raised homocysteine, because of a lack of B vitamins. This has been shown in four trials – in the UK, Holland, Sweden and China. The combination of B vitamins given to people sufficient in omega-3 DHA improved the reduction in brain shrinkage from 53% to 73%. 

Pollution exposure is a risk factor but, in those with lower homocysteine, this effect is much reduced. Poor sleep is a risk factor, but less so in those who exercise. 

For the past five years leading UK researchers, led by neurologist Professor Peter Garrard, who is the Director of the dementia research group in the St George’s, University of London Neuroscience Research Section, have tried to get funding to test the most promising combination – B vitamins and omega-3 – to no avail. Such a trial is badly needed and would cost a fraction of that being spent on amyloid or p-tau.

So. What if a person does everything right – enough B vitamins to keep homocysteine low, sufficient omega-3, low sugar, high fibre diet, enough vitamin D (Alzheimer’s is four times less likely in those with sufficient vitamin D), and an active physical, intellectual and social lifestyle, plus good sleep and not too much stress? 

The only ongoing study and database that assesses all these risk factors as well as including blood tests of four critical biomarkers, homocysteine, omega-3 index, vitamin D and HbA1c, which measures glucose control, is our COGNITION Biobank. We describe it as ‘citizen science’ because anyone can get involved doing a free online Cognitive Function Test, filling in a questionnaire about their diet, lifestyle and medical history, and sending in a blood sample from our home test kit available for purchase. 

So far, over 400,000 people have done our test. But, unlike the £10 million trial, funded by the People’s Lottery, the Gates Foundation, ARUK and the Alzheimer’s Society, it gets no funding. It is literally funded by our citizen scientists who chip in £50 a year and pay for their own tests. Their message is simple: prevention is better than cure – don’t jump.

Action:

Take the FREE Cognitive Function Test here
Order your at-home blood tests here
Support our research and become a FRIEND here
Participate in Alzheimer’s Prevention Day

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A world-class group of Alzheimer’s prevention experts are launching Alzheimer’s Prevention Day on May 15^th. See alzheimersprevention.info.

(The 3-minute Alzheimer’s Prevention Check goes live on May 1^st).

—

Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References & Info

These are key papers regarding stated facts in this article.

New York Times article: https://www.nytimes.com/2024/03/04/health/alzheimers-amyloid-diagnosis.html

Homocysteine and p-tau: https://brainhealthcheck.foodforthebrain.org/the-p-tau-delusion/

Donanemab review in the British medical Journal: BMJ 2023;382:p1852 

http://dx.doi.org/10.1136/bmj.p1852; 

Telegraph reports 7 deaths and brain shrinkage: https://www.telegraph.co.uk/news/2024/02/19/alzheimers-drugs-shrink-brain-scientists-warn/

Health economics of B vitamins: Tsiachristas A, Smith AD. B-vitamins are potentially a cost-effective population health strategy to tackle dementia: Too good to be true? Alzheimers Dement (N Y). 2016 Aug 11;2(3):156-161. doi: 10.1016/j.trci.2016.07.002. PMID: 29067302; PMCID: PMC5651357.

Omega-3 and B vitamin interactions and studies: Smith AD, Jernerén F, Refsum H. ω-3 fatty acids and their interactions. Am J Clin Nutr. 2021 Apr 6;113(4):775-778. doi: 10.1093/ajcn/nqab013. PMID: 33711096.

Less brain shrinkage and cognitive decline with B vitamins and sufficient omega-3: Jernerén F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H, Smith AD. Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. Am J Clin Nutr. 2015 Jul;102(1):215-21. doi: 10.3945/ajcn.114.103283. Epub 2015 Apr 15. PMID: 25877495; see also  Oulhaj A, Jernerén F, Refsum H, Smith AD, de Jager CA. Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment. J Alzheimers Dis. 2016;50(2):547-57. doi: 10.3233/JAD-150777. PMID: 26757190; PMCID: PMC4927899.

NIH Alzheimer’s prevention review: Beydoun MA, Beydoun HA, Gamaldo AA, Teel A, Zonderman AB, Wang Y. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 2014 Jun 24;14:643. doi: 10.1186/1471-2458-14-643. PMID: 24962204; PMCID: PMC4099157.

Meta-analysis of 396 studies favouring homocysteine-lowering B vitamin treatment: Prof Yu study Yu JT, Xu W, Tan CC, Andrieu S, Suckling J, Evangelou E, Pan A, Zhang C, Jia J, Feng L, Kua EH, Wang YJ, Wang HF, Tan MS, Li JQ, Hou XH, Wan Y, Tan L, Mok V, Tan L, Dong Q, Touchon J, Gauthier S, Aisen PS, Vellas B. Evidence-based prevention of Alzheimer’s disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials. J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1201-1209. doi: 10.1136/jnnp-2019-321913. Epub 2020 Jul 20. PMID: 32690803; PMCID: PMC7569385.

Tau is a structural protein that helps build the skeleton, much like pipes, through which nutrients and nerve signals are delivered to different parts of the brain. Our brains contain a balance of tau protein and phosphorylated-tau, abbreviated to p-tau. An abnormal accumulation of p-tau makes these tubular channels tangled and dysfunctional and triggers brain-cell death.¹

Too much p-tau also messes up the mitochondria, the cells’ energy factories, potentially leading to brain fatigue. The more p-tau accumulates, the greater the risk of cognitive problems and Alzheimer’s dementia. Also, those with memory decline have been shown to have relatively more p-tau to tau protein.

The next target for dementia drugs is reducing p-tau. Consequently, drugs are being developed and tested that block the kinase enzyme and activate the phosphatase enzyme,² which is exactly what the homocysteine-lowering B vitamins do. But so far, there are no human clinical trials reporting significant benefit.

The critical prevention question is what stops too much of the tau protein from turning into the potentially harmful p-tau in the first place and what helps restore p-tau to normal tau protein.

The answer is remarkably simple – a lack of B vitamins raises the blood levels of homocysteine, which activates an enzyme, Cdk5 kinase, which adds the bad ‘p’ to tau and blocks another enzyme, protein phosphatase A2, which removes the dangerous ‘p’.^3,4 High homocysteine levels also damage the tiny blood vessels in the brain, leading to ‘mini strokes’ or transient ischemic attacks (TIAs), which further raise the levels of p-tau. Homocysteine not only raises the levels of the dangerous p-tau,⁵ but can also bind to tau,⁶ further generating the neurofibrillary tangles that then trigger brain-cell death.

So, the simplest way to stop the formation of p-tau, and neurofibrillary tangles, and keep your brain healthy, is to keep your plasma homocysteine level below 10mcmol/l. Half of those above 65 have a homocysteine level higher than this.

By now you’re surely wondering why, if these natural approaches are at least as good, if not better, than drug treatments, and without adverse effects, why this isn’t common knowledge and common practice, especially if the cost is a fraction of the drug treatments. For example, supplementing B vitamins and omega-3 fish oils might cost you £100 a year while anti-amyloid drugs are pitched at around £20,000 a year.

I’m convinced that it is exactly this last point that explains the anomaly. Naturally occurring nutrients cannot be patented; only a man-made invention, such as a drug, can be. Holding a patent means only the company making that product can sell it, and they can determine the price. The price of a drug will include a hefty margin for marketing the drug and creating all the hype to get you, the media and the medical profession to buy into it. Once the patent expires, the price plummets. The price of a leading branded statin dropped by 93 per cent, from close to £30 down to just over £2 a month,⁷ That’s a lot of margin for marketing. By then, the manufacturers are on to the next ‘new’ patented drug. Up to 2022 $45 billion⁸ has been spent so far developing the latest ineffective dementia drugs, but the real cost, including the most recent trials and marketing, could be double this. That’s a lot of money to recoup. The first stage is to develop a test that convinces you and your doctor that you ‘need’ the drug. That’s what these tests in the £10 million trial are all about. If you test high, instead of taking an ineffective drug why not do prevention? That’s what the free Cognitive Function Test at foodforthebrain.org is all about.

Extract, used with permission, from Patrick Holford’s Upgrade Your Brain (Thorsons 2024)

REFERENCES

1. Balasu S et al. Science14 Sep 2023 Vol 381, Issue 6663 pp. 1176-1182 DOI: 10.1126/science.abp9556

2. Xia, Y., Prokop, S. & Giasson, B.I. “Don’t Phos Over Tau”: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies. Mol Neurodegeneration 16, 37 (2021). https://doi.org/10.1186/s13024-021-00460-5.

3. Smith AD, Refsum H. Homocysteine, B Vitamins, and Cognitive Impairment. Annu Rev Nutr. 2016 Jul 17;36:211-39. doi: 10.1146/annurev-nutr-071715-050947. PMID: 27431367.

4. LiJ-G,ChuJ,BarreroC,MeraliS,Pratico`D.2014.Homocysteine exacerbatesβ-amyloid, tau pathology, and cognitive deficit in a mouse model of Alzheimer’s disease with plaques and tangles. Ann. Neurol. 75:851–63.

5. Shirafuji N et al Homocysteine Increases Tau Phosphorylation, Truncation and Oligomerization. Int J Mol Sci. 2018 Mar 17;19(3):891. doi: 10.3390/ijms19030891. PMID: 29562600; PMCID: PMC5877752.

6. Bossenmeyer-Pourié C et al. N-homocysteinylation of tau and MAP1 is increased in autopsy specimens of Alzheimer’s disease and vascular dementia. J Pathol. 2019 Jul;248(3):291-303. doi: 10.1002/path.5254. Epub 2019 Mar 19. PMID: 307349

7. https://www.pulsetoday.co.uk/news/clinical-areas/cardiovascular/price-of-atorvastatin-plummets-93-as-patent-ends/

8. Cummings JL, Goldman DP, Simmons-Stern NR, Ponton E. The costs of developing treatments for Alzheimer’s disease: A retrospective exploration. Alzheimers Dement. 2022 Mar;18(3):469-477. doi: 10.1002/alz.12450. Epub 2021 Sep 28. PMID: 34581499; PMCID: PMC8940715.

If you ask the man on the street what’s driving Alzheimer’s, they’ll probably say it’s in the genes or that it is just what happens when you age. 

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Now, neither of these statements are strictly true. 

Alzheimer’s is a largely preventable disease. 

The big question though is WHAT exactly needs to be done and HOW do we do this?

This is why Patrick recently interviewed two experts in these areas who are also members of our Scientific Advisory Board:

Dr. Tommy Wood is an Assistant Professor of Pediatrics and Neuroscience at the University of Washington in Seattle. His research program focuses on factors associated with brain health and function across the lifespan. He received his undergraduate degree in Natural Sciences from Cambridge in 2007, a Medical Degree from Oxford in 2011, and a PhD from the University of Oslo in 2017. Alongside his academic training, Tommy has provided Performance Consulting for Olympians and world champions in a dozen different sports. He is a founding trustee of the British Society of Lifestyle Medicine and associate editor for the journal Lifestyle Medicine.

Dr Kristina Curtis is an Expert in Digital Behaviour Change Interventions (DBCIs). She has a multidisciplinary background spanning across industry, research, teaching, training and consultancy. Her primary research interests are in the development and evaluation of mHealth (mobile health) interventions, in particular how the convergence of behavioural science and UX design promotes effective engagement.

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(Want to learn more about the Citizen Science Research Team? Click here to find out more)

Interview:

Diagnosis & the difference between Alzheimer’s, dementia and mixed dementia.

Patrick Holford (PH)

My guests today are tackling the two fundamental questions. 

Firstly, what are the positive and negative behaviours, diet lifestyle and environment that both either drive dementia or prevent it?
And then the big question is, how do you encourage people to change those behaviours? 

So we have a system Professor, Tommy Wood from the University of Washington about the ‘what’.  Then to Dr. Kristina Curtis, a behavioural scientist and honorary lecturer at the University College London who heads the applied behaviour change team about how to affect behaviour change. 

Now, your background in relation to the brain is broad I see, from your time at Cambridge and Oxford University then Norway and now as assistant professor of Paediatrics and Neuroscience at the University of Washington. I believe you’ve also brain-trained Formula One drivers. Tell us about your background and how you became involved in this challenge to prevent Alzheimer’s.

Tommy Wood (TW)

I essentially fell into neuroscience initially, around 20 years ago when I was an undergraduate at Cambridge. I spent a summer in the neonates neuroscience lab looking at brain injury in babies. This is still partly what I do 20 years later.  

In between, I then went to medical school where I trained as a doctor and I also developed a lot of interest in other neurodegenerative conditions. For instance, I spent a lot of time looking at a systems approach to multiple sclerosis because my step brother was diagnosed with multiple sclerosis when he was a similar age to me in his mid 20s.  

Then, as I worked through my PhD in my early formal academic career as a professor, I worked increasingly with athletes as a performance consultant. So anything related to their cognitive and physical performance which could be sleep, diet and other stresses that they are frequently exposed to.  So, as this story of my career comes together, I work with brain injury at the beginning of life, then as I work with athletes, I do more around concussions and traumatic brain injury. And then you think, well, there were all these factors that start early in life, probably even before you’re born, that create this trajectory of how your brain functions. And that continues as you get older. So then, that makes me think about, how do we intervene at any life stage to ensure that we have cognitive function that lasts as long as possible, ideally preventing significant cognitive decline and dementia in old age. Then you start to see that these same risk factors are important at every stage so that you can start to build this idea of what the brain needs, and then you can figure out how you might want to intervene. 

PH 

I was just interviewing Professor Michael Crawford, age 93, and using some sort of quantum physics, he’s worked out how the photons that hit our eye turn into the image that we actually see. And I remember at the same age of 93, filming Linus Pauling on his theory of lipoprotein A. So I’ve witnessed people well into their 90s as sharp as a razor.

But before that, a little bit of background, what is the difference between Alzheimer’s and dementia overall, and we also hear about vascular dementia?

TW  

Dementia is essentially a catch-all diagnosis for when an individual has reached a point of cognitive decline where they are no longer able to perform regular daily tasks or usually look after themselves. So it’s a clinical diagnosis based on overall cognitive functioning. 

Then you might ask, Well, what’s causing this dementia in an individual and then we we have the sub categories, so Alzheimer’s dementia, which, if you asked Alzheimer himself, apparently he was unsure whether they should all be classified as the same thing, but that’s a sort of semantic argument.

But what we would call Alzheimer’s clinically makes up maybe 60 to 80% of dementia. Vascular dementia, which is more directly focused on blood supply to the brain, makes up something like 5 to 10%. Then there are other dementias that have very special effects on very specific parts of the brain but overall, their effect on broad cognitive function eventually ends up in a similar place. 

So with Alzheimer’s, dementia is often thought to be this continuous, gradual decline in function. Whereas with vascular dementia, what is often thought to happen is you have these very small strokes that happen throughout the brain. And each time that happens, you lose a portion of function, so you have more of this step change over time. However, in reality, there tends to be lots of overlap between say vascular and Alzheimer’s dementia, because blood supply to the brain is also important, for Alzheimer’s and sometimes it can be difficult to differentiate between the two. 

PH

And how is Alzheimer’s diagnosed as you know, in that form of dementia?

Usually, it’s going to involve some cognitive function tests. So there are lots of standardised tests like the MACA, MMSE appeal  – you may have heard of these. But there’s a whole range of tests that you’re usually going to do in person with a neurologist or an old age psychiatrist and part of it is going to be a diagnosis of exclusion. So you want to make sure that somebody doesn’t have something else going on, like a very significant vitamin deficiency or other things that can be significant like depression as they can look like significant cognitive decline or dementia, but they aren’t necessarily the same thing. So part of it is going to be excluding these other causes. Then you will probably do some brain scans and look at how the brain looks either on a CT scan or an MRI and then that, in conjunction with cognitive function, and some part of the medical history is going to tell you this is likely Alzheimer’s dementia. Often, we hear of someone being diagnosed with mixed dementia. 

PH

Is that mainly part Alzheimers, part vascular? 

TW

Yes, that’s the most common combination, but if you think about Lewy body dementia, or Frontotemporal dementia, these can also occur in different combinations in different people. But usually, because of the overlap in terms of the risk factors, Alzheimer’s with some vascular component is relatively common. 

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Preventing Alzheimer’s

PH

Now, if a person could change all their circumstances, and we’re sort of talking from early life as well, – their diet, their lifestyle, the environment that they’re born into, and their education, to what extent could we say that Alzheimer’s is a preventable disease?

TW  

It depends on how you want to try and tackle the question. But if you can change everything about an individual’s circumstances other than their genetics, then the vast majority is preventable. Depending on who you ask, some will say that it’s maybe 40 to 50%. Others will say that it’s up to maybe 70 to 80%. In some populations around the world, usually hunter-gatherer or indigenous populations, dementia is almost entirely unheard of. So it’s definitely possible that there are some combinations of environment and genetics where dementia just doesn’t occur and in that scenario, it is entirely preventable. 

PH

Now, do these same prevention steps, which obviously we’re going to go into, also prevent vascular dementia? And if so, if we put Alzheimer’s and vascular and a chunk of mixed dementia together, are we talking about 80% of dementia for example, being potentially 80% preventable?

TW  

Yes. So, as I mentioned briefly earlier, there’s a lot of overlap between the risk factors for vascular dementia. And those are also related to cardiovascular disease risk factors. So things that affect your body’s ability to move blood to the places that you want it to move to, the health of your blood vessels. There is a lot of overlap between those risk factors or things that affect negatively and those are risk factors for Alzheimer’s disease.

In fact, cardiovascular disease and poor vascular health are risk factors for Alzheimer’s dementia more directly. So if we think about the upper end of the subcategories of dementia that, 80% is Alzheimer’s disease, 10% is vascular dementia, which based on estimates could be up to 90% then yes, up to 90% of dementia is probably at least 70 ish to 80 ish percent preventable.

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How important a role do genes play?

PH

It’s often said that early onset Alzheimer’s, which is defined as before the age of 65, is that small genetic part, but a study that came out earlier this year questioned that. It was on the basis of data from the UK Biobank and it actually said that many of the same factors that are driving dementia or Alzheimer’s later in life are also present in those who develop a diagnosis before 65. So that sort of de-emphasises the genes to some extent. 

Is this true, that early onset is much the same phenomena that we’re looking at.

TW  

Yes and no. 

So traditionally, early onset Alzheimer’s, is thought to be almost entirely genetic, and driven by single significant, high penetrance genetic mutations that result in early cognitive decline. In Alzheimer’s dementia, which is thought to be more similar to what Alzheimer himself was describing when he first described the disease, it was thought to be maybe five to 10% of dementia. Now, as Alzheimer’s diseases become more prevalent,  it’s maybe around 1% of cases. However, I certainly know clinicians who have patients who have one of these mutations in a presenilin gene, or the amyloid precursor protein gene and by attending to lifestyle factors, they managed to maintain good cognitive function late into life. So even if you have some of these mutations, which are thought to almost definitely lead to Alzheimer’s disease, there does seem to be an interaction with lifestyle and other health related factors. 

Then, at the same time, we’re seeing earlier diagnosis of non-monogenic Alzheimer’s disease, which is what this paper you described, was talking about. And that’s probably because the health of the population is declining, such that we’re seeing pre-diabetes earlier, we’re seeing people that are less physically active, maybe they’re less cognitively stimulated.  All these other risk factors are adding up and they’re affecting our brains earlier in life. So now there’s more of a mix, in early onset Alzheimer’s disease, as those risk factors become prevalent earlier in life. 

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Diagnosed with Alzihemrs at age 19?  A growing tsunami of cognitive decline 

PH

I saw a report from China, of a man aged 19 diagnosed with Alzheimer’s, it said it was non-genetic, so presumably, they tested and there wasn’t the Apoe gene or the pre Senlin gene, I can’t confirm that. But can it really happen that fast, this cognitive decline that we are seeing that is so prevalent?

TW  

If you think about cognitive function as a trajectory, over time, there are three or four different components to that. 

So first of all, as you get older, cognitive function generally peaks on average, towards the end of your formal period of education. So if that education extends into university or maybe a graduate degree, then that’s going to peak sometime in your 20s or early 30s. But if you don’t even complete secondary school or high school, then it’s going to peak much earlier, and it’s going to have a much lower peak. After the peak, then you have a period of decline, and the speed of that decline depends on a number of factors, the majority of them related to ongoing stimulus to the brain as well as a whole host of health-related and nutritional factors, as you know very well. So there’s certainly a possibility where if you had a low peak of cognitive function, and that may even be based on something like maternal nutrition and epigenetics related to the health of your parents, so you had a low peak, and you have poor overall health, you’d have a more rapid decline. It’s certainly possible that this could happen very early in life, though, thankfully, at least right now, that’s very rare.

PH  

Yeah, we’ve seen the youngest with type two adult onset diabetes age three, so quite extraordinary. 

So is Alzheimer’s, just the tip of the iceberg of a growing tsunami of cognitive decline that is likely to start happening earlier?

TW  

Yes and no.

I say no, because having had lots of conversations, including with one of your close colleagues and mentors, David Smith. When you look at the specific prevalence of Alzheimer’s disease, it has not increased over time. And in fact, in some populations, it’s decreased.  It’s probably decreased a little bit more in men, because we focus very heavily on cardiovascular disease risk factors, which are more important in men in terms of causes of death.

And that has come with some improvement in terms of age-specific incidence of Alzheimer’s disease, when the reason why Alzheimer’s disease is becoming more prevalent, and it’s going to double or triple in the next few decades, is because we’re living longer. So there’s a combination of we’re living longer, and in general, our health is declining. 

So you could say, there’s this oncoming wave of Alzheimer’s disease, and that is expected. But we know that if we target specific risk factors, that doesn’t have to be the case. So I don’t think it’s all bad news.

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Our Citizen Science Research Team

PH  

Now, you’re the principal investigator at Food for the Brain heading, the research and the science there. So what does that involve? 

What’s your goal as a principal investigator?

TW  

One of the most important tools that we have when we’re looking at diseases or specific functions or health of the population are our population datasets, and there are lots of these. 

Governments around the world organise them, there’s Haynes in the US, there’s the UK Biobank in the UK that people have heard of, and you collect lots of data from lots of people, and at that kind of scale, you can start to maybe pick up relationships that you couldn’t otherwise. 

When we think about the risk factors for cognitive decline, and dementia, specifically, none of the datasets that exist so far are really designed to focus on that. So one of the most important ideas is to collect data, specifically related to risk factors for Alzheimer’s, dementia, and hopefully those that are modifiable. So it’s kind of a citizen science idea, right?  We’re going to people who are interested in this or maybe interested in this for their loved ones.  They are providing their data and part of it is to help understand their own risk, but then allowing us to look at a wide variety of risk factors. 

There are over a hundred questions in a questionnaire that look at different risk factors and we have the cognitive function test and blood tests. So then, when you have very large datasets like this, we can start to look for complex interactions between risk factors, and we can figure out which risk factors are most important. These are things that still need to be done as it pertains to most Alzheimer’s disease. I think, hopefully, Food for the Brain is going to be in a good position to help people understand that.

Figuring out the perfect food and lifestyle combo – what matters more!

PH

So what’s your ultimate goal from this data set – to find the sort of perfect diet lifestyle combo?

TW 

I think that there are two main things. In reality, I think that we know what is going to be best for most people.  If we look across all the evidence, we probably know that already we can have a good guess of what you should aim for.

When you say, here are the 50 things you need to fix to improve your brain health. There’s just an overwhelming amount of information – you don’t know where to start, what should I do? 

First, what’s most important to me, what’s most impactful? So figuring out which factors an individual should focus on first, which gives the biggest bang for their buck is what’s going to be a big, big part of this. Then the million dollar question is how do you actually change a person’s often highly entrenched behaviour, especially if we want to reach hundreds of 1000s across a digital platform?

PH 

So Dr. Kristina Curtis, welcome. 

You’re a behaviour change expert and an associate of UCLA Centre of Behaviour Change and founder of Applied Behaviour Change, which focuses on digital health programmes to help prevent and manage chronic conditions. 

Can you explain a bit about your background and the reason you are interested and involved in this Alzheimer’s prevention project? 

Khristina Curtis KC

After my psychology degree, I had a few years out working in industry because I hadn’t found the area of psychology that I wanted to specialise in. And so this led me to return to studies to specialise in health psychology, which is all about health behaviours. And then immediately afterwards, I then started a PhD, which really culminated my experience back then, which was web to technology, with my academic knowledge of health psychology at the Institute of Digital Healthcare at Warwick University.  

My PhD was really focused on how we would embed behaviour change models into mobile health apps and digital health interventions. And really, I feel passionate about preventing chronic conditions and particularly Alzheimer’s disease, as there are a lot of misconceptions about it. And we’ve talked a lot about them today. And in terms of many people think it’s a symptom of ageing, and largely down to our genes. Whereas, as we’ve heard, we can do a lot to reduce our risk by adopting healthier habits. 

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How do we implement these ‘risk-reducing’ behaviours and habits?

PH

And what are you doing in the cognition project at Food for the Brain? What’s your game plan? 

KC

Let’s talk about the kinds of preventative behaviours. 

For example, increasing physical activity, eating a healthier diet, social interaction, brain training, might all help to reduce our risk of developing things like Alzheimer’s and dementia. One of the issues here is that actually sustaining these long term changes and making them long term habits is extremely challenging. 

There is quite a good evidence base on which behaviour change techniques work but we’re still really in the early stages of understanding how to implement these techniques in a way that engages different groups of people. There is strong evidence which suggests that we should have a tailored approach.

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We are a small but mighty team and charity running on donation alone – please donate to our continued research here.

Also, you can learn more about our Citizen Science Research Team here.

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Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

Everyone knows that Alzheimer’s and cognitive decline are preventable IF you can find out who is at risk. 

While those selling anti-amyloid or p’tau drugs will exaggerate the importance of blood testing for amyloid or p’tau, which are damaged proteins found in the brains of people with Alzheimer’s, so far lowering these markers hasn’t worked. In other words, they are a marker, but not a cause.

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So, what is a biomarker that predicts risk? 

And therefore what biomarkers, if corrected, reduce risk?

To date, there are four:

Homocysteine, a toxic amino acid, which goes up when your intake of B vitamins (B6, B12, folate, as well as zinc) is low. If you then lower homocysteine with B vitamins, it stops the brain shrinkage associated with Alzheimer’s and improves cognitive function. Brain shrinkage stops below 10 mcmol/l, and that’s what you’re aiming for. So that’s both ‘biomarker’ and ‘causal’ ticked.

At Food for the Brain, we are offering the first accurate at home, pinprick test for homocysteine that is both painless and accurate.

Omega-3 index is another. This is the % of your red blood cell membranes that are omega-3 EPA and DHA. The higher your % (ideally above 8) the better your cognition. Low levels also predict risk. So that’s also two boxes ticked. 

Vitamin D is another. Low levels predict risk and supplementing it reduces risk. Again, two boxes ticked but we don’t really know how it does this.

Combining these three to make a ‘nutritional index’ shows that the better you score, the lower a person’s future risk of dementia is.

HBA1c is another. This is a measure of your blood sugar resilience. It measures the spikes in your blood sugar that then damage red blood cells. Below 5.4% (or 37 mmol/mol) is the idea.

We divide your scores across four levels – worst is RED, then ORANGE, then YELLOW, then GREEN, which is what you’re shooting for. 

That’s what our DRIfT test measures – all four as a Dementia Risk Index functional Test.

This chart shows you why these four measures are so essential. 

What about antioxidants?

But you might have noticed there’s no ‘antioxidant’ measure.

Well, actually there is. It’s the body’s most important antioxidant called glutathione. Think of it like the body’s fire department with glutathione being the water. Every time there’s an oxidant fire, glutathione rushes in to put the fire out. The water, then, turns into steam. Glutathione is called GSH. It’s not bad as a measure of ‘antioxidant potential’. That’s why most functional medicine doctors measure red blood cell glutathione. But what if it all gets used up? It becomes oxidised or spent, much like the water putting out a fire turns into steam. This is called oxidised glutathione or GSSG. Think of the fully loaded glutathione (GSH) as cold water. It’s going to protect you much better from inflammation than spent (oxidised) glutathione (GSSH), a highl level of which means you’ve been trying to put out a lot of inflammatory fires in your brain and body. Neuro-inflammation is a key driver of brain degeneration and dementia, as well as ageing in general, which is why this is important to know.

We’ve been researching the ratio that is your GSH/GSSG. If you’ve got lots of fully loaded glutathione, and very little oxidised/spent glutathione, your GSH/GSSG ratio or index is high. That’s good news. If you’ve got very little fully loaded glutathione and lots of oxidised glutathione then you’re ‘oxidising’ –  which is an aspect of ageing that we want to prevent.

We want to be able to research this and test your Glutathione Index. This is exactly what we are working on right now with the hope of releasing another ‘world first’ home test kit for your Glutathione Index soon. This kind of research is funded by you, as a Friend of Food for the Brain.

An example would be a person who smokes a lot, lives in a polluted environment, eats no fresh veg, berries, herbs and spices. Their Glutathione Index will be low and their body and brain will likely be ageing faster. If you did smoke but also ate well and took vitamin C daily, (they say you need 50mg of vitamin C for each cigarette) would that mitigate the effect? 

Would you join our research, support our charitable work and upgrade your own brain by ordering one of our DRIftT tests?

If you’ve also done the Cognitive Function Test and Dementia Risk Index questionnaire (which we strongly recommend) that’s even better because we can see how you score in the ANTIOXIDANT domain and in future, how that will correlate with your Glutathione Index (which is coming soon).

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Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

by Patrick Holford

This is the headline from the New York Times exposing a proposal from an ‘Alzheimer’s Working Group’ that we should all have an amyloid blood test to then be prescribed anti-amyloid drugs. This is a similar strategy to statins which are given to anyone with ‘high cholesterol’ despite no evidence of heart disease and limited benefit from taking the statins, except in the drug companies own trials. Their representatives also reduced the ‘acceptable’ blood test level in a process known as ‘diagnostic creep’.

The working group, many of whose members, say the NYT, are ‘employed by companies developing drugs and diagnostics’ is chaired by Dr Clifford R. Jack Jr., an Alzheimer’s researcher at the Mayo Clinic.  “Someone who has biomarker evidence of amyloid in the brain has the disease, whether they’re symptomatic or not,” said Dr Jack. “The pathology exists for years before symptom onset,” he added. “That’s the science. It’s irrefutable.”

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But wait…

Let’s back up here a minute.

Amyloid has never been proven to be a cause of Alzheimer’s. 

In fact, the repeated failure of anti-amyloid drugs that do successfully lower amyloid to deliver any meaningful clinical effect has proven, time and time again, that raised amyloid is not the cause of Alzheimer’s. It is, I believe, an effect, an artefact. Not all who develop Alzheimer’s have raised amyloid but most do. But the fact that it is present doesn’t mean removing it with anti-amyloid drugs will ‘cure’ the disease. The real pathology of Alzheimer’s is both a reduction in cognitive function and brain shrinkage.

The last drug trial reported that those on the drugs had 20% more brain shrinkage than those on the placebo. In other words the pathology got worse, not better. We reported this because it was in the published research paper but no newspaper coverage mentioned it. (Perhaps journalists only read the press release, not the study itself).  This was finally reported in the Telegraph two weeks ago: ‘‘Breakthrough’ Alzheimer’s drugs can shrink the brain, scientists warn’.

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The risk-to-benefit ratio is terrible

According to Dutch researchers, 10 percent of cognitively normal 50 year-olds would test amyloid positive, as would almost 16 percent of 60-year-olds and 23 percent of 70-year-olds. Most of those individuals would never develop dementia. But, if this scenario were to roll out, they would be prescribed the anti-amyloid drug treatment at an estimated £40,000 a year. Given that there were seven deaths of participants in the last two anti-amyloid drug trials, reported by ourselves and the Telegraph, and over a third of patients got potentially fatal brain bleeding or swelling, that’s a hell of a downside for something that isn’t likely to deliver any benefit. 

“Anti-amyloid trials raise scientific and ethical questions.” Writes Professor David Smith in the British Medical Journal (1). “Ackley and colleagues found that lowering brain β-amyloid levels in Alzheimer’s disease had no significant effect on cognition in 14 clinical trials on a total of 4,596 patients. Is it justifiable to ask patients to undergo yet more trials of anti-amyloid treatments? Moreover, we should all question the morality of the drug companies that declined to give these researchers access to data for 20 of the 34 trials they wanted to study.”.

“These findings” he says  “should direct our attention to the prevention of Alzheimer’s disease by slowing down the disease process, for which there are many possible approaches.”

Professor David Smith is one of the many scientific advisors instrumental in shaping our prevention policy which goes like this:

Test actual cognitive function, which is known to show changes up to 40 years before a diagnosis. That’s the Cognitive Function Test which you can do here.
As part of this assessment, you will complete a questionnaire covering all known risk factors. That’s the Dementia Risk Index which follows the Cognitive Function Test.
Then measure actual blood markers of things that predict risk – homocysteine, omega-3 index, HbA1c for sugar control, and vitamin D. That’s the DRIfT test, available here.
Then advise the individual on how to reduce their risk by targeting the risk factors that they can change, which, in turn, bring down the biomarkers in the DRIfT test.

There are no downsides, only benefits, with this kind of prevention approach. 

There is only one problem – prevention is not profitable.

Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References

1 http://dx.doi.org/10.1136/bmj.n805

This week CNN ran a story about a dementia prevention clinic in the US, run by neurologist Professor Richard Isaacson, who used our Cognitive Function Test in his prevention study at Cornell University.

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The basic concept, much like what Food for the Brain is doing online, is that people get screened with blood tests, complete a cognitive function test and are assessed for diet and lifestyle factors that increase future risk. The article highlights nutrition, insulin resistance, genetic, behavioural and lifestyle risk factors along with the ability to track your progress with new ‘experimental blood tests’.

What’s the difference between this and what Food for the Brain is offering? 

This screening would set you back at least $2000 compared to Food for the Brain’s, with the DRIfT blood test, costing closer to £200.

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Brain Blood Tests that Predict Risk

In Alzheimer’s there are increases in Amyloid and p-tau. That’s not in dispute. Despite all the hype, the anti-amyloid drugs such as Lecanemab, featured in last week’s Panorama programme, have produced what is widely regarded as a clinically insignificant benefit with very high risk of adverse effects, including a small risk of death. Five people died as a consequence of the drug treatment in the last two trials, which is approximately one in 500. The British Medical Journal editorial concluded  ‘No clinically meaningful effect. 30% get brain bleeding or swelling. Two trial deaths under investigation.’ 

The ‘just’ statistically significant benefit, which got the drug its licence, was several times less than that reported in a comparative trial of omega-3 in those with low homocysteine (sufficient B vitamins) and the rate of brain shrinkage actually increased by 20% compared to a 73% reduction in a trial of homocysteine lowering B vitamins in those with sufficient omega-3 DHA in their blood (read more about that here.)

So, yes, test amyloid but no – there is not sufficient evidence that lowering it with anti-amyloid drugs is going to realistically make much difference.

The trouble with the anti-amyloid monthly injection (which costs circa £20,000 a year) is that each injection will need to be followed by an expensive brain scan precisely because of the risk of brain bleeding and swelling, experienced by a third in trials. That’s also why the BBC reported that Alzheimer’s Research UK has warned that the NHS is ‘not ready’ for new Alzheimer’s drugs Lecanemab and Donanemab. It’s not prepared for such a treatment rollout due to the benefit it delivers versus the cost of on going assessment. Together with the medical costs it will probably cost closer to £50,000 per year per person. 

While in contrast, £50,000 would fund 1,000 people follow our COGNITION programme for a year.

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All eyes on p-tau lowering drugs…

With the failure of the amyloid hypothesis, all eyes are on p-tau lowering drugs. 

Yet none have worked. 

But, much like cholesterol for heart disease, the media messaging will be to test p-tau rather than prescribe a drug. The irony here is that a lack of B vitamins, or rather raised homocysteine (which you can test here), is well established to increase p-tau so the simplest way to stop the formation of p-tau, and neurofibrillary tangles, and keep your brain healthy, is to keep your plasma homocysteine level below 10mcmol/l. In addition, the fact that there is no solid evidence that lowering levels of p-tau or amyloid protein prevents dementia or slow down progression is why these are called ‘‘experimental blood tests” in the CNN coverage.

We have combined four tests (omega-3 index, vitamin D, HBA1c for sugar balance, homocysteine for B vitamins) that each have clear evidence that

a) good levels correlate with less risk
b) bringing blood test levels into the optimal range reduces risk. 

So we are ahead in that respect. This is the 4-in-1 DRIfT test which calculates a biological Dementia Risk Index. 

We want you to take this test, not only for your benefit but also, when we have enough results of tests and retests, together with FREE Cognitive Function Test results we can research the correlation to find out how your DRIfT score predicts cognitive function. 

Genetic Fears

The other issues raised are around genes that predict Alzheimer’s risk. 

There’s quite some confusion here which, if misunderstood, creates unnecessary fear. ‘Causative’ genes (APP and Presenelin) are very rare – less than 1 in 100. The Panorama programme included a younger person with this gene. Much more common is having the ApoE4 gene, which one in seven people have. This doesn’t cause Alzheimer’s. Technically, it increases risk by 4 to 6% but all the changes we recommend to your diet mitigate even this increased risk. That is why, in studies where people ate better or took the right supplements, there was no difference in the outcome of the individuals with or without the ApoE4 gene variant.

The bottom line is that almost no-one needs to develop dementia if they follow ‘optimum nutrition’ advice – diet, supplements and lifestyle and that is what we are here to do.

Food for the Brain is making prevention a reality.

Join us in our mission, research and reclaim your brain this year. The first things you want to do are:

Complete the FREE Cognitive Function Test. This is an online, validated assessment of your current cognitive function and your dementia risk. Over 400k have completed this test and upgraded their brain in the process.
Order your DRIfT test. These accurate, at-home blood tests are the perfect way to improve your brain health and reduce your risk.

Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

Early-onset dementia, often talked about as ‘genetic’, has been linked to exactly those factors that our Dementia Risk Index questionnaire, part of the Cognitive Function test, assesses. 

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In other words, what you do and how you live protects you from losing cognitive function at any age.

This study from the UK Bio Bank’s data defined young-onset dementia (YOD) as a diagnosis before the age of 65, but many people experience degrees of cognitive decline at younger and younger ages. This report (1) from China even confirms a 19-year-old man, with no causative Alzheimer’s genes being diagnosed with Alzheimer’s!

Thankfully there is lots you can do to reduce your risk and prevent the loss of your mind and memories.

This UK BioBank study (2) identified 485 people out of 356,000 who developed dementia before the age of 65. The estimate is that 70,000 people in the UK suffer from young-onset dementia. It identified 15 risk factors, many of which we already address within our 8 domains

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Particularly predictive were a person’s vitamin D level, diabetes and depression. (The 15 identified risk factors were lower formal education, lower socioeconomic status, carrying 2 apolipoprotein ε4 allele, no alcohol use, alcohol use disorder, social isolation, vitamin D deficiency, high C-reactive protein levels, lower handgrip strength, hearing impairment, orthostatic hypotension, stroke, diabetes, heart disease, and depression.)

Vitamin D is vital to supplement in the winter. Those who do have a 40% lower incidence of dementia according to a recent study. A study in France those with low vitamin D levels, below 50 nmol/L, had a nearly three-fold increased risk of Alzheimer’s. Over sixty per cent of people in the UK have lower levels than this. This is why we are now offering vitamin D testing to everyone who has taken the Cognitive Function Test.

Diabetes, and pre-diabetes, is best identified from a blood test for HbA1c which determines glucose control. Levels above 6.5% indicate diabetes while adolescents with levels above 5.4% have been shown to have a degree of cognitive impairment. In young adults having the early signs of poor glucose control is a future predictor of dementia.

The incidence of depression goes up substantially in those with low vitamin D, poor glucose control as well as a lack of omega-3 (now included in the tests we offer.) It may also reflect lack of stimulation for example from loneliness, unemployment, lack of mental stimulation through education and lack of opportunity.

Diet wasn’t sufficiently investigated, nor homocysteine, because the UK Biobank questionnaire doesn’t ask sufficient questions to go close up, nor is homocysteine part of the blood test data. That is why Food for the Brain’s growing data bank – the result of people like you taking the time to do the test – is going to prove so invaluable. (This is one of the reasons we have launched our highly accurate, affordable, at-home Homocysteine test kits which will be back in stock later this week.

Prof Llewellyn, one of the study authors, said the study “reveals that we may be able to take action to reduce risk of this debilitating condition”.

Even with this data gap, this study shows that a lot of the risk factors for early-onset dementia are preventable. At the end of January, we are launching the DRIfT (Dementia Risk Index Functional Test) home test, measuring both vitamin D, omega-3, HBA1c and homocysteine with a home test kit.

When you address these factors, which is what our Cognitive Function Test and follow-up COGNITION program is designed to do, you can mitigate your risk of dementia.

While we have had over 400,000 do the test and see many people’s dementia risk index decrease and Cognitive Function Score increase, this research confirms our work and mission.

As our founder and CEO Patrick Holford says:

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Take the Cognitive Function Test today, learn your current brain health status and take our easy at-home blood tests (like vitamin D) so that you know exactly how to reduce your risk and prevent dementia at any age.

Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References

1 – https://pubmed.ncbi.nlm.nih.gov/36565128/

2 – https://pubmed.ncbi.nlm.nih.gov/38147328/

The largest study of its kind, involving over a quarter of a million people (267,000) from the UK Bio Bank, has reported 30 per cent less risk of dementia in those with a higher omega-3 status in their blood (1). 

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One of the study authors, Professor Bill Harris from Stanford University’s Department of Medicine in South Dakota, says “There is now overwhelming evidence from no less than four studies this year that increasing your intake and blood levels of omega-3 is strongly associated with reducing future dementia risk. Ideally a person wants to get their blood omega-3 index above 8%”.

This UK study confirmed the results of a US study (2) earlier this year that found a 49 per cent reduced risk for dementia in those with the highest omega-3 DHA level (top fifth) in their red blood cells versus the lowest (bottom fifth). Oily fish and fish oil supplements contain two kinds of omega-3 fat called DHA and EPA. DHA is the main fat found in brain cells of all animals.

What’s more a meta-analysis of 48 studies in the American Journal of Clinical Nutrition in 2023 (3) also concludes that ‘a moderate-to-high level of evidence suggested that dietary intake of omega-3 fatty acids could lower risk of all-cause dementia or cognitive decline by about 20 per cent, especially for DHA intake’. 

Each 100mg increment of DHA was associated with an 8–10 per cent lower risk of dementia. 

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But it also predicts the actual size of your brain.

A recent study by psychologists at the Linda Loma University in California and published in the journal Brain Sciences (4), reported that the higher a person’s omega-3 index was in their blood, the more white matter there was in their brain meaning they had more brain volume, and the better they performed on cognitive tests that predict less risk for dementia.

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This is why we have launched our omega-3 campaign and offer our home test kits to measure the omega-3 index from a pinprick of blood, the measure used in this research. Alongside the blood test, you are invited to complete a free online Cognitive Function Test and a Dementia Risk Index questionnaire that not only calculates your risk but tells you what to do to lower it. 

We hope to enrol hundreds of thousands of people interested in protecting their brains and willing to have a yearly pinprick blood test and assess their memory with a validated online test. 

This is ‘citizen science’ with the research results shared back to everyone involved. 

Less than one per cent of Alzheimer’s is caused by genes. This is a largely preventable disease and getting your omega-3 level up by eating oily fish and taking supplements is likely to cut risk by a third. We need to both research and educate people to take prevention action from their 30s.

Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References

¹ Sala-Vila, A.; Tintle, N.; Westra, J.; Harris, W.S. Plasma Omega-3 Fatty Acids and Risk for Incident Dementia in the UK Biobank Study: A Closer Look. Nutrients 2023, 15,4896. https://doi.org/10.3390/ nu15234896

² Sala-Vila, A.; Satizabal, C.L.; Tintle, N.; Melo van Lent, D.; Vasan, R.S.; Beiser, A.S.; Seshadri, S.; Harris, W.S. Red Blood Cell DHA Is Inversely Associated with Risk of Incident Alzheimer’s Disease and All-Cause Dementia: Framingham Offspring Study. Nutrients 2022, 14, 2408. https://doi.org/10.3390/ nu14122408

³ Wei BZ, Li L, Dong CW, Tan CC; Alzheimer’s Disease Neuroimaging Initiative; Xu W. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers. Am J Clin Nutr. 2023
⁴ Loong, S.; Barnes, S.; Gatto, N.M.; Chowdhury, S.; Lee, G.J. Omega-3 Fatty Acids, Cognition, and Brain Volume in Older Adults. Brain Sci.2023,13,1278. https://doi.org/ 10.3390/brainsci13091278

 By Sophie Barret – Hifas da Terra & Patrick Holford

Two medicinal mushrooms are particularly relevant when it comes to optimising your brain health, here we discuss Reishi (Ganoderma Lucidum) and Lion’s Mane (Hericium erinaceus); in terms of their potency and use in both Alzheimer’s and Dementia as well as the studies and clinical research into both these significant strains.

Alzheimer’s disease is the most common form of dementia and, according to the WHO, accounts for 60-70% of cases. It is a progressive neurological disorder that involves a steady decline in thinking, behaviour and social skills that affects a person’s ability to live independently. Although age is the main risk factor for dementia, the disease is not an inevitable consequence of ageing. This type of dementia does not exclusively affect older people. Early-onset dementia (onset of symptoms before the age of 65) accounts for up to 9% of cases. Regular physical and mental exercise, avoiding cigarette smoke and alcohol, controlling weight and blood pressure, as well as following a healthy diet and premium quality supplementation can reduce the risk of Alzheimer’s or even slow down the process.

The application of Mycotherapy for Alzheimer’s focuses on the use of pure, standardised, organic extracts of Lion’s Mane (Hericium erinaceus) and Reishi (Ganoderma lucidum), the supplementation of which has been associated in clinical studies with a reduction in the likelihood of mild cognitive impairment and in vivo with anti-dementia activity in cognitive deficits.

The neurodegenerative mushroom: lion’s mane

Lion’s Mane, (Hericium erinaceus) is a medicinal mushroom with diverse pharmacological activities in the prevention of many age-associated neurological dysfunctions, including Alzheimer’s disease and Parkinson’s disease. (5). Supplementation of H. erinaceus has been shown to improve cognitive function and memory in people with mild cognitive impairment (4) and slow cognitive decline and dementia. Its extract is highly recommended in the treatment of neurodegenerative diseases.

The action of Lion’s Mane is based both on its ability to regenerate damaged nerve axons and to enhance myelinization. This is thanks to the rich content of hericenones found in Lion’s mane extract that act as a Nerve Growth Factor (NGF) enhancing agent.

European Biotech, Hifas da Terra, conducted the Neurofood study in people using a unique Lion’s Mane strain. The results showed significant improvements in participants’ attention, memory, concentration, processing speed and visuospatial skills.

The neuroprotective mushroom: reishi

Reishi has demonstrated neuroprotective capacity due to its potent antioxidant properties. Thanks to the antioxidant capacity of G. lucidum’s active biomolecules, especially terpenes such as ganoderic acid, it can improve the reduction of age-related oxidation linked to impaired cognitive function (12,13,14), alleviating neuronal damage and inhibiting apoptosis in Alzheimer’s disease (15).

Several studies and reviews have demonstrated its preventive and therapeutic effect on neuronal damage and cognitive impairment (9).

The antioxidant effect of G. lucidum, thanks to the ability of its active ingredients to scavenge free radicals, may enhance the reduction of age-related oxidation linked to cognitive function decline. (10).

What about ‘magic mushrooms’ & psychedelics ?

One of the hottest areas of brain research is the effects of various hallucinogenic compounds, notably psilocybin – a hallucinogenic substance in certain types of mushrooms, but also LSD and the Amazonian plant potion Ayahuasca, a rich source of DMT, on mental health and brain function. These compounds are tryptamines and share a quality of activating a key receptor site in the brain for serotonin, called 5-HT2 receptors.  As a group, they are all shown to be potential promoters of neuroregeneration and neuroplasticity, helping make neuron connections and perhaps new neurons. They also stimulate brain-derived neurotrophic factor (BDNF), a key brain signaller that stimulates growth. 

With many studies (13) now showing the potential of psychedelics to help those with treatment-resistant depression, drug addiction and also anxiety in terminal patients, much attention is being focussed on what they actually do in the brain. On a psychological level, breakthroughs in debilitating depression and anxiety seem to occur through the experience of patients ‘exorcising the demons’ of early traumas through psychotherapy assisted trips. But there may be more going on at a biological level. Also, studies are underway testing less heroic doses – microdoses – of these agents. It is too early to say whether they could have a helpful role in those with early cognitive decline and brain shrinking but it is certainly plausible and an area of ongoing research. It’s a case of ‘watch this space’.

In summary, the application of Mycotherapy for any type of dementia seeks to provide a neuroprotective effect, improving quality of life. It focuses also on the use of pure, standardised organic extracts of Lion’s Mane (Hericium erinaceus) and Reishi (Ganoderma lucidum), the supplementation of which has been associated in clinical studies with a reduction in the probability of suffering mild cognitive impairment (MCI) and in vivo with anti-dementia activity in cognitive deficits.

Lion’s Mane, (Hericium erinaceus) is a medicinal mushroom with a variety of pharmacological activities in preventing many age-associated neurological dysfunctions, including Alzheimer’s and Parkinson’s (1). As mentioned, supplementation of H. erinaceus (Lion’s Mane) has been shown to improve cognitive function and memory in people with mild cognitive impairment (2) and is therefore highly recommended in the integrative treatment of neurodegenerative diseases.

The action of H. erinaceus is based both on its ability to regenerate myelin and to regenerate new synapses thanks to its content of hericenones and erinacines, which act as Nerve Growth Factor (NGF) enhancing agents, both at the level of expression and secretion. This contribution of Hericium erinaceus has been shown to both prevent (5) and slow cognitive decline and dementia, as well as showing neuroprotective effects.

Several studies and reviews have also demonstrated as mentioned the neuroprotective capacity of Reishi, (Ganoderma lucidum), as well as its preventive and therapeutic effect on neuronal damage and cognitive impairment (9). While other studies have demonstrated its antioxidant effect concluding that, thanks to the ability of its active ingredients to scavenge free radicals, can enhance the reduction of age-related oxidation linked to the (10)

If you are going to consider two medicinal mushrooms for both these conditions these are the two medicinal mushrooms with the most scientific research behind them.

Want to learn more about how medicinal mushrooms can support you brain and mental health? Join us for the Mushrooms & the Mind webinar!

Click here to join the webinar

Thank you for reading!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References

1. Li IC, Chang HH, Lin CH, et al. Prevention of Early Alzheimer’s Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study. Front Aging Neurosci. 2020;12:155. Published 2020 Jun 3. doi:10.3389/fnagi.2020.00155.

2. Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T (2009) Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytotherapy Research 23, 367-372.

3. Kim, Y. O., Lee, S. W., & Kim, J. S. (2014). A comprehensive review of the therapeutic effects of Hericium erinaceus in neurodegenerative disease. Journal of Mushroom, 12(2), 77-81.

4. Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N (2008) Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells. Biologicaland Pharmaceutical Bulletin 31, 1727-1732.

5. Li IC, Lee LY, Tzeng TT, et al. Neurohealth Properties of Hericium erinaceus Mycelia Enriched with Erinacines. Behav Neurol. 2018;2018:5802634. Published 2018 May 21. doi:10.1155/2018/5802634.

6. Kawagishi, H., Zhuang, C., & Yunoki, R. (2008). Compounds for dementia from Hericium erinaceum. Drugs of the Future, 33(2), 149.

7. Ma BJ, Shen JW, Yu HY, Ruan Y, Wu TT, Zhao X (2010) Hericenones and erinacines: stimulators of nerve growth factor (NGF) biosynthesis in Hericium erinaceus. Mycology 1,

8. Moldavan M, Grygansky AP, Kolotushkina OV, Kirchhoff B, Skibo GG, Pedarzani P (2007) Neurotropic and trophic action of Lion’s Mane mushroom Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae) extracts on nerve cells in vitro. International Journal of Medicinal Mushrooms 9, 15-28.

9. Yu, N., Huang, Y., Jiang, Y., Zou, L., Liu, X., Liu, S., … & Zhu, Y. (2020). Ganoderma lucidum triterpenoids (GLTs) reduce neuronal apoptosis via inhibition of ROCK signal pathway in APP/PS1 transgenic Alzheimer’s disease mice. Oxidative medicine and cellular longevity,

10. Huang, S., Mao, J., Ding, K., Zhou, Y., Zeng, X., Yang, W., … & Pei, G. (2017). Polysaccharides from Ganoderma lucidum promote cognitive function and neural progenitor proliferation in mouse model of Alzheimer’s disease. Stem cell reports, 8(1), 84-94.

11. Klaus AS, Kozarski MS, Nikšić MP (2011) Antioxidant properties of hot water extracts from carpophore and spores of mushroom Ganoderma lucidum. Proceedings for Natural Science, Matica Srpska Novi Sad 120, 277-286.

12. ozarski MS, Klaus AS, Nikšić MP (2011) Extract from wild strain of mushroom Ganoderma lucidum as natural antioxidant. Proceedings for Natural Science, Matica Srpska Novi Sad 120, 287-295.

13. Saeger HN, Olson DE. Psychedelic-inspired approaches for treating neurodegenerative disorders. J Neurochem. 2022 Jul;162(1):109-127. doi: 10.1111/jnc.15544. Epub 2021 Dec 5. PMID: 34816433; PMCID: PMC9126991.

Everyone knows that vitamin D is vital for healthy bones and a stronger immune system but could low levels also be a major driver of Alzheimer’s and  age-related cognitive decline?

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What new research is saying

New research suggests they could, and that levels of vitamin D commonly found in the UK are accelerating cognitive decline and increasing the risk of a dementia diagnosis (1). Supplementing vitamin D, especially in the winter, may reduce future dementia risk.

And it’s not just the UK. A study in France showed that those with low vitamin D levels, below 50nmol/l, had a nearly three-fold increased risk of Alzheimer’s (2). In the UK, over 60 percent of people aged 11 and over have lower levels than this (3).

Supplements also help ward off dementia, according to a large-scale study earlier this year involving over 12,000 dementia-free 70+ year olds (4). More than a third (37%) took supplements of vitamin D and had a 40% lower incidence of dementia. Professor Zahinoor Ismail, of the University of Calgary and University of Exeter, who led the research, said: “We know that vitamin D has some effects in the brain that could have implications for reducing dementia, however so far, research has yielded conflicting results. Overall, we found evidence to suggest that earlier supplementation might be particularly beneficial, before the onset of cognitive decline.”

Did you know we just launched our at-home vitamin D blood tests and MIND Vitamin D Research Project? Will you join our research project and test and track your own vitamin D with us?

Find out more here.

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If you’re not supplementing vitamin D in the winter they are heading for cognitive decline…

Vitamin D expert and Director of the Sunlight, Nutrition and Health Research Center in San Francisco and a member of our Scientific Advisory Board, Dr William Grant, says we’ve vastly under-estimated the importance of vitamin D on the brain and how much you need.

 “All the evidence for bone and immune health shows that you need a blood level of vitamin D above 75nmol/l to be healthy, and the same is proving true for the brain. This optimal level is impossible to achieve without supplementation in the winter. I recommend every adult and teenager supplement 3,000iu a day from October to March. The government’s recommendation of 400iu (10mcg) is not enough for optimal brain health. Supplementing 800iu (20mcg) a day for 12 months has already been shown to improve cognitive function but you need more than this to achieve anything close to an optimal level.” says Dr Grant. “If you’re not supplementing vitamin D in the winter they are heading for cognitive decline.” Yet only eight percent of UK adults take vitamin D in the winter, says the British Nutrition Foundation (6).

Under the direction of Dr Grant, we have launched a research project to test both vitamin D levels, using a home test kit, and cognitive function, with a free online Cognitive Function Test.

“We have tested over 400,000 people’s cognitive function and now we want to discover their vitamin D levels. This will establish how much vitamin D you really need to stay free from dementia” says Dr Grant.

If you’d like to take part in this research and discover your vitamin D level and cognitive function click here . The free online Cognitive Function test also works out what’s driving future dementia risk and tells you what to do about it

Did you know we just launched our at-home vitamin D blood tests and MIND Vitamin D Research Project? Will you join our research project and test and track your own vitamin D with us?

Find out more here.

Thank you for reading!
Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References

1 Chai B et al. Vitamin D deficiency as a risk factor for dementia and Alzheimer’s disease: an
updated meta-analysis. BMC Neurol. 2019 Nov 13;19(1):284. doi: 10.1186/s12883-019-
1500-6. PMID: 31722673; PMCID: PMC6854782.

2 Jia J et al. Effects of vitamin D supplementation on cognitive function and blood Aβ-related
biomarkers in older adults with Alzheimer’s disease: a randomised, double-blind, placebo-
controlled trial. J Neurol Neurosurg Psychiatry. 2019 Dec;90(12):1347-1352. doi:
10.1136/jnnp-2018-320199. Epub 2019 Jul 11. PMID: 31296588.

3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353432/pdf/nutrients-12-01868.pdf
4 Ghahremani M et al. Vitamin D supplementation and incident dementia: Effects of sex,
APOE, and baseline cognitive status. Alzheimers Dement (Amst). 2023 Mar 1;15(1):e12404.
doi: 10.1002/dad2.12404. PMID: 36874594; PMCID: PMC9976297.

5 Płudowski P et al Guidelines for Preventing and Treating Vitamin D Deficiency: A 2023
Update in Poland. Nutrients. 2023 Jan 30;15(3):695. doi: 10.3390/nu15030695. PMID:
36771403; PMCID: PMC9920487.

6 Ames BN, Grant WB, Willett WC. Does the High Prevalence of Vitamin D Deficiency in
African Americans Contribute to Health Disparities? Nutrients. 2021 Feb 3;13(2):499. doi:
10.3390/nu13020499. PMID: 33546262; PMCID: PMC7913332.

7 Engelsen O. The relationship between ultraviolet radiation exposure and vitamin D status.
Nutrients. 2010 May;2(5):482-95. doi: 10.3390/nu2050482. Epub 2010 May 4. PMID:
22254036; PMCID: PMC3257661.

8 Ekwaru JP et al The importance of body weight for the dose response relationship of oral
vitamin D supplementation and serum 25-hydroxyvitamin D in healthy volunteers. PLoS
One. 2014 Nov 5;9(11):e111265. doi: 10.1371/journal.pone.0111265. PMID: 25372709;
PMCID: PMC4220998.
9 Feart C et al.. Associations of lower vitamin D concentrations with cognitive decline and
long-term risk of dementia and Alzheimer’s disease in older adults. Alzheimers Dement.
2017 Nov;13(11):1207-1216. doi: 10.1016/j.jalz.2017.03.003. Epub 2017 May 16. PMID:
28522216.

10 https://apigateway.agilitypr.com/distributions/history/4db5dd81-e4c6-4503-b961-
ca44baed4423

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Both brain size and IQ are falling in modern humans, coinciding with a big increase in mental illness.

What we eat is to blame, says Professor Michael Crawford, author of a new book ‘The Shrinking Brain’ and Sir David Attenborough is convinced he is right.

The Falling IQ

IQ scores have also been steadily falling for the past few decades. Norwegian researchers, headed by Ole Rogeberg, a senior research fellow at the Ragnar Frisch Center for Economic Research in Norway, analysed the IQ scores of Norwegian men born between 1962 and 1991 and found that scores steadily decreased among those born after 1975 (1). “Similar studies in Denmark, Britain, France, the Netherlands, Finland and Estonia have demonstrated a similar downward trend in IQ scores” says Rogeberg. “The decline is due to environmental factors,” 

This coincides with a change in Western diet away from fat, towards carbohydrates and sugar, based on the mistaken belief that it was fat, not sugar, that was causing heart disease and that we should all eat a low-fat diet. Since then, our IQ scores have been dropping by about 7 per cent per generation. 

“We are heading for an idiocracy” says Professor Crawford who is Director of the Institute of Brain Chemistry and Human Nutrition. Currently one in five of the world’s children and adolescents have a mental health condition (2).’  If this trend continues, by 2080 he predicts that more than a third of the world’s population will have a mental disability.

The World Health Organisation report says ‘there has been a 13% rise in mental health conditions. One in eight now suffers from mental illness. The incidence of depression is through the roof. Last year in the UK there were over 100 million prescriptions for antidepressants. 

Crawford is convinced it is the modern-day diet that is causing us to dumb down. “Our genome is adapted to eating the wild foods we ate during our species’ evolution. Today’s diet bears no resemblance to this.”

Key nutrients from land & sea

In his book, The Shrinking Brain, he says “Our ancestors evolved a unique 1,600cc brain evolving from our ancestral 350cc brain of the chimpanzee, despite our genome only differing by 1.5% (3). This could only have happened by providing brain-specific building nutrients from land and sea. There is incontrovertible evidence of early Homo sapiens exploiting the marine food web in coastal Africa.” In other words, we were the waterside ape who became smart, with bigger brains, by eating mussels, oysters, crabs and fish. 

Professor Crawford discovered, in 1971, that the brains of all mammals are rich in omega-3 DHA. Their brain size varied according to their dietary supply of DHA found in seafood. A dolphin, for example, has a 1,700cc brain, slightly larger than ours, while a lion has a 320cc brain about that of a chimpanzee. “The mix of wildland and aquatic foods powered by the encephalization of the brain from the 340cc of the chimp to the 1,500-1,700 of cro-magnon. DHA is not only involved in signalling but it stimulates gene expression in the brain so the rich aquatic food sources constantly, every day, would have powered the increase in brain size and function.” says Crawford.

“Today’s diet contains less than a tenth of the omega-3 fats that our ancestors ate and this is having dire consequences on mental health. Increased rates of depression, autism, ADHD and dementia are all strongly linked to lack of seafood. Increased intake from eating fish or supplementing omega-3 fish oils reduces dementia risk by 20 per cent (4). While a plant-based diet has many benefits, those who eat no fish, are especially vulnerable and must supplement omega-3 DHA, derived from algae. The only way to be sure you have enough is to get a blood test to specifically test your levels.” Says our CEO and founder Patrick Holford.  

This is why we have just launched a simple ‘do it at home’ pin-prick test that can give you a clear indication of your Omega-3 levels, which done alongside our Cognitive Function Test, can help identify what’s driving future risk and show you how to dementia-proof your diet and lifestyle. 

Canadian neuroscientist and brain expert Professor Stephen Cunnane at the University of Sherbrook in Canada agrees “A shore-based diet, i.e., fish, molluscs, crustaceans, frogs, bird’s eggs and aquatic plants, provides the richest known dietary sources of brain selective nutrients.” says Cunnane. “Change in diet away from marine foods is the likely explanation for this decrease in brain size.”  

Sir David Attenborough, a supporter of the waterside ape theory, agrees “Gathering molluscs is far easier than chasing elephants and wildebeests across the savannah.” 

Children & omega-3

Today, under 5 per cent of children achieve the basic requirement for omega-3 from seafood (5).

Professor Michael Crawford, who is a visiting professor at Imperial College’s Chelsea & Westminster campus and on our Scientific Advisory Board, was part of the team that has recently established that, if a pregnant woman lacks omega-3 DHA she produces a substitute fat, oleic acid, to fill the baby’s brain. But it doesn’t work. Levels of oleic acid in a pregnant woman’s blood predicted preterm birth which carries the highest risk of developmental brain problems and mental deficits in their offspring, as well as a risk of learning and cognitive disabilities. Low omega-3 and B vitamins in mothers increase risk for lower IQ, learning and emotional problems in children (6).

A new study shows that the higher the omega-3 index and DHA, the greater both the brain size and the cognition of older people (7). Brain size predicts cognitive abilities, which is why we have started offering these vital tests – which are both easy and affordable to do at home.

Brain size is worked out from skull capacity. Homo sapiens skulls dating back to 29,000 years ago had a brain capacity of 1,660cc. By 10,000 years ago it was around 1,500cc or 1.5 kilograms. The average brain size today is a fifth smaller, at 1,336cc. Brain size may have started to shrink from 10,000 years ago, coinciding with mankind developing more land-based agriculture and eating less marine food along rivers and coasts.

 So we are inviting you to join our ‘citizen science’ study to track the impact of diet and Omega-3 on cognitive function over time.

Our brains and mental health are suffering as a result of our dietary changes.

So if you are concerned about your levels of Omega-3 and how it might be impacting your brain, body and life – you can now test your levels with our Omega-3 hometest kit here, which is offered alongside the free Cognitive Function Test, which assesses how well your diet is supporting your brain health.

Thank you for reading!
Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

Supporting Research

IQ FALLING

Bratsberg B, Rogeberg O. Flynn effect and its reversal are both environmentally caused. Proc Natl Acad Sci U S A. 2018 Jun 26;115(26):6674-6678. doi: 10.1073/pnas.1718793115. Epub 2018 Jun 11. PMID: 29891660; PMCID: PMC6042097.

DECREASE IN BRAIN SIZE

Cunnane SC, Crawford MA. Energetic and nutritional constraints on infant brain development: implications for brain expansion during human evolution. J Hum Evol. 2014 Dec;77:88-98. doi: 10.1016/j.jhevol.2014.05.001. Epub 2014 Jun 11. PMID: 24928072.

MENTAL HEALTH RISING

OMEGA-3 PREDICTS COGNITIVE PROBLEMS IN CHILDREN

Montgomery P, Burton JR, Sewell RP, Spreckelsen TF, Richardson AJ. Low blood long chain omega-3 fatty acids in UK children are associated with poor cognitive performance and behavior: a cross-sectional analysis from the DOLAB study. PLoS One. 2013 Jun 24;8(6):e66697. doi: 10.1371/journal.pone.0066697.

OMEGA-3 PREDICTS RISK FOR DEMENTIA AND COGNITIVE DECLINE

Wei BZ, Li L, Dong CW, Tan CC; Alzheimer’s Disease Neuroimaging Initiative; Xu W. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers. Am J Clin Nutr. 2023 Jun;117(6):1096-1109. doi: 10.1016/j.ajcnut.2023.04.001. Epub 2023 Apr 5. PMID: 37028557; PMCID: PMC10447496.

OMEGA-3 LEVELS PREDICT BRAIN SIZE IN OLDER PEOPLE

Loong, S.; Barnes, S.; Gatto, N.M.; Chowdhury, S.; Lee, G.J. Omega-3 Fatty Acids, Cognition, and Brain Volume in Older Adults. Brain Sci.2023,13,1278. https://doi.org/ 10.3390/brainsci13091278 

References

¹ Bratsberg B, Rogeberg O. Flynn effect and its reversal are both environmentally caused. Proc Natl Acad Sci U S A. 2018 Jun 26;115(26):6674-6678. doi: 10.1073/pnas.1718793115. Epub 2018 Jun 11. PMID: 29891660; PMCID: PMC6042097.

² https://www.who.int/publications/i/item/9789240049338

³ Cunnane SC, Crawford MA. Energetic and nutritional constraints on infant brain development: implications for brain expansion during human evolution. J Hum Evol. 2014 Dec;77:88-98. doi: 10.1016/j.jhevol.2014.05.001. Epub 2014 Jun 11. PMID: 24928072.

⁴ Wei BZ, Li L, Dong CW, Tan CC; Alzheimer’s Disease Neuroimaging Initiative; Xu W. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers. Am J Clin Nutr. 2023 Jun;117(6):1096-1109. doi: 10.1016/j.ajcnut.2023.04.001. Epub 2023 Apr 5. PMID: 37028557; PMCID: PMC10447496.

⁵ Kranz, S.; Jones, N.R.V.; Monsivais, P. Intake Levels of Fish in the UK Paediatric Population. Nutrients 2017, 9, 392. https://doi.org/10.3390/nu9040392

⁶ Montgomery P, Burton JR, Sewell RP, Spreckelsen TF, Richardson AJ. Low blood long chain omega-3 fatty acids in UK children are associated with poor cognitive performance and behavior: a cross-sectional analysis from the DOLAB study. PLoS One. 2013 Jun 24;8(6):e66697. doi: 10.1371/journal.pone.0066697. Erratum in: PLoS One. 2013;8(9); see also Veena SR, Krishnaveni GV, Srinivasan K, Wills AK, Muthayya S, Kurpad AV, Yajnik CS, Fall CH. Higher maternal plasma folate but not vitamin B-12 concentrations during pregnancy are associated with better cognitive function scores in 9- to 10- year-old children in South India. J Nutr. 2010 May;140(5):1014-22. doi: 10.3945/jn.109.118075. Epub 2010 Mar 24. PMID: 20335637; PMCID: PMC3672847; see also McNulty H, Rollins M, Cassidy T, Caffrey A, Marshall B, Dornan J, McLaughlin M, McNulty BA, Ward M, Strain JJ, Molloy AM, Lees-Murdock DJ, Walsh CP, Pentieva K. Effect of continued folic acid supplementation beyond the first trimester of pregnancy on cognitive performance in the child: a follow-up study from a randomized controlled trial (FASSTT Offspring Trial). BMC Med. 2019 Oct 31;17(1):196. doi: 10.1186/s12916-019-1432-4. PMID: 31672132; PMCID: PMC6823954.

⁷ Loong, S.; Barnes, S.; Gatto, N.M.; Chowdhury, S.; Lee, G.J. Omega-3 Fatty Acids, Cognition, and Brain Volume in Older Adults. Brain Sci.2023,13,1278. https://doi.org/ 10.3390/brainsci13091278 

Developing dementia is the second biggest health fear, after cancer. But what can you do about it? 

The conventional view is that genes play a big part and that factors under our control, including diet, lifestyle and health status, account for up to 40% of risk and therefore up to 40% of dementia cases could be prevented or delayed. Genes actually account for less than 1% of Alzheimer’s cases. But a new study from the UK BioBank, following 344,000 people over 15 years, estimates that “up to 73% of cases could be prevented” by targeting risk factors largely under our control. 

The authors of the study, published in the Nature Human Behaviour journal (1), investigated 210 modifiable risk factors. They found that increased hand grip strength (a good reflection of physical strength), increasing leisure or social activities or time spent in sports clubs or gyms, spending less time watching TV or on a computer, having better dental health, drinking more water, not dozing off in the day and sleeping between 7 to 9 hours a night, not smoking or being exposed to smoke and having better lung function were all associated with less risk of Alzheimer’s. Being unemployed, having a low income, having diabetes, high blood pressure or having had a stroke or brain injury all increased risk. Inheriting the so-called ‘Alzheimer’s gene’, ApoE4, didn’t make any significant difference to overall risk.

However, even this figure of 73% may be an underestimate as this study excluded blood test measures. “We have under-estimated the power of prevention,” says Professor David Smith from the University of Oxford, one of the study authors. “Even this figure of up to 73% of cases preventable could be higher if a person’s omega-3 and B vitamin status, measured by a blood test for homocysteine that any GP can do, were taken into account.”

While the BioBank study didn’t include blood test measures of either homocysteine or omega-3, scientists at the US National Institutes of Health have attributed 22% of the risk of Alzheimer’s to raised blood homocysteine and 22% to a lack of omega-3 (2). “These have been shown to predict risk but were beyond the scope of this study.” confirmed the study author, Professor Jin-Tai Yu from Shanghai’s Fudan University. “Homocysteine-lowering treatment with B vitamins, especially B12, is one of the most promising interventions for dementia prevention.” 

The Impact of B Vitamins & Omega-3

Professor Smith’s group at Oxford University tested the effects of giving B vitamins (B6, B12, folate) versus placebo to those with pre-dementia and found that the 10p a day supplements halved the rate of brain shrinkage in one year and virtually stopped further memory loss (3). “The greatest effect we found in our trial was in those in the top third of DHA blood levels (an omega-3 found in fish or fish oil supplements). Those with high DHA reduced their rate of brain shrinkage by 73%, down to the level normally seen in older people with loss of cognitive function. They also had virtually no further memory loss and almost a third ended the trial with no clinical dementia rating at all.”

The benefit of omega-3 was also confirmed in a major study this year of over 100,000 people, finding that increased omega-3 cut the risk of dementia or cognitive decline by around 20%. An increase in intake of omega-3 DHA of 200 mg decreased risk by almost a fifth (4). 

And here at Food for the Brain, we take prevention seriously.

Alzheimer’s is preventable, but not curable

We developed the free online Cognitive Function Test,  which includes a Dementia Risk Index questionnaire assessing your diet, omega-3 and B vitamin status, and lifestyle and an optional home-test kit for pinprick blood tests that will be available soon.

“Over 400,000 people have taken our validated Cognitive Function Test, which not only shows a person their cognitive status right now but also their future risk based on our Dementia Risk Index questionnaire, the factors driving future risk and what they can easily do right now to lower it. If all modifiable risk factors are taken into account, including B vitamins and omega-3, it is highly likely a person could reduce risk by over 80%.” says our CEO, Patrick Holford.

“The government has pledged £160 million a year for dementia prevention research but we are not seeing any of this going into easy prevention wins. Most seem to be fueling drug research for an apparent ‘cure’.

Alzheimer’s is preventable, but not curable. You cannot reverse holes in the brain. With over 200,000 people diagnosed every year with dementia, if prevention were taken seriously we could halve the number of people developing this terrible, but preventable disease.”

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Thank you for reading!
Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

———

References

¹ Zhang, Y., et al. Nature Human Behaviour. 2023 7, 1185–1195

² Beydoun MA., et al. BMC Public Health. 2014 Jun 24;14:643.

 Jernerén F., et al. Am J Clin Nutr. 2015 Jul;102(1):215-21.

³ Oulhaj A., et al. J Alzheimers Dis. 2016;50(2):547-57.

⁴ Wei B., et al. Am J Clin Nutr 2023 Jun;117(6):1096-1109. 

Last month’s newspaper headlines pitched the new anti-amyloid Alzheimer’s drug as a ‘turning point’. The pitch has a lot in common with the statin story.

Last month’s newspaper headlines pitched the new anti-amyloid Alzheimer’s drug as a ‘turning point’. (Read our response here) The pitch has a lot in common with the statin story.

Is high cholesterol the cause of heart disease? No. 

Do statins lower it? Yes.

Are amyloid deposits the cause of cognitive decline? No. 

Do anti-amyloid drugs lower it? Yes.

No doubt there will be a blood test soon for amyloid, just like a blood test for cholesterol, the effect of which pushed millions into taking statins.

Both statins, given to people with very high cholesterol, and anti-amyloid drugs, given to people with very high amyloid levels, do have marginal benefit but not enough to establish causation. In the case of the new Alzheimer’s drug, the benefit is considerably less than half that shown by the combination of B vitamins and omega-3. 

But, even more than statins, they come with a high risk of quite serious adverse effects – over a third in the recent trial got brain bleeding or swelling and three died. Also, the whole brain shrinkage accelerated by twenty percent compared to placebo, a fact not reported in any newspaper. Any vitamin showing such adverse effects would be immediately banned.

But the important question is: what’s causing these diseases, be it cognitive decline or heart disease? To the extent that cholesterol or amyloid is relevant, what makes them go up? Cholesterol gets damaged by sugar and oxidants and is protected by antioxidants such as vitamin C and a low-carb diet. Brain cells get damaged by homocysteine and are protected by B vitamins and omega-3.

Mind the gap 

Also, in those with cognitive decline, there’s an energy deficit in brain cells. Ironically, they can’t get the glucose they need due to ‘insulin resistance’ which is driven by eating too much sugar and ultra-processed carbs. So, the effect of too much sugar is to starve the brain of fuel which then leads to mental tiredness and cognitive decline. 

There is a way around this – and that is to give the brain an alternative fuel – ketones. 

Ketones can either be supplied as ketone salts or esters, both of which taste disgusting or made from a type of fat – principally C8 oil, which is a medium-chain triglyceride. About 7 percent of coconut oil is C8. Studies giving people with cognitive decline a C8-rich MCT oil have shown clear improvements in cognition by increasing the brain’s energy supply and production. Ripping out amyloid deposits isn’t going to fill this energy gap. Eating less carbs, reversing diabetes, which is a big risk factor for dementia, and having C8 oil will. Our podcast with Professor Stephen Cunnane, who heads the Brain Research Team at Sherbrooke University in Sherbrooke, Quebec, Canada and holds the clinical research chair in ketotherapeutics and on the Food for the Brain Scientific Advisory Board, discusses this area with Patrick Holford – listen to the podcast here.

Also, in those with cognitive decline, there’s an energy deficit in brain cells. Ironically, they can’t get the glucose they need due to ‘insulin resistance’ which is driven by eating too much sugar and ultra-processed carbs. So, the effect of too much sugar is to starve the brain of fuel which then leads to mental tiredness and cognitive decline. 

An increase in amyloid in the brain is really a consequence of the disease, not the cause. It’s part of an inflammatory reaction, much like the nodules in joints that occur from inflammation resulting in arthritis. Should you cut out the nodules or reduce inflammation? Do you eliminate the root cause or target the consequences? Inflammation is both a function of a bad diet high in ultra-processed and fried food, smoking, lack of antioxidants, omega-3 fats and vitamin C to name a few key nutrients. Having an active lifestyle is also important.

The same story exists with all major diseases. Cancer cells thrive on sugar. Do you starve them and in the process protect healthy cells, or cut or drug them out?

The big difference in approach – treat the cause or the consequences – is money.  You can’t patent nutrients, but you can patent drugs that stop you from making cholesterol or amyloid. More than $1 billion has been spent on the anti-amyloid approach and the push isn’t going to stop. Pharma needs a return on their investment. This latest drug treatment, according to the Financial Times, will be sold for $26,000 a year. Taking B vitamins, eating fish and/or supplementing omega-3, which has shown more clinical benefit and reduced the rate of brain shrinkage by over 70% with no side-effects – actually side-benefits – might cost £100 a year. Which would you choose?

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

Friday’s Guardian article on ‘I refuse to get old’ about how readers strive to keep dementia at bay, on the face of it, seems like a good message. Most cases given focussing on people increasing physical and mental activity, as an active lifestyle is certainly a positive step towards prevention. But these two prevention steps reduce risk by less than B vitamins, omega-3 and reducing sugar and carbs.

The first error is the extent to which dementia can be prevented. The article says by 40%, which is based on the inaccurate Lancet Commission’s Livingston report which, despite being sent all the evidence, doesn’t even mention B vitamins and homocysteine, which is the single most important prevention step. There’s also only one mention of omega-3 from a redundant study so this risk factor is also ignored to arrive at the ‘40% preventable’ figure.

80% of dementia cases could be prevented, not 40%

The latest assessment of how much can be prevented, based on UK Biobank data is “47%–73% of dementia cases could be prevented.” This was published last week in Nature and even this is an underestimate because, while including B vitamins, it excludes the impact of omega-3 and seafood. If that modifiable risk factor were included it is likely that around 80% of dementia cases could be prevented. This would mean that the Guardian is halving the impact of prevention.

The next error is no-one quoted in the article mentions diet, let alone B vitamins or omega-3, except for Professor David Smith. He rightly says: ‘The large leap forward in what we know about preventability has informed his own retirement lifestyle: he walks for half an hour a day, spends at least 15 minutes on an exercise bike, drinks alcohol sparingly, and follows a Mediterranean diet.

Having led a clinical trial into the benefits of B vitamins in people with mild cognitive impairment – a memory-loss condition that increases the chance of those who have it developing dementia – Smith takes 500mcg of vitamin B12 daily and fish oil with Omega 3. Nutrition, he believes, is not given enough prominence when we talk about prevention.’

When we calculated the attributable risk for each risk factor for our online Dementia Risk Index questionnaire each domain scores as follows, adding up to 100%:

B Vitamins           18%

Brain Fats             17%

Glycemic Load     15%

Active Body          15%

Active Mind          10% 

Sleep & Calm       10%

Antioxidants         10%

Gut  Health          5%

So, the biggest impact you can have on your risk is to supplement B vitamins, especially B12, and omega-3 fish oils, as David Smith does. But the Guardian article then downplays the role of supplements with this statement ‘Alzheimer’s Research UK does not recommend any supplements in particular, but says “there is no harm in people taking a supplement to reduce the risk of deficiency”.

B12 Reference Ranges are wrong

This is not only wrong because brain shrinkage occurs well within the ‘normal’ range of either B12 dietary intake or blood tests, but also ARUK, who largely promotes drug-based solutions, happened to know what they are saying is wrong because they funded, back in 2010, a top level, randomised placebo controlled trial on B vitamins that, virtually stopped cognitive decline and reduced brain shrinkage by 52% – in the group with higher omega 3 , by 73% – that is the most effective disease modifying treatment to date! In fact, David Smith and I have written to ARUK to stop making this inaccurate statement. Here’s why it’s wrong:

The reason so many people are low in B12 is less to do with dietary intake and more due to malabsorption which often becomes worse with age, due to lack of stomach acid secretions which are needed to absorb B12. So relying only of analysing what someone eats (meat, fish, eggs, dairy being the only sources of B12) doesn’t prove sufficiency. Note that David Smith says he supplements 500mcg of B12 daily, while the basic ‘Nutrient Reference Value’ (NRV) that you’ll see on the back of a vitamin supplement is 2.5mcg. So, why does he take two hundred times this amount? Because you cannot rely on your dietary intake to confirm sufficiency. Also, there is growing body of evidence from well designed studies showing that supplements giving nutrients at levels beyond the basic ‘recommended intakes’ delay, eliminate or ameliorate symptoms of dementia.

So, what about blood tests? One UK study reports that 2 in five people over 61 have insufficient levels of B12 to prevent accelerated brain shrinkage. Serum B12 is the ‘standard’ test used by doctors. The UK reference range of above 180pg/ml being sufficient (and the US lower level of 200pg/ml) is out of date and in need of revision. In Europe and Japan anything below 500pg/ml is considered deficient. Accelerated brain shrinkage due to a lack of B12 does happen with B12 levels below 500pg/ml.

In conclusion, while it is good to recommend a physically and intellectually lifestyle, ignoring the need to supplement B vitamins, especially B12, eat fish and supplement omega-3, and cut your intake of carbs and sugar, is not doing anyone any favours.

Take the free test here to work out which simple steps will most reduce your risk.

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

Don’t be fooled by the rhetoric promoting the new Alzheimer’s anti-amyloid drug. The results – increased brain shrinkage, a third getting brain bleeding or swelling and questionable clinically meaningful benefit – are not good.

However, reading this week’s headlines claiming a ‘turning point’ in the fight against Alzheimer’s you’d be mistaken in thinking something new has occurred since Eli Lilly’s press release regarding their new drug, donanemab, a month ago. What stimulated this week’s front pages was publication of the actual study in the Journal of the American Medical Association [1] giving more details of the results. This was reported positively in every major newspaper. Yet not one reported the fact that the drug treatment accelerated the rate of brain shrinkage by over 20% compared to placebo. This is clearly stated in the paper as “At 76 weeks, MRI [scans] showed a greater decrease in whole brain volume”.

This is consistent with a meta-analysis of all anti-amyloid treatments including donanemab, in the journal Neurology [2] earlier this year, which concluded that “Mild cognitively impaired participants treated with anti-amyloid drugs were projected to have a material regression toward brain volumes typical of Alzheimer dementia approximately 8 months earlier than if they were untreated.”

In stark contrast, treatment with homocysteine-lowering B vitamins, given to those with sufficient omega-3, ‘the rate of atrophy was significantly slowed by circa 70%’.[3] B vitamins and omega-3 are but two out of eight established prevention steps you can take yourself.

Alzheimer’s is characterised by brain shrinkage, and particularly in the central ‘hippocampus’ area of the brain. The new drug treatment was not associated with shrinkage of the hippocampus, just the whole brain. In fact, there was a very small reduction of about one per cent in shrinkage in this area of the brain compared to the placebo. In the B vitamin study there was an 80% reduction in shrinkage in the medial temporal lobe. While it is theoretically possible that, having selected people with lots of plaques, then targeting them with an aggressive drug, the brain may have shrunk as part of the process of amyloid destruction, this is not yet known and therefore this increased brain shrinkage is worrying

The other main measure of Alzheimer’s and dementia, made by a health professional, include interviewing the patient’s carer or partner – thus potentially subject to ‘hopeful’ bias – is the Clinical Dementia Rating (CDR).

The new drug treatment results do show a statistically significant improvement, showing just over half a point  (0.67) less worsening, compared to placebo, on the 18 point CDR scale. But is this small change meaningful? A study in the Lancet suggests that minimum changes of 0.98 in mild cognitive impairment and 1.63 in mild Alzheimer’s disease are meaningful. [4] This study was on those with early Alzheimer’s.

In contrast, a trial giving omega-3 fish oils to those with adequate B vitamin status, showed three times this beneficial clinical effect [5]. In another, giving homocysteine lowering B vitamins to those with adequate omega-3, almost two thirds of the trial participants ended the trial with an overall Clinical Dementia Rating of zero [6]. This means they were no longer diagnostically labelled as having cognitive impairment. In other words, not less worse, but actually better. 

Serious adverse effects including deaths

More details in the recent donanemab paper were given on the adverse effects and trial deaths. ‘Treatment-emergent adverse events’ were reported by 759 of 853 participants (89%) receiving donanemab’ and ‘Either amyloid-related imaging abnormalities of edema/effusion [swelling] or microhaemorrhages [bleeding] occurred in 314 participants (37%) receiving donanemab’. Also, in the donanemab group, ‘3 participants with serious amyloid-related imaging abnormalities subsequently died.’ This means that more than a third had brain bleeding or swelling and 1 in 287 died. This compares to no adverse events in the B vitamin and omega-3 trials, or other prevention approaches. If any nutritional supplement had anything like these adverse effects it would be banned, not licenced.

According to the Financial Times, this new treatment will cost $26,000 a year (in addition to medical costs including numerous scans). In the UK this would be paid by the taxpayer. In contrast, taking homocysteine-lowering B vitamins, eating fish and/or having fish oil supplements would cost perhaps 20p or cents a day.

So, the question is would you rather take a treatment that markedly slows both whole brain and medial temporal lobe shrinkage than a treatment that is associated with a greater loss of brain volume, a high risk of adverse effects and costs.

The big push is now on to get approval of the UK’s NICE  (National Institute for Health & Care Excellence) and the drug licensed in Europe. NICE have previously refused to consider the evidence for homocysteine-lowering B vitamins and omega-3, which is now overwhelmingly positive, when both these nutrients are combined.

That is why we, at Food for the Brain, aim to make sure as many people as possible know that the real ‘turning point’ for Alzheimer’s is prevention through diet, nutrition and lifestyle improvements, not expensive drugs with dangerous side-effects.

Please take the Cognitive Function Test yourself at foodforthebrain.org, and encourage all you know to do the same. We appreciate your support by becoming a Friend at foodforthebrain.org/friend. 

REFERENCES

1. Simms J., et al JAMA July 17, 2023.

2. Alves, F., et al Neurology 2023 May 16;100(20):e2114-e2124. 

3. Jernerén F., et al. Am J Clin Nutr. 2015 Jul;102(1):215-21.

4. Liu KY., et al Lancet Psychiatry 2021;8:-6.

5. Jernerén F., et al J Alzheimers Dis. 2019;69(1):189-197. doi: 10.3233/JAD-181148. PMID: 30958356

6. de Jager C et al Int. J. Geriatr. Psychiatry 27:592–600 2012

Autism is one disease where there is a very high ‘inherited’ component.

In studies with genetically identical twins, if one twin has it, the odds of another having a diagnosis is about 60%. But it’s not in the ‘in the genes’ since we share the same ‘environment’ as our siblings.

Perhaps the more interesting question is why the number of children diagnosed with Attention-deficit /hyperactivity disorder (ADHD), autism and other neurodevelopmental disorders classifying them as ‘neurodivergent’, has rocketed in both the UK and US.

One in six children is ‘neurodivergent’ as autism numbers quadruple.

UK figures (see here) which show that just under 1.5 million pupils in England have special educational needs which is one in six children. Autism is the biggest part of this, has been steadily rising in both the Uk and US.

“Now, one in six children in the US are classified as neurodivergent and one in 36 as autistic – a fourfold increase in 20 years.” says pediatric Professor Alessio Fasano from Massachusetts General Hospital for Children, Harvard Medical School.  

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All down to our increased awareness & better diagnosis?

According to Dr Rona Tutt OBE, past president of the UK’s National Association of Head Teachers “There has been a dramatic increase in the number of people being diagnosed with ASD. Although some of this is due to a broader definition of autism as well as better diagnosis, it raises the question of whether it may also be the result of environmental changes, which have also been dramatic.” 

Some UK schools are reporting as many as one in four children having problems.

Have our genes changed in the past few decades?

Since the genes cannot have changed this rapidly, the increase points to the influence of environmental factors of which there are many candidates.

The main suspects are:

Gut problems
Wheat, milk and sugar
Vaccines
Environmental anti-nutrients and toxins
Social media overuse and social issues
Maternal nutrition and brain formation essential fats 

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The gut’s role

World-renowned pediatric gastroenterologist, and research scientist Professor Alessio Fasano, MD, directs the Center for Celiac Research and Treatment at Massachusetts General for Children thinks something is going wrong in the gut, with many ASD children reporting gut problems including diarrhoea, constipation, belching and excessive flatulence and ‘dysbiosis’ – abnormal patterns of gut bacteria. In some children, wheat and milk may contribute to these symptoms. His research finds that neurodivergent children show high levels of ‘zonulin’, a family of proteins that regulate the barrier between intestinal cells in the digestive tract that can lead to “leaky gut.” ASD children are often found to have opioid-like wheat and milk proteins in their urine, making these foods especially ‘addictive’.

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Prenatal nutrition?

Professor Michael Crawford, who heads the Institute of Brain Chemistry and Human Nutrition at the Chelsea & Westminster Hospital says “We can predict which babies are going to have developmental problems from the fats in the mother’s blood. When omega-3 levels are low, the mother produces a non-functional ‘brain fat substitute’ to build their baby’s brain during pregnancy, high levels of which predict problems. The brain is 50% fat, and omega-3 DHA should make up most of the structural fat in brain cells.” Less than 5 per cent of children in the UK achieve the basic dietary recommendations for omega-3 and fish.

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Methylation & B vitamins

Vitamins may help. ‘A high level of homocysteine, a marker for B vitamin deficiency, predicts ASD and studies have shown that giving homocysteine-lowering vitamin B6, B12 and folate help reduce symptoms.” says Patrick Holford from the Food for the Brain Foundation, which is hosting the masterclass. “Vitamin A improves eye coordination and vision, helping those with autism who don’t look you in the eye and have visual problems.”

A 12-month randomised controlled trial giving omega-3, vitamins, digestive enzymes and a healthy gluten-free, casein-free diet showed major improvement in both autistic symptoms and raising IQ.

Nutrition and functional medicine therapist Anne Pemberton, who specialises in helping those with ASD, is spoke at the Autism Masterclass reports considerable success, not just by improving nutrition but by addressing the psychological and social circumstances of neurodivergent children. “It is critical to work with both mother and child, and not only address critical nutritional issues, stress triggers including early life traumas, and suppressed emotions as a result of their condition and conditioning, and to help them develop a sense of self and mindset. I have seen hundreds of children and adults who usually have major improvements. Peter, age 8, is a case in point. He was diagnosed with ASD and classified as needing special education. 15 months later he’s no longer even classified as ASD.”

So, as you can see, there are many layers to Autism and Neurodivergence.

For more information you can:

Get instant access to our Autism Masterclass to learn from the expert
Find out more about our Smart Kids & Teens Programme here to learn about the program, conference and more!

Failure of yet another anti-amyloid drug is hailed as ‘the beginning of the end for Alzheimer’s’, according to the Times headline today. It certainly was the end for two, possibly three volunteers given the experimental drug, according to the BBC [1] .

Like other anti-amyloid drugs, the level of significant adverse effects was unacceptably high. According to the Eli Lilly’s press release [2] (no trial has been published) one quarter (24%) of those on the drug developed brain swelling and 24% brain bleeding. It is these adverse effects that can cause death. I’m not quite sure how the BBC conclude only ‘1.6% developed dangerous brain swelling’. Perhaps they meant the level of swelling that could be fatal? But brain swelling and bleeding is not a good idea in elderly people with pre-dementia. Apart from anything else this means they’d need frequent and expensive brain scans to check whether or not this was occurring with each monthly treatment.

The press release inflated the apparent benefit in the usual way saying ‘29% less reduction, compared to placebo’ on the main measure of Clinical Dementia Rating , thus showing the relative, not absolute effect on cognitive assessment. What it actually means is that those on the placebo degenerated from a clinical perspective and those on the drug degenerated a bit less so.

The measure in question, Clinical Dementia Rating (Sum of Boxes), is a questionnaire, administered by a health professional who asks the patient’s partner or carer to rate their memory and 6 aspects of their general functional ability as being normal, questionable, mild, moderate or severe. Depending on the carer’s assessment each question adds either zero (if normal), 0.5, 1, 2 or 3 to the ‘Sum of Boxes’ score, which can therefore range from zero (nothing wrong) to 18 (severe impairment in everything). This is balanced by an interview with the participant who answers questions related to each of the domains/aspects of functional ability, and the doctor or rater scores the CDR taking both the subjective and objective evidence into account. The previous anti-amyloid drug trial, which reported less than half a point (0.45) difference, has been criticised for potential ‘unblinding’. This means that the carer or partner, when asked about how they thought the ‘patient’ was doing, might be biased to provide a more optimistic assessment because they knew they were on the drug from the adverse effects and thus hoped there was some improvement.

So, what happened in this trial? Those on the placebo got 2.4 points worse over 18 months and those on the drug treatment got 1.7 points worse. That’s relatively 29% less worse, but the absolute improvement is the difference, namely 0.49 points, similar to the previous ant-amyloid treatment reporting 0.45 points. So, no meaningful difference between the previous failed drug, nor the one before it which reported 0.39 points on an 18-point scale. According to a British Medical Journal editorial “minimum changes of 0.98 in mild cognitive impairment and 1.63 in mild Alzheimer’s disease are meaningful.” [3] This means that these results were clinically meaningless. All data from the drug company’s own press release.

How this hails the ‘beginning of the end’ of Alzheimer’s beggar’s belief. When compared with the effect of B vitamins or omega-3 fish oil in similar randomised controlled placebo trials [4], these results pale into insignificance, and especially the combination of the two[5]. In those with high homocysteine, given B vitamins, and with sufficient omega-3, there was 73% less brain shrinkage [6] and a third ended the trial with an overall Clinical Dementia Rating of zero [7] – i.e. no longer diagnostically labeled as having dementia. In other words, not less worse, but actually better. Why does this not get reported?

Foodforthebrain.org offers a free, validated online Cognitive Function test that includes an assessment of a person’s Dementia Risk Index with guidance on how to reduce that risk.

>> Take the Test here <<

Reference & Links

¹ https://www.bbc.co.uk/news/health-65471914

²  https://investor.lilly.com/news-releases/news-release-details/lillys-donanemab-significantly-slowed-cognitive-and-functional

³  Walsh S, Merrick R, Richard E, Nurock S, Brayne C. Lecanemab for Alzheimer’s disease. BMJ. 2022 Dec 19;379:o3010. doi: 10.1136/bmj.o3010. PMID: 36535691.

⁴  Jernerén F, Cederholm T, Refsum H, Smith AD, Turner C, Palmblad J, Eriksdotter M, Hjorth E, Faxen-Irving G, Wahlund LO, Schultzberg M, Basun H, Freund-Levi Y. Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer’s Disease: The OmegAD Study. J Alzheimers Dis. 2019;69(1):189-197. doi: 10.3233/JAD-181148. PMID: 30958356; see also Jernerén F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H, Smith AD (2015). Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. Am J Clin Nutr. 2015 Jul;102(1):215-21

⁵  Oulhaj, A et al, ‘homocysteine as a predictor of cognitive decline in Alzheimer’s Disease’, Int J Geriatric psychiatry, 25(1): 82-90 (2010)

⁶  Douaud G, Refsum H, de Jager CA, Jacoby R, Nichols TE, Smith SM, Smith AD. Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci U S A 2013; 110: 9523-8.

⁷ Oulhaj A, Jernerén F, Refsum H, Smith AD, de Jager CA. Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment. J Alzheimers Dis. 2016;50(2):547-57. doi: 10.3233/JAD-150777. PMID: 26757190; PMCID: PMC4927899.

In the UK progress in putting these breakthroughs into action is slow. The two leading charities, the Alzheimer’s Society and Alzheimer’s Research UK (ARUK) fail to mention the importance of homocysteine lowering B vitamins and omega-3 at all and have confirmed that they are not funding any research on their use in prevention or planning to do so. ARUK’s chief medical officer Professor Jon Schott and the Alzheimer’s Society’s associate director of research, Richard Oakley, declined to comment.

ARUK’s Brain Health Check-In, a short 13 question check list, with only one very basic question on diet, says nothing at all about B vitamins or whether or not a person supplements omega-3 fish oils despite ARUK having part-funded the Oxford University research. According to Professor Smith, who was the first Chair of their Scientific Advisory Board “ARUK part-funded our trial on B vitamins, and are aware of the results. I don’t understand why they make no mention of such an effective preventive intervention, that is taking a 10p a day B vitamin supplement if your homocysteine is high. Now we know that those who also supplement with omega-3 fish oil, or eat fish regularly, reduce their risk. These are the easiest two prevention actions anyone can take, with a significant impact on reducing the risk for dementia. Everyone needs to know this.”

“We’ve been applying to UK and EU agencies for the past 8 years to fund the obvious next trial – testing the effects of B vitamins and omega-3 combined to see if they slow, or prevent, conversion from cognitive impairment to dementia, but to no avail.” Says Professor Smith.

Neither the Alzheimer’s Society, nor ARUK are funding any vitamin or omega-3 research and spend virtually none of their annual research pot, which exceeded £37 million last year, on diet or lifestyle prevention which offer the most potential, despite these representing up to half of the risk for Alzheimer’s. Neither would confirm the percentage of their research funds that were being spent on prevention research.

UK Government have pledged to deliver ‘Dementia Moonshot’, doubling dementia research funding to £160 million to ‘fast-track the development of new treatments’, meanwhile ignoring the biggest breakthroughs in diet and lifestyle prevention. Most support is feeding failed drug research. With an estimated $50 billion [12] spent so far on amyloid drugs and research, all of which have failed to produce any clinical benefit, isn’t it time governments and Alzheimer’s charities took prevention seriously?

In contrast, the Food for the Brain Foundation are doing just that. “At Foodforthebrain.org we are testing almost 4,000 people every month on our free online Cognitive Function Test, and assessing all risk factors on a 140 question questionnaire, including the need for B vitamins and omega-3. We hope, soon, to introduce a pinprick blood test for both omega-3 and homocysteine. We don’t know why the most evidence-based, easy to action and inexpensive prevention steps are being ignored” says Holford. “Why world class scientists such as Professor David Smith’s team at Oxford University have been unable to get funding for the most essential research is shameful. Right now we know enough to cut the average person’s risk of developing Alzheimer’s by up to two thirds and the number of people developing dementia by a third if only there was the political will to do so.”

One of the reasons for complacency in the UK is the Lancet’s commissioned report on Alzheimer’s prevention chaired by Gillian Livingston, Professor of Psychiatry for Older  People, at the University College London (UCL). The report, first published in 2017, didn’t include B vitamins. Despite being sent all the evidence by Smith. The 2020 revised report still excluded this vital research, as did a follow up report specifically on supplements in 2022. “There are no trials that show that lowering homocysteine has any benefit” she told us yet she had been sent the unequivocal evidence that the B vitamins reduced brain shrinkage by up to 73%, compared to the 2% reduction of anti-amyloid drugs and the combination of omega-3 and B vitamins has lowered the Clinical Dementia Rating (CDR) in placebo controlled trials by three times that reported by the recent anti-amyloid drug, Lecanemab. (see charts below).

When asked about the recent finding of a synergistic effect of B vitamins and omega-3 she said “It sounds a good hypothesis. I hope they can get the funding for it, but raised homocysteine is not common in the wider population and drug companies can’t be expected to fund nutrition trials, so money would have to come from some government agency.”

There is one prevention study, called AppleTree, underway at University College London. It focuses on reducing risk for Alzheimer’s by eating a Mediterranean style diet and lifestyle advice, including encouraging smokers to quit, which is a known risk factor for cognitive decline. One recent study shows that being a smoker increases risk for dementia by 1.5 times and quitting for at least 3 years reduces much of that risk. [13] One in twelve people over 65 smoke.

In contrast, almost half of all people over 65 have raised homocysteine [14] which increases risk for cognitive impairment by up to ten times, according to Chinese research published last year[15]. Lowering homocysteine with B vitamins, and sufficient omega-3, would virtually eliminate that risk. This suggests that targeting B vitamins and omega-3 would be about twenty times more impactful in preventing dementia than quitting smoking. Yet the need for supplemental intake of these nutrients is not part of the Apple Tree protocol.

If you’d like to test your cognitive function and find out how to reduce your risk, register here and join our citizen science campaign.

References

[1] Jernerén F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H, Smith AD (2015). Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. Am J Clin Nutr. 2015 Jul;102(1):215-21

[2] Oulhaj, A et al, ‘homocysteine as a predictor of cognitive decline in Alzheimer’s Disease’, Int J Geriatric psychiatry, 25(1): 82-90 (2010)

[3] van Soest, A.P.M., van de Rest, O., Witkamp, R.F. et al. DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial. Eur J Nutr (2022). https://doi.org/10.1007/s00394-022-02924-w

[4] Jernerén F, Cederholm T, Refsum H, Smith AD, Turner C, Palmblad J, Eriksdotter M, Hjorth E, Faxen-Irving G, Wahlund LO, Schultzberg M, Basun H, Freund-Levi Y. Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer’s Disease: The OmegAD Study. J Alzheimers Dis. 2019;69(1):189-197. doi: 10.3233/JAD-181148. PMID: 30958356.

[5] Walsh S, Merrick R, Richard E, Nurock S, Brayne C. Lecanemab for Alzheimer’s disease. BMJ. 2022 Dec 19;379:o3010. doi: 10.1136/bmj.o3010. PMID: 36535691.

[6] Li M, Li W, Gao Y, Chen Y, Bai D, Weng J, Du Y, Ma F, Wang X, Liu H, Huang G. Effect of folic acid combined with docosahexaenoic acid intervention on mild cognitive impairment in elderly: a randomized double-blind, placebo-controlled trial. Eur J Nutr. 2021 Jun;60(4):1795-1808. doi: 10.1007/s00394-020-02373-3. Epub 2020 Aug 28. PMID: 32856190.

[7] Yu JT, Xu W, Tan CC, Andrieu S, Suckling J, Evangelou E, Pan A, Zhang C, Jia J, Feng L, Kua EH, Wang YJ, Wang HF, Tan MS, Li JQ, Hou XH, Wan Y, Tan L, Mok V, Tan L, Dong Q, Touchon J, Gauthier S, Aisen PS, Vellas B. Evidence-based prevention of Alzheimer’s disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials. J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1201-1209. doi: 10.1136/jnnp-2019-321913. Epub 2020 Jul 20. PMID: 32690803; PMCID: PMC7569385.

[8] Huang Y, Deng Y, Zhang P, Lin J, Guo D, Yang L, Liu D, Xu B, Huang C, Zhang H. Associations of fish oil supplementation with incident dementia: Evidence from the UK Biobank cohort study. Front Neurosci. 2022 Sep 7;16:910977. doi: 10.3389/fnins.2022.910977. PMID: 36161159; PMCID: PMC9489907.

[9] Jeong SM, Park J, Han K, Yoo J, Yoo JE, Lee CM, Jung W, Lee J, Kim SY, Shin DW. Association of Changes in Smoking Intensity With Risk of Dementia in Korea. JAMA Netw Open. 2023 Jan 3;6(1):e2251506. doi: 10.1001/jamanetworkopen.2022.51506. PMID: 36656579; PMCID: PMC9857334.

[10] Beydoun MA, Beydoun HA, Gamaldo AA, Teel A, Zonderman AB, Wang Y. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 2014 Jun 24;14:643. doi: 10.1186/1471-2458-14-643. PMID: 24962204; PMCID: PMC4099157.

[11] Witte AV, Kerti L, Hermannstädter HM, Fiebach JB, Schreiber SJ, Schuchardt JP, Hahn A, Flöel A. Long-chain omega-3 fatty acids improve brain function and structure in older adults. Cereb Cortex. 2014 Nov;24(11):3059-68. doi: 10.1093/cercor/bht163. Epub 2013 Jun 24. PMID: 23796946.

[12] Cummings JL, Goldman DP, Simmons-Stern NR, Ponton E. The costs of developing treatments for Alzheimer’s disease: A retrospective exploration. Alzheimers Dement. 2022 Mar;18(3):469-477. doi: 10.1002/alz.12450. Epub 2021 Sep 28. PMID: 34581499; PMCID: PMC8940715.

[13] Lu Y, Sugawara Y, Zhang S, Tomata Y, Tsuji I. Smoking cessation and incident dementia in elderly Japanese: the Ohsaki Cohort 2006 Study. Eur J Epidemiol. 2020 Sep;35(9):851-860. doi: 10.1007/s10654-020-00612-9. Epub 2020 Feb 15. PMID: 32060675; PMCID: PMC7525275.

[14] Pfeiffer CM, Osterloh JD, Kennedy-Stephenson J, Picciano MF, Yetley EA, Rader JI, Johnson CL. Trends in circulating concentrations of total homocysteine among US adolescents and adults: findings from the 1991-1994 and 1999-2004 National Health and Nutrition Examination Surveys. Clin Chem. 2008 May;54(5):801-13. doi: 10.1373/clinchem.2007.100214. Epub 2008 Mar 28. PMID: 18375482.

[15] Teng Z, Feng J, Liu R, Ji Y, Xu J, Jiang X, Chen H, Dong Y, Meng N, Xiao Y, Xie X and Lv P (2022) Cerebral small vessel disease mediates the association between homocysteine and cognitive function. Front. Aging Neurosci. 14:868777. doi: 10.3389/fnagi.2022.868777

Study Finds Mediterranean and MIND Diets Are Linked to Fewer Alzheimer’s Brain Changes

Research suggests these eating patterns may help support long-term brain health

Following a Mediterranean or MIND diet has consistently been associated with better cognitive health. In recent years, the connection between the mind diet, Alzheimer’s disease and overall brain health has become a focus of research. Research also suggests that people who adhere more closely to these dietary patterns have fewer of the brain changes associated with Alzheimer’s disease.

One study published in Neurology found that people who most closely followed the Mediterranean or MIND diet had fewer amyloid plaques and tau tangles, the two hallmark features of Alzheimer’s disease. They also had lower overall Alzheimer’s pathology at autopsy.

Although this research cannot prove that diet prevents Alzheimer’s disease, it adds to a growing body of evidence linking healthy dietary patterns with better brain health as we age.

One of the study’s most striking findings was that participants with the highest adherence to the MIND diet had levels of amyloid plaques and tau tangles comparable to those seen in people around 12 years younger than those with the lowest adherence. This comparison reflects differences in Alzheimer’s-related brain pathology rather than actual biological age.

The researchers also found that even meeting the recommended intake for a single food group, such as vegetables or fruit, was associated with lower amyloid pathology, equivalent to around four years less brain ageing. The strongest association was seen with green leafy vegetables, with people eating the most greens showing substantially fewer Alzheimer’s-related brain changes than those eating the least.

What are amyloid plaques and tau tangles?

Amyloid plaques are deposits of beta amyloid protein that accumulate between brain cells. Tau tangles are abnormal bundles of tau protein that build up inside neurons.

Both are considered hallmark features of Alzheimer’s disease and are commonly found in the brains of people with dementia.

However, Alzheimer’s disease is complex. Scientists now recognise that inflammation, vascular disease, genetics, insulin resistance and other lifestyle factors all contribute to the disease process. Amyloid and tau are important, but they are only part of the story.

Can diet reduce amyloid plaques?

There is currently no evidence that any diet can remove existing amyloid plaques.

However, research suggests that people who consistently follow dietary patterns such as the Mediterranean and MIND diets tend to have fewer Alzheimer’s-related brain changes and a lower risk of cognitive decline.

Rather than reversing Alzheimer’s disease, these diets appear to support long-term brain health through multiple mechanisms, including reduced inflammation, improved vascular health and better overall nutrition.

Why might diet influence brain health?

Researchers believe several mechanisms may explain these findings.

Healthy dietary patterns are rich in nutrients that may help:

reduce chronic inflammation
improve blood flow to the brain
protect brain cells from oxidative stress
support healthy nerve cell function
maintain cardiovascular health, which is closely linked to brain health

Rather than relying on a single nutrient, these dietary patterns combine many foods that work together over time.

Why were leafy greens highlighted?

Among all the foods analysed, green leafy vegetables showed one of the strongest associations with lower Alzheimer’s pathology.

Leafy greens provide several nutrients that support normal brain function, including:

folate
vitamin K
lutein
magnesium
dietary nitrates

Although researchers cannot say that leafy greens alone reduce Alzheimer’s risk, regularly eating them is consistently associated with better cognitive ageing across multiple studies. The findings from this study suggest that increasing the intake of foods such as leafy greens, berries, whole grains, olive oil and fish as part of an overall healthy dietary pattern may help support long-term brain health.

How strong is the evidence?

This study was observational, meaning it identified associations rather than proving cause and effect.

That means researchers cannot conclude that the Mediterranean or MIND diet directly prevented Alzheimer’s disease.

However, these findings are consistent with many previous studies linking healthy dietary patterns with better cognitive health and a lower risk of dementia.

Taken together, the evidence suggests that diet is likely to be one important part of maintaining brain health, alongside regular physical activity, quality sleep, social engagement and management of cardiovascular risk factors.

What this research means?

This study adds another piece to the growing evidence that long-term dietary habits may influence how the brain ages.

Rather than focusing on individual “superfoods,” the findings support the importance of an overall healthy eating pattern that includes plenty of vegetables, healthy fats, legumes, whole grains and other minimally processed foods.

While more research is needed, studies suggest that the Mediterranean and MIND diets may help reduce Alzheimer’s disease related brain changes and support long term brain health when followed consistently as part of a healthy lifestyle.

Practical takeaways

The greatest benefits are likely to come from following these habits consistently over many years, rather than relying on short-term dietary changes or individual foods or supplements.

Want to learn more? Explore our guide to the Mediterranean and MIND diets to discover how these eating patterns compare and how to incorporate them into your daily routine.

Related reading:

The Alzheimer’s Prevention Diet
Alzheimer’s: Why Prevention is Better than Cure
Groundbreaking New Research: The Key to Reducing Dementia Risk
Mediterranean Diet & Depression

By Patrick Holford

Taking vitamin D supplements may help ward off dementia, according to a new, large-scale study involving over twelve thousand dementia-free 70+ year olds in the US. More than a third (37%) took supplements of vitamin D. After adjusting for baseline age, sex, education, race, cognitive diagnosis, depression, and APOE4 status, exposure to prescribed vitamin D supplements was associated with 40% lower incidence of dementia during a ten-year period.

The study, carried out by researchers from the University of Calgary’s Hotchkiss Brain Institute in Canada and the University of Exeter in the UK, has been published in the journal Alzheimer’s & Dementia. The team found that taking vitamin D was associated with living dementia-free for longer, and they also found 40 per cent fewer dementia diagnoses in the group who took supplements.

Professor Zahinoor Ismail, of the University of Calgary and University of Exeter, who led the research, said: “We know that vitamin D has some effects in the brain that could have implications for reducing dementia, however so far, research has yielded conflicting results. Our findings give key insights into groups who might be specifically targeted for vitamin D supplementation. Overall, we found evidence to suggest that earlier supplementation might be particularly beneficial, before the onset of cognitive decline.”

One of the problems in relation to vitamin D and cognition is the use of variable amounts of vitamin D, and the lack of reporting regarding blood levels at baseline and conclusion of trials. This study has the same issue. We do not know the dose taken nor the starting and end blood levels of those supplementing or not.

A review by Dr William Grant, Director of Sunlight, Nutrition and Health Research Center, who is the expert on our Scientific advisory Board shows that the higher the blood level of vitamin D (25-hydroxyvitamin D [25(OH)D] is the form measured in the blood serum) the lower is the risk of developing Alzheimer’s as well as dementia in general. The mechanisms identified as potentially explaining its benefit include reduced brain aging, cellular senescence, mitochondrial dysfunction and oxidative stress as well as higher high-density lipoprotein (HDL). Observational study findings indicate that blood levels above 30 ng/mL (75 nmol/L) reduce dementia risk by about 40% and Alzheimer’s risk by about 30% compared to those with blood levels below 12 ng/mL (30 nmol/L) which is broadly consistent with the scale of benefit reported in this trial. You can read Dr William Grant’s full review entitled “The role of vitamin D in reducing risk of Alzheimer’s disease” here.

 “In this study, while Vitamin D was effective in all groups, the team found that the beneficial effects were significantly greater in females, compared to males. Similarly, effects were greater in people with normal cognition, compared to those who reported signs of mild cognitive impairment – changes to cognition which have been linked to a higher risk of dementia.

Dr William Grant says “It is unlikely that vitamin D supplementation is of much use for treating advanced stages of these diseases, although it would be useful in reducing risk of other vitamin D-sensitive adverse health outcomes.” Overall, he says “The evidence regarding vitamin D satisfies the criteria for causality in a biological system for reducing risk of cognitive function, Alzheimer’s and vascular dementia. Thus, vitamin D supplementation can be recommended as an additional way to reduce risk of these diseases. It should also be useful for reducing the rate of progression of these diseases.”

The mechanism(s) for explaining the beneficial effects of vitamin D are not yet clear, however one interesting finding was that the effects of vitamin D were also significantly greater in people who did not carry the APOEe4 gene, known to present a higher risk for Alzheimer’s dementia, compared to non-carriers. The authors suggest that people who carry the APOE4 gene absorb vitamin D better from their intestine, which might reduce the vitamin D supplementation effect due to higher baseline vitamin D levels. However, no blood levels were drawn to test this hypothesis.

Co-author Dr Byron Creese, at the University of Exeter, said: “Preventing dementia or even delaying its onset is vitally important given the growing numbers of people affected.  The link with vitamin D in this study suggests that taking vitamin D supplements may be beneficial in preventing or delaying dementia, but we now need clinical trials to confirm whether this is really the case.  The ongoing VitaMIND study at the University of Exeter is exploring this issue further by randomly assigning participants to either take vitamin D or placebo and examining changes in memory and thinking tests over time.”

At Food for the Brain those taking the Cognitive Function Test also answer questions about their use, and level of vitamin D, if known. We hope, soon, to start offering vitamin D testing to further research the effects of vitamin D in relation to cognitive decline to be able to track progress both cognitive changes against vitamin D blood levels and intake, to help determine an optimal daily intake or blood level. We are also working with the charitable Grassroots Health Nutrient Research Institute who have tested thousands of people’s blood vitamin D level and are now encouraging them to take Food for the Brain’s Cognitive Function Test. You can join their Vitamin D action group here.

Listen to Patrick Holford’s podcast explaining the role of vitamin D in Alzheimer’s disease here.

Originally published on Orthomolecular Medicine News Service [15th February 2023]

In the days of Hippocrates, diseases were blamed on the gods. He didn’t buy that and explored the causes of disease saying ‘let food be thy medicine’. Nowadays a lot of diseases are being blamed on genes – because knowledge about genes and their effects has advanced tremendously over the last several decades. Genes are the code, or instructions, to assemble proteins, for example to make an enzyme, a hormone or a biochemical such as cholesterol or phospholipids.

Take Alzheimer’s, which accounts for two thirds of dementia, as an example. There are only three genes that can cause Alzheimer’s (APP, PSEN1, PSEN2), and these account for considerably less than one in a hundred cases of Alzheimer’s. [1]

There are, however, 76 other genes [2] which appear to confer a very small additional risk. Taken together, estimates suggest that 75-85% of the risk can be explained by combining these into a polygenic risk score. [3] The single greatest predictor is the presence of the ApoE4 variant of the ApoE gene, carried by about one in five people. It is considered to contribute 4 to 6% of the absolute risk for Alzheimer’s disease. [4,5]

This is often exaggerated as a risk factor because, if a person has the ApoE4 gene, and changes nothing, they have about a 20% greater chance of developing Alzheimer’s later in life than someone who doesn’t. This is called ‘relative risk’. It doesn’t mean, however, that someone with the ApoE4 gene has a 20% chance of developing Alzheimer’s. This is because, as an example, a person without the ApoE4 gene at a certain age might have a 5% chance of developing Alzheimer’s, while someone with the ApoE4 gene might have a 6% chance, so their risk has gone up by, in this example, 20%. In absolute terms, the risk would be only 1% higher.

Predicting risk and actually reducing risk with modifications of diet and lifestyle are two different things. The predictive risk for Alzheimer’s of having a low intake of seafood and/or omega-3 fats is 22%, and so is having a low intake of B vitamins resulting in a high blood homocysteine level. Smoking confers a similar risk. [6] Other big risk factors are an inactive lifestyle and low level of education. Add in predictive genes and apparent risk adds to well over 100% partly because there is overlap.

But the only way to find out how much you can actually reduce a person’s risk by is to either conduct ‘observational’ studies looking at, e.g. smokers vs non-smokers, or people with a good versus a bad diet, and see how many develop dementia. Even better is to change something, such as looking at what happens when a person stops smoking, or supplements omega-3 fish oils or homocysteine lowering B vitamins.

Modifying ApoE4 with orthomolecular medicine

All these so-called Alzheimer’s genes, with the exception of the causative ones, can only exert effects via non-genetic mechanisms and these mechanisms are often susceptible to modification with a person’s nutrition having the most direct influence. In other words, gene variants that are present are not either active or inactive. Even if you have a gene variant such as ApoE4 it is more like a dimmer switch and can be ‘over-expressed’ or ‘down-regulated’, turned up or dimmed down. That is why approximately half of women with the BRCA gene develop breast cancer and half don’t. The environment the gene is exposed to makes all the difference.

The expression and harmful effects of the ApoE4 gene appear to be downregulated by eating a low-glycemic load (GL) diet or a more ketogenic diet with specific Mediterranean-style food choices including fatty fish, cruciferous vegetables, olive oil, and low alcohol consumption. Six supplemental nutrients have reasonably good evidence of down-regulating ApoE4. These are omega-3 DHA, B vitamins (B2, B6, B12 and folate) vitamins D3 and K2, quercitin and resveratrol. [7] This approach to modifying the effects of the genes we inherit with personalised nutrition is a fundamental tenet of orthomolecular medicine, sometimes called personalised, precision or optimum nutrition.

But what happens to risk if a person is doing these things already? A good example of this is a recent study in China, involving 29,072 people of which 20% had the ApoE4 gene. [8] Each participant had their diet and lifestyle assessed over the 10 year period of the study to see who would or wouldn’t develop cognitive decline or dementia.

The study showed that whether or not a person had the ApoE4 ‘Alzheimer’s gene’ made no difference to the positive reduction in risk achievable by simple diet and lifestyle changes. “These results provide an optimistic outlook, as they suggest that although genetic risk is not modifiable, a combination of more healthy lifestyle factors is associated with a slower rate of memory decline, regardless of the genetic risk,” wrote the study authors.

Eating a healthy diet was the most important prevention step, followed by an active lifestyle, with one’s intellectual life, then physical activity, then social interactions being the next most important steps. Eating a healthy diet was about twice as important as exercise in predicting cognitive decline. Those with a healthy diet were about seven times less likely to have age-related cognitive decline or dementia than those with an ‘average’ diet and about nine times less likely to develop dementia than those with an unfavorable diet.

The assessment of a healthy diet was based on intake of fish, eggs, fruits, vegetables, legumes, nuts and tea, among other foods known to predict lower risk.

B vitamins modify methylation of genes linked to dementia

Other Alzheimer’s related genes affect a process called methylation. Healthy methylation depends on adequate B vitamin intake, primarily B6, B12 and folate. Inheriting a variant of a key methylation gene, MTHFR 677TT increases risk for Alzheimer’s. [9-11] About one in three people have this gene variant. It impacts risk by raising homocysteine, a toxic amino acid that damages the brain and blood vessels. Having a raised homocysteine level increases risk for cerebrovascular dysfunction 17-fold. [12]

Since methylation is needed to make phospholipids, biochemicals essential for the brain also found in eggs and fish, having a poor diet in this respect creates more methylation demand and, consequently, greater need for B vitamins.

In a placebo controlled study of older people with mild cognitive impairment, about a third of participants had the MTHFR variant that increases Alzheimer’s risk. But supplementing with B vitamins effectively lowered homocysteine in both those with and without this ‘Alzheimer’s’ gene. The B vitamin supplement almost arrested further memory decline and slowed the rate of brain shrinkage by 52%, [13,14] reducing shrinkage of the Alzheimer’s areas of the brain by 9-fold. [15] Whether a person did or didn’t have this ‘Alzheimer’s’ gene made no difference to the beneficial effect of the B vitamins.

Those with adequate omega-3 blood levels had even less brain shrinkage – 73% less than the placebo group. [16-17] Two other studies have found major protection either by giving B vitamins to those with adequate omega-3 intake, [18] or by supplementing omega-3 to those with lower homocysteine levels [19] further confirming that you need both B vitamins and omega-3 fats to keep neurons healthy – an example of synergy – regardless of one’s genes. Whether a person did or didn’t have the MTHFR variant made no significant difference.

Too often genes are blamed as drivers of disease even though (with the exception of rare causative genes) the primary drivers are what you put in your mouth or how you live your life – both factors under our control. For example, DNA genetic testing can cause panic when an individual is informed they have a dozen or more gene variants. Over-emphazing the importance of genes discourages people from preventing their own disease by improving diet and lifestyle.

Find out your dementia risk

You can find out what’s driving your risk and which diet and lifestyle changes will make the biggest difference by doing the Cognitive Function Test at foodforthebrain.org and joining COGNITION, the brain upgrade program. Not only do you help yourself, you also help the hundreds of thousands of people who would benefit from the research we support at Food for the Brain to reduce risk of dementia.

About Patrick Holford

(Patrick Holford , BSc, DipION, FBANT, NTCRP is widely published and a member of the Orthomolecular Medicine Hall of Fame. He is the director of the non-profit, UK-based “Alzheimer’s is Preventable” campaign [ foodforthebrain.org].)

References

1. Bekris LM, Yu CE, Bird TD, Tsuang DW. (2010) Genetics of Alzheimer disease. J Geriatr Psychiatry Neurol. 23:213-227. https://pubmed.ncbi.nlm.nih.gov/21045163

2. Bellenguez C, Küçük F, Jansen IE, et al. (2022) New insights into the genetic etiology of Alzheimer-s disease and related dementias. Nat Genet. 54:412-436. https://pubmed.ncbi.nlm.nih.gov/35379992

3. Escott-Price V, Myers AJ, Huentelman M, Hardy J. (2017) Polygenic risk score analysis of pathologically confirmed Alzheimer disease. Ann Neurol. 82:311-314. https://pubmed.ncbi.nlm.nih.gov/28727176

4. Heininger K (2000), A unifying hypothesis of Alzheimer’s disease. III. Risk factors. Hum Psychopharmacol Clin Exp. 15:1-70. https://pubmed.ncbi.nlm.nih.gov/12404343

5. Ridge PG, Mukherjee S, Crane PK, Kauwe JSK, (2013) Alzheimer’s Disease: Analyzing the Missing Heritability. PLoS One. 8(11): e79771. https://pubmed.ncbi.nlm.nih.gov/24244562

6. Beydoun MA, Beydoun HA, Gamaldo AA, et al. (2014) Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 14:643. https://pubmed.ncbi.nlm.nih.gov/24962204

7. Norwitz NG, Saif N, Ariza I.E, Isaacson RS (2021) Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers. Nutrients 13:1362. https://pubmed.ncbi.nlm.nih.gov/33921683

8. Jia J, Zhao T, Liu Z et al. (2023) Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study. BMJ 380:e072691. https://pubmed.ncbi.nlm.nih.gov/36696990

9. Morris AA, Kožich V, Santra S, et al. (2017) Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency. J Inherit Metab Dis. 40:49-74. https://pubmed.ncbi.nlm.nih.gov/27778219

10. Bouguerra K, Tazir M, Melouli H, Khelil M. (2022) The methylenetetrahydrofolate reductase C677T and A1298C genetic polymorphisms and plasma homocysteine in Alzheimer’s disease in an Algerian population. Int J Neurosci. 29:1-6. https://pubmed.ncbi.nlm.nih.gov/36580407

11. Zuin M, Cervellati C, Trentini A, et al. (2021) Methylenetetrahydrofolate reductase C667T polymorphism and susceptibility to late-onset Alzheimer’s disease in the Italian population. Minerva Med. 112:365-371. https://pubmed.ncbi.nlm.nih.gov/32700867

12. Teng Z, Feng J, Liu R, et al. (2022) Cerebral small vessel disease mediates the association between homocysteine and cognitive function. Front. Aging Neurosci. 14:868777. https://pubmed.ncbi.nlm.nih.gov/35912072

13. Smith AD, Smith SM, de Jager CA, et al. (2010) Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One. 5(9):e12244. https://pubmed.ncbi.nlm.nih.gov/20838622

14. Smith AD, Refsum H. (2016) Homocysteine, B vitamins, and cognitive impairment. Annu Rev Nutr. 36: 211-239. https://pubmed.ncbi.nlm.nih.gov/27431367

15. Douaud G, Refsum H, de Jager CA, et al. (2013) Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci USA 110:9523-9528. https://pubmed.ncbi.nlm.nih.gov/23690582

16. Jernerén F, Elshorbagy AK, Oulhaj A, et al. (2015) Brain atrophy in cognitively impaired elderly: the importance of long-chain omega-3 fatty acids and B vitamin status in a randomized controlled trial. Am J Clin Nutr. 102:215-221. https://pubmed.ncbi.nlm.nih.gov/25877495

17. Oulhaj A, Jernerén F, Refsum H, et al. (2016) Omega-3 fatty acid status enhances the prevention of cognitive decline by B vitamins in Mild Cognitive Impairment. J Alzheimer’s Dis. 50:547-557. https://pubmed.ncbi.nlm.nih.gov/26757190

18. van Soest, A.P.M., van de Rest, O., Witkamp, R.F. et al. (2022) DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial. Eur J Nutr. 61:3731-3739. https://pubmed.ncbi.nlm.nih.gov/35704085

19. Jernerén F, Cederholm T, Refsum H, et al. (2019) Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer’s Disease: The OmegAD Study. J Alzheimers Dis. 69:189-197. https://pubmed.ncbi.nlm.nih.gov/30958356

By Patrick Holford

How does cognitive decline happen?

One theory was that it was to do with the accumulation of amyloid protein, producing amyloid plaque that interferes with brain cell communication. But, despite over 30 clinical trials, lowering amyloid protein has had close to zero clinical effect. But, even if this was part of the problem, one would have to ask why?

There are plenty of left-field theories. One, for example, is that it’s an auto-immune disease whereby the brain starts to destroy itself. There are plenty of diet and lifestyle diseases that tip over into auto-immune diseases. For example, type-2 diabetes can convert to type-1 diabetes and osteoarthritis can convert to rheumatoid arthritis. But even so, one would have to ask why? What would be driving this?

Risk Factors for Alzheimer’s – what do they have in common?

There are over 20 known risk factors that predict future risk for cognitive decline, dementia and/or Alzheimer’s. These include:

Anon-adherence to Mediterranean diet principles
Cardiovascular disease, and high blood pressure
Depression/social isolation/loneliness
Diabetes
Genes (such as senilin) and predisposing genes (eg ApoE4)
Head trauma
High blood homocysteine (a measure of B vitamins)
Insulin resistance
Lack of antioxidants/polyphenols in plant foods
Lack of cognitive stimulation
Lack of exercise and muscle mass – frailty
Lack of folate, B12 and B6
Lack of sleep
Low education level
Low phospholipid and choline intake (in eggs and fish)
Low seafood consumption and a lack of omega-3
Low sunlight exposure
Low vitamin C, D and E intake
Low zinc levels
Medication – antiacids, metformin, diuretics
Metabolic syndrome
Poor gut health and dental health
Poor hearing
Smoking
Stress
Strokes and TIAs (transient ischemic attacks )
Too much sugar, refined, processed, carb-rich foods

So far researchers have looked at individual known risk factors for Alzheimer’s, then tried to change them with some success. The nutritionists have tried to change diet, or give supplements. The pharmacologists have tried to give drugs to lower, for example, high blood pressure or insulin levels. The psychologists have tried to increase cognitive stimulation and address depression and isolation, and insomnia. The sports physiologists have tried to increase exercise. But what do all these factors have in common? Is there a way of looking that ties all these risk factors together into an understanding as to what is actually driving dementia?

The old, but still dominant mindset in science is ‘reductionism’. The idea is to look at one thing, or one risk factor, then change it in a randomised placebo-controlled trial. The idea is that if everyone does this then you could pool all the interventions together to produce a cure. This reminds me of a comment made in the G8 summit on dementia in 2010, in London, when we succeeded in getting a discussion on dementia prevention added to the agenda. The pharma representative said words to the effect of ‘we will solve dementia with multiple drugs, just like we solved AIDS’. The reality is studies giving drugs[1] to lower blood sugar for diabetics, lower blood pressure with anti-hypertensive drugs, lower cholesterol with statins, even lower amyloid protein, have failed. The official cost of all this research is $42.5 billion to date.[2] This is five times more than the cost of the James Webb telescope. This approach clearly isn’t working. The only ‘drugs’ that have worked are homocysteine lowering B vitamins and omega-3 fish oils – and the recent discovery is that they work together, in cooperation.

There’s a new emerging way of doing science which is called ‘systems-based’ science. The physicist, Fritjof Capra, has explained this way of doing science in his book ‘The Web of Life’. He says “Systems thinking emerged from a series of interdisciplinary dialogues among biologists, psychologists, and ecologists, in the 1920s and ’30s. In all these fields, scientists realized that a living system—organism, ecosystem, or social system—is an integrated whole whose properties cannot be reduced to those of smaller parts. The “systemic” properties are properties of the whole, which none of its parts have. So, systems thinking involves a shift of perspective from the parts to the whole. The early systems thinkers coined the phrase, “The whole is more than the sum of its parts.”[3]

Us humans are a complex adaptive system. What’s also been learnt about complex adaptive systems is that they have a certain amount of ‘resilience’ which you can think of as the credit in your health deposit account. When that runs out, disease occurs. Many leaders in the field of nutritional and naturopathic medicine consider that many of the same underlying processes are going wrong in our bodies, which then cause the emergence of a ‘disease’ depending on the organ it strikes – so heart disease, diabetes, arthritis and dementia have similar contributing factors.

At Food for the Brain, we can organise all these risks above into eight domains shown below. It is certainly true that these eight domains of ‘risk’ cover much of what we know about the risks for heart disease, diabetes and arthritis, for example. This partly, but not fully. answers the question about what is actually driving dementia.

Another understanding within systems-based thinking is well illustrated by asking the question ‘what is the difference between an inanimate object, like a bicycle, and an animate organism, such as us?’ A bicycle has ‘parts’ and the parts related to each other, as in functioning together. So do we. But also, there is ‘life’ running through us. You can imagine your brain’s neural network lighting up, with ‘energy’ or signals shooting this way and that. If you have healthy parts, all functioning, but no signals, you’re kind of ‘switched off’.

We call the parts – structure; the relationship of the parts – function; and the life running through the neural network – utilisation. These are shown visually below in a way to illustrate that they are integral, with each dependent on the other.

Now, let’s reorganise all those risk factors accordingly into whether they are primarily required for the structure or function of the neural network, or send messages across it.

If you’ve watched the short animated film ‘how to keep building brain cells at any age‘ you’ll know that the membrane of every brain cell is made by binding omega-3 DHA, rich in seafood, to phospholipids and especially Phosphatidylcholine, rich in eggs and fish, to produce what called ‘phosphorylated DHA’. You need this to have a functioning brain. It actually makes up more than 90 per cent of the structure of your brain.

You’ll also know that the ‘binding’ of these two parts depends on B vitamins, which drive a process called methylation. So, without enough B vitamins your brain and nervous system fall apart. The best measure of methylation, and whether you are getting enough B vitamins, is your blood homocysteine level.  If your homocysteine level is high, you’ve got a problem. Above 11mcmol/l and you’ve got a shrinking brain. More than half of all people over 70 have a homocysteine level above this. It should, therefore, be no surprise to find that, if you have a raised homocysteine level, and are given B vitamins, if you also have a low omega-3 DHA intake or blood level, the B vitamins won’t work. Conversely, if you supplement omega-3 fish oils, but have a raised homocysteine level or lack of B vitamins, the omega-3 won’t work. The full story of the dynamic duo of Omega-3 and  B vitamins is explained here.

It is likely that choline deficiency, which is especially common in those who rarely eat fish or eggs, may also create a similar structural problem in the brain. In animals supplementing choline prevents Alzheimer’s related brain changes.[4]

Protecting the Function of Your Brain

There are many aspects of ‘function’ of the brain. Using a simple car analogy, one thinks of the need for fuel and the need for oil to lubricate the parts. The two main fuels of brain cells are either glucose, derived from carbs, or ketone derived from fat.

If you’ve watched the animated film ‘how to fuel your brain for better memory’, you’ll know about the need for slow-releasing carbs and ketones from a type of fat called a medium chain triglyceride (MCT) and specifically C8 oil.

Too much sugar, and especially fructose and high fructose corn syrup (now used by the food industry to sweeten foods), and too much refined carbohydrates interferes with fuel supply to brain cells by making you ‘insulin resistant’. Insulin receptors, embedded in neuronal membranes, transport glucose into brain cells. If these receptors, which are like doors, are largely shut down, the brain starves of clean fuel. Read professor Robert Lustig’s article “Is sugar killing your brain?’ for the full story.

The alternative brain fuel – ketones, which neurons actually prefer, can be made in the liver from a type of fat called C-8 (caprylic acid triglyceride) which makes up 7 per cent of coconut oil. In a study giving people with memory problems two tablespoons of C8 oil, their brains produced 230 per cent more energy from ketones and their memory improved. The article ‘Is fat the best brain fuel?’ gives you the full story.

The lubricating ‘oil’ in a car analogy would be both dealing with the ‘exhaust fumes’ of the brain’s energy production, namely oxidants. These are mopped up by antioxidants and polyphenols rich in plant foods. That where food such as blueberries and cacao, or vitamin C and E, come in. It’s also why smoking is such a big risk factor.

Another part of ‘function’ is circulation – anything that improves circulation helps the function. Many of the things we’ve mentioned –  lowering homocysteine with B vitamins, omega-3, antioxidants, polyphenols – also help circulation.

Another part of ‘function’ is inflammation. Behind all those ‘metabolic’ diseases -diabetes, heart disease, arthritis to name a few – lies inflammation which doesn’t just affect the specific organ, be it heart of joint, but also the brain.

Use it or Loss it – Why Your Brain Needs Stimulation

One of our experts, Tommy Wood, assistant research professor at the University of Washington in Seattle, focussing on neuroscience, has developed an excellent model for understanding the ‘use it or lose it’ principle. He’s big into exercise.

‘Exercise is important because it makes the brain do things that keep it healthy, such as growth and repair and maintaining temperature and weight,’ he says. ‘When they aren’t stimulated, the health of brain tissues deteriorates with a knock-on effect on memory and thinking.’

And it’s not just physical exercise that does this, we also benefit from the mental exercise involved in likes of solving puzzles or learning a new language. ‘For many people the worst thing they can do for their brain is to retire’, says Wood. ‘They lose much of the stimulation that kept it healthy.’

Sleep as a brain protector also fits in here. It’s vital for recovering from both physical and intellectual exercise and to store and organise what you have learnt in the day.

‘But sleep and exercise aren’t enough on their own,’ Wood continues. ‘All that repair and maintenance needs a good supply of nutrients.’

Stress also fits in here because stress, as well as environmental and dietary ‘pollution’ be it from drinking and smoking, dirty air, moulds, even allergens like gluten with can induce ‘brain fog’ often experienced by those with coeliac disease, promote inflammation and inhibit repair and regeneration.

A Unified Model for the Drivers of Cognitive Decline

This systems-based approach to what’s potentially driving cognitive decline makes it obvious that there will never be a single drug or single factor that stops a person developing dementia. Instead, if a person has enough ‘interference’ with the structure, function or utilisation of their brain then there will, inevitably be cognitive decline with age.

At Food for the Brain, when you complete your Cognitive Function Test, you know objectively how you are doing and how much room for improvement there is. Then you are invited to complete the Dementia Risk Index questionnaire, which not only gives you a score out of 100% (you are aiming for a score closer to 0%) but also shows you in which domain you have the most room for improvement.

You are then invited to join COGNITION, which is an interactive brain upgrade programme that targets your weakest areas and shows you the simplest changes that will make the biggest difference to reduce your risk.

The goal is to turn all your reds, oranges and yellows into green, then reassess your cognitive function. By joining you are becoming part of a group of hundreds of thousands of citizen health scientists helping to discover what really works to dementia-proof your diet and lifestyle.

Take the FREE Cognitive Function Test today.

References

[1] Peters R, Breitner J, James S, Jicha GA, Meyer PF, Richards M, Smith AD, Yassine HN, Abner E, Hainsworth AH, Kehoe PG, Beckett N, Weber C, Anderson C, Anstey KJ, Dodge HH. Dementia risk reduction: why haven’t the pharmacological risk reduction trials worked? An in-depth exploration of seven established risk factors. Alzheimers Dement (N Y). 2021 Dec 8;7(1):e12202. doi: 10.1002/trc2.12202. PMID: 34934803; PMCID: PMC8655351.

[2] Cummings JL, Goldman DP, Simmons-Stern NR, Ponton E. The costs of developing treatments for Alzheimer’s disease: A retrospective exploration. Alzheimers Dement. 2022 Mar;18(3):469-477. doi: 10.1002/alz.12450. Epub 2021 Sep 28. PMID: 34581499; PMCID: PMC8940715.

[3] Fritjof Capra (2009) The New Facts of Life: Connecting the Dots on Food, Health, and the Environment, Public Library Quarterly, 28:3, 242-248, DOI: 10.1080/01616840903110107

[4] Velazquez R, Ferreira E, Knowles S, Fux C, Rodin A, Winslow W, Oddo S. Lifelong choline supplementation ameliorates Alzheimer’s disease pathology and associated cognitive deficits by attenuating microglia activation. Aging Cell. 2019 Dec;18(6):e13037. doi: 10.1111/acel.13037. Epub 2019 Sep 27. PMID: 31560162; PMCID: PMC6826123.

Responding to the ‘feverish media coverage heralding a new era of disease modifying treatments’, described by the BBC as a ‘momentous breakthrough’ a scathing editorial in the British Medical Journal says: “Hyperbolic rhetoric gives patients and their families false hope, which clinicians must address, and pre-empts regulatory decision making.”

“Such treatment has been long hoped for,” they say. “However, the null effects on cognition of other anti-amyloid agents, the tiny effect on cognition reported for [the new drug] lecanemab and concerns about safety mean that perspective is needed.”

“The prevailing narrative is that this trial “succeeded” where others have “failed.” In reality, lecanemab, like other anti-amyloid agents, successfully cleared amyloid from the brain. This clearance had no discernible effect on cognition in some trials, a very small and non- significant effect in other trials, and a very small significant effect in the latest trial. The overall trial evidence tells us that successful amyloid clearance in adults with early Alzheimer’s disease has either no effect or a tiny effect on cognitive decline.” 

“Previous attempts to quantify the minimum clinically important difference in the trial’s primary outcome measure—the Clinical Dementia Rating (CDR) sum of boxes score (range 0-18 —suggested that minimum changes of 0.98 in mild cognitive impairment and 1.63 in mild Alzheimer’s disease are meaningful. After 18 months of treatment with lecanemab, differences of 0.35 and 0.62 for those with mild cognitive impairment and mild Alzheimer’s disease, respectively, fell well short, representing only around a third of what a minimum clinically important difference might look like.”

Both B vitamins and omega-3 have achieved a clinically significant reduction in the CDR by these criteria, as well as improving other measures of cognition, and in reducing the rate of brain shrinkage. The rate of brain shrinkage reduction of this kind of drug is 2% compared to up to 73% less shrinkage with B vitamins in those with sufficient omega-3. Yet both UK, US and EU government and medical agencies have repeatedly declined funding a definitive trial of both B vitamins and omega-3.

The BMJ editorial expresses serious concerns about safety of this class of drug, which is really an antibody injection. “As with other anti-amyloid agents, lecanemab comes with substantial safety concerns. During the trial, 12.6% of participants treated with lecanemab developed brain oedema (swelling), 22% of whom were symptomatic.  A further 17.3% experienced brain haemorrhage; and 6.9% experienced adverse events severe enough to discontinue the trial.” That means that 30% of drug trial participants had a serious adverse effect.

While the number of deaths in the main trial were comparable between the drug and placebo group “more information is needed about two deaths reported during the trial’s open label extension. Both participants had brain haemorrhage, possibly associated with taking lecanemab alongside anticoagulants or thrombolysis.”

They say that “Lecanemab if licensed is likely to cost tens of thousands of pounds a year for each patient. In addition, health systems would need to provide PET scans or lumbar puncture to determine eligibility, fortnightly infusions of the drug indefinitely, and repeated MRI [scans] to monitor for adverse events, all of which is far beyond the capacity of most countries, even those with well-resourced healthcare systems.” B vitamins and omega-3 have no side-effects, other than knock-on health improvements, and cost pennies, not thousands of pounds.

Pressure for approval and clinical use, the BMJ says, is likely to be fierce. “Viewed objectively, however, lecanemab is not the hoped for “game changer.” Rather, it is further evidence that anti-amyloid therapies do not produce clinically meaningful benefits for people with Alzheimer’s disease. Weighed against the scale and severity of adverse events and substantial practical barriers to widespread use, lecanemab is unlikely to represent a favourable risk-benefit balance for patients or value for money for health systems.”

The fully referenced BMJ editorial can be viewed here.

If you are concerned about age-related cognitive decline, dementia or Alzheimer’s please take our free, validated Cognitive Function Test here and sign up to join our COGNITION programme, to help dementia-proof your diet and lifestyle. Also, please support our work in helping teach people who to prevent dementia by becoming a FRIEND of Food for the Brain here.

A hugely significant study in the British Medical Journal into age-related cognitive decline and dementia has stated that changing your diet and lifestyle from bad to good cuts your future risk of developing dementia by a massive nine times [1]

The study shows, significantly, that whether or not you inherit the ApoE4 ‘Alzheimer’s gene’ that one in five people carry, it makes no difference to the positive reduction in risk achievable by simple diet and lifestyle changes [2].

Eating a healthy diet was also the most important prevention step, followed by an active lifestyle, with one’s intellectual life, then physical activity, then social interactions being the next most important steps. Eating a healthy diet was about twice as important as exercise in predicting cognitive decline.

This study, published on 25th January 2023, followed over 30,000 people over a decade and found that those with a healthy diet were about seven times less likely to have age-related cognitive decline or dementia than those with an ‘average’ diet and about nine times less likely to develop dementia than those with an unfavourable diet.

The assessment of a healthy diet was based on intake of fish, eggs, fruits, vegetables, legumes, nuts and tea, among other foods known to predict lower risk.

Increasing evidence that Alzheimer’s and Dementia are preventable

“These results provide an optimistic outlook, as they suggest that although genetic risk is not modifiable, a combination of more healthy lifestyle factors are associated with a slower rate of memory decline, regardless of the genetic risk,” wrote the study authors.

This study has been warmly welcomed by charity Food for the Brain, as it backs up their own research and the work they have been actively carrying out for 10  years, to help people reduce their risk of age-related cognitive decline.

Food for the Brain offers a free online assessment of a participant’s diet and lifestyle, called the Dementia Risk Index, which works out a person’s overall risk. The assessment also includes a cognitive function test to assess your memory. This charitable ‘citizen science’ action group have also just launched COGNITION, an interactive, personalised ‘brain upgrade’ programme that then shows you, week-by-week, how to make positive changes to bring your risk closer to zero.

Indeed, the on-line test assesses all the same risk factors the British Medical Journal study has shown impact a person’s future risk – diet, active physical, intellectual, social lifestyle, smoking and drinking habits.  

According to Professor David Smith from the University of Oxford, one of the charity’s scientific advisors, “Genes can only exert effects via non-genetic mechanisms and these mechanisms are often susceptible to modification by, for example, improving one’s diet. This study shows that diet and lifestyle are much more important than inheriting a gene variant such as ApoE4. Less than 1% of Alzheimer’s is directly caused by genes. With no clinically effective drugs, and minimal role of genes, this study confirms that the focus must be on making diet and lifestyle changes that reduce risk of developing dementia, as foodforthebrain.org are doing. It also shows that switching from an average to a healthy lifestyle, with positive diet changes being key, can dramatically reduce a person’s future risk of developing cognitive decline and dementia.” 

Another member of the science team, Dr Celeste de Jager Loots, Research Associate at Imperial College’s  AGE Unit where she researches risk factors and prevention of Alzheimer’s and dementia, explains that “While having inherited certain genes can be used to predict risk of dementia, that risk is changed by making positive diet and lifestyle changes. The emphasis needs to be on changing diet and lifestyle, especially since one cannot change one’s genes. The earlier one starts with a healthy lifestyle the better the chance of preventing effects of genetic risk.”

Risk for dementia can be detected from the age of 35 and subtle changes, picked up by Food for the Brain’s cognitive function test, can be seen up to 40 years before a diagnosis. The charity wants anyone over 35 to take the test and start making positive diet and lifestyle changes. “The average person can cut their future risk by three quarters just by making simple diet and lifestyle changes.” says Patrick Holford, who is directing the Alzheimer’s prevention project. “This prevention approach, if we reach enough people, could cut cases of dementia in the UK by a third. That’s why we are urging everyone over 35 to tell everyone they know to take the free and scientifically – validated and free Cognitive Function Test. Alzheimer’s dementia, which accounts for the vast majority of dementia, is irreversible. But it is preventable, as this study shows.”

Two thousand people every month are joining this campaign, assessing and reducing their risk. Over 380,000 people have now taken the test.

References

Jia, J. et al. (2023) “Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective Cohort Study,” BMJ [Preprint]. Available at: https://doi.org/10.1136/bmj-2022-072691. [1]

The evidence that only 1% of Alzheimer’s is caused by genes is here: Bekris, L.M. et al. (2010) “Review article: Genetics of Alzheimer Disease,” Journal of Geriatric Psychiatry and Neurology, 23(4), pp. 213–227. Available at: https://doi.org/10.1177/0891988710383571. [2]

Useful links

The free Cognitive Function test and Dementia Risk Index assessment is accessed here: https://brainhealthcheck.foodforthebrain.org.

For more information on the citizen science campaign see ‘Alzheimer’s is Preventable – A Manifesto for Change’.

Patrick Holford, founder of Food for the Brain and voluntary director of the Alzheimer’s Prevention Project and Jessica Ferrari-Wells, Chair of the Board of trustees are available for interview, as are members of the the Scientific Advisory Board are available for interview and comment. 

A recent study of 1,178 women found that those carrying the APOE4 gene taking Hormone Replacement Therapy (HRT) had a better delayed memory score compared to APOE4 carriers that were not taking HRT, and to non-APOE4 carriers.[1] They also had slightly larger brain volumes in certain areas. This study suggested that HRT may help to prevent Dementia. This study was an observational trial, not a clinical trial, meaning the statement remains a hypotheses and requires further randomised controlled trials to investigate further. We analysed the paper and provided our comments below.

Clinical Trials on HRT

Clinical trials to date have not shown benefit of HRT with improving cognitive function. A systematic review of the clinical trial evidence for the effect of HRT on cognitive outcomes did not find benefit.[2] The Women’s Health Initiative Memory Study (WHIMS) conducted a double-blind, placebo-controlled clinical trial examining 8300 women 65 years of age or older over a 2- year period to observe the effects of HRTs and dementia progression. The trial failed to find a beneficial effect for HRT in reducing dementia risk, instead finding an increase in all types of dementia.[3]

The ApoE4 Gene

Roughly 1 in 5 people carry the ApoE4 gene, which accounts for 4 to 6% of risk for dementia and can be modified, downregulating the gene, with positive diet, nutritional supplement and lifestyle changes.[1]

Find out your risk for Dementia

In our Dementia Risk Index, as part of the Cognitive Function test, and COGNITION programme to reduce dementia, we excluded HRT because the evidence was not conclusive or consistent.

Have you tried our free Cognitive Function Test yet? Find out your Alzheimer’s disease risk using our evidence backed Dementia Risk Index. If your risk is high, our clever new programme COGNITION can help you make the right nutrition and lifestyle changes to help improve your score.

References

[1] Saleh RNM, Hornberger M, Ritchie CW, Minihane AM. Hormone replacement therapy is associated with improved cognition and larger brain volumes in at-risk APOE4 women: results from the European Prevention of Alzheimer’s Disease (EPAD) cohort. Alzheimers Res Ther. 2023 Jan 9;15(1):10. doi: 10.1186/s13195-022-01121-5. PMID: 36624497; PMCID: PMC9830747.

[2] Marjoribanks J, Farquhar C, Roberts H, Lethaby A, Lee J. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2017;1(1):CD004143.

[3] Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in post- menopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289(20):2651-2662.

By Patrick Holford

Why Dementia rates are higher in the west

In some countries, for example India and China, that proportion appears to be less than half that occurring in Britain. When people in one country suffer much more from a disease than people of a similar age in another country, this is a sure sign that the difference has something to do with diet, lifestyle or other environmental factors – or genetic variance. We can rule out genetic differences as the major factor, particularly because Chinese and Indian people who emigrate to Britain soon acquire a similar risk for developing dementia. In any event only one in a hundred cases of Alzheimer’s is caused by genes.²

How many people get diagnosed with dementia?

A decline in memory and concentration is not the same thing as a diagnosis of dementia or probable Alzheimer’s, although it does mean your chances of developing these conditions are higher. Every year roughly 10 million people are diagnosed with dementia – that is one person every 3 seconds³ . Currently, around 900,000 people in the UK have dementia.⁴ By 2050 this will be over 1.53 million. Globally over 50 million have dementia. By 2050 this is expected to increase to 152 million.⁵

Two in three people diagnosed with dementia will end up diagnosed with probable Alzheimer’s, while 17 per cent will be given a diagnosis of vascular dementia, caused by constricted blood flow to the brain due to blocked arteries, and 10% will be given a ‘mixed’ diagnosis, which is usually part Alzheimer’s, part vascular dementia. But the risk factors, and prevention treatments, for Alzheimer’s and vascular dementia are the same. So, combined, well over 80% of all dementia diagnoses should be preventable.

What is dementia?

There are other forms, such as dementia with Lewy bodies, fronto-temporal dementia and dementia caused by a stroke, a bleed in the brain or a brain tumour. But as Alzheimer’s is the most widespread, let’s look at it in depth.

Dementia – including Alzheimer’s – is an insidious condition. In the early stages, sufferers have increasing symptoms of absentmindedness, low mood and an inability to learn new things. Judgement, and their ability to function intellectually and socially, begin to go awry. The person may repeatedly forget to turn off the iron, or may not recall which medicines they took in the morning. They may start to show mild personality changes, such as a lack of spontaneity or a sense of apathy and a tendency to withdraw from social interactions.

Later on, there will be a loss of logic and memory, disorientation and poor coordination. Speech deteriorates and paranoia may appear. At this point, a diagnosis of probable Alzheimer’s disease may be given. Why ‘probable’? Because Alzheimer’s is properly diagnosed, not simply by symptoms, but by the presence of a specific kind of degeneration in a specific part of the brain – and this is difficult to see without the aid of expensive scans.

How was Alzheimer’s discovered?

The German neuropathologist Alois Alzheimer discovered this characteristic degeneration in the brain back in 1906. Using a technique known as silver stain, he examined the brain cells of a woman who died prematurely at 55 with signs of dementia, and found a tangled mess of proteins and clusters of degenerating nerve endings, called neurofibrillary tangles. This condition is associated with a gradual dying-off of neurons and poor communication between neurons. There is also often a build-up of something called beta-amyloid plaque, a protein-like substance that shouldn’t be there.

Since that time, research into Alzheimer’s has continued apace. Largely thanks to the pioneering work of Professor David Smith and colleagues in the University of Oxford’s pharmacology department, we now know that Alzheimer’s is a specific disease process, not just a random, gradual decline in brain cells, and that it originates in a particular brain region. Their Optima (Oxford Project to Investigate Memory and Ageing) study has been running since 1988 and has proved, among other things, that the damage leading to Alzheimer’s begins in a central part of the brain known as the medial temporal lobe.^6-7

Pinpointing the problem area

The medial temporal lobe is vital for both mood and memory. Even though this lobe accounts for only 2 per cent of the brain’s total area, it is essential for the processing of everything we sense, feel or think.

Precisely because it’s in the middle of the head, it’s a difficult region to scan. This is also where there are more neurofibrillary tangles and beta-amyloid plaques – the hallmarks of Alzheimer’s. These indicate damage and chaos to the normal network of neurons and their connections.

Since information is passed from and to the medial temporal lobe from other parts of the brain, as this area becomes more damaged, fewer signals are sent to other parts of the brain. These then also start to decline, becoming more and more disconnected, with ever-decreasing blood flow. The beginning of damage is estimated to occur as early as 40 years before a person is diagnosed with dementia. That is why it is important to start your prevention plan young.

So far we’ve talked about the spread of damage seen in Alzheimer’s, starting with the medial temporal lobe, and radiating out to other areas of the brain, which are in effect starved of signals, much as a muscle atrophies through lack of use. Other indicators of Alzheimer’s are neurofibrillary tangles (p’tau), the lack of blood flow in the brain, and the presence of beta-amyloid plaques. There is also the presence of high levels of homocysteine in the blood.

Exactly which of these factors ‘causes’ Alzheimer’s, or kickstarts the process of damage, is the subject of much debate and ongoing research.

Clues to curbing the epidemic

At the other end of the spectrum, scientists have been looking for ways to prevent Alzheimer’s disease, and are conducting more and more studies revealing the specific dietary and lifestyle factors that greatly increase or decrease risk. Around half of the risk can be prevented.⁸For example, having a high intake of omega-3 fats and B vitamins appears to reduce risk, while consuming a lot of sugar increases the risk. The National Institutes of Health attributes 22% of Alzheimer’s to high homocysteine and 22% to low omega-3/seafood consumption.⁹ What’s more people with pre-dementia with good omega-3 status, given extra B vitamins have a 73% less brain shrinkage than those on placebo.¹⁰

Somewhere in the middle, scientists are discovering how changes in diet could cause changes in the brain. An example of this is the discovery of an enzyme that both regulates insulin – the key hormone for keeping your blood sugar in balance – and beta-amyloid.  There are, however, many other ways, and growing evidence, that sugar and high carb diet driven by eating junk food damages the brain.

The most exciting discovery is the role of B vitamins and how too little can lead to increases in homocysteine in the blood. Since neither beta-amyloid nor those neurofibrillary tangles can be measured before its too late, the discovery that levels of a simple chemical in your blood could be the best predictor of all is the most welcome news – and it should, in our opinion, have revolutionised the early diagnosis and preventative treatment of those most likely to develop Alzheimer’s. There is good evidence that homocysteine, a measure of faulty methylation, is a primary driver of Alzheimer’s for a number of reasons:

Giving people with raised homocysteine and pre-dementia (mild cognitive impairment or MCI) extra homocysteine lowering B vitamins has been shown to reduce the rate of shrinkage of the medial temporal regions by nine fold.
Amyloid blocking drugs have little to marginal effects on the actual disease. A meta-analysis of these drugs that did effectively lower amyloid found virtual no significant cognitive benefit from doing so.¹¹ Measures of Clinical Dementia Ratings show that both homocysteine-lowering B vitamins and Omega-3 fish oil supplements surpass anti-amyloid drugs. (See our newsletter)
The formation of neurofibrillary tangles, associated with p-tau proteins, could be a consequence of faulty methylation (eg raised homocysteine). When p-tau is high so is homocysteine. There are three known ways whereby raised homocysteine would raise p-tau.
Homocysteine is found in the regions of brain damage and is capable itself of causing brain damage.
A raised homocysteine increases the risk of cerebral vascular dysfunction by a remarkable 17 times.¹¹
Every study that has effectively lowered homocysteine in people at risk, eg with MCI or mild Alzheimer’s, has shown benefit, except in the later stages of the disease which may just be too late.

An International Consensus Statement in 2018 concluded that moderately raised plasma total homocysteine (>11mcmol/L), found in half of those over age 70 ¹², is a main cause of age-related cognitive decline and dementia.¹³ Two major meta-analyses of hundreds of studies conclude that raised homocysteine is one of the best evidenced risk factors for AD and accounts for around a fifth of all risk ¹⁴, ¹⁵.

The key to prevention is to understand the contributing factors and to do something about them as soon as possible. Right now, because the thought of Alzheimer’s is so terrifying, most people avoid even seeing their doctor and are usually diagnosed only in the late stages, usually reported by a relative who has found their partner becoming unmanageable. That’s why it is critical to look for the earliest possible signs of cognitive decline, then there’s time to reverse the trend.

The Cognitive Function Test

The Food for the Brain Foundation offer an excellent free online Cognitive Function test and a simple Dementia Risk Index questionnaire which also works out your risk factors and which simple changes will have the most effect. Do please do this yourself and encourage everyone you know over 50 to do the test as well. Prevention, in this case, is the only likely ‘cure’ for this terrible disease.

For more on Alzheimer’s see our article on Preventing Alzheimer’s Disease

Help support Food for the Brain

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References

Rowe J., Kahn R., ‘Human ageing: usual and successful’, Science, 237 (4811): 143-9 (1987).
 Bekris, L et al., ‘Genetics of Alzheimer disease’ Journal of Geriatric Psychiatry and Neurology 2010, 23(4) 213-227).
Smith A.D., ‘Homocysteine, B vitamins and cognitive deficit in the elderly’, American Journal of Clinical Nutrition, 75:785-6 (2002).
https://www.alzheimers.org.uk/about-us/policy-and-influencing/dementia-scale-impact-numbers
World Alzheimer Report. (2018). Available online at: https://www.alzint.org/resource/world-alzheimer-report-2018
Bradley K.M. et al., ‘Cerebral perfusion SPET correlated with Braak pathological stage in Alzheimer’s disease’, Brain, 125:1772-81 (2002); see alsp Jobst K.A. et al., ‘Detection in life of confirmed Alzheimer’s disease using a simple measurement of medial temporal lobe atrophy by computed tomography’, Lancet, 340:1179-83 (1992).
Jobst K.A. et al., ‘Association of atrophy of the medial temporal lobe with reduced blood flow in the posterior parietotemporal cortex in patients with a clinical and pathological diagnosis of Alzheimer’s disease’, J Neurol  Neurosurg Psychiat, 55:190-4 (1992); see also Jobst K.A. et al., ‘Rapidly progressing atrophy of medial temporal lobe in Alzheimer’s disease’, Lancet, 343:829-30 (1994).
Smith,D., Jaffe,K. ‘Dementia (Including Alzheimer’s Disease)can be Prevented: Statement Supported by International Experts’ Journal of Alzheimer’s Disease 38 (2014) 699–703
M. Beydoun et al, ‘Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis BMC Public Health 2014, 14:64 [http://www.biomedcentral.com/1471-2458/14/643]
Jernerén F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H, Smith AD. Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. American Journal of Clinical Nutrition. 2015;102:215-21.
Teng Z, Feng J, Liu R, Ji Y, Xu J, Jiang X, Chen H, Dong Y, Meng N, Xiao Y, Xie X, Lv P. Cerebral small vessel disease mediates the association between homocysteine and cognitive function. Front Aging Neurosci. 2022 Jul 15;14:868777. doi: 10.3389/fnagi.2022.868777. PMID: 35912072; PMCID: PMC9335204.
Smith AD Effect of reductions in amyloid levels on cognitive change in randomized trials: instrumental variable meta-analysis BMJ 2021;372:n156
Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment. A randomized controlled trial. PLoS ONE. 2010; 5: e12244.
Smith AD, Refsum H, Bottiglieri T, Fenech M, Hooshmand B, McCaddon A, et al. Homocysteine and dementia: An international consensus statement. J Alzheimers Dis. 2018; 62: 561-70
Beydoun MA, Beydoun HA, Gamaldo AA, Teel A, Zonderman AB, Wang Y. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 2014; 14: 643.
Yu JT, Xu W, Tan CC, Andrieu S, Suckling J, Evangelou E, et al. Evidence-based prevention of Alzheimer’s disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials. J Neurol Neurosurg Psychiatry. 2020; 91: 1201-9

By Patrick Holford

A global conference of leading world experts in dementia prevention has today identified four easy ways that could reduce risk of dementia by half and eight that could cut your risk by two thirds. 

The research was shared, for the first time, at the Alzheimer’s Prevention Conference, organised by the charitable foundation Food for the Brain. 

The new research showed that there are four easy ways to cut your risk of dementia in half:

1. Supplementing omega-3 fish oils

According to a new study of almost half a million participants of the UK’s Biobank supplementing fish oils cuts dementia risk.^[i] This new research was presented at the conference by China’s leading dementia prevention expert from Shanghai’s Fudan University, Professor Jin-Tai Yu, “Our current research, using data from the UK Bio Bank, shows that having a higher blood levels of omega-3, and supplementing fish oils, is associated with less risk of dementia.”

Other studies reported by Dr Simon Dyall, clinical neuroscientist at the University of Roehampton, showed that a higher intake of fish was associated with cutting risk of Alzheimer’s disease by a third.^[ii] “Half your brain is fat, and a type of omega- 3 called DHA has a very important role in the communication between brain cells.” said Dyall.

2. B Vitamins

According to Professor Yu, another very promising prevention treatment is B vitamins.^[i] “Lowering blood homocysteine levels, an established indicator of Alzheimer’s risk, with B vitamins is a most promising treatment.” Raised homocysteine is found in one in two people over 70.

In a trial at Oxford University by Professor David Smith, who was presenting at the conference, giving high dose B vitamins versus placebos, resulted in 52% less brain shrinkage and little further memory loss.^[ii]

Combining omega-3 and vitamin B. The discovery of the synergistic role of omega-3 led the Oxford Professor to reanalyse blood samples taken at the start of the trial for omega-3. They found that those with low omega-3 DHA blood levels, one of the main nutrients found in fish and fish oil supplements, had no benefit from the B vitamins, while those with high omega-3 DHA had 73% less shrinkage and almost nine times less shrinkage of the Alzheimer’s related areas of the brain.^[iii]

Furthermore, another study in Sweden, that had given omega-3 fish oil supplements, reanalysed their results and found those with good B vitamin status substantially reduced their dementia risk.^[iv]

A third study in the US, called ‘B proof’, that had given B vitamins with marginal improvements, reanalysed their results and found that those with higher omega-3 levels also had a much greater improvement.^[i]

“Research shows that you get impressive results if you give omega-3 and B vitamins together rather than on their own.” Says Professor Smith. 

While US National Institutes of Health researchers attributed 22% to lack of seafood or omega-3 and another 22% to the B vitamin factor they also attributed 32% of risk to inactive lifestyle.^[ii]

3. Exercise

“For many people the worst thing they can do for their brain is to retire”

Keeping your brain active. Another expert at the conference, Tommy Wood, Assistant Professor at the University of Washington, showed that your muscle mass predicts brain volume. “Exercise, especially resistance exercise, is important because it makes the brain do things that keep it healthy, such as growth and repair.” he says. “When they aren’t stimulated, the health of brain tissues deteriorates, with a knock-on effect on memory and thinking.”

And it’s not just physical exercise that does this, we also benefit from the mental exercise involved in activities like solving puzzles or learning a new language. “For many people the worst thing they can do for their brain is to retire”, says Wood. “They lose much of the stimulation that kept it healthy.” 

4. Sugar

“Sugar levels at age 35 predict Alzheimer’s risk later in life”

While it has long been known that diabetics have a much higher risk for dementia, a recent study at Boston University School of Medicine, found that higher blood sugar levels at age 35, but still in the ‘normal’ non-diabetic range, predict Alzheimer’s later in life.^[i] Talking at the conference Professor Robert Lustig, from the University of California, said, ”A high level of sugar and insulin in the blood – linked with a high carbohydrate diet – is definitely a driver for Alzheimer’s.” 

The conference, hosted by the UK charity foodforthebrain.org, identified eight domains of risk, in other words, four more actions you can take to reduce your risk of dementia: eating antioxidants from fruit and veg; having a healthy gut; sleeping well; and controlling stress. 

Targeting all eight risk factors earlier in life may reduce risk by two thirds. 

But how do you know what your risk is and what and how to change to reduce your risk? That’s what the charity, the Food for the Brain Foundation has been working on for a decade. On their website, foodforthebrain.org, you can do a free Cognitive Function Test. Almost 380,000 people have taken the test and, according to research by NHS and University College London researchers, 88% find it useful. You then complete a questionnaire that works out your future dementia risk index. It also tells you exactly what’s driving your risk up and what to do about it. By downloading the COGNITION app you can tack your progress, get advice on how to reduce your risk further, and get support to help you dementia-proof your diet and lifestyle.

Do the test now and reduce your risk!

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research bybecoming a Friend of Food for the Brain.

References:

^[1] Yu JT et al, Circulating polyunsaturated fatty acids, fish oil supplementation, and risk of incident dementia: a prospective cohort study of 440,750 participants, BMC medicine (pending publication)

^[2] Wu S, Ding Y, Wu F, Li R, Hou J, Mao P. Omega-3 fatty acids intake and risks of dementia and Alzheimer’s disease: a meta-analysis. Neurosci Biobehav Rev. 2015 Jan;48:1-9. doi: 10.1016/j.neubiorev.2014.11.008. Epub 2014 Nov 21. PMID: 25446949.

^[3] Yu JT, Xu W, Tan CC, Andrieu S, Suckling J, Evangelou E, Pan A, Zhang C, Jia J, Feng L, Kua EH, Wang YJ, Wang HF, Tan MS, Li JQ, Hou XH, Wan Y, Tan L, Mok V, Tan L, Dong Q, Touchon J, Gauthier S, Aisen PS, Vellas B. Evidence-based prevention of Alzheimer’s disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials. J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1201-1209. doi: 10.1136/jnnp-2019-321913. Epub 2020 Jul 20. PMID: 32690803; PMCID: PMC7569385.

^[4] Smith, A.D. et al., ‘Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial’, Public Library of Science ONE, 5(9) (2010)

^[5] Jernerén F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H, Smith AD (2015). Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. Am J Clin Nutr. 2015 Jul;102(1):215-21

^[6] Jernerén F, Cederholm T, Refsum H, Smith AD, Turner C, Palmblad J, Eriksdotter M, Hjorth E, Faxen-Irving G, Wahlund LO, Schultzberg M, Basun H, Freund-Levi Y. Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer’s Disease: The OmegAD Study. J Alzheimers Dis. 2019;69(1):189-197. doi: 10.3233/JAD-181148. PMID: 30958356.

^[7] van Soest, A.P.M., van de Rest, O., Witkamp, R.F. et al. DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial. Eur J Nutr (2022). https://doi.org/10.1007/s00394-022-02924-w

^[8] Beydoun MA, Beydoun HA, Gamaldo AA, Teel A, Zonderman AB, Wang Y. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 2014 Jun 24;14:643. doi: 10.1186/1471-2458-14-643. PMID: 24962204; PMCID: PMC4099157.

^[9] Zhang X, Tong T, Chang A, Ang TFA, Tao Q, Auerbach S, Devine S, Qiu WQ, Mez J, Massaro J, Lunetta KL, Au R, Farrer LA. Midlife lipid and glucose levels are associated with Alzheimer’s disease. Alzheimers Dement. 2022 . doi: 10.1002/alz.12641. Epub ahead of print. PMID: 35319157.

By Patrick Holford

After 40 failed trials for drugs injecting anti-amyloid antibodies (AAAs) one, Lecanemab^[i], has finally shown a modest benefit on cognitive function in those with early-stage Alzheimer’s. But they come with a terrible cost – adverse effects that include brain swelling and haemorrage which occurred in one in five trial participants.. When a similar drug, Aducanumab, was conditionally approved by the US FDA last year, despite nine out of ten of their experts voting against it, many resigned in protest^[ii]. Yet the pressure on pharma to get an amyloid drug to market, having spent over $42 billion^[iii], is immense.

Let’s consider the alternative 

Prevention with simple, doable changes to diet, lifestyle and supplementation with B vitamins and omega-3 fish oils.

The two most relevant measures of success of any treatment are reduction in the rate of brain shrinkage and a reduction in clinical dementia symptoms which lead to a diagnosis.

In relation to brain shrinkage the best AAAs have achieved is 2% less brain shrinkage. In a landmark trial by Professor David Smith and colleagues at the University of Oxford, B vitamin supplements, given to those with pre-dementia (mild cognitive impairment) have achieved a reduction in the rate of brain shrinkage of 52%, up to 73% in those with sufficient omega-3.^[i] This effect was shown in those with raised blood levels of homocysteine, a marker for B vitamin status that is raised in approximately half of pre-dementia patients and many more with Alzheimer’s. We now know that B vitamins need omega-3 to make the biggest difference, and vice versa.^[ii]

Figure 1. Reduction in brain shrinkage B vitamins and omega 3 vs AAAs. Sources: Jernerén F, Elshorbagy AK, Oulhaj A, et al. Am J Clin Nutr. 2015 Jul;102(1):215-21;  Schwarz AJ, Sundell KL, Charil A, et al. Alzheimers Dement (N Y). 2019 Jul 30;5:328-337; Smith AD, Smith SM, de Jager CA, et al. PLoS One. 2010;5(9):e12244.

Clinical Dementia Rating (CDR) with B vitamins and Omega 3’s

What about actual clinical improvement, called Clinical Dementia Rating (CDR), which is what counts for the person concerned? A CDR score of zero means no clinically significant cognitive impairment. In the Oxford trial on B vitamins  65% of participants on B vitamins with higher omega-DHA status ended the 2 year trial with a clinical dementia rating of zero compared with 25% receiving placebo.^[i] It was more than twice as effective as the recent drug. In a Swedish omega-3 trial those with sufficient B vitamin status, also had a marked reduction in clinical dementia rating, which was reduced by 1.5 points compared with placebo after 6 month’s treatment with omega-3.^[ii] The improvement in clinical dementia rating reported for Lecanemab, which was a modest 0.45 point reduction. This was marginally better than a 0.39 difference for Aducanumab, compared to placebo.^[iii] [iv] In other words, no AAA drug has even reduced  a CDR score by 1 point but both B vitamins and omega-3 have.

Figure 2. Comparison of Clinical Dementia Rating (CDR) reduction between synergistic B vitamin/Omega-3 supplementation and two AAA drugs. Sources: Oulhaj A, Jernerén F, Refsum H, et al. J Alzheimers Dis. 2016;50(2):547-57; Eisai press release; Tampi RR, Forester BP, Agronin M. Drugs Context. 2021 Oct 4;10:2021-7-3; Jernerén F, Cederholm T, Refsum H, et al. J Alzheimers Dis. 2019;69(1):189-197.

A trial in Holland, called B-proof, which had shown no significant effects overall in those supplementing B vitamins, recently reported that those with higher Omega-3 levels had a significant improvement in cognitive function. A French^[i] and Chinese study^[ii] reported a similar finding – the combination of B vitamins and omega-3 shows clear improvements in cognitive function – better than achieved by AAA drugs, without adverse effects.

So, on all three counts – brain shrinkage, cognitive function and clinical dementia rating – B vitamins plus omega-3 – wins out at a fraction of the cost since nutrients cannot be patented which is the requirement for the scale of profitability required by pharma.

Blood Sugar Levels and their impact

But, there’s two other points to make. Firstly, B vitamin and omega-3 status are but two of eight known actions that reduce risk or improve these critical criteria. Others are sugar, antioxidant rich fruit and veg, vitamin D, exercise, cognitive stimulation, gut health, sleep and stress.^[i] Having a high blood sugar level from age 35 predicts Alzheimer’s risk.^[ii] Being diabetic or having high insulin levels, which is a consequence of eating too many refined sugar and carbs, doubles risk.^[iii] Having a high carb intake is associated with increasing amyloid plaques in the brain – so why not tackle the upstream cause? One study reported that “Those who ate the healthiest diet had an 88% decreased risk of developing dementia and a 92% decreased risk of developing Alzheimer’s disease.”^[iv] Increasing lean muscle mass with resistance exercise is associated with better cognitive function and brain volume.^[v] The charity foodforthebrain.org have a free, validated online Cognitive Function Test, followed by a Dementia Risk Index questionnaire, that not only measures your cognitive function, but also shows you exactly what your risk is and how to reduce it by targeting your ‘weakest links’ in these eight known prevention steps.

Then, there’s the issue of side-effects. For each of these prevention steps there are none. Or rather, there are plenty – less risk for diabetes, heart disease, arthritis, premature ageing, better energy, sleep and weight control to name a few.

For the AAA drugs the side-effects are potentially devasting. Since one in five can be expected to experience brain swelling and microbleeds, regular brain scans will be necessary to monitor for these frequent complications. Is it right to expose an older person with cognitive decline to this scale of risk and medical intervention for such a modest benefit? The annual cost of treatment is expected to be above $10,000 but that doesn’t include the cost of medical monitoring or the cost of treatment when things go wrong. The cost benefit equation just doesn’t add up.

Early Intervention

Writing in the Financial Times last year Professor Smith says “ Your editorial is correct in saying ‘A resurrection of the amyloid approach must not divert resources and attention away from other ways to tackle dementia, which are in earlier stages of research and might give better results.’ These alternative approaches include identifying and then treating modifiable risk factors for dementia, of which about a dozen are already known. These account for about half of the cases of Alzheimer’s disease .” The high price proposed for the drug is disturbing, especially when a very much cheaper alternative treatment is available: high-doses of B vitamins and omega-3 from seafood or supplements. He estimates that early intervention , targeting all the prevention steps recommended by the Food for the Brain Foundation could cut a person’s risk by two thirds. 

For more details on Alzheimer’s prevention visit: https://brainhealthcheck.foodforthebrain.org/preventing-alzheimers-disease/

Alzheimer’s Is Preventable – LEARN more now

WE currently have 2 events on sale so that you can take a deep dive on this topic:
⭐️ MASTERCLASS – 4 hour conference with world leading experts on Alzheimer’s – Practitioner level. Book tickets here: https://brainhealthcheck.foodforthebrain.org/aipmasterclass/

🧠 Upgrade Your Brain – 8 steps to reduce your Alzheimer’s risk with with Patrick Holford – A condensed version of the masterclass that is 90 minutes long and aimed at the general public. Book your tickets here: https://www.eventbrite.co.uk/e/upgrade-your-brain-tickets-415953948457

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References:

^[1] Oulhaj A, Jernerén F, Refsum H, Smith AD, de Jager CA. Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment. J Alzheimers Dis. 2016;50(2):547-57. doi: 10.3233/JAD-150777. PMID: 26757190; PMCID: PMC4927899.

^[2]  Jernerén F, Cederholm T, Refsum H, Smith AD, Turner C, Palmblad J, Eriksdotter M, Hjorth E, Faxen-Irving G, Wahlund LO, Schultzberg M, Basun H, Freund-Levi Y. Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer’s Disease: The OmegAD Study. J Alzheimers Dis. 2019;69(1):189-197. doi: 10.3233/JAD-181148. PMID: 30958356.

^[3] Cummings JL, Goldman DP, Simmons-Stern NR, Ponton E. The costs of developing treatments for Alzheimer’s disease: A retrospective exploration. Alzheimers Dement. 2022 Mar;18(3):469-477. doi: 10.1002/alz.12450. Epub 2021 Sep 28. PMID: 34581499; PMCID: PMC8940715.

^[4] Jernerén F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H, Smith AD (2015). Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. Am J Clin Nutr. 2015 Jul;102(1):215-21

^[5] https://brainhealthcheck.foodforthebrain.org/campaigns/alzheimers-prevention/omega-3-and-b-vitamins/

^[6] Oulhaj A, Jernerén F, Refsum H, Smith AD, de Jager CA. Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment. J Alzheimers Dis. 2016;50(2):547-57. doi: 10.3233/JAD-150777. PMID: 26757190; PMCID: PMC4927899.

^[7] Jernerén F, Cederholm T, Refsum H, Smith AD, Turner C, Palmblad J, Eriksdotter M, Hjorth E, Faxen-Irving G, Wahlund LO, Schultzberg M, Basun H, Freund-Levi Y. Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer’s Disease: The OmegAD Study. J Alzheimers Dis. 2019;69(1):189-197. doi: 10.3233/JAD-181148. PMID: 30958356.

^[8] https://www.fiercepharma.com/pharma/eisai-and-biogen-need-meet-cms-halfway-after-lecanemabs-alzheimers-clinical-trial-win

^[9] Awaiting actual Lecanemab, trial – see press release ref 1 above

^[10] Maltais M, de Souto Barreto P, Bowman GL, Smith AD, Cantet C, Andrieu S, Rolland Y. Omega-3 Supplementation for the Prevention of Cognitive Decline in Older Adults: Does It Depend on Homocysteine Levels? J Nutr Health Aging. 2022;26(6):615-620. doi: 10.1007/s12603-022-1809-5. PMID: 35718871.

^[11] Li M, Li W, Gao Y, Chen Y, Bai D, Weng J, Du Y, Ma F, Wang X, Liu H, Huang G. Effect of folic acid combined with docosahexaenoic acid intervention on mild cognitive impairment in elderly: a randomized double-blind, placebo-controlled trial. Eur J Nutr. 2021 Jun;60(4):1795-1808. doi: 10.1007/s00394-020-02373-3. Epub 2020 Aug 28. PMID: 32856190.

^[12] https://brainhealthcheck.foodforthebrain.org/8-ways-to-upgrade-your-brain/

^[13] Zhang X, Tong T, Chang A, Ang TFA, Tao Q, Auerbach S, Devine S, Qiu WQ, Mez J, Massaro J, Lunetta KL, Au R, Farrer LA. Midlife lipid and glucose levels are associated with Alzheimer’s disease. Alzheimers Dement. 2022 Mar 23. doi: 10.1002/alz.12641. Epub ahead of print. PMID: 35319157.

^[14] https://brainhealthcheck.foodforthebrain.org/is-sugar-killing-your-brain/

^[15] Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M. Midlife healthy-diet index and late-life dementia and Alzheimer’s disease. Dement Geriatr Cogn Dis Extra. 2011 Jan;1(1):103-12. doi: 10.1159/000327518. Epub 2011 Apr 27. PMID: 22163237; PMCID: PMC3199886.

^[16] https://brainhealthcheck.foodforthebrain.org/exercise-and-keep-physically-active/

By Patrick Holford

What makes us humans so different to other apes is our larger brain, especially the cortex. It is three times larger than a chimpanzee. How did this happen? How did Homo Sapiens evolve our level of intelligence despite sharing almost the same genes? 

The brain’s origin, for all species, is from the ocean. It had to be as that is where life began. Millions of years ago the rudimentary eye cell, dinoflagellate, which is a type or marine phytoplankton, used a specific fat – the omega-3 fat docosahexanoic acid (DHA) – to convert solar photon energy into the first nerve impulse or twitch – a twitch towards food. That is the origin of the nervous system and brain.

Back in the ‘80’s, when zoologist Professor Michael Crawford analysed the types of fat in different animal’s organs and muscles they varied according to their dietary environment, except the brain. He discovered that the brain is always rich in DHA. The more DHA the brighter the animal, with the sea mammals and us humans having exceptionally high levels.

Recently it has been proven that DHA (docosahexanoic acid) has a unique structure involving six double bonds, arranged in a horseshoe shape, which actually makes it a semi-conductor with unique electrical properties. Its close cousins, ALA (alpha linolenic acid) in chia or flax, and EPA (eicosapentanoic acid) don’t have this potential. It’s all about DHA. While some EPA converts into DHA less than 1 per cent of ALA in plant-based sources of omega-3 such as chia seeds converts to DHA, the richest source of which is marine-based food from rivers and the sea.

Over 6 million years ago our hominid ancestors split from other apes (chimps, gorillas and bonobos), culminating in Homo Sapiens around 100,000 years ago. It clearly wasn’t genes that made us different. We share 98.5% of the same genome. It had to be the environment our ancestors exploited. During this time brain size steadily increased up to 1.45kg 10,000 years ago, roughly three times the size of a chimpanzee, at 384g.

Homo Aquaticus

We have over twenty profound anatomical, physiological and biochemical differences apart from our vastly different psychological advancement as in intelligence and language. More than anything, it is this, illustrated by our brain size, that makes us different. But, before looking closely at the circumstances, and diet, that almost certainly drove our gain in brain size and intelligence, let’s take a look at the fundamental differences we have. These have been so clearly delineated in an excellent book, The Waterside Ape, by Peter Rhys-Evans, and ear, nose and throat surgeon. He explores why we:

Stand upright
Have (virtually) no body hair
Have a layer of sub-cutaneous fat
A waxy, waterproof layer, the vernix, at birth
A diving reflex at birth, meaning we are able to swim before we can walk, and hold our breath underwater
A descended larynx, a precursor of being able to have complex language/speaking
Enlarged sinus cavities
A nose shape that is good for keeping the water out while swimming
Ears that actually form a protective boney protusion in those who spend a lot of time diving
Different kidneys, in how they filter salt and water 
Manual dexterity
Crinkly fingers when in water for a few minutes

Of course, the story we’ve all been told is that we came out of the trees, into the savannah and stood upright for better hunting. Anyone who has been on safari will know that a) you don’t stand a chance catching anything by standing upright – you crawl; and b) all the good hunters can sprint much faster than man (lion 80kph, leopard 60kph, cheetah 100kph, man under 30kph) precisely because four legs are better than two. But, can you explain any one of these other changes, let alone our increase in intelligence, by moving from the trees into the savannah for hunting? If so, how did we suddenly develop manual dexterity, tools and spears overnight to even survive? Also, why do certain ‘sea nomad’ tribes exist, such as the Moken and Bajou, who can hold their breath for up to 10 minutes under water, spending up to five hours a day in the sea, giving birth in the sea? Their spleen is adapted to oxygenate tissue, as it is in dolphins, to enable long dives. Where did that evolutionary adaptation come from?

The only logical explanation that I have encountered, which eloquently fits all these adaptations, in that our hominid ancestors exploited the waterside – wetlands, swamplands, rivers, estuaries and coasts. In the process of so doing, became upright, and started to eat a diet high in marine foods, providing the essential nutrients for brain development, that is omega-3 DHA, phospholipids, plus vitamin B12, iodine, and all those other essential elements from magnesium to selenium. From this perspective let’s briefly examine all the changes listed above, between us and other apes:

Stand upright – better for wading in water, so gradually our anatomy adapts but, even so, we are prone to the problems of uprightness, eg hips and knees because it is  anatomically inferior to walk on all fours, with better weight distribution.
Have (virtually) no body hair and a layer of sub-cutaneous fat – consistent with semi-aquatic mammals better for floating and insulation
A waxy, waterproof layer, the vernix, at birth – found in no land mammals, only other semi-aquatic mammals such as seals and chemically identical
A diving reflex at birth, meaning we are able to swim before we can walk, and hold our breath underwater
A descended larynx, a precursor of being able to have complex language/speaking – being upright, and diving, could have led to this vital adaptation. This, by the way, only occurs after a year or so, before which a baby’s language cannot develop the complexity of sounds and voice control only we have
Enlarged sinus cavities, which help to keep the head above water, but still have drainage holes in the ‘wrong’ place, eg good if on all fours but bad if upright, which is why we are prone to sinus problems.
A nose shape that is good for keeping the water out while swimming
Ears that actually form a protective boney protusion in those who spend a lot of time diving
Manual dexterity – if we were wading, and swimming, not walking on all fours, we have ‘free’ hands. Opening shells would develop manual dexterity.
Crinkly fingers when in water for a few minutes – perfect for catching fish.

Part of the idea of the ‘savannah’ theory is that food became scarce with climate changes so we switched to hunting. But the water’s edge was, until recently, abundant with easily accessible food. Even 200 years ago, in 1706, Daniel Dafoe wrote this regarding the Firth of Forth. “Off the Pentland Firth the sea was one third water and two thirds fish; the operation of taking them could hardly be call’d fishing, for they did little more than dip for them into the water and take them up.” Our estuaries were packed with mussels, oysters and crabs.

Historically, wherever early man is found so too is evidence of seafood consumption, with remains of shells, fish bones etc. from Pinnacle Point in South Africa, where early remains are found together with sea shells, to Wales. When a 40,000 year old Homo sapiens was found in the Gower peninsular DNA evidence showed that a quarter of their diet was seafood.

A marine food diet high in critical brain building nutrients, especially DHA, phospholipids and B12, is the best explanation for our cerebral expansion. “Docosahexaenoic acid (DHA), the omega-3 fatty acid that is found in large amounts in seafood, boosts brain growth in mammals. That is why a dolphin has a much bigger brain than a zebra, though they have roughly the same body sizes. The dolphin has a diet rich in DHA. The crucial point is that without a high DHA diet from seafood we could not have developed our big brains. We got smart from eating fish and living in water.” says Crawford.

The dry weight of the brain in 60 per cent fat and DHA makes up over 90 per cent of the structural fat of neurons (brain and nerve cells). The intelligent membrane that makes up all neurons is composed of phosphorylated DHA – that is DHA attached to phospholipids. The most abundant phospholipid is phosphatidyl choline, found predominantly in fish, eggs and organ meats. These are bound together by a process called methylation, itself dependent on vitamins B12, folate and B6. While folate and B6 is found in both plant foods and seafood, B12 is only found in foods of animal origin, and is especially high in all marine foods.

The evidence that exists suggests we were eating a diet rich in marine food, as well as  plant foods along the water’s edge, enjoying the ‘fruité del mare’. We would have eaten much more than we do today – at least double the calories. Today’s convenience world has dramatically reduced the calories we need to expend hunting and gathering food, travelling and staying warm.

The idea that we were eating twice as much and at least a quarter from marine foods makes sense of what we know about the optimal intake of both omega-3 fats rich in DHA, phospholipids and vitamin B12, lack of which are the main drivers of today’s endemic dementia. This would be equivalent to at least half our diet today needing to be from marine foods rich in fats.

Optimal amounts of omega-3 from seafood is estimated at 2 grams a day by Joseph Hibbeln at the US National Institute’s of Health, while choline is estimated at 400mg to 800mg. An optimal intake of B12 is probably 10mcg. None of these can easily be achieved even by eating seven servings of oily fish a day. (Choline is rich in all fish, but DHA is only rich in oily fish, fish roe and liver.)

In the chart below the last column combines EPA and DHA and shows the amount provided in an 85g serving. None provide 2,000mg, although they do get close, suggesting that we would have needed to eat at least a serving of fish or seafood a day, if not more. 

Brain size remains reasonably constant from 100,000 to 10,000 years ago, then starts to shrink, perhaps coinciding with the birth of agriculture and diets based more on meat, milk and plants than marine foods. Today, average brain size is 1.35kg. 

The evolution of intelligence and self-awareness

Apart from brain size and, more pertinently, brain to body size ratio, what sets us apart from other animals is self-awareness. Animals have the equivalent of thoughts and feelings but humans are relatively unique in being able to witness one’s own thoughts and feelings, that is self- awareness. This is not an easy thing to measure, but some other mammals, notably dolphins, gorillas and chimpanzees, also have a degree of self-awareness. Other contenders for higher cognition include octopuses and elephants, all large brained creatures. However, it isn’t just size that counts. In essence, there are three evolutions of the brain. First, the reptilian brain located on the brain stem, which programmes basic survival needs. Then there’s the mammalian brain, with more cognitive and emotive functions (think dog), then the neo-cortex, associated with higher cognition. But, while elephants have larger brains they have smaller neo-cortexes. It’s the neo-cortex that starts to grow in our hominid ancestors.

An indication of an advancing intelligence could be supposed from the earliest evidence of ancient rock art, as well as use of complex tools and adornments.  The earliest rock art is found in South Africa, dating back 77,000 years ago, and in Western Europe about 37,000 years ago, and possibly in Australasia (Sulawesi) around that time.

The richest concentration of ancient rock art over 6,000 years ago, however, is found in sub-Saharan Africa, the Nile Valley and Red Sea hills, then a green belt with vast lakes, rivers and wetlands, hence abundant marine foods, which lasted until about 3,500 years ago when much of Egypt is becoming a desert. Whether the drying up of the Sahara was linked to the Younger Dryas (see below), a change in the Earth’s tilt or over grazing is a subject of debate.^[i]

Meanwhile, groups of our early ancestors who had left Africa, living in Europe as far west as Ireland, north as Scandinavia, East as China and Australia, were also struck by cataclysmic weather changes. In Europe the Magdalenian culture, with advanced stonework, exists from 17,000 years ago, coinciding with the end of the Ice Age, until 12,000 years ago, coinciding with the Younger Dryas, a period of extreme cooling which lasted for circa 1,000 years, possibly triggered by a meteor shower^[i]. One theory has ancestors migrating south, towards warmer climates with available water, possibly carrying with them the sticky grains they had previously gathered, and may have planted them in moist soil as a means to survive, thus giving birth to the agricultural age whereby mankind moves away from a hunter gatherer lifestyle towards an agricultural lifestyle. This also makes sense as these two pockets of humanity, in Mesopotamia (now Iraq), between the Tigris and Euphrates river, and Egypt, becoming more densely populated with the need for stored food, supplied by grains and domesticating animals. This stable food supply would have allowed expansion of these populations. (There is another evolutionary hotspot in Asia and China^[i].)

Early Enlightenment

The likely existence of an ‘enlightened’ culture, Atlantis, is eluded to in the writings of Plato, possibly existing around the fertile region of the then much smaller Black Sea, which is thought to have flooded across the Bosphorus peninsular when the Mediterranean sea levels rose to a critical mass, dated back to around 7,000 years ago. This may also be the origin of the Flood myth, which occurs in ancient Sumerian lore dating back 5,000 years and later Hebrew lore.

Thus we have this triangle between the Black Sea to the North, Egypt to the South, and Mesopotamia to the East, all with evidence of evolved culture, including monotheism. The Sumerian culture appears over 6,000 years ago in the fertile crescent of Mesopotamia. Later, circa 2,500 years ago, we have the enlightened Zoroastra in Mesopotamia forming the Parsi culture in what is now Iran. Also,The Aryan-(Dru)Vedic culture, sometimes located east of the Black sea, migrated into the Indus valley in northern India as the main influence of the now Hindu culture, and the start of the Greek culture, considered to be the origin of our Western culture. The earliest hint of a Druidic culture dates back to this time. One stream of ancient druidic lore talks of a cataclysmic event, stones pouring from the sky, raising the possibility that early stone structures and barrows were built effectively as ‘bomb shelters’.^[i] While the meaning of the word ‘dru’ is associated with oak (those who meet by the oak) and truth, it also may also mean worshippers of the red Sun (du rua). Sun and fire worship is shared by the early Egyptians (Ra), (dru)vedic culture (Agni and Surya), Zoroastrian culture(Mithra) and even Sumerian culture (Utu). The use of fire started much earlier, with it’s discovery a million years ago, and widespread use from 500,000 years ago, which expanded humanity’s ability to derive energy from previously indigestible carbohydrates, as evidenced in the DNA with the emergence of multiple variations in carbohydrate- digesting amylase enzymes. This is also linked to an expansion in brain size.^[ii]

Is Homo Sapiens devolving?

Globally, there is an increase in mental illness which is fast becoming the biggest health threat, according to the World Health Organisation. There is also evidence that our brain size has reduced by 10 per cent, from 1.45kg 10,000 years ago^[1] to an average now of 1.35kg, coinciding with a more land-based food supply. According to Scandinavian research, our IQ is also falling by 7 per cent a generation. Global rates of depression and dementia, suicide and stress-related disorders of anxiety and insomnia are escalating. One in six children in the UK are classified with ‘special educational needs’ (SEN). Suicide, globally, has become the most cause of violent deaths, ahead of all wars and murders. In the UK 790 people a day, nine double decker buses worth, are diagnosed with dementia. Global incidence will top 100 million this decade, already costing over 1% of GDP.

On the assumption that our brains still require at least the same supply of nutrients that our semi-aquatic ancestors were able to eat during the period of maximum brain evolution – although one could argue that the digital age has put more stress on our brain function, hence we might even need more nutrients – and the fact that we are simply not achieving anything like the same intake of the brain’s essential fats, phospholipids and micronutrients, is it any wonder that mental health is in sharp decline? With a growing population and declining available seafood, coupled with contamination with heavy metals, PCBs and micro-plastic particles, matters are likely to get much worse.

High sugar intake, in animals, has been shown to lead to shrinking of the brain’s hippocampal region. This is where the nucleus accumbens, the seat of the brain’s dopamine-based ‘reward’ system, stimulated by sugar, caffeine and tech addiction, (especially that based on variable rewards such as the ‘like’ button) resides. Marketeers have learnt how to create addiction to their products by stimulating the reward system, selling short-term pleasure, the dopamine-based feeling, in the guise of happiness. The happy hour, the happy meal, happiness in a bottle etc. Over-stimulation of the reward system ultimately leads to dopamine depletion and brain cell death, coupled with a decline in serotonin, the tryptamine associated with happiness, connection, love, empathy and other essential qualities of a harmonious society – and the very qualities that make us human.

We are therefore witnessing the devolution of the brain, the decline and fall of mental health and harmonious society, a situation that is likely to get worse as population expands, unless we rapidly find a way to optimally nourish the brain.

Building Healthy Brains

The emphasis in human nutrition has, for too long, been on the body. With more protein, meat and dairy products, we have grown taller, but not smarter. As director of the Institute of Brain Chemistry at the Chelsea and Westminster Hospital, Professor Michael Crawford has been able to accurate predict which pregnant women are most likely to have pre-term babies, with an increased risk of cognitive delay or impairment. This is based on determining the supply, by analysing the pregnant woman’s blood, of DHA. In its absence levels of a surrogate fat, oleic acid, rises to fulfil the requirement of the neonatal brain, when DHA is in short supply. It is, however, an inadequate substitute and thus cognitive development is impaired. Babies born of mothers with low blood DHA levels, compared to those supplementing DHA, have smaller brains.^[2]

According to Crawford, with a growing population and shrinking fish supply, we must develop marine agriculture on a massive scale to survive and protect the brain. In the same way that man moved from hunter gatherer on the land to peasant farmer, we too must move from hunter gatherer in the oceans to marine farmer. In Japan he has been instrumental to the creation of artificial reefs in the estuaries to attract back the marine food web, from mussels to crustaceans, and fish, as well as farming seaweed on a massive scale. By processing seaweed it is possible to create DHA, the critical brain fat that is crucially lacking in a plant-based diet. As Crawford says “We now face a world in which sources of DHA – our fish stocks – are threatened. That has crucial consequences for our species. Without plentiful DHA, we face a future of increased mental illness and intellectual deterioration. We need to face up to that urgently.”

At the other end of the lifecycle, more and more older people are slipping into dementia, which is a preventable but not reversible condition. At the University of Oxford, Professor David Smith has shown that inadequate omega-3 fats (DHA and EPA) and B vitamins, especially vitamin B12, are the principle drivers of cognitive decline. Yet, by providing these nutrients to those with pre-dementia, further memory decline and brain shrinkage can be arrested. B12 is only found in animal foods and is especially rich in seafood. A plant-based diet alone does not provide sufficient DHA, B12 or phospholipids require for optimal brain development.

Therefore, it is vital that the needs for optimal brain function are put at the top of the health agenda to prevent the decline of our mental health and potentially the fall of Homo Sapiens. Without our fully functioning brains humanity will neither have the insight nor cooperation to face and resolve the challenges we face with a growing population, reducing food supply, increasing pollution, climate changes and ever-increasing energy demands.

Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.

Please support our research by becoming a Friend of Food for the Brain.

References

^[1] https://www.astrobio.net/news-exclusive/how-earths-orbital-shift-shaped-the-sahara/; see also https://phys.org/news/2019-01-sahara-swung-lush-conditions-years.html; see also https://www.ncdc.noaa.gov/abrupt-climate-change/End%20of%20the%20African%20Humid%20Period

^[2] https://en.wikipedia.org/wiki/Younger_Dryas_impact_hypothesis

^[3] https://www.nature.com/news/how-china-is-rewriting-the-book-on-human-origins-1.20231

^[4] https://www.youtube.com/watch?v=t9Zjd0TIHsY

^[5] K. Hardy et al., ‘The importance of dietary carbohydrate in human evolution’, Quarterly Review of Biology(2015), vol 90(3):251–268.

^[6] https://www.discovermagazine.com/planet-earth/the-human-brain-has-been-getting-smaller-since-the-stone-age

^[7] Randomized controlled trial of brain specific fatty acid supplementation in pregnant women increases brain volumes on MRI scans of their newborn infants.

Ogundipe E, Tusor N, Wang Y, Johnson MR, Edwards AD, Crawford MA.

Prostaglandins Leukot Essent Fatty Acids. 2018 Nov;138:6-13. doi: 10.1016/j.plefa.2018.09.001. Epub 2018 Sep 21.

PMID:

30392581

Today, the US FDA has licenced aducanumab, an amyloid protein drug developed for dementia treatment. It has already failed in clinical trials, adding to the 300 studies that have failed. In a normal world, if you test a theory 300 times and it fails 300 times you discard the theory – that amyloid plaques in the brain are what causes Alzheimer’s.

While aducanumab has been demonstrated to reduce brain amyloid, it hasn’t been shown to deliver any meaningful improvement in cognition. A recent meta-analysis of 14 anti-amyloid drug trials found no significant slowing of cognitive decline despite lowering of amyloid. Nor has it been shown to reduce the rate of brain shrinkage.

In contrast, the combination of B vitamins and sufficient omega-3 has been shown to reduce brain shrinkage by 68% over the period of one year in research by Professor David Smith and colleagues at Oxford University. No drugs have shown such a positive effect on brain shrinkage. What’s more, memory loss was not observed to decline further and 70% of participants were classified with a Clinical Dementia Rating of zero.

In many cases dementia may be preventable – not with drugs but with nutrition and lifestyle changes.

Omega-3 and B vitamins are a Dynamic Duo

B vitamins and omega-3 are so important for mental health because the membrane through which brain signals are passed is made out of an omega-3 fat called DHA, which attaches to a phospholipid. DHA is 98% of the structural fat of the brain. Seafood is a rich source of DHA and phospholipids, and phospholipids can also be found in eggs.

These two vital components of brain cells are actively bound together by a process called methylation. Methylation is dependent on B vitamins, especially B12, folate and B6. Zinc also has a vital role to play. If these nutrients are low a toxic amino acid called homocysteine starts to accumulate in the blood stream. More often than not the critical deficiency is vitamin B12, found in fish, eggs, milk and meat. The ‘deficiency’ may be due to dietary deficiency, but also may be due to malabsorption triggered by a lack of stomach acid, potentially exacerbated by certain drugs.

Putting Prevention into Action

Scientific research shows that the following factors are key in the prevention of dementia:

·     Sufficient intake and absorption of B vitamins
·     Sufficient intake of omega-3
·     Sufficient intake of antioxidants including Vitamin C
·     A low sugar diet
·     Good digestion
·     Having an active mind and social life
·     Regular physical activity
·     Good sleep and reducing stress

These are all areas in which you can make simple changes to support your brain health. Take our popular Cognitive Function Test today to discover the actions you can take that will make the biggest difference. We encourage everyone over 40 to take this test.

Like our Cognitive Function Test? Help us Upgrade It

Food for the Brain is crowdfunding to support the upgrade of its Cognitive Function Test, already taken by 360,000 people around the world.

COG-NITION® is a personalised and interactive ‘brain upgrade’ programme designed to help people make positive changes step by step, with the support of an engaging and encouraging community. It has been created in collaboration with leading dementia experts including Professors David Smith and Jin-Tai Yu.

By supporting our crowdfunding campaign, you can help us launch COG-NITION® this autumn. The ultimate goal is to save a third of people from getting dementia, which means a 100,000 fewer cases a year in the UK alone.

As a charitable foundation, we rely on donations to continue our vital work in this area. Please give whatever you can – every £1 you give helps someone somewhere make the changes to prevent dementia.

Thank you for your support.

Estimated reading time: 9 mins

Chronic fatigue syndrome (CFS) is a debilitating condition that is otherwise known as myalgic encephalomyelitis (ME). Due to the diverse set of seemingly unrelated symptoms that people with this condition present with, it is commonly misdiagnosed and can often be confused with other conditions such as depression. 

Typical symptoms of CFS can be: 

Sleep problems
Muscle and joint pain
Headaches
Memory and concentration problems
Flu-like symptoms
Feeling dizzy or nauseous
Low mood

A mysterious illness 

CFS has long been stigmatised and ignored by many doctors due to its mysterious aetiology, often leaving many physicians baffled. This has commonly led to doctors concluding that it is purely a psychiatric illness, rather than a disease of some kind. Sadly, this means that many patients go through years of seeing various doctors before they get a proper diagnosis. 

According to the National Institutes of Health, CFS impacts 15 million to 30 million people worldwide, and leaves 75% of those affected unable to work and 25% homebound or bedridden. Although the aetiology of CFS is unclear, the condition commonly arises following a viral illness, in particular Epstein-Barr virus, herpes and mononucleosis. Since the coronavirus outbreak, there has been a large number of reports of people suffering with long-term symptoms that are akin to those of CFS. This has led to a new line of research opening, to examine the biochemical mechanisms that are leading to symptoms, such as debilitating fatigue, low mood and brain fog, headaches and more in those who have been infected with COVID-19.

A new angle to understanding COVID-19?

According to a report¹ published by the Centers of Disease Control and Prevention, more than a third of those who have tested positive for COVID-19 and have symptoms don’t feel like they’re fully recovered, even weeks and months later. Why might this be occurring at such alarming rates? Some researchers, such as Mady Hornig, Immunologist at Colombia University, have proposed that this may be due to inflammation levels going haywire in the body. COVID-19 patients exhibit abnormally high levels of inflammatory molecules², such as certain cytokines like interferon gamma, which are coincidentally the same inflammation driving molecules that are chronically present in CFS patients. This overactivation of the immune system, which has frequently been labelled the ‘cytokine storm’ in the acute phase of COVID-19, may be what is leading to long-term problems.  

Neurovirologists such as Avindra Nath, at the National Institute of Neurological Disorders and Stroke, believe that there should be more attention placed on the long term risks of COVID-19. Nath purported, in an article published in The Scientist, that viruses can seek long-term refuge in organs to hide from the immune system, which can essentially cause a constant trickling of virus particles to escape into the bloodstream leading to a chronic trigger of inflammation. However, the most obvious mechanism by which viruses can cause symptoms related to CFS is autoimmunity. Nath explains how during the acute phase of a viral infection, the body’s immune system can mistake its own proteins with viral proteins, due to an overactivation of inflammation. This, over time, can lead to mitochondrial dysfunction

A defect in the batteries of our cells?

The mitochondria are the battery-like organelles of our cells, which play an important role in a wide range of physiological processes, such as creating APT (the energy currency of our body), as well as neurotransmitter synthesis, production of insulin, iron metabolism, heat production and many more. Damage to the mitochondria can therefore have a global effect on the body, and many chronic diseases such as diabetes, psychiatric conditions and heart disease, are related to poor mitochondrial function. A key example is in the lack of ATP production that can occur in mitochondrial dysfunction – without enough ATP, we begin to experience symptoms of overall malaise, exhaustion, muscle pain, brain fog and low mood. A chronic inflammatory response that can be triggered by acute viral infections, can literally wear down the mitochondria, altering the metabolism and functioning of cells. This can have a far-reaching impact on our body and even lead to problems in normal bodily functions such as sleep. 

An example of this was seen in a case-controlled study³ carried out in 2011 and published in BMC Neurology, which looked at 22 healthcare workers who had been infected in 2003 with SARS-CoV-1 and were left with chronic exhaustion, musculoskeletal pain and sleep disturbances. After performing EEGs (electroencephalogram) on the study participants, they found elevated levels of alpha EEG anomaly and apnea. The alpha-EEG anomaly has been found to interrupt normal restorative aspects of sleep and many studies⁴ have identified this anomaly as a consistent feature in patients with fibromyalgia, a condition that leads to similar symptoms to CFS. 

The best offence is a good defence 

As the well-known adage goes, ‘the best offence is a good defence’ – the most important thing we can do to protect ourselves from the negative impact of viral infections like COVID-19, as well as prevent potential long term effects, is to optimise our health via nutrition and lifestyle approaches. A key trigger for mitochondrial impairment is oxidative stress⁵, caused by the following factors:

High blood sugar levels/insulin resistance
Consumption of inflammatory foods 
Chronic stress 
Alcohol
Cigarette smoking 

Oxidative stress is a term used to describe the impact that reactive oxygen species (ROS) can have on our health, which are chemically reactive unstable molecules that contain oxygen. These molecules scavenge electrons from other molecules, leaving a trail of disruption called free radical damage.  It is well known that under normal conditions, our bodies maintain a healthy balance between ROS and antioxidants, which are molecules that can donate electrons without becoming ‘unstable’ themselves and are therefore able to halt free radical damage. 

Having chronically high blood sugar levels, drinking too much alcohol, smoking, eating too many processed foods and chronic stress, are a recipe for free radical damage and therefore mitochondrial dysfunction. Here are some simple dietary changes to prevent this from happening:

Avoid sugar, in all its forms

Sugar can come in many forms, which is why it’s important to read ingredient labels. Food manufacturers often try to sneak sugar in by using other types of sweeteners such as dextrose, maltodextrin, syrups, fructose, sucrose, high-fructose corn syrup, agave, fruit concentrates and honey. Avoid products that contain any added sugars in them, as well as using sugar at home in foods and drinks.

Prioritise protein, fibre and healthy fats

To help avoid chronically high blood sugar levels, it’s important to base your diet on wholefoods rich in proteins, fibre and healthy fats. Protein can be found in meats, poultry, fish, eggs and pulses and healthy fats in oily fishes, nuts and seeds, coconut (and its oil), extra virgin olive oil and avocado (and its oil). Aiming for 50g of fibre a day is also incredibly important to help balance blood sugar levels. This means eating various types of vegetables throughout the day in your main meals. You can do this by aiming to dedicate half of your plate to a variety of vegetables at lunch and dinner.

Avoid processed foods

Processed, ready-made meals, often contain ingredients that can be detrimental to our health if eaten too often. Hydrogenated oils, sugars and additives feature frequently in packaged foods, which can trigger oxidative stress and can have a negative impact on mitochondrial health. Focus on whole foods and cooking from scratch as much as possible, so that you have control over what’s going into your meals. 

Eat a rainbow

The pigments in plants that cause them to have vibrant colours, such as the red in tomatoes, orange in carrots and sweet potatoes and greens in spinach and kale, are rich in antioxidants like polyphenols and flavonoids. These molecules scavenge free radicals from the body’s cells and help mop up any damage left by them. Try to vary your vegetable intake so that you make sure you’re benefitting from a wide variety of antioxidants. 

Nutrients and enzymes to support mitochondrial health

Aside from the above dietary changes, there are a few nutrients and enzymes that have been well researched in the context of supporting mitochondrial function.

Enzyme CoQ10

CoQ10 is an important endogenous antioxidant and enzyme that is produced by the body, which plays an important role in something called the electron transport chain, an important process that occurs in the mitochondria, which triggers the production of ATP or energy in simpler terms. CoQ10 is something that is created inside the body, however, we can get small amounts directly from external sources such as our diet. Foods such as organ meats and oily fish have been shown to contain some CoQ10. In addition, deficiencies in cofactor nutrients such as B2, B3 and vitamin E have been shown to play a role in CoQ10 deficiency, as well as the use of statin medication⁶. 

L-carnitine

Carnitine is an amino acid that’s synthesised from dietary sources of lysine and methionine, also amino acids. It is responsible for the transport of long-chain fatty acids into the mitochondria to be oxidised and used to create ATP. In previous studies, patients with CFS have displayed significantly lower levels of acetyl-L-carnitine, total carnitine, and free carnitine; and those with the lowest levels have shown the worst functional capacity ⁷. Whilst carnitine deficiency is rare, those on long term restrictive diets, as well as those with poor liver function may have issues synthesising carnitine. Lysine and methionine are widely found in many foods such as meats, poultry, eggs, fish, as well as in nuts and seeds, wholegrains such as oats, brown rice, and finally, in pulses.  

Alpha lipoic acid

Alpha lipoic is an important antioxidant that plays an essential role in supporting mitochondrial enzymes involved in glucose metabolism and energy production. In particular, Alpha lipoic acid has been shown to prevent damage caused to the mitochondria by increased levels of a substance called nitrous oxide (NO) in the body. Whilst NO is essential for blood vessel health, too much of it can be detrimental to our cells. This often occurs in acute inflammation, such as during the initial stages of an infection. Alpha lipoic acid has been shown to effectively restore mitochondrial enzyme activities inhibited by excess NO, which has a consequent positive impact on ATP production⁸. 

Supplementation with these nutrients has been explored in some studies⁹. However, it is important to work with a nutritional therapist or a nutritionist to make sure you’re taking the right dose and to investigate potential drug-nutrient interactions, for those taking medication. In the meantime, following the above dietary and lifestyle guidelines can have a profound impact on health and mitochondrial function. 

References

1.  Tenforde MW, Kim SS, Lindsell CJ, et al. Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network — United States, March–June 2020. MMWR Morb Mortal Wkly Rep 2020;69:993-998. DOI: http://dx.doi.org/10.15585/mmwr.mm6930e1external icon  

2.  Distinct plasma immune signatures in me/cfs are present early in the course of illness

3.  Moldofsky, H., Patcai, J. Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study. BMC Neurol 11, 37 (2011). https://doi.org/10.1186/1471-2377-11-37 

4.  A. M. Drewes, Pain and sleep disturbances with special reference to fibromyalgia and rheumatoid arthritis, Rheumatology, Volume 38, Issue 11, November 1999, Pages 1035–1038, https://doi.org/10.1093/rheumatology/38.11.1035

5.  Guo, Chunyan et al. “Oxidative stress, mitochondrial damage and neurodegenerative diseases.” Neural regeneration research vol. 8,21 (2013): 2003-14. doi:10.3969/j.issn.1673-5374.2013.21.009. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145906/ 

6.  Kristin Filler, Debra Lyon, James Bennett et al, ‘Association of mitochondrial dysfunction and fatigue: A review of the literature’, BBA Clinical, Volume 1, June 2014, Pages 12-23. https://doi.org/10.1016/j.bbacli.2014.04.001

7.  Sanford H. Levy MD, FACP, ABIHM, in Integrative Medicine (Fourth Edition), 2018. https://www.sciencedirect.com/topics/medicine-and-dentistry/carnitine 

8.  Sylvia Hiller, Robert De Kroon, Eric D.Hamlett et al, ‘Alpha-lipoic acid supplementation protects enzymes from damage by nitrosative and oxidative stress’,  Biochimica et Biophysica Acta (BBA) – General Subjects, Volume 1860, Issue 1, Part A, January 2016, Pages 36-45. https://doi.org/10.1016/j.bbagen.2015.09.001 9.  Kristin Filler, Debra Lyon, James Bennett et al, ‘Association of mitochondrial dysfunction and fatigue: A review of the literature’, BBA Clinical, Volume 1, June 2014, Pages 12-23. https://doi.org/10.1016/j.bbacli.2014.04.001

Worldwide 46.8 million people have dementia. In the UK, 1 in 14 people over 65 have Alzheimer’s, the most prevalent form of dementia; and increasingly dementia sufferers are also struggling with other chronic conditions, such as diabetes and depression. Research on new strategies for earlier diagnosis is among the most active areas in Alzheimer’s science. This is as the majority of cases are diagnosed when irreversible brain damage or mental decline has already occurred. 

The amyloid protein test used for earlier diagnosis

Amyloid beta is a protein found in the brain that is involved in the pathophysiology of Alzheimer’s and cognitive decline. This 2019 study found that a blood test to measure amyloid, is 94% accurate in earlier diagnosis of Alzheimer’s disease. This is specifically when in combination with age and genetics (testing positive for the APOE4 gene) as risk factors. Whilst this is a positive development for future considerations in treating Alzheimer’s, there has been no successful amyloid-lowering drug trial to date.

In addition, it is well-known that the damaging clumps of amyloid protein can begin to develop and lead to brain atrophy decades before an individual even begins to experience symptoms of memory loss and cognitive function, so unless testing is given earlier on in life as a preventative measure, an amyloid-lowering drug when the damage has already been caused may not be very effective. 

Amyloid, a protective mechanism?

To date, the majority of research into the treatment of Alzheimer’s has been focused on the “amyloid hypothesis”. In 2018 alone, the US National Institutes of Health spent $1.9 billion on Alzheimer’s research. However, according to this study, there has been a 99% failure rate in the development of drugs that target this disease. Questions about the reliability of the amyloid protein hypothesis are being posed by scientists, after various studies discovering how amyloid plaques actually function as a type of sticky defence against bacterial invasion, lead to a different hypothesis. In one significant study, where mice that were genetically engineered to make Alzheimer’s proteins had bacteria injected into their brains, researchers found that amyloid plaques engulfed bacterial cells overnight, suggesting a protective mechanism.  

Why we cannot ignore the link between high homocysteine levels and Alzheimer’s 

According to a Consensus Statement released by an international panel of experts on dementia: Research has shown, time and time again, that having high homocysteine (Hcy) levels, and low folic acid and B12 levels in the blood correlate with an increased risk for Alzheimer’s disease.

An earlier review written by Professor David Smith in 2008, highlighted that there are a total of ‘seventy-seven cross-sectional studies on more than 34,000 subjects and 33 prospective studies on more than 12,000 subjects’…that…‘have shown associations between cognitive deficit or dementia and homocysteine and/or B vitamins.’ 

In a meta-analysis published in 2014 by BMC Public Health, raised homocysteine was considered to be one of the three strongest risk factors, along with low education and decreased physical activity.

Two further trials have clearly shown that lowering homocysteine, through the supplementation of B vitamins, reduced age-related cognitive decline in normal ageing and also slowed down both brain atrophy and cognitive decline in people with Mild Cognitive Impairment.

The efficacy of B vitamins to prevent the progression of Alzheimer’s.

In one study, 270 people over 70 with Mild Cognitive Impairment were recruited to trial the efficacy of B vitamins to prevent the progression of Alzheimer’s. MRI scans were done at recruitment and half the participants were given high doses of three B vitamins (B6, B9 and B12), half took a placebo tablet.

After 2 years, participants were scanned again and scientists found that the rate of brain atrophy in those treated with the B vitamins was on average 30% slower than those taking placebo. In addition, in those that had the highest homocysteine levels at baseline, the effect of B vitamin treatment was even more potent, helping to slow down brain atrophy by 53%. This result fits all the criteria for a disease-modifying treatment and so is especially important. There is, therefore, ample evidence to propose that lowering homocysteine by giving appropriate supplemental levels of homocysteine lowering nutrients, including B6, B12 and folic acid, would reduce risk.

In a commission published by the Lancet, 9 modifiable risk factors were outlined, clearly excluding homocysteine:  

Ignoring homocysteine is surprising, since a meta-analysis from the National Institute of Aging estimated that about 22% of Alzheimer’s disease may be caused by raised levels of homocysteine.

Integrating homocysteine testing and inexpensive B vitamin-based treatment into the heart of mainstream health strategies on Alzheimer’s could potentially play a vital role in the prevention of dementia, if caught early enough.