‘Don’t Waste Your Money on Supplements’

By Patrick Holford

How often have you read this phrase from supposed experts, apparently described as “based on science”? It usually comes from “foodies” who believe that you can get all the nutrients you need from a well-balanced diet. I found an example of this in a recent book by Professor Tim Spector, who dismisses the need for vitamin C or vitamin D supplementation.

I will deal with what the science and relevant studies actually show, especially regarding supplements that are claimed to help prevent cognitive decline. But first, let’s look more deeply at the mindset behind such claims.

The idea that we can get all the nutrients we need from food makes intuitive sense. Underneath this lies the belief that we evolved to grow and survive using the nutrients available in food. Darwin reached a similar conclusion when he argued that “the conditions of existence” were the main driving force in evolution.

Our Ancestors Ate Differently, Ate More, And Had Larger Brains

Extending this logic, consider the period of prehistory when hominid brain size grew steadily, culminating in Homo sapiens brain size (calculated from skull size) of almost 1,700 grams, circa 20,000 to 30,000 years ago. It has since shrunk by about 20% to today’s average brain size of less than 1,350 grams. So it is equally logical to ask: what has changed in our “conditions of existence” to result in our shrinking brains? If what we were eating over 20,000 years ago was closer to optimal, and what we eat now is often pathological, what are the main differences?

The first difference is the quantity of food. Today the average person expends roughly 200 to 400 calories a day on physical activity, compared to 600 to 1,200 calories per day for our ancestors; at least three times more than the average modern adult. They had to eat around three times as much as us, just to maintain weight. So even if we ate the same foods with the same nutrient density, we would still be more likely to fall short. But of course today’s food is often less nutrient-dense as well.

A simple, far less “prehistoric” illustration is a comparison of the diet of mid-Victorian workers. A study in the Journal of the Royal Society of Medicine found that the nutrient intake of a mid-Victorian worker, while not necessarily constituting an “optimal” diet, had a far higher intake of vitamins, minerals and essential fatty acids than we do today. They concluded that this “constitutes a persuasive argument for a more widespread use of food fortification and/or food supplements” to make up the difference. (1)

Marine Food And Brain Development

So which nutrients that were abundant in our ancestors’ diets are widely missing now? The starting point has to be marine food. Early humans had to migrate and live along the water’s edge for basic survival. Rivers, estuaries, swamplands and coasts would have provided a plentiful supply of marine foods, rich in both omega-3 and phospholipids such as choline, plus vitamin D, vitamin B12, selenium, zinc and iodine: all completely essential for brain development. Nutrient-dense foods such as molluscs, crustaceans and small fish caught in rock pools were also highly accessible. For gatherers, most likely women, these “fruits de mer” were rich pickings, and since brain development happens largely during pregnancy, maternal nutrition was especially crucial.

There is also the “aquatic” or “waterside ape” hypothesis promoted by brain researcher Professor Michael Crawford, and discussed widely in popular science. Support for this hypothesis includes an analysis of the diet of a 40,000-year-old Homo sapiens discovered in a cave on the coast of South Wales. Based on bone analysis, it has been estimated that at least 20% of this individual’s diet was marine food. Considering their much higher level of physical activity, roughly half of a modern diet would need to consist of marine food in order to achieve an intake of nutrients equivalent to that consumed during the period when the brain of Homo sapiens reached its largest size.

In short, it is hard to explain human brain evolution without abundant omega-3, choline and vitamin B12, alongside a high intake of folate from plants (previously all organic).

Omega-3 & Choline

Omega-3 DHA, which is primarily found in marine foods, is a keystone nutrient for brain structure and function. Typical modern intake is often very low. The optimal intake for brain health and dementia prevention may be as much as 1,000 mg a day. The lowest risk of several diseases occurs with around 2,000 mg of omega-3 (both EPA and DHA). This kind of intake is entirely consistent with an ancestral diet rich in marine food, but it is not so easy in the average diet today without eating marine foods almost every day, which would also help provide enough choline.

The average intake of choline for women is just 278 mg, and it is even lower in vegans or those who don’t eat fish, which is expensive for those on lower incomes. To achieve an optimal intake from food alone, one would need to eat several eggs or frequent servings of fish or other marine foods most days of the week. This is unrealistic for many people.

Let’s test this from a different angle, using studies examining intakes of these nutrients and their effects on brain health, including risk of cognitive decline.

Take choline, which is richest in marine food, eggs and organ meats. A study of 125,000 people followed over 12 years, using UK Biobank data and published in the American Journal of Clinical Nutrition, found a relationship between higher dietary intake of choline and reduced dementia risk, with greatest benefits around 400 mg a day. Risk for Alzheimer’s was also lowest around this level of intake. (2)

Vitamin B12 And The “Brain Shrinking Zone”

Why current B12 reference ranges miss dementia risk

Then there is vitamin B12, found only in foods of animal origin, and especially in marine foods and eggs. When you correctly define sufficiency (and its counterpart, deficiency) as optimal health and minimal disease risk, including dementia risk, it becomes clear that many older people need up to 500 mcg of B12 to normalise serum B12 above 500 pg/ml and to keep homocysteine below 10 µmol/L. Roughly half of those above 60 fail to meet these thresholds.

Accelerated brain shrinkage occurs below 500 pg/ml, as established by Professor David Smith’s research at Oxford University more than a decade ago. This is why several countries, such as Japan, set the “normal” range for serum B12 as above 500 pg/ml. Despite clear evidence over the past decade, both UK and US health authorities have failed to correct the reference range for vitamin B12, which is set at less than half this, namely around 180 pg/ml. (3)

Absorption, ageing, and how to know if you need more

A recent study of 3,000 EU children reported that the median B12 level was 347 pg/ml and one third were below 200 pg/ml. (4) This means that many children are already in the risk zone, and deficiency is more prevalent in vegan children. In older adults the problem is compounded by poor absorption, made worse by antacids, since stomach secretions are required to absorb vitamin B12. Hence, those taking PPI antacids such as omeprazole for more than 4.4 years have a 30% increased risk of dementia. (5) There is no realistic way for many older adults to achieve these required intakes of B12 from diet alone.

How do you know what you need? I recommend testing homocysteine, which tells you whether you are in the brain shrinkage risk zone above 10 µmol/L, or testing serum B12 and ensuring it is above 500 pg/ml, then supplementing accordingly with vitamin B12 or, better still, a homocysteine-lowering formula if levels fall outside the ideal range.

Vitamin D: Supplementation Is Essential In Winter Months

Vitamin D, also found in marine foods, is insufficient for a third of the year due to lack of synthesis from sunlight acting on the skin, if you rely solely on diet. A recent scientific report states: “Vitamin D3 plays a pivotal role not only in bone health but also in the functioning of the nervous system, particularly in the context of age-related neurodegenerative diseases such as Alzheimer’s disease, multiple sclerosis, and Parkinson’s disease.” (6)

Vitamin D Levels, Brain Health and Dementia Risk

Cognitive decline is far more likely if vitamin D is low, and Alzheimer’s risk is lower when levels are higher. In one large study, those who supplement vitamin D had a lower incidence of dementia. (7) Anyone who implies you can still get enough from food in winter is less enlightened than the UK Government, who recommend everyone supplements vitamin D from October to March.

Why Testing and Target Levels Matter in Winter

Vitamin D’s protective effect depends on your blood level. I supplement 800 IU in the summer months and 3,000 IU daily in the winter months. However, the true indicator is whatever keeps my blood vitamin D level above 75 nmol/L (30 ng/ml). Bear in mind that I also eat oily fish and make a point of getting at least 20 minutes of sun exposure a day in summer months, plus a winter holiday in the sun. Factors such as darker skin, excess weight, low fish intake or low sun exposure increase your needs. That is why we recommend testing vitamin D, ideally as winter approaches and again towards the end of winter, so you know you are on track with supplementation.

A recent Chinese study published earlier this year on women over 100 found those in the highest quarter for vitamin D had an 87% reduced risk of dementia compared to those in the lowest quarter. (8) Risk was lowest in those with a blood level above 73.5 nmol/L (29.3 ng/ml). This is remarkably consistent with levels associated with benefits for bone health, immunity and many other outcomes. It is also the level our scientists set to achieve “green” on the DRIfT test. The vast majority of people in the western world do not reach this level.

Vitamin C: An Essential Brain And Body Nutrient

This essential vitamin is produced by almost all animals but not humans. Guinea pigs also do not make it, which is why they became an experimental animal of choice: they share our vulnerability. We are dependent on vitamin C for many functions in the body, and thousands of studies support its roles, including as a key antioxidant, as a maker of collagen, and as a vital nutrient for immunity.

Why vitamin C is repeatedly underestimated

Yet I still read so-called experts who claim vitamin C “does nothing” for colds, cancer or anything else. Are they simply not reading the science? In very high intravenous doses, it has been used in some hospital settings, including trials in critical illness. Additionally, there are examples of trials in cancer therapy, such as a randomised trial of pharmacological ascorbate alongside chemotherapy which reported improved outcomes in metastatic pancreatic cancer. (9)

If you look at recent reviews, you’ll see statements like these:

“Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses.” (10)

“Supplementation with vitamin C appears to be able to both prevent and treat respiratory and systemic infections… treatment of established infections requires significantly higher (gram) doses.” (11)

Yet we still see claims that vitamin C does nothing for colds. One survey asked people if they took vitamin C and found no difference in incidence of COVID between those who did and did not supplement. But why would it? Vitamin C does not necessarily prevent infection. What it does, especially in higher doses upon infection, is support immune function and may reduce symptom severity and duration.

Even the critical comments in the media often refer to the meta-analysis of cold studies by Professor of Public Health Dr Harri Hemilä in Finland. What he actually concludes is that vitamin C shortens cold duration, with dose-response effects reported in some controlled trials, and evidence of reduced pneumonia risk in certain contexts. (12)

Vitamin C, dose, and long-term brain health

I take 2 grams a day. This is consistent with what many primates achieve in the wild. We struggle to get 100 mg from food alone, a fraction of what our biology seems designed to handle.

Vitamin C also appears relevant to dementia risk. In observational research, vitamin C (especially alongside vitamin E) has been associated with lower risk of cognitive decline and Alzheimer’s, and evidence reviews have included vitamin C and E among “grade 1” prevention factors in large-scale evidence mapping. (13,14)

Supplements Are Necessary For Good Health

Why deficiency-based nutrition targets are no longer fit for purpose

In conclusion, Professor David Smith, former Deputy Head of the Faculty of Medical Science at Oxford University, and I drafted this statement on supplements for Food for the Brain:

‘The conventional view regarding nutritional supplements is that they are largely unnecessary if a person eats a “well-balanced diet”. This is based on recommended intakes (RDAs, RNIs) designed to prevent classical symptoms of deficiency, such as scurvy in the case of vitamin C. Blood levels of nutrients that prevent classical deficiencies are then extended to imply that a person has sufficient nutrient status if they are above these levels.

But there is abundant evidence that levels above those used to define “deficiency” may be associated with better outcomes, and these levels define a zone of “nutritional insufficiency”. There is also a growing body of evidence from well-designed studies on specific diseases showing that supplements providing nutrients beyond basic RDAs can delay, reduce or ameliorate symptoms, and that risk often reduces steadily as nutrient status rises beyond arbitrary cut-offs.

Redefining sufficiency through disease risk and biological individuality

This illustrates that the definition of “deficiency” is outdated. Deficiency means a lack of efficiency. If deficiency, and its counterpart sufficiency, were to be defined as the level of a nutrient that reduces symptoms or lowers disease risk, that definition is scientifically supportable and takes into account biochemical individuality, including genetics, environment, the microbiome and an individual’s ability to absorb nutrients.

At Food for the Brain, our overarching principle is scientific integrity: consistency with the prevailing science. We share that growing body of knowledge in a way that enables people to restore, maintain, and improve mental health.

What To Do Next?

1. Get guidance, not guesswork

If you want ongoing support, the simplest place to start is by becoming a FRIEND of Food for the Brain. For £50 a year, you get access to our full programme of free education webinars and monthly group coaching. You also get access to the COGNITION programme. This programme is designed to help you turn evidence into practical, lasting habits. It is guidance you can trust, rooted in science. It is delivered with the support of a community working towards the same goal: better brain health for all.

2. Test your brain health with a validated tool

One of the most powerful free resources we offer is the Cognitive Function Test. The test is a validated, research-backed way to check how your brain is functioning right now, across key cognitive domains.

It provides a meaningful baseline. It also helps track change over time, and can highlight where nutrition and lifestyle support may be most needed. If you want to understand your brain health before symptoms appear, this is the place to begin.

3. Take supplements, but test first

Many people take supplements with good intentions but no real clarity about whether they are helping. This is where DRIfT comes in.

DRIfT allows you to measure key brain-related biomarkers. You can see whether what you are taking is actually working, and where your priorities should lie. Instead of guessing, you can focus on what your brain genuinely needs, based on objective data.

Food for the Brain is a not for profit educational and research charity. It offers a free Cognitive Function Test and assesses your Dementia Risk Index. This allows them 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:

P. Clayton, J Rowbotham, ‘An unsuitable and degraded diet? Part one: Public health lessons from the mid-Victorian working class diet’. Journal of the Royal Society of Medicine 2008: 101: 282–289. DOI 10.1258/jrsm.2008.080112; also see P. Clayton, J Rowbotham, ‘An unsuitable and degraded diet?. Part two: Realities of the mid-Victorian diet’ Journal of the Royal Society of Medicine 2008: 101: 350– 357. DOI 10.1258/jrsm.2008.080113
Ying-ying Niu, Hao-yu Yan, Jian-feng Zhong, Zhi-quan Diao, Jing Li, Cheng-ping Li, Lian-hong Chen, Wen-qi Huang, Miao Xu, Zhi-tong Xu, Xiao-feng Liang, Zhi-hao Li, Dan Liu. Association of dietary choline intake with incidence of dementia, Alzheimer disease, and mild cognitive impairment: a large population-based prospective cohort study. The American Journal of Clinical Nutrition, Volume 121, Issue 1, 2025, Pages 5-13, ISSN 0002-9165, https://doi.org/10.1016/j.ajcnut.2024.11.001
Smith AD, Refsum H. Do we need to reconsider the desirable blood level of vitamin B12? J Intern Med. 2012 Feb;271(2):179-82. doi: 10.1111/j.1365-2796.2011.02485.x. Epub 2011 Dec 11. PMID: 22092891.
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.
Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study. Carin Northuis, Elizabeth Bell, Pamela Lutsey, Kristen M George, Rebecca F. Gottesman, Tom H. Mosley, Eric A Whitsel, Kamakshi Lakshminarayan, Neurology Aug 2023, 10.1212/WNL.0000000000207747; DOI: 10.1212/WNL.0000000000207747
Pietruszkiewicz J, Mrozek K, Zwierz M, Wińska A, Suprunowicz M, Oracz AJ, Waszkiewicz N. The Neuroprotective Potential of Vitamin D₃. Nutrients. 2025 Oct 12;17(20):3202. doi: 10.3390/nu17203202. PMID: 41156455; PMCID: PMC12566728.
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.
Li Y, Wang X, Yu M, Wang F, Song D, Liu M,Liang X, Liu H, Liu J, Fu S and Liu X (2025). The relationship between vitamin D levels and Alzheimer’s disease risk: insights from a centenarian study of Chinese women. Front. Nutr. 12:1628732.doi: 10.3389/fnut.2025.1628732
Bodeker KL, Smith BJ, Berg DJ, Chandrasekharan C, Sharif S, Fei N, Vollstedt S, Brown H, Chandler M, Lorack A, McMichael S, Wulfekuhle J, Wagner BA, Buettner GR, Allen BG, Caster JM, Dion B, Kamgar M, Buatti JM, Cullen JJ. A randomized trial of pharmacological ascorbate, gemcitabine, and nab-paclitaxel for metastatic pancreatic cancer. Redox Biol. 2024 Nov;77:103375. doi: 10.1016/j.redox.2024.103375. Epub 2024 Oct 2. PMID: 39369582; PMCID: PMC11491967.

The Midlife Biomarker Proven to Drive Alzheimer’s – And How to Bring It Down

Homocysteine is one of the few Alzheimer’s risk factors that is causal and modifiable, and it often begins rising in midlife, making it a valuable Alzheimer’s biomarker to monitor.

It is the only measurable Alzheimer’s risk factor where lowering it has been shown to slow the disease process itself. When homocysteine rises, the brain shrinks faster. When it is lowered with the right nutritional support, shrinkage slows and thinking skills stabilise [1][3][4].

Yet despite decades of evidence, most people have never been told to test it. Most health systems never mention it at all.

This matters because homocysteine begins to rise years before symptoms develop. It gives us a glimpse into the future health of the brain long before memory changes appear. And midlife is the moment where this shift becomes easiest to detect and easiest to change. Far from being the start of inevitable decline, it is a powerful opportunity for prevention.

What Is Homocysteine and Why Does the Brain Care?

Homocysteine is a natural amino acid produced during methylation, the process the body uses to build and repair cells, process toxins, create neurotransmitters and maintain healthy brain tissue. When methylation runs smoothly, homocysteine stays low. When the system struggles, homocysteine rises.

Elevated homocysteine affects the brain in several ways:
• It accelerates shrinkage of the hippocampus, the brain’s memory centre [3].
• It increases oxidative stress and inflammation [1].
• It injures small blood vessels, increasing microvascular damage seventeen-fold [2].
• It disrupts the formation of neuronal membranes [1].

These are not abstract processes. They are part of the biology that leads to cognitive decline.

Homocysteine is therefore both a predictor and a causal contributor to these mechanisms. Scientists use the word causal when lowering a factor has been shown to change the underlying disease process. Homocysteine meets this definition because reducing it slows brain shrinkage and slows cognitive decline, which no amyloid-targeting drug has yet achieved [1][3][4].

Why Homocysteine Is a Causal Alzheimer’s Risk Factor

A causal relationship in medicine is established when different kinds of evidence all point in the same direction. Homocysteine fulfils these criteria in a way no other Alzheimer’s biomarker has been shown to do in human intervention trials

Large population studies show that higher homocysteine levels predict faster cognitive decline and a greater risk of dementia [6][10]. These relationships are consistent, and they follow a clear pattern: the higher the level, the faster the decline.

Researchers also understand why this happens. Homocysteine places strain on the brain in multiple ways. It injures the lining of small blood vessels, increases oxidative stress, disrupts methylation and accelerates the atrophy characteristic of Alzheimer’s disease [1][2].

But the strongest evidence comes from intervention. In the Oxford trials, people with raised homocysteine who were given vitamin B6, B12 and folate experienced a remarkable slowing of brain shrinkage. In those with sufficient omega 3, the reduction in atrophy reached up to 73 per cent [3]. Cognitive decline slowed or even stopped for many participants [4]. When changing a factor changes the outcome, that factor can be considered causal.

This makes homocysteine fundamentally different from more widely discussed markers such as amyloid or p-tau.

Why Homocysteine Rises in Midlife

Homocysteine does not increase because the brain is failing. It rises slowly and quietly in midlife for many reasons that are understandable and often reversible.

During these decades, the body begins to handle nutrients slightly differently, and small shifts in lifestyle or physiology can place more demand on the pathways that keep homocysteine under control.

One of the earliest changes is a gradual reduction in stomach acid that happens in many, which makes it harder for the body to absorb vitamin B12. Many people also take acid-suppressing medication long term, which compounds the issue. At the same time, daily stress tends to increase during these years. Stress uses up B vitamins more quickly, increasing the strain on methylation.

Blood sugar regulation also plays a role. Diets higher in sugar and refined carbohydrates push the body towards insulin resistance, and this metabolic pressure can lift homocysteine levels [8]. Women often face an additional shift: the natural decline in oestrogen during perimenopause. Oestrogen normally supports methylation and antioxidant capacity, so its fall makes the brain more sensitive to nutritional gaps.

There is also the modern reality that many midlife adults eat less oily fish or plant-based omega 3 sources. Without enough DHA, the brain cannot use B vitamins as effectively for repair [5][11]. And for some, medications such as metformin or certain anticonvulsants further deplete essential vitamins.

By themselves, these changes are small. But together (plus others not mentioned), they create a gentle upward drift in homocysteine that can continue for years without noticeable symptoms. The hopeful part is that every single one of these factors is modifiable. Midlife is not a point of no return. It is the moment where small corrections create the greatest long-term benefit.

How Rising Homocysteine Changes the Brain

As homocysteine increases, a series of changes begins to shape how the brain functions long before any formal diagnosis is made. 

MRI studies show that higher homocysteine is linked with faster atrophy in regions most affected in Alzheimer’s disease, particularly the hippocampus [3]. This shrinkage is not sudden. It reflects long-term strain on neurons and on the methylation pathways the brain relies on to repair itself.

Homocysteine also affects the brain’s vascular system. It damages the delicate lining of small blood vessels, increasing the likelihood of microvascular injury and transient ischaemic events [2]. These events are often too small to be noticed clinically, yet they can gradually reduce mental clarity, processing speed and resilience.

Another important effect is its influence on neurotransmitters. Methylation is essential for producing dopamine, serotonin and acetylcholine, which underpin mood, motivation and memory. When methylation slows, people often describe feeling foggy, flat or less emotionally steady. Although this article focuses on Alzheimer’s processes, the effects of raised homocysteine reach far beyond memory alone.

All of this is amplified by increased oxidative stress, which makes the brain more vulnerable to inflammation and everyday wear and tear. This combination of structural, vascular and chemical changes explains why midlife is often the first time people notice subtle shifts such as word-finding pauses, irritability, lower stress tolerance or difficulty multitasking. They are small clues that the brain’s repair systems are under pressure, long before disease takes hold.

Learn more about oxidative stress in the video below:

The Omega 3 Link: Why B Vitamins Work Better Together

One of the most striking discoveries in homocysteine research is how closely it interacts with omega 3 fatty acids. The brain is structurally rich in DHA, the omega 3 found in oily fish, and it depends on DHA to build and maintain healthy neuronal membranes. B vitamins play a crucial role here because they enable DHA to be incorporated into the phospholipids that make up these membranes.

When DHA levels are low, the brain cannot carry out this repair process efficiently, which means B vitamins have far less impact on slowing cognitive decline. But when DHA is sufficient, the picture changes. In clinical studies, the combination of high DHA and adequate B vitamins produced the greatest reduction in brain shrinkage, particularly in areas vulnerable to Alzheimer’s pathology [5][11]. This synergy is one of the clearest examples of how nutrients work together, rather than in isolation, to support long-term brain health. This is why the Food for the Brain DRIfT test measures both homocysteine and the omega 3 index. These markers do more than signal different aspects of nutritional need. They interact in a way that shapes the brain’s ability to repair itself, making them essential parts of an effective prevention strategy.

What You Can Do: How to Lower Homocysteine Safely

The hopeful part of this story is that homocysteine is one of the simplest biomarkers to measure and improve.

1. Measure it

Optimal levels are generally between 6 and 8 micromoles per litre. Order your at home test here – available internationally.

2. Increase key nutrients

Homocysteine is lowered by vitamin B6, folate, vitamin B12 and choline [1][9]. These nutrients can be supplemented and are found in foods such as leafy greens, eggs, lentils, beef, salmon, chickpeas and nutritional yeast. Many people benefit from targeted supplementation: read more here.

3. Support omega-3 intake

DHA from oily fish or algae helps the brain use B vitamins effectively [11].

4. Reduce sugar and ultra-processed foods

This lowers metabolic stress and improves methylation [8].

5. Address underlying factors

Gut health, stomach acid, hormonal changes and medication use all play a role.

Together these simple changes create powerful momentum. Midlife becomes a decade of opportunity rather than ‘inevitable’ decline.

Homocysteine gives us one of the clearest signals of how the brain is ageing long before symptoms appear. It rises for understandable, reversible reasons and responds quickly to targeted support. More importantly, lowering it has been shown to slow the disease process itself.

This means midlife is not a waiting room for cognitive decline. 

It is the moment when we can influence our long-term brain health most powerfully.

Checking homocysteine is one of the simplest and most effective ways to do that.

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.

Smith AD, Refsum H. Homocysteine, B vitamins and cognitive impairment. Annu Rev Nutr. 2016;36:211-239.
Smith AD, Refsum H, Bottiglieri T, et al. Homocysteine and dementia: an international consensus statement. J Alzheimers Dis. 2018;62(2):561–570.
Douaud G, Refsum H, de Jager CA, et al. Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci USA. 2013;110(23):9523–9528.
de Jager CA, Oulhaj A, Jacoby R, et al. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment. Int J Geriatr Psychiatry. 2012;27(6):592–600.
Jernerén F, Elshorbagy AK, Oulhaj A, et al. Brain atrophy in cognitively impaired elders: the role of homocysteine and long-chain omega 3 fatty acids. Clin Chem Lab Med. 2015;53(3):435–443.
Zhang X, Huang Y, Wang Y, et al. Elevated plasma homocysteine levels contribute to increased risk of dementia: a meta-analysis. J Alzheimers Dis. 2016;52(4):1227–1237.
McCaddon A. Homocysteine and cognitive decline: a vitamin B story. Br J Nutr. 2014;111(2):279–280.
Smith AD, Refsum H. Can nutrition prevent Alzheimer’s disease? Nutrients. 2021;13(1):1–33.
Smith AD. B vitamins and the prevention of cognitive decline and dementia. Adv Nutr. 2021;12(5):1836–1844.
Nurk E, Refsum H, Tell GS, et al. Plasma homocysteine and memory in the elderly. Am J Clin Nutr. 2005;82(3):493–498.
Oulhaj A, Jernerén F, Refsum H, et al. Omega 3 fatty acids interact with B vitamins in slowing cognitive decline in mild cognitive impairment. Am J Clin Nutr. 2016;103(6):1041–1048.
Ford AH, Almeida OP. Effect of homocysteine lowering treatment on cognitive outcomes. J Alzheimers Dis. 2019;69(2):443–456.

A National Step Forward for Brain Health

Food for the Brain awarded an Innovate UK grant to advance early dementia detection and prevention

We are delighted to announce that Food for the Brain Foundation has been awarded a prestigious grant from Innovate UK, part of UK Research and Innovation (UKRI) – national recognition of our pioneering work in dementia prevention and early detection.

Importantly, this funding marks a milestone for us as a UK-based research charity. It also represents a significant step forward for our global community of citizen scientists, clinicians, and individuals dedicated to preventing Alzheimer’s, dementia, and cognitive decline.

For us, this is not just a charity and research achievement – it’s a sign that the world is waking up to prevention.

Why this matters?

Right now, someone in the UK develops dementia every three minutes. Across the globe, it’s every three seconds. And despite this, dementia cost the world over US$1.3 trillion in 2019, yet countless cases remain undiagnosed.

For nearly two decades, we have led the charge in prevention. So far, over 400,000 people worldwide have taken our Cognitive Function Test (CFT) – a free, validated online tool that helps you understand your brain health, assess your risks, and take action to improve.

This grant from Innovate UK, part of the UK’s national innovation agency, provides crucial funding to further validate and expand our tools for early dementia detection and – ultimately – prevention.

It forms part of the Blood Biomarker Challenge, a UK-wide research initiative, which aims to integrate blood-based biomarker testing into NHS diagnostic pathways.

Our Cognitive Function Test (CFT) has been selected to assess cognitive performance in the READ-OUT trial – part of this Innovate UK-funded programme, supported by the Department of Health and Social Care, the NIHR, and Alzheimer’s Research UK.

It will allow us to:

Integrate our Cognitive Function Test into NHS-linked research, workflows, and clinical studies, thereby bridging science and healthcare delivery.
Further expand access to our evidence-based prevention tools – making them mobile-friendly, multilingual, and culturally inclusive for global use.

About Innovate UK

Innovate UK is the UK government’s innovation agency, supporting organisations that deliver real-world impact across science, technology, and health. Each year, it invests over £1 billion in ideas that can transform industries, economies, and lives – from sustainable energy and biotech to healthcare innovation.

Receiving an Innovate UK grant means your project has been rigorously evaluated for its scientific quality, innovation, feasibility, and potential global impact.

What this means for global brain health and dementia detection?

Our Cognitive Function Test (CFT) is the only freely available online tool that measures cognitive performance. It also provides a personalised Dementia Risk Index, based on eight key lifestyle and biological factors.

With this grant, we can now take the next step – integrating this digital test with blood test data from our DRIfT (Dementia Risk Index Functional Test).

The DRIfT test measures five critical nutritional biomarkers proven to influence cognitive ageing:

Omega-3 Index – vital brain fats that support memory and neuronal health

Vitamin D – essential for mood, immunity, and brain protection

Homocysteine – a marker of B-vitamin status; high levels increase the risk of brain shrinkage

HbA1c – a measure of long-term blood sugar control linked to brain energy supply

Glutathione Index – the body’s master antioxidant defence

Combining these markers with our multilingual, free Cognitive Function Test means that more and more people can detect early warning signs of cognitive decline. This can happen decades before diagnosis. This empowers them to take action early – and prevent it. Together, these innovations represent the future of dementia detection and prevention.

Why prevention and early dementia detection must come first?

Despite billions spent on drug development, no Alzheimer’s medication to date has shown meaningful improvement in cognitive outcomes. In fact, many come with serious side effects, including brain swelling and bleeding. (Read more Alzheimer’s drugs here and here.)

That’s why our focus, and now Innovate UK’s, is on early dementia detection.

Identifying risk early, addressing nutritional and metabolic imbalances, and protecting the brain before damage occurs.

Take part – protect your brain, advance the science, stay sharp for life

Ultimately, this work only matters if people like you take part.

By joining our global citizen-science movement, you’ll help us refine and accelerate the world’s first large-scale dementia prevention database.

Step 1: Take the free Cognitive Function Test

A quick, 20-minute online test that shows you how well your brain is performing and what to do next.

Take the free CFT now

Step 2: Complete the DRIFT biomarker test

A simple at-home finger-prick blood test that measures your omega-3, vitamin D, B-vitamin, blood sugar, and antioxidant status.

Order your DRIFT test

Step 3: Become a FRIEND of Food for the Brain

For just £50 a year or £5 a month, you can support our research and charitable work. You’ll also gain access to – your personalised brain upgrade programme. Additionally, enjoy monthly group coaching sessions and live webinars.

Become a FRIEND here

Looking ahead: the future of dementia detection and prevention

With the support of Innovate UK, the NHS, and thousands of citizen scientists and Friends, we’re building a future where Alzheimer’s is preventable, not inevitable.

Ultimately, this grant strengthens our ability to deliver credible, evidence-based tools that empower everyone to take charge of their cognitive health – starting today.

Take the test. Join the study. Be part of prevention.
👉 foodforthebrain.org/tests | foodforthebrain.org/driftstudy

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.

Reference:

1 https://www.alzint.org/about/dementia-facts-figures/

2 UK Research and Innovation 

3  UK Government Press Release)

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Homocysteine may not be a household word, but at Food for the Brain, we want it to become one!

It is arguably one of the most important blood biomarkers for your brain and overall health, predicting the risk of over 100 diseases, from cardiovascular issues to cognitive decline, depression, and developmental disorders in children (1,2,3). For many years it was difficult to obtain accurate testing privately or at home – which is why we developed a new, accurate at-home pin-prick test that is one of our most popular options.

The reason we think this is such a good biomarker to track and research is that whilst high homocysteine is linked to increased risk of over 100 diseases – it can be quick and easy to lower!

Learn more about homocysteine and why it matters in the video below:

What level should you be aiming for?

Based on Patrick Holford’s research in his book Upgrade Your Brain, the recommended homocysteine levels are:

Ideal/Optimal Level: Below 7.5 µmol/L –  This is especially important for women preparing for pregnancy, as higher levels are linked to increased risk of chromosomal damage and developmental problems in children.

Treatment Threshold: Above 10 µmol/L  – Anyone with a homocysteine level above this should be treated with B vitamins to reduce brain shrinkage and risk of dementia.

Warning Level: Above 11 µmol/L – Associated with increased brain shrinkage and elevated risk for Alzheimer’s and cardiovascular disease.

Ideally, with regular testing, you should maintain homocysteine levels well below 10 µmol/L to support optimal brain health and reduce the risk of neurodegenerative conditions.

Here are eight proven ways to bring your homocysteine levels into the optimal range and keep your brain firing on all cylinders:

1. Supplement Smart: The B Vitamin Trio (and Friends)

The fastest way to reduce homocysteine is through targeted supplementation. The ‘magic trio’ is vitamin B6 (20mg), B12 (500µg as methylcobalamin), and methylfolate (400µg). A major paper has shown that supplementing these B vitamins not only lowers homocysteine, but also slows brain shrinkage and cognitive decline in people with mild cognitive impairment. Add trimethylglycine (TMG), zinc, and N-acetyl cysteine (NAC) for additional support, particularly in older adults with memory concerns. These nutrients work synergistically to support methylation and brain function. (1) Get our supplement guidelines here.

2. Eat for B12: Fish, Eggs, Dairy and Meat

Vitamin B12 is primarily found in animal-derived foods. Aim to eat oily fish three times a week, eggs most days, and small amounts of organic meat or dairy (if tolerated). Pescatarians thrive here. For vegans, the focus should be on fortified foods and sources such as shiitake mushrooms. However, supplementation and regular testing are strongly recommended to ensure optimal levels. Poor B12 absorption – particularly in older adults or those taking proton pump inhibitors – is a common risk factor for elevated homocysteine and brain shrinkage (1,2).

3. Load Your Plate with Greens and Beans

Folate is critical for methylation. Aim for seven servings of fruit and vegetables ​​a day. Prioritise leafy greens, broccoli, lentils, chickpeas, and asparagus. These naturally support homocysteine metabolism and keep your methylation processes running smoothly (1).

4. Move Your Body

Regular physical activity helps lower homocysteine. Studies show that consistent aerobic or resistance exercise can reduce levels, improve circulation, and support metabolic health. Aim for at least 30 minutes of brisk walking, cycling, or swimming five times a week to complement your nutritional strategy (3).

5. Cut Back on Coffee – Especially Excessive Intake

Drinking more than two cups of coffee a day can raise homocysteine levels. While low to moderate coffee intake may  offer  some antioxidant benefits, high intake (six or more cups a day) has been linked to elevated homocysteine levels and an increased risk of dementia (4).

6. Mind Your Alcohol

Keep it light. Up to seven small glasses (125ml) of red wine or two pints of beer per week is the maximum. Excess alcohol increases homocysteine levels and impairs nutrient absorption – particularly of B vitamins (1).

7. Manage Stress and Prioritise Quality Sleep

Chronic stress may indirectly raise homocysteine by increasing inflammation and depleting vitamin B6 – both linked to higher mortality and accelerated cellular ageing (5).Make stress reduction a priority. Meditation, yoga, deep breathing, regular exercise, and talking therapies are all effective. Equally important is prioritising restorative sleep. The brain clears toxins and resets during deep sleep – both are vital for healthy methylation. Learn more about sleep and your brain here.

8. Test, Don’t Guess – Know Your Level

You can’t manage what you don’t measure. Have your homocysteine levels tested.. We now offer at-home pinprick tests, which also contribute to our ongoing research. Don’t be surprised if your levels are higher than expected. Forty per cent of people over 60 have homocysteine levels above 11 µmol/L. As we age, our ability to absorb vitamin B12 declines (3).

Homocysteine is a key indicator for cognitive and overall health. As we can see, with a few dietary tweaks, lifestyle upgrades, and targeted nutrients, you can lower your homocysteine, support methylation, and quite literally upgrade your brain!

Start today:

Join our research and test your homocysteine level today. Purchase a single homocysteine test here or get it as part of the DRIfT 5 in 1 test, which also measures your antioxidant status (another world first in accurate home testing), omega-3, vitamin D and HbA1c.
Read more in the Upgrade Your Brain book – This fully referenced guide offers practical strategies to improve your brain health – including how to lower homocysteine through diet, lifestyle, and supplementation.
Support our charitable work by becoming a FRIEND. From just £5 a month, you can help fund vital research and public education. Become a FRIEND today

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 Smith AD, Refsum H. Homocysteine – from disease biomarker to disease prevention. J Intern Med. 2021 Oct;290(4):826-854.

2 Vogiatzoglou A, Refsum H, Johnston C, et al. Vitamin B12 status and rate of brain volume loss. Neurology. 2008 Sep 9;71(11):826-32.

3 Vincze G, et al. Physical activity and plasma homocysteine in the elderly: the Rotterdam Study. Am J Clin Nutr. 2011;93(5):1025–31.

4 Grubben MJAL, et al. Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial. Am J Clin Nutr. 2000;71(2):480–4.

5 Pusceddu I, et al. Subclinical inflammation, telomere shortening, homocysteine, vitamin B6, and mortality: the Ludwigshafen Risk and Cardiovascular Health Study. Eur J Nutr. 2020;59:1399–411.

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What can you do, practically and quickly, to reduce your risk of developing Alzheimer’s?

The International Alzheimer’s Prevention Expert Group, including our founder Patrick Holford, has identified four key areas that could cut your future risk by over 80% – down to less than a quarter – if addressed early.

The four “quick wins”? Increase your vitamin D, omega-3, and B vitamins, and reduce your intake of sugar and refined carbs.

1. Vitamin D: The Sunshine Factor

Vitamin D is primarily made in your skin through sun exposure, particularly at midday in the summer. However, in the winter – especially in the UK and other northern countries – you cannot make enough, so supplementation is essential. A Dutch study found that people with low levels of vitamin D, omega-3s, and B vitamins were over four times more likely to develop dementia¹. Those who supplement with vitamin D have around a third less risk².

Even levels below 62.5 nmol/L (25 ng/mL) increase risk. A French study found that low vitamin D levels tripled Alzheimer’s risk³. The darker your skin, the more sun exposure you need – which makes supplementation all the more vital for many.

2. Omega-3: Feed Your Brain with Fish

Fish is a true brain food – rich in omega-3s, vitamin D, and B12. Eating fish at least once a week reduces Alzheimer’s risk by a third⁴. A recent review confirmed that a daily serving cuts the risk of cognitive decline by 30%⁵.

Omega-3 fats (especially DHA) quite literally build brain cells. The UK Biobank study of over 250,000 people found that those with higher omega-3 levels had a 20% lower risk of dementia⁶. A US study also found that a higher omega-3 index correlated with more white matter in the brain and better cognitive function⁷.

Professor William Harris of the Fatty Acid Research Institute calls it “a safe, simple, cheap and effective tool to forestall Alzheimer’s.”

3. B Vitamins: The Brain Fixers

B6, B12, and folate don’t just support brain function – they’re essential for fixing omega-3s into your brain’s cell membranes. Without them, homocysteine – a toxic amino acid – builds up in your blood. High levels (above 11 μmol/L) are strongly linked to brain shrinkage and Alzheimer’s.

Half of people over 60 in the US have homocysteine levels above 11. The Dutch study found that risk rises even above 8 – a level many people exceed.

As Professor Joshua Miller from Rutgers University says, raised homocysteine is an early warning sign: “a canary in the coal mine.” The good news? It’s easily lowered with a B vitamin supplement – ideally one containing 500 mcg of B12, methylfolate, and B6.

More greens, beans, nuts, and lentils also help. A recent study showed that replacing just one serving of processed meat with nuts or beans (rich in folate) cut dementia risk by 19%⁸.

4. Sugar and Refined Carbs: Silent Brain Saboteurs

The more sugar a person eats – including refined white carbohydrate foods such as bread, pastries, pasta, and rice – the higher their risk of both diabetes and dementia. Fizzy drinks and ultra-processed foods, sweetened with high-fructose corn syrup, are particularly bad for the brain.
“The brain needs the most energy of any organ, so it has the most mitochondria to make it. Sugar damages mitochondria,” says Dr Robert Lustig from the University of California, San Francisco.

A study just published this month in Neurology involving 2 million people shows that those with sugar problems (metabolic syndrome) are 24% more likely to develop dementia early¹⁰.
Keeping blood glucose levels in the low–normal range is reflected by a low glycosylated haemoglobin (HbA1c), which is the blood test doctors use to diagnose diabetes. Having a lower HbA1c is associated with reduced risk for dementia in several studies⁹. A recent study of 374,021 older men with diabetes found that keeping HbA1c stable over three years cut the risk of dementia by a third¹¹.

Want to know what’s driving your brain risk?

Take our free 3-minute Alzheimer’s Prevention Check at alzheimersprevention.info – or, for the full picture, order the four-in-one home blood test to measure your omega-3 index, vitamin D, homocysteine and HbA1c: foodforthebrain.org/tests

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  van Soest APM., et al Alzheimers Dement. 2024 Jul;20(7):4594-4601

2 Ghahremani M, et al. Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status. Alzheimers Dement (Amst). 2023 Mar;15(1):e12404. doi: https://doi.org/10.1002/dad2.12404

 3 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: https://doi.org/10.1016/j.jalz.2017.03.003

4 Beydoun MA, et al. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 2014;14:643. doi: https://doi.org/10.1186/1471-2458-14-643

5 Godos J, et al. Fish consumption, cognitive impairment and dementia: an updated dose-response meta-analysis of observational studies. Aging Clin Exp Res. 2024;61:3731–3739. doi: https://doi.org/10.1007/s40520-024-02823-6

6 Sala-Vila A, et al. Plasma Omega-3 Fatty Acids and Risk for Incident Dementia in the UK Biobank Study: A Closer Look. Nutrients. 2023 Nov;15(23):4896.

7 Loong S, et al. Omega-3 Fatty Acids, Cognition, and Brain Volume in Older Adults. Brain Sci. 2023;13:1278. doi: https://doi.org/10.3390/brainsci13091278

8 Li Y, et al. Long-term intake of red meat in relation to dementia risk and cognitive function in US adults. Neurology.2025;104(3):e210286. doi: https://doi.org/10.1212/WNL.0000000000210286

9 Luchsinger JA, et al. Hyperinsulinemia and risk of Alzheimer disease. Neurology. 2004;63(7):1187–92. doi:https://doi.org/10.1212/01.WNL.0000140292.04932.04932.87;  see also Abbatecola AM, et al. Insulin resistance and executive dysfunction in older persons. J Am Geriatr Soc.2004;52(10):1713–

8. https://doi.org/10.1111/j.1532-5415.2004.52466.x ;see also Xu WL, et al. Uncontrolled diabetes increases the risk of Alzheimer’s disease: a population-based cohort study. Diabetologia. 2009;52(6):1031–

9. doi: 10.1007/s00125-009-1323-x ;see also Hassing LB, et al. Type 2 diabetes mellitus contributes to cognitive decline in old age: a longitudinal population-based study. J Int Neuropsychol Soc. 2004;10(4):599–607. https://doi.org/10.1017/S1355617704104165
; see also Yaffe K, et al. Glycosylated hemoglobin level and development of mild cognitive impairment or dementia in older women. J Nutr Health Aging. 2006;10(4):293–5. https://pubmed.ncbi.nlm.nih.gov/16886099/ ; see also Roberts RO, et al. Diabetes and elevated hemoglobin A1c levels are associated with brain hypometabolism but not amyloid accumulation. J Nucl Med. 2014;55(5):759–64. https://jnm.snmjournals.org/content/55/5/759 

10  Lee JY, Han K, Kim J, Lim JS, Cheon DY, Lee M. Association Between Metabolic Syndrome and Young-Onset Dementia: A Nationwide Population-Based Study. Neurology. 2025 May 27;104(10):e213599. doi: 10.1212/WNL.0000000000213599. Epub 2025 Apr 23. PMID: 40267374.11 Underwood PC, et al. HbA1c time in range and dementia. JAMA Netw Open. 2024;7(8):e2425354. doi: https://doi.org/10.1001/jamanetworkopen.2024.25354

Patrick Holford’s new book claims that almost no one needs to develop Alzheimer’s.

Fewer than 1% of Alzheimer’s cases are genetic, and amyloid deposits – long targeted by new drugs – are neither the cause of the disease nor its cure.

Alzheimer’s is the consequence of a ‘perfect storm’ – a combination of poor diet, unhealthy lifestyle and harmful environmental factors that affect the structure, function or utilisation of the brain, says Patrick Holford,  our founder and author of Alzheimer’s: Prevention is the Cure. He says: “Every single known risk factor affects one of these, and it is combinations of these risk factors – which are under our control – that lead to cognitive decline, first experienced as brain fog and forgetfulness”.

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The book stems from a major global Alzheimer’s prevention project by the charity Food for the Brain, which has assessed the cognitive function of hundreds of thousands of people through a free test, followed by a comprehensive diet and lifestyle questionnaire that calculates their future risk – and shows how to lower it.

“We can detect declining cognitive function from as young as 18. The youngest non-genetic Alzheimer’s diagnosis is just 19,” says Holford, who founded the charity to help prevent Alzheimer’s. “We see a steady decline in cognitive function from the early twenties, with most people starting to show significant cognitive impairment in their seventies and eighties. But this decline cannot only be arrested – it can be reversed with the right diet, supplements and lifestyle choices.”

“Becoming an Alzheimer’s patient is almost always a choice,” says neurologist Dr David Perlmutter, a member of the charity’s Alzheimer’s Prevention Expert Group who also believes that diet and lifestyle, much more than genes, are driving the increase in Alzheimer’s.

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The book  (out today!) explains all the known risk factors we can change – and the extent to which doing so reduces future risk. Particularly important are what Holford calls ‘the four horsemen of the brain health apocalypse’: lack of brain fats, lack of B vitamins, lack of antioxidants, and too much sugar and refined foods. Increasing omega-3 intake from oily fish and supplements cuts risk by about 20%, as does optimising vitamin D levels. Vitamin D is produced in the skin when exposed to sunlight, with some also obtained from oily fish, but supplementation is needed during the winter months. Those who supplement with vitamin D have about one third less risk of developing dementia.

The single biggest–and most easily eliminated–risk factor, is lack of B vitamins, leading to high levels of the toxic amino acid homocysteine. “Homocysteine, if raised above 11 µmol/L, causes brain shrinkage and cognitive decline. If lowered with B vitamins, both shrinkage and decline are arrested. It is the only risk factor for which the evidence is strong enough to say it is causal.” says Holford. “Mine is 7 µmol/L but my wife’s, despite eating the same food, was 15µmol/L – right in the brain-shrinking zone. She now supplements high-dose B12, B6 and folate and her level has dropped to the same as mine. You would never know without testing. We are both in our sixties.” He estimates that half of those over-60 have a homocysteine level above 11, increasing their risk by about one-third.

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“This is why we are now testing people, with a home-test kit, for homocysteine, vitamin D and omega-3 index. If the omega-3 index is below 8% – as it is for many – that predicts cognitive decline and loss of brain density.”

The test kit also measures HbA1c, which GPs use to diagnose diabetes. However, the optimal level for Alzheimer’s prevention is lower than the threshold used to diagnose diabetes. Eating less sugar, fewer refined and ultra-processed foods, and reducing total carbohydrate intake also cuts dementia risk by about 20%.

Another big risk reducer is increasing intake of fruits and vegetables rich in antioxidants, and supplementing with vitamin C. Those in the top third of antioxidant intake have half the risk of cognitive decline, according to a study of 2,716 people over age 60 (1). The home-test kit also measures antioxidant status, specifically glutathione levels.  Greens and beans are rich sources of the B vitamin folate. A recent study found that swapping one serving of processed meat for a serving of nuts or beans – foods high in folate – was associated with a 19% lower risk of dementia (2).

Getting your diet right is only half the story, says Holford. “Minimising alcohol, not smoking, staying physically active, and having a socially and intellectually stimulating lifestyle are all vital parts of dementia-proofing. So too are getting enough sleep, managing stress, and ensuring good hearing and vision. Cataracts, for example, increase risk, but having cataract surgery significantly lowers it. Women also need to support hormonal health after menopause. Often using ‘natural’ HRT makes a big difference.”

The book is out in the UK, EU today and you can pre-order for USA & Australia too (they will be shipped ot you in 3-5 weeks) .

Also join us in May for the Alzheimer’s Prevention Day

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.

As parents or caregivers, nothing matters more than our children’s future. We want them to thrive – mentally, emotionally and physically – and to feel confident and capable in a complex, ever-changing world. Yet when it comes to their brain development, many of us are left wondering: are we doing enough? Are they getting what they need to build healthy, resilient minds?

This is why we’re proud to introduce our groundbreaking Smart Kids Cognitive Function Test. Developed by the team behind the widely respected Adult Cognitive Function Test, this tool is designed to empower parents with the knowledge, insight and practical strategies to support their child’s cognitive and emotional development, right from the start.

Why Early Brain Health Matters

From the moment they’re born, a child’s brain is growing at an extraordinary pace – forming up to a million new neural connections every second. These formative years are a critical window of opportunity, where the right nutrition, environment, and emotional support can set the foundation for a lifetime of strong cognitive function, balanced mood and behavioural wellbeing.

This test doesn’t just measure ‘smarts’ – it helps you understand how your child’s brain is functioning, what might be holding them back, and most importantly, what you can do about it.

What’s Involved?

Tailored for children aged 4 to 17, the test includes three essential elements:

Cognitive Function Assessment. An engaging 15-minute digital test that challenges attention, memory and problem-solving in a fun, interactive way.
Nutrition & Lifestyle Questionnaire. This helps highlight which of the eight key lifestyle areas may be influencing brain health, from sleep and gut health to sugar balance and essential fats.
Strengths & Difficulties Questionnaire. A validated tool assessing emotional and behavioural wellbeing, giving you a fuller picture of how your child is feeling and functioning.

With this holistic insight, you’ll receive tailored guidance and practical steps to help your child move forward – cognitively, emotionally and behaviorally.

 What Parents Are Saying

“COGNITION helped me understand why my son was struggling with focus—and what I could do to help. The emails made it so easy to build new habits. We saw a real change.”
– Parent of a 9-year-old

“It was like someone had finally put the pieces together. We started with sugar balance and sleep—and within weeks, our daughter’s mood and energy improved.”
– Mum of a 13-year-old

A Mission for Change: Your Role as a Pioneer

By joining the first 1,000 families to complete the free Smart Kids Test, you’re helping us shape a healthier, smarter future for the next generation. Together, we can build a new model of prevention and wellbeing that begins not at midlife, but in childhood where it can make the biggest difference.

Have You Taken the Adult Test?

Many parents in our community have already taken the free Adult Cognitive Function Test – designed to help dementia-proof your diet and lifestyle. If you haven’t yet done so, we urge you to take this important step. Your brain matters too, and change is possible at any age.

Also, did you know that you can complete our at home pin prick DRIfT blood test on children over 2 years of age and they are available internationally. So that you can gather more data on what your child needs to thrive.

To Our Dementia Prevention Community

We know that many of you found us through our mission to prevent Alzheimer’s and cognitive decline. This children’s test is a natural extension of that work, because optimising brain health starts young. Helping your child now doesn’t just support their academic success, it lays the foundation for lifelong mental wellbeing.

Take the Smart Kids Cognitive Function Test today – and invest in your child’s brain, their wellbeing, and their future. 

Because every child deserves the chance to shine.

Actions:

Take the Smart Kids test here
Find out more about our at home pin prick blood test here – suitable from age 2+

Do the adult Cognitive Function Test here if you haven’t done so yet, so you can model what supporting your brain health looks like to your child and family.

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.

Lowering Homocysteine: Why It Matters and How to Do It

Lowering homocysteine: Why It Matters and How to Do It

Homocysteine is a natural amino acid produced during a vital process in the body called methylation. It is fast becoming one of the most important biomarkers of long term health, and understanding lowering homocysteine is becoming equally important.

Methylation is a fundamental biochemical process happening in every cell, every second. It helps switch genes on and off, build and regulate neurotransmitters, repair DNA, support detoxification, and maintain healthy blood vessels. For methylation to run smoothly, the body depends on key nutrients, particularly B vitamins.

Homocysteine sits at the centre of this process. When methylation is working well, homocysteine is efficiently recycled and kept within a healthy range. When it rises, it reflects strain within the methylation cycle.

This matters because disrupted methylation affects brain chemistry, vascular integrity, and cellular repair. It is a systems issue, not a single pathway problem.

Despite this, homocysteine is rarely discussed in routine healthcare, and access to accurate, affordable testing has historically been limited. Yet the research is extensive. Elevated homocysteine has been linked to more than 100 health conditions, including cardiovascular disease, depression, and neurodevelopmental delays in children (1, 2, 3).

Levels above approximately 10 to 11 µmol/L are considered a red flag. This is not uncommon. Studies in the United States suggest that around 40% of adults over 60 have levels above 11 µmol/L (4). In the UK, nearly 40% of older adults are thought to have low vitamin B12 status, which is associated with accelerated brain shrinkage (5).

Lowering homocysteine through understanding Methylation and B Vitamins

Homocysteine is recycled through the methylation cycle.

The body uses this process to activate nutrients and manage many chemical reactions every day.

For example, folate (and folic acid, its synthetic form) needs to change into its active form, methylfolate. This change helps support cellular functions. Key enzymes that aid in methylation depend on vitamins B6, B12, and folate. They also need cofactors like zinc, riboflavin (B2), niacin (B3), and trimethylglycine (TMG).

When this system is under-resourced or less efficient, homocysteine levels go up. This can happen with age or certain diets like veganism (3). Homocysteine can act as a “functional” marker of methylation efficiency, a bit like HbA1c reflects longer-term blood glucose control.

Why lowering homocysteine matters for health?

So how much does this biomarker matter really? Here at Food for the Brain, we let the science lead – here are some of the ways it can impact your health:

Cardiovascular Disease and Stroke

Elevated homocysteine is associated with damage to the inner lining of blood vessels, promoting atherosclerosis. One study found that people with levels over 20 µmol/L have almost five times the risk of death. For every 5 µmol/L increase, the risk rises by about one-third (6).

. Another study, involving nearly three thousand cardiovascular patients, found that those in the highest homocysteine quartile had a threefold higher risk of death compared to those in the lowest quartile (7). Furthermore, other research shows that two-thirds of heart attacks and strokes in older adults could be predicted by homocysteine levels rather than by cholesterol (2).

Brain Shrinkage and Cognitive Decline

High homocysteine levels are linked to faster brain shrinkage and p-tau buildup. P-tau is a protein involved in Alzheimer’s disease (8). Studies show that taking B vitamins to lower homocysteine can slow brain atrophy and reduce cognitive decline (1).

Pregnancy and Child Development

Even small increases (above 9 µmol/L) in pregnant women are associated with increased risk of miscarriage and other issues. They may also affect child development. This can lead to issues like withdrawn behaviour, anxiety, and social difficulties later on (9, 10, 11).

Mental Health Disorders

High homocysteine levels have been associated with a wide range of neurological and psychiatric conditions, including autism, anxiety, and bipolar disorder. They also relate to children’s behavioural issues and cognitive decline in both kids and adults. Additionally, elevated homocysteine is tied to dementia, depression, and hearing loss. Other associations include migraines, multiple sclerosis, motor neuron disease, and neural tube defects. It also connects to obsessive-compulsive disorder, post-traumatic stress disorder, and schizophrenia (1).

This breadth of association reflects how central methylation is to brain chemistry and neurological stability.

Lowering Homocysteine 

The encouraging news is that there is a lot you can do to lower homocysteine levels!

The simplest and most effective way for lowering homocysteine is with B vitamin supplements at the right dosage. Click here to see our guide to supplementation including doses and specific brands.

Most critical is the amount of vitamin B12 they provide.

The basic Dietary Reference Value that you see on supplements is 2.5mcg. Few provide more than 10mcg, which is sufficient if you don’t have raised Hcy. Standard low-dose supplements are unlikely to significantly reduce an elevated homocysteine level. Professors Smith and Refsum recommend 500mcg a day – substantially higher than standard reference intakes. This is both safe and effective especially if taken alongside B6 (20mg) and methylfolate (400mcg). Also, it doesn’t take long to bring your level down.

In addition to these core nutrients, extra support from zinc, TMG (trimethylglycine), and N-acetyl cysteine (NAC) may be beneficial. NAC, for instance, may help channel homocysteine toward SAMe production by boosting the body’s antioxidant defences and glutathione production (1).

Lifestyle choices that support lowering homocysteine

Eat greens, beans, nuts and seeds which are high in folate
Include seafood and eggs, high in B12 and phospholipids as well as omega-3, which methylation helps bind together to make healthy cell membranes
Avoid smoking and excess alcohol (one 125ml glass of red wine does not appear to raise homocysteine levels)
Limit coffee to one cup a day
Reduce chronic stress
Prioritise quality sleep
Stay physically active and keep fit

Want to learn more about homocysteine? There are few more things you can do:

1. Join us for the B Vitamin Blueprint Webinar with Patrick Holford, where he’ll break down this key health marker and its impact on you.

2. Join our research and order your homocysteine test to understand your body and take action toward lowering homocysteine effectively. Prevention is power and you can start today.

3. You can test your homocysteine in a single test or as part of our DRIfT 5 in 1 which also tests Vitamin D, HbA1c, Omega-3 status and Glutathione. 

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.

Reference list

Dementia, including Alzheimer’s is not only the greatest cause of death entailing huge healthcare costs, it is the major fear for many about aging. The great news is that dementia and Alzheimer’s are preventable. Less than 1% of Alzheimer’s is caused by genes so for most of us, the risk for dementia and age-related cognitive decline relates to things we can easily change. 

At foodforthebrain.org we have tested (for free) almost half a million people with a validated Cognitive Function Test, followed by a questionnaire which calculates your future Dementia Risk Index and crucially, advises what to do about it. 

Your risk is divided into eight domains (see image), highlighting areas to focus on to enable brain and cognitive powers to stay intact. 

Here are 25 simple steps you can take to dementia-proof your diet and lifestyle taken from our advice and my recent book, Upgrade Your Brain, which gives more detail for those who want to dig deeper.

Brain Fats – Up your brain fats – omega-3, phospholipids and vitamin D 

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Get your omega-3 index above 8%

You can measure your omega-3 index with a home test kit. Psychologists at the Linda Loma University in California did this for a group of older people, publishing their results in the journal Brain Sciences (1). They found that the higher a person’s omega-3 index was, the more white matter there was in their brain and the better they performed in cognitive tests. 
Omega-3 index is part of the DRIfT home test kit from foodforthebrain.org/tests

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Eat oily fish three times a week or SMASH it

S for salmon, M for mackerel, A for anchovies, S for sardines, and H for herrings or kippers. Caviar has the highest known levels of omega-3 DHA, which  builds your brain. Even having one serving a week almost halves the risk of Alzheimer’s. (2, 3)(not sure what to actually eat? Subscribe to our Upgrade Your Brain Cook App. Get access to over 100 recipes, including many that are high in omega-3 options!

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Supplement omega-3 fish oils

Aim for any supplement that provides 500mg of omega-3 DHA. This may mean two capsules a day. See this recent study in the American Journal of Clinical Nutrition of over 100,000 people (4). If you’re vegan, supplement with algal omega-3 DHA. 
Read more about omega-3 supplementation here.

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Eat an egg and/or nuts and seeds every day 

Organic and free range are the preferred options.

Eating  two eggs a week halves future risk of Alzheimer’s (5). The best seeds are chia, flax, hemp and pumpkin. The best nuts are walnuts, pecans, and macadamia, but all nuts are a good source of protein and minerals.

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Exercise outdoors and supplement vitamin D

Low blood levels of vitamin D make cognitive decline 19 times more likely. If your vitamin D level is high, Alzheimer’s disease is 4 times less likely. People who take vitamin D, which is especially important in winter, have a one-third lower risk. 
A vitamin D test is part of the DRIfT test at foodforthebrain.org/tests

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Low Carb and GL – Eat a low-carb, low sugar, low GL diet

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Avoid sugar and don’t eat junk food

Avoid the white stuff – flour, sugar, rice and especially ultra-processed foods. Fructose and high fructose corn syrup are common sweeteners. They are especially harmful to the brain.

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Eat your fruit, don’t drink it

Stay away from fruit juices as they contain no fibre but lots of sugar. A glass of orange juice is worth three oranges’ worth of juice, but no fibre. Fibre fills you up.

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Limit your intake of bread, pasta, and potatoes

If you eat more than 100 to 150 g a day of grains or potatoes, which is one or two servings max, your risk of dementia goes up .

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Limit alcohol to a glass of wine a day or equivalent

Drinking alcohol, particularly red wine, can lower risk if done in moderation. However, the benefits are limited. . Abstinence increases risk, as does having more than 14 units of alcohol a week, according to a study in the British Medical Journal (6).

Add C8 oil to your coffee

The brain can run on either glucose or ketones, made in the liver from a ‘medium chain triglyceride’ called C8 oil. Two tablespoons of a C8-rich oil improve cognitive abilities and help provide the brain with energy (7).  Read more about MCT oil here.

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B vitamins – Keep your homocysteine low with B vitamins 

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Test your blood homocysteine level with a home test kit and supplement B vitamins if needed

A level above 10 mmol/l, which is extremely common in people over 60, is strongly associated with accelerated brain shrinkage and increases risk of Alzheimer’s ten-fold. Homocysteine is easily lowered by supplementing vitamin B6, B12 and folate but the amounts needed are much higher if your homocysteine level is high. We recommend everyone to supplement 10 mcg of B12, which is what you’ll find in a good multivitamin but if your homocysteine is raised, you’ll need 500 mcg a day to lower it. It’s completely safe so there’s no harm in taking this much.
It’s in the pin prick DRIfT test from foodforthebrain.org/tests

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Eat a serving a day of both greens and either beans, lentils, nuts or seeds

These are all high in the B vitamin folate as well as vitamin B6. A study in Holland gave 818 people aged 50 to 70 a folic acid supplement of 800mcg for three years, versus a placebo. At the end of the study, compared to those taking the placebo, those taking folic acid were functioning at the equivalent of being 5.5 years younger (8).

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Antioxidants – Eat and drink anti-ageing antioxidants and polyphenols [4]

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Eat lots of fresh fruit and veg

The more you eat, the better, though the benefits start to plateau at 500g a day, which is about five to six servings. People who ate the most greens had much less Alzheimer’s-related issues than those who ate the least.(9) . Berries are particularly protective, especially blueberries and strawberries.

Drink Tea

The more you drink, the better as confirmed by a recent study from Singapore (8). However, other studies are conflicting (9). My view is to drink tea, green over black, in preference to coffee, and limit your intake to one or two cups a day.

Eat dark (70%+) chocolate

The benefit peaks at 10g, or about 3 pieces. More recent studies on cocoa, a rich source of flavanols, have shown improved cognition, possibly by improving circulation (11).

Supplement vitamins C and E – and don’t smoke!

A study of 4,740 elderly people in Utah found that those taking both vitamin E and C reduced their risk of developing Alzheimer’s by 23%.

Taking either cut risk by a quarter (12).   Overall, a meta-analysis of vitamin C studies concludes thta supplementation lowers risk by about 26% (12). Smokers need at least twice as much vitamin C as non-smokers, just to have basic vitamin C levels in their blood. Smoking also raises homocysteine levels, another risk factor.

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Healthy Gut – A healthy gut is a healthy brain [5]

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Eat plenty of soluble fibre and prebiotic foods

Fibre from foods like oats, chia, and flax seeds benefits our gut microbiome. Prebiotic foods like garlic, artichoke, leeks, and onions nourish and support healthy gut bacteria.

When you eat potatoes or rice, cook them ahead of time. Then, store them in the fridge. Reheating food increases the amount of prebiotics, also known as resistant starch.

Supplementing vitamin C helps promote lactobacillus and bifidobacteria.

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Active Body – Exercise and keep physically active [6]

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Get active for 20 minutes … and build and maintain muscle 

Spend at least 20 minutes doing activities such as walking, gardening, housework or repairing things – anything that gets you moving. Don’t limit yourself to ‘exercise’– anything that gives you a faster heart rate and engages different sets of muscles is good. Muscle mass best predicts both your brain volume and risk of cognitive decline in later years (13).

Get balancing!

The brain works hard in exercise, especially if it involves complex movements and learning, such as learning to dance, or doing different movements in a yoga or t’ai chi class or running or walking on uneven surfaces. The brain is processing a lot of information, triggering patterns of muscle movement and keeping you in balance.

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Active Mind – Keep yourself socially and intellectually active [7] 

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Read, watch, or listen to stimulating content

A simple yardstick is to ask, ‘Am I learning anything? Am I using my mind?’ Reading books or listening to podcasts can be great ways to stimulate your mind, depending entirely on what you engage with.

Be social

Aim to spend at least two hours a week with other people in a social (not work) setting – groups, friends, family, etc.

Test your brain in the morning

Do Sudoku, the crossword or Wordle – check out this link. You may prefer an app; two that have high ratings are Brain HQ and Lumosity.

Learn something new and challenging

Learning a new language, sport or musical instrument are all good – anything that you keep practising. This fascinating study looked at the brains of musicians and showed that amateur musicians benefited most (14).

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Sleep and Calm – Sleep well, stay calm and live purposefully

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Avoid alcohol before bed and limit any caffeine intake after midday 

Caffeine suppresses melatonin, which helps you sleep, for up to 10 hours. 

Aim to follow a soothing bedtime routine

Ensure your bedroom is quiet and dark and you are comfortable. Turn off mobile phones and Wi-Fi connections at night.  Prioritise relaxing activities in the few hours before you go to bed.

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So, while you do not need to implement all 25 things this week, think about what 2-3 things you could focus on this month.

For further support, monthly coaching and detailed personalised email guidance make sure you join us as a FRIEND so you get access to COGNITION – your 6 month programme to help you upgrade your brain and improve your cognitive function. All for just £5 a month or £50 a year!

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Also, to accompany your 6-month programme we highly recommend completing the DRIfT at home blood test.

Not only will you be contributing to our research you will also get additional data so you know exactly what to do and what to supplement. 

Everyone is different but these tests help you know exactly what YOU need and are available worldwide, are done in the comfort of your own home and are suitable from age 2+!

Most of all – remember that Alzheimer’s and dementia is preventable and the best time to start is TODAY.

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.

1 Hibbeln JR, Nieminen LR, Blasbalg TL, Riggs JA, Lands WE. Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity. Am J Clin Nutr. 2006 Jun;83(6 Suppl):1483S-1493S. doi: 10.1093/ajcn/83.6.1483S. PMID: 16841858.

2 Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Wilson RS, Aggarwal N, Schneider J. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol. 2003 Jul;60(7):940-6. doi: 10.1001/archneur.60.7.940. PMID: 12873849.

3 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.

4 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

5 Pan Y, Wallace TC, Karosas T, Bennett DA, Agarwal P, Chung M. Association of Egg Intake With Alzheimer’s Dementia Risk in Older Adults: The Rush Memory and Aging Project. J Nutr. 2024 Jul;154(7):2236-2243. doi: 10.1016/j.tjnut.2024.05.012. Epub 2024 May 22. PMID: 38782209; PMCID: PMC11347793.

6 Sabia S, Fayosse A, Dumurgier J, Dugravot A, Akbaraly T, Britton A, Kivimäki M, Singh-Manoux A. Alcohol consumption and risk of dementia: 23 year follow-up of Whitehall II cohort study. BMJ. 2018 Aug 1;362:k2927. doi: 10.1136/bmj.k2927. PMID: 30068508; PMCID: PMC6066998.

7 Croteau E, Castellano CA, Richard MA, Fortier M, Nugent S, Lepage M, Duchesne S, Whittingstall K, Turcotte ÉE, Bocti C, Fülöp T, Cunnane SC. Ketogenic Medium Chain Triglycerides Increase Brain Energy Metabolism in Alzheimer’s Disease. J Alzheimers Dis. 2018;64(2):551-561. doi: 10.3233/JAD-180202. PMID: 29914035.

8 Durga J, van Boxtel MP, Schouten EG, Kok FJ, Jolles J, Katan MB, Verhoef P. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. 2007 Jan 20;369(9557):208-16. doi: 10.1016/S0140-6736(07)60109-3. PMID: 17240287.

9 Devore E et al, ‘Dietary intakes of berries and flavonoids in relation to cognitive decline’, Annals of neurology 2012; 72: 135-43; see also Agarwal P, Holland TM, Wang Y, Bennett DA, Morris MC. Association of Strawberries and Anthocyanidin Intake with Alzheimer’s Dementia Risk. Nutrients. 2019 Dec 14;11(12):3060. doi: 10.3390/nu11123060. PMID: 31847371; PMCID: PMC6950087.

11 Lamport DJ, Pal D, Moutsiana C, Field DT, Williams CM, Spencer JP, Butler LT. The effect of flavanol-rich cocoa on cerebral perfusion in healthy older adults during conscious resting state: a placebo controlled, crossover, acute trial. Psychopharmacology (Berl). 2015 Sep;232(17):3227-34. doi: 10.1007/s00213-015-3972-4. Epub 2015 Jun 7. PMID: 26047963; PMCID: PMC4534492.

12 Basambombo LL, Carmichael PH, Côté S, Laurin D. Use of Vitamin E and C Supplements for the Prevention of Cognitive Decline. Ann Pharmacother. 2017 Feb;51(2):118-124. doi: 10.1177/1060028016673072. Epub 2016 Oct 5. PMID: 2770818; see also 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;91(11):1201-9. Epub 2020/07/22. doi: 10.1136/jnnp-

13 Wang W, Luo Y, Zhuang Z, Song Z, Huang N, Li Y, Dong X, Xiao W, Zhao Y, Huang T. Total and regional fat-to-muscle mass ratio and risks of incident all-cause dementia, Alzheimer’s disease, and vascular dementia. J Cachexia Sarcopenia Muscle. 2022 Oct;13(5):2447-2455. doi: 10.1002/jcsm.13054. Epub 2022 Jul 20. PMID: 35856185; PMCID: PMC9530585.

14 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.

(Originally posted in IHCAN magazine. Written by Patrick Holford, edited by Carol Ludlam)

What is really going on as we age? What contributes to the wrinkles, stiffer joints, slower cognitive function and other health problems?

It begins with the brain.

Your brain consumes more energy than any other organ, burning either glucose or ketones. This combustion creates oxidants that age your brain. The ability to rapidly extinguish these oxidants, which ultimately age your brain and body, is what helps you live longer with less wrinkles, more flexible joints, healthier blood vessels and organs, especially your brain, which has 400 miles of blood vessels. 

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Top level prevention factors

Keeping oxidants down is perhaps the single most important thing you can do for vascular health. Vascular dementia, for example, is strongly associated with the amount of oxidation, determined by antioxidant intake from fruit and vegetables on the one side and smoking and pollution for example, on the other. Those in the top quarter of Total Antioxidant Capacity (TAC) in their diet halve their risk, in a study of 2,716 people over age 60 (1).

Additionally, critical antioxidants such as vitamin C and vitamin E, if supplemented together, reduced the risk of developing Alzheimer’s by as much as two-thirds, whilst taking either cut risk by a quarter in a study of 4,740 elderly residents of Cache County, Utah (2). Another study shows that ‘either a high vitamin E or C intake showed a trend of attenuating risk by about 26 per cent’, according to China’s leading prevention expert Professor Jin Tai Yu of Fudan University in Shanghai, making these nutrients ‘grade 1’ top level prevention factors (3). 

Vitamin C, which is water based and protects you against smoke and pollution, and vitamin E, which is fat based and protects you from burnt and fried fats, including sunburn, are in the bloodstream outside of cells. Inside cells, especially brain cells, is the most potent antioxidant of all, which is glutathione.

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Glutathione is the Master Intracellular Antioxidant 

Nutritionists have been measuring red cell glutathione (GSH) for decades as an indicator of a person’s antioxidant capacity. GSH is the most important antioxidant and free radical scavenger that is found to be decreased in the brains of people with a wide range of mental and neurological illnesses from schizophrenia (4) to dementia (5, 6). 

However, the problem with just measuring glutathione is two-fold. Firstly, since it oxidises so rapidly, it has to be ‘fixed’ immediately to avoid any degradation to its oxidised form glutathione disulfide (GSSG). Testing of glutathione levels is therefore usually dependent on going to a lab for blood to be drawn and then immediately tested or fixed, to limit any oxidation. The reliability of glutathione measurements, unless done under strictly controlled conditions such as these, may be questionable due to the rapid oxidation once blood is taken.

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The Glutathione Index (GSH/GSSG) is the best measure of antioxidant status

Additionally, it is the amount of ‘spent’ or oxidised glutathione (GSSG) that reflects the extent of oxidative stress a person is under. Think of glutathione as the water in the fire engine. It gets rapidly used up keeping your brain protected. The ‘spent’ or oxidised glutathione (GSSG), much like steam, then has to be cooled to reload the fire engine. This recycling is done by vitamin C and an enzyme called Glutathione Reductase (GR), returning Glutathione back to its fully loaded ‘reduced’ form. Another enzyme, Glutathione Peroxidase (GP), is involved. GR is riboflavin (vitamin B2) dependent and GP is selenium dependent.

Dr Konrad Kowalski, the Food for the Brain’s analytic chemist, explains: “Reductions in GR enzyme levels in patients with dementia are well established. GR levels alone are therefore a fairly good biomarker of dementia.” However, the mere presence of the enzyme does not guarantee its high activity. GR needs to consume NADP molecules to function properly.  As shown by Irene Martinez de Toda et al 2019 data, patients with dementia have a reduction in both the enzymes (GR and GP) that recycle glutathione.  Thus, in general it can be said that the glutathione metabolism (recycling) loop in those with dementia ‘spins’ much slower than in healthy patients. 

“The advantage of our measurement of the Glutathione Index (GSH/GSSG) is therefore, that it shows changes in GR activity, not only due to higher/lower GR gene activity but also due to the absence of the reaction cofactor NADP.”

“As a result, dementia patients have a lower potential to dynamically fight free radicals and will have a worse GSH/GSSG, which we call the Glutathione Index (7). The worse the ratio the worse a person’s cognitive function is likely to be. It’s a bit like having a direct measure of how fast your brain is ageing. Patients with dementia have a reduction in glutathione and its ability to be recycled (8). This ratio, the Glutathione Index, is a biomarker for many diseases, including both type 1 and 2 diabetes, liver cirrhosis, multiple sclerosis and Alzheimer’s disease.” says Dr Konrad Kowalski, who has developed this test for us.

One of the biggest challenges in developing the Glutathione Index, which is a home test kit involving a pin prick of blood dripped onto a dry blood spot card, is that the conventional DBS cards didn’t provide enough stability for the rapidly oxidising GSH, so we developed a method that instantly ‘fixes’ the sample for a guaranteed 12 week stability from taking the sample.

The red arrows indicate reduced or increased activity in dementia patients

So we want people to both measure their Glutathione Index and complete our validated Cognitive Function Test along with the follow-on Dementia Risk Index questionnaire, which calculates an ‘antioxidant’ domain score. 

As a result of our research where we have tracked these against the person’s blood level of Glutathione Index, enabling us to establish what an optimal level is. This means those boundaries, which we show in colours from green (good), yellow (OK), orange (not good), red (bad) will evolve and become more accurate thanks to you and people like you.

We now know that a desirable level is above 800. Below 500 is an indicator that you need to increase your intake of antioxidants from food and/or supplements, and/or reduce your intake of oxidants from smoking, pollution or fried food. Glutathione is related to the pace of aging and the activity of antioxidant enzymes which are depleted in those with cognition decline. It is also part of your DRIfT (Dementia Risk Index functional Test) score.

 This is unique and vital research funded by the people for the people – Citizen Scientists.

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How Glutathione and vitamin C recycle each other 

Vitamin C helps ‘reload’ glutathione and glutathione helps reload vitamin C as you’ll see in the figures below. This glutathione – vitamin C cycle is one of the hottest discoveries in anti-ageing science. You’ll see that NADPH, derived from niacin (vitamin B3) and its cousin NAD are involved. Co-enzyme Q10 in its reduced form ubiquinol is also involved and although not shown in this diagram, low levels are also found in those with Alzheimer’s (9).

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Raising glutathione – the role of NAC

Nutritional therapists have been measuring red cell glutathione and supplementing glutathione or its precursor N-Acetyl-Cysteine (NAC) for decades. However oral GSH supplementation has poor bioavailability largely because it is so rapidly oxidised to GSSG as it disarms free radicals. N-Acetyl Cysteine (NAC), a precursor of glutathione, is therefore often used instead and has been shown to successfully raise plasma glutathione levels, for example, in those with schizophrenia. Anthocyanins also recycle glutathione thus sparing it if supplemented together (12).

NAC has plenty of evidence to support its use as a promoter of glutathione and mental health, thus reducing the brain’s oxidative stress. The latest 2022 review states: “N-acetyl-L-cysteine (NAC) is a compound of increasing interest in the treatment of psychiatric disorders. Primarily through its antioxidant, anti-inflammatory, and glutamate modulation activity, NAC has been investigated in the treatment of neurodevelopmental disorders, schizophrenia spectrum disorders, bipolar-related disorders, depressive disorders, anxiety disorders, obsessive compulsive-related disorders, substance-use disorders, neurocognitive disorders, and chronic pain. Currently NAC has the most evidence of having a beneficial effect as an adjuvant agent in the negative symptoms of schizophrenia, severe autism, depression, and obsessive compulsive and related disorders.” (13) For example a large RCT of 140 participants observed significant improvements on global symptomatology, and general and negative symptoms of schizophrenia in the NAC supplementation (2 g/d; in addition to anti-psychotic medication) group in comparison to the placebo group over a 24 week period (14).

According to Dr Chris Palmer, assistant professor at Harvard Medical School, “Glutathione (GSH), the brain’s primary antioxidant, plays a crucial role in maintaining redox balance (the process of maintaining the balance of reactive oxygen and nitrogen species in cells to maintain homeostasis) . Magnetic resonance studies have provided mixed results regarding GSH levels in schizophrenia patients, with some studies indicating decreased levels in chronic schizophrenia, while others found no significant differences. However, these inconsistencies may be due to variations in disease chronicity, age, and symptom severity among study participants. The findings from these studies suggest several potential therapeutic targets for schizophrenia. Addressing mitochondrial dysfunction, redox imbalance, and impaired energy metabolism could lead to more effective treatments. For instance, N-acetylcysteine (NAC), a precursor to GSH, has shown promise in increasing brain GSH levels and improving symptoms in first episode psychosis patients.”

NAC is so medically effective that it has been classified a medicine, hence not a food, and is no longer available over the counter in the US.

Our Glutathione Index test costs £69 – order it and be a part of this new exciting research, whilst learning how you can protect and upgrade your brain.

It is also available as part of their 5-in-1 DRIfT test also measuring Homocysteine, HbA1c, vitamin D and Omega-3 Index.

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Actions

Join COGNITION by becoming a FRIEND to get access to a personalised 6-month program to upgrade your brain
Join our research and order the single Glutathione test OR the 5 in 1 DRIfT test.
Take the FREE Cognitive Function Test 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 Peng, M., et al. Dietary Total Antioxidant Capacity and Cognitive Function in Older Adults. J Nutr Health Aging (2023).

² Basambombo LL, Carmichael PH, Côté S, Laurin D. Use of Vitamin E and C Supplements for the Prevention of Cognitive Decline. Ann Pharmacother. 2017 Feb;51(2):118-124. doi: 10.1177/1060028016673072. Epub 2016 Oct 5. PMID: 27708183.

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 Yao JK, Leonard S, Reddy R: Altered glutathione redox state in schizophrenia. Dis Markers 2006, 22(1):83–93 ; see also Gawryluk JW, Wang J-F, Andreazza AC, Shao L, Young LT: Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders. Int J Neuropsychopharmacol 2011, 14(01):123–130. 

⁵ Torres LL, Quaglio NB, de Souza GT, Garcia RT, Dati LM, Moreira WL, Loureiro AP, de Souza-Talarico JN, Smid J, Porto CS, Bottino CM, Nitrini R, Barros SB, Camarini R, Marcourakis T. Peripheral oxidative stress biomarkers in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis. 2011;26(1):59-68. doi: 10.3233/JAD-2011-110284. PMID: 21593563 

⁶ Park SA, Byeon G, Jhoo JH, Kim HC, Lim MN, Jang JW, Bae JB, Han JW, Kim TH, Kwak KP, Kim BJ, Kim SG, Kim JL, Moon SW, Park JH, Ryu SH, Youn JC, Lee DW, Lee SB, Lee JJ, Lee DY, Kim KW. A Preliminary Study on the Potential Protective Role of the Antioxidative Stress Markers of Cognitive Impairment: Glutathione and Glutathione Reductase. Clin Psychopharmacol Neurosci. 2023 Nov 30;21(4):758-768. doi: 10.9758/cpn.23.1053. Epub 2023 Jul 14. PMID: 37859449; PMCID: PMC10591176.

⁷ Park SA, Byeon G, Jhoo JH, Kim HC, Lim MN, Jang JW, Bae JB, Han JW, Kim TH, Kwak KP, Kim BJ, Kim SG, Kim JL, Moon SW, Park JH, Ryu SH, Youn JC, Lee DW, Lee SB, Lee JJ, Lee DY, Kim KW. A Preliminary Study on the Potential Protective Role of the Antioxidative Stress Markers of Cognitive Impairment: Glutathione and Glutathione Reductase. Clin Psychopharmacol Neurosci. 2023 Nov 30;21(4):758-768. doi: 10.9758/cpn.23.1053. Epub 2023 Jul 14. PMID: 37859449; PMCID: PMC10591176.

⁸ Martínez de Toda I, Miguélez L, Vida C, Carro E, De la Fuente M. Altered Redox State in Whole Blood Cells from Patients with Mild Cognitive Impairment and Alzheimer’s Disease. J Alzheimers Dis. 2019;71(1):153-163. doi: 10.3233/JAD-190198. PMID: 31356205.

⁹ J. Frontiñán-Rubio et al. Molecular and Cellular Neuroscience 92 (2018 

¹⁰  Witschi A, Reddy S, Stofer B, Lauterburg B: The systemic availability of oral glutathione. Eur J Clin Pharmacol 1992, 43(6):667–669.

¹¹ Lavoie S, Murray MM, Deppen P, Knyazeva MG, Berk M, Boulat O, Bovet P, Bush AI, Conus P, Copolov D, Fornari E, Meuli R, Solida A, Vianin P, Cuénod M, Buclin T, Do KQ: Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients. Neuropsychopharmacology 2008, 33(9):2187–2199.

¹² Ohlenschlager G,Treusch G, patent number: 5925620 International Classification A61K 3800 for synergistic action of anthocyanidins and glutathione

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