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

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

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

They wrote:

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

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

A Systematic Omission

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

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

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

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

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

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

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

Criticism 1: Misunderstanding Who Benefited in the VITACOG Trial

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

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

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

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

Criticism 2: No Benefit in the Hong Kong Trial?

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

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

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

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

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

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

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

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

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

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

What Does the Evidence Really Say?

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

Their conclusion is clear:

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

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

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

The perfect time to start? Today.

What Can You Do?

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

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

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

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

As a Friend, you’ll also gain access to:
• Monthly group coaching
• Your personalised brain upgrade programme: COGNITION™

Share the knowledge – public awareness can change public health.
We need a paradigm shift, and it starts with us.

by Patrick Holford

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Choline is an often-overlooked but vital nutrient for brain health.

A new study suggests the optimal intake is 400mg, yet there is no Recommended Daily Allowance or widespread promotion of this crucial nutrient. It is also notably low in vegetarian and especially vegan diets.

(We discuss this and more in our COGNITION 6-month brain upgrade programme – available when you become a FRIEND of Food for the Brain.)

A major study published this year found that higher choline intake lowers the risk of dementia, Alzheimer’s, and cognitive decline.

Researchers tracked 125,000 people from the UK Biobank for 12 years and the study was published in the American Journal of Clinical Nutrition. It showed that higher choline intake reduced risk, with the most benefit around 400mg per day.

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Why does it matter?

Brain cells are made of a membrane containing choline (and other phospholipids) attached to the omega-3 fat DHA. Without choline the omega-3 doesn’t work. The attaching of the two depends on methylation, a process that is dependent on B vitamins, especially B12, folate and B6. Choline helps methylation and healthy methylation, indicated by low homocysteine, helps synthesise choline.

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Also previous studies (2) have found remarkable effects supplementing 480-900mg of choline in pregnancy on promoting ‘smart’ babies with faster reflexes and cognitive processes. It’s important for all ages and a key topic in our Smart Kids & Teens Programme.

What should you do or eat?

Choline is essential for the body, especially the brain, yet it has no Recommended Daily Allowance.

Choline is abundant in eggs, fish, and meat. An egg provides about 120mg, while a 50g serving of beef or salmon contains around 50mg. Beef liver is the richest source, but eggs are the best overall because they contain phosphatidylcholine which is more easily absorbed by the body. Plant-based sources include soy, quinoa, nuts, seeds, beans, and broccoli. A 50g serving of almonds or broccoli provides about 25mg. Phosphatidylcholine, found in lecithin capsules and granules, is an easy supplement option for vegans and vegetarians.

We recommend eating two eggs most days, with a minimum of six per week. Include fish and some meat if you eat it, or soy, quinoa, broccoli, nuts, and seeds if you don’t. Supplementing is likely beneficial, especially for vegetarians. Taking two high-PC lecithin 1,200mg capsules daily provides 250mg of phosphatidylcholine (PC), the form used by the body. These supplements are available at your local health food store.

Remember, your brain is built from what you feed it – and how you use it (as covered in COGNITION). What choline-rich foods can you add to your diet this week?

If you’re unsure what to eat to support your brain or need inspiration, the Cook App is here to help! With over 100 recipes at your fingertips, eating delicious, brain-boosting foods has never been easier—all for just £30 a year.

Actions:

Take the Cognitive Function Test today – our validated online assessment – to find out exactly what you need to focus on.
Become a FRIEND and get access to your 6-month COGNITION programme so you know how to upgrade your brain.

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

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

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

—Reference list

Reference

Niu YY, Yan HY, Zhong JF, Diao ZQ, Li J, Li CP, Chen LH, Huang WQ, Xu M, Xu ZT, Liang XF, Li ZH, Liu D. Association of dietary choline intake with incidence of dementia, Alzheimer disease, and mild cognitive impairment: a large population-based prospective cohort study. Am J Clin Nutr. 2025 Jan;121(1):5-13. doi: 10.1016/j.ajcnut.2024.11.001. Epub 2024 Nov 7. PMID: 39521435.
Caudill, M. et al, ‘Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study’ FASEB Journal (Apr 2018); 32(4): 2172-80. doi: 10.1096/fj.201700692RR.

How can we lift our mood and nourish our brain? 

Depression, now the leading cause of disability globally, affects millions. According to the World Health Organization, it represents a significant disease burden, particularly in high-income countries (1). With a staggering 100 million antidepressant prescriptions issued annually—a 70% increase in five years—it’s clear that something is going wrong in our modern western world (1).

Thankfully, nutrition and lifestyle changes provide science-backed ways to boost our mood naturally.

(If you want to know more about how to overcome depression then make sure you watch our webinar ‘Finding your way out of depression’).

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Understanding Depression

Depression manifests through persistent feelings of hopelessness, low energy, disrupted sleep, and even physical changes such as weight loss or gain (2). The root causes can be multifactorial—psychological stress, biochemical imbalances, or nutritional deficiencies.

But here’s the good news: you can take simple, practical steps to nourish your brain, boost serotonin, and improve your mood naturally.

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7 Ways to Boost Mood and Brain Function

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1. Increase Your Omega-3 Fats

Your brain is 60% fat, and omega-3 DHA and EPA are critical for its structure and function. Countries with high fish consumption have lower depression rates. A study from Harvard Medical School found that EPA, specifically, has potent antidepressant effects.

A meta-analysis published in Psychopharmacology Bulletin found that higher omega-3 intake reduces depressive symptoms by 53%. Omega-3 helps build brain cell membranes and boosts serotonin receptor function, which improves mood and cognition.

What to do: Eat oily fish like salmon, sardines, and mackerel at least twice a week or supplement with high-dose omega-3 fish oil. Aim for 1,000–2,000 mg of EPA and DHA combined daily (4, 5, 6).

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2. Optimise Your B Vitamins and Lower Homocysteine

The little-known amino acid, homocysteine, may double your risk for depression if levels are elevated. This toxic by-product accumulates when you’re deficient in B6, B12, and folic acid, impairing brain chemistry. 

Studies by Professor David Smith from Oxford show that lowering homocysteine can dramatically slow brain shrinkage and improve mood. Which is why we now offer at home homocysteine test kits so you can monitor your own level and prevent disease (7,8,9).

What to do: Eat leafy greens, whole grains, and fortified foods. Test your homocysteine and aim for levels below 7 μmol/L. Supplement with a methylated B complex (20 mg B6, 500 μg B12, and 400 μg methylfolate).

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“B vitamins are brain-makers; without them, key neurotransmitters like serotonin can’t be synthesised” – Patrick Holford, Upgrade Your Brain.

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3. Fuel Your Brain with Serotonin Precursors

Serotonin, your “happy hormone”, is made from tryptophan, an amino acid found in protein-rich foods like fish, poultry, beans, and eggs. For some, tryptophan conversion to serotonin is impaired due to poor digestion or low stomach acid, common with age and stress.

Supplementing with 5-HTP can bypass these barriers. Clinical studies show 5-HTP compares favourably with SSRIs in treating depression (10, 11, 12, 13).

What to do: Include tryptophan-rich foods daily and consider a 5-HTP supplement (100–200 mg twice daily). Always consult your doctor if combining with antidepressants.

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4. Balance Your Blood Sugar

Maintaining stable blood sugar levels is essential for mood regulation, as uneven glucose supply to the brain can lead to irritability, fatigue, and depressive symptoms. Diets high in refined carbohydrates and sugar contribute to these fluctuations and are linked to poor mood and an increased risk of depression. A study of 3,456 adults found that individuals consuming diets rich in processed foods had a 58% greater risk of depression, whereas those eating whole foods experienced a 26% reduced risk (14, 14, 16).

 Refined sugars also deplete mood-enhancing nutrients like B vitamins, essential for energy production, and divert chromium, which is vital for glucose regulation. Adopting a low glycaemic load (GL) diet, avoiding caffeine and alcohol, and focusing on whole foods, fruits, and vegetables can help stabilise blood sugar levels and improve mood.

What to do: Follow a Low-GL diet with whole foods, low-GL carbs, and protein at every meal. Avoid sugar, caffeine, and alcohol .

5. Boost Your Vitamin D Levels

The “sunshine vitamin,” vitamin D, is essential for mood regulation. Research shows a 40% lower incidence of depression in those with adequate vitamin D. Alarmingly, over 60% of the UK population is deficient during winter (17, 18, 19, 20).

What to do: Get tested and aim for levels above 75 nmol/L. Supplement with 2,000–3,000 IU daily in winter months.

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6. Include Chromium to Combat Atypical Depression

If you suffer from atypical depression—characterised by weight gain, fatigue, and carbohydrate cravings—you might benefit from chromium. Studies show chromium supplementation can improve mood scores by up to 83% (21, 22, 23).

What to do: Include whole grains and vegetables or supplement with 600 mcg of chromium picolinate daily.

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7. Bring on the Sunshine and Movement

Exercise and sunlight have a direct effect on serotonin levels and mood. Regular exercise boosts brain-derived neurotrophic factor (BDNF), which helps build new brain cells and connections】.

What to do: Aim for 30 minutes of exercise daily and sun exposure for 15 minutes, when safe.

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Key Action Plan

Eat oily fish twice weekly or supplement omega-3s with at least 1,000 mg EPA and DHA.
Test and lower homocysteine with B6, B12, and folic acid supplements.
Try 5-HTP to boost serotonin naturally.
Follow a Low-GL diet to stabilise blood sugar.
Supplement vitamin D during winter. Find out more about dose here.
Add chromium for atypical depression.
Exercise regularly and get sensible sun exposure.

—

—

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

World Health Organization. Depression and Other Common Mental Disorders: Global Health Estimates. WHO; 2017.
Brown G, et al. Social support, self-esteem and depression. Psychol Med. 1986;16(4):813-31.
Hibbeln JR. ‘Fish consumption and major depression’. Lancet, vol 351(9110), pp. 1213 (1998)
M. Peet and R, Stokes, Omega 3 Fatty Acids in the Treatment of Psychiatric Disorders Drugs, vol 65(8), pp. 1051-9 (2005)
S Kraguljac NV, Montori VM, Pavuluri M, Chai HS, Wilson BS, Unal SS (2009) Efficacy of omega-3 Fatty acids in mood disorders – a systematic review and metaanalysis. Psychopharmacology Bulletin 42(3):39-54
Hibbeln JR. Fish consumption and major depression. Lancet. 1998;351(9110):1213.
Coppen A, Bailey J. Folic acid and affective disorders. J Affect Disord. 2000;60(2):121-30.
Taylor MJ, Carney SM, Goodwin GM, Geddes JR. Folate for depressive disorders. Cochrane Database Syst Rev. 2003;(2):CD003390.
Smith AD, Refsum H. Homocysteine, B vitamins, and cognitive impairment. Annu Rev Nutr. 2016;36:211-39.
Poldinger W et al. A comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology. 1991;24(2):53-81.
E. Turner, Serotoninalacarte: Supplementation with the serotonin precursor 5-hydroxytryptophan.’ Pharmacology&Therapeutics (2005) [article in press].
W. Poldinger et al. A functional-dimensional approach to depression: serotonin deficiency and target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine, Psychopathology vol 24(2), pp. 53-81 (1991)
Associate editor: K.A. Neve ‘Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan’ ErickH. Turner a,c,d,*, Jennifer M. Loftis a,b,c, AaronD. Blackwell a,b,e Pharmacology & Therapeutics(2005) www.elsevier.com/locate/pharmthera
Akbaraly TN, Brunner EJ, Ferrie JE, et al. Dietary pattern and depressive symptoms in middle age. Br J Psychiatry. 2009;195:408–13.
Benton D, Owens DS, Parker PY. Blood glucose influences memory and mood in an everyday setting. Biol Psychol. 1982;14(1-2):129–35.
Christensen L. Psychological distress and diet – effects of sucrose and caffeine. J Appl Nutr. 1988;40(1):44–50.
Lansdowne AT, Provost SC (1998): Demonstrates that vitamin D3 supplementation enhances mood in healthy subjects during winter.
C. Wilkins et al. (2006): Links vitamin D deficiency to low mood and poorer cognitive performance in older adults.
A. Nanri et al. (2009): Discusses the association between vitamin D levels and depressive symptoms across seasonal changes.
R. Jorde et al. (2008): Shows that vitamin D supplementation alleviates depressive symptoms in overweight and obese individuals
Lifting Depression – The Chromium Connection by Dr Malcolm McLeod (Basic Health Publications):
J. R. Davidson et al, Effectiveness of chromium in atypical depression: a placebo-controlled trial, Biol Psychiatry, vol 53(3), pp. 261-4 (2003)
Docherty, J et al, ‘A Double-Blind, Placebo-Controlled, Exploratory Trial of Chromium Picolinate in Atypical Depression’. Journal of Psychiatric Practice. Vol 11(5), pp. 302-314, (2005)
Holford P. Upgrade Your Brain. HarperCollins; 2024.

By Patrick Holford. This is part one, read part two here.

Few people realise the catastrophic decline in mental health that has occurred over the past 50 years.

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‘Brain health conditions have become a global health emergency,’ according to the Federation of European Neuroscience Societies last year (1).

Globally, 15 per cent of all disability is due to brain and mental health disorders. The lifetime cost of Alzheimer’s in 2022 was estimated to be €1.2 trillion across the EU which is half the UK’s total GDP! This burden and costs exceeds that of all diseases, including cancer and heart disease. But most worrying are the trends of falling IQ at a rate of about 7 per cent a generation and the steady increase in young people with four in ten now reporting persistent feelings of sadness or hopelessness and almost a quarter (22 per cent) contemplating suicide (2).

On this flight path, by 2080, suicide may well become the leading cause of death in those under 24. Also, more than a third of children will have severe neurodevelopmental impairment, defined as significantly below the norm for IQ. That’s the conclusion of Professor Michael Crawford who discovered the essentiality of omega-3 DHA for the brain. Alarmingly, brain size, deduced from cranial capacity of skulls, has shrunk by a staggering 20 per cent over a mere 30,000 years. It took over six million years for brain size to increase from that of a chimpanzee (350cc) to a peak of 1,600 to 1,700 cc with Cro Magnon man thirty thousand years ago. Today, brain size averages 1,350cc (3). There is no question that we are devolving mentally with an endless escalation of rates of ADHD, autism, depression, anxiety, insomnia, schizophrenia, dementia and Alzheimer’s, as well as strokes, Parkinson’s and multiple sclerosis.

The big question is: why?

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Introducing the four horsemen…

I’m proposing that there are four main biological drivers of our demise which I’m calling the four horsemen of the mental health apocalypse: a lack of brain fats, messed up methylation, loss of glucose control and excessive oxidation.

The first two – brain fats and methylation – are vital for the integral structure of neuronal membranes. The second two are vital for the function of brain cells, supplying fuel and coping with the oxidant ‘exhaust fumes’ of energy metabolism.

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Brain fats in short supply

The dry weight of the brain is 60 per cent fat, and omega-3 DHA makes up the majority of the structural fat of neurons, followed closely by Arachidonic Acid (AA), an omega-6 fat. ALL BRAINS OF ALL ANIMALS contain predominantly these two essential brain fats. It is the available supply of these that determine whether an animal ends up with a big or small brain. The link between omega-3 DHA and brain function is beyond doubt, with study after study confirming the scientific evidence. Only last month, a study from the UK BioBank reported a 30 per cent lower risk of dementia in those with a higher omega-3 status in their blood (4). This confirmed the results of a US study (5) that found a 49 per cent reduced risk for dementia in those with the highest DHA level (top fifth) in their red blood cells versus the lowest (bottom fifth). A meta-analysis of 48 studies in the American Journal of Clinical Nutrition in 2023 (6) concludes that ‘a moderate-to-high level of evidence suggested that dietary intake of omega-3 fatty acids could lower risk of all-cause dementia or cognitive decline by about 20 per cent, especially for docosahexaenoic acid (DHA) intake’. Each 100mg increment of DHA was associated with an 8–10 per cent lower risk of dementia. And a 2023 study, by psychologists at the Linda Loma University in California and published in the journal Brain Sciences (7), reported that the higher a person’s omega-3 blood index was, the more white matter there was in their brain, and the better they performed on cognitive tests that predict less risk for dementia.

It’s compelling science. That is why my first recommendation is to always test your omega-3 index.

This is the percentage of omega-3 DHA and EPA in the membrane of red blood cells, and it is a direct reflector of the membrane levels in your brain. Red cells last for three months so this is a long-term measure of your omega-3 status. In countries such as Japan, known for a high fish diet, the omega-3 index is around 10 per cent on average. Ideally, a level of above 8 per cent is optimal. I thought I was doing well, supplementing daily 575mg of EPA and DHA combined, plus eating oily fish three times a week but I scored just under – 7.7 per cent. I’ve since upped my intake of DHA by 500 mg, to 750 mg total daily intake.

In its pure form, DHA isn’t enough, it has to become ‘phosphorylated’ to work. It’s a bit like using those glues where you have two tubes and have to mix a squeeze of one with the other for the glue to work. The ‘mixer’ in this case is the B vitamins in your body attaching the DHA to the phospholipids such as phosphatidylcholine (PC). If you have no phospholipids, or no DHA or B vitamins, the mix is not going to work. While the body can synthesise DHA, to reach the levels we need requires good quality food sources such as seafood, by far the richest source of (already) phosphorylated DHA. If fish isn’t your thing, supplementing with lecithin (granules or capsules) is a must – aim for two 1200mg capsules or 250mg of PC per day.

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Vitamin D is a mental health essential

The other essential brain fat, which is actually a hormone, is vitamin D.

A large-scale study earlier this year, involving over twelve thousand dementia-free 70+ year olds (8), found that more than a third (37 per cent) took supplements of vitamin D and those that did had a 40 per cent lower incidence of dementia. Many nutrition professionals recommend supplementing around 3,000 iu in the winter to achieve an adequate blood level of 75 nmol/L or more, advice that is backed up by a consortium of some 35 vitamin D researchers.(9)  The UK Government also recommends supplementing vitamin D, although the recommended 400iu falls far short of the amount needed for brain health. In a study in France, those with low vitamin D levels, below 50 nmol/L, had a nearly three-fold increased risk of Alzheimer’s (10) and worryingly, over sixty per cent of people in the UK have lower levels than this (11), while half are unaware of the need to supplement in the winter and only one in ten actually do (12). (Back in 2010, I was reported to the Advertising Standards Agency for suggesting that people had to supplement vitamin D in the winter because diet alone was not sufficient – how times change!)

Research continues to investigate whether having a higher blood level of vitamin D, perhaps 100 nmol/L, is even better for brain health. If you know your vitamin D level, you can help with this research by completing the Cognitive Function Test, and providing your vitamin D level. Or you can join our MIND project which includes a home test kit to measure your vitamin D level. We’ve tested 410,000 people’s cognitive function so far but need more people who know, or are willing to test their vitamin D.

Methylation and homocysteine-lowering B vitamins

Omega-3 DHA can only become active by the process of methylation, which attaches the DHA to a phospholipid and thereby enables it to be incorporated into the neuronal membrane. The process of methylation is totally dependent on vitamins B6, B12 and folate. Our methylation-ability is beautifully defined by our homocysteine level. Homocysteine rises if the biochemical pathway between the amino acid methionine converting to the methyl-donor SAMe is blocked. Without adequate vitamin B6, B12, folate or, in the liver, zinc and tri-methyl glycine (TMG), homocysteine will rise.

Lowering homocysteine with B vitamins is the greatest evidenced disease-modifying treatment, as shown in the best meta-analysis of 396 trials (13) by China’s leading Alzheimer’s prevention expert, Professor Jin-Tai Yu, whom we are honoured to have in our Scientific Advisory Board. It was also rated so by the US National Institutes of Health researchers (14). 

Homocysteine is also a biomarker for over 100 diseases including almost all mental and neurological diseases. The seminal paper by Professors David Smith and Helga Refsum on the subject is vital for all to read. For example, just one recent meta-analysis showed that both homocysteine, vitamin B12, and folic acid predict the onset and development of Parkinson’s. Homocysteine levels above 11µmol/L are a clear indicator that the brain is shrinking. Professor David Smith, another member of our Scientific Advisory Board, recommends treatment with B vitamins for anyone with a homocysteine above 10µmol/L , giving 20 mg of B6, 400 mcg of methylfolate and 500µg of B12.

Increasingly, raised homocysteine is extremely common. In America, 40 per cent of those over 60 have a homocysteine of over 11 (15). In China ‘the mean (average) homocysteine levels in adult males less than 30 years of age and greater than 60 years were higher than the upper limit of normal (15 µmol/L).’ And in the UK, two in five adults over 61 have insufficient B12 to prevent accelerated brain shrinkage (16).

Homocysteine not only predicts Alzheimer’s dementias but also vascular dementia which, combined, make up almost 90 per cent of all dementias. Raised homocysteine is a major driver of cardiovascular and cerebrovascular disease. Raised homocysteine increases the risk of cerebrovascular disease by seventeen times (17)! Joe Rogan dedicated his recent show to exactly this (18) and stressed why testing homocysteine is vital for anyone with any form of cardiovascular, neurological or mental health disease.

The trouble with homocysteine is you just don’t know if your level is raised without testing it, which is why we have create our own at-home, highly accurate test kit. While up to 20 per cent of people have a methylation gene mutation (MTHFR677TT) making them more likely to have a raised level, it’s likely that most people with raised homocysteine are just not good at absorbing vitamin B12, a condition that becomes more common with age. This is why antacid proton pump inhibitor (PPI) drugs are such bad news. They drive down B12 and four years use cranks up Alzheimer’s risk by over 33 per cent (19). 

Breakthrough in homocysteine testing

It is essential to test homocysteine level for anyone over 50 and anyone with any brain or mental health or cardiovascular disorder including hypertension. Treatment with B vitamins is also essential if the level is above 10µmol/L. While a homocysteine level above 11 means increased brain shrinkage, research shows that even a homocysteine level of above 9 during pregnancy predicts more problems, specifically withdrawn behaviour, anxiety/depression, social problems and aggressive behaviour in the child by the age of six (20). Raised homocysteine is a well known predictor of miscarriage and pregnancy problems, which is why I recommend that women can best prepare for a healthy pregnancy by ensuring their homocysteine level is below 7.5 mcmol/l. Above this, the evidence points to chromosomal damage (21).

All these studies refer to plasma homocysteine, that is the level found in the clear serum part of blood (rather than the red blood cells). The difficulty with many test kits is the need to separate or spin the blood shortly after taking the sample or pass the blood through a plasma separator. Many fall short of the correlation with serum/plasma homocysteine, the gold standard of testing. Excitingly, a breakthrough with both the fixing of blood (taken using a dry blood spot) and the testing process now means that we now have an accurate and inexpensive way to test homocysteine with our home test kit. This is going to be made available all over the world, starting with the UK and EU in January 2024. The validation of this test is extremely good, with no false positives or negatives. Accuracy can be further improved if the test is taken after fasting for 12 hours with water only. Both coffee and alcohol affect homocysteine levels, as does eating a protein-rich meal.

Please, join our Citizen Science research by both testing homocysteine and completing the Cognitive Function Test here

A consensus of world experts (22) has concluded that lowering homocysteine with B vitamins is the easiest and most cost-effective prevention action, which Oxford University’s health economists estimate would save the UK £66 million per year (23).

However, it’s vital to test both homocysteine and Omega-3 levels, as they are co-dependent. Homocysteine-lowering B vitamins only work in those with sufficient omega-3, and omega-3 only works if homocysteine is low. This short film shows how this works here.

It explains why studies giving omega-3 or giving B vitamins have not consistently been effective. However, in re-analyses of three studies, B vitamins are highly effective, both in reducing the rate of brain shrinkage and improving cognition, in those with sufficient omega-3, and conversely, omega-3 is highly effective, but only in those with homocysteine below 11 mcmol/L (24). 

…Read part two here!

Want to learn more about homocysteine and how to reclaim your brain? Join us for the Homocysteine Unplugged webinar.

Thank you for reading!

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

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

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

References

1 https://www.politico.eu/sponsored-content/global-data-is-key-to-tackling-the-rise-in-brain-health-conditions/

2  van Os J, Guloksuz S. Population Salutogenesis—The Future of Psychiatry? JAMA Psychiatry. Published online December 20, 2023. doi:10.1001/jamapsychiatry.2023.4582

3 Crawford M, Marsh, D ‘The Shrinking Brain’ 2023

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

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

6 Wei BZ, Li L, Dong CW, Tan CC; Alzheimer’s Disease Neuroimaging Initiative; Xu W. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers. Am J Clin Nutr. 2023

7 Loong, S.; Barnes, S.; Gatto, N.M.; Chowdhury, S.; Lee, G.J. Omega-3 Fatty Acids, Cognition, and Brain Volume in Older Adults. Brain Sci.2023,13,1278. https://doi.org/ 10.3390/brainsci13091278 

8 Ghahremani M et al. Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status. Alzheimers Dement (Amst). 2023 Mar 1;15(1):e12404. doi: 10.1002/dad2.12404. PMID: 36874594; PMCID: PMC9976297.

9 Płudowski P et al Guidelines for Preventing and Treating Vitamin D Deficiency: A 2023 Update in Poland. Nutrients. 2023 Jan 30;15(3):695. doi: 10.3390/nu15030695. PMID: 36771403; PMCID: PMC9920487.

10 Jia J et al. Effects of vitamin D supplementation on cognitive function and blood Aβ-related biomarkers in older adults with Alzheimer’s disease: a randomised, double-blind, placebo-controlled trial. J Neurol Neurosurg Psychiatry. 2019 Dec;90(12):1347-1352. doi: 10.1136/jnnp-2018-320199. Epub 2019 Jul 11. PMID: 31296588.

11 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353432/pdf/nutrients-12-01868.pdf

12 https://www.nutrition.org.uk/news/2021/british-nutrition-foundation-survey-reveals-49-adults-unaware-of-uk-government-guidelines-for-vitamin-d/

13 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.

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.

15 Pfeiffer C, Clin Chem. 2008; R. Xu, Nature Scientific Reports 2022; Vogiatzlou A, Neurology, 2008

16 Vogiatzoglou A, Refsum H, Johnston C, Smith SM, Bradley KM, de Jager C, Budge MM, Smith AD. Vitamin B12 status and rate of brain volume loss in community-dwelling elderly. Neurology. 2008 Sep 9;71(11):826-32. doi: 10.1212/01.wnl.0000325581.26991.f2. PMID: 18779510.

17 Teng Z, Feng J, Liu R, Ji Y, Xu J, Jiang X, Chen H, Dong Y, Meng N, Xiao Y, Xie X, Lv P. Cerebral small vessel disease mediates the association between homocysteine and cognitive function. Front Aging Neurosci. 2022 Jul 15;14:868777. doi: 10.3389/fnagi.2022.868777. PMID: 35912072; PMCID: PMC9335204.

18  See the Joe Rogan show https://www.youtube.com/watch?v=-oqYoNwnOs0.

19 Northuis CA, Bell EJ, Lutsey PL, George KM, Gottesman RF, Mosley TH, Whitsel EA, Lakshminarayan K. Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study. Neurology. 2023 Oct 31;101(18):e1771-e1778. doi: 10.1212/WNL.0000000000207747. Epub 2023 Aug 9. PMID: 37558503; PMCID: PMC10634644.

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

21 Fenech M, Aitken C, Rinaldi J. Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults. Carcinogenesis. 1998 Jul;19(7):1163-71. doi: 10.1093/carcin/19.7.1163. PMID: 9683174.

22 Smith AD, Refsum H, Bottiglieri T, Fenech M, Hooshmand B, McCaddon A, Miller JW, Rosenberg IH, Obeid R. Homocysteine and Dementia: An International Consensus Statement. J Alzheimers Dis. 2018;62(2):561-570. doi: 10.3233/JAD-171042. PMID: 29480200; PMCID: PMC5836397.

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

24 Jernerén F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H, Smith AD (2015). Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. Am J Clin Nutr. 2015 Jul;102(1):215-21; see also van Soest, A.P.M., van de Rest, O., Witkamp, R.F. et al. DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial. Eur J Nutr 61, 3731–3739 (2022). https://doi.org/10.1007/s00394-022-02924-w; see also Jernerén F, Cederholm T, Refsum H, Smith AD, Turner C, Palmblad J, Eriksdotter M, Hjorth E, Faxen-Irving G, Wahlund LO, Schultzberg M, Basun H, Freund-Levi Y. Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer’s Disease: The OmegAD Study. J Alzheimers Dis. 2019;69(1):189-197. doi: 10.3233/JAD-181148. PMID: 30958356.

25 Lakhan, S.E., Kirchgessner, A. The emerging role of dietary fructose in obesity and cognitive decline. Nutr J 12, 114 (2013). 

This was the title of a report in the British Medical Journal (1), pointing out that choline is an essential nutrient, much like omega-3 fats, that is vital for health and especially the brain, but not sufficiently supplied in many people’s diets, and especially those who are largely vegan.

While the body can make a little, it does not make enough and thus choline is being reclassified as an essential nutrient with an adequate intake defined as between 400mg and 520mg a day, the latter for pregnant and breast-feeding women. But these levels don’t relate to brain function. They relate to the EFSA allowed claims of “choline is needed for lipids metabolism”, “maintaining healthy liver functioning” and “reduction in homocysteine levels”. You need choline to do the right thing with cholesterol in the liver. 

But even more important is choline’s role in building and maintaining a healthy brain. A pregnant woman’s intake defines the cognitive abilities of their child. Twenty years ago we knew that pregnant rats fed choline half way through their pregnancy have more connections between brain cells, plus improved learning ability and better memory recall. Now we know it’s true for babies. In fact, a lack of choline can lead to a shrinking of a woman’s brain as the foetus robs their brain to build its own – a case of ‘Mummy I shrank your brain’. Babies are born with blood choline levels three times higher than their mother, illustrating how vital this nutrient is for building neuronal connections, which newborn babies do at a rate of up to a million new connections a second! An optimal intake for brain function is likely to be a lot higher than the 400mg recommended for adults.

Brain cells are made of a membrane containing choline (and other phospholipids) attached to the omega-3 fat DHA. Without choline the omega-3 doesn’t work. The attaching of the two depends on methylation, a process that is dependent on B vitamins, especially B12, folate and B6. Choline helps methylation and healthy methylation, indicated by low homocysteine, helps synthesize choline.

The reason the BMJ says ‘crisis’ is that more people are eating a plant-based diet and shunning eggs, fish and meat, which are the best sources of, not only choline, but also B12. There’s a tiny bit of choline in broccoli and in nuts, but not enough. An egg provides around 120mg, a 50g beef or salmon steak around 50mg. The same amount of almonds or broccoli is about 25mg. Cow’s milk has a little, but a fraction of that found in human milk. Beef liver is the richest source.

Twenty years ago I found the evidence sufficiently compelling to recommend eating an egg a day, three servings of fish and one of meat (or another portion of fish) a week, a handful of nuts, plus daily supplementation of circa 100mg, which is what I do in my ‘brain food’ formula. If you also ate a serving of broccoli a day, you’d be achieving something like 2,100mg a week, or 300mg a day – still short of daily requirements.

If you don’t eat eggs, fish or meat and don’t supplement there’s no way of getting even close. That’s why it’s time to add choline, along with omega-3 DHA and B12, to the list of nutrients that must be supplemented by those eating a vegan diet. Lecithin granules and capsules are the richest vegan source of choline, derived from soya. It will not work in building the brain, without a source of DHA which can be derived, in supplements, from algae or seaweed. 

If you want more strategies on what to eat and do to support ad upgrade your brain make sure you complete the Cognitive Function Test below to get your plan of action for improving your brain over the next 6 months.

Reference:

Derbyshire E. ‘Could we be overlooking a potential choline crisis in the United Kingdom?’ BMJ Nutrition, Prevention and Health, 2019; 0:1–4

Methylation and mental health are intricately related. We take a deeper look into the association and why it is important.

What is methylation? 

Methylation has been a buzzword in the integrative health sphere for some time now. This is unsurprising considering its importance to our overall health and wellbeing. You may have heard of it before – or even googled it… Were you then promptly turned off by it after just one glance at its complexity?

We don’t blame you; understanding methylation is not for the faint-hearted. 

However, let us break it down for you into bite sized chunks. Hopefully you can finally make sense of it and apply this knowledge to your everyday life.

Think of it as a biological switch

Methylation is a critical biochemical process that happens billions of times in every single cell of the human body. It’s responsible for a vast range of biological functions such as: 

Detoxification
DNA expression
Neurotransmitter production
Hormone regulation

Whilst it can be complex in nature, the process of methylation simply entails the transfer of four atoms: one carbon atom and three hydrogen atoms. These are transferred from one substance to another.  

Let’s say that methylation is a type of biological switch that turns on and off to help keep our health in check. 

How does methylation impact mental health?

While we know that methylation plays an intrinsic role in many important body functions, for the purpose of this article, we will focus on its role in mental well-being and brain health. 

Put simply, methylation helps us make neurotransmitters, such as serotonin, dopamine, adrenaline, norepinephrine and melatonin. 

(For more in-depth information and references, please read the Upgrade Your Brain Book)

Methylation does this in a number of ways. It helps:

Convert tryptophan (building block for serotonin) to 5-HTP (precursor to serotonin) 
Transport dopamine, norepinephrine and adrenaline
Convert norepinephrine to adrenaline (important for focus and attention)
Lastly, convert serotonin to melatonin (sleep neurohormone) 

So as you can see, it’s pretty vital to a balanced mood and overall brain health. 

What impacts methylation? 

Unfortunately there are many things that can negatively impact methylation, such as our diet, exposure to environmental toxins, genetic factors and lifestyle habits. 

Let’s look at this in a little more detail. 

—

Anything that triggers oxidative stress can have a negative effect on methylation. Oxidative stress is a natural biological process that’s usually offset by our body’s own endogenous antioxidant production. But when there’s an imbalance between the two, and factors in our environment generating oxidative stress are tipping the scale in their favour, that’s when we can see prolonged inflammation and problems with methylation. 

What specific environmental factors can impact methylation?

Our modern environment is plagued with reactive oxygen species ROS that generate oxidative stress in the body. Key examples are environmental endocrine disruptors, like PCBs, herbicides, pesticides and plasticisers, as well as air pollution. 

Whilst we can’t necessarily fully control these aspects in our environment, we can control our defence against them, as well as making wise dietary choices that will have less of these substances in them. 

But first, let’s talk about what else can impact methylation.

Dietary factors and methylation

What you eat can impact how well you methylate, especially the intake of processed foods and sugars, which has been shown to play a negative role in methylation.

Perhaps unsurprisingly, research shows that eating a wholefood diet that includes wholemeal cereals, fish, legumes, fruits and vegetables can have a positive effect on methylation. 

Aside from dietary factors, there are a few nutrients that play a critical role in methylation.

Folate

Perhaps the most important nutrient is folate or B9. Methylation is almost entirely dependent on the availability of folate in the diet. It uses this nutrient to create the methyl donors – SAMe and methionine – to spark enzymatic reactions that are required for neurotransmitter production and transport. 

A large body of research (1) confirms that folate deficiency – something that is incredibly common – is frequently seen in those with depression, and is remediated with the supplementation of this nutrient.

When we consider the role that optimal methylation plays in producing serotonin and other neurotransmitters, it’s easy to see why folate is so important.

What about folic acid?

Many are drawn to supplementing folate in the form of folic acid, the synthetic version of this nutrient. You can often find folic acid in fortified foods such as breakfast cereals and breads. 

However, what people don’t realise is that this version of folate needs to be converted in the body to l-methylfolate and many people lack the ability to do this efficiently due to gene variations. 

This means the body is unable to utilise the folic acid properly.  We go into gene variants in a little more depth further down, so hold on for more information.

Where can we get folate in our diet? 

The best food sources of folate are dark leafy greens (like spinach and kale), legumes (such as lentils and chickpeas), liver, asparagus, Brussels sprouts, and fortified grains, so be sure to be getting these in your diet frequently. 

B12

Whereas folate is important to initiate the methylation cycle, B12 is required for the activation of folate from dietary folate to  5-methyltetrahydrofolate, so that it can go on to create the methyl groups – SAMe and methionine.  

If there isn’t enough B12 in the diet, folate can get stuck in the cycle, which halts methylation.

B12 is a nutrient that’s found in animal foods, such as meats, fish, eggs, poultry and dairy products. This means that if you’re vegan or vegetarian, you will likely need to supplement your B12 and consider eating fortified foods, such as plant milks.

Choline

Choline – plays an important role in various junctions in the methylation cycle. It is widely known that when folate is low, the body uses choline as its back up methyl donor to help keep methylation ticking along. 

It helps with activation of folate, as well as the recycling of homocysteine to methionine – a critical step in methylation.

The test that shows how well you are methylating…

Having high homocysteine is a key way of indicating whether your methylation is struggling and whether this recycling process isn’t functioning properly. 

We don’t want accumulating levels of homocysteine as it is a neurotoxin that has been linked to psychiatric disorders such as depression, schizophrenia, bipolar and Alzheimer’s disease (2). 

This is why if mental health is a concern, testing for homocysteine is a great way to find out whether you may have issues methylating. 
You can order and test your homocysteine level accurately from the comfort of your own home. Join our research and order your homocysteine test.

(Bear in mind that levels are not static and can change based on how well you’re methylating, as well as certain dietary factors, such as caffeine and alcohol consumption, which have been shown in some cases to tax methylation.)

Testing methylation

In addition to homocysteine, which is explained in further detail below, you can also take a DNA test to see whether you have any mutations on the MTHFR gene – the primary gene that is responsible for folate activation and homocysteine recycling – both of which are necessary for optimal methylation and therefore neurotransmitter production.

Testing for MTHFR

Variants or mutations on the MTHFR gene are inherited from your parents and can either be heterozygous (meaning you have one mutation) or homozygous (two mutations). 

It’s well known that having a homozygous mutation is more likely to cause health problems and having a heterozygous mutation is unlikely to cause issues. 

Common variants are:

C677T 
A1298C

Testing for these variants is done by a simple saliva test and is usually done privately. Here in the UK, there are various providers such as Lifecode GX, however, if you’re not based in the UK there are likely many more providers globally.

How do we optimise methylation?

As well as eating a wholefood diet that is devoid of sugar and processed foods, if you suspect methylation may be an issue for you, it’s important to take the environmental factors listed above into consideration. 

In order to avoid toxins and pollutants you can:

Eat organic produce as much as possible and wash any inorganic vegetables properly before consumption.
Drink filtered water
Buy toxin free cosmetics that don’t include typical endocrine disruptors such as parabens, benzophenones, bisphenols, and phthalates
Avoid plastics (bottled water, cling film, plastic tupperware etc)
If you smoke or vape – stop. 
Supplementation might also be considered, you can find out more about supplementation and brain health here.

Work with a nutritionist – find out more at our Brain Bio Centre Practitioners here.

Key takeaway: there is so much you can do to support your methylation pathways and support your mental health!

Eating a healthy, balanced diet, as well as engaging in healthy lifestyle practices as we outline in our COGNITION Programme, is key. We cannot change our genes but we can create the right environment for them.

When you become a FRIEND and gain access to your personalised 6-month COGNITION programme you will learn how to create the right environment to ‘upgrade your brain’.

—

Actions:

Order your homocysteine test here.
Dive deeper into the topic with our expert-led Methylation Webinar – you can get instant access here.
Complete the Cognitive Function Test here to get a personalised plan of action for upgrading your brain and to contribute to our research.
Become a FRIEND here

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

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

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

References:
1 https://doi.org/10.1016/j.jpsychires.2017.07.019

2 Silva, V. C. da S., et al. (2015). “Homocysteine and Psychiatric Disorders.” Journal of Integrative and Environmental Sciences

In the UK, at any one time about 220,000 people are being treated for schizophrenia by the NHS. Whilst it is a less common mental health condition, statistics show that there is a higher risk associated to suicide and greater vulnerability to physical conditions like diabetes, perhaps due to medications such as antipsychotics. Due to this, statistics show that people with schizophrenia die on average 10 – 20 years earlier than the general population.

Schizophrenia is characterised by two different groups of symptoms, which are classified as ‘positive’ and ‘negative’. Positive symptoms are the changes in behaviour and thoughts described as hallucinations (hearing voices or seeing things that others don’t), delusions and paranoia. The negative symptoms include feeling disconnected from other people, less interested in life, emotionless and sometimes disorganised thought and speech. 

The exact cause of schizophrenia is still misunderstood, with various theories pointing to a number of different biochemical imbalances, including genetic mutations that can provide the foundations for the disorder to develop. 

What causes schizophrenia?

One of the most popular theories on the cause of schizophrenia, which is widely accepted by the scientific and medical community, is the dopamine excess hypothesis, that is, too much dopamine in the brain that can cause the positive symptoms of psychosis to occur. Antipsychotics are the most commonly prescribed medications to target positive symptoms and prevent psychosis. Whilst they have proven to be critical in targeting excessive dopamine signalling in the brain, antipsychotics can also lead to health complications such as metabolic syndrome, the worsening of negative symptoms and nutrient depletion, which overall can be detrimental to a patients’ health over a long period of time. Studies show that common antipsychotics such as clozapine can lead to the depletion of selenium and l-tryptophan. Both nutrients are incredibly important to maintain health – selenium is an essential mineral, which is a precursor to glutathione, the body’s most important antioxidant and l-tryptophan is an amino acid precursor to serotonin, which is known to prevent depression and enhance mental wellbeing.

Another key theory, founded by the late Dr Abraham Hoffer and his colleagues Humphrey Osmand and John Smythies in 1954, is the adrenochrome theory. This theory initially came about after studying the symptoms caused by hallucinogenic drugs such as LSD, mescaline and amphetamines. The researchers noted these symptoms were similar to those experienced by schizophrenics including euphoria, derealisation and hallucinations, accompanied by paranoia and depression. They then discovered that the chemical structure of adrenaline was also similar to mescaline and LSD, which lead them into researching the effect of adrenochromes on the brain. 

What are adrenochromes? 

Adrenochromes are metabolites of adrenaline, the hormone and neurotransmitter that is responsible for our body’s ‘fight or flight’ response. It is believed that derivatives of adrenaline and other similar compounds such as dopaminochrome and noradrenochrome, can be neurotoxic in large quantities and cause mood-altering effects. 

The adrenochrome theory is further supported by studies that have shown how in those with schizophrenia, the enzyme glutathione s-transferase, (responsible for clearing the brain from neurotoxic compounds such as adrenochrome, dopaminochrome and noradrenochrome) is commonly defective, thus leading to an accumulation of these substances in the brain. 

What is niacin’s (B3) role in preventing symptoms of schizophrenia? 

Abraham Hoffer and his team theorised that in order to reduce the production of adrenochromes, a methyl acceptor such as B3 would be needed. Methyl acceptor is the name for nutrients, mainly in the B vitamin family, which each play an important role in a biochemical process known as methylation. This process is needed for a variety of biochemical reactions, such as building and breaking down neurotransmitters, supporting liver detox pathways and DNA repair, to name a few.  

Upon studying the pathway for adrenaline production in the brain and the cofactor nutrients supporting and inhibiting this pathway, Hoffer deduced that by giving large doses of vitamin B3, which is a methyl acceptor, this would effectively prevent the conversion of noradrenaline to adrenaline, and by limiting the amount of adrenaline, this would then prevent the build up of adrenochromes. 

In addition, B3 is also a precursor to nicotinamide adenine dinucleotide (NAD), a compound that is involved in redox reactions, which prevents oxidative stress caused by free radicals. These are unstable molecules that scavenge electrons from other molecules, causing a chain reaction that can eventually damage tissues in the body. NAD prevents the oxidation of adrenaline, which is what turns adrenaline into adrenochromes, therefore preventing the production of these neurotoxins that over time can damage the brain.


How reliable is the adrenochrome theory? 

Between the years 1953 to 1960, Hoffer researched and studied patients with schizophrenia, publishing a total of six double-blindclinical trials. In one study, conducted in 1962, 82 patients (39 in the niacin group and 43 in the placebo group) were involved and were given niacin throughout a period of 33 days. The results showed that 79.5% in the niacin group improved significantly in comparison to the placebo group, which was 41.9%. 

Despite the positive results that these 6 studies showed, other studies on patients with chronic schizophrenia who had been suffering for longer periods of time, demonstrated how B3 was not as effective. In one particular study using 32 patients, after two years of niacin use no positive effect was registered. However, Hoffer realised after performing initial studies that niacin treatment needed to be carried out for longer periods of time in those with chronic schizophrenia. 

A recent meta-analysis of the effects of vitamins and minerals on schizophrenia identified 18 clinical trials in which 832 patients on antipsychotics were involved. The analysis found that high dose B vitamins (including B3, B6 B9 and B12) were consistently effective for reducing psychiatric symptoms, in comparison to studies where low dose B vitamins were used. 

How safe is niacin treatment? 

Doses of niacin for schizophrenia are recommended between 3,000mg – 18,000mg a day in order to have a substantial effect. It should be noted, however, that niacin treatment must be monitored by a qualified health professional or doctor and should not be self-prescribed. Due to niacin’s side-effects, which are characterised by hot flushes and red skin rashes, many may choose to opt for a ‘no-flush’ version of the niacin supplement. However, studies have shown the risk of liver toxicity with high doses of the timed release and no-flush version of niacin, so this should be avoided. 

In addition, niacin on its own is rarely enough to address symptoms of schizophrenia. Each person is unique, and therefore there are many other factors which should be taken into consideration, such as digestion and inflammation.