What if the key to protecting women’s brains from Alzheimer’s isn’t a drug, but a nutrient most of us are not getting enough of?
That’s the conclusion of new research linking low omega-3 status with a higher risk of dementia, particularly in women. It adds to a growing body of evidence that what you eat today directly shapes your brain health tomorrow.
You may have seen headlines this year reporting that women with Alzheimer’s disease tend to have unusually low levels of omega-3 fatty acids in their blood. This new evidence adds weight to what our research has been highlighting for years: your brain needs these essential fats to stay healthy, sharp, and resilient.
What The New Study Shows?
A study led by Wretland and colleagues, published in Alzheimer’s & Dementia, analysed blood lipid profiles and found that those at greater risk of Alzheimer’s disease had lower levels of lipids containing the long-chain omega-3 fats EPA and DHA. Importantly, this association was stronger in women than in men [1].
Professor William Harris, a member of Food for the Brain’s Scientific Advisory Board and one of the world’s leading omega-3 researchers, commented on the study, saying:
“Measurement of blood omega-3 levels may be especially useful in identifying women at increased risk for Alzheimer’s. Why women? Possibly because of the widespread abandonment of hormone replacement therapy after the Women’s Health Initiative study, which may have inadvertently left many women more vulnerable. Oestrogen supports cognitive health and also helps maintain omega-3 status. Without it, low omega-3 levels may pose an even greater risk.”
(Want to learn more about how to support women’s brains and hormones? Find out more here.
Learn more about maintaining healthy omega-3 levels from OmegaQuant, founded by Professor William Harris.)
Why Omega-3 Is So Vital For The Brain?
The brain is about 60% fat by dry weight, with DHA the dominant structural fat in brain cells [2].
Higher omega-3 status is consistently linked to slower brain shrinkage and lower dementia risk [3,4].
Just one serving of oily fish a week has been associated with a 60% lower risk of Alzheimer’s disease [5].
But omega-3 rarely works in isolation. Research from the University of Oxford shows that the combination of good omega-3 levels and homocysteine-lowering B vitamins can reduce brain shrinkage by 73% in those at risk of dementia [6,7].
Why Women’s Brains Need Special Attention After Menopause?
After menopause, falling oestrogen increases the risk of memory decline. Following the 2002 Women’s Health Initiative report, HRT prescribing plummeted worldwide due to perceived risks. Although use is now rising again, this shift has raised important questions about how hormones interact with brain health.
While decisions about HRT are individual and should be made with the guidance of a medical professional, supporting brain health through nutrition is relevant for all women. Because oestrogen helps maintain levels of the omega-3 fats EPA and DHA, women with a low intake of these nutrients may be at particular risk of deficiency. Ensuring adequate omega-3 – through oily fish or supplements – remains a practical, evidence-based step for long-term brain protection.
How Do You Know If You’re Protected?
The easy answer is to test, not guess. That is why we offer our at-home pinprick blood tests as part of our research and prevention support.
Our DRIfT 5-in-1 test includes the omega-3 index, homocysteine, vitamin D, blood sugar control (HbA1c), and glutathione – together providing a powerful snapshot of your brain’s future resilience. This allows you to see whether you are eating enough oily fish, supplementing properly, or at greater risk of future disease.
The Bigger Picture Of Brain Health
This new study is another reminder that Alzheimer’s is not an inevitable part of ageing. It is largely preventable when we address the eight modifiable risk domains – from brain fats and B vitamins to diet, lifestyle, and gut health – which we cover in our COGNITION brain upgrade programme.
Women’s brain health has been historically under-researched, particularly in relation to hormones and cognitive ageing. Studies like this are a vital step towards closing that gap and ensuring prevention strategies work for everyone.
Learn more
Join Menopause and the Mind with Dr Ghazala Aziz – find out more here.
Are you supplementing correctly? Eating enough fish? The only way to know is to test – order your DRIfT 5-in-1 test today to discover what you need to do to protect your brain.
Complete the free, validated Cognitive Function Test today to receive personalised information on how you can protect your brain and your future.
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
Wretland A, et al. Lipid profiling shows reduced long-chain omega-3 lipids in individuals at risk for Alzheimer’s, especially women. Alzheimer’s Dement. 2024. PMID: 40832908.
Crawford MA, et al. The role of essential fatty acids and phospholipids in brain development and health. Prostaglandins Leukot Essent Fatty Acids. 2001;64(2):95-111.
Tan ZS, et al. Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging. Neurology. 2012;78(9):658-664.
Yassine HN, et al. Long-chain omega-3 fatty acids and brain health. Alzheimers Dement. 2016;12(7):759-768.
Morris MC, et al. Fish consumption and the risk of Alzheimer disease. Arch Neurol. 2003;60(7):940-946.
Smith AD, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment. Proc Natl Acad Sci U S A.
Jernerén F, et al. Homocysteine-lowering B-vitamin treatment modifies the effect of omega-3 fatty acids on brain atrophy in mild cognitive impairment. Am J Clin Nutr. 2015;102(1):215-221.
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.
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.
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.
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Food for the Brain is a not-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.
By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices. Please support our research by becoming a Friend of Food for the Brain.
References
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.
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).
The four horsemen of the mental health apocalypse
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).
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.
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
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.
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).
