Everyone knows that Alzheimer’s and cognitive decline are preventable IF you can find out who is at risk.
While those selling anti-amyloid or p’tau drugs will exaggerate the importance of blood testing for amyloid or p’tau, which are damaged proteins found in the brains of people with Alzheimer’s, so far lowering these markers hasn’t worked. In other words, they are a marker, but not a cause.
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So, what is a biomarker that predicts risk?
And therefore what biomarkers, if corrected, reduce risk?
To date, there are four:
Homocysteine, a toxic amino acid, which goes up when your intake of B vitamins (B6, B12, folate, as well as zinc) is low. If you then lower homocysteine with B vitamins, it stops the brain shrinkage associated with Alzheimer’s and improves cognitive function. Brain shrinkage stops below 10 mcmol/l, and that’s what you’re aiming for. So that’s both ‘biomarker’ and ‘causal’ ticked.
At Food for the Brain, we are offering the first accurate at home, pinprick test for homocysteine that is both painless and accurate.
Omega-3 index is another. This is the % of your red blood cell membranes that are omega-3 EPA and DHA. The higher your % (ideally above 8) the better your cognition. Low levels also predict risk. So that’s also two boxes ticked.
Vitamin D is another. Low levels predict risk and supplementing it reduces risk. Again, two boxes ticked but we don’t really know how it does this.
Combining these three to make a ‘nutritional index’ shows that the better you score, the lower a person’s future risk of dementia is.
HBA1c is another. This is a measure of your blood sugar resilience. It measures the spikes in your blood sugar that then damage red blood cells. Below 5.4% (or 37 mmol/mol) is the idea.
We divide your scores across four levels – worst is RED, then ORANGE, then YELLOW, then GREEN, which is what you’re shooting for.
That’s what our DRIfT test measures – all four as a Dementia Risk Index functional Test.
This chart shows you why these four measures are so essential.
What about antioxidants?
But you might have noticed there’s no ‘antioxidant’ measure.
Well, actually there is. It’s the body’s most important antioxidant called glutathione. Think of it like the body’s fire department with glutathione being the water. Every time there’s an oxidant fire, glutathione rushes in to put the fire out. The water, then, turns into steam. Glutathione is called GSH. It’s not bad as a measure of ‘antioxidant potential’. That’s why most functional medicine doctors measure red blood cell glutathione. But what if it all gets used up? It becomes oxidised or spent, much like the water putting out a fire turns into steam. This is called oxidised glutathione or GSSG. Think of the fully loaded glutathione (GSH) as cold water. It’s going to protect you much better from inflammation than spent (oxidised) glutathione (GSSH), a highl level of which means you’ve been trying to put out a lot of inflammatory fires in your brain and body. Neuro-inflammation is a key driver of brain degeneration and dementia, as well as ageing in general, which is why this is important to know.
We’ve been researching the ratio that is your GSH/GSSG. If you’ve got lots of fully loaded glutathione, and very little oxidised/spent glutathione, your GSH/GSSG ratio or index is high. That’s good news. If you’ve got very little fully loaded glutathione and lots of oxidised glutathione then you’re ‘oxidising’ – which is an aspect of ageing that we want to prevent.
We want to be able to research this and test your Glutathione Index. This is exactly what we are working on right now with the hope of releasing another ‘world first’ home test kit for your Glutathione Index soon. This kind of research is funded by you, as a Friend of Food for the Brain.
An example would be a person who smokes a lot, lives in a polluted environment, eats no fresh veg, berries, herbs and spices. Their Glutathione Index will be low and their body and brain will likely be ageing faster. If you did smoke but also ate well and took vitamin C daily, (they say you need 50mg of vitamin C for each cigarette) would that mitigate the effect?
Would you join our research, support our charitable work and upgrade your own brain by ordering one of our DRIftT tests?
If you’ve also done the Cognitive Function Test and Dementia Risk Index questionnaire (which we strongly recommend) that’s even better because we can see how you score in the ANTIOXIDANT domain and in future, how that will correlate with your Glutathione Index (which is coming soon).
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Thank you for reading!
Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.
By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices. Please support our research by becoming a Friend of Food for the Brain.
This is the headline from the New York Times exposing a proposal from an ‘Alzheimer’s Working Group’ that we should all have an amyloid blood test to then be prescribed anti-amyloid drugs. This is a similar strategy to statins which are given to anyone with ‘high cholesterol’ despite no evidence of heart disease and limited benefit from taking the statins, except in the drug companies own trials. Their representatives also reduced the ‘acceptable’ blood test level in a process known as ‘diagnostic creep’.
The working group, many of whose members, say the NYT, are ‘employed by companies developing drugs and diagnostics’ is chaired by Dr Clifford R. Jack Jr., an Alzheimer’s researcher at the Mayo Clinic. “Someone who has biomarker evidence of amyloid in the brain has the disease, whether they’re symptomatic or not,” said Dr Jack. “The pathology exists for years before symptom onset,” he added. “That’s the science. It’s irrefutable.”
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But wait…
Let’s back up here a minute.
Amyloid has never been proven to be a cause of Alzheimer’s.
In fact, the repeated failure of anti-amyloid drugs that do successfully lower amyloid to deliver any meaningful clinical effect has proven, time and time again, that raised amyloid is not the cause of Alzheimer’s. It is, I believe, an effect, an artefact. Not all who develop Alzheimer’s have raised amyloid but most do. But the fact that it is present doesn’t mean removing it with anti-amyloid drugs will ‘cure’ the disease. The real pathology of Alzheimer’s is both a reduction in cognitive function and brain shrinkage.
The last drug trial reported that those on the drugs had 20% more brain shrinkage than those on the placebo. In other words the pathology got worse, not better. We reported this because it was in the published research paper but no newspaper coverage mentioned it. (Perhaps journalists only read the press release, not the study itself). This was finally reported in the Telegraph two weeks ago: ‘‘Breakthrough’ Alzheimer’s drugs can shrink the brain, scientists warn’.
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The risk-to-benefit ratio is terrible
According to Dutch researchers, 10 percent of cognitively normal 50 year-olds would test amyloid positive, as would almost 16 percent of 60-year-olds and 23 percent of 70-year-olds. Most of those individuals would never develop dementia. But, if this scenario were to roll out, they would be prescribed the anti-amyloid drug treatment at an estimated £40,000 a year. Given that there were seven deaths of participants in the last two anti-amyloid drug trials, reported by ourselves and the Telegraph, and over a third of patients got potentially fatal brain bleeding or swelling, that’s a hell of a downside for something that isn’t likely to deliver any benefit.
“Anti-amyloid trials raise scientific and ethical questions.” Writes Professor David Smith in the British Medical Journal (1). “Ackley and colleagues found that lowering brain β-amyloid levels in Alzheimer’s disease had no significant effect on cognition in 14 clinical trials on a total of 4,596 patients. Is it justifiable to ask patients to undergo yet more trials of anti-amyloid treatments? Moreover, we should all question the morality of the drug companies that declined to give these researchers access to data for 20 of the 34 trials they wanted to study.”.
“These findings” he says “should direct our attention to the prevention of Alzheimer’s disease by slowing down the disease process, for which there are many possible approaches.”
Professor David Smith is one of the many scientific advisors instrumental in shaping our prevention policy which goes like this:
Test actual cognitive function, which is known to show changes up to 40 years before a diagnosis. That’s the Cognitive Function Test which you can do here. As part of this assessment, you will complete a questionnaire covering all known risk factors. That’s the Dementia Risk Index which follows the Cognitive Function Test.
Then measure actual blood markers of things that predict risk – homocysteine, omega-3 index, HbA1c for sugar control, and vitamin D. That’s the DRIfT test, available here.
Then advise the individual on how to reduce their risk by targeting the risk factors that they can change, which, in turn, bring down the biomarkers in the DRIfT test.
There are no downsides, only benefits, with this kind of prevention approach.
There is only one problem – prevention is not profitable.
Thank you for reading!
Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.
By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices. Please support our research by becoming a Friend of Food for the Brain.
On April 24th we are gathering experts from around the world to present at our Upgrade Your Brain Conference to explore solutions for the escalating incidence of mental health problems, described as a ‘global brain health emergency’ by the European Federation of Neuroscience Societies.
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In the last three years, The Children’s Society report that the likelihood of a young person having a mental health issue has increased by 50 per cent.
One in six children aged 5-16 are now likely to have a mental health problem.
Antidepressant prescriptions are close to 100 million in the last year representing a 70% increase in the past five years.
Mental illness is now costing health services more than cancer and heart disease.
So we have joined forces with the Nutrition Collective to bring together some world-class experts so that we all learn how to protect and upgrade our brains.
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The Experts
Professor Michael Crawford from Imperial College’s Institute of Brain Chemistry and Human Nutrition, who discovered the essentiality of omega-3 DHA for brain function;
Professor Bill Harris, leading US omega-3 researcher;
Sugar expert, Professor Robert Lustig;
Neurologist Dr David Perlmutter;
Neuroscientist Assistant Professor Tommy Wood from the University of Washington, expert in active lifestyle;
Metabolic psychiatrist Dr Georgia Ede, whose speciality is low-carb keto diets;
Professor Julia Rucklidge on children’s mental health and nutrition;
Dr Sabine Donnai, presenting on fixing a leaky blood-brain barrier for dementia prevention;
Harvard psychiatrist Uma Naidoo on the mood food connection;
Dr Victoria Sampson on the oral and gut microbiome and brain connection.
This virtual conference focuses both on the latest science and solutions, and is focused on giving practitioners practical advice from leading clinicians.
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The Mission
Our mission at Food for the Brain is to stem the rising tide of mental illness in children and adults.
The growth in mental illness is not sustainable.
In some poorer areas one in two women are now on antidepressants.
Close to a million in the UK have dementia.
On the current trend, by 2080, one in three children will have severe neurodevelopment impairment with major functional and communication deficits.
These children are our future.
It is literally our humanity that is at stake.
We need a united and progressive understanding of what’s driving this brain drain to enable the right solutions.
We need governments to wake up to the reality of this cerebral tsunami otherwise we are heading for an idiocracy.
All healthcare practitioners, and anyone in mental health and education, need to be there.
Further information:
The Nutrition Collective:The ground-breaking educational platform for Healthcare Professionals. The Nutrition Collective is a leading educational community for Healthcare Professionals bringing a wealth of knowledge and the latest research on a broad range of healthcare and wellbeing topics, including brain and mental health. We offer cutting-edge education to professionals in the form of webinars, seminars, in-person and virtual conferences and events, led by world class experts. Healing chronic disease with insights from the leaders in nutrition.
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.
Brain size is shrinking, IQ is falling, mental health problems are rising.
A recent EU report has declared a ‘global brain health emergency’.
One in six children are neurodivergent, many with autism or ADHD.
While one in four over 80 have pre-dementia – memory decline is happening for many in their 30’s.
One in four adults are on anti-depressants, sleeping pills or tranquillisers.
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What is going wrong and how do we recover?
After 45 years of research Patrick Holford, our founder and CEO, has the answers and has written them all down in his brand new book Upgrade Your Brain!
This book, coming out on April 25th 2024, will be your guide on how to reclaim your brain. This coincides with our national Upgrade Your Brain campaign, where we will not only focus on Alzheimer’s prevention but also on supporting wider brain and mental issues.
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No matter your age or stage you CAN upgrade your brain and we are here to help you.
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In the book you will learn how to :
Improve your mood and get a good night’s sleep
Deprogram anxiety and build stress resilience
Free your brain from addiction (including sugar, alcohol and coffee)
Recover your memory and rebuild the brain’s connections
Build healthy young brains to prevent neurodivergence
You will be able to preorder the book soon but there is also a live seminar book tour where you can see Patrick live and receive a signed copy. There is also an Upgrade Your Brain Conference for health professionals who want to hear from world-class speakers like Dr David Perlmutter, Professors Robert Lustig, Michael Crawford, William Harris and Tommy Wood, who heads our research team – and more.
The book will be available for preorder soon.
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Thank you for reading!
Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.
By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices. Please support our research by becoming a Friend of Food for the Brain.
This week CNN ran a story about a dementia prevention clinic in the US, run by neurologist Professor Richard Isaacson, who used our Cognitive Function Test in his prevention study at Cornell University.
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The basic concept, much like what Food for the Brain is doing online, is that people get screened with blood tests, complete a cognitive function test and are assessed for diet and lifestyle factors that increase future risk. The article highlights nutrition, insulin resistance, genetic, behavioural and lifestyle risk factors along with the ability to track your progress with new ‘experimental blood tests’.
What’s the difference between this and what Food for the Brain is offering?
This screening would set you back at least $2000 compared to Food for the Brain’s, with the DRIfT blood test, costing closer to £200.
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Brain Blood Tests that Predict Risk
In Alzheimer’s there are increases in Amyloid and p-tau. That’s not in dispute. Despite all the hype, the anti-amyloid drugs such as Lecanemab, featured in last week’s Panorama programme, have produced what is widely regarded as a clinically insignificant benefit with very high risk of adverse effects, including a small risk of death. Five people died as a consequence of the drug treatment in the last two trials, which is approximately one in 500. The British Medical Journal editorial concluded ‘No clinically meaningful effect. 30% get brain bleeding or swelling. Two trial deaths under investigation.’
The ‘just’ statistically significant benefit, which got the drug its licence, was several times less than that reported in a comparative trial of omega-3 in those with low homocysteine (sufficient B vitamins) and the rate of brain shrinkage actually increased by 20% compared to a 73% reduction in a trial of homocysteine lowering B vitamins in those with sufficient omega-3 DHA in their blood (read more about that here.)
So, yes, test amyloid but no – there is not sufficient evidence that lowering it with anti-amyloid drugs is going to realistically make much difference.
The trouble with the anti-amyloid monthly injection (which costs circa £20,000 a year) is that each injection will need to be followed by an expensive brain scan precisely because of the risk of brain bleeding and swelling, experienced by a third in trials. That’s also why theBBC reported that Alzheimer’s Research UK has warned that the NHS is ‘not ready’ for new Alzheimer’s drugs Lecanemab and Donanemab. It’s not prepared for such a treatment rollout due to the benefit it delivers versus the cost of on going assessment. Together with the medical costs it will probably cost closer to £50,000 per year per person.
While in contrast, £50,000 would fund 1,000 people follow our COGNITION programme for a year.
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All eyes on p-tau lowering drugs…
With the failure of the amyloid hypothesis, all eyes are on p-tau lowering drugs.
Yet none have worked.
But, much like cholesterol for heart disease, the media messaging will be to test p-tau rather than prescribe a drug. The irony here is that a lack of B vitamins, or rather raised homocysteine (which you can test here), is well established to increase p-tau so the simplest way to stop the formation of p-tau, and neurofibrillary tangles, and keep your brain healthy, is to keep your plasma homocysteine level below 10mcmol/l. In addition, the fact that there is no solid evidence that lowering levels of p-tau or amyloid protein prevents dementia or slow down progression is why these are called ‘‘experimental blood tests” in the CNN coverage.
We have combined four tests (omega-3 index, vitamin D, HBA1c for sugar balance, homocysteine for B vitamins) that each have clear evidence that
a) good levels correlate with less risk b) bringing blood test levels into the optimal range reduces risk.
So we are ahead in that respect. This is the 4-in-1 DRIfT test which calculates a biological Dementia Risk Index.
We want you to take this test, not only for your benefit but also, when we have enough results of tests and retests, together with FREE Cognitive Function Test results we can research the correlation to find out how your DRIfT score predicts cognitive function.
Genetic Fears
The other issues raised are around genes that predict Alzheimer’s risk.
There’s quite some confusion here which, if misunderstood, creates unnecessary fear. ‘Causative’ genes (APP and Presenelin) are very rare – less than 1 in 100. The Panorama programme included a younger person with this gene. Much more common is having the ApoE4 gene, which one in seven people have. This doesn’t cause Alzheimer’s. Technically, it increases risk by 4 to 6% but all the changes we recommend to your diet mitigate even this increased risk. That is why, in studies where people ate better or took the right supplements, there was no difference in the outcome of the individuals with or without the ApoE4 gene variant.
The bottom line is that almost no-one needs to develop dementia if they follow ‘optimum nutrition’ advice – diet, supplements and lifestyle and that is what we are here to do.
Food for the Brain is making prevention a reality.
Join us in our mission, research and reclaim your brain this year. The first things you want to do are:
Complete the FREE Cognitive Function Test. This is an online, validated assessment of your current cognitive function and your dementia risk. Over 400k have completed this test and upgraded their brain in the process.
Order your DRIfT test. These accurate, at-home blood tests are the perfect way to improve your brain health and reduce your risk.
Thank you for reading!
Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.
By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices. Please support our research by becoming a Friend of Food for the Brain.
Are You Wasting Money On Your Omega-3 Supplements?
Are You Wasting Money On Your Omega-3 Supplements?
Omega-3 supplements are becoming increasingly popular – and rightly so – as another recent UK BioBank study (1) reported a 30% lower risk of dementia in those with higher omega-3 status in their blood.
Another study (2) found a 49% reduced risk for dementia in those with the highest omega-3 DHA level (top fifth) in their red blood cells compared with those having the lowest (bottom fifth).
Oily fish and fish oil supplements contain two types of omega-3 fat, called DHA and EPA. DHA is the main fat found in the brain cells of all animals. What’s more, your omega-3 index predicts both your brain size and cognitive abilities, according to this study (3) from Loma Linda University (featured in the Blue Zones film), so you might want to check that you’re above 8%.
The Benefits Go Beyond Preventing Dementia.
A person’s omega-3 index, which is a composite score of both EPA and DHA bound into red blood cell membranes, predicts both the risk of depression (4) and poorer reading ability, lower IQ, worse memory, sleep difficulties as well as aggression and emotional instability in children – hallmarks of ADHD (5).
It also predicts the risk of heart disease (6) and developmental problems in babies, based on measures taken in women both before and during pregnancy. Pregnant women with a higher omega-3 index have a much lower likelihood of having a baby with developmental problems, according to research from Imperial College London Institute of Brain Chemistry at the Chelsea & Westminster Hospital campus.
The Missing Piece…
However, omega-3s do not act alone. To become biologically active, DHA must be attached to phospholipids – a process entirely dependent on methylation. This, in turn, requires adequate levels of B vitamins: B6, folate, and B12.
A landmark study (7) concluded that the combination of B vitamins and fatty acids improves cognitive function. This is because, during methylation, DHA attaches to a phospholipid, enabling it to be incorporated into the neuronal membrane of the brain. The process of methylation is entirely dependent on vitamins B6, B12, and folate. When omega-3 and B vitamin status are both sufficient, the brain can build new, functional neuronal membranes – literally the structural basis of thought.
So, you need both a high omega-3 status (over 8%) and adequate B vitamins to incorporate DHA into the brain. You can be confident that methylation is working properly if your homocysteine level is below 11 µmol/L. In a large omega-3 study, people with early-stage dementia were given 2.3 grams a day (equivalent to two large fish oil capsules), but only those with lower homocysteine levels benefited (7).
Having a raised homocysteine level, above 11mcmol/L, is extremely common. In the US around 40% of people over the age of 60 have elevated levels. This is often due to poor absorption of vitamin B12 and may require high-dose supplementation to normalise homocysteine. (Read more about homocysteine here.)
Why Testing is Essential
This means two things are critical for protecting your brain:
A high omega-3 index – ideally over 8%.
A low homocysteine level – ideally below 11µmol/L, with the optimal level being around 7 µmol/L
If either is lacking, the protective effect is lost. Taking fish oils without ensuring good B vitamin status will not deliver full benefit – and vice versa.
That is why testing both is essential for protecting your brain.
To make this simple, Food for the Brain has launched the DRIFt 5-in-1 home test – a quick pinprick blood test you can do yourself. It measures:
Omega-3 Index – how much brain-building DHA and EPA are in your cells
Homocysteine – the key methylation marker, linked to brain shrinkage
Vitamin D – vital for brain health, mood, and immunity
HbA1c – the gold-standard measure of blood sugar balance
Omega-6:3 Ratio – shows whether you’re getting the right fats for your brain
Together, these five markers account for more than half of the modifiable risk for Alzheimer’s disease and dementia.
By testing these markers, you will know exactly what to supplement and what to change in order to protect your brain. And by joining the DRIFt study, you will also become a Citizen Scientist, helping to advance dementia prevention research worldwide.
Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.
By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices. Please support our research by becoming a Friend of Food for the Brain.
References
1 Sala-Vila, A.; Tintle, N.; Westra, J.; Harris, W.S. Plasma Omega-3 Fatty Acids and Risk for Incident Dementia in the UK Biobank Study: A Closer Look. Nutrients 2023, 15,4896. https://doi.org/10.3390/ nu15234896
2 Sala-Vila, A.; Satizabal, C.L.; Tintle, N.; Melo van Lent, D.; Vasan, R.S.; Beiser, A.S.; Seshadri, S.; Harris, W.S. Red Blood Cell DHA Is Inversely Associated with Risk of Incident Alzheimer’s Disease and All-Cause Dementia: Framingham Offspring Study. Nutrients 2022, 14, 2408. https://doi.org/10.3390/ nu14122408
4 Yonezawa K, Kusumoto Y, Kanchi N, Kinoshita H, Kanegae S, Yamaguchi N, Ozawa H. Recent trends in mental illness and omega-3 fatty acids. J Neural Transm (Vienna). 2020 Nov;127(11):1491-1499. doi: 10.1007/s00702-020-02212-z. Epub 2020 May 25. PMID: 32451632.
5 Montgomery P, Burton JR, Sewell RP, Spreckelsen TF, Richardson AJ. Low blood long chain omega-3 fatty acids in UK children are associated with poor cognitive performance and behavior: a cross-sectional analysis from the DOLAB study. PLoS One. 2013 Jun 24;8(6):e66697. doi: 10.1371/journal.pone.0066697. Erratum in: PLoS One. 2013;8(9).doi:10.1371/annotation/26c6b13f-b83a-4a3f-978a-c09d8ccf1ae2. PMID: 23826114; PMCID: PMC3691187; see also Raine A, Ang RP, Choy O, Hibbeln JR, Ho RM, Lim CG, Lim-Ashworth NSJ, Ling S, Liu JCJ, Ooi YP, Tan YR, Fung DSS. Omega-3 (ω-3) and social skills interventions for reactive aggression and childhood externalizing behavior problems: a randomized, stratified, double-blind, placebo-controlled, factorial trial. Psychol Med. 2019 Jan;49(2):335-344. Doi 10.1007/s11920-018-0894-y. PMID: 29623453. ; see also Liu, J., Cui, Y., Li, L. et al. The mediating role of sleep in the fish consumption – cognitive functioning relationship: a cohort study. Sci Rep 7, 17961 (2017). https://doi.org/10.1038/s41598-017-17520-w
6 Gutierrez L, Folch A, Rojas M, Cantero JL, Atienza M, Folch J, Camins A, Ruiz A, Papandreou C, Bulló M. Effects of Nutrition on Cognitive Function in Adults with or without Cognitive Impairment: A Systematic Review of Randomized Controlled Clinical Trials. Nutrients. 2021 Oct 22;13(11):3728. doi: 10.3390/nu13113728. PMID: 34835984; PMCID: PMC8621754.
7 Jernerén F, Cederholm T, Refsum H, Smith AD, Turner C, Palmblad J, Eriksdotter M, Hjorth E, Faxen-Irving G, Wahlund LO, Schultzberg M, Basun H, Freund-Levi Y. Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer’s Disease: The OmegAD Study. J Alzheimers Dis. 2019;69(1):189-197. doi: 10.3233/JAD-181148. PMID: 30958356.
Alzheimer’s is a preventable, but not reversible disease.
Less than one in a hundred cases are directly caused by genes. Prevention is entirely possible if you can identify who is at risk early enough and encourage the right diet and lifestyle changes.
This is why we have designed our new pinprick blood test which not only aims to predict your future risk for dementia but tells you how to reduce it. We now have a limited number available on pre-order as part of a global prevention research study aiming to involve a million people worldwide.
This much-awaited home-test kit measures your blood sugar, vitamin D, omega-3 and B vitamin status which account for more than half the modifiable risk for dementia. The results show how a person can reduce their risk with specific diet changes.
“By tracking a person’s blood sugar, vitamin B, D and omega-3 status against changes in cognitive function over time, in addition to lifestyle factors such as sleep and physical activity, we can learn what really helps prevent cognitive decline.” says Dr Wood, Assistant Professor at the University of Washington and the principal investigator for the prevention project.
We have already tested over 410,000 people with our free Cognitive Function Test, and hope to enrol a million people, to make this the largest Citizen Science global prevention initiative.
Subtle changes in cognition occur at least 30 years before a diagnosis, which is why we screen people online with a free Cognitive Function Test. And four simple blood tests are not only predictive but can help a person to understand how to drive down that risk. We call them the four horsemen of the mental health apocalypse because they also drive depression and ADHD. The incidence of both of these are on the increase.
(Read more about the four horsemen of the mental health apocalypse here and here).
The four tests, called DRIfT (the Dementia Risk Index functional Test) is carried out using a simple home-test kit and a single pinprick of blood, adding further predictive capability, and helping guide the individual to make diet changes to reduce future risk.
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Why these four markers?
Blood sugar (HbA1c) – Even raised blood sugar levels from age 35, but within ‘reference’ ranges, predict a 15 per cent increased risk of Alzheimer’s disease 35 years later, according to research by Boston University School of Medicine (1). This confirms other research from the University of Washington showing an 18% increased risk with raised sugar levels in older people seven years later and a 40% increased risk in those with diabetes (2). Even better than your blood sugar level, which varies across the day, is a long-term measure of blood sugar, called HbA1c, used to predict diabetes, which is what this test measures.
B vitamins (Homocysteine) – Low levels of B12, found in animal products, and folate, found in greens, raise blood levels of homocysteine. Raised homocysteine is considered a top marker for dementia risk, and is a causative driver of the disease process (3). Studies lowering homocysteine with B vitamins have more than halved the rate of age-related brain shrinkage. A Swedish study, started in 1968, found that those in the top third of homocysteine scores in their 40’s had double the risk for Alzheimer’s almost 35 years later (4). When homocysteine goes up memory gets worse and when it goes down memory gets better, according to a six-year study in Norway (5).
About half of all people over 60 have homocysteine levels above 11mcmol/l (6), which is the level associated with increased brain shrinkage. A study in Italy found that those with a homocysteine above 15mcmol/l have five times the risk of developing Alzheimer’s, compared to those with a level below 10 (7).
Last year, a study in China showed that raised homocysteine increases risk of cognitive decline by ten times (8). Homocysteine is easily lowered by supplementing vitamin B6, B12 and folate but at levels higher than achievable from diet because many older people do not absorb B12 well.
Oxford University’s health economist Dr Apostolos Tsiachristas estimates “Screening for homocysteine in people over 60 in the UK and treating those with raised levels with B vitamins could save the UK economy approximately £60 million per year.”
Omega-3 – Increased intake of omega-3, either from diet or supplements and having a higher omega-3 blood level, is associated with cutting risk for dementia by a fifth (20%), according to a study of 48 studies involving over 100,000 people (9).
Supplementing fish oils (10) cuts risk of dementia by 9%, according to research from the UK Bio Bank. Being in the top third for omega-3 blood levels, compared to the lowest third, reduced the rate of brain shrinkage in a year by more than two-thirds in those given B vitamins with mild cognitive impairment (11).
The omega-3 index, which is what the DRIfT test measures, predicts both brain size and cognitive function (12). This Oxford University research establishes that the brain needs both sufficient B vitamins and omega-3 to stay healthy.
Vitamin D – Having a higher vitamin D above 75nmol/l (25 ng/ml) cuts risk for Alzheimer’s and dementia by a third (13). In turn, those with a vitamin D level below 50nmol/l, increase their risk for Alzheimer’s and dementia by a third (14).
Six out of 10 adults in the UK (15) and three out of 10 in the US (16) have a vitamin D level below this. Taking vitamin D supplements may help ward off dementia, according to a 2023 study involving over twelve thousand dementia-free 70+ year olds in the US. Those taking vitamin D supplements had 40% lower incidence of dementia during a ten-year period. Vitamin D is essential to supplement during winter months.
These four risk factors, measured in the DRIfT test, are thought to account for over half the modifiable risk for Alzheimer’s disease and dementia. Having an active lifestyle, both physically, socially and intellectually further reduces risk substantially.
Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.
By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices. Please support our research by becoming a Friend of Food for the Brain.
References
1 Zhang X, Tong T, Chang A, Ang TFA, Tao Q, Auerbach S, Devine S, Qiu WQ, Mez J, Massaro J, Lunetta KL, Au R, Farrer LA. Midlife lipid and glucose levels are associated with Alzheimer’s disease. Alzheimers Dement. 2023 Jan;19(1):181-193. doi: 10.1002/alz.12641. Epub 2022 Mar 23. PMID: 35319157; PMCID: PMC10078665.
2 P.K. Crane et al., ‘Glucose levels and risk of dementia’, New England Journal of Medicine (2013), vol 369(6):540–548.
3 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.
4 Zylberstein DE, Lissner L, Bjorkelund C, Mehlig K, Thelle DS, Gustafson D, Ostling S, Waern M, Guo X, Skoog I (2011) Midlife homocysteine and late-life dementia in women. A prospective population study. Neurobiol Aging 32, 380-386
5 Nurk E, Refsum H, Tell GS, Engedal K, Vollset SE, Ueland PM, Nygaard HA, Smith AD (2005) Plasma total homocysteine and memory in the elderly: The Hordaland Homocysteine study. Ann Neurol 58, 847-857.
6 Pfeiffer CM, Osterloh JD, Kennedy-Stephenson J, Picciano MF, Yetley EA, Rader JI, Johnson CL. Trends in circulating concentrations of total homocysteine among US adolescents and adults: findings from the 1991-1994 and 1999-2004 National Health and Nutrition Examination Surveys. Clin Chem. 2008 May;54(5):801-13. doi: 10.1373/clinchem.2007.100214. Epub 2008 Mar 28. PMID: 18375482.
7 Ravaglia G, Forti P, Maioli F, Martelli M, Servadei L, Brunetti N, Porcellini E, Licastro F (2005) Homocysteine and folate as risk factors for dementia and Alzheimer disease. Am J Clin Nutr 82, 636-643.
8 Teng Z, Feng J, Liu R, Ji Y, Xu J, Jiang X, Chen H, Dong Y, Meng N, Xiao Y, Xie X and Lv P (2022) Cerebral small vessel disease mediates the association between homocysteine and cognitive function. Front. Aging Neurosci. 14:868777. doi: 10.3389/fnagi.2022.868777
9 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 Perspective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers. Am J Clin Nutr. 2023 Apr 5:S0002-9165(23)46320-4. doi: 10.1016/j.ajcnut.2023.04.001. Epub ahead of print. PMID: 37028557.
10 Huang Y, Deng Y, Zhang P, Lin J, Guo D, Yang L, Liu D, Xu B, Huang C and Zhang H (2022) Associations of fish oil supplementation with incident dementia: Evidence from the UK Biobank cohort study.Front. Neurosci. 16:910977.doi: 10.3389/fnins.2022.910977
11 Jernerén F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H, Smith AD. Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. Am J Clin Nutr. 2015 Jul;102(1):215-21. doi: 10.3945/ajcn.114.103283. Epub 2015 Apr 15. PMID: 25877495.
14 Chai et al. BMC Neurology (2019) 19:284 https://doi.org/10.1186/s12883-019-1500-6
15 Calame W, Street L, Hulshof T. Vitamin D Serum Levels in the UK Population, including a Mathematical Approach to Evaluate the Impact of Vitamin D Fortified Ready-to-Eat Breakfast Cereals: Application of the NDNS Database. Nutrients. 2020 Jun 23;12(6):1868. doi: 10.3390/nu12061868. PMID: 32585847; PMCID: PMC7353432.
16 Liu X, Baylin A, Levy PD. Vitamin D deficiency and insufficiency among US adults: prevalence, predictors and clinical implications. Br J Nutr. 2018 Apr;119(8):928-936. doi: 10.1017/S0007114518000491. PMID: 29644951.
What is the forgotten factor of mental health – despite the research being positive?
Homocysteine.
This is why we launched our highly accurate and groundbreaking at-home homocysteine test just before Christmas (and quickly sold out) because knowing this marker – your H factor – can help predict over 100 diseases. Specifically, homocysteine is an indicator of a person’s B vitamin status, and knowing this, can help reduce the risk of mental illness.
Yet it hasn’t been easily available or affordable to test this at home and is often not a marker checked by Dr’s.
But not any more!
Homocysteine & the Central Nervous System
“Homocysteine is a biomarker for over 100 diseases, but especially those of the central nervous system.” says pharmacology professor David Smith FMedSci, formerly Deputy Head of the Faculty of Medical Sciences at the University of Oxford. “It is a biomarker of impaired cognitive abilities in children, and in adults is a risk marker for stroke, dementia and Alzheimer’s, but also possibly for depression, anxiety, bipolar, schizophrenia, obsessive-compulsive disorder, Parkinson’s and multiple sclerosis. It is very much the forgotten factor, despite the research evidence being strongly positive (1). And the good news is, it is so easily corrected.”
Patrick Holford, psychologist and our CEO and founder says “A raised homocysteine level means something is going wrong with a vital process that controls how we think, feel and perceive. It’s called methylation and is dependent on B vitamins. Some people absorb B12 less well. Some just need more of the B vitamin than others and that biochemical individuality, especially if their diet is already deficient, can tip them into a mental or neurological illness.”
Depression & Homocysteine
Those suffering from depression are also more likely to have higher homocysteine levels (2, 3). Amanda-Jane is a case in point. She was suffering with chronic fatigue and low mood, so she decided to check her homocysteine level. She was shocked when she found her score was 26 mcmol/l (7 or less is considered optimal). After changing her diet and supplementing the B vitamins her sleep improved almost immediately and within four weeks, she had much more energy. Two months later she re-tested her homocysteine level and found it had dropped to 9. “I feel much better. My mood is very positive– no panic or depression. I feel buoyant, energetic and enthusiastic. I’m sleeping much better and my PMS has disappeared.” she said.
Also, every 5-point increase in homocysteine increases risk of being diagnosed with schizophrenia by a staggering 70%! (4) Yet very few sufferers are ever checked for raised homocysteine.
Homocysteine & B Vitamins
Professor Joseph Levine from the Stanley Research Centre and Beersheva Mental Health Centre in the Ben Gurion University in Israel devised a study to see what effect lowering homocysteine with B vitamins would have (5). He gave half of a group of 42 schizophrenic patients B vitamins (B6, B12 and folic acid) and the other half a placebo. Those taking the B vitamin supplements had both a dramatic reduction in their homocysteine levels and a significant improvement in their symptoms, except for one patient, who didn’t comply with the B vitamin treatment, didn’t improve and didn’t have a reduction in their homocysteine level. They were the exception that proves the rule.
Professor David Smith, writing in the Journal of Internal Medicine, together with world leading expert on homocysteine, Professor Helga Refsum from the University of Oslo, Norway, say “There are five diseases that can, at least in part, be prevented by lowering total homocysteine: neural tube defects, impaired childhood cognition, macular degeneration, primary stroke, and cognitive impairment in the elderly. We conclude from our review that total homocysteine values in adults of 10 mcmol/L or below are probably safe, but that values of 11 above may justify intervention. Homocysteine is more than a disease biomarker: it is a guide for the prevention of disease.” Not only does it predict an increased risk for a stroke, but having a lower homocysteine level, achieved by eating B12 rich foods such as fish and eggs, and folate and B6 rich foods such as whole foods, vegetables, nuts, seeds and beans, and supplementing B vitamins, helps those who’ve had a stroke recover faster (6).
We recommend anyone with a homocysteine level over 10 mcmol/L to supplement extra B vitamins, especially B6 (20mg), folate (400mcg) and B12 (500mcg). Homocysteine is a toxic amino acid that accumulates when there is a lack of B vitamins and damages your brain as well as your arteries.
Professor Smith’s research group at Oxford University has shown that giving people with pre-dementia these vitamins reduced the rate of brain shrinkage to less than half of that in those given placebos.
“Further cognitive decline virtually stopped in those taking the B vitamins.” says Smith.
Homocysteine, Pregnancy & Children’s School Grades
As many as two in five people over 60 have a raised homocysteine level. The reason why the B vitamin folic acid is recommended in pregnancy is because it lowers homocysteine. In ‘normal’ pregnancies with no complications in either mother or child, homocysteine remains below 7mcmol/L. In five out of seven studies women who have spontaneous abortions or miscarriages have a level above 15. The risk for having a pre-term baby is four times higher in women with a homocysteine level above 12 (7). A study of 81 healthy women who then became pregnant found that the children of the women whose homocysteine before conceiving was above 9 were significantly more withdrawn, anxious and depressed and had more social problems including increased aggressive behaviour (8).
“It is vital that a woman intending to become pregnant first checks her homocysteine level. Raised homocysteine, plus a lack of omega-3 fats found in fish is a major promoter of developmental problems and mental illness in children later in life.” says Holford.
A child’s homocysteine level even predicts their school grades. A study compared the sum of school grades for ten core subjects, with homocysteine levels in a group of 692 Swedish school children aged 9 to 15. Increasing homocysteine levels were strongly associated with reducing grades as was inadequate folate intake (9).
Join us in our Citizen Science Project by testing your homocysteine! The home pin prick blood test is now back in stock.
Thank you for reading!
Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.
By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.
Please support our research by becoming a Friend of Food for the Brain.
References
1 Smith AD, Refsum H. Homocysteine – from disease biomarker to disease prevention. J Intern Med. 2021 Oct;290(4):826-854. doi: 10.1111/joim.13279. Epub 2021 Apr 6. PMID: 33660358.
2 Moradi F, Lotfi K, Armin M, Clark CCT, Askari G, Rouhani MH. The association between serum homocysteine and depression: a systematic review and meta- analysis of observational studies. Eur J Clin Invest 2021: e13486.
3 Nabi H, Bochud M, Glaus J, Lasserre AM, Waeber G, Vollenweider P, Preisig M. Association of serum homocysteine with major depressive disorder: results from a large population-based study. Psychoneuroendocrinology 2013; 38: 2309-18.
5 Levine J, Stahl Z, Sela BA, Ruderman V, Shumaico O, Babushkin I, Osher Y, Bersudsky Y, Belmaker RH. Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia. Biol Psychiatry. 2006 Aug 1;60(3):265-9. doi: 10.1016/j.biopsych.2005.10.009. Epub 2006 Jan 17. PMID: 16412989.
6 Yahn GB, Leoncio J, Jadavji NM. The role of dietary supplements that modulate one-carbon metabolism on stroke outcome. Curr Opin Clin Nutr Metab Care. 2021 Jul 1;24(4):303-307. doi: 10.1097/MCO.0000000000000743. PMID: 33631772; see also
7 Dai C, Fei Y, Li J, Shi Y, Yang X. A Novel Review of Homocysteine and Pregnancy Complications. Biomed Res Int. 2021 May 6;2021:6652231. doi: 10.1155/2021/6652231. PMID: 34036101; PMCID: PMC8121575.
8 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.
9 Torbjörn K. Nilsson, Agneta Yngve, Anna K. Böttiger, Anita Hurtig-Wennlöf, Michael Sjöström; High Folate Intake Is Related to Better Academic Achievement in Swedish Adolescents. Pediatrics August 2011; 128 (2): e358–e365. 10.1542/peds.2010-1481
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).
Boosting GABA: Natural Support for Anxiety and Low Mood This Winter
By Patrick Holford
Boost gaba naturally this winter. For many people, the darker months are when anxiety creeps up and mood dips. Shorter days, colder weather and more indoor time often leave the nervous system running on empty. Yet winter does not have to feel this way. Once you understand what is happening in your brain, you can support it with simple, effective tools that help you stay calm, steady and more resilient.
Why alcohol and cannabis feel calming: the GABA effect
How these substances create short term calm
When anxiety builds, many people instinctively reach for something to take the edge off. In one ordinary week in the UK, around 10 million tranquilliser pills are taken, 10 million cannabis joints are smoked and 120 million alcoholic drinks are consumed.
These substances all act on the same calming messenger in the brain: GABA, short for gamma aminobutyric acid. GABA is your neurological dimmer switch. It helps turn down adrenaline, settles the nervous system and makes you feel relaxed and more sociable. A drink or a joint can temporarily boost GABA and give you that familiar sense of relief.
Why the calming effect backfires
The problem comes shortly afterwards. GABA rises, then dips. Once levels fall, irritability, low mood and cravings follow, pushing people towards another drink or smoke. Alcohol also disrupts dreaming sleep which is essential for mental rejuvenation. The result is that you wake tired, flat and anxious with GABA still suppressed and the body working hard to detoxify last night’s alcohol.
Over time, alcohol raises anxiety rather than reducing it. Cannabis, used habitually, tends to lower drive and motivation while offering the same short-lived GABA response.
The good news is that you can support your GABA system in ways that build resilience rather than deplete it.
Natural ways to boost GABA and restore calm
GABA and taurine supplements
GABA is both a neurotransmitter and an amino acid. Supplementing it can help support healthy GABA activity in the brain, offering a gentle, natural way to unwind. In the UK it is regulated as a medicine so you cannot purchase it, though it remains easily available online in other countries. Several natural calming formulas include taurine and glutamine which help the body boost GABA production.
If using GABA directly, most people benefit from 250 to 500 mg once or twice a day. It is not addictive. Higher doses can cause nausea, vomiting or a rise in blood pressure, especially above 3 g a day. Taken in the evening it can also support sleep.
Taurine is structurally and functionally similar to GABA and helps settle the stress response. Despite its inclusion in energy drinks, taurine is not a stimulant. Research shows taurine supplementation slows key markers of ageing (2). It is richest in animal foods, so vegetarians may be more prone to low levels. A typical supportive dose is 500 to 1,000 mg twice daily.
B vitamins and vitamin C for steadier mood
Several B vitamins, especially vitamin B6, are tightly linked to how efficiently your body produces GABA. A recent trial found that 100 mg of B6 reduced self-reported anxiety (3). A large-scale study found women with higher vitamin B6 intake had lower depression and anxiety risk (4). Combined B vitamins also correlate with lower levels of both stress and mood disorders (5).
B6 is part of the same biochemical pathway that keeps homocysteine in check. When homocysteine rises, methylation slows and the brain becomes more vulnerable to low mood and anxiety. Keeping this pathway supported can make a meaningful difference. If you are curious about your levels, homocysteine is included in the DRIfT test.
Another review concluded that B6, magnesium and essential fatty acids can reduce anxiety and blood pressure responses to stress, particularly in women (6).
Vitamin C also plays an important role in stress resilience. It sits alongside cortisol in the adrenal cortex and rises in the bloodstream during stress. Since humans, unlike most animals, do not produce vitamin C internally, low intake can heighten vulnerability to stress. Several trials show vitamin C supplementation reduces anxiety and boosts mental vitality (7, 8). Earlier work from the 1970s showed that intakes above 400 mg reduced fatigue (9).
Calming herbs: valerian, hops and passionflower
Valerian (Valeriana officinalis) is a well-established natural relaxant used for restlessness, nervousness and insomnia. It enhances GABA receptor activity and can help boost GABA in a gentle way that supports deeper relaxation. Typical amounts are 50 to 100 mg twice daily, with double that amount before bed if sleeplessness is an issue. Valerian should not be combined with sedative medication or alcohol and not taken without medical guidance.
Hops (Humulus lupulus) has been used historically for sleep and nervous tension. It acts directly on the central nervous system and is most effective when combined with valerian or passionflower.
Passionflower (Passiflora incarnata) offers gentle calming support, promotes sleep and has no known side effects at normal doses. Around 100 to 200 mg a day is typical. It is also thought to be useful for children who struggle to settle. For those who want to avoid excessive drowsiness, hops and passionflower used without valerian may be preferable.
Magnesium to relax body and mind and to help boost GABA pathways
Magnesium supports muscle relaxation, nerve function and mood. Diets high in sugar, refined foods, calcium rich dairy, caffeine and alcohol may lead to depleted magnesium status. Too much calcium relative to magnesium can contribute to muscle tension, nervousness, insomnia and irregular heartbeat.
Magnesium also helps stabilise blood sugar and works alongside B6 and zinc in stress regulation. Several trials show that magnesium, especially combined with B6, reduces anxiety and depression within weeks (10, 11).
Most people would benefit from around 300 mg from supplements, alongside a diet rich in vegetables, nuts, seeds and whole foods. Seeds, nuts, beans and leafy greens provide very good levels.
Theanine: why tea feels calming
Tea delivers caffeine but never feels as jittery as coffee. That is because tea naturally contains L-theanine, an amino acid that increases alpha wave activity associated with relaxed alertness (13). Around 50 mg can noticeably shift the nervous system into a calmer state. Supplements that combine theanine with GABA can can boost gaba effects even further (14).
Balance blood sugar to reduce anxiety physiology
Alongside supporting neurotransmitters like GABA, keeping blood sugar steady is one of the simplest ways to reduce anxiety. When glucose drops, the body releases adrenaline and cortisol to raise it again, which can create sudden waves of anxiety, shakiness and irritability. Research shows that unstable glucose control increases stress reactivity and mood volatility, while balanced meals with protein, fibre and lower GL carbohydrates help stabilise both blood sugar and mood (15). This is particularly relevant in winter, when comfort eating, irregular routines and higher sugar intake are more common.
Support omega 3 levels for calmer mood and boost GABA function
Another key factor underpinning calmness is omega-3 status. EPA and DHA play an essential role in how flexible and responsive brain cell membranes are, which directly affects how well GABA and serotonin receptors function. Keeping omega three levels optimal helps the brain boost GABA signalling more effectively.
Several clinical studies show omega-3 supplementation can lower symptoms of anxiety and improve overall mood stability, especially in those with low baseline levels (16). Since omega-3 cannot be produced in meaningful amounts by the body, keeping levels optimal makes a measurable difference to stress resilience.
Winter is also the time when vitamin D levels typically fall, and low vitamin D has repeatedly been linked with lower mood, poorer stress tolerance and greater anxiety. A large meta analysis found that adults with low vitamin D were significantly more likely to experience depression, and supplementation helped improve mood in those who were deficient (17). Vitamin D also influences serotonin production and inflammation, two pathways that strongly affect how the brain responds to stress. Checking levels during winter and supplementing if needed is a simple step with meaningful impact.
A notes on panic attacks, lactic acid and the breath
Panic attacks can be terrifying, with palpitations, rapid breathing and a sense of impending doom. While psychological factors play a role, there can be a biochemical layer too. High levels of lactic acid can drive symptoms. When breathing becomes fast and shallow, carbon dioxide drops and lactic acid rises, which can quickly trigger an anxiety surge.
Breathing slowly into a paper bag or through cupped hands can help restore balance by raising carbon dioxide and reducing lactic acid. Keeping blood sugar stable by eating regularly also helps prevent abrupt dips that can trigger hyperventilation.
A systems based approach to boost GABA and reduce anxiety
Anxiety rarely comes from one place. Biology, psychology, sleep, nutrients, hormones, blood sugar and daily habits all interact, which is why a systems based approach often works best. Supporting several of these pathways at once helps the nervous system become steadier and more resilient, especially in winter when stress loads tend to rise. When you strengthen blood sugar balance, reduce stimulants, restore nutrient status, improve sleep and use targeted herbs, you naturally boost GABA and shift the whole stress response.
Explore the DRIfT test to join our research and check key nutritional and metabolic markers linked to mood and cognitive health.
Food for the Brain is a non-for-profit educational and research charity that offers a freeCognitive Function Testand assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.
By completing theCognitive Function Testyou 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.
3 Field DT, Cracknell RO, Eastwood JR, Scarfe P, Williams CM, Zheng Y, Tavassoli T. High-dose Vitamin B6 supplementation reduces anxiety and strengthens visual surround suppression. Hum Psychopharmacol. 2022 Nov;37(6):e2852. doi: 10.1002/hup.2852. Epub 2022 Jul 19. PMID: 35851507; PMCID: PMC9787829.
4 Kafeshani M, Feizi A, Esmaillzadeh A, Keshteli AH, Afshar H, Roohafza H, Adibi P. Higher vitamin B6 intake is associated with lower depression and anxiety risk in women but not in men: A large cross-sectional study. Int J Vitam Nutr Res. 2020 Oct;90(5-6):484-492. doi: 10.1024/0300-9831/a000589. Epub 2019 Jun 11. PMID: 31188081.
5 Mahdavifar B, Hosseinzadeh M, Salehi-Abargouei A, Mirzaei M, Vafa M. Dietary intake of B vitamins and their association with depression, anxiety, and stress symptoms: A cross-sectional, population-based survey. J Affect Disord. 2021 Jun 1;288:92-98. doi: 10.1016/j.jad.2021.03.055. Epub 2021 Mar 26. PMID: 33848753.
6 McCabe D, Lisy K, Lockwood C, Colbeck M. The impact of essential fatty acid, B vitamins, vitamin C, magnesium and zinc supplementation on stress levels in women: a systematic review. JBI Database System Rev Implement Rep. 2017 Feb;15(2):402-453. doi: 10.11124/JBISRIR-2016-002965. PMID: 28178022.
7 de Oliveira IJ, de Souza VV, Motta V, Da-Silva SL. Effects of Oral Vitamin C Supplementation on Anxiety in Students: A Double-Blind, Randomized, Placebo-Controlled Trial. Pak J Biol Sci. 2015 Jan;18(1):11-8. doi: 10.3923/pjbs.2015.11.18. PMID: 26353411.
8 Sim M, Hong S, Jung S, Kim JS, Goo YT, Chun WY, Shin DM. Vitamin C supplementation promotes mental vitality in healthy young adults: results from a cross-sectional analysis and a randomized, double-blind, placebo-controlled trial. Eur J Nutr. 2022 Feb;61(1):447-459. doi: 10.1007/s00394-021-02656-3. Epub 2021 Sep 2. PMID: 34476568; PMCID: PMC8783887.
9 E. Cheraskin et al., ‘Daily vitamin consumption and fatigability’, Journal of the American Geriatrics Society (1976), vol 24(3), pp. 136–137.
10 Noah L, Dye L, Bois De Fer B, Mazur A, Pickering G, Pouteau E. Effect of magnesium and vitamin B6 supplementation on mental health and quality of life in stressed healthy adults: Post-hoc analysis of a randomised controlled trial. Stress Health. 2021 Dec;37(5):1000-1009. doi: 10.1002/smi.3051. Epub 2021 May 6. PMID: 33864354; PMCID: PMC9292249.
11 Tarleton EK, Littenberg B, MacLean CD, Kennedy AG, Daley C. Role of magnesium supplementation in the treatment of depression: A randomized clinical trial. PLoS One. 2017 Jun 27;12(6):e0180067. doi: 10.1371/journal.pone.0180067. PMID: 28654669; PMCID: PMC5487054.
12 Hindmarch I et al, Psychopharmacology, 1998; see also Hindmarch I et al, Psychopharmacology, 2000
13 Nobre AC et al., a report to Unilever by the Department of Experimental Psychology, University of Oxford, 2003; see also Unno K et al, Pharmacol Biochem Behav, 2013
14 Lyon et al, Altern Med Rev, 2011
15 Benton D, Donohoe RT. The effects of nutrients on mood. Public Health Nutr. 1999 Dec;2(3A):403–9.
16 Su KP, Matsuoka Y, Pae CU. Omega 3 fatty acids in mood disorders. J Clin Psychiatry. 2003;64 Suppl 2:32–7.
17 Anglin RE, Samaan Z, Walter SD, McDonald SD. Vitamin D deficiency and depression in adults: systematic review and meta analysis. Br J Psychiatry. 2013 Feb;202:100–7.
