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

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

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

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

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

The big question is: why?

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Introducing the four horsemen…

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

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

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Brain fats in short supply

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

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

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

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

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Vitamin D is a mental health essential

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

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

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

Methylation and homocysteine-lowering B vitamins

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

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

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

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

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

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

Breakthrough in homocysteine testing

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

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

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

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

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

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

…Read part two here!

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

Thank you for reading!

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

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

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

As our founder and CEO Patrick Holford says:

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

Thank you for reading!

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

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

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

References

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

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

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.

If you are unsure of your status,  then order your DRIfT blood test to find out  – available globally.

Top up vitamin D for winter mood 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.

Next steps:

Read more about sugar and brain health here.
Take the free Cognitive Function Test to understand your personal profile.
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 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

2 https://www.science.org/doi/10.1126/science.abn9257

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.

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

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

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

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

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

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But it also predicts the actual size of your brain.

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

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

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

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

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

Thank you for reading!

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

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

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

References

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

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

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

by Patrick Holford

We want to introduce you to our Mascot, Tommy Gun.

He arrived with two other boys (Vincent and Oran) at our farm in the Black Mountains, just in time for Christmas. On the farm we are experimenting with ways of growing food using zero-dig, organic methods, to maximise nutrient content – food for the brain!

(The alpacas, by the way, keep the foxes off the chickens. Down on the farm, we are learning how to grow foods with the highest nutrient content including omega-3-rich eggs – of course organic, wild and free!) 

Why Tommy Gun? 

Well, largely in honour of my (Patrick’s) father-in-law who said his dementia was getting so bad he forgot he had dementia.

Tom was one of the people who started Carnaby Street with his shop Gear, and then Kids in Gear in the swinging 60’s and invented the Union Jack pop art, putting it on everyday items from mugs to tea trays. He then became the Grateful Dead’s European tour manager. Not everything consumed in those days was exactly good for the brain!  His ‘son-out-law’ was Joe Strummer of the Clash (Tommy Gun is a Clash song). 

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Tommy Gun reminds us that the reason we all work so hard is to prevent another lovely person from developing this terrible and unnecessary disease.

Every bit of prevention you can do is worth it.

Every person you can get to complete the Cognitive Function Test and take one of our easy, accurate, at-home blood tests, is worth it. 

Will you join us in our mission?

We rely solely on donations and word of mouth, so please spread the word this festive season.

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.

Is the H Factor still the biggest health breakthrough of the century?
By Patrick Holford

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You may have never heard of it, let alone know your ‘H’ score, but in your bloodstream there exists a toxic amino acid, largely a consequence of sub-optimal B vitamin status, which if raised (above 11µmol/L), is associated with an increased risk of over one hundred diseases and accelerates brain shrinkage.

It’s called homocysteine and I consider it more important to know than your weight, your glucose, cholesterol, iron or any other marker, especially if you intend to become pregnant, are over 40, or have any memory, mental health, neurological or cardiovascular concerns.

I first wrote about it in 2003 in my book ‘The H Factor’ describing it as ‘the biggest health breakthrough of the century’. Reviewing the book ITV’s This Morning Doctor, Chris Steele, said ‘Homocysteine is the new cholesterol. It’s potentially your most important health statistic.’ In Ireland’s Late Late Show, I tested the host, Pat Kenny, and revealed his level to be way too high (above 15µmol/L). It was his wake up call as he was, according to his wife, heading for a heart attack with a poor diet and lots of stress, coffee and alcohol, all of which raise homocysteine.

Now, twenty years on, we know that homocysteine is associated with an increased risk of over 100 diseases or adverse outcomes which are listed at the end of this article, including almost all brain and mental health disorders, from childhood to old age, including dementia and Alzheimer’s. 

Technically we can call homocysteine a ‘biomarker’ which is the title of a very important paper ‘Homocysteine – from disease biomarker to disease prevention’ by Professors David Smith and Helga Refsum (1). If you are a health professional or nutritional therapist, I strongly recommend you read this seminal paper. 

David Smith is the Emeritus Professor of pharmacology at the University of Oxford, where he was the Deputy Head of the Faculty of Medical Science. Helga Refsum is a Professor of Nutrition at the University of Oslo in Norway and formerly a professor of pharmacology. Helga could rightly be called the Queen of Homocysteine because her research (Hordland study that started back in 1992, measuring homocysteine in 18,000 men and women in Norway and tracking their health and the diseases), more than any other, has put this vital biomarker on the map. 

Homocysteine first came to my attention when Dr Kilmer McCully in the US discovered that children who were dying young from heart attacks had high levels. This was due to a genetic disorder that leads to homocysteine accumulation in the blood, which then damages the arteries. I wrote about this in my first book, The Whole Health Manual, in 1981. 

So, here we are 40 years later and still, few people know about it, far less know their H score and, worse than that, there has been a concerted effort, largely orchestrated by misleading and wrongful science, to keep the lid on it.

Why?

I believe because there is no patentable drug that lowers homocysteine – only inexpensive vitamins. 

What is more, having a level above 11µmol/L is not at all uncommon. If you are over 60 the odds are high: 40% in the US over 60 have an H score of over 11 (2). It’s probably not much different in the UK but all we know is that two in five adults over 61 in the UK have insufficient B12 to prevent accelerated brain shrinkage (3). In China it’s much worse – those under 30 or over 60 average a score above 15 (4). It is realistic to assume that over a third of older people have an H score over 11.

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What is homocysteine and why is it so important? 

Many nutrients in the body do not work in the form you ingest them – that is until they get ‘methylated’. This is true, for example, for folate or folic acid. It has to turn into methylfolate to become biologically active. Many vital biochemicals, from adrenalin to insulin, need to be made and broken down – by methylation. Histamine and hormones such as oestrogen are examples. Also toxins, from mercury to arsenic need to be detoxified – by methylation. The genes you’re born with can be ‘activated or expressed’ or ‘downregulated’ or turned off. Methylation does that too. Two-thirds of all cancers are associated with faulty methylation which messes up gene messaging. 

Homocysteine rises if you’re not doing methylation properly. This is because there’s a log jam on the way to making the body’s most important ‘methylator’ called s-adenosyl methionine or SAMe for short. Think of it as the conductor of the methylation orchestra. It’s made from an amino acid you eat – methionine. It’s another example of a food nutrient that doesn’t work until it is methylated. This happens thanks to enzymes dependent on vitamins B6, B12 and folate turning it into SAMe. This film shows you how: Methylation & Homocysteine explained

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How does your body and brain juggle and keep all these thousands of biochemicals you need every second in the right balance? 

It is a veritable biochemical symphony going on 24/7. That’s what SAMe does, adding on and taking away methyl groups with literally billions of methylation reactions every minute. If your homocysteine level is above 11 you are not doing it right.

At a very simplistic level, you could say that a raised homocysteine indicates that you don’t have enough vitamin B6, B12 or folate. These, together with zinc, trimethylglycine (TMG) and N-acetylcysteine (NAC) are given to lower a high homocysteine level (which is abbreviated to Hcy here on in).

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Get homocysteine down before getting pregnant

We call Hcy a biomarker, as opposed to a risk factor, as we don’t always know if it is actually causing the problem or just associated with it. That’s also where the chicken and egg story starts. Given that these B vitamins lower Hcy it’s not so surprising to find that many of the diseases that are associated with high Hcy are also associated with low folate or B12. Pregnancy problems are a classic example. Above 9 µmol/L risk of miscarriage and pregnancy complications are higher. Even a Hcy level of above 9 in the mother during pregnancy predicts more problems, specifically withdrawn behaviour, anxiety/depression, social problems and aggressive behaviour in their child at age 6 (5). 

Raised Hcy is a well-known predictor of miscarriage (6)  and pregnancy problems (7). But is it homocysteine or a lack of folate or B12? Similarly, neural tube defects, for example, spina bifida, is strongly associated with both lack of folate and raised Hcy. Giving folic acid supplements reduces risk and lowers Hcy. Is Hcy a marker for folate deficiency (yes)? Or is folate deficiency a cause for raised Hcy (yes) and is it actually the Hcy that does the damage (probably)? That’s harder to answer but there are a number of ‘toxic’ consequences of raised Hcy such as damaging the arteries and the brain. Also, many things are generally bad for your health – drinking too much alcohol or coffee, smoking, not exercising, being stressed, having diabetes, not sleeping, all of which are associated with higher Hcy. Suffice it to say that there are plenty of advantages in having an H score below 9, and possibly even lower, and no disadvantages – including less risk of dying. 

In those with cardiovascular disease having a H score above 20 increases risk of death by almost five times. Every 5 point increase increases risk by a third (8). A recent report of almost three thousand cardiovascular patients found that risk of death was almost three times higher for those in the top quartile of Hcy (>15.6) compared with those in the lowest quartile below <9.8 (9). 

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Protect your brain by lowering homocysteine

Hcy damages the arteries including blood vessels in the brain. That’s what Dr Kilmer McCully discovered back in 1969 in children with a genetic disorder. A recent study showed that being in the top quarter for Hcy meant 17 times more risk of cerebrovascular damage (10). But it also cranks up things like p’tau which is a toxic substance known to cause ‘neurofibrillary tangles’ which are one of the hallmarks of Alzheimer’s that big pharma is trying to develop a drug for. They needn’t bother because lowering Hcy with inexpensive B vitamins lowers p’tau (11).  It’s just not profitable.

Not surprisingly, if high, Hcy increases the risk of stroke, and giving folate or B12 lowers risk. In this case we can say Hcy is ‘causal’ –  as in high levels cause things to happen that lead to stroke or dementia and lowering homocysteine stops or very much slows down those things happening, slowing down brain shrinkage and virtually stopping further memory loss. But, as with many diseases, if you’ve already had a stroke or got Alzheimer’s there is little room for improvement.

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Homocysteine for heart disease and stroke

While no one disagrees that high homocysteine predicts risk for heart disease or stroke, some dodgy science more than a decade ago, when the full dynamics of homocysteine and B vitamins weren’t known, cast doubt. One such study in Sweden, called NORVIT, apparently showed no effect from giving B vitamins to people who had had a stroke. ‘The homocysteine hypothesis is dead. Homocysteine is not a causal risk factor. It is an innocent bystander’ declared the author, Dr Bonaa. 

We now know he was wrong, and why he was wrong. Smith and Refsum’s paper goes into all the detail but what has since been learned is this: 

>> B vitamins don’t lower risk if you don’t already have a high homocysteine level. 

Anti-platelet drugs (think aspirin) and statins interfere with the beneficial action of B vitamins. 
B12 is poorly absorbed and certain older patients with poor absorption or kidney disease are less likely to respond to oral B12 (but might get benefit from B12 injections). 
Also, lowering homocysteine with B vitamins BEFORE a person has had a stroke or a heart attack, does much more effectively reduce the likelihood of them having one. 

This has led to serious cardiology scientists, such as Professor David Spence, who realised the problems with a major study he had conducted, called VISP, and reanalysed the results to find a clear benefit. ‘Call off the funeral’, he declared.

But, for some, sadly, including the so-called National Institute of Clinical Excellence (NICE), now called the National Institute of Health and Care Excellence there will be no exhumation for homocysteine. 

That’s unfortunate because two-thirds of cardiovascular deaths in the elderly happen to people with high Hcy. Not paying any attention to the actual scientific evidence due to a former misguided bias is not health, care or excellence.

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Is there a mental or neurological illness that isn’t cranked up by high homocysteine?

Have a look at the list of diseases below, all strongly associated with homocysteine. Take Parkinson’s for example. A recent meta-analysis shows that both homocysteine, vitamin B12, and folate status predict the onset and development of Parkinson’s (12).

The point is that if you’re over 60 or have any concerns about any of these conditions, and especially if you already have a serious degenerative disease such as Parkinson’s, multiple sclerosis, dementia or cardio or cerebrovascular disease it is vital to check your homocysteine level and then act accordingly. If your specialist hasn’t done this they are not doing their job properly. The science is in plain sight.

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Plasma total homocysteine as a disease biomarker

The table lists diseases and syndromes for which there are reports of association with raised total homocysteine. Reproduced with the permission of the authors Professors David Smith and Helga Refsum from the paper 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.  © 2021 The Association for the Publication of the Journal of Internal Medicine 3 Journal of Internal Medicine

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Testing and Lowering Homocysteine (it’s now easier than ever!)

Despite almost 29,000 studies on homocysteine, getting your doctor to test your homocysteine is close to impossible. It shouldn’t be because every hospital laboratory can do this simple laboratory test. It need not be expensive.

All these studies refer to total plasma homocysteine, that is the level found not in red blood cells but in the clear serum part of blood. The issue there regarding testing has been the need to separate or spin the blood shortly after taking the sample or pass the blood through a plasma separator as some home test kits have attempted. I’ve tested home test kits and have not been impressed with the correlation with serum/plasma homocysteine, which is the gold standard.

However, a breakthrough with both the fixing of blood taken using a dry blood spot, and the testing process, has occurred which now means that we have an accurate and inexpensive way to test homocysteine from a dry blood spot supplied from a home test kit. This is now.

The validation of this test is extremely good (with a R2 of 0.93 for those who know statistics). This also means that there will be no false positives or negatives.

Homocysteine, however, is only truly accurate if measured after fasting for 12 hours with water only being drunk. Both coffee and alcohol affect homocysteine levels, as does eating a protein-rich meal. I also advise not taking B vitamin supplements during this time or possibly for 24 hours before you test.

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Fortunately, Hcy is easily lowered. 

The simplest and most effective way to do this is with B vitamin supplements at the right dosage. Click here to see not only how much to supplement but which supplements there are that provide these doses. 

Most critical is the amount of vitamin B12 they provide.

The basic Dietary Reference Value that you see on supplements is 2.5mcg. Few provide more than 10mcg, which is sufficient if you don’t have raised Hcy. This will do nothing to lower a high H score. Professor’s Smith and Refsum recommend 500mcg a day – that’s two hundred times higher. This is both safe and effective especially if taken alongside B6 (20mg) and methylfolate (400mcg). Also, it doesn’t take so long you bring your level down. I’ve had clients with H levels from 30 up to over 100 µmol/L bring theirs down to below 9 in under three months.

Other wise choices are to eat greens, beans, nuts and seeds which are high in folate; eat seafood and eggs, high in B12 and phospholipids, as well as omega-3, which methylation helps bind together to make healthy cell membranes; don’t smoke or drink in excess (one 125ml of red wine doesn’t affect homocysteine levels); don’t drink more than one coffee a day; reduce stress and insomnia and keep fit.

We are now excited to announce that after much work we have our at-home pin prick homocysteine blood test that you can order and test in your own home.

Click the link above to preorder your test today, then please also do the charity’s free online Cognitive Function Test, followed by the diet and lifestyle questionnaire. In that way, you become a Citizen Scientist. 

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 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.

³ 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.

⁴ Xu R, Huang F, Wang Y, Liu Q, Lv Y, Zhang Q. Gender- and age-related differences in homocysteine concentration: a cross-sectional study of the general population of China. Sci Rep. 2020 Oct 15;10(1):17401. doi: 10.1038/s41598-020-74596-7. PMID: 33060744; PMCID: PMC7566483.

⁵ 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.

⁶ Li J, Feng D, He S, Wu Q, Su Z, Ye H. Meta-analysis: association of homocysteine with recurrent spontaneous abortion. Women Health. 2021 Aug;61(7):713-720. doi: 10.1080/03630242.2021.1957747. Epub 2021 Aug 1. PMID: 34334120.

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 Fan R, Zhang A, Zhong F. Association between homocysteine levels and all-cause mortality: A dose-response meta-anal- ysis of prospective Studies. Sci Rep. 2017;7:4769. 

⁹ Pusceddu I, Herrmann W, Kleber ME, Scharnagl H, Hoff- mann MM, Winklhofer-Roob BM, et al. Subclinical inflam- mation, telomere shortening, homocysteine, vitamin B6, and mortality: the Ludwigshafen Risk and Cardiovascular Health Study. Eur J Nutr. 2020;59:1399–411. 

¹⁰ 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 

¹¹ Read both Xia, Y., Prokop, S. & Giasson, B.I. “Don’t Phos Over Tau”: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies. Mol Neurodegeneration 16, 37 (2021). https://doi.org/10.1186/s13024-021-00460-5; also LiJ-G,ChuJ,BarreroC,MeraliS,Pratico`D.2014.Homocysteine exacerbatesβ-amyloid, tau pathology, and cognitive deficit in a mouse model of Alzheimer’s disease with plaques and tangles. Ann. Neurol. 75:851–63; also  Shirafuji N et al Homocysteine Increases Tau Phosphorylation, Truncation and Oligomerization. Int J Mol Sci. 2018 Mar 17;19(3):891. doi: 10.3390/ijms19030891. PMID: 29562600; PMCID: PMC5877752; also Bossenmeyer-Pourié C et al. N-homocysteinylation of tau and MAP1 is increased in autopsy specimens of Alzheimer’s disease and vascular dementia. J Pathol. 2019 Jul;248(3):291-303. doi: 10.1002/path.5254. Epub 2019 Mar 19. PMID: 307349

¹² Quan Y, Xu J, Xu Q, Guo Z, Ou R, Shang H and Wei Q (2023) Association between the risk and severity of Parkinson’s disease and plasma homocysteine, vitamin B12 and folate levels: a systematic review and meta-analysis. Front. Aging Neurosci. 15:1254824. doi: 10.3389/fnagi.2023.1254824 

If you set your mind to a target, such as dementia-proofing yourself, anything is possible. 

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Drew is a perfect example.

He is the architect behind COGNITION, and his son Alex, does all our design. Drew decided he wanted to swim the channel and even though it was a daunting, huge task, he did it! 

Watch this inspiring 5-minute film made by his daughter of what is an amazing achievement and know that even if taking the Cognitive Function Test or doing our at-home blood tests and working on your brain health feels scary or off-putting – anything is possible.

You can reclaim your brain…and swim the channel if you really want to!

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We hope it inspires you to go for it, whatever it is. 

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Here at Food for the Brain, we are shooting for millions of people learning how to never get Alzheimer’s. 

That’s the channel we are swimming and we appreciate your support. 

How you can help? 

1. Do the Cognitive Function Test (and then redoing it every six or 12 months)

2. Taking a test such as vitamin D, omega-3 and HbA1c, are not only finding out the ’truth’ about where your body and brain are at, giving you a target to aim for (that are easier than swimming the channel), but you are also helping us research what drives cognitive decline and how to prevent it. 

3. We are an independent charity so rely on donations to continue our research and work. Whatever you can donate helps us move forward. Patrick and Drew, together with Professor Julia Ruckledge are now working on COGNITION for Smart Kids because, after all, the future depends on them. Donate here.

Thank you for reading!

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

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

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

Whether your goal is to protect your memory from getting worse, or enhance and optimise your mental acuity, you need three things.

The first is having the best ‘structure’ – that is building brain cells and their connections; then it’s about the best ‘function’ as in fuel supply; and ‘utilisation’ and the importance of having an active physical, social and intellectual lifestyle.

The thing about memory is that it is very subjective.

One person’s perception of how good their memory is will be very different from someone else. Many people, later in life, think their memory is getting worse, while for others, they choose the path of denial that anything is wrong, even when it’s becoming obvious to those around them. Yet the specific aspects of cognition that decline on the road to dementia can, in fact, be objectively mapped and measured decades before any diagnosis might occur and, most importantly, can enable us to ‘course correct’ if we are ready to take the right actions soon enough. 

That is why we created a roadmap – our objective and validated Cognitive Function Test. 

Many people who worry their memory is worse find that they score well into the healthy green zone. Only by having enough people of different ages completing the Cognitive Function Test, can we explore what is optimum and possible, to further improve, and what people with higher scores are doing differently to those with lower scores to stay in the green zone.

For example, if a person is aged 50 to 70, a score of 54 is the average expected score and we expect most respondents to score between 43 and 65. Scores below 43 and above 38 we classify as ‘amber’ or ‘at risk’ – that is not ideal. Below 38 is in the red zone and is consistent with mild cognitive impairment (MCI) sometimes called pre-dementia. 

So, the first step to improving your memory is to take the Cognitive Function Test, and complete the questionnaire that follows, to find out which bits of your brain could benefit from an MOT and some proverbial ‘bodywork’. It will give you the very best road map to improve those areas that are not serving you well, while keeping up the bits that do work. This is what the COGNITION programme is all about.

We spend time and care looking after our cars – why not our minds and brains too?

The good news is, that there are some great shortcuts to improving your memory that you can start taking now. 

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Diana first took the Cognitive Function Test when she was 60.

“I‘ve been doing the Cognitive Function Test for about 10 years. I’m no longer worried that I’m losing my mental abilities.” Now, age 70, her cognitive function has improved. “In fact, my memory is better, my vocabulary has improved and I’m no longer searching for that “right” word – it’s springing to mind much more readily. People are even complimenting me on my great memory whereas in the past, I used to joke that I had the memory retention of a goldfish. Doing the test annually has given me confidence that ageing and Alzheimer’s are not to be feared and has played a significant role in reinforcing the lifestyle changes I’ve made.”

The B vitamin – Omega-3 Dynamic Duo

The first, relating to how we build neurons and their connections, is the dynamic duo of homocysteine-lowering B vitamins and omega-3 fats, especially DHA. 

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Homocysteine is an amino acid and B vitamins play a crucial role in breaking down homocysteine into other chemicals your body needs. 

In trials, participants with memory problems were given homocysteine-lowering B vitamins and had a massive 73% reduction in the annual rate of brain shrinkage compared to those on a dummy placebo pill. Another trial, giving just 2.3 grams of omega-3 fish oils to participants (who already had adequate B vitamin status) produced a halving of the participant’s clinical dementia rating (CDRsob), and an improvement in their memory on the mini-mental state exam (MMSE). Omega 3 is vital to keep our brain membranes fluid and supports the action of neurotransmitters (our brain’s chemical couriers) so the combination is a clear freeway to better brain health.

So what levels are optimal? Getting your omega-3 index above 8%, whether by eating fish or supplementing with capsules, is a good starting point. Psychiatrist Joe Hibbeln gives 4 grams a day – that’s four large fish oil capsules. Also, higher homocysteine levels (above 7 to 7%) indicate that your body needs more B vitamins to break down the amino acids. A broad spectrum supplement that includes B12, folate, B6, TMG, zinc and NAC is a great option. 

The Food for the Brain DRIfT 4 in 1 home blood test kit allows you to measure homocysteine, omega-3, vitamin D and Hba1c and your need for B vitamins, as well as your Omega-3 Index based on the amount of EPA and DHA in red blood cells (RBC).

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Up Antioxidants

The next stop on the brain upgrade road trip is to fill up on those antioxidants. Two of the key antioxidants in your body are glutathione and melatonin. They help detox the brain and play an important role in protecting the brain from ‘free radicals’, a byproduct of energy production. Think of antioxidants as the ‘fuel filter’ for your brain.

Glutathione is made from NAC (N-acetylcysteine), an amino acid that should be included in your homocysteine-lowering formula. It is also ‘recycled’ by anthocyanins – that’s all those blue/red foods, such as blueberries, green leafy vegetables like spinach, and dark chocolate, while onions, asparagus and eggs are rich in glutathione. You could aim to have a serving of berries every day, but also supplement glutathione or NAC. 

Having sufficient melatonin is a product of both your serotonin status, made from tryptophan or 5-HTP, and getting good quality sleep. If you have a neurodegenerative disease, cognitive impairment, high stress or poor sleep, and especially if you have more than one of these, supplementing 1 to 5mg of melatonin every night, the higher level being for those with sleeping problems, may have anti-ageing benefits for the brain (1).

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Don’t Forget Niacin

One B vitamin that has a benefit for your memory is Vitamin B3, in the form of niacin. In animal studies, the combination of melatonin and NMN (nicotinamide mononucleotide, also in the family of vitamin B3) has been shown to protect the central hippocampus area of the brain, slowing down ageing, improving mitochondrial energy production and cognition (2). They are the hot new nutrients in brain research, with the potential to protect against amyloid and p-tau formation, two key markers of brain degeneration.

In a long-term study looking at nutrient levels in people aged 18 to 30, then measuring their memory 25 years later, niacin intake most predicted better memory, followed by folate, B6 and B12 (3). Another study found niacin intake protects against Alzheimer’s. Those with higher niacin intakes had a third of the risk (4) than those with lower intakes.

A small study giving supplements of niacin at a dose of 141 mg (which is almost ten times the basic ‘nutrient reference value’ of 16mg), produced measurable improvement in memory in eight weeks in healthy people without cognitive decline (5).

I hedge my bets and supplement 50mg daily in my multivitamin.

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Fill the Energy Gap with C8 oil

In previous articles, we have explained how the brain loves ketones as fuel, primarily derived from a specific type of medium-chain triglyceride (MCT) called C8 oil. The main sources of C8 oil are coconut, palm oil, butter and milk, though coconut is the most common, containing about 7% C8 oil.

People with blood sugar problems such as diabetes, as well as many older people, become less able to get sufficient glucose (the other critical brain fuel), into the brain’s mitochondrial energy factories within neurons and end up with a brain energy deficit. Filling this energy gap with one or two tablespoons (15-30 g) of C8 oil is a quick win for increased brain energy. 

This has proven to work in those with cognitive decline, thanks to the excellent research of Professor Stephen Cunnane. Four out of six studies have shown improvements in memory from MCT oil supplementation in those without dementia (6). And the benefits are there if you’re younger and healthier too. One study at Liverpool Hope University giving healthy young adults between 12-18 g of C8/C10 in combination found cognitive improvements in just three weeks.

To support memory, start with a tablespoon of C8 oil a day for younger, healthier people, or twice this if you’re older, are already experiencing some cognitive decline, or have blood sugar problems, such as a raised HBA1c level above 6% or 53 nmol/mol.

The other way to boost your brain with ketones is to eat a low-carb high-fat diet or do intermittent fasting. I recommend two or three days a week doing ‘18:6’ (18 hours fasting, six hours eating). After your last evening meal, fast until lunch the next day, but start your day with a Hybrid Latté containing a tablespoon of C8 oil. Your brain is more likely to convert the C8 to ketones if you are ‘starved’ of carbohydrates in this way.

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Vitamin D protects your brain and memory

Vitamin D is considered a true all rounder as far as your brain and mental health is concerned and it’s worth ensuring your level is optimal for both brain and body. It helps neurotransmission and exerts anti-inflammatory and neuroprotective activities within the brain by reducing inflammation and oxidative stress (8), both of which are drivers of cognitive decline.

Vitamin D deficiency increases the risk of Alzheimer’s (9). In a study in France involving 912 elderly patients followed for twelve years, a total of 177 dementia cases occurred. Those with low vitamin D levels had a nearly three-fold increased risk of Alzheimer’s (10). 

Supplements may also help ward off dementia, according to a recent, large-scale study involving over twelve thousand dementia-free 70+ year olds in the US (12). More than a third (37%) took supplements of vitamin D. Those who did had a 40% lower incidence of dementia. Professor Zahinoor Ismail, of the University of Calgary and University of Exeter, who led the research, said: “We know that vitamin D has some effects in the brain that could have implications for reducing dementia, however so far, research has yielded conflicting results. Overall, we found evidence to suggest that earlier supplementation might be particularly beneficial, before the onset of cognitive decline.”

So what is considered a ‘good’ level? Ideally, a blood level above 75 nmol/l (30 ng/ml) is recommended, which usually means supplementing 3,000 iu during the winter months (October to March for those in the Northern hemisphere) and up to 1,000iu in the summer months depending on your sun exposure. But even supplementing just 800 iu (20 mcg) a day for 12 months has been shown to improve cognitive function (11). And we also have an at-home Vitamin D research project you can join here by simply testing your vitamin D with us.

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Mushrooms and Your Mind

Various plants and fungi have positive effects on memory that are worth knowing about.

Those that stand out are the oldest living tree Ginkgo biloba and the fungus Lion’s Mane. A trial in healthy adults given Gingko for 30 days showed memory improvements. Ginkgo is a potent antioxidant, anti-inflammatory and neuroprotective compound (13). The usual doses given are 120–300 mg of standardized Ginkgo biloba. It slightly thins the blood so should be used with caution for those on blood thinners. It’s an optional extra.

Lion’s Mane has been shown to improve aspects of memory and cognitive function in three trials, on healthy volunteers (14), those with mild cognitive impairment (15) and dementia (16). 

The best-researched mushroom, used for thousands of years in Japan as an anti-ageing compound, is Reishi. It is a potent antioxidant, thus protecting the brain from damage (17). Many people in Japan take it on a daily basis.

There are other brain-friendly plant remedies that fall more into the ‘stimulant’ category. 

Maca root from Peru (18), Ginseng, Siberian Ginseng (Eleutherococcus)and Rhodiola are other potentially brain-friendly plants, perhaps best used by those with low brain energy, mental fatigue or high stress as they have effects on stress hormones and may support stress resilience. Some stimulating supplements (see Resources) use combinations of these.

There are others, such as guarana, whose main active ingredient is caffeine. I’m not so keen on these as caffeine ultimately causes downregulation, making you less responsive to your own adrenal hormones. In this way, the more you have the more you need.

(And if you want to know more about Mushroom and the Mind then get instant access to a Webinar on this topic here.)

Keeping our brains healthy is a lifelong journey that changes with the different stages of life. And just like a road trip, we can sometimes get lost. The good news is, we can get back on track. Knowing where we are is key, and Food for the Brain is there to support you on your way. Here are some simple things you can do today to begin to rebuild your brain and protect your precious memories along the ride. 

Step 1 – Take the Cognitive Function Test – HERE
Step 2 – Test your levels of omega 3, vitamin D, hbA1c and homocysteine – HERE
Step 3 – Implement 1-2 pieces of the advice above within the next 7 days.

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 Martín Giménez VM, de Las Heras N, Lahera V, Tresguerres JAF, Reiter RJ, Manucha W. Melatonin as an Anti-Aging Therapy for Age-Related Cardiovascular and Neurodegenerative Diseases. Front Aging Neurosci. 2022 Jun 3;14:888292. doi: 10.3389/fnagi.2022.888292. PMID: 35721030; PMCID: PMC9204094.

² Read https://www.lifespan.io/topic/melatonin-benefits-side-effects/; also seeHosseini L, Farokhi-Sisakht F, Badalzadeh R, Khabbaz A, Mahmoudi J, Sadigh-Eteghad S. Nicotinamide Mononucleotide and Melatonin Alleviate Aging-induced Cognitive Impairment via Modulation of Mitochondrial Function and Apoptosis in the Prefrontal Cortex and Hippocampus. Neuroscience. 2019 Dec 15;423:29-37. Doi: 10.1016/j.neuroscience.2019.09.037. Epub 2019 Oct 31. PMID: 31678348.

³ Qin B, Xun P, Jacobs DR Jr, Zhu N, Daviglus ML, Reis JP, Steffen LM, Van Horn L, Sidney S, He K. Intake of niacin, folate, vitamin B-6, and vitamin B-12 through young adulthood and cognitive function in midlife: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Am J Clin Nutr. 2017 Oct;106(4):1032-1040. doi: 10.3945/ajcn.117.157834. Epub 2017 Aug 2. PMID: 28768650; PMCID: PMC5611785.

⁴ Morris MC, Evans DA, Bienias JL, Scherr PA, Tangney CC, Hebert LE, Bennett DA, Wilson RS, Aggarwal N. Dietary niacin and the risk of incident Alzheimer’s disease and of cognitive decline. J Neurol Neurosurg Psychiatry. 2004 Aug;75(8):1093-9. doi: 10.1136/jnnp.2003.025858. PMID: 15258207; PMCID: PMC1739176.

⁵ Loriaux SM, Deijen JB, Orlebeke JF, De Swart JH. The effects of nicotinic acid and xanthinol nicotinate on human memory in different categories of age. A double blind study. Psychopharmacology (Berl). 1985;87(4):390-5. doi: 10.1007/BF00432500. PMID: 3936095.

⁶ Giannos, P., Prokopidis, K., Lidoriki, I. et al. Medium-chain triglycerides may improve memory in non-demented older adults: a systematic review of randomized controlled trials. BMC Geriatr 22, 817 (2022). https://doi.org/10.1186/s12877-022-03521-6

⁷ Jake S. Ashton, James W. Roberts, Caroline J. Wakefield, Richard M. Page, Don P.M. MacLaren, Simon Marwood, James J. Malone, The effects of medium chain triglyceride (MCT) supplementation using a C8:C10 ratio of 30:70 on cognitive performance in healthy young adults, Physiology & Behavior, Volume 229, 2021, 113252, ISSN 0031-9384, https://doi.org/10.1016/j.physbeh.2020.113252.

⁸ Jayedi A, Rashidy-Pour A, Shab-Bidar S. Vitamin D status and risk of dementia and Alzheimer’s disease: A meta-analysis of dose-response †. Nutr Neurosci. 2019 Nov;22(11):750-759. doi: 10.1080/1028415X.2018.1436639. Epub 2018 Feb 15. PMID: 29447107

⁹ Chai B, Gao F, Wu R, Dong T, Gu C, Lin Q, Zhang Y. Vitamin D deficiency as a risk factor for dementia and Alzheimer’s disease: an updated meta-analysis. BMC Neurol. 2019 Nov 13;19(1):284. doi: 10.1186/s12883-019-1500-6. PMID: 31722673; PMCID: PMC6854782.

¹⁰0 Jia J, Hu J, Huo X, Miao R, Zhang Y, Ma F. 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.

¹¹1 Feart C, Helmer C, Merle B, Herrmann FR, Annweiler C, Dartigues JF, Delcourt C, Samieri C. Associations of lower vitamin D concentrations with cognitive decline and long-term risk of dementia and Alzheimer’s disease in older adults. Alzheimers Dement. 2017 Nov;13(11):1207-1216. doi: 10.1016/j.jalz.2017.03.003. Epub 2017 May 16. PMID: 28522216.

¹²Ghahremani M, Smith EE, Chen HY, Creese B, Goodarzi Z, Ismail Z. Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status. Alzheimers Dement (Amst). 2023 Mar 1;15(1):e12404. doi: 10.1002/dad2.12404. PMID: 36874594; PMCID: PMC9976297.

¹³ Stough C, Clarke J, Lloyd J, Nathan PJ. Neuropsychological changes after 30-day Ginkgo biloba administration in healthy participants. Int J Neuropsychopharmacol. 2001 Jun;4(2):131-4. doi: 10.1017/S1461145701002292. PMID: 11466162. ; see also Mix JA, Crews WD Jr. A double-blind, placebo-controlled, randomized trial of Ginkgo biloba extract EGb 761 in a sample of cognitively intact older adults: neuropsychological findings. Hum Psychopharmacol. 2002 Aug;17(6):267-77. doi: 10.1002/hup.412. PMID: 12404671.

¹⁴ New proper study ref, study details ot confirm Neurofood – https://hifasdaterra.com/en/blog/new-product-memory-neurofood/

¹⁵ Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T (2009) Improving effects of the mushroom 

Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo- 

controlled clinical trial. Phytotherapy Research 23, 367-372. 

¹⁶ Li IC, Chang HH, Lin CH, et al. Prevention of Early Alzheimer’s Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study. Front Aging Neurosci. 2020;12:155. Published 2020 Jun 3. doi:10.3389/fnagi.2020.00155. 

¹⁷ Huang, S., Mao, J., Ding, K., Zhou, Y., Zeng, X., Yang, W., Wang, P., Zhao, C., Yao, J., Xia, P., & Pei, G. (2017). Polysaccharides from Ganoderma lucidum Promote Cognitive Function and Neural Progenitor Proliferation in Mouse Model of Alzheimer’s Disease. Stem cell reports, 8(1), 84–94. https://doi.org/10.1016/j.stemcr.2016.12.007

¹⁸ https://www.scielosp.org/pdf/rpmesp/2014.v31n1/100-110/es

¹⁹ 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  

²⁰ Marek K, Cichoń N, Saluk-Bijak J, Bijak M, Miller E. The Role of Vitamin D in Stroke Prevention and the Effects of Its Supplementation for Post-Stroke Rehabilitation: A Narrative Review. Nutrients. 2022 Jul 4;14(13):2761. doi: 10.3390/nu14132761. PMID: 35807941; PMCID: PMC9268813.

²¹ Jadavji NM, Emmerson JT, MacFarlane AJ, Willmore WG, Smith PD. B-vitamin and choline supplementation increases neuroplasticity and recovery after stroke. Neurobiol Dis. 2017 Jul;103:89-100. doi: 10.1016/j.nbd.2017.04.001. Epub 2017 Apr 7. PMID: 28396257.

²² Dimpfel W., Wedekind W., Keplinger I. Efficacy of dimethylaminoethanol (DMAE) containing vitamin-mineral drug combination on EEG patterns in the presence of different emotional states. Eur. J. Med. Res. 2003;8:183–191. [PubMed] [Google Scholar]

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By Patrick Holford

If you are eating a healthy whole food diet, do you need supplements? Surely the food you eat should be enough?

When it comes to supplements, the conventional view is based on government supported recommended intakes (RDAs, RNIs, NRVs or DRVs) designed to prevent classical symptoms of deficiency, such as scurvy in the case of vitamin C. The implication here is that if blood levels of nutrients are enough to prevent classical deficiencies then nutrient status is considered to be sufficient.  However, there is abundant evidence that even levels above those used to define ‘deficiency’, may still often be associated with adverse signs or symptoms or increased risk of diseases such as dementia. These levels therefore define a zone of ‘nutritional insufficiency’.

There is furthermore, a growing body of evidence from well-designed studies on specific mental health diseases, showing that supplements giving nutrients at levels beyond the basic ‘RDAs’, delay or reverse the disease or eliminate or ameliorate symptoms of disease, including cognitive decline. 

There are also many studies showing a steady reduction in symptoms or diseases, when blood levels of nutrients increase beyond the arbitrary cut-off levels, set to prevent classical deficiencies. Thus, neither RDAs nor normal reference ranges given for blood levels of nutrients, are ‘optimal’.

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Outdated definitions

This illustrates that the definition of ‘deficiency’ is outdated. Deficiency means a lack of efficiency. If the definition of nutrient deficiency, and its counterpart, sufficiency, were to be defined as the level of a nutrient that relieves symptoms of disease or promotes its prevention, that definition is scientifically supportable. It also takes into account the unique biochemical individuality that occurs as a function of both genetics, environmental exposure, microbiomics and an individual’s ability to absorb nutrients.

While medical and advertising law prohibits the description of a nutritional supplement or food as ‘preventing, reversing or treating a disease’ this is scientifically not correct. Nutrients do prevent, reverse and treat disease.

The overarching principle of the Food for the Brain Foundation is that of scientific integrity – that is to be consistent with the prevailing science and share that growing body of knowledge in a way that enables people like you to restore, maintain and improve mental health.

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What nutrients should we pay special attention to?

Four nutrients are especially significant in this regard.

Vitamin D – it is now well established that anyone living far from the Equator has to supplement vitamin D for several months (October to March in the UK and for cooler months in most of Europe, Australia, New Zealand and the US). The UK Government, in 2016, recommended that everyone should supplement during the Autumn and Winter. Almost a decade earlier, in 2007, I made the same point but was reported to the Advertising Standards Agency whose rule says “A well-balanced diet should provide the vitamins and minerals needed each day by a normal, healthy individual …”. I felt like reporting the government to the ASA!

Vitamin B12 – many people, especially people over age 50, simply do not absorb vitamin B12 well enough for food alone to be a sufficient supply. The ignorance regarding vitamin B12 is compounded by the inaccurate lower reference range for serum B12 in the UK of anything above 180pg/ml being sufficient (and the US level of 200pg/ml) being out of date and urgently in need of revision. In Europe and Japan anything below 500pg/ml is considered deficient. Against this yardstick, two in five over 60 have levels of B12 which are too low to stop accelerated brain shrinkage. 

Ignorance regarding B12, and the inability of doctors to prescribe it to those with cognitive concerns, is feeding the epidemic of dementia.

Omega-3 DHA – In the UK doctors are not allowed to prescribe omega-3 supplements for any condition, be it depression or dementia, despite all the evidence. I first wrote about omega-3 in 1981, and recommendations have gradually increased with each decade. However, there is still no official Nutrient Reference Value. The current guideline is to have 250mg of combined EPA and DHA a day but this is well below the level of DHA that confers the greatest protection from cognitive decline.

Choline – despite clear evidence of the need for choline, which makes the phospholipid phosphatidylcholine, in pregnancy for normal infant brain development, there is no recommended intake. Vegans can be assumed to be deficient unless supplementing.

I prefer to err on the side of caution, that is to provide the highest optimal level that research suggests would improve mood, memory, mental alertness and is consistent with minimising the risk of cognitive decline.

Click here to find out more on our supplement guidelines

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How many have developed dementia waiting for health officials to catch up?

Don’t be one of them and if you want to know more about what you can do to support your brain then make sure you:

1. Complete your DRIfT test to check your Omega-3 and Vitamin D status, alongside your HbA1c and Homocysteine markers. These are at home, pin-prick, accurate test kits available from UK, EU USA and soon Australia too!
(There is also the option of the DRIfT 5 in 1 test where you also test all of the above PLUS your antioxidant status via our unique Glutathione Index marker – find out more here.)
>> Learn about all our tests here.

2. Complete the FREE Cognitive Function Test. This validated online assessment will create a personalised set of results so you know exactly what you need to work on.
>> Do the online test here

3. Become a FRIEND. Join our mission and become one of our Citizen Scientists, you will get access to a community of like minded people in additionl to COGNITION, your 6-month interactive personalised programme to ensure you upgrade your brain.
>> Find out more here.

Thank you for reading!

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

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

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

by Patrick Holford

Shakespeare actually said “the world’s mine oyster, which I with sword will open.” 

This is, in essence, what we are doing at Food for the Brain. The pearl is your brain. 

Tragically, it is shrinking. As a species, we have lost 20% of our brain size in the last 29,000 years. As individuals, brain shrinkage causes dementia and every three seconds someone in the world is diagnosed with this unnecessary and preventable disease.

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The perfect storm of factors – that are under your control

The pharmaceutical industry, supporting the medical profession to an unhealthy extent, would like to pretend that only they know what’s inside the brain and only they know how to prevent this preventable disease with a magic bullet. But there never will be a magic drug because there is nowhere in your brain where this disease is driven from. It is a ‘perfect’ storm of factors directly under your control.

At Food for the Brain, thanks to already well over 400,000 ‘citizen scientists’ who’ve taken the time, often initially for personal interest, to discover their actual cognitive function, and completed a comprehensive questionnaire. We are now testing the key biochemical processes with a home test pin prick blood test (omega-3, HbA1c(sugar), homocysteine (B vitamins) and vitamin D.

We have, with the sword of digital technology, opened the oyster to uncover the true causes – all under your control – that are driving this terrible and unnecessary shrinkage. Alzheimer’s, which is two-thirds of dementia, is a disease of ignorance that creates ignorance and leaves sufferers like empty shells upon the shore.

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Size Matters

Yet, we know how to stop this. There is no magic. There is just pure science and common sense – not so common these days and too easily hijacked in the name of profit.

With your help, by spreading the word, we can realistically end next year with data on a million people who have both taken the Cognitive Function Test, which is the first fully comprehensive and validated free online test and completed the most comprehensive Dementia Risk Index questionnaire (integrated into the above test) on your diet and lifestyle organised to reveal the eight domains that are driving risk. Think of these keystones as the pearls of prevention; then adding the data of thousands of people testing the four functional tests that determine your glucose resilience, your methylation ability (that’s B vitamins and homocysteine), and your omega-3 and vitamin D status. With that we will have the largest and most comprehensive database of real information, twice the size of the UK BioBank, with which to work.

That work is to prise open exactly which combinations of diet and lifestyle changes protect your mind and which insidiously destroy it year upon year. No one’s memories or life history should be erased or fade.

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A Systems-Based Approach

We are a complex, adaptive system. It is the breakdown in fundamental systems that causes dementia.

Our research aims to show, for example that an ‘index’ of HbA1c, omega-3, homocysteine and vitamin D can be used to predict cognitive decline – and thus highlight key prevention steps. That, as a person’s Dementia Risk Index reduces their Cognitive Function improves or stops declining. This is systems-based science that mirrors who we are, not drug-based science that hunts for a target in order to create profit.

Then, the real mission of our charity begins: to motivate and educate, to empower and transform individuals, millions of individuals to take up their own sword, prise open the oyster and discover the pearl of optimal brain health, connection and intelligence.

Humanity is losing with IQ falling by 7 per cent a generation. On this flight path, a third of children will have mental disabilities by 2080.

I have spent my entire working life learning from bright and committed humanitarian scientists – from Professor Michael Crawford who discovered that the majority, 90% of long-chain fatty acids in the brain are omega-3 DHA ; to Professors David Smith and Helga Refsum, who found that homocysteine was an exquisite predictor of a shrinking brain and that B vitamins, with sufficient omega-3, reduce brain shrinkage in those with pre-dementia by two thirds, compared to the latest anti-amyloid drugs which accelerate shrinkage by 20%; to Dr Abram Hoffer who treated over 6,000 schizophrenics successfully with vitamins and omega-3, not with drugs and stopped seeing patients two weeks before his death, aged 92; and to his partner in crime, twice Nobel prize winner, Dr Linus Pauling, whom Einstein called the real genius, who said, in 1968 “that orthomolecular therapy, the provision for the individual person of the optimum concentrations of important normal constituents of the brain, may be the preferred treatment for many mentally ill patients.” He was the inspiration and the patron of the Institute for Optimum Nutrition, which I founded in 1984 and spawned a new professional of nutritional therapy now practising nutrition and lifestyle medicine. Before he died, as I filmed him at age 93, as sharp as a razor, he said: ‘Patrick follow the logic. It is the logic that counts.”

It is this nutrition and lifestyle medicine we wish to give away to every individual until it is the new paradigm. Until every child is taught these principles. Until every government and medical establishment is forced to support this paradigm, which is the paradigm that is the most true to who we are and capable of saving humanity from its rapid demise.

We will be successful. Our prediction, on good evidence and impeccable logic, is that Alzheimer’s may be entirely preventable in those 99% who do not have the rare causative genes and act early to optimise all diet and lifestyle factors. It is not an inevitable consequence of the ageing process. Our aim at Food for the Brain foodforthebrain.org is to show people how to vastly reduce their future risk of cognitIve decline. 

But will we be successful fast enough?

How many people continue to slip into the fog of dementia, now the number one cause of death, the greatest health care cost and the greatest fear of so many?

How many will you have known?

And how much loss of intelligence can humanity stand before the house of cards comes crumbling down?

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Will you support us?

That is why we ask you, not for financial gain, but from the realisation of what is at stake, to give us your support by:

1. Taking the Cognitive Function Test, and encourage proactively everyone you know over 40 to do the same.

2. Donate to us in your will. Create or update your will for free and leave a lasting legacy – find out more here.

3. Make as big a donation as you can so we can accelerate this educational mission, which has to be underpinned by impeccable research. One million pounds, or £100 from 10,000 people, will ensure we reach millions. Three million pounds is what it costs leading UK professors to run the definitive trial of B vitamins and omega-3, which they have struggled to get funded for five years, despite just two UK Alzheimer’s charities having over £ 30 million to spend on research every year and the Uk government pledging £166 million a year, yet spending nothing on real prevention.

If you’d like to give more and need some assurance of the real return your investment will bring please contact me at patrick@foodforthebrain.org. 

We have to take the sword and prise the oyster of our brains open. The time is now.

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And PS – the reason for the oyster analogy is…

…that oysters literally built the human brain. They were the easiest source along rivers, estuaries and coasts for women to collect and nourish themselves and their babies. It is likely we developed our manual dexterity opening them. 

“Lessons would have been gained from the sea birds opening oysters and diving into the water to catch fish, enticing our ancestors to investigate more than the rocks. Thus our ape ancestors may have started wading into water and becoming upright.”
(Extracts from Prof Michael C rawford’s book The Shrinking Brain)

When Henry Hudson arrived in 1609, there were some 350 square miles of oyster reefs in the waters around what is today the New York metro area – European settlers wasted no time in turning this natural resource into a powerful industry. One million: That’s roughly the number of oysters New Yorkers ate, every day, in the mollusks’ 19th-century heyday. New York was surrounded by immense natural oyster reefs. By 1880 New York was the undisputed capital of history’s greatest oyster boom. By 1880, steam power increased the oyster haul 12-fold compared to the previous sail-powered vessels. People thought there was no end to their availability and New Yorkers simply loved their large oysters, raw, fried, stewed or any way described in the cookbooks which proliferated. 

As New York grew, oyster stands became as common as hot dog stands today. A story goes that an English Earl on returning to England arrived at New York harbour too early. “What shall we do?” his American travelling friend asked. His lordship replied “Return to Broadway and have some more oysters!”

London pubs provided oysters from the Thames estuary free with the purchase of a pint of beer. In the UK, by 1990 the East-London public house owners were still placing oysters on the bar for people to have free with their beer. In New York as with London, the pollution and overfishing was starting to set the rot in progress.

Oysters are a perfect image to exemplify the need for marine nutrients to support brain health.  However, the richest source of DHA is actually caviar.

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.