By Patrick Holford

Read part one here to learn about the first two ‘horsemen’ – Brain Fats & Methylation.

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

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

The big question is: why?

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Introducing the four horsemen (recap)

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 fuel

While omega-3 and B vitamins literally build a healthy brain, it is glucose and ketones that fuel it.

As a result of this process, oxidants are created which age the brain through the process of oxidation. Of course, oxidation can also occur through external causes, which is why smoking and air pollution are also established risk factors for Alzheimer’s.

Which leads us to the next two ‘horses of the mental health apocalypse’: the brain’s fuel supply and antioxidant protection. The brain consumes more energy than any other organ of the body. Neurons can only run on glucose or ketones. The irony is that the consequence of eating too many carbs and sugar is that the brain develops insulin resistance – effectively blocking the glucose from entering the mitochondria within the neurons. Starved of their energy source, we experience the consequences as mental fatigue and forgetfulness. According to Dr Robert Lustig,  Emeritus Professor of Pediatrics at the University of California, San Francisco and a member of our Scientific Advisory Board, “This cognitive decline starts young. Cognitive decline in overweight children is associated with a high GL diet (1), and adolescents with metabolic dysfunction, driven by a high GL diet, have been shown to have shrinkage of the hippocampal area of the brain, as well as other structural changes and cognitive deficits (2).” This particular study showed actual shrinkage of the Alzheimer’s associated area of the brain in teenagers with metabolic syndrome as a consequence of too much sugar and ‘white’ carbs. The youngest age of an Alzheimer’s diagnosis, which requires proof of shrinkage of the hippocampal area of the brain, is age 19, in a young man in China who had no genetic risk factors (2).

It’s a biochemical storm.

As well as the fuel starvation that insulin resistance generates, the converse of blood sugar spikes, create Advanced Glycation End-products, or AGEs, that literally damage neurons. This ‘glycosylation’ is also seen in red blood cells, and why the HbA1c test which measures glycosylated haemoglobin is so good at predicting our health. If over 6.5% (or 48 mmol/mol) of these erythrocytes are sugar damaged, it’s a clear basis for a diabetes diagnosis. Just as for the omega-3 index, HbA1c is a reliable long-term measure showing the average sugar spikes over the past three months. You can assume what’s happening in the membranes of red blood cells is also happening to the neuronal membranes in the brain. 

This is why the next brain essential is to measure HbA1c.

If 6.5% is the cut-off for a diabetes diagnosis, the ideal level is actually considerably lower. In what is usually considered to be the ‘normal range’, teenagers with HbA1c above 5.4% show cognitive decline and shrinkage of the hippocampus in the central area of the brain compared to those with lower HbA1c levels (3). “In teenagers with raised, but normal levels of HbA1c, there is clear evidence of the same kind of memory problems, and the same areas of brain shrinkage seen in patients with Alzheimer’s Disease” says Dr Robert Lustig.

Shrinkage of the hippocampus is the hallmark of Alzheimer’s and is used to diagnose the disease. A new study shows that 40-year-old adults with so-called normal glucose levels, but at the higher end of the normal range, have increased their risk of Alzheimer’s by 15%. (4) 

A primary function of sleep is to repair all the neuronal membrane damage that occurs during the day. No sleep, no repair and the brain ages fast. This is mainly why lack of sleep is also a strong risk factor for Alzheimer’s.

(Click here to test your HbA1c and be a part of our Citizen Science Research)

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Do ketones fill the energy gap?

There’s a growing interest in the role of ketogenic diets and ketone promoting supplements for brain health. Professor Stephen Cunnane, our expert in the new science of ‘keto therapeutics’ has shown that giving C8 oil or supplementing ketones can help to prevent Alzheimer’s, slow down cognitive decline, improve mood and lessen anxiety. His studies showed, in those with mild cognitive impairment, that taking 30g (two tablespoons) of mainly C8 oil, resulted in a 230% increased brain energy production from ketones with no change in energy derived from glucose (5), thus filling the ‘energy gap’ so often experienced by older people or those drifting towards insulin resistance. “Our research shows that the areas of the brain that have trouble using glucose for energy are able to use ketones perfectly well, even in moderately advanced dementia. This may explain why many people later in life who are given a supplement of C8 oil or MCT oil have improvements on a battery of cognitive tests. They often feel it brings their brain power back to life” says Cunnane. 

Many people also report feeling calmer, less anxious and less depressed on ketogenic diets. A new book, Change Your Diet, Change Your Mind, out next month by psychiatrist Dr Georgia Ede digs deep into the growing evidence that a ketogenic diet, or at least one low in carbohydrates, is brain-friendly and helps people out of various mental health disorders. Or you can watch the recent webinar she did with us here.

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Antioxidant and polyphenol power

The more biologically active an essential fat is (with DHA at the top), the more prone it is to oxidation.

It is literally this ability of DHA to absorb energy (photons from light) that creates the impulse that passes information from the eye to the brain. It explains the origin of the brain and nervous system, going back a billion years to a rudimentary single cell called dynoflagellate. This little organism basically used the electric shock from photons to create the first ‘twitch’ towards light. Where there was light, there was food, and ultimately the evolution of the nervous system and brain. In simple terms, we can see that the brain is really an extension of the eye. How do we see with such precision and speed? Until now, no-one has been able to explain this satisfactorily. At the age of 93, Professor Michael Crawford, who helped our charity get started, has worked out how this occurs and how we see in colour. It requires knowledge of quantum physics, explained in a recent paper entitled ‘Docosahexaenoic Acid Explains the Unexplained in Visual Transduction’.(6)

With all this volatile fatty acid and mitochondrial energy production, cleaning up the oxidant exhaust fumes is a vital function for a healthy brain. So how do we achieve protection and how do we measure it?

There are hundreds, if not thousands of antioxidants and polyphenols in our food. Foods can be measured for their ‘Total Antioxidant Capacity’ or TAC for short. It’s worked out from an equation involving eight key antioxidants from vitamin A, carotenes (think carrots), lycopenes (rich in tomatoes), lutein and zeaxanthine (rich in green vegetables), vitamin E (in nuts and seeds), but most of all vitamin C (rich in berries, broccoli, peppers and other vegetables).

Vitamin C is a keystone nutrient as far as swinging the antioxidant equation in our favour. Individually, the impact of these nutrients on our health may be less than when combined. For example, a study of 4,740 Cache County Utah elderly residents found that those supplementing both vitamin E and C cut their risk of developing Alzheimer’s by two thirds (66%). Taking just one cut the risk by a mere quarter (25%).  (7)

The higher the TAC score of our diet, the lower our risk of memory decline becomes. This was the finding of a recent study of 2,716 people over age 60. Higher TAC scores correlated with better memory function (8). Those in the highest quarter of TAC scores had half the risk of decreasing memory. Powerful stuff!

Tea, cacao, red wine, red onions, olives and berries are rich sources of polyphenols. Many of these polyphenol-rich foods improve circulation, lower blood pressure and dampen down inflammation which lies behind many brain and heart health problems. 

More than a decade ago research in Norway (9) found that the more tea you drink the better; a small glass of wine (125ml) a day (preferably red, as it is rich in resveratrol) reduces the risk of cognitive decline. Cacao is also beneficial, ideally no more than 10g, (about 3 pieces) of dark, 70 percent or more. Other studies based on adding cacao to the diet have shown improved cognition, possibly by improving circulation. This was recently confirmed in a big ‘COSMOS’ trial involving over 20,000 people given a cacao extract supplement versus a placebo for five years (10). The reduction in cardiovascular risk was even greater than that of a Mediterranean diet.

The take-away message? Polyphenols are a vital part of a healthy diet for both our heart and our brain.

So, what do we need to eat and drink to protect our brain and body? Basically, eat a Mediterranean-style ‘rainbow coloured’ diet. A Mediterranean diet has more fish, less meat and dairy, more olive oil, fruit and vegetables including tomatoes, legumes (beans and lentils), and whole grain cereals than a standard Western diet. It also includes small quantities of red wine. There are variations of this kind of diet, called the MIND diet and the DASH diet, but the core components are the same. As researchers drill down, we are learning what to eat and drink and how much, to keep our minds sharp and brain young.

The trick is to really start thinking of the colours we are eating and gravitate to the strong colours, choosing organic where possible. Mustard and turmeric, for example, are strong yellows. Bright oranges include butternut squash, sweet potato, carrots. For red, think tomatoes and watermelons. Anything purple, magenta or blue is brilliant for us too. From beetroots (eat them raw, grated into salads) to blueberries, blackberries to raspberries, all these foods are fantastically good for us, so tuck in!

In addition to food, as a health aspiring 65-year-old, I both supplement 1 gram of vitamin C twice a day and take an AGE Antioxidant containing Co-Q10, alpha lipoic acid, n-acetyl cysteine (NAC – as a precursor to glutathione which is the master antioxidant) and resveratrol as well as vitamin E and A – both beta-carotene and retinol. Many people think that there is no point supplementing glutathione because it is so rapidly oxidised, or sacrificed, to disarm oxidants, but it is also rapidly recycled by anthocyanidins in blue/red berries. So, combining the two reloads glutathione. This film shows how.

But how do we measure our antioxidant status?

My research team is working on exactly this challenge and we are finding that the ratio between reduced glutathione (GSH) and oxidised glutathione (GSSG) in red blood cells is probably the best biological determinant. We hope to introduce that into our panel of functional indicators, and research how it correlates with dietary intake and lifestyle habits as well as cognitive function.

We are due to launch a DRIfT Test as part of a global prevention initiative, which will be a 4 in 1 test

The UK Biobank has collected data on 500,000 people since 2006, inviting people to fill in questionnaires, give blood and carry out certain tests. We are funded by ‘Friends’ who pay £50/$60/€60 a year.  So far we have collected data on 410,000 people and this number is growing by about a hundred a day. 

In addition to taking the blood test, participants are invited to complete a validated online Cognitive Function Test (not a questionnaire), followed by a comprehensive 144 question Dementia Risk Index diet and lifestyle questionnaire which takes 20-25 minutes. This works out a person’s future risk and shows what’s driving the risk. This is a free service.

We run the UK’s leading dementia prevention charity which is running the prevention project together with Dr Tommy Wood, Assistant Professor at the University of Washington. “By tracking a person’s blood sugar, vitamin B, D and omega-3 status against changes in cognitive function over time, in addition to lifestyle factors such as sleep and physical activity, we can learn what really helps prevent cognitive decline.” says Dr Wood, the principal investigator for the study. 

Citizen Science

All donations are put back into research, and the results of the research are shared back to the people. 

This is science for the people, funded by the people, shared back with the people. We call them Citizen Scientists and we hope to reach a million people around the world within a year or so making this the biggest prevention-focussed study of its kind. The purpose of research is to help people. Too often great scientists do great studies, which get published and ignored. We have to face the fact that, in the UK as an example, the Government has commissioned four reports on mental health and Wellcome did a further independent report, all showing we have a cerebral tsunami with brain and mental health disorders ahead of every other disease.

They have ignored every single one.

Change is not going to come from the Government or the NHS. It is going to have to come from us, the people. I urge everyone in natural medicine to take the test themselves, share it with others and support us by becoming Friends and donating £50 a year, getting so much in return.

This is how we are funding our amazing research team. We are a lean, keen, small but mighty team. 

Every donation, big or small, goes right back into helping people prevent these preventable and terrible diseases such as dementia. 

Together, we can change the world. 

We need to because time is running out. 

We will lose our humanity if we don’t stop this brain drain.

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

2 https://www.psychiatrist.com/news/a-19-year-old-is-youngest-ever-to-be-diagnosed-with-alzheimers/

3 Yau PL, Castro MG, Tagani A, Tsui WH, Convit A. Obesity and metabolic syndrome and functional and structural brain impairments in adolescence. 

Pediatrics. 2012 Oct;130(4):e856-64. doi: 10.1542/peds.2012-0324. Epub 2012 Sep 

4  Zhang X, et al Midlife lipid and glucose levels are associated with Alzheimer’s disease. Alzheimers Dement. 2023

5  Fortier M, Castellano CA, St-Pierre V, Myette-Côté É, Langlois F, Roy M, Morin MC, Bocti C, Fulop T, Godin JP, Delannoy C, Cuenoud B, Cunnane SC. A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT. Alzheimers Dement. 2021 Mar;17(3):543-552. doi: 10.1002/alz.12206. Epub 2020 Oct 26. PMID: 33103819; PMCID: PMC8048678.

6 Crawford, M.A..; Sinclair, A.J.; Wang, Y.;
Schmidt, W.F.; Broadhurst, C.L.; Dyall, S.C.; Horn, L.; Brenna, J.T.; Johnson, M.R.; Docosahexaenoic Acid Explains the Unexplained in Visual Transduction. Entropy 2023, 25, x. https://doi.org/10.3390/xxxxx 

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

8 Peng, M., Liu, Y., Jia, X. et al. Dietary Total Antioxidant Capacity and Cognitive Function in Older Adults in the United States: The NHANES 2011–2014. J Nutr Health Aging 27, 479–486 (2023). https://doi.org/10.1007/s12603-023-1934-9

9 Nurk E, Refsum H, Drevon CA, Tell GS, Nygaard HA, Engedal K, Smith AD. Intake of flavonoid-rich wine, tea, and chocolate by elderly men and women is associated with better cognitive test performance. J Nutr. 2009 Jan;139(1):120-7. doi: 10.3945/jn.108.095182. Epub 2008 Dec 3. PMID: 19056649.

10 Sesso HD, Manson JE, Aragaki AK, Rist PM, Johnson LG, Friedenberg G, Copeland T, Clar A, Mora S, Moorthy MV, Sarkissian A, Carrick WR, Anderson GL; COSMOS Research Group. Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial. Am J Clin Nutr. 2022 Jun 7;115(6):1490-1500. doi: 10.1093/ajcn/nqac055. PMID: 35294962; PMCID: PMC9170467.

What is the forgotten factor of mental health – despite the research being positive?

Homocysteine.

This is why we launched our highly accurate and groundbreaking at-home homocysteine test just before Christmas (and quickly sold out) because knowing this marker – your H factor – can help predict over 100 diseases. Specifically, homocysteine is an indicator of a person’s B vitamin status, and knowing this, can help reduce the risk of mental illness.

Yet it hasn’t been easily available or affordable to test this at home and is often not a marker checked by Dr’s.

But not any more!

Homocysteine & the Central Nervous System

“Homocysteine is a biomarker for over 100 diseases, but especially those of the central nervous system.” says pharmacology professor David Smith FMedSci, formerly Deputy Head of the Faculty of Medical Sciences at the University of Oxford. “It is a biomarker of impaired cognitive abilities in children, and in adults is a risk marker for stroke, dementia and Alzheimer’s, but also possibly for depression, anxiety, bipolar, schizophrenia, obsessive-compulsive disorder, Parkinson’s and multiple sclerosis. It is very much the forgotten factor, despite the research evidence being strongly positive (1). And the good news is, it is so easily corrected.” 

Patrick Holford, psychologist and our CEO and founder says “A raised homocysteine level means something is going wrong with a vital process that controls how we think, feel and perceive. It’s called methylation and is dependent on B vitamins. Some people absorb B12 less well. Some just need more of the B vitamin than others and that biochemical individuality, especially if their diet is already deficient, can tip them into a mental or neurological illness.”

Depression & Homocysteine

Those suffering from depression are also more likely to have higher homocysteine levels (2, 3).  Amanda-Jane is a case in point. She was suffering with chronic fatigue and low mood, so she decided to check her homocysteine level. She was shocked when she found her score was 26 mcmol/l (7 or less is considered optimal). After changing her diet and supplementing the B vitamins her sleep improved almost immediately and within four weeks, she had much more energy. Two months later she re-tested her homocysteine level and found it had dropped to 9. “I feel much better. My mood is very positive– no panic or depression. I feel buoyant, energetic and enthusiastic. I’m sleeping much better and my PMS has disappeared.” she said.

Also, every 5-point increase in homocysteine increases risk of being diagnosed with schizophrenia by a staggering 70%! (4) Yet very few sufferers are ever checked for raised homocysteine.

Homocysteine & B Vitamins

Professor Joseph Levine from the Stanley Research Centre and Beersheva Mental Health Centre in the Ben Gurion University in Israel devised a study to see what effect lowering homocysteine with B vitamins would have (5). He gave half of a group of 42 schizophrenic patients B vitamins (B6, B12 and folic acid) and the other half a placebo. Those taking the B vitamin supplements had both a dramatic reduction in their homocysteine levels and a significant improvement in their symptoms, except for one patient, who didn’t comply with the B vitamin treatment, didn’t improve and didn’t have a reduction in their homocysteine level. They were the exception that proves the rule.

Professor David Smith, writing in the Journal of Internal Medicine, together with world leading expert on homocysteine, Professor Helga Refsum from the University of Oslo, Norway, say “There are five diseases that can, at least in part, be prevented by lowering total homocysteine: neural tube defects, impaired childhood cognition, macular degeneration, primary stroke, and cognitive impairment in the elderly. We conclude from our review that total homocysteine values in adults of 10 mcmol/L or below are probably safe, but that values of 11 above may justify intervention. Homocysteine is more than a disease biomarker: it is a guide for the prevention of disease.” Not only does it predict an increased risk for a stroke, but having a lower homocysteine level, achieved by eating B12 rich foods such as fish and eggs, and folate and B6 rich foods such as whole foods, vegetables, nuts, seeds and beans, and supplementing B vitamins, helps those who’ve had a stroke recover faster (6).

We recommend anyone with a homocysteine level over 10 mcmol/L to supplement extra B vitamins, especially B6 (20mg), folate (400mcg) and B12 (500mcg). Homocysteine is a toxic amino acid that accumulates when there is a lack of B vitamins and damages your brain as well as your arteries.

Professor Smith’s research group at Oxford University has shown that giving people with pre-dementia these vitamins reduced the rate of brain shrinkage to less than half of that in those given placebos.

 “Further cognitive decline virtually stopped in those taking the B vitamins.” says Smith. 

Homocysteine, Pregnancy & Children’s School Grades

As many as two in five people over 60 have a raised homocysteine level. The reason why the B vitamin folic acid is recommended in pregnancy is because it lowers homocysteine. In ‘normal’ pregnancies with no complications in either mother or child, homocysteine remains below 7mcmol/L. In five out of seven studies women who have spontaneous abortions or miscarriages have a level above 15. The risk for having a pre-term baby is four times higher in women with a homocysteine level above 12 (7).  A study of 81 healthy women who then became pregnant found that the children of the women whose homocysteine before conceiving was above 9 were significantly more withdrawn, anxious and depressed and had more social problems including increased aggressive behaviour (8).  

“It is vital that a woman intending to become pregnant first checks her homocysteine level. Raised homocysteine, plus a lack of omega-3 fats found in fish is a major promoter of developmental problems and mental illness in children later in life.” says Holford. 

A child’s homocysteine level even predicts their school grades. A study compared the sum of school grades for ten core subjects, with homocysteine levels in a group of 692 Swedish school children aged 9 to 15. Increasing homocysteine levels were strongly associated with reducing grades as was inadequate folate intake (9).

Join us in our Citizen Science Project by testing your homocysteine! The home pin prick blood test is now back in stock.

Thank you for reading!

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

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

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

References

1 Smith AD, Refsum H. Homocysteine – from disease biomarker to disease prevention. J Intern Med. 2021 Oct;290(4):826-854. doi: 10.1111/joim.13279. Epub 2021 Apr 6. PMID: 33660358.

2 Moradi F, Lotfi K, Armin M, Clark CCT, Askari G, Rouhani MH. The association between serum homocysteine and depression: a systematic review and meta- analysis of observational studies. Eur J Clin Invest 2021: e13486. 

3 Nabi H, Bochud M, Glaus J, Lasserre AM, Waeber G, Vollenweider P, Preisig M. Association of serum homocysteine with major depressive disorder: results from a large population-based study. Psychoneuroendocrinology 2013; 38: 2309-18. 

4 JW Muntjewerff,Molecular Psychiatry (2006) 11, 143–149. doi:10.1038/sj.mp.4001746 

5 Levine J, Stahl Z, Sela BA, Ruderman V, Shumaico O, Babushkin I, Osher Y, Bersudsky Y, Belmaker RH. Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia. Biol Psychiatry. 2006 Aug 1;60(3):265-9. doi: 10.1016/j.biopsych.2005.10.009. Epub 2006 Jan 17. PMID: 16412989.

6 Yahn GB, Leoncio J, Jadavji NM. The role of dietary supplements that modulate one-carbon metabolism on stroke outcome. Curr Opin Clin Nutr Metab Care. 2021 Jul 1;24(4):303-307. doi: 10.1097/MCO.0000000000000743. PMID: 33631772; see also 

7 Dai C, Fei Y, Li J, Shi Y, Yang X. A Novel Review of Homocysteine and Pregnancy Complications. Biomed Res Int. 2021 May 6;2021:6652231. doi: 10.1155/2021/6652231. PMID: 34036101; PMCID: PMC8121575.

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

9 Torbjörn K. Nilsson, Agneta Yngve, Anna K. Böttiger, Anita Hurtig-Wennlöf, Michael Sjöström; High Folate Intake Is Related to Better Academic Achievement in Swedish Adolescents. Pediatrics August 2011; 128 (2): e358–e365. 10.1542/peds.2010-1481

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/

By Patrick Holford

The winter months aren’t always the happiest of times. Come December, January or February it has become normal for people’s mood to be low and anxiety to be high. 

But what if you could reduce your anxiety and boost your mood this winter?

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What cannabis, wine and prescription drugs have in common

Anxiety affects many people to varying degrees. 

It’s common, when faced with intense or constant feelings of anxiety, to ‘self-medicate’ with alcohol or cannabis. 

It’s socially acceptable to ‘need a drink’ after a bad day, or if we are feeling down. And, if that anxiety is more extreme, we turn to our GP for something stronger, such as prescription tranquillisers, or mood stabilisers. In one week in the UK, we pop something like 10 million tranquillisers, puff 10 million cannabis joints and drink 120 million alcoholic drinks. 

The choice of these three drugs – alcohol, cannabis and tranquillisers – is no coincidence.

They all promote GABA (gamma-aminobutyric acid), which is the brain’s peacemaker, helping to turn off excess adrenaline and calm us down. That’s why that beer or glass of wine makes us feel sociable, relaxed, happy and less serious, at least for an hour as GABA levels rise. But after an hour or so, GABA starts to fall, leaving us irritable and disconnected, and craving another – and another. 

The problem is that after a session of drinking, GABA levels become very suppressed and those negative feelings stay around. Most of us avoid this by drinking in the evening and going to sleep under the influence but alcohol also disturbs the normal cycle of dreaming, and it’s dreaming that regenerates the mind. So, when you wake up in the morning, you’re mentally tired, grumpy and irritable because of the low level of GABA, as well as dehydrated and sluggish as your body detoxifies the alcohol from the night before. 

The net effect is that alcohol, in the long run, makes you more anxious, not less. 

The same is true for cannabis, which, if habitually smoked, also reduces drive and motivation. 

So what are some other options? Here are some alternative ideas.

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Supplement GABA and Taurine

GABA is not only a neurotransmitter, it’s also an amino acid. This means it’s a nutrient and, by supplementing it, you can help to promote normal healthy levels of GABA in the brain.

There is one problem. In the EU, GABA has been classified as a medicine, meaning it is no longer available over the counter in the UK. However, GABA supplements are available online from countries such as the US.  GABA is made from taurine and glutamine and some ‘chill’ supplements contain these GABA promoters.

If you can get hold of GABA, supplement 250mg to 500mg, once or twice a day as a highly effective natural relaxant. But note that while it is not addictive, that doesn’t mean there are no side-effects in large amounts. Up to 2g a day has no reported downside; however, if you go up to 10g a day, this can certainly induce nausea or even vomiting, and a rise in blood pressure. So use GABA wisely, especially if you already have high blood pressure, starting with no more than 1g a day, and do not exceed 3g a day. If you take it in the evening it also helps you get to sleep.

Taurine is another relaxing amino acid, similar in structure and effect to GABA. Many people think taurine is a stimulant because it is used in so-called ‘energy drinks’, but it is not. It helps you relax and unwind from high levels of adrenalin, much like GABA. It’s also often recommended as an anti-ageing supplement as supplementation slows key markers of ageing (2).

Taurine is highly concentrated in animal foods such as fish, eggs and meat. Vegetarians are therefore more likely to be at risk of deficiency. Try 500 to 1,000mg of taurine, twice daily. There are no known cautions or adverse effects at reasonable doses.

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B vitamins and Vitamin C

B vitamins also help support your mood.

Vitamin B6 supplementation increases GABA and supplementation of 100mg reduced self‐reported anxiety in a recent study (3).  Another study found that higher vitamin B6 intake is associated with lower depression and anxiety risk in women but not in men (4). 

The combination of B6 and magnesium has proven particularly effective in reducing pre-menstrual anxiety. A higher intake of B vitamins is associated with lower levels of both anxiety and depression (5). A review of all the evidence on nutrients concluded: “Magnesium and vitamin B6 may be effective in combination in reducing pre-menstrual stress, and vitamin B6 alone may reduce anxiety effectively in older women. High-dose sustained-release vitamin C may reduce anxiety and mitigate increased blood pressure in response to stress (6).

Vitamin C, which is made in all animals bar a few, including primates, acts like a stress hormone. It is stored in the adrenal cortex, along with cortisol, and released into the blood raising blood levels several fold under conditions of stress. It actually helps cortisol to work such that animals who make vitamin C don’t have to produce so much vitamin C. It is logical that our evolutionary loss of the ability to make vitamin C has made us more prone to stress and anxiety. A number of studies show that increasing vitamin C reduces anxiety. A 14 day trial of 500mg of vitamin C versus placebo, given to high school students found exactly this (7). Another, giving 500mg twice a day, improved ‘mental vitality’ and attention and reduced fatigue (8).

Vitamin C’s energy-increasing effects have been known since the 1970s, when Dr Emanuel Cheraskin at the University of Alabama showed much lower levels of fatigue in those with an intake of vitamin C above 400mg a day (9). I recommend 1,000mg taken twice a day, especially when you are under stress or feeling anxious.

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Relaxing herbs – valerian, hops and passion flower

Valerian is an excellent anti-anxiety herb (Valeriana officinalis). As a natural relaxant, it is useful for several disorders such as restlessness, nervousness, insomnia and hysteria, and it has also been used as a sedative for ‘nervous’ stomach. Valerian acts on the brain’s GABA receptors, enhancing their activity and thus offering a similar tranquillising action as the valium-type drugs but without the same side-effects. As a relaxant you need 50 to 100mg twice a day, and twice this amount 45 minutes before retiring for a good night’s sleep.

Since valerian potentiates sedative drugs, including muscle relaxants and antihistamines, don’t take it if you are on prescribed medication without your doctor’s consent. Valerian can also interact with alcohol, as well as certain psychotropic drugs and narcotics.

Hops (Humulus lupulus) is an ancient remedy for a good night’s sleep and probably included in beer for that reason. Hops helps to calm nerves by acting directly on the central nervous system, rather than affecting GABA receptors. You need about 200mg per day, but the effect is much less than kava or valerian and most effective when taken in combination with these and other herbs such as passion flower.

Passionflower (Passiflora incarnata) was a favourite of the Aztecs, who used it to make relaxing drinks. It has a mild sedative effect and promotes sleep much like hops, with no known side-effects at normal doses. Passionflower can also be helpful for hyperactive kids. You need around 100 to 200mg a day. Combinations of these herbs are particularly effective for relieving anxiety and can really help break the pattern of reacting stressfully to life’s challenges.

These final two, hops and passionflower, are a better choice,  if you want to avoid excessive drowisness.

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Increase magnesium

Magnesium is another important nutrient that helps relax both muscles and mind. It is often included in sleep formulas for this reason. The worst diet for magnesium is one that is high in meat, milk, refined foods and sugar. Not only is such a diet deficient in magnesium, but it’s also high in calcium. The body needs the right balance of these two ‘push-me-pull-you’ minerals, which control both brain, nerve and muscle function. Too much calcium in relation to magnesium can cause muscle cramping, irregular heartbeat, high blood pressure, nervousness, irritability, insomnia and depression. Stress, coffee and alcohol also deplete magnesium. Magnesium is also a potent antioxidant and helps stabilise your blood sugar. It works together with zinc and B vitamins, especially B6, in many key enzymes in the body.

A study giving stressed, but otherwise healthy, adults either just magnesium or a combination of vitamin B6 (30mg) and magnesium (300mg), reported significant improvement in both anxiety and depression, with the combination being more effective. The study was 8 weeks long but most improvement had occurred within four weeks. Another, giving 248mg of magnesium, reported improvement in depression after six weeks (11).

Most people eat about 270mg but need closer to 500mg.  Eating a diet rich in vegetables, nuts and seeds can get your intake up to 500mg. Much like omega-3, our ancestors will have been eating twice as much as we do today. A small handful, or heaped tablespoon of chia or pumpkin seeds (28g or 1 ounce) will give you in excess of 100mg. A similar amount of almonds, peanuts or cashews will give you 80mg. A serving of oats, brown rice, potato or beans, black beans being the best, delivers about 50mg. The best vegetables are greens, especially spinach, kale, chard, green beans and peas in that order. A decent serving – think half a plate – can easily deliver 100mg. Another great food for magnesium is wheatgerm. 

Nutritional therapists know to supplement around 300mg of magnesium to anyone who needs more, for example, for sleep, anxiety, depression, muscle cramps or heart disease with the antioxidant capacity being an added bonus.. Very few multis contain more than 50mg, the best providing up to 150mg.

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Theanine: why tea is better than coffee

In studies when caffeine levels are matched, the effects of tea and coffee on mood are very different (12). This may be because tea also contains the natural amino acid l-theanine – a relaxant. Research suggests that 50mg L-theanine naturally stimulates activity in the brain, known as alpha waves, which are associated with a relaxed but alert mental state (13). Supplements containing L-theanine and the amino acid GABA can help to make you feel more relaxed and less ‘edgy’ (14). A trial of 400mg of theanine has been shown to help boys with ADHD get to sleep (15).

Supplements providing combinations of GABA (or its precursors), theanine, magnesium and relaxing herbs, are most effective.

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Panic attacks, lactic acid & the power of breath

Some people experience panic attacks, characterised by extreme feelings of fear. These are not at all uncommon. Symptoms often experienced during a panic attack include palpitations, rapid breathing, dizziness, unsteadiness and a feeling of impending death. Those who suffer with agoraphobia (a fear of being alone or in public places) often know that they can go out or can be alone but are afraid of having a panic attack (16).

As ‘psychological’ as this sounds, there is a biochemical imbalance behind many people’s anxiety attacks, apart from, or as well as, any psychological factors. It’s too much lactic acid. When muscles don’t get enough oxygen, they make energy from glucose without it. The trouble is, there’s a by-product called lactic acid. As strange as this might seem, giving lactic acid to those prone to anxiety attacks can induce an anxiety attack.

One way to increase lactic acid levels is to hyperventilate. Many people will do this when they’re experiencing anxiety attacks. Hyperventilation changes the acid level of the blood by altering the balance of carbon dioxide. The body responds by producing more lactic acid. The solution is to breathe into a paper bag during a hyperventilation attack and concentrate on breathing deeply for a minute. This helps redress the balance. Moments of blood sugar dips can also both bring on hyperventilation and increase lactic acid. So, keep your blood sugar level even by eating little and often.

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An integrated approach works best

While the causes for high levels of anxiety are often psychological, by balancing blood sugar (read more about sugar here), reducing stimulants, ensuring optimum nutrition, plus judicially using these natural anti-anxiety herbs and nutrients, you can break the habit of reacting with fear and anxiety to life’s inevitable stresses. Addressing the potential underlying triggers for anxiety is also important.

One of the best things you can do to support your mood is to support and upgrade your brain by doing the following:

Read more about the impact of sugar on your brain here
Take the Cognitive Function Test – so that you can get personalised results on how to support your brain and reduce the risk of disease.
Take part in our research and do an at home blood tests! Optimise your mental health with the DRIfT 4 in 1 test here.

Congratulate yourself on joining us as a Citizen Scientist and changing your brain while helping our research.

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

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. 

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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 Pitts FN and McClure JN, New Engl J Med, 1967

16 Rakhimov A, Normal Breathing – The key to Vital Health; see also Fried R, The Hyperventilation Syndrome