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The Four Horsemen of the Mental Health Apocalypse #1 – Brain Fats & Methylation

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.

โ€˜Brain health conditions have become a global health emergency,โ€™ 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 Alzheimerโ€™s in 2022 was estimated to be โ‚ฌ1.2 trillion across the EU which is half the UKโ€™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. Thatโ€™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 Alzheimerโ€™s, as well as strokes, Parkinsonโ€™s and multiple sclerosis.

The big question is: why?

Introducing the four horsemen…

Iโ€™m proposing that there are four main biological drivers of our demise which Iโ€™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 โ€“ brain fats and methylation โ€“ 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 โ€˜exhaust fumesโ€™ of energy metabolism.

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 โ€˜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) intakeโ€™. Each 100mg increment of DHA was associated with an 8โ€“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 personโ€™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.

Itโ€™s compelling science. That is why my first recommendation is to always test your omega-3 index.

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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 โ€“ 7.7 per cent. Iโ€™ve since upped my intake of DHA by 500 mg, to 750 mg total daily intake.

In its pure form, DHA isnโ€™t enough, it has to become โ€˜phosphorylatedโ€™ to work. Itโ€™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 โ€˜mixerโ€™ 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 isnโ€™t your thing, supplementing with lecithin (granules or capsules) is a must – aim for two 1200mg capsules or 250mg of PC per day.

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 Alzheimerโ€™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. Weโ€™ve tested 410,000 peopleโ€™s cognitive function so far but need more people who know, or are willing to test their vitamin D.

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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 Chinaโ€™s leading Alzheimerโ€™s prevention expert, Professor Jin-Tai Yu, whom we are honoured to have in our Scientific Advisory Board. It was also rated so by the US National Institutes of Health researchers (14). 

The four horsemen of the mental health apocalypse

Homocysteine is also a biomarker for over 100 diseases including almost all mental and neurological diseases. The seminal paper by Professors David Smith and Helga Refsum on the subject is vital for all to read. For example, just one recent meta-analysis showed that both homocysteine, vitamin B12, and folic acid predict the onset and development of Parkinsonโ€™s. Homocysteine levels above 11ยตmol/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 10ยตmol/L , giving 20 mg of B6, 400 mcg of methylfolate and 500ยตg 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 ยตmol/L).โ€™ And in the UK, two in five adults over 61 have insufficient B12 to prevent accelerated brain shrinkage (16).

Homocysteine not only predicts Alzheimerโ€™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 donโ€™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, itโ€™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 Alzheimerโ€™s risk by over 33 per cent (19). 

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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 10ยตmol/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 Universityโ€™s health economists estimate would save the UK ยฃ66 million per year (23).

However, itโ€™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). 

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

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References

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

3 Crawford M, Marsh, D โ€˜The Shrinking Brainโ€™ 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 Alzheimerโ€™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; Alzheimerโ€™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 Pล‚udowski 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 Aฮฒ-related biomarkers in older adults with Alzheimerโ€™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 Roigรฉ-Castellvรญ J, Murphy M, Fernรกndez-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 Jernerรฉn F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H, Smith AD (2015). Brain atrophy in cognitively impaired elderly: the importance of long-chain ฯ‰-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, 3731โ€“3739 (2022). https://doi.org/10.1007/s00394-022-02924-w; see also Jernerรฉn 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). 

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Early Dementia Prevented by Our 8 Domains, Shows UK BioBank Study

Early-onset dementia, often talked about as โ€˜geneticโ€™, has been linked to exactly those factors that our Dementia Risk Index questionnaire, part of the Cognitive Function test, assesses. 

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

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 ฮต4 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 Alzheimerโ€™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 wasnโ€™t sufficiently investigated, nor homocysteine, because the UK Biobank questionnaire doesnโ€™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:

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.

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References

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

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

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In Pursuit of GABA: the Antidote to Anxiety this Winter

By Patrick Holford

The winter months arenโ€™t always the happiest of times. Come December, January or February it has become normal for peopleโ€™s mood to be low and anxiety to be high. 

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

What cannabis, wine and prescription drugs have in common

Anxiety affects many people to varying degrees. 

Itโ€™s common, when faced with intense or constant feelings of anxiety, to โ€˜self-medicateโ€™ with alcohol or cannabis. 

Itโ€™s socially acceptable to โ€˜need a drinkโ€™ 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 โ€“ alcohol, cannabis and tranquillisers โ€“ is no coincidence.

They all promote GABA (gamma-aminobutyric acid), which is the brainโ€™s peacemaker, helping to turn off excess adrenaline and calm us down. Thatโ€™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 itโ€™s dreaming that regenerates the mind. So, when you wake up in the morning, youโ€™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.

Supplement GABA and Taurine

GABA is not only a neurotransmitter, itโ€™s also an amino acid. This means itโ€™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 โ€˜chillโ€™ 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 doesnโ€™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 โ€˜energy drinksโ€™, but it is not. It helps you relax and unwind from high levels of adrenalin, much like GABA. Itโ€™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.

B vitamins and Vitamin C

B vitamins also help support your mood.

Vitamin B6 supplementation increases GABA and supplementation of 100mg reduced selfโ€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: โ€œMagnesium 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 donโ€™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 โ€˜mental vitalityโ€™ and attention and reduced fatigue (8).

Vitamin Cโ€™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.

Relaxing herbs โ€“ 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 โ€˜nervousโ€™ stomach. Valerian acts on the brainโ€™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 nightโ€™s sleep.

Since valerian potentiates sedative drugs, including muscle relaxants and antihistamines, donโ€™t take it if you are on prescribed medication without your doctorโ€™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 nightโ€™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 lifeโ€™s challenges.

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

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 itโ€™s also high in calcium. The body needs the right balance of these two โ€˜push-me-pull-youโ€™ 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 โ€“ think half a plate โ€“ 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.

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 โ€“ 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 โ€˜edgyโ€™ (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.

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 โ€˜psychologicalโ€™ as this sounds, there is a biochemical imbalance behind many peopleโ€™s anxiety attacks, apart from, or as well as, any psychological factors. Itโ€™s too much lactic acid. When muscles donโ€™t get enough oxygen, they make energy from glucose without it. The trouble is, thereโ€™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 theyโ€™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.

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 lifeโ€™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:

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

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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., โ€˜Daily vitamin consumption and fatigabilityโ€™, Journal of the American Geriatrics Society (1976), vol 24(3), pp. 136โ€“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 Pitts FN and McClure JN, New Engl J Med, 1967

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

Further info

Omega-3 cuts dementia risk by a third

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). 

One of the study authors, Professor Bill Harris from Stanford Universityโ€™s Department of Medicine in South Dakota, says โ€œThere 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%โ€.

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.

Whatโ€™s more a meta-analysis of 48 studies in the American Journal of Clinical Nutrition in 2023 (3) also concludes that โ€˜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 intakeโ€™. 

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

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 personโ€™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.

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 โ€˜citizen scienceโ€™ with the research results shared back to everyone involved. 

Less than one per cent of Alzheimerโ€™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.

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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 Alzheimerโ€™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; Alzheimerโ€™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

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The Food for the Brain Mascot – Tommy Gun

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 โ€“ 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 (Patrickโ€™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 60โ€™s and invented the Union Jack pop art, putting it on everyday items from mugs to tea trays. He then became the Grateful Deadโ€™s European tour manager. Not everything consumed in those days was exactly good for the brain!  His โ€˜son-out-lawโ€™ was Joe Strummer of the Clash (Tommy Gun is a Clash song). 

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.
Buy Blood test here button.
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Further info

Raised Homocysteine Predicts over 100 Diseasesย 

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

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

Itโ€™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 โ€˜The H Factorโ€™ describing it as โ€˜the biggest health breakthrough of the centuryโ€™. Reviewing the book ITVโ€™s This Morning Doctor, Chris Steele, said โ€˜Homocysteine is the new cholesterol. Itโ€™s potentially your most important health statistic.โ€™ In Irelandโ€™s Late Late Show, I tested the host, Pat Kenny, and revealed his level to be way too high (above 15ยตmol/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 Alzheimerโ€™s. 

Technically we can call homocysteine a โ€˜biomarkerโ€™ which is the title of a very important paper โ€˜Homocysteine โ€“ from disease biomarker to disease preventionโ€™ 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.ย 

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 โ€“ only inexpensive vitamins. 

What is more, having a level above 11ยตmol/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). Itโ€™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 โ€“ 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.

What is homocysteine and why is it so important? 

Many nutrients in the body do not work in the form you ingest them โ€“ that is until they get โ€˜methylatedโ€™. 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 โ€“ by methylation. Histamine and hormones such as oestrogen are examples. Also toxins, from mercury to arsenic need to be detoxified โ€“ by methylation. The genes youโ€™re born with can be โ€˜activated or expressedโ€™ or โ€˜downregulatedโ€™ 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 youโ€™re not doing methylation properly. This is because thereโ€™s a log jam on the way to making the bodyโ€™s most important โ€˜methylatorโ€™ called s-adenosyl methionine or SAMe for short. Think of it as the conductor of the methylation orchestra. Itโ€™s made from an amino acid you eat โ€“ methionine. Itโ€™s another example of a food nutrient that doesnโ€™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

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. Thatโ€™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 donโ€™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).

Get homocysteine down before getting pregnant

We call Hcy a biomarker, as opposed to a risk factor, as we donโ€™t always know if it is actually causing the problem or just associated with it. Thatโ€™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 ยตmol/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)? Thatโ€™s harder to answer but there are a number of โ€˜toxicโ€™ consequences of raised Hcy such as damaging the arteries and the brain. Also, many things are generally bad for your health โ€“ 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). 

Protect your brain by lowering homocysteine

Hcy damages the arteries including blood vessels in the brain. Thatโ€™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 pโ€™tau which is a toxic substance known to cause โ€˜neurofibrillary tanglesโ€™ which are one of the hallmarks of Alzheimerโ€™s that big pharma is trying to develop a drug for. They neednโ€™t bother because lowering Hcy with inexpensive B vitamins lowers pโ€™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 โ€˜causalโ€™ –  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 youโ€™ve already had a stroke or got Alzheimerโ€™s there is little room for improvement.

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 werenโ€™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. โ€˜The homocysteine hypothesis is dead. Homocysteine is not a causal risk factor. It is an innocent bystanderโ€™ declared the author, Dr Bonaa. 

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

>> B vitamins donโ€™t lower risk if you donโ€™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. โ€˜Call off the funeralโ€™, 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. 

Thatโ€™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.

Is there a mental or neurological illness that isnโ€™t cranked up by high homocysteine?

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

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

Plasma total homocysteine as a disease biomarker
Disease/Syndrome
Insufficient B vitamin status
Folate, B12, B6, B2
Inborn errors of homocysteine and vitamin metabolism and transport
Cardiovascular diseases

Myocardial infarction
Severity of coronary artery disease
Hypertension
Restenosis of coronary arteries and adverse outcomes after angioplasty
Stroke
Stroke mortality
Silent brain infarct
Carotid plaque area, stenosis, intima-media thickness
Intracerebral arterial stenosis
Peripheral vascular disease
Venous thrombosis
Arterial aneurysm
Arterial stiffness
Atrial fibrillation
Cerebral small vessel disease
Cerebral microbleeds
Disruption of blood-brain-barrier
Endothelial mediated dilatation โ€“ impairedVascular complications of diabetes
Raynaudโ€™s syndrome
Takayasu arteritis
Thromboangiitis obliterans (Buergerโ€™s disease)
Moyamoya disease
Behรงet disease
Erectile dysfunction
Other syndromes
Mortality
Frailty
Cancer
Metabolic syndrome
Obesity
Bone disease, osteoporosis
Inflammatory bowel disease, Crohns
Non-alcoholic fatty liver disease
Renal insufficiency, chronic kidney disease
Chronic obstructive pulmonary disease
Alcohol abuse
Psoriasis
Vitiligo
Sclerosis
Sickle-cell disease
Burning mouth syndrome
Atrophic glossitis
Quality of life in centenarians
Obstructive sleep apnea
Hypothyroidism
Telomere shortening
Systemic lupus erythematosus (SLE)
Dermatomyositis
Inflammatory response
Periodontal disease
Hearing loss
Gout
Blood lead concentration
Maternal tHcy 
Pregnancy complications
Outcomes in child
โ€“ small for gestational age, fetal growth
โ€“ neural tube defects
โ€“ congenital heart disease
โ€“ orofacial clefts
โ€“ renal function
โ€“ child cognition
โ€“ child behaviour
โ€“ schizophrenia
โ€“ autism spectrum disorder
Central nervous system diseases
Incident Alzheimerโ€™s disease/dementia
Vascular dementia, vascular cognitive impairment
Post-stroke cognitive impairment
Cognitive decline after concussion
Cognition in children
Cognition in elderlyInitiation of cognitive decline in ageing
Conversion from cognitive impairment to dementia
Cognitive decline in dementia 
Atrophy of brain tissue/gray matter
Atrophy of brain white matter
White matter damage
Alzheimer brain pathology (P-tau)
Multiple sclerosis
Cognitive decline in Parkinsonโ€™s disease
Depression
Bipolar disorder
Schizophrenia
Amyotrophic lateral sclerosis/ Motor Neuron Disease
Multiple System Atrophy
Impaired motor development in infant
Early neurological deterioration after stroke
Glasgow coma scale
Migraine
Autism spectrum disorder

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.  ยฉ 2021 The Association for the Publication of the Journal of Internal Medicine 3 Journal of Internal Medicine

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 shouldnโ€™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. Iโ€™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.

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 donโ€™t have raised Hcy. This will do nothing to lower a high H score. Professorโ€™s Smith and Refsum recommend 500mcg a day โ€“ thatโ€™s two hundred times higher. This is both safe and effective especially if taken alongside B6 (20mg) and methylfolate (400mcg). Also, it doesnโ€™t take so long you bring your level down. Iโ€™ve had clients with H levels from 30 up to over 100 ยตmol/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; donโ€™t smoke or drink in excess (one 125ml of red wine doesnโ€™t affect homocysteine levels); donโ€™t drink more than one coffee a day; reduce stress and insomnia and keep fit.

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

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 Roigรฉ-Castellvรญ J, Murphy M, Fernรกndez-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;59:1399โ€“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. โ€œDonโ€™t Phos Over Tauโ€: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimerโ€™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 exacerbatesฮฒ-amyloid, tau pathology, and cognitive deficit in a mouse model of Alzheimerโ€™s disease with plaques and tangles. Ann. Neurol. 75:851โ€“63; alsoย  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-Pouriรฉ 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 Parkinsonโ€™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 

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The Channel We Are Swimming…

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

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. 

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

Thatโ€™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 โ€™truthโ€™ 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.

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Further info

Recovering Your Memory & Rebuilding 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 โ€˜structureโ€™ โ€“ that is building brain cells and their connections; then it’s about the best โ€˜functionโ€™ as in fuel supply; and โ€˜utilisationโ€™ and the importance of having an active physical, social and intellectual lifestyle.

The thing about memory is that it is very subjective.

One personโ€™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 itโ€™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 โ€˜course correctโ€™ 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 โ€˜amberโ€™ or โ€˜at risk’ โ€“ 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 โ€˜bodyworkโ€™. 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.ย 

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

โ€œIโ€˜ve been doing the Cognitive Function Test for about 10 years. Iโ€™m no longer worried that Iโ€™m losing my mental abilities.โ€ Now, age 70, her cognitive function has improved. โ€œIn fact, my memory is better, my vocabulary has improved and Iโ€™m no longer searching for that โ€œrightโ€ word – itโ€™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 Alzheimerโ€™s are not to be feared and has played a significant role in reinforcing the lifestyle changes Iโ€™ve made.โ€

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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. 

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 participantโ€™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 brainโ€™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 – thatโ€™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 โ€˜free radicalsโ€™, a byproduct of energy production. Think of antioxidants as the โ€˜fuel filterโ€™ 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 โ€˜recycledโ€™ by anthocyanins – thatโ€™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).

Donโ€™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 Alzheimerโ€™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 โ€˜nutrient reference valueโ€™ 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.

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 brainโ€™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 youโ€™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 youโ€™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 โ€˜18:6โ€™ (18 hours fasting, six hours eating). After your last evening meal, fast until lunch the next day, but start your day with a Hybrid Lattรฉ containing a tablespoon of C8 oil. Your brain is more likely to convert the C8 to ketones if you are โ€˜starvedโ€™ 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 itโ€™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 Alzheimerโ€™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 Alzheimerโ€™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: โ€œWe 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.โ€

So what is considered a โ€˜goodโ€™ 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.

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 Lionโ€™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 120โ€“300 mg of standardized Ginkgo biloba. It slightly thins the blood so should be used with caution for those on blood thinners. Itโ€™s an optional extra.

Lionโ€™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 โ€˜stimulantโ€™ 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. Iโ€™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.


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. 

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References

1 Martรญn Gimรฉnez 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 Alzheimerโ€™s disease: A meta-analysis of dose-response โ€ . 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 Alzheimerโ€™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 Aฮฒ-related biomarkers in older adults with Alzheimerโ€™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 Alzheimerโ€™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), 84โ€“94. https://doi.org/10.1016/j.stemcr.2016.12.007

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, Cichoล„ 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;8:183โ€“191. [PubMed] [Google Scholar]

23 Sergio W. Use of DMAE (2-dimethylaminoethanol) in the induction of lucid dreams. Med. Hypotheses. 1988;26:255โ€“257. doi: 10.1016/0306-9877(88)90129-6. [PubMed] [CrossRef] [Google Scholar]

24 Baumgaertel A. Alternative and Controversial Treatments for Attention-Deficit/Hyperactivity Disorder. Pediatr. Clin. N. Am. 1999;46:977โ€“992. doi: 10.1016/S0031-3955(05)70167-X. [PubMed] [Google Scholar]

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26 Moldavan M, Grygansky AP, Kolotushkina OV, Kirchhoff B, Skibo GG, Pedarzani P (2007) Neurotropic and trophic action of Lion’s Mane mushroom Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae) extracts on nerve cells in vitro. International Journal of Medicinal Mushrooms 9, 15-28; see also Yadav SK, Ir R, Jeewon R, Doble M, Hyde KD, Kaliappan I, Jeyaraman R, Reddi RN, Krishnan J, Li M, Durairajan SSK. A Mechanistic Review on Medicinal Mushrooms-Derived Bioactive Compounds: Potential Mycotherapy Candidates for Alleviating Neurological Disorders. Planta Med. 2020 Nov;86(16):1161-1175. doi: 10.1055/a-1177-4834. Epub 2020 Jul 14. PMID: 32663897.

Further info

Your Brain Needs Supplements Beyond a โ€˜Well-Balanced Dietโ€™…

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 โ€˜deficiencyโ€™, 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 โ€˜nutritional insufficiencyโ€™.

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 โ€˜RDAsโ€™, 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 โ€˜optimalโ€™.

Outdated definitions

This illustrates that the definition of โ€˜deficiencyโ€™ 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 individualโ€™s ability to absorb nutrients.

While medical and advertising law prohibits the description of a nutritional supplement or food as โ€˜preventing, reversing or treating a diseaseโ€™ 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 โ€“ 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.

What nutrients should we pay special attention to?

Four nutrients are especially significant in this regard.

Vitamin D โ€“ 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 โ€“ 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 โ€“ 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 โ€“ 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.

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

Donโ€™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.

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Your Brain is Our Oyster

by Patrick Holford

Shakespeare actually said โ€œthe world’s mine oyster, which I with sword will open.โ€ 

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.

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 whatโ€™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 โ€˜perfectโ€™ storm of factors directly under your control.

At Food for the Brain, thanks to already well over 400,000 โ€˜citizen scientistsโ€™ whoโ€™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 โ€“ all under your control โ€“ that are driving this terrible and unnecessary shrinkage. Alzheimerโ€™s, which is two-thirds of dementia, is a disease of ignorance that creates ignorance and leaves sufferers like empty shells upon the shore.

Size Matters

Yet, we know how to stop this. There is no magic. There is just pure science and common sense โ€“ 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 (thatโ€™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 โ€˜indexโ€™ of HbA1c, omega-3, homocysteine and vitamin D can be used to predict cognitive decline โ€“ and thus highlight key prevention steps. That, as a personโ€™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 โ€œthat 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.โ€ 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: โ€˜Patrick follow the logic. It is the logic that counts.โ€

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 Alzheimerโ€™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?

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 ยฃ100 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 Alzheimerโ€™s charities having over ยฃ 30 million to spend on research every year and the Uk government pledging ยฃ166 million a year, yet spending nothing on real prevention.

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

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

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. 

โ€œLessons 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 rawfordโ€™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: Thatโ€™s roughly the number of oysters New Yorkers ate, every day, in the mollusksโ€™ 19th-century heyday. New York was surrounded by immense natural oyster reefs. By 1880 New York was the undisputed capital of historyโ€™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. โ€œWhat shall we do?โ€ his American travelling friend asked. His lordship replied โ€œReturn to Broadway and have some more oysters!โ€

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.

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