By Patrick Holford
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‘Brain health conditions have become a global health emergency,’ according to the Federation of European Neuroscience Societies last year (1).
The big question is: why?
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I’m proposing that there are four main biological drivers of our demise which I’m calling the four horsemen of the mental health apocalypse: a lack of brain fats, messed up methylation, loss of glucose control and excessive oxidation.
The first two – brain fats and methylation – are vital for the integral structure of neuronal membranes.
The second two are vital for the function of brain cells, supplying fuel and coping with the oxidant ‘exhaust fumes’ of energy metabolism.
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While omega-3 and B vitamins literally build a healthy brain, it is glucose and ketones that fuel it.
As a result of this process, oxidants are created which age the brain through the process of oxidation. Of course, oxidation can also occur through external causes, which is why smoking and air pollution are also established risk factors for Alzheimer’s.
Which leads us to the next two ‘horses of the mental health apocalypse’: the brain’s fuel supply and antioxidant protection. The brain consumes more energy than any other organ of the body. Neurons can only run on glucose or ketones. The irony is that the consequence of eating too many carbs and sugar is that the brain develops insulin resistance – effectively blocking the glucose from entering the mitochondria within the neurons. Starved of their energy source, we experience the consequences as mental fatigue and forgetfulness. According to Dr Robert Lustig, Emeritus Professor of Pediatrics at the University of California, San Francisco and a member of our Scientific Advisory Board, “This cognitive decline starts young. Cognitive decline in overweight children is associated with a high GL diet (1), and adolescents with metabolic dysfunction, driven by a high GL diet, have been shown to have shrinkage of the hippocampal area of the brain, as well as other structural changes and cognitive deficits (2).” This particular study showed actual shrinkage of the Alzheimer’s associated area of the brain in teenagers with metabolic syndrome as a consequence of too much sugar and ‘white’ carbs. The youngest age of an Alzheimer’s diagnosis, which requires proof of shrinkage of the hippocampal area of the brain, is age 19, in a young man in China who had no genetic risk factors (2).
It’s a biochemical storm.
As well as the fuel starvation that insulin resistance generates, the converse of blood sugar spikes, create Advanced Glycation End-products, or AGEs, that literally damage neurons. This ‘glycosylation’ is also seen in red blood cells, and why the HbA1c test which measures glycosylated haemoglobin is so good at predicting our health. If over 6.5% (or 48 mmol/mol) of these erythrocytes are sugar damaged, it’s a clear basis for a diabetes diagnosis. Just as for the omega-3 index, HbA1c is a reliable long-term measure showing the average sugar spikes over the past three months. You can assume what’s happening in the membranes of red blood cells is also happening to the neuronal membranes in the brain.
This is why the next brain essential is to measure HbA1c.
If 6.5% is the cut-off for a diabetes diagnosis, the ideal level is actually considerably lower. In what is usually considered to be the ‘normal range’, teenagers with HbA1c above 5.4% show cognitive decline and shrinkage of the hippocampus in the central area of the brain compared to those with lower HbA1c levels (3). “In teenagers with raised, but normal levels of HbA1c, there is clear evidence of the same kind of memory problems, and the same areas of brain shrinkage seen in patients with Alzheimer’s Disease” says Dr Robert Lustig.
Shrinkage of the hippocampus is the hallmark of Alzheimer’s and is used to diagnose the disease. A new study shows that 40-year-old adults with so-called normal glucose levels, but at the higher end of the normal range, have increased their risk of Alzheimer’s by 15%. (4)
A primary function of sleep is to repair all the neuronal membrane damage that occurs during the day. No sleep, no repair and the brain ages fast. This is mainly why lack of sleep is also a strong risk factor for Alzheimer’s.
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There’s a growing interest in the role of ketogenic diets and ketone promoting supplements for brain health. Professor Stephen Cunnane, our expert in the new science of ‘keto therapeutics’ has shown that giving C8 oil or supplementing ketones can help to prevent Alzheimer’s, slow down cognitive decline, improve mood and lessen anxiety. His studies showed, in those with mild cognitive impairment, that taking 30g (two tablespoons) of mainly C8 oil, resulted in a 230% increased brain energy production from ketones with no change in energy derived from glucose (5), thus filling the ‘energy gap’ so often experienced by older people or those drifting towards insulin resistance. “Our research shows that the areas of the brain that have trouble using glucose for energy are able to use ketones perfectly well, even in moderately advanced dementia. This may explain why many people later in life who are given a supplement of C8 oil or MCT oil have improvements on a battery of cognitive tests. They often feel it brings their brain power back to life” says Cunnane.
Many people also report feeling calmer, less anxious and less depressed on ketogenic diets. A new book, Change Your Diet, Change Your Mind, out next month by psychiatrist Dr Georgia Ede digs deep into the growing evidence that a ketogenic diet, or at least one low in carbohydrates, is brain-friendly and helps people out of various mental health disorders. Or you can watch the recent webinar she did with us here.
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The more biologically active an essential fat is (with DHA at the top), the more prone it is to oxidation.
It is literally this ability of DHA to absorb energy (photons from light) that creates the impulse that passes information from the eye to the brain. It explains the origin of the brain and nervous system, going back a billion years to a rudimentary single cell called dynoflagellate. This little organism basically used the electric shock from photons to create the first ‘twitch’ towards light. Where there was light, there was food, and ultimately the evolution of the nervous system and brain. In simple terms, we can see that the brain is really an extension of the eye. How do we see with such precision and speed? Until now, no-one has been able to explain this satisfactorily. At the age of 93, Professor Michael Crawford, who helped our charity get started, has worked out how this occurs and how we see in colour. It requires knowledge of quantum physics, explained in a recent paper entitled ‘Docosahexaenoic Acid Explains the Unexplained in Visual Transduction’.(6)
With all this volatile fatty acid and mitochondrial energy production, cleaning up the oxidant exhaust fumes is a vital function for a healthy brain. So how do we achieve protection and how do we measure it?
There are hundreds, if not thousands of antioxidants and polyphenols in our food. Foods can be measured for their ‘Total Antioxidant Capacity’ or TAC for short. It’s worked out from an equation involving eight key antioxidants from vitamin A, carotenes (think carrots), lycopenes (rich in tomatoes), lutein and zeaxanthine (rich in green vegetables), vitamin E (in nuts and seeds), but most of all vitamin C (rich in berries, broccoli, peppers and other vegetables).
Vitamin C is a keystone nutrient as far as swinging the antioxidant equation in our favour. Individually, the impact of these nutrients on our health may be less than when combined. For example, a study of 4,740 Cache County Utah elderly residents found that those supplementing both vitamin E and C cut their risk of developing Alzheimer’s by two thirds (66%). Taking just one cut the risk by a mere quarter (25%). (7)
The higher the TAC score of our diet, the lower our risk of memory decline becomes. This was the finding of a recent study of 2,716 people over age 60. Higher TAC scores correlated with better memory function (8). Those in the highest quarter of TAC scores had half the risk of decreasing memory. Powerful stuff!
Tea, cacao, red wine, red onions, olives and berries are rich sources of polyphenols. Many of these polyphenol-rich foods improve circulation, lower blood pressure and dampen down inflammation which lies behind many brain and heart health problems.
More than a decade ago research in Norway (9) found that the more tea you drink the better; a small glass of wine (125ml) a day (preferably red, as it is rich in resveratrol) reduces the risk of cognitive decline. Cacao is also beneficial, ideally no more than 10g, (about 3 pieces) of dark, 70 percent or more. Other studies based on adding cacao to the diet have shown improved cognition, possibly by improving circulation. This was recently confirmed in a big ‘COSMOS’ trial involving over 20,000 people given a cacao extract supplement versus a placebo for five years (10). The reduction in cardiovascular risk was even greater than that of a Mediterranean diet.
The take-away message? Polyphenols are a vital part of a healthy diet for both our heart and our brain.
So, what do we need to eat and drink to protect our brain and body? Basically, eat a Mediterranean-style ‘rainbow coloured’ diet. A Mediterranean diet has more fish, less meat and dairy, more olive oil, fruit and vegetables including tomatoes, legumes (beans and lentils), and whole grain cereals than a standard Western diet. It also includes small quantities of red wine. There are variations of this kind of diet, called the MIND diet and the DASH diet, but the core components are the same. As researchers drill down, we are learning what to eat and drink and how much, to keep our minds sharp and brain young.
The trick is to really start thinking of the colours we are eating and gravitate to the strong colours, choosing organic where possible. Mustard and turmeric, for example, are strong yellows. Bright oranges include butternut squash, sweet potato, carrots. For red, think tomatoes and watermelons. Anything purple, magenta or blue is brilliant for us too. From beetroots (eat them raw, grated into salads) to blueberries, blackberries to raspberries, all these foods are fantastically good for us, so tuck in!
In addition to food, as a health aspiring 65-year-old, I both supplement 1 gram of vitamin C twice a day and take an AGE Antioxidant containing Co-Q10, alpha lipoic acid, n-acetyl cysteine (NAC – as a precursor to glutathione which is the master antioxidant) and resveratrol as well as vitamin E and A – both beta-carotene and retinol. Many people think that there is no point supplementing glutathione because it is so rapidly oxidised, or sacrificed, to disarm oxidants, but it is also rapidly recycled by anthocyanidins in blue/red berries. So, combining the two reloads glutathione. This film shows how.
But how do we measure our antioxidant status?
My research team is working on exactly this challenge and we are finding that the ratio between reduced glutathione (GSH) and oxidised glutathione (GSSG) in red blood cells is probably the best biological determinant. We hope to introduce that into our panel of functional indicators, and research how it correlates with dietary intake and lifestyle habits as well as cognitive function.
We are due to launch a DRIfT Test as part of a global prevention initiative, which will be a 4 in 1 test
The UK Biobank has collected data on 500,000 people since 2006, inviting people to fill in questionnaires, give blood and carry out certain tests. We are funded by ‘Friends’ who pay £50/$60/€60 a year. So far we have collected data on 410,000 people and this number is growing by about a hundred a day.
In addition to taking the blood test, participants are invited to complete a validated online Cognitive Function Test (not a questionnaire), followed by a comprehensive 144 question Dementia Risk Index diet and lifestyle questionnaire which takes 20-25 minutes. This works out a person’s future risk and shows what’s driving the risk. This is a free service.
We run the UK’s leading dementia prevention charity which is running the prevention project together with Dr Tommy Wood, Assistant Professor at the University of Washington. “By tracking a person’s blood sugar, vitamin B, D and omega-3 status against changes in cognitive function over time, in addition to lifestyle factors such as sleep and physical activity, we can learn what really helps prevent cognitive decline.” says Dr Wood, the principal investigator for the study.
All donations are put back into research, and the results of the research are shared back to the people.
This is science for the people, funded by the people, shared back with the people. We call them Citizen Scientists and we hope to reach a million people around the world within a year or so making this the biggest prevention-focussed study of its kind. The purpose of research is to help people. Too often great scientists do great studies, which get published and ignored. We have to face the fact that, in the UK as an example, the Government has commissioned four reports on mental health and Wellcome did a further independent report, all showing we have a cerebral tsunami with brain and mental health disorders ahead of every other disease.
They have ignored every single one.
Change is not going to come from the Government or the NHS. It is going to have to come from us, the people. I urge everyone in natural medicine to take the test themselves, share it with others and support us by becoming Friends and donating £50 a year, getting so much in return.
This is how we are funding our amazing research team. We are a lean, keen, small but mighty team.
Every donation, big or small, goes right back into helping people prevent these preventable and terrible diseases such as dementia.
Together, we can change the world.
We need to because time is running out.
We will lose our humanity if we don’t stop this brain drain.
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Want to learn more about homocysteine and how to reclaim your brain? Join us for the Homocysteine Unplugged webinar.
Thank you for reading!
Food for the Brain is a non-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.
By completing the Cognitive Function Test you are joining our grassroots research initiative to find out what really works for preventing cognitive decline. We share our ongoing research results with you to help you make brain-friendly choices.
Please support our research by becoming a Friend of Food for the Brain.
1 Lakhan, S.E., Kirchgessner, A. The emerging role of dietary fructose in obesity and cognitive decline. Nutr J 12, 114 (2013).
3 Yau PL, Castro MG, Tagani A, Tsui WH, Convit A. Obesity and metabolic syndrome and functional and structural brain impairments in adolescence.
Pediatrics. 2012 Oct;130(4):e856-64. doi: 10.1542/peds.2012-0324. Epub 2012 Sep
4 Zhang X, et al Midlife lipid and glucose levels are associated with Alzheimer’s disease. Alzheimers Dement. 2023
5 Fortier M, Castellano CA, St-Pierre V, Myette-Côté É, Langlois F, Roy M, Morin MC, Bocti C, Fulop T, Godin JP, Delannoy C, Cuenoud B, Cunnane SC. A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT. Alzheimers Dement. 2021 Mar;17(3):543-552. doi: 10.1002/alz.12206. Epub 2020 Oct 26. PMID: 33103819; PMCID: PMC8048678.
6 Crawford, M.A..; Sinclair, A.J.; Wang, Y.; Schmidt, W.F.; Broadhurst, C.L.; Dyall, S.C.; Horn, L.; Brenna, J.T.; Johnson, M.R.; Docosahexaenoic Acid Explains the Unexplained in Visual Transduction. Entropy 2023, 25, x. https://doi.org/10.3390/xxxxx
7 Basambombo LL, Carmichael PH, Côté S, Laurin D. Use of Vitamin E and C Supplements for the Prevention of Cognitive Decline. Ann Pharmacother. 2017 Feb;51(2):118-124. doi: 10.1177/1060028016673072. Epub 2016 Oct 5. PMID: 27708183.
8 Peng, M., Liu, Y., Jia, X. et al. Dietary Total Antioxidant Capacity and Cognitive Function in Older Adults in the United States: The NHANES 2011–2014. J Nutr Health Aging 27, 479–486 (2023). https://doi.org/10.1007/s12603-023-1934-9
9 Nurk E, Refsum H, Drevon CA, Tell GS, Nygaard HA, Engedal K, Smith AD. Intake of flavonoid-rich wine, tea, and chocolate by elderly men and women is associated with better cognitive test performance. J Nutr. 2009 Jan;139(1):120-7. doi: 10.3945/jn.108.095182. Epub 2008 Dec 3. PMID: 19056649.
10 Sesso HD, Manson JE, Aragaki AK, Rist PM, Johnson LG, Friedenberg G, Copeland T, Clar A, Mora S, Moorthy MV, Sarkissian A, Carrick WR, Anderson GL; COSMOS Research Group. Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial. Am J Clin Nutr. 2022 Jun 7;115(6):1490-1500. doi: 10.1093/ajcn/nqac055. PMID: 35294962; PMCID: PMC9170467.
