Last month’s newspaper headlines pitched the new anti-amyloid Alzheimer’s drug as a ‘turning point’. The pitch has a lot in common with the statin story.

Last month’s newspaper headlines pitched the new anti-amyloid Alzheimer’s drug as a ‘turning point’. (Read our response here) The pitch has a lot in common with the statin story.

Is high cholesterol the cause of heart disease? No. 

Do statins lower it? Yes.

Are amyloid deposits the cause of cognitive decline? No. 

Do anti-amyloid drugs lower it? Yes.

No doubt there will be a blood test soon for amyloid, just like a blood test for cholesterol, the effect of which pushed millions into taking statins.

Both statins, given to people with very high cholesterol, and anti-amyloid drugs, given to people with very high amyloid levels, do have marginal benefit but not enough to establish causation. In the case of the new Alzheimer’s drug, the benefit is considerably less than half that shown by the combination of B vitamins and omega-3. 

But, even more than statins, they come with a high risk of quite serious adverse effects – over a third in the recent trial got brain bleeding or swelling and three died. Also, the whole brain shrinkage accelerated by twenty percent compared to placebo, a fact not reported in any newspaper. Any vitamin showing such adverse effects would be immediately banned.

But the important question is: what’s causing these diseases, be it cognitive decline or heart disease? To the extent that cholesterol or amyloid is relevant, what makes them go up? Cholesterol gets damaged by sugar and oxidants and is protected by antioxidants such as vitamin C and a low-carb diet. Brain cells get damaged by homocysteine and are protected by B vitamins and omega-3.

Mind the gap 

Also, in those with cognitive decline, there’s an energy deficit in brain cells. Ironically, they can’t get the glucose they need due to ‘insulin resistance’ which is driven by eating too much sugar and ultra-processed carbs. So, the effect of too much sugar is to starve the brain of fuel which then leads to mental tiredness and cognitive decline. 

There is a way around this – and that is to give the brain an alternative fuel – ketones. 

Ketones can either be supplied as ketone salts or esters, both of which taste disgusting or made from a type of fat – principally C8 oil, which is a medium-chain triglyceride. About 7 percent of coconut oil is C8. Studies giving people with cognitive decline a C8-rich MCT oil have shown clear improvements in cognition by increasing the brain’s energy supply and production. Ripping out amyloid deposits isn’t going to fill this energy gap. Eating less carbs, reversing diabetes, which is a big risk factor for dementia, and having C8 oil will. Our podcast with Professor Stephen Cunnane, who heads the Brain Research Team at Sherbrooke University in Sherbrooke, Quebec, Canada and holds the clinical research chair in ketotherapeutics and on the Food for the Brain Scientific Advisory Board, discusses this area with Patrick Holford – listen to the podcast here.

Also, in those with cognitive decline, there’s an energy deficit in brain cells. Ironically, they can’t get the glucose they need due to ‘insulin resistance’ which is driven by eating too much sugar and ultra-processed carbs. So, the effect of too much sugar is to starve the brain of fuel which then leads to mental tiredness and cognitive decline. 

An increase in amyloid in the brain is really a consequence of the disease, not the cause. It’s part of an inflammatory reaction, much like the nodules in joints that occur from inflammation resulting in arthritis. Should you cut out the nodules or reduce inflammation? Do you eliminate the root cause or target the consequences? Inflammation is both a function of a bad diet high in ultra-processed and fried food, smoking, lack of antioxidants, omega-3 fats and vitamin C to name a few key nutrients. Having an active lifestyle is also important.

The same story exists with all major diseases. Cancer cells thrive on sugar. Do you starve them and in the process protect healthy cells, or cut or drug them out?

The big difference in approach – treat the cause or the consequences – is money.  You can’t patent nutrients, but you can patent drugs that stop you from making cholesterol or amyloid. More than $1 billion has been spent on the anti-amyloid approach and the push isn’t going to stop. Pharma needs a return on their investment. This latest drug treatment, according to the Financial Times, will be sold for $26,000 a year. Taking B vitamins, eating fish and/or supplementing omega-3, which has shown more clinical benefit and reduced the rate of brain shrinkage by over 70% with no side-effects – actually side-benefits – might cost £100 a year. Which would you choose?

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.

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By Patrick Holford

Life is a balancing act between making energy by combusting glucose or ketones with oxygen, which generates ‘oxidant’ exhaust fumes and dealing with these ‘oxidant fumes’ which harm the body.

Skin goes crinkly, age spots develop all due to oxidation. That’s what makes apples go brown, leaves change colour and iron rust. In the end, we lose, which is why all oxygen-based life forms have a finite life – and why your brain and body do inevitably age.

However, you can not only add years to your life, but also life to your years by improving your intake of antioxidants and polyphenols found in whole foods, fruits, vegetables and herbs and spices. A study in Finland and Sweden compared those with a ‘healthy’ versus ‘unhealthy’ diet in mid-life for future risk of developing Alzheimer’s disease and dementia 14 years later (1). Those who ate the healthiest diet had an 86-90% decreased risk of developing dementia and a 90-92% decreased risk of developing Alzheimer’s disease. Some of the benefit comes from low sugar diets, high in omega-3 and B vitamins and some from foods high in antioxidants and polyphenols which we will focus on here.

Your intake of these versus your intake and generation of oxidants, for example from smoking and pollution, is a major determinant of brain health. An illustration of this is the fact that both smoking and pollution exposure increase risk of cognitive decline and dementia, while vitamin C, which is the antioxidant par excellence, reduces risk.

(This is why we have developed our brand new Glutathione at home blood test – the first of its kind where you can accurately test your antioxidant status from home and support our further research into this important area. You can find out more and pre order the test here )

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Oxidants vs antioxidants – moving the balance in your favour

Smoking increases risk of Alzheimer’s just as much as having low B vitamin or omega-3 status, according to the US National Institute of health’s analysis (2). Smoking is something a person can easily change. Air pollution, for many, is not. It is measured in the amount of particulate matter (PMs) and people living in polluted cities are exposed to more. A study of women living in cities in the US found that those exceeding the ‘safe’ levels (greater than 12 μg/m3) had ‘increased the risks for global cognitive decline and all-cause dementia respectively by 81% and 92%’. (3)

While you may not be able to change where you live, can you mitigate the effects of pollution? The answer is yes – in two ways. Firstly, by increasing your intake of antioxidants and also by improving your B vitamin status since the body detoxifies many toxins, including toxic metals from lead to mercury, by methylation. A similar study to the one above found that residing in locations with PM exposure above the safe level was associated with a higher risk of dementia but only among people with lower intakes of the homocysteine lowering B vitamins (B6, folate, b12) (4). ‘Vitamin C in the diet or taken as supplements might help’ concludes another.(5)

Smokers need at least twice as much vitamin C as non-smokers just to have basic vitamin C levels in their blood (serum). Men do worse than women. Even with an intake of 200mg a day they do not achieve this basic blood level, which is already two to three times the recommended dietary intake and what you’d get in four oranges (6). It is certainly wise for any smoker to supplement vitamin C, perhaps adding 50mg per cigarette – 500mg if you smoke 10 a day, although there is a good case for everyone to supplement 1,000mg a day, or 2,000mg a day if over 50.

Nature always provides a solution to help us with our evolution. It seems obvious to me we need vitamin C to combat excessive pollution.

Vitamin C is a keystone nutrient as far as swinging the antioxidant equation in your favour. It’s made in all living things, from animals to plants, including yeasts and funghi. It’s probably been the essential ‘exhaust recycler’ of all oxygen-based lifeforms. Production is even activated when oxidants are sensed. Animals also make more when stressed or exposed to viruses. Us humans, and all other primates, are one of very few species who can’t make it. The first non-vitamin C making animal to be discovered was the guinea pig. That’s how it became the ‘guinea pig’ for research since, like us, it’s dependent every second of every day on vitamin C from diet. Bats, a few birds and the teleost family of fish have also lost the ability to make vitamin C. 

You’ll see in this figure below and from watching the film above, that vitamin C disarms water-based oxidants, such as smoke, and vitamin E disarms fat-based oxidants such as burnt fat. Then, there are other key antioxidant team players that help to neutralise the reactive oxidants that damage our brain and body.

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Your best bet is probably to both eat a diet with a broad spectrum of antioxidants and also supplement them. The older you are the more you are likely to need. Key antioxidants are:

Vitamin A, C and E – associated with reducing Alzheimer’s risk
Lipoic acid (7) – protects the memory-friendly neurotransmitter acetylcholine and dampens down brain oxidation and inflammation)
Glutathione (8) or N-acetyl Cysteine (NAC)(9) – protects the brain and improves methylation thus having potential in dementia prevention.
Co-enzyme Q10 – protects the mitochondria in the brain from oxidative stress (10)
Resveratrol – resveratrol has antioxidant, anti-inflammatory and neuroprotective properties and prevents hippocampal brain damage. (11)

It doesn’t really make a lot of sense to supplement one without the others.

Individually, their impact on your brain health may be less than when combined. 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. Taking either cut risk by a quarter (12). A recent meta-analysis of all studies on factors that could prevent Alzheimer’s by one of our Scientific Advisory Board members – Professor Jin Tai Yu of Fudan University in Shanghai, China – shows that ‘either a high vitamin E or C intake showed a trend of attenuating risk by about 26%’ making these nutrients ‘grade 1’ top level prevention risk factors (13).

All those listed above – vitamin C, E, glutathione and N-acetyl cysteine, Coenzyme Q10 and resveratrol – work together and are often found in combined antioxidant supplement formulas. There are many other team player ‘cousins’ from B vitamins to minerals such as magnesium, selenium and zinc found respectively in greens, seafood, nuts and seeds.

There are two ways to increase your intake – through food and from supplements. 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 (is nuts and seeds), but most of all vitamin C (rich in berries, broccoli, peppers and other vegetables).

(Click here to read our guidance on supplements)

The higher the TAC score of your diet the lower is your risk of cognitive and memory decline. This was the finding of a recent study of 2,716 people over age 60. The researchers measured the TAC score from their diet, splitting them into the highest to lowest quarter of TAC score, and compared this to a number of memory tests. Those in the highest quarter, eating the most antioxidant-rich foods had half the risk of decreasing memory. The higher the TAC score the better their memory function was. (14)

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Go Rainbow, ‘Mediterranean’ and eat five or more servings of fruit and vegetables a day

So, what do you need to eat and drink to preserve your memory and protect your brain?

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 and as researchers drill down, we are learning what to eat and drink to keep your mind sharp and brain young, and how much.

The trick is to really start thinking of the colours you’re eating and gravitate for the strong colours.

Mustard and turmeric, for example, are strong yellows. Dijon mustard is great – no sugar. But if you like good old-fashioned English mustard go for it. Have a teaspoon every other day.

Add turmeric to almost any steam-fry, curry or soup. 

Bright oranges include butternut squash, sweet potato, carrots – but do buy organic. Translucent mass produced carrots are tasteless and have a higher water content, ie less actual carrot. 

Tomatoes are particularly good for you. Buy seeded, not seedless watermelons. Blend the flesh in a blender, perhaps with some ice. The black husk of the seeds drops to the bottom. The flesh of the seeds, full of essential nutrients, becomes part of this mouth-wateringly refreshing drink. Great for detox. Strawberries are a low GL fruit. Red, yellow, green and orange peppers are all rich in vitamin C.

Anything purple, magenta or blue is brilliant for you. From beetroots (eat them raw, grated into salads) to blueberries, blackberries and raspberries. Strawberries are particularly good. According to a study, part of the Rush Memory and Aging Project at Rush University, Chicago, having a higher intake cut Alzheimer’s risk by a quarter. They are high in both vitamin C and flavanoids, a high level of which were also confirmed to cut risk by a third. (15)

Strong greens are always beneficial – from spinach, kale, Brussels sprouts, broccoli, tender stem, watercress, rocket, asparagus, artichoke, green beans, peas, kohlrabi, and cauliflower (although not green).

Polyphenol power

Some of these foods are particularly rich in ‘polyphenols’ a group of health promoting molecules which also includes flavonoids, sometimes called flavanols.  Blue foods such as blueberries contain another polyphenol called anthocyanins. Tea, the cacao in chocolate, red wine, red onions, olives and all the blueish berries are rich sources of polyphenols. Many of these polyphenol rich foods act as antioxidants but they do much more than this. They improve circulation in the brain, lower blood pressure and dampen down inflammation which lies behind many conditions from depression to dementia. Once again, the principle of what’s good for the heart is good for the brain.

One of the first important studies was carried out in Norway more than a decade ago by Eha Nurk and Helga Refsum and colleagues in Norway. (16)(17) They found that:

Tea – the more you drink the better. The tea benefit has been confirmed more recently in a study in Singapore, with green tea being marginally better than black tea.(18) However, this benefit was not found in a UK Biobank study, which reported tea and coffee drinking to be associated with worsening cognition compared to abstainers. (19)

Chocolate – peaks at 10g, or about 3 pieces – and let’s say dark, 70 or more percent, thus with less sugar, is likely to be better, as sugar is a strong indicator of cognitive decline. If a chocolate is 80% cacao that means almost 20% will be sugar. More recent studies giving cocoa, a rich source of flavanols, have shown improved cognition, possibly by improving circulation.(20) This has been confirmed in a big COSMOS trial involving over 20,000 people given a cacao extract supplement rich in flavanols versus a placebo for five years. (21) The reduction in cardiovascular risk was even greater than that of a Mediterranean diet.

Wine – consumption reduces risk of cognitive decline up to an intake of 125ml a day, which is a small glass. A thorough study in the British Medical Journal in 2018, which had followed over 9,000 people over 23 years, showed that both abstinence and drinking more than 14 units of alcohol a week, which is equivalent to a medium glass of wine (2.3 units) every day, also increases risk (22). This is consistent with studies showing that a small glass of wine a day decreases risk of cardiovascular disease. Red wine, high in resveratrol is likely to be most beneficial.

All the above are rich in a polyphenol called epicatechin. Jeremy Spencer, an advisor to Food for the Brain, who is Professor of Nutritional Biochemistry and Medicine at the University of Reading, where he specialises in studying the health benefits of polyphenols and other compounds in plants, has shown that these polyphenol rich plants improve blood brain flow in specific regions of the brain that improve attention, decision-making, impulse control and emotion, thus improving overall ‘executive’ function (23). What’s more, the level of flavanols you have in your bloodstream predicts your memory. The biggest impact of increasing flavanols, was seen in the COSMOS study, in those in the lowest third for dietary intake specifically seeing improvement in aspects of memory that link to the hippocampus, that central area of the brain that degenerates in Alzheimer’s (24).

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The Best Fruit and Veg to Eat for Your Brain

Which vegetables pack the biggest punch as far as polyphenols and antioxidants are concerned and are also lower in sugar or low GL?

Taking all these factors into account – the GL, antioxidants and polyphenols these are the dozen best rated fruit and veg. But do not think of this list as finite as more and more research reveals the amazing healing power of nature’s fruits and vegetables.

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The optimal intake for brain protection is 5 to 6 servings of fruit and veg a day. 

Half a plate of a main meal counts as two. A handful of berries would count as one. So, if half your plate for two main meals is vegetables, and you had some berries with your breakfast and another piece of fresh fruit or perhaps some broccoli heads or tenderstem or carrots dipped in hummus as a snack, or half an avocado with some high polyphenol olive oil, you’ve achieved six servings.

The first step is to eat ‘whole’ foods, and especially fresh plant foods with an emphasis on those listed above that are more likely to be high in antioxidants and polyphenols. (Also see the Alzheimers Prevention Diet.) There are some nutrients such as vitamin C for which just eating whole foods doesn’t guarantee you are achieving an optimal intake and are well worth supplementing.

My advice is to supplement 500mg to 1,000mg of vitamin C twice a day and also take an antioxidant formula or antioxidant rich multivitamin containing vitamins A, C, E, lipoic acid, glutathione or NAC, resveratrol and CoQ10.

Summary

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

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

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

References

Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M. Midlife healthy-diet index and late-life dementia and Alzheimer’s disease. Dement Geriatr Cogn Dis Extra. 2011 Jan;1(1):103-12. doi: 10.1159/000327518. Epub 2011 Apr 27. PMID: 22163237; PMCID: PMC3199886.
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.
Cacciottolo M, Wang X, Driscoll I, Woodward N, Saffari A, Reyes J, Serre ML, Vizuete W, Sioutas C, Morgan TE, Gatz M, Chui HC, Shumaker SA, Resnick SM, Espeland MA, Finch CE, Chen JC. Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models. Transl Psychiatry. 2017 Jan 31;7(1):e1022. doi: 10.1038/tp.2016.280. PMID: 28140404; PMCID: PMC5299391.
 Chen C, Whitsel EA, Espeland MA, Snetselaar L, Hayden KM, Lamichhane AP, Serre ML, Vizuete W, Kaufman JD, Wang X, Chui HC, D’Alton ME, Chen JC, Kahe K. B vitamin intakes modify the association between particulate air pollutants and incidence of all-cause dementia: Findings from the Women’s Health Initiative Memory Study. Alzheimers Dement. 2022 Nov;18(11):2188-2198. doi: 10.1002/alz.12515. Epub 2022 Feb 1. PMID: 35103387; PMCID: PMC9339592.
 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.
 Carr AC, Lykkesfeldt J. Factors Affecting the Vitamin C Dose-Concentration Relationship: Implications for Global Vitamin C Dietary Recommendations. Nutrients. 2023 Mar 29;15(7):1657. doi: 10.3390/nu15071657. PMID: 37049497; PMCID: PMC10096887.
 A. Maczurek, et al., ‘Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer’s disease’, Advance Drug Delivery Review, 2008;60(13-14):1463-70 
 Pocernich CB, Butterfield DA. Elevation of glutathione as a therapeutic strategy in Alzheimer disease. Biochim Biophys Acta. 2012 May;1822(5):625-30. doi: 10.1016/j.bbadis.2011.10.003. Epub 2011 Oct 12. PMID: 22015471; PMCID: PMC3277671.
 Hara Y, McKeehan N, Dacks PA, Fillit HM. Evaluation of the Neuroprotective Potential of N-Acetylcysteine for Prevention and Treatment of Cognitive Aging and Dementia. J Prev Alzheimers Dis. 2017;4(3):201-206. doi: 10.14283/jpad.2017.22. PMID: 29182711.
 Yang X, Zhang Y, Xu H, Luo X, Yu J, Liu J, Chang RC. Neuroprotection of Coenzyme Q10 in Neurodegenerative Diseases. Curr Top Med Chem. 2016;16(8):858-66. doi: 10.2174/1568026615666150827095252. PMID: 26311425.
 Gomes BAQ, Silva JPB, Romeiro CFR, Dos Santos SM, Rodrigues CA, Gonçalves PR, Sakai JT, Mendes PFS, Varela ELP, Monteiro MC. Neuroprotective Mechanisms of Resveratrol in Alzheimer’s Disease: Role of SIRT1. Oxid Med Cell Longev. 2018 Oct 30;2018:8152373. doi: 10.1155/2018/8152373. PMID: 30510627; PMCID: PMC6232815.
 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.
 See reference 5.
 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
 Agarwal P, Holland TM, Wang Y, Bennett DA, Morris MC. Association of Strawberries and Anthocyanidin Intake with Alzheimer’s Dementia Risk. Nutrients. 2019 Dec 14;11(12):3060. doi: 10.3390/nu11123060. PMID: 31847371; PMCID: PMC6950087.
 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.
 Nurk E, Refsum H, Drevon CA, Tell GS, Nygaard HA, Engedal K, Smith AD. Cognitive performance among the elderly in relation to the intake of plant foods. The Hordaland Health Study. Br J Nutr. 2010 Oct;104(8):1190-201. doi: 10.1017/S0007114510001807. Epub 2010 Jun 16. PMID: 20550741.
 Feng L, Chong MS, Lim WS, Lee TS, Kua EH, Ng TP. Tea for Alzheimer Prevention. J Prev Alzheimers Dis. 2015;2(2):136-141. doi: 10.14283/jpad.2015.57. PMID: 29231231.
 Cornelis MC, Weintraub S, Morris MC. Caffeinated Coffee and Tea Consumption, Genetic Variation and Cognitive Function in the UK Biobank. J Nutr. 2020 Aug 1;150(8):2164-2174. doi: 10.1093/jn/nxaa147. PMID: 32495843; PMCID: PMC7398783.
 Lamport DJ, Pal D, Moutsiana C, Field DT, Williams CM, Spencer JP, Butler LT. The effect of flavanol-rich cocoa on cerebral perfusion in healthy older adults during conscious resting state: a placebo controlled, crossover, acute trial. Psychopharmacology (Berl). 2015 Sep;232(17):3227-34. doi: 10.1007/s00213-015-3972-4. Epub 2015 Jun 7. PMID: 26047963; PMCID: PMC4534492.
 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.
 Sabia S, Fayosse A, Dumurgier J, Dugravot A, Akbaraly T, Britton A, Kivimäki M, Singh-Manoux A. Alcohol consumption and risk of dementia: 23 year follow-up of Whitehall II cohort study. BMJ. 2018 Aug 1;362:k2927. doi: 10.1136/bmj.k2927. PMID: 30068508; PMCID: PMC6066998.
 See Professor Peremy Spencer’s presentation at the Alzheimer’s is preventable masterclass (2022); also see Spencer JP. The impact of fruit flavonoids on memory and cognition. Br J Nutr. 2010 Oct;104 Suppl 3:S40-7. doi: 10.1017/S0007114510003934. PMID: 20955649.
 Brickman AM, Yeung LK, Alschuler DM, Ottaviani JI, Kuhnle GGC, Sloan RP, Luttmann-Gibson H, Copeland T, Schroeter H, Sesso HD, Manson JE, Wall M, Small SA. Dietary flavanols restore hippocampal-dependent memory in older adults with lower diet quality and lower habitual flavanol consumption. Proc Natl Acad Sci U S A. 2023 Jun 6;120(23):e2216932120. doi: 10.1073/pnas.2216932120. Epub 2023 May 30. PMID: 37252983; PMCID: PMC10265949.

Friday’s Guardian article on ‘I refuse to get old’ about how readers strive to keep dementia at bay, on the face of it, seems like a good message. Most cases given focussing on people increasing physical and mental activity, as an active lifestyle is certainly a positive step towards prevention. But these two prevention steps reduce risk by less than B vitamins, omega-3 and reducing sugar and carbs.

The first error is the extent to which dementia can be prevented. The article says by 40%, which is based on the inaccurate Lancet Commission’s Livingston report which, despite being sent all the evidence, doesn’t even mention B vitamins and homocysteine, which is the single most important prevention step. There’s also only one mention of omega-3 from a redundant study so this risk factor is also ignored to arrive at the ‘40% preventable’ figure.

80% of dementia cases could be prevented, not 40%

The latest assessment of how much can be prevented, based on UK Biobank data is “47%–73% of dementia cases could be prevented.” This was published last week in Nature and even this is an underestimate because, while including B vitamins, it excludes the impact of omega-3 and seafood. If that modifiable risk factor were included it is likely that around 80% of dementia cases could be prevented. This would mean that the Guardian is halving the impact of prevention.

The next error is no-one quoted in the article mentions diet, let alone B vitamins or omega-3, except for Professor David Smith. He rightly says: ‘The large leap forward in what we know about preventability has informed his own retirement lifestyle: he walks for half an hour a day, spends at least 15 minutes on an exercise bike, drinks alcohol sparingly, and follows a Mediterranean diet.

Having led a clinical trial into the benefits of B vitamins in people with mild cognitive impairment – a memory-loss condition that increases the chance of those who have it developing dementia – Smith takes 500mcg of vitamin B12 daily and fish oil with Omega 3. Nutrition, he believes, is not given enough prominence when we talk about prevention.’

When we calculated the attributable risk for each risk factor for our online Dementia Risk Index questionnaire each domain scores as follows, adding up to 100%:

B Vitamins           18%

Brain Fats             17%

Glycemic Load     15%

Active Body          15%

Active Mind          10% 

Sleep & Calm       10%

Antioxidants         10%

Gut  Health          5%

So, the biggest impact you can have on your risk is to supplement B vitamins, especially B12, and omega-3 fish oils, as David Smith does. But the Guardian article then downplays the role of supplements with this statement ‘Alzheimer’s Research UK does not recommend any supplements in particular, but says “there is no harm in people taking a supplement to reduce the risk of deficiency”.

B12 Reference Ranges are wrong

This is not only wrong because brain shrinkage occurs well within the ‘normal’ range of either B12 dietary intake or blood tests, but also ARUK, who largely promotes drug-based solutions, happened to know what they are saying is wrong because they funded, back in 2010, a top level, randomised placebo controlled trial on B vitamins that, virtually stopped cognitive decline and reduced brain shrinkage by 52% – in the group with higher omega 3 , by 73% – that is the most effective disease modifying treatment to date! In fact, David Smith and I have written to ARUK to stop making this inaccurate statement. Here’s why it’s wrong:

The reason so many people are low in B12 is less to do with dietary intake and more due to malabsorption which often becomes worse with age, due to lack of stomach acid secretions which are needed to absorb B12. So relying only of analysing what someone eats (meat, fish, eggs, dairy being the only sources of B12) doesn’t prove sufficiency. Note that David Smith says he supplements 500mcg of B12 daily, while the basic ‘Nutrient Reference Value’ (NRV) that you’ll see on the back of a vitamin supplement is 2.5mcg. So, why does he take two hundred times this amount? Because you cannot rely on your dietary intake to confirm sufficiency. Also, there is growing body of evidence from well designed studies showing that supplements giving nutrients at levels beyond the basic ‘recommended intakes’ delay, eliminate or ameliorate symptoms of dementia.

So, what about blood tests? One UK study reports that 2 in five people over 61 have insufficient levels of B12 to prevent accelerated brain shrinkage. Serum B12 is the ‘standard’ test used by doctors. The UK reference range of above 180pg/ml being sufficient (and the US lower level of 200pg/ml) is out of date and in need of revision. In Europe and Japan anything below 500pg/ml is considered deficient. Accelerated brain shrinkage due to a lack of B12 does happen with B12 levels below 500pg/ml.

In conclusion, while it is good to recommend a physically and intellectually lifestyle, ignoring the need to supplement B vitamins, especially B12, eat fish and supplement omega-3, and cut your intake of carbs and sugar, is not doing anyone any favours.

Take the free test here to work out which simple steps will most reduce your risk.

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

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

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

Is coffee good or bad for you?

On the one hand is contains polyphenols that act like antioxidants, but on the other hand even two coffees a day raises markers of inflammation, including homocysteine which is an established indicator of dementia risk.

A major study involving almost 400,000 people in the UK’S Biobank shows that those having 6+ coffees a day, or three double expressos, have more than double the risk of dementia compared to 1 to 2 coffees a day. They also had increased brain shrinkage in the hippocampal region associated with Alzheimer’s. Why? Two studies in the Netherlands found that two coffees a day raise homocysteine, a toxic amino acid, by about 10%, while caffeine tablets without coffee increased it by 5%. It appears that it is mainly the caffeine content that is increasing risk. However, those having none, or only decaf, had very slightly higher, but not significant risk compared to those having 1 or 2 coffees.  Much like alcohol especially red wine, a little may offer protection, a lot of increases risk.

Another study, again using UK Bio Bank data, found significant dose-dependent association beyond three cups/d coffee with dementia risk if those with degenerative nervous system disorders not related to dementia were removed from the analysis, while moderate-to-high tea intake was negatively associated with incident dementia therefore reducing risk.

Coffee does, however, have some plus sides. Four meta-analyses examining liver cancer, report a risk reduction of 38% in those who drank 2-3 cups of coffee per day and 41% in those who drank more than 4 cups.  Drinking six cups of coffee a day, while bad for the brain, was shown to halve the risk of fatal prostate cancer, according to a study published in the Journal of the National Cancer Institute with each cup of coffee reducing overall prostate cancer risk by about 5%.

What’s the protective factor in coffee?

Exactly why coffee has these protective effects is a subject of much debate. While there is evidence that caffeine itself has benefits tea,  which also contain caffeine, doesn’t show the same protective benefit for cancer. Paraxanthine, the main primary metabolite of caffeine, has been shown to slow down pre-cancerous liver cell growth, and in turn the progression of liver fibrosis, alcoholic cirrhosis and liver cancer. Chlorogenic acid, may reduce oxidative stress in the liver, in turn reducing the risk of fibrosis and development of cancers. There are about 1,000 different compounds in coffee.

Both caffeine and chlorogenic acid, however, raise homocysteine, which is a concern especially regarding Alzheimer’s risk.

Coffee may help protect against diabetes and weight gain. 

Two studies have shown that coffee doesn’t cause the release of insulin, and may even reduce insulin resistance. Interestingly, this effect is true for both coffee and decaf coffee, suggesting that it is isn’t the caffeine that reduces insulin resistance. In fact, decaf may even help keep insulin producing cells healthy. 

Before you hit the coffee, there’s something you need to know. Rather than reducing insulin resistance, if you combine coffee with a carb snack such as a croissant or a muffin, it has the opposite effect. To explore the consequence of this much loved combination researchers at Canada’s University of Guelph gave volunteers a carbohydrate snack, such as a croissant, muffin or toast, together with either a decaf or coffee. Those having the coffee/carb combo had triple the increase in blood sugar levels and insulin sensitivity, the hormone that controls blood sugar levels, was almost halved.

Caffeine, hence coffee, is an addictive stimulant. If, for example, you can’t wake up without it, then you have a level of dependence probably due to ‘down-regulation’ of adrenalin receptors. In other words you’ve become adrenalin resistant in much the same way that we can become insulin resistant. Coffee can, in this sense, be an energy depleter, although the immediate effect is energy increase. I liken this to a wave hitting the shore. The latent energy we have is in the wave. As it crashes into the shore there’s an energy surge or release occurs, as it also does with caffeine, but the after-effect is energy depletion.

How coffee is decaffeinated makes a difference to both the taste and what’s left behind. Almost all decaf uses a chemical solvent. The exception are those that use the “swiss water” process which is used almost exclusively used for decaffeination of organic coffee. This is probably the best to choose if you like the taste of coffee but not the buzz. 

If you want to know more about how you can support your brain, make sure you complete our free Cognitive Function Test here to give you your plan of action on how you can upgrade your own brain in the next 6 months.

Help support Food for the Brain

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.

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

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

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

References

 1 Zhang Y, Yang H, Li S, Li WD, Wang Y. Consumption of coffee and tea and risk of developing stroke, dementia, and poststroke dementia: A cohort study in the UK Biobank. PLoS Med. 2021 Nov 16;18(11):e1003830. doi: 10.1371/journal.pmed.1003830. PMID: 34784347; PMCID: PMC8594796.

2 Schaefer SM, Kaiser A, Behrendt I, Eichner G, Fasshauer M. Association of Alcohol Types, Coffee, and Tea Intake with Risk of Dementia: Prospective Cohort Study of UK Biobank Participants. Brain Sciences. 2022; 12(3):360. https://doi.org/10.3390/brainsci12030360

3  Grubben MJ, Boers GH, Blom HJ, Broekhuizen R, de Jong R, van Rijt L, de Ruijter E, Swinkels DW, Nagengast FM, Katan MB. Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial. Am J Clin Nutr. 2000 Feb;71(2):480-4. doi: 10.1093/ajcn/71.2.480. PMID: 10648261; P. Verhoef et al., ‘Contribution of caffeine to the homocysteine-raising effect of coffee: a randomized controlled trial in humans’, American Journal of Clinical Nutrition, 2002 Dec; 76(6): 1244-1248; J. Geleijnse, ‘Habitual coffee consumption and blood pressure: An epidemiological perspective’, Vascular Health Risk Management, 2008 Oct; 4(5): 963–970; 

4 Wilson KM et al., ‘Coffee consumption and prostate cancer risk and progression in the Health Professionals Follow-up Study.’J Natl Cancer Inst. 2011 Jun 8;103(11):876-84.

 5 T. Wu et al., ‘Caffeinated coffee, decaffeinated coffee, and caffeine in relation to plasma C-peptide levels, a marker of insulin secretion, in U.S. women’, Diabetes Care, 2005 Jun; 28(6):1390-6; see also R. C. Loopstra-Masters et al., ‘Associations between the intake of caffeinated and decaffeinated coffee and measures of insulin sensitivity and beta cell function’, Diabetologia, 2010 Nov, [Epub ahead of print]
University of Guelph

6 Moisey LL, Kacker S, Bickerton AC, Robinson LE, Graham TE. Caffeinated coffee consumption impairs blood glucose homeostasis in response to high and low glycemic index meals in healthy men. Am J Clin Nutr. 2008 May;87(5):1254-61. doi: 10.1093/ajcn/87.5.1254. PMID: 18469247.