because prevention is better than cure.

because prevention is better than cure.

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How to cut your dementia risk by three quarters.

Developing dementia is the second biggest health fear, after cancer. But what can you do about it? 

The conventional view is that genes play a big part and that factors under our control, including diet, lifestyle and health status, account for up to 40% of risk and therefore up to 40% of dementia cases could be prevented or delayed. Genes actually account for less than 1% of Alzheimer’s cases. But a new study from the UK BioBank, following 344,000 people over 15 years, estimates that “up to 73% of cases could be prevented” by targeting risk factors largely under our control. 

The authors of the study, published in the Nature Human Behaviour journal (1), investigated 210 modifiable risk factors. They found that increased hand grip strength (a good reflection of physical strength), increasing leisure or social activities or time spent in sports clubs or gyms, spending less time watching TV or on a computer, having better dental health, drinking more water, not dozing off in the day and sleeping between 7 to 9 hours a night, not smoking or being exposed to smoke and having better lung function were all associated with less risk of Alzheimer’s. Being unemployed, having a low income, having diabetes, high blood pressure or having had a stroke or brain injury all increased risk. Inheriting the so-called ‘Alzheimer’s gene’, ApoE4, didn’t make any significant difference to overall risk.

However, even this figure of 73% may be an underestimate as this study excluded blood test measures. “We have under-estimated the power of prevention,” says Professor David Smith from the University of Oxford, one of the study authors. “Even this figure of up to 73% of cases preventable could be higher if a person’s omega-3 and B vitamin status, measured by a blood test for homocysteine that any GP can do, were taken into account.”

While the BioBank study didn’t include blood test measures of either homocysteine or omega-3, scientists at the US National Institutes of Health have attributed 22% of the risk of Alzheimer’s to raised blood homocysteine and 22% to a lack of omega-3 (2). “These have been shown to predict risk but were beyond the scope of this study.” confirmed the study author, Professor Jin-Tai Yu from Shanghai’s Fudan University. “Homocysteine-lowering treatment with B vitamins, especially B12, is one of the most promising interventions for dementia prevention.” 

The Impact of B Vitamins & Omega-3

Professor Smith’s group at Oxford University tested the effects of giving B vitamins (B6, B12, folate) versus placebo to those with pre-dementia and found that the 10p a day supplements halved the rate of brain shrinkage in one year and virtually stopped further memory loss (3). “The greatest effect we found in our trial was in those in the top third of DHA blood levels (an omega-3 found in fish or fish oil supplements). Those with high DHA reduced their rate of brain shrinkage by 73%, down to the level normally seen in older people with loss of cognitive function. They also had virtually no further memory loss and almost a third ended the trial with no clinical dementia rating at all.”

The benefit of omega-3 was also confirmed in a major study this year of over 100,000 people, finding that increased omega-3 cut the risk of dementia or cognitive decline by around 20%. An increase in intake of omega-3 DHA of 200 mg decreased risk by almost a fifth (4). 

And here at Food for the Brain, we take prevention seriously.

Alzheimer’s is preventable, but not curable

We developed the free online Cognitive Function Test,  which includes a Dementia Risk Index questionnaire assessing your diet, omega-3 and B vitamin status, and lifestyle and an optional home-test kit for pinprick blood tests that will be available soon.

“Over 400,000 people have taken our validated Cognitive Function Test, which not only shows a person their cognitive status right now but also their future risk based on our Dementia Risk Index questionnaire, the factors driving future risk and what they can easily do right now to lower it. If all modifiable risk factors are taken into account, including B vitamins and omega-3, it is highly likely a person could reduce risk by over 80%.” says our CEO, Patrick Holford.

“The government has pledged £160 million a year for dementia prevention research but we are not seeing any of this going into easy prevention wins. Most seem to be fueling drug research for an apparent ‘cure’.

Alzheimer’s is preventable, but not curable. You cannot reverse holes in the brain. With over 200,000 people diagnosed every year with dementia, if prevention were taken seriously we could halve the number of people developing this terrible, but preventable disease.”

Test Your Cognitive Function Now green banner.

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

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

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

———

References
Further info

Use it or Lose it. Why an active lifestyle is a brain essential.

Keeping our brain’s structure and neural network healthy may seem like a mystery at times, but often the best advice is simple: ‘use it or lose it!’

The exercise and stimulation your brain gets from an active physical, social and intellectual lifestyle is vital to keeping it healthy. Just like our bodies need movement and exercise to function well, our brains need their own workout to thrive, too.

Lifestyle expert at Food for the Brain, Assistant Professor Tommy Wood, from the University of Washington has advised people at the top of their game, from Formula 1 drivers and Olympians to world champions, on how to maximise their performance, both mentally and physically.  His top tip for keeping our brains sharp?  

“In short, use it or lose it. The brain is an amazing organ, and it’s more resilient and adaptable than we’ve been led to believe. I’m sure you’ve heard that adults have a fixed amount of brain cells. Then, as we get older (or every time we take a sip of wine) we “lose” some of those brain cells as part of an unstoppable decline towards dementia or Alzheimer’s disease.”

“That’s not necessarily true” says Professor Wood. “I like to think about the brain like I think about muscles. In order to grow our muscles, we need to provide a stimulus – like lifting weights in the gym – followed by a period of rest. The opposite also happens – if we stop going to the gym or if we stop using a limb after breaking a bone – our muscles get smaller. Most have experienced this personally, and there’s every indication that your cognitive “muscle” behaves in the same way.”

A classic example of this is a study of London taxi drivers in training who have to learn ‘The Knowledge’. Many spend three years driving the 25,000 streets of London, logging up tens of thousands of miles, on foot or on a scooter. Not all pass the first time. Katherine Woollett at University College London decided to find out if acquiring the knowledge actually changed a person’s brain by measuring the density of grey matter as an indicator of brain volume. About half of her group of training taxi drivers passed first time and the other half failed. She also had a control group of people of the same age, most in their late 30’s with similar other demographics such as IQ. Sure enough, those who passed had increased their brain density of grey matter, and specifically in the central hippocampus area most associated with cognitive resilience. (1)

Keep Cognitively Active

There’s a pattern in our society – we are meant to learn every day as we go through school in childhood and teenage years, then we get a job, which, past a training phase, may not require much more learning, then around 65 we are meant to retire, with no more ‘need’ to work or learn.

Every indicator that you can think of – leaving school early, having a lower educational standard (2), or retiring early (3), has been associated with an increasing risk of cognitive decline.

When Professor May Beydoun, at the US National Institutes of Health (NIH) did a comprehensive study of the biggest risk factors for developing Alzheimer’s, she attributed 24% of risk to educational status and 32% of risk to physical activity(4). So, using our brains, reflected in educational and physical activity, is a huge part of keeping your brain healthy. (It’s worth remembering that  omega-3/seafood and homocysteine-lowering B vitamins account for 22% each while smoking racks up 31% in the risk stakes).

Think about how you use your mind. How much time do you spend stimulated, learning something? How much time do you spend engaged in relatively mindless mental activities? 

Television can be stimulating, or mind-numbing – engaging your attention but not really making you think. Social media activity, like scrolling through TikTok or Instagram, could be mind-numbing, while digital engagement with others could be stimulating. A simple yardstick is to ask ‘am I learning anything? Am I using my mind?’ 

While these activities are keeping your brain busy, what our brains really needs is to be engaged in learning or working something out, ideally without too much stress. Many films are designed to engage you by stimulating a stress response, keeping you on the edge of our seat. On the other hand, doing Wordle or a crossword, or playing a game of backgammon or chess involves concentration and thinking without cranking up your stress response. 

Two high-rating apps designed to engage our minds Brain HQ and Lumosity. Brain HQ (www.brainhq.com) adapts according to your needs – do you want better memory, better attention or faster processing? Three 20-minute sessions weekly are recommended. Lumosity (www.lumosity.com) is also adaptive and achieves much the same improvement in cognition. In just the same way you become physically fitter by increasing the duration or intensity of an exercise, it seems the same is true with your mind.

Reading books, or listening to podcasts can also be a great way to stimulate the old grey matter, mind but it does depend on what you are reading or listening to. The golden question is  ‘am I learning anything from this?’. Even better – join a bookclub for the social stimulation, sharing views, hearing others, and working out where you stand. 

Learn by failing

Land on any social media platform and we are bombarded with stories of people succeeding, urging us to try the latest self-help, diet or exercise programme, meditation or music app (who didn’t try and learn the guitar in lockdown!) but failure, according to Professor Tommy Wood, is when the magic really happens for our brains:

“Failure constitutes protective cognitive demand. The cocktail of hormones released as we try, fail, repeat, and learn, provides the ideal environment for the brain to grow and adapt. This is a real sticking point for improving brain health – as adults we hate the feeling of being bad at something.”

Professor Wood recommends picking an activity that’s truly challenging. “Cognitive demand requires failure, so pick something you’ll be bad at initially. What’s cognitively challenging is personal, but learning a new language is better than sudoku, picking up a guitar is better than listening to music, building model airplanes is probably better than reading the news, and playing chess is definitely better than scrolling through Instagram. As you get better, add challenges to keep stimulating your brain.”

“A fascinating study looked at the brains of musicians.  While both professional and amateur musicians’ brains looked younger compared to non-musicians of the same age, the benefit was greatest in amateur musicians (5) – it’s harder, so they got more benefit. The cocktail of hormones released as we try, fail, repeat, and learn, provides the ideal environment for the brain to grow and adapt.”

In fact, learning an instrument, or a language, are considered heavy lifters when it comes to brain stimulation – it’s challenging and can take a long time to become completely proficient. But every step along the way, even just a few minutes a day, learning new words, processing the grammar, learning chords and finger positions, is a significant mental challenge.  And there are so many language learning apps, like DuoLingo now, playing on the ‘reward’ and game theory to keep us cognitively engaged and coming back for more. 

Speaking two languages is not only associated with less risk of cognitive decline but, according to one study, ‘the neuroprotective effects of lifelong bilingualism act both against neurodegenerative processes and through the modulation of brain networks connectivity.’ (6) Your brain ends up more connected – literally hardwired for brain health.

Keep physically active

The brain also benefits from physical exercise, especially if it involves complex movements and learning – think dance, yoga or t’ai chi or trail running or walking on uneven surfaces. The brain is processing a lot of information, triggering patterns of muscle movement, keeping you in balance. You want a bit of both – movement and balance. Just working out on a fixed machine or walking on a flat, straight, tarmacked path, is not nearly as challenging as hill walking up an uneven path, cycling, surfing, skateboarding or anything where your body is micro-adjusting to keep you in balance.

One study of retired people assigned to walk briskly for 40 minutes three times a week showed increased hippocampal brain volume (7).  Another study showed benefits from doing one or two sessions of resistance or strength training twice a week (8).

Of all the measures relating to how fit or fat we are, muscle mass best predicts brain volume and risk of cognitive decline in later years. 

One big study from the UK Biobank data found that those with a lower fat-to-muscle ratio) in their legs had around 40% less risk for dementia later in life (9). Muscle uses energy and ‘soaks up’ glucose. This helps keep your blood sugar stable and prevent insulin resistance. Often, as we age, it can seem like an uphill battle to keep our weight down, even if we are not eating any more than we used to. This is often simply because we’ve lost muscle mass with age. So hitting those weights can be extra beneficial in later years and many gyms offer classes especially for older clients. Even body weight exercise can build resistance, though, and there are plenty of free videos on the internet – just check with your GP first.

Step it up

A good general guideline is to aim for 30 minutes of brisk walking every day. Some days you may do none and others twice this, so this is a good weekly average to shoot for. Over time you can step it up by walking faster, jogging or including some hills in your circuit. 

A good way to monitor and up our exercise level is to count steps. Smart phones and watches have apps that do this for you. Shoot for increasing daily steps between 10% and 20% a week. If you start at 2,000 and add 200 steps per day each week, that’s a great start. If you’re at 4,000 steps already then getting up to 4,400 daily in this week is also going to stimulate our muscles and brains. While 8,000 steps a day is considered optimal, what’s much more important is to make sustainable improvements as you ‘activate’ your lifestyle.

But, we don’t need to limit ourselves to ‘exercise’. Gardening, mowing the lawn, playing a sport, vigorous cleaning, or clearing out a yard – anything that gives us a faster heart rate, a bit of sweat and engages different sets of muscles, thus including ‘resistance’(10), counts as well, especially if we can do them faster or more energetically.

Aerobic plus resistance exercise anti-ages your brain

As previously mentioned, of all the measures relating to how fit or fat we are, muscle mass best predicts brain volume and risk of cognitive decline in later years. 

Including exercise that helps build and maintain muscle tone correlates most strongly with brain health. A good weekly guideline is to include two resistance training sessions a week. Perhaps you are a member of a gym, go to a pilates or yoga class or have some equipment at home for your own workout.

If you’re not sure where to start, “Burn Fat Fast” (Piatkus, 2013), written by Patrick Holford and exercise guru and former Gladiator (Zodiac) Kate Staples, is a great resource.  Staples devised a series of strength building exercises that anyone can do at home in eight minutes, three times a week, including  beginner version, and intermediate and advanced versions (light to medium weight dumbbells (2kg – 6kg) are needed for these).

The exercises are all explained in the book and  Kate Staples demonstrates each one HERE so you can follow along until you feel comfortable. A five minute warm-up (marching on the spot is great, or stepping side to side) will get your heart rate up and help avoid injury. 

The beginner sequence includes wall sits and reverse lunges, while the advance sequence progresses to jumping squats and mountain climbers. It’s important to build up gradually, keep hydrated, and learn to do the moves safely, so watching the videos is a great way to get started. 

The secret is to find an activity that engages both mind and body, builds muscle, and is not too repetitive. As an example, our very own Patrick Holford says “I’ve taken up paragliding, and qualified at the age of 65. I had to pass an exam on meteorology, aerodynamics and air law, and failed the first time, but now I have to think about these things before and during flight. Then there’s the exercise of carrying an 11 kg pack up a mountain, and the balance and strength and adjustments my brain is having to make to keep the canopy stable even before take off.” This may not be your thing but it shows how one activity can tick so many brain boxes. It is good to learn new sports for this very reason.

Be Social

A lack of meaningful social interaction, and loneliness, is also a major driver of both low mood and cognitive decline later in life (11). 

How often do you go to social gatherings, meet new people and have engaging conversations? This could be meeting friends, going to the movies, a museum, a gallery, a show, church or temple, or a restaurant?

There are times in your lives where you might find yourself more isolated. For example, when relationships break up and you lose connection with ‘their’ friends, or if a partner dies and most of your social interaction was with them. These are extremely challenging times, but facing our fears and getting out there to meet friends can help us on the road to recovery. 

Unset your mind

It’s all too easy to get locked into routines that remove any form of challenging social interaction yet this is not only how we learn, it also nourishes the social aspect of who we are. A good strategy is to make sure you have a significant social event or interaction every week, starting with this week.

As we age, and friends move away, or pass on, it’s important to find ways to expose ourselves to new ideas and new ways of thinking and feeling differently and swapping ideas. Travelling and exploring other cultures can be an incredibly enriching way to broaden our mindset and there are lots of companies that cater for the solo traveller these days.

But there’s no need to go far from home to get the benefits of brain gain. There are many opportunities to ‘use it or lose it’, for example, volunteering at a local garden or school or supporting the local arts club. The brain boost from being out of your comfort zone will reap dividends, whether it’s joining a group of new people, engaging in a new activity you’ve never tried, like drawing, writing or yoga – or even just catching up with old friends you haven’t seen for ages, or striking up a conversation with someone you meet on the daily dog walk.

Local bookshops, art centres, churches or schools can be great sources of information, so check them out. 

Be inquisitive

As Tommy Wood says “The key is to push right at the boundaries of what you’re capable of – with occasional failure showing that you’re at the right level of difficulty. Keep at it, and you’ll be more likely to be healthy and sharp for decades to come.”

And if you want more personalised information on how you can improve and support your brain through nutrition and lifestyle changes then make sure you complete our Cognitive Function Test. A FREE, online and validated test to assess your current cognitive function and dementia risk and then get a clear plan of action on how you can improve your brain health and score over the next 6 months.

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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.

Test Your Cognitive Function Now green banner.

References:

1 Woollett K, Maguire EA. Acquiring “the Knowledge” of London’s layout drives structural brain changes. Current biology: CB. 2011;21(24):2109-14. Epub 2011/12/08. doi: 0.1016/j.cub.2011.11.018. PubMed PMID: 22169537.

2 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;91(11):1201-9. Epub 2020/07/22. doi: 10.1136/jnnp-2019-321913. PubMed PMID: 32690803; PMCID: PMC7569385.

3 Hale JM, Bijlsma MJ, Lorenti A. Does postponing retirement affect cognitive function? A counterfactual experiment to disentangle life course risk factors. SSM – Population Health. 2021;15:100855. doi: https://doi.org/10.1016/j.ssmph.2021.100855; see also Dufouil C, Pereira E, Chêne G, Glymour MM, Alpérovitch A, Saubusse E, Risse- Fleury M, Heuls B, Salord JC, Brieu MA, Forette F. Older age at retirement is associated with decreased risk of dementia. Eur J Epidemiol. 2014;29(5):353-61. Epub 2014/05/06. doi: 10.1007/s10654-014-9906-3. PubMed PMID: 24791704.

4 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.

5 Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF. Exercise training increases size of hippocampus and improves memory. Proceedings of the National Academy of Sciences. 2011;108(7):3017. doi: 10.1073/pnas.1015950108.

6 Sala A, Malpetti M, Farsad M, Lubian F, Magnani G, Frasca Polara G, Epiney JB, Abutalebi J, Assal F, Garibotto V, Perani D. Lifelong bilingualism and mechanisms of neuroprotection in Alzheimer dementia. Hum Brain Mapp. 2022;43(2):581-92. Epub 2021/11/04. doi: 10.1002/hbm.25605. PubMed PMID: 34729858; PMCID: PMC8720191.

7 Ludyga S, Gerber M, Pühse U, Looser VN, Kamijo K. Systematic review and meta- analysis investigating moderators of long-term effects of exercise on cognition in healthy individuals. Nature Human Behaviour. 2020;4(6):603-12. doi: 10.1038/s41562-020-0851-8.

8 Herold F, Törpel A, Schega L, Müller NG. Functional and/or structural brain changes in response to resistance exercises and resistance training lead to cognitive improvements – a systematic review. Eur Rev Aging Phys Act. 2019;16:10. Epub 2019/07/25. doi: 10.1186/s11556-019-0217-2. PubMed PMID: 31333805; PMCID: PMC6617693.

9 Wang W, Luo Y, Zhuang Z, Song Z, Huang N, Li Y, Dong X, Xiao W, Zhao Y, Huang T. Total and regional fat-to-muscle mass ratio and risks of incident all-cause dementia, Alzheimer’s disease, and vascular dementia. J Cachexia Sarcopenia Muscle. 2022 Oct;13(5):2447-2455. doi: 10.1002/jcsm.13054. Epub 2022 Jul 20. PMID: 35856185; PMCID: PMC9530585.

100 Gallardo-Gómez D, Del Pozo-Cruz J, Noetel M, Álvarez-Barbosa F, Alfonso-Rosa RM, Del Pozo Cruz B. Optimal dose and type of exercise to improve cognitive function in older adults: A systematic review and bayesian model-based network meta-analysis of RCTs. Ageing Res Rev. 2022 Apr;76:101591. doi: 10.1016/j.arr.2022.101591. Epub 2022 Feb 17. PMID: 35182742.

111 Penninkilampi R, Casey AN, Singh MF, Brodaty H. The Association between Social Engagement, Loneliness, and Risk of Dementia: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2018;66(4):1619-33. Epub 2018/11/20. doi: 10.3233/jad- PubMed PMID: 30452410.

Further info

How to stop your brain cells dying

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Last week a discovery, published in the journal Science, showed that a high level of an abnormal ‘phosphorylated-tau’ protein triggers brain cells to self-destruct. It also gives a vital clue as to how to stop your brain cells dying with specific vitamins.

When cells become largely dysfunctional, they self-destruct. This process in neurons (brain cells) is called ‘necroptosis’. The recent discovery, made by researchers at the UK’s Dementia Research Institute at University College London (1), showed that an abnormal accumulation of a protein called tau that then becomes phosphorylated, making it tangled and dysfunctional, triggers a specific molecule called MEG3 that triggers brain cell death.

“For the first time we get a clue to how and why neurons die in Alzheimer’s disease. There’s been a lot of speculation for 30-40 years, but nobody has been able to pinpoint the mechanisms. It really provides strong evidence it’s this specific suicide pathway.” researcher Prof Bart De Strooper, from the UK’s Dementia Research Institute. told the BBC.

Even before this, too much phosphorylated-tau (abbreviated to p-tau) interferes with the cell’s energy factories (called mitochondria), potentially leading to brain fatigue. The more p-tau accumulates, the greater a person’s risk for cognitive problems and Alzheimer’s dementia. Also, those with memory decline have been shown to have relatively more p-tau to tau protein.

The critical prevention question is, then, what stops too much of the tau protein from turning into the potentially harmful p-tau and what helps restore p-tau to normal tau protein. 

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The answer is remarkably simple – a lack of B vitamins and raised blood levels of homocysteine which is an established risk factor for memory decline, measurable in the blood. When levels of B vitamins (B6, B12 and folate) are low, blood levels of homocysteine go up. This activates one enzyme (Cdk5 kinase) that adds the bad ‘p’ to tau and blocks another enzyme (protein phosphatase A2) which removes the dangerous ‘p’ restoring normal tau protein (2)(3).  High homocysteine also damages the tiny blood vessels in the brain, leading to ‘mini strokes’ or transient ischemic attacks (TIAs), which further raise levels of p-tau (4). Homocysteine both raises levels of the dangerous p-tau and can also bind to tau (5), further generating the neurofibrillary tangles that then trigger brain cell death.

So, the simplest way to stop the formation of p-tau, and neurofibrillary tangles, and keep your brain healthy, is to keep your plasma homocysteine level below 10 mcmol/L. Half of those above 65 have a level of homocysteine higher than this. The easiest way to lower your homocysteine below 10 mcmol/L is to supplement B6, B12 and folate. 

But it’s also good to eat greens and beans that are high in folate. While B12 is only in animal foods – meat, seafood, eggs and milk. While an optimal supplemental intake for a middle-aged person might be 20mg of B6, 10 mcg of B12, and 400 mcg of folate, many older people start to dramatically lose their ability to absorb B12, the absorption of which requires stomach secretions. Antacid ‘PPI’ medication such as omeprazole accelerates this decline, promoting B12 deficiency. And, over four years of use, increases dementia risk by a third (6). Then, as studies show, you might need a lot more B12, such as 500 mcg, to get a little more into your bloodstream, and possibly more supplemental folate, in the region of 500 to 800 mcg.

This is the cheapest, safest and most logical solution to lower p-tau and prevent brain cells from committing suicide. The problem is that these nutrients, invented by nature, cannot be patented. Therefore it is not in the interest of the pharmaceutical industry to research them.

Consequently, drugs are being developed and tested that block the kinase enzyme and activate the phosphatase enzyme (7), which is exactly what the homocysteine-lowering B vitamins do. But, so far, there are no human clinical trials reporting significant benefit. 

On the other hand, trials giving these kinds of doses of B6, B12 and folic acid have shown up to a two-thirds slower rate of brain shrinkage (8) and virtually no further memory loss in those with pre-dementia (9).

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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.

———

Test Your Cognitive Function Now green banner.

References

1 https://www.science.org/doi/10.1126/science.abp9556 Balasu S et al. Science
14 Sep 2023 Vol 381, Issue 6663 pp. 1176-1182 DOI: 10.1126/science.abp9556

2 Smith AD, Refsum H. Homocysteine, B Vitamins, and Cognitive Impairment. Annu Rev Nutr. 2016 Jul 17;36:211-39. doi: 10.1146/annurev-nutr-071715-050947. PMID: 27431367.

3 LiJ-G,ChuJ,BarreroC,MeraliS,Pratico`D.2014.Homocysteine exacerbatesβ-amyloid, tau pathology, and cognitive deficit in a mouse model of Alzheimer’s disease with plaques and tangles. Ann. Neurol. 75:851–63 

4 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.

5 Bossenmeyer-Pourié C et al. N-homocysteinylation of tau and MAP1 is increased in autopsy specimens of Alzheimer’s disease and vascular dementia. J Pathol. 2019 Jul;248(3):291-303. doi: 10.1002/path.5254. Epub 2019 Mar 19. PMID: 307349

6 Northuis C, Bell E, Lutsey P, 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 Aug 9:10.1212/WNL.0000000000207747. doi: 10.1212/WNL.0000000000207747. Epub ahead of print. PMID: 37558503.

7 Xia, Y., Prokop, S. & Giasson, B.I. “Don’t Phos Over Tau”: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies. Mol Neurodegeneration 16, 37 (2021). https://doi.org/10.1186/s13024-021-00460-5

8 Smith AD, Refsum H. Homocysteine, B Vitamins, and Cognitive Impairment. Annu Rev Nutr. 2016 Jul 17;36:211-39. doi: 10.1146/annurev-nutr-071715-050947. PMID: 27431367; see also Jernerén F., et al. Am J Clin Nutr. 2015 Jul;102(1):215-21.

Further info

Warning: Your Brain Is Being Hijacked… by Junk Food, Tech & Stimulants

We now know that today’s diet, lacking in brain-friendly fats and other nutrients, yet high in sugar and ultra-processed food, is likely to be shrinking our brains, dumbing us down and triggering a big increase in mental health problems. But it isn’t just nutrition that is creating the perfect storm for our mental demise.

The digital culture we exist in is pushing us towards a whole new paradigm of background stress. This is partly because the marketeers have learnt how to get us addicted to their products – applying a level of stress and variable reward to trick the brain’s reward system – leaving you with a ‘gotta have it’ feeling.

This mechanism of ‘variable reward’

This was first discovered in the 1930’s by the psychologist B.F. Skinner. He found that mice responded most frequently to reward-associated stimuli when the reward was given after a varying number of responses – so the animal didn’t know when it would get the prize. It seems we are no different; if we perceive a reward to be delivered at random, and if checking for that reward comes at little or no cost, we end up checking habitually.

So is this where smartphone addiction comes from?

This manipulation of the stress/reward response is one of the oldest mechanisms of the brain. It is both core for our survival, but also makes us more impulsive, manipulatable and, effectively, stupid.

Most of all, it makes us good consumers. Reward, based on dopamine, equals pleasure. We are living in space-age times with stone age minds and multinational companies have learnt how to get us hooked – literally neurochemically addicted to consuming their products.

We are being sold pleasure in the guise of happiness: the happy hour, the happy meal, happiness in a can. But joy and happiness are regulated by the neurotransmitter serotonin, not the latest special offer. And in fact, this pleasure-seeking may be counterproductive.

“The more pleasure you seek, the more unhappy you get” says Professor Robert Lustig, author of ‘Hacking the American Mind’. This is because too much dopamine (the ‘reward’ neurotransmitter) suppresses serotonin (the ‘happy’ neurotransmitter) and we end up feeling unhappy and depressed. This brain hijack may be why depression, suicide and psychiatric drug prescriptions have rocketed to the point where, in the UK and US (and probably elsewhere), there are almost twice as many prescriptions for psychiatric drugs per year than there are people.  

“We are the most in debt, the most obese, the most medicated and the most drugged up adult population in human history” says Lustig. We have literally learnt how to fool our brains and in doing so have fooled ourselves, by creating addictive behaviours and addictive foods. 

An example of this is what happens in your brain if you eat sugar and/or fat. 

Sugar…just like cocaine and heroin?

Sugar, just like cocaine and heroin, stimulates dopamine and endorphins. It triggers the reward system but with overuse, leads to reward deficiency (1). Dr Candace Pert, Research Professor in the Department of Physiology and Biophysics at Georgetown University Medical Center in Washington DC, and author of the seminal book ‘The Molecules of Emotion’, was the first to point this out in no uncertain terms: “I consider sugar to be a drug, a highly purified plant product that can become addictive. Relying on an artificial form of glucose – sugar – to give us a quick pick-me-up is analogous to, if not as dangerous as, shooting heroin. (2)” At the time, this was heresy but, today, most people are well aware of this. But it’s not just sugar that’s feeding our addiction.

Neuropharmacologist Professor Paul Kenny, a Dubliner now working in his Manhattan lab at Mount Sinai Hospital, discovered this when he started feeding rats different diets. When he fed one group of rats either lots of sugary foods and another group lots of fatty foods, neither group would gain much weight. They’d control their intake and it would take over a month to see a small weight gain. 

However, when he fed them a combination of 50% sugar and 50% fat, such as in a cheesecake, he noted the mice would “dive head first into a slice and gorge so vigorously that it covered its fur in blobs. It’s not pleasant.” After a binge on cheesecake they continued to graze, constantly eating food, he says, as if the off-switch telling them they were full had malfunctioned. “It completely changed them.” They stopped exercising and gained significant weight after only seven days. They also became addicted (3). When he took away the junk food and replaced it with healthy food they went on a hunger strike, refusing to eat it. 

He even tried to stop them by giving them an electric shock to their feet. “We then warned the rats as they were eating—by flashing a light—that they would receive a nasty foot shock. Rats eating the bland chow would quickly stop and scramble away, but time and again the obese rats continued to devour the rich food, ignoring the warning they had been trained to fear. Their hedonic desire overruled their basic sense of self-preservation.” 

Overeating, he found, juices up the reward systems in the brain — so much so, that in some people, it can overpower the brain’s ability to tell them to stop eating when they have had enough. As with alcoholics and drug addicts, the more they have, the more they want, creating a vicious cycle of dopamine resistance, eventually leading to the brain’s receptors for dopamine to shut down. 

It seems dopamine, the brain’s main neurotransmitter of reward and desire, is the key. 

Obese people and drug addicts have been shown to have less dopamine D2 receptors (D2R)s (4). People who are born with reduced levels of D2R are therefore at greater genetic risk of developing obesity and drug addiction – so you can be genetically predisposed to addiction. Researchers at Brookhaven National Laboratory and the Oregon Research Institute have shown that the reward system in obese people responds weakly to food, even to junk food(5). How does an individual overcome this absence of pleasure? By eating more pleasure foods to gain a temporary boost, thereby perpetuating the cycle. The researchers found that obese people may overeat just to experience the same degree of pleasure that lean individuals enjoy from less food.

Nicole Avena of the University of Florida, and others, have found that particular fats or sugars, sugars together with fats, and possibly salt, are the most addictive (6). A study by Professor David Ludwig of Boston Children’s Hospital suggests that highly processed, quickly digested fast carbs could trigger cravings (7). But research overall indicates that no one ingredient stokes food addiction better than the combo of fats and sugars, high in calories. Nature just doesn’t make these kinds of foods. Only the food industry does.

Similarly, cola drinks combine the stimulant caffeine, with sugar and salt, to make you drink more. And we crave sugary food and drink even more when fructose is used instead of glucose. Why? Because our cells run on glucose and quickly feedback when we’ve had enough. Fructose (or high fructose corn syrup, derived from corn) takes longer to send us that signal, leading us to consume more. No wonder then that glucose has been replaced by fructose and is a key ingredient in today’s ultra-processed foods.

Are you addicted to your smartphone?

Of all the changes that have taken place in the 21st century, the ‘digital revolution’ has changed our world beyond recognition, seemingly speeding up time. Yes, our diet and environment have changed a lot, but what’s really changed, especially in cities that now house half of humanity and an estimated two-thirds of the world’s population by 2035, is the pace of life. People all over the world are sleeping less, having less downtime, feeling more anxious and stressed and burning out at a far higher rate. This is reflected in the increasing rate of work absenteeism, depression and suicide, especially in cities.

The speeding up of communication – emails, smartphones and digital media – means that we are supposed to react to demands, and are bombarded with them, at an ever-increasing speed. 

We have literally become addicted to our phones(8). The average person picks up their phone 352 times a day – more than every three minutes, and swipes it thousands of times a day. A UK survey reports 62% cannot make it through dinner without checking their phone. Almost half of us report anxiety if we don’t have our phone, or a signal, suffering ‘nomophobia’. We are going to sleep with our phones and checking them first thing on waking up. One survey found that one in ten university students in the US admitted to having checked their smartphones during sex! 

Why? Basically, to sell stuff. “I feel tremendous guilt,” admitted Chamath Palihapitiya, former Vice President of User Growth at Facebook, to an audience of Stanford students. “The short-term, dopamine-driven feedback loops that we have created are destroying how society works.” Whether it’s Facebook, Instagram, Twitter, Snapchat, LinkedIn or any other platform, the core design is to get your attention, then show you ads tailored to your attributes and behaviours which the technology learns about you. Facebook, for example, has learnt how to do this with prompts, swipe downs, red icons that you press and don’t know what you receive. Is it a ‘like’? Do I have more ‘friends’? Or has another person ‘linked’ to me on LinkedIn etc. 

Facebook even knows when you’re feeling ‘insecure’, ‘worthless’ and ‘need a confidence boost’ or are ‘bored’, and can make sure you receive a notification of a ‘like’ at just the right time to keep you hooked. If you find yourself checking your phone at the slightest feeling of boredom, purely out of habit, know that programmers work very hard behind the screens to keep you doing exactly that. A study of 143 undergraduates at the University of Pennsylvania, limiting use to 30 minutes a day versus a control group found significant reductions in loneliness and depression (9). The researchers concluded, “Our findings strongly suggest that limiting social media use to approximately 30 minutes per day may lead to significant improvement in well-being.”

Whether it’s a text, a notification or a ‘like’, just like sugar, this digital consumption triggers a reward signal in our brains. The marketing algorithms schedule the precise times to deliver our digital diet and serve up the extra addictive quality of a variable reward.

Your brain’s reward system

It’s to do with a tiny organ in the central hippocampal area of the brain called the nucleus accumbens. This is the headquarters of our dopamine-based ‘reward’ system.

The more dopamine you release the more receptors shut down, so you seek more pleasurable behaviours and foods. Insidiously and unknowingly your brain has been hijacked and the symptoms you feel are the direct consequences of an intended addiction. Gambling, gaming, overeating, sex, drugs, food, social media and other digital addictions are all part of it. We end up needing this constant stimulation and, to fuel that, need instant energy foods and drinks – sugar and coffee. 

Alcohol – the opiate of the masses

Whether you’ve become addicted to sugar, food, caffeinated drinks, social media, gambling, gaming or non-stop stimulation, or simply get caught in the stress trap, perhaps due to work and life demands and debts, this often results in an inability to switch off with a background feeling on anxiety and stress without alcohol, and difficulty sleeping. 

You may find, in time, that your need for alcohol increases – from a glass a night to two, three, half a bottle or even more. Alcohol, a well-established neurotoxin (10), surely is the opiate of the masses. Consumption keeps going up. It’s the currency of a good time, normalised as a response to stress, glorified in movies and at the core of our modern culture, with a 1.5 trillion dollar industry, expected to rise to 2 trillion by 2027 (11), promoting its use. While smoking has become frowned upon, anything other than heavy drinking is considered socially acceptable. Yet according to WHO alcohol is in the top five causes of death and disability, and has become the most common cause of death in men under 50 (and soon will be for women), accounting for one-fifth of all deaths under 50 and almost 30,000 deaths a year overall, roughly a third that of smoking and ten times more than opioids (inc heroin) and is ranked more harmful than any other drug, including opioids (12). This addictive drug is so socially acceptable that governments avoid attempts to curtail its use for fear of voter reprisals.

A commonly unknown fact is that death or disability from alcohol doesn’t only occur in heavy drinkers. The risk goes up exponentially with the quantity you drink. The good news is that small reductions have big positive effects on your health. To make this real, a 12.5% vol. bottle of wine contains 75g alcohol: drinkers who have 2/3rds of a bottle of wine (two large glasses) or the equivalent 50g of alcohol, have a lifetime risk of death of 16%. But one medium glass (175ml) of wine (17.5g of alcohol) brings that risk below 1%. In terms of mitigating serious health risks, including death, the advice of the UK government’s former advisor, Professor David Nutt, is for women to consume no more than 15g of alcohol per day  and for men no more than 20g alcohol per day, and to have at least two alcohol-free days per week. Sadly, Professor Nutt was sacked for saying that alcohol was a ‘time bomb’ and more dangerous than Ecstasy, but the statistics point to this being true.

The trouble is, when you get stuck in the cycle of seeking rewards, needing stimulants and relaxants, you become more tired, more anxious and may even have started to feel more depressed. 

When things get bad and you visit your doctor they may prescribe antidepressants, tranquillisers (short-term use only) or sleeping pills. Others learn to use illicit uppers and downers.

Are you addicted to stimulants?

The other major acceptable and glorified drug is caffeine, mainly in the form of coffee, although many people don’t realise that strong tea has as much caffeine as a regular cup of coffee. Like sugar, alcohol and our digital diet, it stimulates dopamine release and the feeling of pleasure or reward. Imagine a day with no coffee, tea, sugar, chocolate or that well-earned glass of something! If you shout, ‘No way!’ there is a very real possibility that you have some level of addiction to these stimulants. This can range from a mild addiction that you can live with quite happily to a major problem that is controlling your life. 

However, whatever the level of addiction, the net consequence is always less energy, not more. One of my clients, Bobbie, serves as a case in point. She was already eating a healthy diet and took a sensible daily programme of vitamin and mineral supplements. She had only two problems: a lack of energy in the morning and occasional headaches. She also had one vice: three cups of coffee a day. After some persuasion, she agreed to stop the coffee for a month. To her surprise, her energy levels rose and the headaches stopped. 

Like Bobbie, it’s useful to audit your stimulant consumption from time to time. Using a Stimulant Inventory below can be helpful, but in making an accurate assessment of your current relationship to stimulants, you need to be honest with yourself about how you use them. There’s a space for alcohol which, while not a stimulant, still triggers those dopamine receptors.

It’s useful to write down the time of day you consume the above and to spend time thinking about what your relationship to these substances is. 

  • Do you, for example, ever buy sweets and hide the wrappers so other people don’t know you’ve eaten them? 
  • Do you swoon at the dessert menu in restaurants? 
  • How much do you think about and look forward to that morning cup of coffee or a mid-morning second cup? 
  • How important is that drink after work?
  • Does everyone really know how much you smoke? 
  • Have you cranked up your caffeine intake to ‘double espresso’ equivalent drinks using more coffee at home than you used to? 
  • Do you need more to get a ‘kick’ if you even get one, or does coffee now just relieve the fuzzy tiredness you feel without it?

This kind of relationship to stimulants, often cloaked in an attitude that they are just some of the innocent pleasures of life, is indicative of an underlying chemical imbalance that depletes your energy and peace of mind and, at its worst, feeds into mental health issues.

Coffee and Caffeine Withdrawal and Sleep

If you wake up feeling good and can function without a coffee, and have no major mental health issues, sleeping well for example, but enjoy one coffee a day which will give you a dopamine kick, that’s not a problem. The best measure of your relationship with coffee or caffeine, and whether your brain has ‘downregulated’ dopamine and adrenaline receptors is what happens when you quit. If the answer is nothing then there’s no issue. If, on the other hand, you get a variety of withdrawal symptoms (13), including headaches, tiredness and irritability that means your neurotransmitter receptors have downregulated and it will take a few days for them to upregulate and bring you back to normal. For many just one cup of coffee a day can result in withdrawal effects if stopped (14). It’s also worth knowing that coffee, or caffeine, consumed 6 hours before sleep, which is about as long as caffeine stays in the system, is associated with disturbed sleep (15) – either difficulty falling asleep or waking in the night so, at least, it is wise to consume no caffeine after noon, especially if you have issues with sleeping.

Tea or coffee?

The caffeine in both coffee and tea increases the release of adrenalin, cortisol and dopamine in your body and brain, while inhibiting the absorption of adenosine, a brain-calming chemical. The release of adrenaline into your system gives you a temporary boost, but frequently makes you fatigued and depressed later. If you take more caffeine to counteract these effects, you end up spending the day in an agitated state, and might find yourself jumpy and edgy by night.

Tea contains caffeine, but also theanine, which has a more calming amino acid shown to enhance cognitive abilities (16). It also protects GABA receptors, which is the brain’s adrenalin off switch. Overall then, tea is better for you. Green tea may also have some benefits over black tea (the same plant, but processed differently such that green tea contains more antioxidants and polyphenols, which are good guys as far as our bodies are concerned).

Benefits or excuses?

Many things could be written on the apparent benefits of tea, coffee, even some forms of alcohol. We read about the beneficial effects of resveratrol in red wine, polyphenols in coffee and cacao and other antioxidants in tea. However, the nature of ANY dependence creates a psychological set of ‘excuses’ that we use to justify our addictive behaviour. 

This could be anything from ‘that’s a lovely sauce’ (sugar), ‘a little bit of what you fancy won’t harm you’ ‘I’m so stressed I have to have a drink’, ‘I’ve got to focus so I need a coffee’ and so on. Of course, all these substances work, otherwise we wouldn’t be attracted to them and, in that sense, mindful consumption in certain circumstances makes sense. For example, if someone experiences a shock, a sugary drink can help. And when a deadline looms and you need to burn the candle at both ends, caffeine can certainly help.

The issue here is to understand how the combination of sugar, caffeinated stimulants, alcohol, tech and social media addiction, shopping, gambling, gaming and so on can hijack your brain’s natural reward system and result in the opposite – you feeling more tired, anxious, unfulfilled and depressed. If that’s happened to you, rest assured there are some simple suggestions that will help you reclaim your brain’s full potential for feeling good, energised, clear, focussed and purposeful.

Simple ways to win back your brain
  • Limit your time spent on social media – 30 minutes a day max is a good target but you may need to build down to this. Turn your phone off (or to ‘airplane’ mode) at least an hour before bed and keep it that way for at least an hour in the morning. If you have to have it on, don’t check social media for a couple of hours. 
  • Limit your intake of caffeine to under 100 grams a day – that’s one strong cup of coffee or two weaker cups of tea. If you have a second cup, use the same tea bag, or have a filter coffee ‘run through’. Avoid all caffeine after noon.
  • Avoid buying food that contains added sugar, dates or raisins – if in doubt, read the label and remember sugar is often disguised as high fructose corn syrup. When looking at food labels remember 5g is a teaspoon of sugar and foods with more than 22.5g per 100g of sugar are considered high sugar and those with 5g or less per 100g are considered low sugar. Ideally, only have sugar in whole fresh fruits. Fruit juice is also high in sugar so best avoided or limited. 
  • Limit your daily intake of alcohol to 20 grams, or a maximum of two small glasses (125ml is one small glass) of wine. Have at least two days a week alcohol-free.

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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.


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References

1 P. Holford, How to Quit Without Feeling S**t, Piatkus, 2008.

2 P. Holford, How to Quit Without Feeling S**t, Piatkus, 2008.

3 P.M. Johnson and P.J. Kenny ‘Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats’, Nature Neuroscience (2010), vol. 13(5), pp. 635-641. 

4 .P. Kenny ‘Reward Mechanisms in Obesity: New Insights and Future Directions’ Neuron. 2011 Feb 24; vol 69(4): pp.664–679. 

 5  See ref 4 above

6 N.M. Avena and M.S. Gold, ‘Food Addiction – Sugars, Fats and Hedonic Eating’, Addiction (2011), vol. 106(7), pp. 1214-1215.

7 B. Lennerz et al., ‘Effects of dietary glycemic index on brain regions related to reward and craving in men’ The American Journal of Clinical Nutrition, Volume 98, Issue 3, 1 September 2013, Pages 641–647

9 https://guilfordjournals.com/doi/10.1521/jscp.2018.37.10.751

10 Nutt, D.;Hayes,A.; Fonville, L.; Zafar, R.; Palmer, E.O.; Paterson, L.; Lingford-Hughes, A. Alcohol and the Brain. Nutrients 2021, 13,3938. https://doi.org/10.3390/ nu13113938

11 https://www.statista.com/forecasts/696641/market-value-alcoholic-beverages-worldwide

12  David J Nutt and Jürgen Rehm J Psychopharmacol 2014 28: 3 DOI: 10.1177/0269881113512038 

The online version of this article can be found at: http://jop.sagepub.com/content/28/1/3

13 https://www.ncbi.nlm.nih.gov/books/NBK430790/

14 Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology (Berl). 2004 Oct;176(1):1-29. doi: 10.1007/s00213-004-2000-x. Epub 2004 Sep 21. PMID: 15448977.

15 Drake C, Roehrs T, Shambroom J, Roth T. Caffeine effects on sleep taken 0, 3, or 6 hours before going to bed. J Clin Sleep Med. 2013 Nov 15;9(11):1195-200. doi: 10.5664/jcsm.3170. PMID: 24235903; PMCID: PMC3805807.

16 Anas Sohail A, Ortiz F, Varghese T, Fabara SP, Batth AS, Sandesara DP, Sabir A, Khurana M, Datta S, Patel UK. The Cognitive-Enhancing Outcomes of Caffeine and L-theanine: A Systematic Review. Cureus. 2021 Dec 30;13(12):e20828. doi: 10.7759/cureus.20828. PMID: 35111479; PMCID: PMC8794723.

Further info

Alzheimer’s drugs – like statins for your brain?

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.


Test Your Cognitive Function Now green banner.
Further info

Polyphenol Power. Keep your Brain Young with Antioxidants.

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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 )

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.

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).

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)

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).

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.

 Lowest GLAntioxidantPolyphenol
Cacao*********
Olives*********
Blueberries*********
Kale********
Blackcurrants*******
Strawberries********
Broccoli********
Artichokes********
Cabbage (red)********
Asparagus*******
Onions (red)******
Avocado*******
Apples******
Beetroot*****
Cherries******
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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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.

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References

  1. 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.
  2. 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.
  3. 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.
  4.  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.
  5.  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.
  6.  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.
  7.  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 
  8.  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.
  9.  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.
  10.  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.
  11.  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.
  12.  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.
  13.  See reference 5.
  14.  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
  15.  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.
  16.  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.
  17.  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.
  18.  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.
  19.  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.
  20.  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.
  21.  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.
  22.  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.
  23.  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.
  24.  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.
Further info

How the Guardian halves impact of prevention – and what steps make the biggest difference.

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.


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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Further info

Coffee – is it good for your 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.

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New Alzheimer’s Drug Accelerates Rate of Brain Shrinkage by 20%

Don’t be fooled by the rhetoric promoting the new Alzheimer’s anti-amyloid drug. The results – increased brain shrinkage, a third getting brain bleeding or swelling and questionable clinically meaningful benefit – are not good.

However, reading this week’s headlines claiming a ‘turning point’ in the fight against Alzheimer’s you’d be mistaken in thinking something new has occurred since Eli Lilly’s press release regarding their new drug, donanemab, a month ago. What stimulated this week’s front pages was publication of the actual study in the Journal of the American Medical Association [1] giving more details of the results. This was reported positively in every major newspaper. Yet not one reported the fact that the drug treatment accelerated the rate of brain shrinkage by over 20% compared to placebo. This is clearly stated in the paper as “At 76 weeks, MRI [scans] showed a greater decrease in whole brain volume”.

This is consistent with a meta-analysis of all anti-amyloid treatments including donanemab, in the journal Neurology [2] earlier this year, which concluded that “Mild cognitively impaired participants treated with anti-amyloid drugs were projected to have a material regression toward brain volumes typical of Alzheimer dementia approximately 8 months earlier than if they were untreated.”

In stark contrast, treatment with homocysteine-lowering B vitamins, given to those with sufficient omega-3, ‘the rate of atrophy was significantly slowed by circa 70%’.[3] B vitamins and omega-3 are but two out of eight established prevention steps you can take yourself.

Alzheimer’s is characterised by brain shrinkage, and particularly in the central ‘hippocampus’ area of the brain. The new drug treatment was not associated with shrinkage of the hippocampus, just the whole brain. In fact, there was a very small reduction of about one per cent in shrinkage in this area of the brain compared to the placebo. In the B vitamin study there was an 80% reduction in shrinkage in the medial temporal lobe. While it is theoretically possible that, having selected people with lots of plaques, then targeting them with an aggressive drug, the brain may have shrunk as part of the process of amyloid destruction, this is not yet known and therefore this increased brain shrinkage is worrying

The other main measure of Alzheimer’s and dementia, made by a health professional, include interviewing the patient’s carer or partner – thus potentially subject to ‘hopeful’ bias – is the Clinical Dementia Rating (CDR).

The new drug treatment results do show a statistically significant improvement, showing just over half a point  (0.67) less worsening, compared to placebo, on the 18 point CDR scale. But is this small change meaningful? A study in the Lancet suggests that minimum changes of 0.98 in mild cognitive impairment and 1.63 in mild Alzheimer’s disease are meaningful. [4] This study was on those with early Alzheimer’s.

In contrast, a trial giving omega-3 fish oils to those with adequate B vitamin status, showed three times this beneficial clinical effect [5]. In another, giving homocysteine lowering B vitamins to those with adequate omega-3, almost two thirds of the trial participants ended the trial with an overall Clinical Dementia Rating of zero [6]. This means they were no longer diagnostically labelled as having cognitive impairment. In other words, not less worse, but actually better. 

Serious adverse effects including deaths

More details in the recent donanemab paper were given on the adverse effects and trial deaths. ‘Treatment-emergent adverse events’ were reported by 759 of 853 participants (89%) receiving donanemab’ and ‘Either amyloid-related imaging abnormalities of edema/effusion [swelling] or microhaemorrhages [bleeding] occurred in 314 participants (37%) receiving donanemab’. Also, in the donanemab group, ‘3 participants with serious amyloid-related imaging abnormalities subsequently died.’ This means that more than a third had brain bleeding or swelling and 1 in 287 died. This compares to no adverse events in the B vitamin and omega-3 trials, or other prevention approaches. If any nutritional supplement had anything like these adverse effects it would be banned, not licenced.

According to the Financial Times, this new treatment will cost $26,000 a year (in addition to medical costs including numerous scans). In the UK this would be paid by the taxpayer. In contrast, taking homocysteine-lowering B vitamins, eating fish and/or having fish oil supplements would cost perhaps 20p or cents a day.

So, the question is would you rather take a treatment that markedly slows both whole brain and medial temporal lobe shrinkage than a treatment that is associated with a greater loss of brain volume, a high risk of adverse effects and costs.

The big push is now on to get approval of the UK’s NICE  (National Institute for Health & Care Excellence) and the drug licensed in Europe. NICE have previously refused to consider the evidence for homocysteine-lowering B vitamins and omega-3, which is now overwhelmingly positive, when both these nutrients are combined.

That is why we, at Food for the Brain, aim to make sure as many people as possible know that the real ‘turning point’ for Alzheimer’s is prevention through diet, nutrition and lifestyle improvements, not expensive drugs with dangerous side-effects.

Please take the Cognitive Function Test yourself at foodforthebrain.org, and encourage all you know to do the same. We appreciate your support by becoming a Friend at foodforthebrain.org/friend. 

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VIDEO: What’s Driving Alzheimer’s with Patrick Holford

Is there a better way to do healthcare?

That was the focus of a conference of the World Council for Health and, given 10 minutes, our founder Patrick Holford, focussed on getting across why Alzheimer’s is a preventable disease. With eight core drivers, and homed in on two – B vitamins and omega-3 – and why one can’t work without the other, to show that we already know how to prevent age-related cognitive decline far better, and safer, than any drug treatment on offer.

This 10 minutes video is well worth a watch and will inspire you that there is so much you can do to upgrade your brain and prevent Alzheimer’s.

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