by Patrick Holford

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Drugs won’t prevent dementia.

Last week’s Lancet Commission on dementia prevention is facing mounting criticism, for favouring targets for drugs including lowering cholesterol and amyloid and completely ignoring quick and easy wins such as supplementing omega-3, homocysteine lowering B vitamins and reducing sugar intake. A very recent report from Cambridge University scientists says that the benefits of new anti-amyloid treatments may be outweighed by the costs and risk of side-effects such as shrinking brain matter.

US National Institutes of Ageing researcher Dr Madhav Thambisetty warned that trial participants lost up to three teaspoons of brain volume. ‘It is far from clear these drugs can ever significantly reduce dementia morbidity at scale’ report the scientists in the journal Alzheimer’s and Dementia and reported in the Telegraph this week.

The Lancet Commission completely ignored, for the third time since 2017, the indisputable evidence that inexpensive B vitamins, given to those with raised homocysteine (half the older population) reduced brain shrinkage in a year by up to 73%, the highest effect being in those with sufficient omega-3 DHA, as well as the substantial evidence in favour of omega-3.

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Our scientists in the Alzheimer’s Prevention Expert Group are actively preparing response letters to the Lancet – and once done, we will give a full report. Against this backdrop of minuscule effect that ‘is so small it would not be recognisable by doctor or patient’ and the need for specialist brain scans with each injection due to one in four getting brain bleeding or swelling we see press-mongering dressing up drugs as prevention; press reports ‘big up’ these unethical drug approaches, as yet unlicensed in the UK, in the guise of prevention – ‘UK needs Covid-style push on dementia drugs’  reports the guardian.

Prevention does not mean drugs, it means tackling the root causes of cognitive decline and brain shrinkage, which is what we are doing at Food for the Brain through our FREE Cognitive Function Test.

“We sent them the indisputable evidence and they ignored it.” Here’s how the Lancet Commission halved the true impact of dementia prevention, says our Founder, Patrick Holford.

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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.

By Patrick Holford

Raised homocysteine, the best indicator of your ‘methylation’ ability, is not only causal for Alzheimer’s disease but probably also for strokes and several other diseases in the 100 diseases for which homocysteine is a biomarker.

However, homocysteine is easily measured and is also easily optimised. It is most directly lowered by vitamin B12, folate and B6. There are other nutrients that also help, but these B vitamins are the most essential.

If you’re new to understanding why improving methylation lowers homocysteine, this film will give you an idea of what’s going on thousands of times every second in your brain and body. Watch it below.

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This further exploration into some close-up details regarding homocysteine comes from lengthy articles I’ve read which have made things too complicated and often inaccurate; such as people being either over- or under-methylated, and folic acid being the devil incarnate and other such things. So, I thought I’d clarify some misconceptions floating around the world of nutritional therapy.  

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What is homocysteine? 

It is a toxic amino acid, an intermediary made from the essential amino acid methionine in your proteinous food, en route to make S-Adenosyl Methionine (SAMe) which juggles methyl groups (CH3) as a methyl donor/acceptor and as the master of the brain and body’s orchestra, with several billion such reactions every minute. And that’s only half the story.

There is no good reason to want homocysteine in your blood because it damages arteries. But if you had absolutely none that would be weird. It would be like having no garbage in your house at all and none in the bins. Now, you don’t want to accumulate garbage, but you’ve always got a rubbish bin on the go. 

While a homocysteine level above 11 mcmol/l is strongly associated with accelerated rate of brain shrinkage and is probably also an appropriate reference point for increasing stroke and cardiovascular risk, problems can occur in children if their mothers had a level above 9 mcmol/l during pregnancy. In one study cognitive decline seemed to increase from 8 mcmol/l. In another study chromosomal damage to genes occurs above a level of 7.3 mcmol/l. My best guess, having seen hundreds of clients, is that having a homocysteine between 4 and 7 mcmol/l is probably optimal, with older people in their 80’s or 90’s often struggling to keep below 9 despite doing the right things.

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Can homocysteine be too low?

Can homocysteine be too low? I think this answer is ‘possibly’. Having a level below 4 is rare in and of itself. Even rarer is for someone to have a level below 4 and a problem. Why could too low be a problem? The second part of the story is that homocysteine can be turned into glutathione, the master antioxidant via the ‘sulphuration’ pathway, through the interaction of B vitamins on homocysteine in the presence of glycine (a sulphur container amino acid). This involves an enzyme, CBS (cystathionine beta synthase) which is dependent on vitamin B6.

Theoretically, if there wasn’t enough homocysteine, then this pathway for making glutathione would be in short supply. Such a finding has been shown in some children with autism, but it is very rare. And how would you know that the very low homocysteine, below 4 mcmol/l, was a bad thing, leading to less glutathione? I’d test the person’s glutathione or, more accurately, their Glutathione Index. Think of glutathione as the good guy, made from recycling rubbish, and homocysteine as the bad guy. 

If both were low I’d be thinking ‘where is the log jam’? You can see in the diagram above that the cheap, stable, inexpensive folic acid should turn into TH Folate, then, via the action of the MTHFReductase enzyme, into 5-methylfolate, or reduced, fully loaded folate, used in the body and brain in a thousand ways. But we must also note that CBS enzyme, dependent on vitamin B6 (itself dependent on zinc to be ‘activated’) must be fully functional. This pathway, if working properly, would naturally create glutathione, the body and brain’s master antioxidant.

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If this pathway is not working effectively, and both homocysteine and Glutathione are low, I’d suspect two ‘faulty’ enzymes. That is either the enzyme DHFR that does the first step in activating folic acid or MTHFR, which does the second step. This is dependent on vitamin B2 (riboflavin).

Enzymes are built from a genetic blueprint. If you inherit a slightly dodgy blueprint, your enzyme factory turns out cheap goods. You might then need a little help from riboflavin (B2) for those who inherited the gene MTHFR677T or TT. We all need B2, but this enzyme won’t work nearly so well if you’re deficient and have this genetic ‘polymorphism’. That is why having MTHFR677T or TT, which is present in about 24% of people (10% in Africans, 34% of Europeans) puts up a person’s risk for Alzheimer’s. But, in studies giving the three main co-factor nutrients – B6, folic acid and B12 – it makes no difference whether or not you have this dodgy gene. Homocysteine still gets lowered. That’s right. Folic acid works, both in combination, and on its own, in lowering high homocysteine and is turned into the activated form methylfolate without a problem. So that suspected enzyme variation, especially if you have enough B12, is not looking so critical. In all studies I’ve seen, where B6, B12 and folic acid is given, the beneficial effect is the same in both those with or without this gene ‘defect’.

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The gene that makes the enzyme DHFR…

The second suspect is a variation in the gene that makes the enzyme DHFR. Think of these gene ‘defects’ as resulting in less of the enzyme. As a consequence your body’s biochemistry wouldn’t be able to turn all folic acid into methyl folate. You’d then accumulate UnMetabolised Folic Acid (UMFA for short). Why would that be a problem? Well, folic acid still looks like methylfolate, and enzymes have a lock shaped for the key – that is their co-factor, such as folate. Too much folic acid in the blood could block all those enzyme receptors such that the enzymes don’t work so well, effectively inducing a folate deficiency. The net result in this scenario would be less glutathione.

A good example of how a less effective form of a vitamin can induce a vitamin deficiency in certain circumstances is vitamin B6. Those familiar with vitamin B6 (pyridoxine) know that it has to be turned into pyroxidal-5-phosphate (P5P) to become active, which requires zinc. If you supplement way too much vitamin B6 – 1 gram for example – and especially if you are zinc deficient, the unmetabolized B6 can block B6 dependent enzymes from working and you end up with similar symptoms of neuropathy also reported in those deficient in vitamin B6.

So, too much folic acid – for example over 1 gram – coupled with a dodgy DHFR gene would be bad news inducing something equivalent to folate deficiency. This then raises two questions: how much folic acid is too much? How many people have DHFR gene mutations?

The first answer depends somewhat on the second since those with a ‘bad DHFR gene’ are less able to cope with folic acid. The worse DHFR status is called a double deletion. How common is it? Not common in Europeans. It is very common in Asian ethnicities. These people would be less likely to benefit from folic acid because they can’t activate it. This is exactly what studies have shown. Folic acid lowers homocysteine and improves cognitive function less well in those with this gene polymorphism. Giving these people lots of folic acid will result in lots of unmetabolized folic acid (UMFA) accumulating and blocking real folate enzyme activity. This is effectively a B vitamin deficiency induced by a B vitamin.

While it could be argued that these people shouldn’t really be supplementing any folic acid there is little evidence to show that a lowish amount, let’s say up to 200 mcg in a multi, for example, is likely to be a great cause for concern.

But, especially for DHFR gene defectives, it is so much better to cut to the chase and supplement the activated methyl-folate form of this vitamin or its precursor folinic acid. An example of this is a study on autistic children, which gave folinic acid and tested an indicator of glutathione status. Those children with poorer glutathione status did better.  Unfortunately they didn’t test DHFR gene status.

They could have given methylfolate but the trouble with methylfolate is that it is very unstable, until the recent developments of three stable versions of methlyfolate:

calcium stabilised methyl folate, (Metafolin, process patented by DSM)
glucosamine stabilised methylfolate, (Quatrafolic, process patented by Gnosis/Lesaffre)
or choline stabilised methylfolate (Ocufolin, made by Aprofol/Generis)

Unlike folic acid, originally patented by Roche, but now expired, these other superior methylfolate forms of the vitamin are more expensive and with that comes more marketing muscle to switch buyers and makers of supplements and food fortification from folic acid to methylfolate. Leaving money to one side, it is generally a good idea to switch to methylfolate. It does lower homocysteine and raise red blood cell folate more effectively.

But it is wrong to say that folic acid doesn’t work in lowering homocysteine. It does and especially in the majority of Europeans without the DHFR gene defect. In East Asians I’d be more inclined to give methylfolate.

Methylfolate has been shown to raise folate levels better than folic acid and to lower homocysteine more effectively. In one study, 100µg of methylfolate lowered homocysteine by 14.6% compared to folic acid which lowered it by 9.3% in 24 weeks.  In another it both raised red blood cell folate by 30% more than folic acid and it also lowered Hcy by 13.8% compared to 9.9% for folic acid.  This means that methylfolate lowers homocysteine 40-50% more than folic acid.

Now, if you’ve had a homocysteine test, which I strongly advise in anyone over 50 or with any of the 100 diseases for which homocysteine is a biomarker, the great news is that almost all homocysteine lowering supplements (see here for more guidance on supplements) only use methylfolate alongside B6, B12, TMG, zinc and NAC or glutathione. 

If your level is below 4 mcmol/l AND you have any symptoms that also occur with folate deficiency (those 100 diseases that homocysteine is a biomarker of is a good starting point) then I’d recommend two things:

Test your Glutathione Index and, if low…
Test for the DHFR polymorphism here. The test is offered by Lifecode GX who will give you a discount as a Friend of Food for the Brain.

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Is too much unmetabolised folic acid or even natural food folate a problem?

The short answer regarding unmetabolised folic acid is probably yes, it probably is bad for you. 

Cancer cells are growing fast and need folates to do so. Having lots of folic acid in your bloodstream, seems to be a problem. Could too much folate in your bloodstream be a problem? Theoretically yes but generally, those eating a high folate diet rich in vegetables for example, have lower risk. But there’s a lot more in vegetables than just folate. 

I asked a folate expert, Dr Martin Ullman, regarding the cancer connection. “Folates are micronutrients, and any micronutrients are growth factors for healthy cells but even more for fast growing cancer cells. If there are precancerous conditions, “high” intake of folate may promote the progression to a cancerous condition. On the other hand, regular satisfactory intake of folate (before any precancerous condition) is preventive.”

Perhaps the riskiest scenario would be in those with that dodgy DHFR polymorphism that’s much more common in Asians, combined with a bad diet fortified with folic acid and unable to metabolise it and also with a pre-cancerous condition. Colorectal polyps, potentially pre-cancerous cells, would grow faster with more folic acid.

Also, bear in mind that raised homocysteine is, in any event, bad news for cancer. The majority of cancers are associated with faulty methylation so it’s one of the first things I’d check for. If raised, bring it down with a homocysteine lowering formula containing methylfolate, not folate.

What next:

Read more about homocysteine lowering supplementation here
Not sure what your homocysteine level is? Order one of our test kits here and support our research and charitable work.
Test for the DHFR genetic polymorphism here. The test is offered by Lifecode GX who will give you a discount as a Friend of Food for the Brain.
Want to know more about how you can upgrade your brain? Complete the free, validated Cognitive Function Test here to see what you can do to reclaim your brain.

For those who would like to dig even deeper, these papers are most relevant:

General: https://www.openaccessgovernment.org/article/who-benefits-cognitive-effects-b-vitamins/148992/
DHFR and cognition: https://academic.oup.com/hmg/article/31/7/1151/6425951

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.

A message from Patrick Holford, our CEO

Thanks to you, Food for the Brain has grown ten-fold in the last year, reaching another half a million people, with over 20,000 taking the Cognitive Function Test bringing the total to 420,000. In the last three months alone we’ve reached 2 million people and tested the cognitive function of a further 20,000.

Yet, every 3 seconds someone in the world is diagnosed with dementia – in the UK that’s 7 double decker buses worth of people every day. 

At the other end of the spectrum, special needs schools are bursting at the seams as autistic spectrum disorder diagnoses go through the roof. 

Thanks to generous donations from the Fieldrose Trust, Viridian and Heights, we’ve finally built our research database and are beginning to find some interesting things. 

Firstly, cognitive function declines, almost in a straight line, from age 18 to 90+. That’s a completely new discovery! Even 25 year olds have less cognitive function than 20 year olds. That’s why the earlier a person starts to make changes the greater are their chances of never developing dementia. You’ll be pleased to hear that the lower your Dementia Risk Index, calcuated from the COGNITION Questionnsaire you complete as part of the free online test, the better your cognitive function is and people making the changes recommended in the COGNITION programme can REVERSE cognitive decline.

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Jan is a case in point. Like the ‘average’ person his cognitive function was declining year on year – until he joined COGNITION. 

Here’s what he says: ‘Food for the Brain’s COGNITION programme has really helped to focus my mind on key changes, a step at a time. Since following their advice, I’m delighted to report that my cognitive function, which was close to the red after 17 months of decline, has returned into the green, better than the average for my age. I had lost my job and my ability to have a productive life, even my ability to speak without long pauses, and any hope of recovery. Food for the Brain’s educational support through COGNITION has demonstrated the potential for recovery such that I now have confidence and increasing hope for the future. Food for the Brain has been my lifeline’. 

Smart Kids – the children are our future

Natalie Coghlan, now appointed as Head of COGNITION for Smart Kids & Teens, is applying everything we’ve learnt from adults to children and teens and is running a small pilot study on 5 to 17 year olds to find out what happens in early years, how we can measure it and – ultimately how we can help children and teens become more mentally and cognitively robust. Please watch this short film from Natalie.

We’ve raised about £5,000 to kick-start this project but need to raise a further £35,000 to see it through to completion. If we can do this, we hope to launch COGNITION for Smart Kids and teens early in 2025. 

That is where SPONSA DONNA comes in.

Donna Von Tunk is sailing around the world and partnering with us so she can raise awareness and funds for this important project. If, collectively, we raise £1 a mile we’ve done it. That means 100 people giving 1p a mile (£400).

Can you help?

>>> Please make a donation and SPONSA DONNA here,
or
>>> Become a FRIEND.

If you’d like to make a more significant donation please contact me at patrick@foodforthebrain.org.

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The shocking fact

Now here’s a shocking fact – the Alzheimer’s Society have told us they don’t fund or focus on prevention. 

Nor do Dementia UK. They focus on supporting carers.

Alzheimer’s Research UK allocates less than 4% to non-drug prevention research, despite 80% of Alzheimer’s and dementia being preventable – and none of their current projects are interventions – to find out if a prevention action works for example.

I’m afraid to say it’s drugs all the way, with £5 million going into a study involving testing blood levels of p-tau in 5000 people as a predictor of cognitive decline. That’s £1,000 per person. 

Since testing cognitive function, which we do FOR FREE, is how you diagnose dementia, why not just do this? The most direct way to best predict who is heading for cognitive decline is to test cognitive function itself since it reduces many years before a diagnosis. £5 million would puts 100,000 people through our COGNITION programme helping them to actually dementia-proof their diet and lifestyle. The only logic for this p-tau test is to then say ‘you need the drug’ just as your cholesterol level became the proof that you need statins – which have not worked in any independent study that’s not funded and controlled by the drug makers.

Having failed to find a single UK charity who are taking prevention seriously it really is down to us to drive the prevention action forwards. 

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Announcing the COGNITION Biobank project

You’ve probably heard of the UK Biobank. People like me, aged 40 to 69 back in 2006, gave blood, filled in questionnaires and did tests. We are all being tracked to see if we’ll develop dementia or other diseases. No-one is being retested.

Here, at Food for the Brain, we have the COGNITION Biobank. 

If you’ve taken the Cognitive Function Tests you’re part of it. To date we’ve tested 420,000 people AND we encourage you to retest cognitive function every six months or year. Also, we are now encouraging you to test blood levels of key biomarkers such as homocysteine. In this way you become a Citizen Scientist. The UK Biobank didn’t do this, so they never mention homocysteine-lowering B vitamins, which is ‘the most promising treatment’ according to the largest reviews of 396 trials on Alzheimer’s prevention. Also, we ask the right questions in our COGNITION questionnaire because, back in 2006, they didn’t really understand what was driving cognitive decline. 

We hope to have the largest Biobank, specific to cognition, tracking hundreds of thousands of people over time AND encouraging them to make changes by sharing back what works from this research. 

This is science for the people, by the people, funded by the people. 

On that note, we need to raise £1 million, £50,000 at a time to take this project global and big-scale. We are looking for impact investors, with at least £10,000 to invest, with a guaranteed return, much like an ISA. Wouldn’t you rather your invested money was saving people’s brains? Also, unlike other charities where, for every £10 given, £3 goes into fund-raising costs, at Food for the Brain 100% of what you donate goes directly into prevention research and education. We are lean and focused, all working virtually.

Our Head of Research and Principal Investigator is neuroscientist Dr Tommy Wood, Assistant Professor at the University of Washington. He’s a systems-based thinker and gave an amazing talk at our recent Upgrade Your Brain conference.

You can watch him in action here giving a stunning presentation on a systems-based approach to cognitive function. The diagram below is from his talk. We’ll be publishing a paper on this soon.

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Prevention is more effective & available right now 

Not only are literally no other charities taking prevention seriously, or keeping up to date with the evidence that is streaming in almost weekly, none have any comprehensive model as to how cognitive decline occurs and how to keep your brain healthy. 

Quoting Alzheimer’s Research UK, whose strapline is ‘we exist for a cure’ they say: “don’t smoke, keep cholesterol and blood pressure under control, be active daily and exercise regularly, maintain a healthy weight, eat a healthy balanced diet, drink fewer than 14 units of alcohol per week.” That’s it. Let’s face it – who didn’t know that? That’s not exactly going to reverse the dementia epidemic. 

Despite part funding the original Oxford trial on B vitamins, which showed up to 73% reduced rate of brain shrinkage, compared to approx. 20% increased brain shrinkage from the latest anti-amyloid drug treatment, their Chief Medical Officer Dr Peter Schott says: “Dietary supplements are big business, and plenty of websites sell vitamins on the promise of boosting brain health. But supplements are only recommended for people with a diagnosed deficiency, and should be taken with a doctor’s support.” 

What on earth does he mean by ‘diagnosed deficiency’? He ignores the fact that about half those over 65 are deficient, indicated by a homocysteine level above 11 mcmol/l. How many doctors even know that, let alone are testing for it? Some test serum B12 but, in the UK, the reference range for this is wrong. In the EU, Japan and Canada if your level is below 500pg/ml you’re deficient. This is correct. In the UK the cut-off level is 180pg/ml. This is wrong. Brain shrinkage is happening below 500 pg/ml. Homocysteine is the most important and predictive test which is why we test it as part of our research. It’s included in the DRIfT test and can be tested on its own – see foodforthebrain.org/tests. Lowering high homocysteine with a 10p a day B vitamin is the single most effective, and cost-effective, prevention action anyone can take. We had it costed by Oxford University’s health economist and found that just this would save £65 million a year in the UK. The next best evidence-based prevention action is to up your omega-3 level (test your omega-3 index here)] to find out how you are doing) and eat a lower carb and low GL diet (glycaemic load goes further than the glycaemic index as it takes into account the portion size of the food). 

Now that would make a difference.

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SEEKING A CEO/OPERATIONS DIRECTOR

Having helped shape Food for the Brain’s strategy, and helped it grow exponentially, I need to focus on getting the word out there – teaching as many people, public and practitioners, as possible, getting media coverage, helping spread the word. That’s what I’m good at. In September we launch in Canada, Australia and New Zealand. In November we launch in Japan and China, thanks to generous donations, and I’m going out there to launch the Cognitive Function Test, teach and spread the word. Next we seek donations to translate all this into Spanish and Portugese.

So now we really need a good leader and team player who knows how to get things done, working with our brilliant, highly functional small-but-mighty team. This is a part-time, paid position, with the potential to grow full-time as the charity expands. If you think you might have what it takes and have the combined skills of marketing and operations, digital development and are also able to lead and represent the charity with my full support, plus a background and passion for nutrition and mental health, get in touch by sending your CV to me at patrick@foodforthebrain.org.

Wishing you the best of health and happiness,

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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.

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Do supplements really help when it comes to cognitive decline or are they money wasted down the toilet?!

We believe that the science supports the use of correct supplementation in order to reduce risk of dementia and Alzheimer’s – so what is going on and what does the research really say?

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The WHO report saying supplements are ‘not recommended’

A 2018 report by the WHO states: ‘Vitamins B and E, PUFA and multi-complex supplementation should not be recommended to reduce the risk of cognitive decline and/or dementia.’ 

This 2018 WHO review makes no reference at all to the effect of B vitamins in slowing brain atrophy (1) and in improving cognition (2) in the rather large sub-group, estimated to be up to half of those over 65, with raised homocysteine. After all, why would B vitamins be expected to have an effect in those not deficient?

On closer inspection, three of the four cited studies in the WHO document are actually one meta-analysis (which is a statistical process of analysing and combining results from several similar studies). It cites only one paper which considered B vitamins (the one part-funded by Alzheimer’s Research UK) which showed a clear effect of B vitamins improving cognition in those with raised homocysteine, and one study on omega-3 DHA, which also shows clear benefit as stated in the studies summaries. Thus, it misrepresented the study that ARUK part funded on B vitamins as negative, when they had a clearly positive effect. 

The only cited B vitamin study (2) states, “The mean plasma total homocysteine was 30% lower in those treated with B vitamins relative to placebo. B vitamins stabilised executive function (CLOX) relative to placebo. There was significant benefit of B-vitamin treatment among participants with baseline homocysteine above the median in global cognition, episodic memory and semantic memory. Clinical benefit occurred in the B-vitamin group for those in the upper quartile of homocysteine at baseline in global clinical dementia rating score… In this small intervention trial, B vitamins appear to slow cognitive and clinical decline in people with mild cognitive impairment (MCI), in particular in those with elevated homocysteine.”

The only cited study on omega-3 fish oils (3) states, “The fish oil group showed significant improvement in short-term and working memory.” The 12-month change in memory was significantly better in the fish oil group. This study suggested the potential role of fish oil to improve memory function in MCI subjects.

So, even based on its own cited evidence, the benefit of both B vitamins and omega-3 fish oils is supported.

How the WHO statement then recommends the opposite, ‘Vitamins B and E, PUFA and multi-complex supplementation should not be recommended to reduce the risk of cognitive decline and/or dementia.’ beggars belief. But the real problem is not the shoddy research, from 2015, used to produce this report but that it is out of date. The WHO ‘rules’ for this report was to ignore any study that was more than 5 years old, yet the WHO authors republished this same report, with the same conclusions, in 2022, by then redundant according to its own rules!

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What we’ve learned since 2018

Also, much has been learnt, and published, since 2018. There is now evidence that homocysteine lowering B vitamins are most effective in those with sufficient omega-3 status and omega-3 fish oils are most effective in those with low homocysteine. This is clinical confirmation of the known mechanism of co-dependence and illustrates why the WHO document is now out of date. We prefer published, peer-reviewed reviews such as the editorial in the American Journal of Clinical Nutrition in 2021 (4) and a meta-analysis in 2023 (5).

Additionally, since 2018, there have been at least 17 studies (6-22), including both randomised controlled trials and cohort studies which show benefit of either omega-3 fish oil supplementation, or higher intake from seafood with resultant higher omega-3 blood levels, in reducing risk for and incidence of dementia or cognitive decline.

This is another example showing why the WHO document is no longer current and relevant. Yet leading Alzheimer’s charities such as the Alzheimer’s Society and Alzheimer’s Research UK (ARUK – who part funded the highly effective B vitamin trial) still refer to this redundant report.

With regard to multivitamins, the latest meta-analysis states (7), “The meta-analysis of COSMOS substudies showed clear evidence of multivitamin-mineral benefits on global cognition and episodic memory; the magnitude of effect on global cognition was equivalent to reducing cognitive ageing by 2 years”. B vitamins, given to those with raised homocysteine, are much more effective than multivitamins given to all – and more effecctive in those with sufficient omega-3 status.

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Summary

In conclusion, the 2018 WHO report is so sloppy, and out of date – by its own rules. It would be wise for WHO to withdraw this misleading report and certainly for both ARUK and the Alzheimer’s Society and any other Alzheimer’s or dementia organisations to stop referring to it in the context of omega-3, B vitamins or multivitamins, if they are to maintain credibility in being science-based.

Note: Many people are not aware that the WHO is no longer only funded by donations from the countries that it is supposed to serve but is now also privately funded, with the second largest funder being the Bill Gates Foundation, which accounts for 10% of its budget, leading to questions over influences on its agenda. 

Thank you for reading!

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

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

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

References

1. Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PloS one 2010;5(9):e12244.

2. de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. International journal of geriatric psychiatry 2012;27(6):592-600.

3. Lee et al 2013 – https://pubmed.ncbi.nlm.nih.gov/22932777/

4. Smith AD, Jernerén F, Refsum H. ω-3 fatty acids and their interactions. Am J Clin Nutr 2021;113(4):775-8.

5. Fairbairn P, Dyall SC, Tsofliou F. The effects of multi-nutrient formulas containing a combination of n-3 PUFA and B vitamins on cognition in the older adult: a systematic review and meta-analysis. The British journal of nutrition 2023;129(3):428-41.

6. Liu X, Zhuang P, Li Y, Wu F, Wan X, Zhang Y, et al. Association of fish oil supplementation with risk of incident dementia: A prospective study of 215,083 older adults. Clinical nutrition (Edinburgh, Scotland) 2022;41(3):589-98.

7. Vyas CM, Manson JE, Sesso HD, Cook NR, Rist PM, Weinberg A, et al. Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial and meta-analysis of 3 cognitive studies within COSMOS. Am J Clin Nutr 2024;119(3):692-701.

8. Jerneren F, Cederholm T, Refsum H, Smith AD, Turner C, Palmblad J, et al. Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer’s Disease: The OmegAD Study. Journal of Alzheimer’s disease : JAD 2019.

9. Rouch L, Virecoulon Giudici K, Cantet C, Guyonnet S, Delrieu J, Legrand P, et al. Associations of erythrocyte omega-3 fatty acids with cognition, brain imaging and biomarkers in the Alzheimer’s disease neuroimaging initiative: cross-sectional and longitudinal retrospective analyses. Am J Clin Nutr 2022;116(6):1492-506.

10. He X, Yu H, Fang J, Qi Z, Pei S, Yan B, et al. The effect of n-3 polyunsaturated fatty acid supplementation on cognitive function outcomes in the elderly depends on the baseline omega-3 index. Food & function 2023;14(21):9506-17.

11. Doughty KN, Blazek J, Leonard D, Barlow CE, DeFina LF, Omree S, et al. Omega-3 index, cardiorespiratory fitness, and cognitive function in mid-age and older adults. Prev Med Rep 2023;35:102364.

12. Loong S, Barnes S, Gatto NM, Chowdhury S, Lee GJ. Omega-3 Fatty Acids, Cognition, and Brain Volume in Older Adults. Brain Sci 2023;13(9).

13. Maltais M, Lorrain D, Léveillé P, Viens I, Vachon A, Houeto A, et al. Long-chain Omega-3 fatty acids supplementation and cognitive performance throughout adulthood: A 6-month randomized controlled trial. Prostaglandins, leukotrienes, and essential fatty acids 2022;178:102415.

14. Andriambelo B, Stiffel M, Roke K, Plourde M. New perspectives on randomized controlled trials with omega-3 fatty acid supplements and cognition: A scoping review. Ageing Res Rev 2023;85:101835.

15. Wei BZ, Li L, Dong CW, Tan CC, Xu W. The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers. Am J Clin Nutr 2023;117(6):1096-109.

16. Grande de França NA, Díaz G, Lengelé L, Soriano G, Caspar-Bauguil S, Saint-Aubert L, et al. Associations Between Blood Nutritional Biomarkers and Cerebral Amyloid-β: Insights From the COGFRAIL Cohort Study. The journals of gerontology Series A, Biological sciences and medical sciences 2024;79(1).

17. Sasaki N, Jones LE, Carpenter DO. Fish consumption and omega-3 polyunsaturated fatty acids from diet are positively associated with cognitive function in older adults even in the presence of exposure to lead, cadmium, selenium, and methylmercury: a cross-sectional study using NHANES 2011-2014 data. Am J Clin Nutr 2024;119(2):283-93.

18. van Soest APM, van de Rest O, Witkamp RF, Cederholm T, de Groot L. DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial. European journal of nutrition 2022;61(7):3731-9.

19. Gao J, Fan H, Wang X, Cheng Y, Hao J, Han S, et al. Association between serum omega-3 PUFAs levels and cognitive impairment in never medically treated first-episode patients with geriatric depression: A cross-sectional study. J Affect Disord 2024;346:1-6.

20. He Y, Huang SY, Wang HF, Zhang W, Deng YT, Zhang YR, et al. Circulating polyunsaturated fatty acids, fish oil supplementation, and risk of incident dementia: a prospective cohort study of 440,750 participants. GeroScience 2023.

21. Chedid G, Malik A, Amangurbanova M, Khraishah H, Welty FK. Docosahexaenoic Acid Levels and Omega-3 Index, but Not Eicosapentaenoic Acid Levels, Are Associated With Improved Cognition in Cognitively Healthy Subjects With Coronary Artery Disease. Arteriosclerosis, thrombosis, and vascular biology 2022.

22. Duchaine CS, Fiocco AJ, Carmichael P-H, Cunnane SC, Plourde M, Lampuré A, et al. Serum ω-3 Fatty Acids and Cognitive Domains in Community-Dwelling Older Adults from the NuAge Study: Exploring the Associations with Other Fatty Acids and Sex. The Journal of nutrition 2022;152(9):2117-24.

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This is the question we get asked all the time from our community.

Normally if they go to the doctor they may get referred to a memory clinic for a Cognitive Function Test. Some get invited to take part in drug trials and there are basically two kinds of drugs under investigation – anti-amyloid and anti-p-tau.  If you’re tempted to participate in any test, we would suggest finding out which type is being tested. So far the anti-amyloid treatments have not delivered any significant clinical benefit and lots of adverse effects including deaths. Anti p-tau drugs have not yet been proven to work. However, p-tau accumulation, making neurofibrillary tangles, is a function of high homocysteine which is lowered with B vitamins (see below).  We know this already. So why not test and lower homocysteine with B vitamins?

Some people get prescribed cholinesterase inhibitor drugs, designed to stop the breakdown of acetylcholine. These include rivastigmine, donepezil (Aricept) and galantamine. They are marginally effective, but the effect runs out after 2 years (see why below and other approaches).

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The first steps:

The first step, with help, is to do the Cognitive Function Test here (which they may struggle with), followed by a questionnaire.

Even if they can’t complete the Cognitive Function Test, do encourage them to continue and complete the questionnaire because this will show where the weak areas that need attention are. An example test result is below.

Ideally, they should then sign up as a FRIEND to get access to COGNITION and a focused brain upgrade but if they are too far progressed to receive and respond to emails, then here are some quick wins.

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At home tests to run & what to do with the results

First, have them do the DRIfT home test to measure HBA1c, homocysteine, omega-3 index and vitamin D. If you know their HbA1c and vitamin D already then you can test these individually (see all test options here).

From a raised HbA1c we’d know if sugar balance is a problem, in which case 2 tablespoons (60g) of C8 oil is likely to help, as well as eating low carbs and avoiding sugar as much as possible (and limit alcohol). The C8 oil helps the brain make ketones which is an alternative fuel source for brain cells and fills the ‘energy gap’ created by poor glucose delivery, a function of insulin resistance.

If Homocysteine is above 10mcmol/l. we’d know they need homocysteine lowering B vitamins (including supplementing vitamin B12 500mcg – see here)

If Omega-3 is below 8%, they need to eat more oily fish and supplement omega-3 fish oils with 500mg of DHA – see here for more info on supplementation. 

If Vitamin D is below 75nmol/l they need to supplement – probably 1,000 to 3,000ius a day or 10,000-20,000ius a week. Click here to read more about what’s needed depending on their level.

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How to support neuronal membranes

Neuronal membranes, which is what breaks down in dementia, are made from phospholipids binding to omega-3, which require B vitamins to drive a process called methylation.

If this process is not working efficiently, homocysteine goes up.

A critical phospholipid is Phosphatidyl Choline (PC), bound to omega-3 DHA (known as PC-DHA, which predicts dementia if low). The cholinesterase inhibitor drugs try to protect this but why not supplement phosphatidyl choline, which is very rich in lecithin capsules or granules? Two high PC lecithin capsules, plus at least 500 mg of omega-3 DHA, plus homocysteine-lowering B vitamin complexes cover all bases. See here for more information on supplements.

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Other things that can help

We can guide you through all 8 lifestyle domains that can help improve cognitive function in our COGNITION program (read how Dorothy got her husband back after implementing these with her husband here). 

A diet low in sugar and carbs, with lots of oily fish, regular exercise and as much social and intellectual stimulation as possible along with good sleep, all make a big difference and we guide you through that in COGNITION for £5 a month or £50 a year. Access COGNITION by joining as a FRIEND here.

Once the Cognitive Function Test is complete, you will get a personalised result showing the areas that are ‘in the green’ and the areas you need to focus on (bear in mind that if dementia is already diagnosed, there will probably be a lot of red and amber colours). 

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Actions:

Complete the Cognitive Function Test as much as possible, then if you wish join our COGNITION program for more guidance.
Order your DRIfT at home blood test here or if you already have some test results you can order single tests here

All tests ordered and completed contribute to our charitable work and independent research and are a part of our Citizen Science mission! 

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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.

Nutritional therapists have been measuring red cell glutathione and supplementing glutathione or its precursor N-Acetyl-Cysteine (NAC) for decades. But it’s really hard, and expensive, to measure accurately. Until now.

So how does the Glutathione Index work? 

All of life is a balance between antioxidants and oxidants. That is why we, an oxygen based lifeform, have a finite life. Inside your cells glutathione (GSH) is working every second to stop harmful oxidants from ageing you. The result is spent or oxidised glutathione (GSSG). Our new test – a world first – measures the ratio between fully loaded glutathione (GSH) and oxidised glutathione (GSSG). The Glutathione index (GSH/GSSG) shows you how much antioxidant potential you have and how many metabolic fires you’ve extinguished. This ratio is the difference between mental health and mental illness.

Why does knowing this single marker help with Alzheimer’s, diabetes, schizophrenia, severe autism, depression & more?

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The Science

NAC has plenty of evidence to support its use as a promoter of glutathione and mental health, thus reducing the brain’s oxidative stress. The latest 2022 review states: “N-acetyl-L-cysteine (NAC) is a compound of increasing interest in the treatment of psychiatric disorders. Primarily through its antioxidant, anti-inflammatory, and glutamate modulation activity, NAC has been investigated in the treatment of neurodevelopmental disorders, schizophrenia spectrum disorders, bipolar-related disorders, depressive disorders, anxiety disorders, obsessive compulsive-related disorders, substance-use disorders, neurocognitive disorders, and chronic pain. Currently NAC has the most evidence of having a beneficial effect as an adjuvant agent in the negative symptoms of schizophrenia, severe autism, depression, and obsessive compulsive and related disorders.” (1)

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Glutathione and Schizophrenia

Quoting Lorraine Wilder (whose MSc in schizophrenia we funded) “Glutathione (GSH) is an important antioxidant and free radical scavenger that has been found to be decreased in the brains of people with schizophrenia [2, 3]. Although oral GSH supplementation has poor bioavailability [4], N-Acetyl Cysteine (NAC) has been shown to successfully raise plasma glutathione levels in those with schizophrenia [5]”.

In a case study of a 24 year old woman with chronic and worsening paranoid-type schizophrenia that was generally unresponsive to anti-psychotic treatment, the addition of NAC supplementation improved the patient’s symptomatology in seven days. In addition to the schizophrenia-specific symptoms, improvements were observed in spontaneity, social skills and family relations by both the patient and family members. A randomised placebo-controlled trial (RCT) including 42 participants with schizophrenia, who were experiencing an acute phase of symptomatology, were randomly assigned to receive up to 2 g/d of NAC plus up to 6 mg/d of risperidone for 8 weeks as an adjunct intervention. 

Significant negative symptoms were found in the active treatment group compared to controls but not in positive or general psychopathology [6]. Furthermore, a larger RCT of 140 participants observed significant improvements on global symptomatology and general and negative symptoms of schizophrenia in the NAC supplementation (2 g/d; in addition to anti-psychotic medication) group in comparison to the placebo group over a 24-week period, but not positive symptoms [7]. Notably, after a 4-week washout period these beneficial effects diminished, with the exception of clinical severity scores. 

According to Dr Chris Palmer, assistant professor at Harvard Medical School, “Glutathione (GSH), the brain’s primary antioxidant, plays a crucial role in maintaining redox balance. Magnetic resonance studies have provided mixed results regarding GSH levels in schizophrenia patients, with some studies indicating decreased levels in chronic schizophrenia, while others found no significant differences. However, these inconsistencies may be due to variations in disease chronicity, age, and symptom severity among study participants. The findings from these studies suggest several potential therapeutic targets for schizophrenia. Addressing mitochondrial dysfunction, redox imbalance, and impaired energy metabolism could lead to more effective treatments. For instance, N-acetylcysteine (NAC), a precursor to GSH, has shown promise in increasing brain GSH levels and improving symptoms in first episode psychosis patients.”

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The Glutathione Index (GSH/GSSG) is the best indicator of brain oxidative stress. 

The GSH/GSSG ratio reflects the activity of the enzyme glutathione reductase which is responsible for the transformation of GSSG (used, oxidised) to GSH (the reduced or fully loaded form that acts as a radical scavenger). 

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Reductions in glutathione reductase (GR) enzyme levels in patients with dementia are well established. GR levels alone are therefore a fairly good biomarker of dementia. But the mere presence of the enzyme does not guarantee its high activity. GR needs to consume NADP molecules to function properly. The advantage of our test is, therefore, that it shows changes in GR activity not only due to higher/lower GR gene activity but also due to the absence of the reaction cofactor NADP. 

As shown by Irene Martinez de Toda et al 2019 (8) data, patients with dementia have a reduction in both the enzymes (GR and GP) that recycle glutathione. Thus, in general, it can be said that the glutathione metabolism (recycling) loop in those with dementia ‘spins’ much slower than in healthy patients. As a result, dementia patients have a lower potential to dynamically fight free radicals and will have a worse Glutathione Index.

In patients, the enzyme GR, which is responsible for recycling spent/oxidised glutathione back to fully loaded, slows down, which leads to the accumulation of oxidised glutathione (GSSG) and the depletion and inability to produce GSH. 

Thus, the concentration of GSH decreases while that of GSSG increases. Hence the Glutathione Index gets worse / is lower.

So will you join us and become a part of our Anti-Age Your Brain Campaign? We need Citizen Scientists to order and complete the test so you can start to protect your brain from ageing and so we can research what the ‘perfect number’ is.

Order your Glutathione test here

Thank you for reading!

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

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

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

References

1. Bradlow RCJ, Berk M, Kalivas PW, Back SE, Kanaan RA. The Potential of N-Acetyl-L-Cysteine (NAC) in the Treatment of Psychiatric Disorders. CNS Drugs. 2022 May;36(5):451-482. doi: 10.1007/s40263-022-00907-3. Epub 2022 Mar 22. Erratum in: CNS Drugs. 2022 Apr 28;: PMID: 35316513; PMCID: PMC9095537.

2 Yao JK, Leonard S, Reddy R: Altered glutathione redox state in schizophrenia. Dis Markers 2006, 22(1):83–93.

3 Gawryluk JW, Wang J-F, Andreazza AC, Shao L, Young LT: Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders. Int J Neuropsychopharmacol 2011, 14(01):123–130.

4  Witschi A, Reddy S, Stofer B, Lauterburg B: The systemic availability of oral glutathione. Eur J Clin Pharmacol 1992, 43(6):667–669.

5. Lavoie S, Murray MM, Deppen P, Knyazeva MG, Berk M, Boulat O, Bovet P, Bush AI, Conus P, Copolov D, Fornari E, Meuli R, Solida A, Vianin P, Cuénod M, Buclin T, Do KQ:Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients. Neuropsychopharmacology 2008, 33(9):2187–2199.

6. Farokhnia M, Azarkolah A, Adinehfar F, Khodaie-Ardakani M-R, Hosseini S-M-R, Yekehtaz H, Tabrizi M, Rezaei F, Salehi B, Sadeghi S-M-H, Moghadam M, Gharibi F, Mirshafiee O:, Akhondzadeh S: N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: a randomized, double-blind, placebo-controlled study. Clin Neuropharmacol 2013, 36(6):185–192.

7. Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Judd F, Katz F, Katz P, Ording-Jespersen S, Little J, Conus P, Cuenod M, Do KQ, Busha AI: N-acetyl cysteine as a glutathione precursor for schizophrenia—a double-blind, randomized, placebo-controlled trial. Biol Psychiatry 2008, 64(5):361–368.

8. Martínez de Toda I, Vida C, Sanz San Miguel L, De la Fuente M. Function, Oxidative, and Inflammatory Stress Parameters in Immune Cells as Predictive Markers of Lifespan throughout Aging. Oxid Med Cell Longev. 2019 Jun 2;2019:4574276. doi: 10.1155/2019/4574276. PMID: 31281577; PMCID: PMC6589234.

In a world often filled with daunting health challenges, Alzheimer’s Prevention Day stood out as a beacon of hope and action.

This year was the first launch of this global initiative and we were privileged to witness an incredible turnout: over 10,000 individuals visited our site, driven by a shared determination to tackle Alzheimer’s disease head-on. The day was not just about awareness but about tangible actions that each person can take to safeguard their cognitive health.

One of the highlights was our interactive 3-minute Alzheimer’s Prevention Check, which 8,000 participants eagerly completed. This simple yet impactful test empowers individuals to assess their cognitive health and take proactive steps towards prevention. 

Moreover, the 30-second challenge captured hearts and imaginations alike. We asked people to share on video what they do to help prevent Alzheimer’s each day?

And the answers are astounding!

From paragliding adventures to quirky activities like standing on one’s head or foraging in local forests, participants demonstrated that preventing Alzheimer’s can be both effective and fun.

Watch the rest of the videos here

Ali’s daring paragliding escapade, Zoe’s upside-down yoga prowess, and Nodge’s foraging adventures exemplify the creativity and commitment shown by our community. These actions not only inspire but also remind us that preventing Alzheimer’s is within everyone’s reach, with room for creativity and enjoyment along the way.

Central to the success of Alzheimer’s Prevention Day were the dedicated individuals behind the scenes. We extend heartfelt thanks to Cath and the team for their meticulous editing of inspiring films, and to Alex for crafting a user-friendly website that hosted invaluable resources and engaging content.

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A BIG thank you!

Behind every groundbreaking initiative are the scientists and professors whose expertise and dedication drive progress. Their research forms the backbone of our mission, guiding us towards effective prevention strategies and empowering individuals to make informed choices about their cognitive health.

As we reflect on the triumphs of Alzheimer’s Prevention Day, we invite you to join us in building a repository of inspiring actions. Visit our website to explore videos showcasing innovative ways people are preventing Alzheimer’s, and most importantly, create your own 30-second film. Share your daily practices that promote brain health, from physical activities to dietary choices, and inspire others to do the same.

>> Click here to submit your video and join the challenge

Together, let’s continue to raise awareness, take meaningful action, and pave the way towards a future where Alzheimer’s is preventable. Visit Alzheimer’s Prevention Day website to learn more and get involved today. 

Your actions today can make a difference tomorrow.

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.

Too much sugar shrinks the brain, but it’s so attractive. Why?

We are led by the science here at Food for the Brain, so we know that one of the best things you can do for your brain is to reduce your sugar and support your insulin control. That is why it is one of our key lifestyle domains in the COGNITION programme. 

However, you probably already know too much sugar isn’t great for health but how can we make eating a lower carb and sugar life easier?

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First, let’s recap the science… 

Dr. Robert Lustig, a renowned expert on brain health and a member of our scientific advisory board, highlights the significant role of insulin control and dietary choices in preventing cognitive decline.

Research from Columbia University in 2004 revealed that individuals with high insulin levels, (a primary indicator of metabolic dysfunction), were twice as likely to develop dementia compared to those with healthy insulin levels (1). Furthermore, those with the highest insulin levels exhibited the worst memory retrieval abilities (1). Similarly, an Italian study linked elevated insulin levels to declining mental function (2).

Several studies have established a connection between high sugar consumption and poor cognitive outcomes. For instance, a study among Puerto Ricans found that high sugar intake doubled the risk of cognitive impairment (3), while another U.S. study correlated elevated blood sugar levels with memory loss (4). The detrimental impact of high dietary glycaemic load (GL) on cognitive function has been observed in studies from Ireland and the United States, indicating that high GL diets are strongly associated with Alzheimer’s-related pathological changes (5,6).

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What is Glycaemic load?

Glycaemic load considers both the quality (GI – glycaemic index) and the quantity (carbohydrate content) of the carbohydrates in a food serving. It provides a more accurate picture of how a food will affect blood sugar levels. The formula for calculating glycaemic load is:

GL  = GI x carbohydrate / 100

A high GL diet measured by the total glucose load on the bloodstream, is linked to increased amyloid plaque formation and cognitive decline, particularly in individuals with the ApoE4 gene, which regulates fat metabolism (7). Even individuals with high-normal blood glucose levels experience greater brain shrinkage and cognitive impairment compared to those with lower levels, as shown in long-term studies (8).

Plus, the damage of a high-GL diet can start early in life. Dr. Lustig points out that overweight children on high-GL diets show signs of cognitive decline, and adolescents with metabolic dysfunction from such diets exhibit hippocampal shrinkage and other brain structure changes (9,10).

So it is clear that eating excess sugar or the wrong types of carbohydrates with a high GL is a problem, so what do you eat?

(Wondering if you’re eating too much sugar? Then test, don’t guess with our home HbA1c test – find out more here.)

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What to eat?

There are two options: following a low GL diet or going a step further and adhering to a ketogenic approach (or switching between the two as Patrick highlights in the Hybrid Diet book). For more info on the ketogenic diet click here to find out more

A low GL diet is focused on consuming foods that have a minimal impact on blood sugar. Basically a diet rich in:

Vegetables: Most non-starchy vegetables like spinach, broccoli, and bell peppers.
Fruits: Berries, cherries, grapefruit, and apples.
Legumes: Lentils, chickpeas, and black beans.
Whole Grains: Barley, quinoa, and whole oats.
Fish and meat or tofu/tempeh: unprocessed
Dairy: Plain yoghurt and milk (unsweetened).
Nuts and Seeds: Almonds, walnuts, chia seeds, and flaxseeds.

Whilst eating this way can support your brain health it can also help you sustain energy levels, help with weight loss and improve heart health.

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So how can we make it easier?

At Food for the Brain we have a few ways to help you feed your brain on the right foods:

Complete the Cognitive Function Test and join COGNITION so we can walk you through how to reduce sugar and upgrade your brain over the next few months.
Upgrade Your Brain Cook App – full of low GL recipes and coming soon. Help us by pre ordering today to get brain-loving recipes at your fingertips.
Here is a recipe sample:

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Almond and coconut porridge

Breakfast Serves 2, generously 

TOTAL GLs: 4

Ingredients:

2 tbsp milled flaxseed
2 tbsp coconut flour
2 tbsp whole flaxseed
2 tbsp chia seeds
2 tbsp coconut flakes, toasted in a dry pan
2 tbsp raspberries
2 tbsp blueberries
2 strawberries
8 walnuts, broken up
1 tbsp soft brown sugar alternative (or sweetener of choice)
300ml unsweetened almond milk
1 tbsp chicory root syrup (or sweetener of choice)

Instructions:

Stir everything (except the desiccated coconut, nuts and berries) together in a saucepan and let sit for 10 mins.
Gently heat through until thickened – add a little more milk if needed to get the consistency you like.
Top with the berries, nuts and toasted coconut – add some natural yoghurt if you like.
Drizzle with the chicory syrup 

Cooks Notes

It’s worth seeking out the chicory syrup – very low sugar and also high fibre. 

Nutrition Highlights

Antioxidants: High in antioxidants, particularly vitamins A, C, and E, which help protect cells from damage and support immune function.
Protein: A moderate source of protein, supporting muscle maintenance and repair.
Fibre: Contains a high amount of fibre, aiding in digestion and promoting satiety.

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Other resources

Here are a few other resources to make low sugar easier, 

FATT bars – easy low GL and low carb snacks for on-the-go. Use the code FFTB10 to save 10% and FATT will donate to the charity with every purchase.

Dillon bread – low carb bread and their brand new high fibre, low GL, Chicory Fibre Syrup perfect for adding to porridge and also suitable for diabetics. Use code FFB10 to save 10% and Dillon will donate 10% with every purchase.

Keto Mojo – if you want to take it a step further and follow a ketogenic diet then grab one of their ketone readers to make life easier and to check you are in ketosis. Use code FFB10 to save 10%.

These companies are some of our supporting organisations – find out more here.

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

Abbatecola AM, Paolisso G, Lamponi M, Bandinelli S, Lauretani F, Launer L, Ferrucci L. Insulin resistance and executive dysfunction in older persons. J Am Geriatr Soc. 2004 Oct;52(10):1713-8. doi: 10.1111/j.1532-5415.2004.52466.x. PMID: 15450050.
Abbatecola AM, Paolisso G, Lamponi M, Bandinelli S, Lauretani F, Launer L, Ferrucci L. Insulin resistance and executive dysfunction in older persons. J Am Geriatr Soc. 2004 Oct;52(10):1713-8. doi: 10.1111/j.1532-5415.2004.52466.x. PMID: 15450050.
Ye X, Gao X, Scott T, Tucker KL. Habitual sugar intake and cognitive function among middle-aged and older Puerto Ricans without diabetes. Br J Nutr. 2011 Nov;106(9):1423-32; doi: 10.1017/S0007114511001760. Epub 2011 Jun 1. PMID: 21736803; PMCID: PMC4876724.
Power SE, O’Connor EM, Ross RP, Stanton C, O’Toole PW, Fitzgerald GF, Jeffery IB. Dietary glycaemic load associated with cognitive performance in elderly subjects. Eur J Nutr. 2015 Jun;54(4):557-68. doi: 10.1007/s00394-014-0737-5. Epub 2014 Jul 18. PMID: 25034880.
Seetharaman S, Andel R, McEvoy C, Dahl Aslan AK, Finkel D, Pedersen NL. Blood glucose, diet-based glycemic load and cognitive aging among dementia-free older adults. J Gerontol A Biol Sci Med Sci. 2015 Apr;70(4):471-9. doi: 10.1093/gerona/glu135. Epub 2014 Aug 22. PMID: 25149688; PMCID: PMC4447796.
Taylor MK, Sullivan DK, Swerdlow RH, Vidoni ED, Morris JK, Mahnken JD, Burns JM. A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults. Am J Clin Nutr. 2017 Dec;106(6):1463-1470. doi: 10.3945/ajcn.117.162263. Epub 2017 Oct 25. PMID: 29070566; PMCID: PMC5698843.
Taylor MK, Sullivan DK, Swerdlow RH, Vidoni ED, Morris JK, Mahnken JD, Burns JM. A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults. Am J Clin Nutr. 2017 Dec;106(6):1463-1470. doi: 10.3945/ajcn.117.162263. Epub 2017 Oct 25. PMID: 29070566; PMCID: PMC5698843.
M.E. Mortby et al., ‘High “normal” blood glucose is associated with decreased brain volume and cognitive performance in the 60s: the PATH through Life Study’, PLoS One (2013), vol 8
.
Yau PL, Castro MG, Tagani A, Tsui WH, Convit A. Obesity and metabolic syndrome and functional and structural brain impairments in adolescence. Pediatrics. 2012 Oct;130(4)
. doi: 10.1542/peds.2012-0324. Epub 2012 Sep 3. PMID: 22945407; PMCID: PMC3457620.
Lakhan, S.E., Kirchgessner, A. The emerging role of dietary fructose in obesity and cognitive decline. Nutr J 12, 114 (2013).
Loef M, Walach H. Fruit, vegetables and prevention of cognitive decline or dementia: a systematic review of cohort studies. J Nutr Health Aging. 2012 Jul;16(7):626-30. doi: 10.1007/s12603-012-0097-x. PMID: 22836704.

By the Alzheimer’s Prevention Expert Group

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You may have heard of a search for new tests to find those most likely to get Alzheimer’s disease? But is this misdirected?

Perhaps so, according to the Alzheimer’s Prevention Expert Group (APEG) –  a collaboration of top UK, American and Chinese academics (which we are a part of – find out more here) who consider this to be “..a misguided waste of money”. 

Controversially, their stance challenges the major thrust of charities such as Alzheimer’s Research (ARUK), which strongly supports search for a reliable test for the disease.

APEG explains that there is already a widely used way to spot failing memory and thinking skills  – hallmarks for dementia and Alzheimer’s. These include a neuropsychological test battery (NTB) and a validated Cognitive Function Test (CFT) similar to the one we provide free. Both are routinely used in memory clinics to diagnose mild cognitive impairment and support the diagnosis of dementia.

Over the last decade the charity Food for the Brain has used the Cognitive Function Test to find people at risk and advise them how to reduce their risk with simple dietary and lifestyle changes. 

Nearly half a million people to date have been tested, with someone taking the test every 2 minutes!

When does Cognitive Decline begin?

Cognitive function declines steadily from the age of 18. This means that it is possible to spot individuals whose cognitive function is dropping off faster than the average, giving time to encourage preventative actions with personalised advice on their diet and lifestyle changes.

Alzheimer’s, which makes up two-thirds of dementia cases, involves the shrinking of certain areas of the brain as neurons die off. It can be detected with a specialised brain scan several years before a diagnosis. These ‘PET’ scans can be used to diagnose Alzheimer’s and/or vascular dementia.  The trouble is that such scans are expensive and not likely performed early enough to discover those ‘at risk’. 

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What about p-tau?

As well as shrinkage, another marker for Alzheimer’s is a toxic protein called p-tau. This creates clumps of tangled nerves in the brain. These can be found in the fluid that bathes the brain but again there is a problem. Detecting it can be done with a lumbar puncture, but this is a risky and expensive process and certainly not suitable to test tens of thousands of people. 

At first sight, if a blood test could identify those heading towards Alzheimer’s earlier this could be a cheaper and less invasive alternative to such scans. However, the search is likely driven by a quite different ulterior motive – to create and sell drugs – much like cholesterol and statins. What’s more it’s unlikely to be an improvement!

A recent New York Times article pointed out that such a test would result in people being diagnosed with ‘pre’ Alzheimer’s, even if they have no obvious symptoms. That’s because having the marker would be considered enough to justify a diagnosis of the disease or, at least, the prescription of a drug.

This is what happens with amyloid protein. Amyloid forms plaque in the brains of those with Alzheimer’s. The latest drugs, such as lecanemab and aducanumab, remove this. But not all those with Alzheimer’s have plaque, and people can develop dementia without plaque. What’s more none of these drugs have a clinically significant effect, and they come with the risk of severe adverse effects, including death from brain bleeding and swelling, especially in those with a history of stroke.

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A very cheap and safe alternative…

Perhaps the most convincing reason why the new blood marker hunt is “misguided” is that there is something very cheap and very safe that can prevent the accumulation of p-tau tangles in the brain – B vitamins.

Suppose you are not taking in enough B6, folate or B12, which becomes harder to absorb as you get older, blood levels of a toxic amino acid called homocysteine rise. This increases the level of p-tau and inhibits the brain from clearing it. According to pharmacology professor David Smith, a member of APEG and our Scientific Advisory Board: “Homocysteine is not a diagnostic marker for dementia but it is a modifiable risk factor. Raised levels of homocysteine account for some 20% of dementia cases and homocysteine testing is relatively inexpensive and available.”

Smith, who was second in charge at Oxford University’s School of Medical Sciences, ran the VITACOG trial which found that high doses of B vitamins given to people with Mild Cognitive Impairment (MCI) and high homocysteine, not only slowed the rate of brain cell death by up to 73% but also arrested cognitive decline.

He, and his APEG colleagues, favour using a Cognitive Function Test, to identify those at risk. Then, testing risk factors and biomarkers such as homocysteine to be included in the research, with funds being made available for testing blood biomarkers because this is one thing you can actually do something about. 

Other useful tests for risk factors include omega-3 and vitamin D levels, since low levels of these nutrients also increase risk; also HbA1c, the standard measure used to diagnose diabetes, since lower levels help protect the brain and high levels indicate those who need to reduce their intake of sugar and processed foods. These tests are corroborative rather than diagnostic but importantly identify prevention actions that people can take. 

We offer at home, accurate pin prick testing for Vitamin D, HbA1c, Omega-3 and Homocysteine (available in US, EU & UK) – order here to be a part of our research and to support our charitable work 

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The new paradigm.

This two-step paradigm of:

1. Testing cognitive function early – you can do so here.

2. Then do further blood tests such as homocysteine, omega-3, vitamin D and HBA1c for glucose control that help guide diet and lifestyle prevention, which is available right now. Order your DRIfT test here

So keep things simple and start today!

Complete our validated Cognitive Function Test, then order your blood tests and be a part of our Citizen Science research and movement.

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

The VITACOG trials, evidence for homocysteine as causal and lowering it with B vitamins as disease modifying and a consensus statement regarding this evidence, in the Journal of Alzheimer’s Disease, is here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836397/

The validation of foodforthebrain.org’s Cognitive Function Test in the International Journal of Geriatric Psychiatry is here: https://onlinelibrary.wiley.com/doi/abs/10.1002/gps.3993

The evidence in relation to p-tau and homocysteine is here: https://foodforthebrain.org/the-p-tau-delusion/

Widespread omega-3 deficiency is cranking up aggression.

Children flying off the handle, fighting at school, increasing rates of ADHD, depression and violent offences, perhaps even more global conflicts – a new study suggests that something very simple could be cranking up aggression. 

Less omega-3 from seafood. 

A study of 4,000 participants over 28 years, has found a clear reduction in aggression when children and adults are given either omega-3 supplements or eat more fish. According to advisor to the US National Institutes of Health, Dr Joseph Hibbeln, a country’s incidence of homicide, depression and suicide ‘tracks’ their seafood consumption. In Australia, a prisoner’s omega-3 index, measured in a pin prick blood test predicts anger, aggression and AHDH. A study in UK prisons found that giving omega-3 supplements to prison inmates, compared to placebos, reduced violent offences by more than a third.

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Omega-3 support in community, clinics and our criminal justice system

“Based on this evidence our considered opinion is that there is now sufficient evidence to begin to implement omega-3 supplementation to reduce aggression in children and adults, whether the setting is community, the clinic or criminal justice system” say the study authors Adrian Raine and Lia Brodrick from the University of Pennsylvania.

“There is now clear evidence that not only are low blood omega-3 levels associated with increased aggressive behaviour but supplementation with fish oil can reduce aggressive tendencies in adults and children.” says Professor William Harris from the Fatty Acid Research Institute in the US, one of our scientific advisors. 

This is why we now offer an easy, pin prick home test for omega-3 to go alongside our free online Cognitive Function Test and diet and lifestyle questionnaire that assesses omega-3 status and other factors that are important to your brain function and development.

We need to treat it the same as vitamin D

“Less than 5% of children in the UK achieve the basic recommended levels of omega-3” says Dr Simon Dyall, clinical neuroscientist at the University of Roehampton who also advises the charity “Even these recommendations are too low, according to the evidence regarding brain function. Many children eat no fish at all and don’t supplement omega-3. The evidence is more than sufficient to recommend that we take action now to protect our children’s brains.”

In the same way that GPs test vitamin D we need to test both children and adults presenting with ADHD, depression, anxiety and aggression for their omega-3 index. 

In Japan, where a lot of seafood is eaten, the level is 10% and rates of violence, depression, suicide and Alzheimer’s are a fraction of those in the UK. People in the UK and US average 4% on the pinprick omega-3 index. You need over 8% for a healthy brain. Many offenders test as low as 2%.

You can’t build a healthy brain without omega-3. Our children are suffering. There is more than enough evidence of this.

Yet there is no government recommendation in the UK of how much omega-3 we need. The advice to eat fish twice a week is neither enough, nor heeded. 

That is why we are helping people help themselves by testing their omega-3 index and advising them accordingly. But we need this done on a national scale, especially in poorer communities.

If doctors can test and prescribe vitamin D, why can’t they test and prescribe omega-3?

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Actions:

Find out your omega-3 status (or your child’s, partner or entire family) with the accurate, simple at home blood test. Order here to be a part of our research and support our charity.
Find out more about our Smart Kids & Teen programme we are developing (and need funding for!)
Complete the Cognitive Function Test to get personalised information on how you can upgrade your brain.

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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

A. Raine, L. Brodrick ‘Omega-3 supplementation reduces aggressive behavior: A meta-analytic review of randomized controlled trials’Aggression and Violent Behavior, 2024, 101956 doi.org/10.1016/j.avb.2024.101956.

Hibbeln JR. Depression, suicide and deficiencies of omega-3 essential fatty acids in modern diets. World Rev Nutr Diet. 2009;99:17-30. doi: 10.1159/000192992.

Meyer BJ, Byrne MK, Collier C, Parletta N, Crawford D, Winberg PC, et al. (2015) Baseline Omega-3 Index Correlates with Aggressive and Attention Deficit Disorder Behaviours in Adult Prisoners. PLoS ONE 10(3): e0120220. doi:10.1371/ journal.pone.0120220 

Gesch CB, Hammond SM, Hampson SE, Eves A, Crowder MJ. Influence of supplementary vitamins, minerals and essential fatty acids on the antisocial behaviour of young adult prisoners. Randomised, placebo-controlled trial. Br J Psychiatry. 2002 Jul;181:22-8. doi: 10.1192/bjp.181.1.22.