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.