Raised Homocysteine and Disease Risk: More Than 100 Associated Conditions

Raised Homocysteine and Disease Risk: More Than 100 Associated Conditions

Raised homocysteine has been associated with an increased risk of a remarkably wide range of diseases and adverse health outcomes. Research spanning cardiovascular disease, cognitive decline, dementia, pregnancy complications and other conditions has made homocysteine an important biomarker of nutritional and metabolic health [1].

Homocysteine is not itself a disease, and an association does not necessarily mean that elevated homocysteine directly causes every condition linked with it. However, an elevated level can provide useful information about B-vitamin status, homocysteine metabolism and wider health risk  [1].

More than 100 diseases, syndromes and adverse health outcomes have been reported in association with raised total homocysteine [1]. These range from cardiovascular and cerebrovascular disease to cognitive decline, dementia, pregnancy complications and neurological disorders.

This article explores that evidence, what these associations actually mean and why homocysteine has attracted increasing attention as a potentially modifiable biomarker.

If you are new to the subject, start with our complete guide to homocysteine, which explains what homocysteine is, why levels can become elevated and why it matters.

What is homocysteine?

Homocysteine is an amino acid produced naturally when the body metabolises methionine, an amino acid obtained from dietary protein.

Normally, homocysteine is recycled or converted into other compounds through metabolic pathways that depend on nutrients including folate, vitamin B12 and vitamin B6. When these pathways do not work efficiently, homocysteine can accumulate in the blood [1].

Age, nutritional status, kidney function, genetics, certain medicines and lifestyle factors can all influence homocysteine levels [1,2,4].

For more detail on the underlying biochemical pathways, see Methylation and Homocysteine.

What diseases are associated with high homocysteine?

More than 100 diseases, syndromes and adverse health outcomes have been reported in association with raised total homocysteine [1].

The most frequently reported associations involve cardiovascular and central nervous system conditions, although associations have also been reported across pregnancy and development, kidney disease, metabolic health, bone health and other areas [1].

Professors David Smith and Helga Refsum reviewed this extensive body of evidence in Homocysteine: from disease biomarker to disease prevention. Their review catalogued reports of associations between raised total homocysteine and more than 100 diseases, syndromes and adverse health outcomes [1].

The strength of evidence is not the same for every condition.

In some cases, raised homocysteine may be a marker of an underlying nutritional, metabolic or health problem. In others, it may contribute to biological processes involved in disease. An association therefore does not necessarily mean that homocysteine directly causes the condition [1].

For clarity, the reported associations are grouped below according to the main area of health affected.

Cardiovascular and circulatory conditions associated with raised homocysteine

Cardiovascular and cerebrovascular diseases are among the most extensively studied conditions associated with raised homocysteine. Smith and Refsum’s review identifies reported associations with myocardial infarction, coronary artery disease, hypertension, stroke, peripheral vascular disease, venous thrombosis and a wide range of other vascular outcomes [1].

Conditions and outcomes reported in association with raised total homocysteine include [1]:

Researchers have investigated several mechanisms that could help explain these associations, including effects involving vascular endothelial function and thrombosis [1]. However, observational associations do not, on their own, establish that elevated homocysteine directly causes cardiovascular disease.

This distinction becomes particularly important when intervention studies are considered.

A meta-analysis of eight randomised trials involving 37,485 participants found that B-vitamin treatment lowered homocysteine by approximately 25%, but did not significantly reduce major vascular events, major coronary events or stroke during the treatment periods studied [14].

Later evidence suggests that stroke may warrant separate consideration. A Cochrane review of 15 randomised trials involving 71,422 participants found no significant reduction in myocardial infarction or all-cause mortality with homocysteine-lowering interventions, but reported a small reduction in stroke [15].

Taken together, the evidence supports an association between raised homocysteine and cardiovascular and cerebrovascular disease, but does not support assuming that lowering homocysteine will prevent cardiovascular disease generally. The effects of intervention may differ according to the outcome, population, nutritional status and treatment context [1,14,15].

Homocysteine, brain health and cognitive decline

The brain is another area in which homocysteine has been extensively studied.

Raised homocysteine has been associated with cognitive decline, brain atrophy, dementia and Alzheimer’s disease [1,11,12].

A meta-analysis of eight cohort studies involving 8,669 participants found an association between serum homocysteine and dementia [11].

A later dose-response meta-analysis incorporating 28 prospective cohort studies found that every 5 µmol/L increase in blood homocysteine was associated with a 15% higher relative risk of Alzheimer-type dementia. Associations with all-cause dementia, vascular dementia and cognitive impairment without dementia were less conclusive [12].

Other reported brain and cognitive associations include vascular dementia and vascular cognitive impairment, post-stroke cognitive impairment, age-related cognitive decline, conversion from cognitive impairment to dementia, grey- and white-matter atrophy, cerebral small vessel disease and white-matter damage [1].

Cerebral small vessel disease has also been investigated as a possible mediator of the association between homocysteine and cognitive function [9].

What happens when homocysteine is lowered?

The VITACOG randomised controlled trial investigated whether lowering homocysteine with B vitamins could affect brain atrophy in older people with mild cognitive impairment.

Participants received folic acid, vitamin B12 and vitamin B6 or placebo for two years. B-vitamin treatment lowered homocysteine and slowed the accelerated rate of brain atrophy [13].

However, intervention evidence is not uniform. A meta-analysis combining cognitive data from 11 trials involving approximately 22,000 participants found that B-vitamin treatment lowered homocysteine but did not demonstrate a significant overall effect on individual cognitive domains or global cognitive function [16].

The effects of B-vitamin intervention may therefore depend on factors including the population studied, baseline homocysteine and nutritional status, disease stage, treatment duration and the outcome being measured [1,13,16].

For a deeper examination of this evidence, read Homocysteine and Brain Health.

For evidence specifically relating to Alzheimer’s disease and dementia, see Homocysteine and Dementia.

Mental health and neurological conditions

Raised homocysteine has also been studied in relation to a range of mental health and neurological conditions.

Smith and Refsum’s review identifies reported associations between raised total homocysteine and conditions including depression, bipolar disorder, schizophrenia, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis or motor neurone disease, multiple system atrophy, migraine and autism spectrum disorder [1].

Parkinson’s disease has been examined more specifically in a systematic review and meta-analysis evaluating homocysteine alongside vitamin B12 and folate. The analysis found associations between these biomarkers and the risk and severity of Parkinson’s disease [10].

These findings do not mean that elevated homocysteine independently causes these conditions. Neurological and mental health disorders are complex and typically involve multiple genetic, biological, nutritional, environmental and lifestyle factors.

Homocysteine may therefore be a biomarker, a contributing factor or part of a wider metabolic picture, depending on the condition [1].

The evidence is strongest when interpreted condition by condition rather than treating all reported associations as equivalent.

Homocysteine and pregnancy

Homocysteine has also been studied in relation to pregnancy and fetal development.

Raised maternal homocysteine has been reported in association with pregnancy complications and outcomes including recurrent miscarriage, impaired fetal growth and small-for-gestational-age babies, neural tube defects, congenital heart defects and orofacial clefts [1,5,6].

A meta-analysis examining recurrent spontaneous abortion found higher homocysteine concentrations among women experiencing recurrent pregnancy loss, supporting an association between elevated homocysteine and recurrent spontaneous abortion [5].

A broader review of homocysteine and pregnancy complications also describes associations across a range of adverse pregnancy outcomes [6].

These findings need careful interpretation. Homocysteine metabolism is closely connected with folate, vitamin B12 and other nutritional factors, while pregnancy outcomes are influenced by many additional maternal, fetal, genetic and environmental factors [1].

An association with elevated homocysteine therefore does not establish that homocysteine directly caused a particular pregnancy outcome.

Anyone who is pregnant, planning a pregnancy or concerned about folate, vitamin B12 or homocysteine status should discuss appropriate testing and supplementation with a qualified healthcare professional.

Other conditions associated with raised homocysteine

The reported associations extend considerably further.

Higher homocysteine has also been associated with all-cause mortality. A dose-response meta-analysis of prospective studies reported an association between homocysteine concentrations and all-cause mortality [7].

Research has additionally examined relationships between homocysteine, inflammation, telomere shortening and mortality [8].

The breadth of these associations is striking, but it should not be interpreted as evidence that homocysteine directly causes every condition listed.

A biomarker can be associated with many diseases without being their single underlying cause. Kidney function, nutritional deficiencies, ageing, lifestyle and existing health conditions can themselves influence homocysteine concentrations [1].

A raised result therefore needs to be interpreted in the context of the individual rather than viewed as a diagnosis in itself.

Why can homocysteine be associated with so many conditions?

One reason homocysteine appears across such a broad range of research is its relationship with fundamental metabolic processes.

Homocysteine sits within pathways involving folate, vitamin B12, vitamin B6, methionine and methylation [1]. Researchers have also investigated potential effects of elevated homocysteine on vascular and neurological processes [1].

However, there is an important distinction between homocysteine being:

a marker of another underlying problem
a contributor to disease processes
a causal factor whose reduction directly changes disease risk.

These roles should not be assumed to be identical across every disease [1].

This is why the more useful question is not simply whether homocysteine is “good” or “bad”. It is why a person’s homocysteine is elevated and what that result may reveal about their nutritional, metabolic and wider health.

How do you know if your homocysteine is high?

Homocysteine is measured with a blood test and is generally reported in micromoles per litre (µmol/L).

A result needs to be interpreted in context because homocysteine can vary according to factors including age, sex and nutritional status [2,4].

If you are thinking about testing, read our complete guide to homocysteine testing.

If you already have a result, see Homocysteine Levels Explained to understand what your level may mean.

Know Your Homocysteine Level

The only way to know your homocysteine level is to measure it.

The Food for the Brain Homocysteine Test is an at-home blood spot test that measures your homocysteine level from a fasted finger-prick sample.

By taking part, you also support Food for the Brain Foundation’s charitable research and work to help reduce the risk of cognitive decline through nutrition and lifestyle.

Take the Homocysteine Test

Already have a result? Find out what your homocysteine level means.

What should you do if your homocysteine is high?

A raised homocysteine result is a reason to consider why the level is elevated rather than treating the number in isolation.

Factors associated with elevated homocysteine include folate and vitamin B12 status, age, kidney function and other nutritional, genetic, medical and lifestyle influences [1,2,4].

The appropriate response therefore depends on the underlying cause.

For a detailed look at nutritional, lifestyle and other factors involved, read our guide to lowering homocysteine.

Can lowering homocysteine reduce disease risk?

B vitamins can lower homocysteine, but demonstrating that an intervention lowers a biomarker is not the same as demonstrating that it prevents every disease associated with that biomarker [1,14-16].

The cardiovascular evidence illustrates this distinction clearly. Large randomised-trial analyses have not demonstrated a general reduction in major cardiovascular events despite substantial reductions in homocysteine [14], although a later Cochrane review found evidence of a small reduction in stroke [15].

A similar complexity exists in cognitive health. The VITACOG trial demonstrated slower brain atrophy in people with mild cognitive impairment receiving B vitamins [13], while a much larger meta-analysis of cognitive trial data did not find a significant overall benefit on cognitive performance [16].

Clinical effects may depend on the outcome being studied, baseline homocysteine and nutritional status, age, treatment context and other factors [1,13-16].

The evidence should therefore be considered outcome by outcome rather than assuming that lowering homocysteine automatically produces the same reduction in risk across all conditions associated with elevated levels.

At Food for the Brain, we are particularly interested in potentially modifiable nutritional and lifestyle factors associated with homocysteine and their relationship with long-term brain health.

Frequently asked questions

The bigger picture

The association between raised homocysteine and such a broad range of diseases is one reason this biomarker continues to attract scientific interest.

An accurate conclusion is that raised homocysteine has been associated with a remarkably broad range of diseases and adverse health outcomes, with particularly substantial research around vascular and cognitive health [1,11,12].

Whether lowering homocysteine changes clinical outcomes depends on the condition, population and intervention being considered [13-16].

Homocysteine sits at the intersection of several important nutritional and metabolic processes, and an elevated level may therefore provide useful information about what is happening within the body.

Understanding your homocysteine level can be one piece of a much larger picture involving nutrition, lifestyle, cardiovascular

Written by Patrick Holford

Last reviewed: 15/09/2026

New to homocysteine? Read our complete guide to homocysteine.
Thinking about testing? Learn how homocysteine testing works.
Already have a result? Use Homocysteine Levels Explained to understand your result.
Want to reduce an elevated level? Read our guide to lowering homocysteine.

The table lists diseases and syndromes for which there are reports of association with raised total homocysteine. Reproduced with the permission of the authors Professors David Smith and Helga Refsum from the paper Smith AD, Refsum H. Homocysteine – from disease biomarker to disease prevention. J Intern Med. 2021 Oct;290(4):826-854. doi: 10.1111/joim.13279. Epub 2021 Apr 6. PMID: 33660358.  © 2021 The Association for the Publication of the Journal of Internal Medicine 3 Journal of Internal Medicine

Can You Recover Your Memory and Rebuild Brain Health?

Author: Kezia Hall · First published: 30/11/2023 · Last reviewed: 08/10/2026

You walk into a room and forget why. A familiar name sits on the tip of your tongue and won’t come out. Changes like these can feel worrying, especially if dementia has touched your family. But the good news is that your brain keeps rewiring itself throughout life, and many of the things that wear memory down are within your control. 

How much you can recover depends on what’s driving the change. Whether you want to stop your memory getting worse or sharpen it, you need three things:

Structure: the nutrients your brain uses to build and maintain brain cells and their connections
Function: a reliable fuel supply
Utilisation: an active physical, social and intellectual life

Think of it as servicing a car. Structure is the bodywork, function is the fuel, and utilisation is actually taking it out on the road.

Can You Recover Your Memory?

Often, yes. It depends on the cause. Memory problems linked to poor sleep, low mood, stress, side effects of some medicines, or a deficiency such as low vitamin B12 or an underactive thyroid often improve once the cause is put right. Depression is the most common of these.[1] That’s why doctors are advised to rule out reversible causes before anything else.[2] If memory decline turns out to be part of a progressive condition such as Alzheimer’s, fully reversible cases are rare. One review of memory-clinic studies found potentially reversible causes in about 9% of people, but only around 0.6% actually recovered.[3] There, the aim is to slow decline and protect the brain function you still have, and that’s why prevention matters so much. The earlier you start, the more there is to protect.

Your brain keeps forming and strengthening connections at every age, a capacity called neuroplasticity. Better nutrition, regular activity, good sleep and a busy mind give it what it needs to adapt.

If your memory changes are persistent, getting worse or have no obvious explanation, see your GP first to rule out medical causes.

Can Brain Cells Recover?

Here it pays to be precise. Brain cells (neurons) that have died aren’t replaced the way skin cells are. Scientists still disagree about whether adults keep growing new neurons in the hippocampus, the brain’s memory hub. One major study found little evidence of it,[4] while another found thousands of new neurons even in people in their eighties.[5]

What isn’t in doubt is that your brain can rewire itself. Surviving neurons grow new branches and form new connections, and the ones you use get stronger. Brain regions can even grow. In one trial, a year of brisk walking enlarged the hippocampus of older adults by about 2% and improved their memory. The comparison group lost volume, as you’d expect with age.[6]

So rebuilding your brain doesn’t mean regrowing damaged tissue. It means protecting the brain cells you have, giving them the raw materials to keep their connections in good repair, and using them enough that those connections stay. For the nutrients your brain uses to build its cells, read how to keep building brain cells at any age.

What Causes Memory and Brain Function to Decline?

Memory is very subjective. One person’s sense of how good their memory is can be very different from the next person’s. Many people later in life are convinced their memory is slipping. Others choose the path of denial, even when it’s becoming obvious to those around them.

Real decline is rarely down to one thing. It’s usually several factors adding up, most of which you can change:

Poor building materials: too little omega-3 and too few B vitamins, which shows up as raised homocysteine

An unreliable fuel supply: years of consuming too much sugar and refined carbohydrate can contribute to insulin resistance and make it harder for the brain to use glucose efficiently (see how the brain gets its fuel).

Oxidative stress: wear and tear from free radicals outpacing your brain’s antioxidant defences

Low vitamin D

Inactivity: physical, mental and social

Poor sleep and chronic stress

Age and genes matter, but they set your starting point, not your destination. These are the same drivers that push up Alzheimer’s risk, which is why how to Alzheimer’s-proof yourself reads so much like the advice here. For the bigger picture, see our systems-based approach to brain health and the 8 domains of brain health. If your main problem is foggy thinking rather than forgetting, start with how to clear brain fog.

The good news is that the parts of cognition that decline on the road to dementia can be measured objectively, decades before any diagnosis. That gives you time to course-correct while there’s plenty of road ahead.

How Is Your Memory Performing?

The free, validated online Cognitive Function Test™ takes about 15-20 minutes. It measures three key areas of cognitive function: episodic memory, attention and executive function, helping to identify signs of cognitive decline and potential cognitive impairment. Afterwards, a short questionnaire shows you which parts of your diet and lifestyle need attention. You’ll need a tablet or computer, not a phone. It isn’t a diagnosis. It’s your road map.

Take the Free Cognitive Function Test

How to Support Memory and Rebuild Brain Health

1. Structure: Give Your Brain the Nutrients It Needs

B Vitamins, Omega-3 and Memory

B vitamins and omega-3 fats are a dynamic duo. Each works best when the other is in good supply.

Homocysteine is an amino acid. Your body uses the B vitamins B6, B12 and folate to break it down. When you’re short of B vitamins, homocysteine builds up, and raised homocysteine is linked to faster brain shrinkage.

Omega-3 fats, especially DHA, are built into the membranes of your brain cells. They keep those membranes fluid and help neurotransmitters, your brain’s chemical couriers, do their job.

The Oxford VITACOG trial gave homocysteine-lowering B vitamins to people with mild cognitive impairment. Their brains shrank more slowly than those of people taking a placebo, and the effect was greatest in people who started with high homocysteine.[7]

Then came the twist. The benefit depended on omega-3.Among people with good omega-3 levels, B vitamins slowed brain shrinkage by 40% compared with placebo. The effect was even more striking in those who also had raised homocysteine levels at the start, with brain shrinkage slowing by an impressive 73%. By contrast, B vitamins made no significant difference in people with low omega-3 levels.8

It works the other way round too. In the Swedish OmegAD trial, people with mild to moderate Alzheimer’s took 2.3g of omega-3 a day. Those who already had good B vitamin status (low homocysteine) did better on memory and clinical measures than those on placebo.[9]

For the full brain-shrinkage story, read omega-3 and B vitamins: nutrients that may slow brain shrinkage. For your memory, here’s what to do:

Get your Omega-3 Index above 8%. Eat oily fish three times a week, or take fish oil capsules. Here’s how much omega-3 you need and what to look for in a supplement.

Keep your homocysteine below 7 µmol/L. If it’s higher, take a broad-spectrum formula containing B12, folate, B6, TMG, zinc and NAC. Find out more about how B vitamins lower homocysteine, and try these 8 natural ways to lower homocysteine.

Up Your Antioxidants

The next stop on the brain upgrade road trip is to fill up on antioxidants. Think of them as your brain’s fuel filter, mopping up the free radicals that energy production leaves behind. Two key players are glutathione and melatonin.

Your body makes glutathione from NAC (N-acetyl cysteine), which belongs in your homocysteine-lowering formula. Glutathione is also recycled by anthocyanins, the pigments in blue and red foods such as blueberries. Spinach and dark chocolate help too, and onions, asparagus and eggs supply its building blocks.

Eat a serving of berries every day.

Read more in how to keep your brain young with antioxidants.

Melatonin is best known as the sleep hormone, but it’s also a powerful antioxidant with a possible anti-ageing role in the brain.[10] Your melatonin depends on two things:

your serotonin status (serotonin is made from tryptophan or 5-HTP)

good-quality sleep

Research has used 1–5mg of melatonin at night, particularly in people with poor sleep or cognitive impairment. In the UK, melatonin is prescription-only, so ask your GP whether it’s right for you.

Don’t Forget Niacin

Vitamin B3, in the form of niacin, has a particular link with memory.

A 25-year US study tracked the diets of adults from ages 18 to 30 and assessed their cognitive function in middle age. Higher intakes of four B vitamins, niacin (B3), folate (B9), B6 and B12, were all significantly associated with better processing speed, with niacin showing the strongest association. Niacin was also linked to better executive function.[11]

A study of older adults in Chicago found that those consuming the most niacin (vitamin B3) from food had approximately 70% lower relative risk of developing Alzheimer’s disease than those consuming the least. Higher niacin intake was also associated with slower cognitive decline.[12]

A small double-blind trial from 1985 gave healthy adults approximately 425 mg of niacin (vitamin B3) daily, more than 26 times the standard 16 mg nutrient reference value. After eight weeks, participants showed measurable improvements in short-term memory and sensory information processing compared with placebo.[13]

The first two studies show associations, not proof of cause, but they all point the same way.

NMN (nicotinamide mononucleotide), a vitamin B3 derivative involved in cellular energy production, is attracting interest in brain ageing research. In animal studies, NMN combined with melatonin improved memory and helped protect the hippocampus by supporting mitochondrial function and reducing markers of cell damage.[14] Human trials have since shown that NMN can raise NAD+ levels, but whether it improves memory or protects against dementia remains unproven. NMN is also subject to novel food authorisation in the UK and EU, with regulatory approval still being finalised as of October 2026.

2. Function: Support Brain Energy and Metabolism

Fill the Energy Gap with C8 Oil

Your brain uses about a fifth of your body’s energy, so it needs a reliable fuel supply. People with blood sugar problems, and many older people, struggle to get glucose into the brain’s energy factories, the mitochondria. The result is a brain energy gap.

Your brain has a back-up fuel: ketones, which your body makes from fat. The fastest food-based way to make them is C8 oil, a particular type of medium-chain triglyceride (MCT).

In older adults without dementia, a 2022 review of six trials found that four showed memory benefits from MCTs, mainly in working memory. The authors call for more research to confirm this and settle the best dose.[15]

It isn’t only older brains. At Liverpool Hope University, 30 healthy young adults took 12g or 18g a day of a C8/C10 blend. Aspects of their working memory and planning improved within two to three weeks.[16]

How much to take:

If you’re younger and healthy, start with one tablespoon of C8 oil a day.

Build up to two tablespoons if you’re older, already noticing some decline, or your blood sugar is raised. An HbA1c above 5.4% (36 mmol/mol) counts as raised.

Increase gradually to avoid an upset stomach.

For more on how ketones work, plus fasting and the Hybrid Latté, read ketones and your brain.

Top Up Vitamin D

Vitamin D is a true all-rounder for the brain. It helps calm inflammation and supports the signalling between nerve cells.

A French study followed 916 adults aged 65 and over for up to 12 years. Those with vitamin D deficiency had nearly three times the risk of developing Alzheimer’s disease compared with those with sufficient levels. Low vitamin D was also associated with faster cognitive decline.[17]

A large US study followed 12,388 adults, averaging 71 years of age, for up to 10 years. Those taking vitamin D supplements had a 40% lower adjusted rate of developing dementia compared with non-users. However, as this was an observational study, it cannot establish whether vitamin D supplementation itself prevented dementia.[18]

These findings come from observational studies, but a randomised, placebo-controlled trial involving 210 people with Alzheimer’s disease also reported encouraging results. Those given 800 IU (20 µg) of vitamin D daily for 12 months showed improvements in several cognitive test scores compared with placebo.[19]

Aim for a blood level above 75nmol/l (30ng/ml). Read vitamin D for mind, memory and mood for how much to take in winter and in summer.

3. Utilisation: Keep Your Brain Active

Structure and fuel only pay off if you take the car out on the road.

Learning: learning something new, especially something hard that you sometimes fail at, is one of the strongest signals you can send your brain to keep its connections.

Exercise: Regular physical activity supports brain health. In a randomised trial involving 120 older adults, moderate-intensity walking three times a week increased hippocampal volume by approximately 2% over 12 months, alongside improvements in spatial memory.[6] Combining aerobic activity with resistance training is a sensible approach to overall health and fitness.

Social contact: keeps you thinking, talking and remembering.

Sleep: this is when your brain files away the day’s memories.

Here’s a simple plan:

Take up one new skill.
Walk briskly every day and do two strength sessions a week.
Spend regular time with people you enjoy.
Protect your sleep.

For the science, including Professor Tommy Wood’s work on learning by failing, read why an active lifestyle is a brain essential.

Mushrooms and Your Mind: Optional Extras

Various plants and fungi have effects on memory that are worth knowing about. The evidence is earlier-stage than for the nutrients above, so think of these as optional extras on top of the foundations, not instead of them.

Lion’s Mane is a fungus that has improved aspects of memory and cognitive function in small trials:

In a small Japanese trial, adults aged 50 and over who took 3.2 g daily for 12 weeks showed improvements on a test of general cognitive function compared with placebo. However, improvements were not significant on two specific memory tests, and larger trials are needed to confirm the benefits.[20]

Another trial involving 30 people with mild cognitive impairment found improved cognitive scores after 16 weeks, although these gains diminished within four weeks of stopping supplementation.[21]

A small Taiwanese pilot trial involving people with mild Alzheimer’s disease also reported encouraging results. After 49 weeks of supplementation with an erinacine A-enriched Lion’s Mane preparation, participants showed improvements in some measures of cognitive function and daily living, although the findings require confirmation in larger trials.[22]

Reishi (Ganoderma lucidum) has a long history of use in traditional East Asian medicine, particularly for promoting health and longevity. Early animal research suggests potential brain benefits. In a study of mice genetically modified to model Alzheimer’s disease, Reishi polysaccharides improved aspects of learning and memory, promoted the growth of new neurons in the hippocampus and reduced amyloid deposits. However, whether these findings translate into cognitive benefits in humans remains uncertain.[23]

Ginkgo biloba, from one of the world’s oldest surviving tree lineages, has shown some benefits for memory and cognitive performance in small, short-term trials. A 30-day study in healthy adults reported improvements in working memory and information processing, while a six-week trial in older adults found improvements in certain memory tests.[24,25] However, a much larger US trial involving 3,069 older adults found that taking Ginkgo for approximately six years did not reduce the risk of developing dementia.[26]

Typical dose: 120–300mg of a standardised extract.

Caution: it slightly thins the blood, so take care if you’re on blood thinners.

Maca, ginseng, Siberian ginseng and rhodiola are traditionally used to support energy and resilience to stress, and are often described as adaptogens. Early research suggests that some may help with fatigue, mood and aspects of cognitive performance. A review of maca research, for example, identified promising effects on memory and fatigue, particularly with black maca, although much of the evidence came from animal studies.[27] More human trials are needed to establish their benefits for brain health.

Guarana is another popular stimulant, but its main active ingredient is caffeine. While it can temporarily improve alertness and concentration, regular use can lead to tolerance, meaning the same dose may have less effect over time. It can also disrupt sleep, potentially undermining the very brain function you’re trying to support.

To explore the potential benefits of medicinal mushrooms for memory, cognitive function and brain health, watch our Mushrooms and the Mind webinar, which takes a closer look at the science behind these fascinating fungi.

What Foods Support Memory and Brain Health?

There’s no single superfood that brings memory back. What works is a way of eating that gives your brain building materials, steady fuel and protection, every day, for years. Here’s how the best foods for memory fit the three-step plan. For a longer list, see our 15 brain foods.

Oily fish: omega-3 for building your brain. Salmon, mackerel, anchovies, sardines and herring (SMASH for short) provide ready-made DHA and EPA, the forms your brain uses directly.

Eat oily fish three times a week.

Choose smaller fish where you can. They’re lower down the food chain and carry less mercury.

If you don’t eat fish, take an algae-based omega-3. Plant sources like flax, chia and walnuts convert only poorly to DHA. See algae oil vs fish oil.

Leafy greens: folate to keep homocysteine down. Spinach, kale, chard, rocket and broccoli are rich in folate, magnesium and antioxidants. Leafy greens are among the foods most consistently linked to slower memory decline in studies of Mediterranean and MIND diets. Eat a big handful every day. Find out more in greens means brains.

Berries and colourful vegetables: antioxidant protection. Blueberries, blackberries, raspberries, strawberries, red cabbage, beetroot and peppers supply polyphenols that back up your brain’s own glutathione defences. Fresh or frozen both count. Aim for as many colours on your plate as you can.

Eggs, fish and meat: B12 and choline. Vitamin B12 comes almost only from animal foods, and low B12 is one of the most common reversible causes of memory problems in older people. It’s harder to absorb as you age, because stomach acid tends to fall. Eggs also provide choline, which your brain uses to make acetylcholine, the memory neurotransmitter. If you’re vegan or over 60, consider a B12 supplement.

Nuts and seeds: steady fuel and minerals. Walnuts, almonds, and pumpkin, sunflower, chia and flax seeds add healthy fats, fibre, magnesium and zinc. Eaten with carbohydrate, they slow the release of sugar and keep your brain’s fuel supply steady.

Beans, lentils and chickpeas: slow-release carbs. They provide folate, protein and fibre with a low glycaemic load (GL). Use them instead of refined white carbohydrates, which are linked to faster memory decline.

Extra virgin olive oil: the Mediterranean staple. It’s rich in polyphenols and is the main fat in the Mediterranean-style diets most consistently linked to healthier brain ageing. Make it your main cooking and dressing oil. To compare the options, read Mediterranean, DASH or MIND diet?

Whole, minimally processed foods: the common thread. Ultra-processed foods tend to be high in sugar and refined starch and low in everything above. The less of your food comes in a packet, the more room there is for food that actually feeds your brain.

What you cut back on matters just as much. Sugar, white flour, fruit juice and too much alcohol all work against a steady brain fuel supply. Keep them to a minimum.

When Should You Seek Help for Memory Problems?

Everyone forgets things. See your GP if your memory or thinking changes are:

persistent: most weeks, not just now and then

getting worse over months

unexplained: with no obvious reason such as a run of bad sleep or stress

noticed by other people, or getting in the way of everyday tasks like managing money, medicines, appointments or finding your way

sudden: if confusion or memory loss comes on suddenly, especially with weakness, slurred speech or a severe headache, get urgent medical help

Your GP can check for common causes that can be put right, such as low B12 or folate, thyroid problems, infections, side effects of medicines, depression and anxiety. If needed, they can refer you to a specialist memory service.[2] Changing your diet and lifestyle works alongside medical care, not instead of it.

How Do You Know if Your Memory Is Improving?

Memory is subjective, so the only reliable way to know is to measure it, make changes, then measure again. Take the Cognitive Function Test now and retest once a year. Each time you do, you become part of our research as a Citizen Scientist. Together, Citizen Scientists help us discover what people with high scores are doing differently from those with low scores. The more people who take part, the more we all learn.

Diana first took the Cognitive Function Test at 60. Now 70, her cognitive function has improved.

Frequently Asked Questions

Start by Understanding Your Brain Health

Keeping your brain healthy is a lifelong journey, and it changes with the different stages of life. Just like on a road trip, you can sometimes get lost. No single food, nutrient or supplement guarantees that lost memory will come back. What works, for many people, is bringing together the right building materials, fuel and use, and checking regularly that you’re on the right road.

The good news is that you can get back on track. Knowing where you are is the first step. Here are three things to do today to start rebuilding your brain and protecting your precious memories:

Take the free Cognitive Function Test to see where you are now.
Test the biology behind it with the DRIfT 5-in-1 home blood test. It measures:
– homocysteine, which shows your need for B vitamins
– your Omega-3 Index
– vitamin D
– HbA1c, a measure of blood sugar control
– your glutathione index, a measure of antioxidant status
Put one or two pieces of the advice above into action within the next seven days

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.

How to Recover from Addiction with Nutrition
Omega-3 and B Vitamins: Nutrients That May Slow Brain Shrinkage
‘My Relative Has Memory Problems, Possibly Dementia. What Do You Recommend?’

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How does our ‘do it at home’ pinprick blood test for omega-3 predict your cognitive ability, dementia risk, brain size and intelligence? 

We are a charity dedicated to researching cognitive function and helping people look after their brain and reduce their risk of dementia and other brain-related health challenges, and TODAY we have launched a new ‘do it at home’ pinprick blood test for omega-3.

Multiple studies, including a new study, by psychologists at the Linda Loma University in California and published in the journal Brain Sciences (1), have found that the higher a person’s omega-3 index was in their blood, the more white matter there was in their brain, and the better they performed on cognitive tests that predict less risk for dementia.

With omega-3 such an important brain-health indicator, we have launched an easy, do it yourself, home pin prick test, so your omega-3 levels can be accurately determined. 

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Research also shows that the test can predict brain size and cognitive function. 

The study in California not only found omega-3 was a clear predictor of cognitive function and dementia risk (the higher the omega-3, the lower the risk), it also found that in older people in good health, levels of omega-3 predicted both their brain volume and their cognitive abilities on tests of memory and speed of thinking (the higher the level the bigger their brain volume and the faster their thinking).

“This confirms previous growing evidence that a person’s omega-3 index, which is a composite score of the two main brain-friendly omega-3 fats found in seafood, called EPA and DHA, predicts both the risk for depression (2) and dementia (3), and poorer reading ability, lower IQ, worse memory, difficulty sleeping, aggression and emotional instability in children – hallmarks of ADHD (4) .” says Patrick Holford, our founder and CEO.

The Omega-3 index, which should be above 8%, also predicts risk for heart disease (5) and developmental problems in babies from measures taken in women both before and during pregnancy. “Pregnant women with a higher omega-3 index have a much lower risk of having a baby with developmental problems, according to research at Imperial College London from the Institute of Brain Chemistry at the Chelsea & Westminster Hospital campus.” adds Holford. “It is wise for a woman considering pregnancy to check their omega-3 index and ensure it is above 8%.”

The home test kit, now available HERE also includes our free Cognitive Function Test and a questionnaire to complete about your diet and lifestyle that then identifies the key changes that lower risk of dementia. 

We have tested over 400,000 people and our goal is now to track people’s blood levels of omega-3 with cognitive function to work out exactly what the optimal intake of omega-3 for brain health actually is – so we need your help!

What about Omega-3 from plants?

While there is a type of omega-3 fat (called linolenic acid) in green leafy vegetables, as well as walnuts, chia and flax seeds, its conversion into EPA and DHA is poor. The ability to convert plant-based omega-3 into EPA, which is associated with better mood, and DHA which is the main brain-building omega-3 fat linked to lower risk of age-related memory decline and dementia, varies from person to person. So we hope to find out whether other factors such as age, sex, alcohol consumption and dietary habits, other than seafood intake, make a difference to the ability to make the brain-friendly types of omega-3 measured in this test.

The intake of marine foods has continued to decline over the past hundred years and countries with the lowest intake have the most risk for depression (6), dementia (7) and suicide (8). Even the rate of homicide is linked to a country’s omega-3 intake according to World Health Organisation data (9). 

Less than 5 per cent of children achieve the basic government guidelines for eating fish and omega-3 (10) however we really don’t know if even these guidelines are optimal for mental health. So the more people who are willing to take this inexpensive test and complete a short questionnaire about their dietary habits, plus take a 10-minute online Cognitive Function Test, the more effectively we can discover what an optimal intake of omega-3 for brain health and the prevention of dementia later in life is.

So will you join us and become citizen scientists in this way and help us advance this much-needed area of research – while also helping improve your own brain health?

The test, which costs £49.95, helps to support this research, so to check your omega-3 status click 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 Loong, S.; Barnes, S.; Gatto, N.M.; Chowdhury, S.; Lee, G.J. Omega-3 Fatty Acids, Cognition, and Brain Volume in Older Adults. Brain Sci.2023,13,1278. https://doi.org/ 10.3390/brainsci13091278 

² Yonezawa K, Kusumoto Y, Kanchi N, Kinoshita H, Kanegae S, Yamaguchi N, Ozawa H. Recent trends in mental illness and omega-3 fatty acids. J Neural Transm (Vienna). 2020 Nov;127(11):1491-1499. doi: 10.1007/s00702-020-02212-z. Epub 2020 May 25. PMID: 32451632.

³ Wei BZ, Li L, Dong CW, Tan CC; Alzheimer’s Disease Neuroimaging Initiative; 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 Jun;117(6):1096-1109. doi: 10.1016/j.ajcnut.2023.04.001. Epub 2023 Apr 5. PMID: 37028557; PMCID: PMC10447496.

⁴ Montgomery P, Burton JR, Sewell RP, Spreckelsen TF, Richardson AJ. Low blood long chain omega-3 fatty acids in UK children are associated with poor cognitive performance and behavior: a cross-sectional analysis from the DOLAB study. PLoS One. 2013 Jun 24;8(6):e66697. doi: 10.1371/journal.pone.0066697. Erratum in: PLoS One. 2013;8(9).doi:10.1371/annotation/26c6b13f-b83a-4a3f-978a-c09d8ccf1ae2. PMID: 23826114; PMCID: PMC3691187; see also Raine A, Ang RP, Choy O, Hibbeln JR, Ho RM, Lim CG, Lim-Ashworth NSJ, Ling S, Liu JCJ, Ooi YP, Tan YR, Fung DSS. Omega-3 (ω-3) and social skills interventions for reactive aggression and childhood externalizing behavior problems: a randomized, stratified, double-blind, placebo-controlled, factorial trial. Psychol Med. 2019 Jan;49(2):335-344. Doi 10.1007/s11920-018-0894-y. PMID: 29623453. ; see also Liu, J., Cui, Y., Li, L. et al. The mediating role of sleep in the fish consumption – cognitive functioning relationship: a cohort study. Sci Rep 7, 17961 (2017). https://doi.org/10.1038/s41598-017-17520-w

⁵ 1 Elagizi A, Lavie CJ, O’Keefe E, Marshall K, O’Keefe JH, Milani RV. An Update on Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health. Nutrients. 2021 Jan 12;13(1):204. doi: 10.3390/nu13010204. PMID: 33445534; PMCID: PMC7827286.

⁷ Yonezawa K, Kusumoto Y, Kanchi N, Kinoshita H, Kanegae S, Yamaguchi N, Ozawa H. Recent trends in mental illness and omega-3 fatty acids. J Neural Transm (Vienna). 2020 Nov;127(11):1491-1499. doi: 10.1007/s00702-020-02212-z. Epub 2020 May 25. PMID: 32451632.

⁸ 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. Epub 2009 Jan 9. PMID: 19136836.

⁹ Hibbeln JR. From homicide to happiness–a commentary on omega-3 fatty acids in human society. Cleave Award Lecture. Nutr Health. 2007;19(1-2):9-19. doi: 10.1177/026010600701900204. PMID: 18309762.

¹⁰ Kranz, S.; Jones, N.R.V.; Monsivais, P. Intake Levels of Fish in the UK Paediatric Population. Nutrients 2017, 9, 392. https://doi.org/10.3390/nu9040392

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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References

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

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

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

⁴ Shirafuji N et al Homocysteine Increases Tau Phosphorylation, Truncation and Oligomerization. Int J Mol Sci. 2018 Mar 17;19(3):891. doi: 10.3390/ijms19030891. PMID: 29562600; PMCID: PMC5877752.

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

⁶ Northuis C, Bell E, Lutsey P, George KM, Gottesman RF, Mosley TH, Whitsel EA, Lakshminarayan K. Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study. Neurology. 2023 Aug 9:10.1212/WNL.0000000000207747. doi: 10.1212/WNL.0000000000207747. Epub ahead of print. PMID: 37558503.

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

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

⁹ Oulhaj A., et al. J Alzheimers Dis. 2016;50(2):547-57.

Have you ever wondered if what you eat has anything to do with your mood, energy levels and ability to concentrate? Do you ever experience ‘brain fog’ and tiredness and wonder why you feel anxious and low when others seem to cope?

 New research is showing that what happens in your gut after eating food has a direct effect on your brain and how you feel. Simple diet changes can have profound effects. Stephanie, a 28-year-old lawyer, is a case in point. “After a week the brain fog and tiredness were significantly better and then after a few weeks, all of my symptoms had gone!” Wanita , age 41, who was signed off work, had complete relief from her anxiety and fatigue and she was then able to return back. Her doctor had recommended anti-depressants. Nicola, age 51, had constantly felt tired and lethargic, with brain fog and the inability to concentrate. “If I didn’t eat regularly, I felt worse, so I was constantly grazing on food. I know now I was eating the wrong foods which didn’t help”. Now she says “I feel so much better in myself and have a lot more energy. The best thing is to not have brain fog.”

What they all had in common were specific food intolerances whereby their gut and immune system reacted, creating a kind of inflammation and reactivity that can both cause gut issues such as IBS, pain and bloating, but also psychological issues such as brain fog, anxiety and depression. The ability of foods to trigger mental health issues has been known for a remarkably long time. Back in 1980 Dr Joseph Egger, writing in the Lancet medical journal (1) reported: “The results showed that allergies alone, not placebos, were able to produce the following symptoms: severe depression, nervousness, feeling of anger without a particular object, loss of motivation and severe mental blankness.” But why certain foods in certain people could produce mood changes and brain fog wasn’t known.

Researchers in the US (2) China (3), Poland (4) and the UK (5) have found out why and it’s all to do with ‘food intolerance’ that is unique to the individual. While classic allergies cause the body to product IgE antibodies that attack the offending allergen, depression, brain fog and even schizophrenia, according to research at Johns Hopkins University School of Medicine in the US, can occur when a person’s immune system produces a different kind of ‘IgG’ antibody that attacks their offending foods. 

What Stephanie, Wanita and Nicola had in common is they are part of research that has involved thousands of people, all having an IgG food intolerance test administered via a home test kit provided by YorkTest, and then avoided their ‘reactive’ foods. 

Scientific Director at YorkTest, Dr Gill Hart, says “YorkTest pioneered food IgG testing developing our first food intolerance test back in 1998 in collaboration with scientists from the University of York. Since then, YorkTest has provided over half a million tests. The tests are accurate, have been shown to be effective and have demonstrated >98% reproducibility. For those with high food IgG reactivity, the pattern of IgG trigger foods is unique to each individual. The tests provide valuable information, and with nutritional advice provided as part of the Food Intolerance Test, people feel fully supported in making the required dietary changes. The good news is that food intolerances aren’t necessarily for life, and those taking the test and changing their diet have reported improvements over a relatively short period of time”. 

Unlike conventional IgE allergies, which can last for life, IgG antibodies “die off” so, theoretically, if you avoid the offending food for at least three months, you may be able to reintroduce the food without reacting. However, it is worth doing this systematically because some people do continue to react.

Nine in ten people having the test, and avoiding their offending foods report improvement in mood, brain fog and lethargy (5). See the table below for reported results from YorkTest’s research.

YorkTest are a supporter of Food for the Brain and offer our Friends £10 off the price of a test in the UK. If you live in the UK go to yorktest.com and enter the discount code FFB10 in the basket.

If you live in the US go to yorktest.com/us and enter FFB10US in the basket for your $10 discount. YorkTest will match your discount with a donation to Food for the Brain to help us help more people regain mental health through optimum nutrition.

CLICK HERE TO GET YOUR YORK TEST IN THE UK & IRL

CLICK HERE TO GET YOUR YORK TEST IN THE USA

REFERENCES

1. Egger J et al, The Lancet 865-869, October 15, 1980

2.. Severance E et al (2015) IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia. Brain Behav Immun. 44:148–58  

3. Tao R et al (2019) Chronic Food Antigen-specific IgG-mediated Hypersensitivity Reaction as A Risk Factor for Adolescent Depressive Disorder. Genomics Proteomics Bioinformatics 17(2):183-189.

4. Karakuła-Juchnowicz H et al (2017) The role of IgG hypersensitivity in the pathogenesis and therapy of depressive disorders. Nutr Neurosci 20:110-8; see also Karakula-Juchnowicz H et al (2018) The Food-Specific Serum IgG Reactivity in Major Depressive Disorder Patients, Irritable Bowel Syndrome Patients and Healthy Controls. Nutrients 10:548; 

5. Hart G (2017) Food-specific IgG guided elimination diet; a role in mental health? BAOJ Nutrition 3:3:033  

6.  Hardman G and Hart G, 2007: Dietary advice based on food-specific IgG results. Nutrition and Food Science 37, 16-23 https://www.emerald.com/insight/content/doi/10.1108/00346650710726913/full/html

By Jerome Burne &  Patrick Holford

New research shows that the combination of B vitamins and omega-3 are a dynamic duo against dementia, stopping the brain shrinkage that is the hallmark of Alzheimer’s. 

The discovery, hailed as the “a major step towards Alzheimer’s prevention” was first made at the University of Oxford, but has now been confirmed by research groups in Holland, Sweden and China.

Headed by Professor David Smith, former Chair of Pharmacology and Deputy Head of the Division of Medical Sciences at Oxford University and director of the Oxford Project to Investigate Memory and Ageing (OPTIMA), the research has found that giving older people with the first signs of cognitive impairment supplemental B vitamins (B6, B12 and folic acid) at higher levels than can be achieved through diet to those with sufficient omega-3 fats produced 73% less brain shrinkage in a year, compared to placebo. This reduction brought brain shrinkage down to the level found in those elderly with no cognitive decline. The trial was part-funded by Alzheimer’s Research UK (ARUK). “The effect is greater than that of any drug treatment to date – with no adverse effects.” says Professor Smith. In contrast the recent trials of anti-amyloid drugs have reduced brain shrinkage by 2%.

“Brain shrinkage is the hallmark of Alzheimer’s so this was a vital discovery for its prevention” says Patrick Holford, director of the Alzheimer’s Prevention Project at foodforthebrain.org, the UK’s leading dementia prevention charity “However we needed confirmation from other research groups. Now we have it.”.

Three other research groups have confirmed the combined effect of omega-3 and B vitamins is greater than either nutrient on its own.

“You literally cannot build brain cells without both omega-3 fats and sufficient B vitamins” says Holford. “If you give a builder a hammer or a bag of nails you don’t get a house. But if you give them both they can build a house. The B vitamins drive a process called methylation which assembles the critical brain-building fats that make up the membrane of neurons, through which all brain communication happens. Both are vital for building brain cells. Neither can work without the other.”

Watch this one minute film, on how to build new brain cells at any age.

Realising that the combination of B vitamins and omega-3 fats is key, researchers in Holland, who had previously run a major trial called B-proof that had tested the effects of B vitamins on memory but had only found very modest benefits decided to take reanalyse the results of their B vitamin trial according to the participants blood levels of omega-3 at the start of the trial. Sure enough, they found no benefit at all from the B vitamins in those with low omega-3 status, but a massive improvement in cognition in those in the top third of omega-3 levels.[i]

Could this need for both explain why some trials testing omega-3 were also not successful?

The Oxford University researchers, led by Dr Frederik Jerneren, were given access to the blood samples from another trial in Sweden called OmegAD. This trial  had given older people a hefty dose of 2.3grams (two large capsules) of omega-3 fish oils. The trial had apparently failed, showing no significant cognitive benefit. Could faulty methylation, a result of lack of B vitamins, be the reason for the omega-3 fish oils not working?

The Oxford researchers therefore measured homocysteine, a consequence of a lack of B vitamins, in the samples from the OmegAD trial. Dr Jerneren split the participants into thirds – from the lowest to highest level of homocysteine. Those given omega-3 who had  the lowest homocysteine, in other words sufficient in B vitamins, had a highly significant improvement in their clinical dementia rating while those with high homocysteine (poor B vitamin status) had no benefit at all.[ii] The group with sufficient vitamin B showed a reduction in their clinical dementia score that was more than three times that reported from the recent Lecanemab drug trial.[iii]

Meanwhile another trial, this time in China, gave those with pre-dementia either the B vitamin folic acid, or omega-3, or both, compared to placebo. Although B vitamin treatment and omega-3 treatment did slightly improve cognitive cores, the improvement was much greater in those given both thee nutrients.[iv]

With 170 million people over 65, Chinese authorities are taking prevention of dementia extremely seriously to avoid a cerebral tsunami. So, one of their top researchers, Professor Jin-Tai Yu at Shanghai’s Institute of Neurology at Fudan University did one of the most thorough reviews of all risk factors for Alzheimer’s to date.[v]

“Lowering blood homocysteine levels, an established indicator of Alzheimer’s risk, with B vitamins is a most promising treatment.” he concluded. He was also given access to the UK’s Bio Bank data of almost half a million people “Our current research, using data from the UK Bio Bank, shows that having higher blood levels of polyunsaturated fats, including omega-3, and supplementing fish oils, is associated with less risk of dementia. [vi] Moreover, recent studies suggest these two factors – homocysteine lowering B vitamins, and omega-3 – may, in combination, be potentially more beneficial. They are easy to implement. This is worthy of further research”

The UK’s Bio Bank data showed that something as simple as taking fish oils had reduced dementia risk by 9%. This is equivalent to the risk reduction found from quitting smoking.[vii]

US researchers at the National Institutes of Health research have confirmed this, attributing almost a quarter (22%) of Alzheimer’s cases to lack of B vitamins and raised homocysteine levels and the same (22%) to a lack of omega-3 and seafood intake.[viii] This means that about one in three cases of Alzheimer’s could be avoided simply by taking a daily high dose B vitamin supplement and an omega-3 fish oil capsule. This could save 95,000 people a year in the UK from developing dementia. Currently, 790 people – seven double decker buses worth – are diagnosed every single day. However, the benefit is not just in preventing people from dementia in the future. A study of healthy 65-year-olds given omega-3 fish oils showed both improvement in memory and healthier brain tissue within six months.[ix]

The Alzheimer’s prevention charity, foodforthebrain.org, targets eight prevention steps in their on-line Cognitive Function test and Dementia Risk Index questionnaire, including B vitamins and omega-3. “These are the two easiest to change and most evidence based prevention steps anyone can take.” Say Patrick Holford who directs their ‘Alzheimer’s is Preventable’campaign.

Scientists are also investigating other micronutrients and minerals that may affect brain ageing, including the potential role of lithium in brain health.

[i] van Soest, A.P.M., van de Rest, O., Witkamp, R.F. et al. DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial. Eur J Nutr (2022). https://doi.org/10.1007/s00394-022-02924-w

[ii] Jernerén F, Cederholm T, Refsum H, Smith AD, Turner C, Palmblad J, Eriksdotter M, Hjorth E, Faxen-Irving G, Wahlund LO, Schultzberg M, Basun H, Freund-Levi Y. 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. J Alzheimers Dis. 2019;69(1):189-197. doi: 10.3233/JAD-181148. PMID: 30958356.

[iii] Walsh S, Merrick R, Richard E, Nurock S, Brayne C. Lecanemab for Alzheimer’s disease. BMJ. 2022 Dec 19;379:o3010. doi: 10.1136/bmj.o3010. PMID: 36535691.

[iv] Li M, Li W, Gao Y, Chen Y, Bai D, Weng J, Du Y, Ma F, Wang X, Liu H, Huang G. Effect of folic acid combined with docosahexaenoic acid intervention on mild cognitive impairment in elderly: a randomized double-blind, placebo-controlled trial. Eur J Nutr. 2021 Jun;60(4):1795-1808. doi: 10.1007/s00394-020-02373-3. Epub 2020 Aug 28. PMID: 32856190.

[v] Yu JT, Xu W, Tan CC, Andrieu S, Suckling J, Evangelou E, Pan A, Zhang C, Jia J, Feng L, Kua EH, Wang YJ, Wang HF, Tan MS, Li JQ, Hou XH, Wan Y, Tan L, Mok V, Tan L, Dong Q, Touchon J, Gauthier S, Aisen PS, Vellas B. Evidence-based prevention of Alzheimer’s disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials. J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1201-1209. doi: 10.1136/jnnp-2019-321913. Epub 2020 Jul 20. PMID: 32690803; PMCID: PMC7569385.

[vi] Huang Y, Deng Y, Zhang P, Lin J, Guo D, Yang L, Liu D, Xu B, Huang C, Zhang H. Associations of fish oil supplementation with incident dementia: Evidence from the UK Biobank cohort study. Front Neurosci. 2022 Sep 7;16:910977. doi: 10.3389/fnins.2022.910977. PMID: 36161159; PMCID: PMC9489907.

[vii] Jeong SM, Park J, Han K, Yoo J, Yoo JE, Lee CM, Jung W, Lee J, Kim SY, Shin DW. Association of Changes in Smoking Intensity With Risk of Dementia in Korea. JAMA Netw Open. 2023 Jan 3;6(1):e2251506. doi: 10.1001/jamanetworkopen.2022.51506. PMID: 36656579; PMCID: PMC9857334.

[viii] Beydoun MA, Beydoun HA, Gamaldo AA, Teel A, Zonderman AB, Wang Y. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 2014 Jun 24;14:643. doi: 10.1186/1471-2458-14-643. PMID: 24962204; PMCID: PMC4099157.

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