By Patrick Holford

In 1965, UK paediatrician Dr Richard Smithells discovered that children with low folate were at significantly higher risk of neural tube defects, then commonly referred to as spina bifida.

It took more than 25 years for his research to be taken seriously. 

It wasn’t until the late 1980s that the Medical Research Council agreed to fund a study, the results of which were published in 1990. In 1991 the UK government told all women who were pregnant or planning pregnancy, to supplement 400 mcg of folic acid.

Folic acid reduces risk by supporting the process of methylation, which can be assessed through homocysteine levels. The process of methylation is vital for neuronal development and it depends not only on folate, but also on vitamins B6 and B12. Nine in ten obese women in the EU fail to achieve basic guidelines for folic acid supplementation in early and pre-pregnancy which would help to prevent such tragic neurodevelopmental problems (1).

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Accelerated Brain Shrinkage & Methylation

More than half of all children, and probably their parents, are deficient in B12. Accelerated brain shrinkage occurs below 500 pg/ml, as established by Professor David Smith’s research at Oxford University more than a decade ago. This is why several countries, such as Japan, set the ‘normal’ range for serum B12 as being above 500 pg/ml. Despite clear evidence to the contrary over the past decade, both UK and US health authorities have failed to correct the wrongful reference range for vitamin B12, set at less than half this, namely 180pg/ml (2).

A recent study of 3,000 EU children reported that the median level was 347 pg/ml and one third were below 200 pg/ml (3). This means that at least half of the children had levels associated with accelerated brain atrophy. This deficiency is especially prevalent in vegan children.

Poor methylation, identified by raised homocysteine, isn’t just an established risk factor or biomarker for neural tube defects. It is also a biomarker for autism, poor cognition in children, epilepsy, congenital heart defects, reduced birth weight and size, pregnancy complications, miscarriages, bipolar disorder, depression and schizophrenia (4). Methylation is required to ‘marry’ omega-3 DHA to phospholipids such as phosphatidylcholine, to form neuronal membranes essential for brain communication. Without healthy, fully functional neuronal membranes, cognition becomes ‘disconnected’.

The Bristol Avon study of 11,875 pregnant women showed a clear relationship between the amount of seafood consumed by a pregnant woman and their child’s development. The less seafood consumed, the worse the child’s social behaviour, fine motor skills, communication, social development, and verbal IQ (5).

At the Chelsea and Westminster campus of Imperial College London, Professor Michael Crawford’s team at the Institute of Brain Chemistry and Human Nutrition, has identified which mothers are likely to have neurodevelopmentally impaired infants based on their blood level of a type of oleic acid, which is produced as a substitute when insufficient omega-3 DHA is available to build the foetal brain (6). DHA is not only critical for brain development, but also essential for optimal visual function.

Insufficient choline, a primary constituent of phospholipids, during pregnancy is strongly linked to poor cognition. Women given choline in the last trimester have infants with faster speed of processing information and memory between four and thirteen months of age (7). The protective intake, 400mg per day, has also been shown to cut the risk of cognitive decline, dementia and Alzheimer’s by about 20% (8). So, lack of folate, B12, omega-3 fats and possibly choline are all extremely common and all strongly linked to many aspects of neurodivergence, including autism.

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How Much is ‘in the Genes’?

The culturally ‘acceptable’ view is that neurodivergence can’t be ‘treated’ – that the challenging symptoms experienced by those classified as neurodivergent or autistic (for example, cognitive and communication problems, anxiety and depression) can never be improved, despite clear evidence to the contrary. It is believed by some that autism, since it sometimes occurs within families, might be largely ‘in the genes’, as it was for Alzheimer’s. But families share environments, including habits from diet, smoking and drinking. We now know that genes cause less than one in a hundred cases of Alzheimer’s (9). Also, the gene hypothesis cannot adequately explain the dramatic rise in autism diagnoses in recent decades nor does it accept the simple fact that genes can only exert their effects across our biology – which is directly affected by nutrition.

That is not to say that genes don’t play a part in neurodivergence. There are several known genetic polymorphisms that do increase risk of neurodivergence such as a key methylation gene polymorphism, MTHFR677TT, which means that a person is less good at methylation, and needs more B vitamins. If present in the mother or child it almost doubles the risk of autism. A recent meta-analysis concludes, “For those mothers and children who are generally susceptible to autism, prenatal folate and vitamin B12 may reduce the risk that children suffer from autism.” (10) This is the same gene polymorphism that increases risk of Alzheimer’s disease.

Associate Professor Murphy’s research in Spain found that those women who had a homocysteine level above 9 mcmol/l, which is not uncommon (ideal is below 7), strongly predicted neurodivergent problems in their children at 4 months and again at 6 years of age, including an increased risk of autism, with children more likely to suffer from anxiety, depression, social problems and aggressive behaviour (11). 

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Personalised Assessment Is Needed

Neurodivergence, including conditions such as autism, is a broad and evolving concept, which currently encompasses so many children. There are many potential contributors including gut-brain problems, neuro-inflammation, nutritional deficiencies, toxic excesses, microbe infections including mould, food and other allergies, smartphone overuse, psychological and social issues, as well as genes. Every child needs a full assessment of these potential contributory factors. Individual assessment is required, with nutrition being one of the key factors to address. 

As Dr Rona Tutt, OBE, past President of the National Association of Head Teachers, an expert in special needs and on the board of Trustees says:

“People come in assorted shapes and sizes with brains that are unique.  A significant minority who are neurodivergent, need to be recognised, valued and supported, so they can maximise their strengths and overcome their challenges. We need to understand what is driving this increase in neurodivergence and how to best support and optimise a child’s potential.”

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We Cannot Repeat Our Past Mistakes

Our goal in launching COGNITION for Smart Kids & Teens is to empower children and their parents to be the best they can be. Children are our future, yet the current system is already struggling, with one in six children identified as having special educational needs. We can no longer ignore the clear and growing body of evidence linking neurodivergence to widespread deficiencies in B vitamins and omega-3 fats – key drivers of impaired methylation. Addressing these foundational nutritional gaps must be the starting point for effective intervention.  Ignoring or opposing this imperative is no different from what happened to Dr Smithell’s research on folic acid and neural tube defects. Initially, they said it wasn’t true and wasn’t important. Twenty five years later, to the cost of many thousands of children, it was finally recognised as both true and very important. 

I hope we do not have to wait as long for the role of nutrition in neurodivergence to be taken seriously. 

What we are campaigning for is widespread social awareness, along with governmental acceptance. The purpose of COGNITION for Smart Kids & Teens is to give parents a direct way to assess their children and identify simple and doable ways to help them reach their full potential for health and happiness.

Visit foodforthebrain.org/smartkids to find out more about the campaign, which launches on April 24th with both a conference for health professionals and a public webinar for parents. This coincides with the launch of the free on-line COGNITION for Smart Kids and Teens – an assessment with personalised advice on how to help children reach their full potential.

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Food for the Brain is a not-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 https://www.cdc.gov/mmwr/volumes/72/ss/ss7202a1.htm?s_cid=ss7202a1_w

² https://researchbriefings.files.parliament.uk/documents/POST-PN-0612/POST-PN-0612.pdf; see also Russell G, Stapley S, Newlove-Delgado T, Salmon A, White R, Warren F, Pearson A, Ford T. Time trends in autism diagnosis over 20 years: a UK population-based cohort study. J Child Psychol Psychiatry. 2022 Jun;63(6):674-682. doi: 10.1111/jcpp.13505

³ https://www.gov.scot/publications/pupil-census-supplementary-statistics/

⁴ https://www.health-ni.gov.uk/news/publication-prevalence-autism-including-aspergers-syndrome-school-age-children-northern-ireland-a nnual-report-2023

⁵ D’Adamo C et al., Reversal of Autism Symptoms among Dizygotic Twins through a Personalized Lifestyle and Environmental Modification Approach: A Case Report and Review of the Literature. J Pers Med. 2024 Jun 15;14(6):641. doi: 10.3390/jpm14060641

⁶ Survey conducted in collaboration with the charity Thinking Autism. The full survey results will be shown at the Smart Kids conference, April 24^th 20025.

⁷ https://www.nhs.uk/conditions/autism/autism-and-everyday-life/treatments-that-are-not-recommended-for-autism/

⁸  https://www.nice.org.uk/guidance/cg142/chapter/Recommendations#interventions-for-autism-2

⁹ Roigé-Castellví J, Murphy M, Fernández-Ballart J, Canals J. Moderately elevated preconception fasting plasma total homocysteine is a risk factor for psychological problems in childhood. Public Health Nutr. 2019 Jun;22(9):1615-1623. doi: 10.1017/S1368980018003610; see also Murphy MM, Fernandez-Ballart JD, Molloy AM, Canals J. Moderately elevated maternal homocysteine at preconception is inversely associated with cognitive performance in children 4 months and 6 years after birth. Matern Child Nutr 2017;13,e12289 . doi: 10.1111/mcn.12289

¹0 Hasler M, Fideli ÜS, Susi A, Hisle-Gorman E. Examining the relationship between autism spectrum disorder and neural tube defects. Congenit Anom (Kyoto). 2023 Jul;63(4):100-108. doi: 10.1111/cga.12516. Epub 2023 Apr 18. PMID: 37073427.¹1 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

By Patrick Holford

Something concerning is happening to our children – an increasing number are experiencing psychological and behavioural challenges, often diagnosed as autism. 

These challenges range from reduced eye contact and language delays to social difficulties, cognitive struggles, emotional meltdowns, aggression, and in some cases, depression. But what is driving this surge?

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Is it down to genetics & better diagnosis?

While mainstream medicine largely attributes autism to genetics, explaining the rise as improved diagnostic recognition, a growing body of independent researchers and clinicians in the US and UK suggests otherwise. The rapid increase in cases across multiple countries cannot be solely explained by genetics, as genes do not change so quickly. In the US, autism rates have skyrocketed from 2 in 10,000 to 1 in 36 over 50 years. In the UK, official government data estimates 1 in 62 children are classified as autistic; an eightfold increase in 20 years.  Meanwhile, school census data from Scotland and Northern Ireland report even higher rates, with 1 in 20 children diagnosed. These numbers strongly indicate that environmental factors, including diet, play a key role. This also suggests that proactive steps could help reduce risk.

That is why we are launching COGNITION for Smart Kids &Teens in April with the online ‘Smart Kids’ conference. We are bringing together leading experts to examine ways to prevent and potentially mitigate the impact of autism through environmental and nutritional interventions. In addition, we also have our ‘Optimising Neurodivergence public webinar for parents, caregivers or any non-practitioners who want to learn how to support our children to reach their full potential.

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New Approaches Show Encouraging Results

Dr. Chris D’Adamo, Assistant Professor at the University of Maryland School of Medicine and Director of the Centre for Integrative Medicine, has been at the forefront of research into environmental influences on autism. His recent paper, published in Personalized Medicine, estimates a 300% rise in autism cases since 2000. The study also documents a case where early intervention reversed autism symptoms by addressing modifiable lifestyle and environmental factors.

The case involved twin toddler girls exhibiting classic autistic traits;limited communication, repetitive behaviours, resistance to change and severe gastrointestinal issues. Under a comprehensive programme, led by a team of physicians, they implemented tailored interventions focused on diet, environment and lifestyle. The results were striking; within months, both girls showed dramatic improvements. Their autism severity scores dropped significantly, with one twin’s score reducing from 76 to 32 and the other from 43 to just 4. (Read more on this case here)

In the UK, Dr. Lorene Amet, a functional nutritionist and founder of The Lauriston Centre, has been applying similar integrative approaches. She has worked with hundreds of families, with remarkable success. A survey conducted with the charity Thinking Autism, assessed 220 children who followed her recommendations. 169 families reported either ‘life-changing’ or ‘very beneficial’ improvements, while only 11 children saw no noticeable change. 

Yet, despite such promising results, the NHS maintains that autism has no cure and advises against interventions such as vitamins, minerals, and dietary modifications.  The NICE guidelines currently offer no targeted nutritional strategies for autism management, leaving many parents with limited options. 

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Can Autism Risk Be Reduced Before Birth?

Another key topic at the Smart Kids Conference is prevention; reducing the likelihood of autism before birth. Research led by Associate Professor Michelle Murphy of the Universitat Rovira I Virgili in Spain, has revealed a crucial link between B vitamin deficiencies in early pregnancy and a child’s likelihood of developing autism-related traits. Her studies show that children of mothers who were low in B vitamins before conception were significantly more likely to display withdrawn behaviour, anxiety, depression or aggression by age six. 

The connection between maternal nutrition and neurological development is well established. For decades, pregnant women have been advised to take folic acid to prevent neural tube defects; a policy delayed by 25 years, resulting in hundreds of thousands of avoidable birth defects. Children with autism are six times more likely to have neural tube defects, further linking B vitamin deficiencies to neurodevelopmental issues.

This aligns with earlier research from Oxford University’s Professor David Smith, one of our scientific advisors.  His work demonstrated that B vitamins lower homocysteine, a toxic amino acid linked to autism, depression, cognitive impairments in children and Alzheimer’s in adults.  Professor Murphy’s research further suggests that even mildly elevated homocysteine levels before pregnancy strongly predict neurodivergent traits in children. This underscores the importance of nutritional screening and intervention before conception.

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There Is So Much That Parents Can Do…

We are inviting parents to take part in a free online assessment of their child’s cognitive, emotional, and behavioural function, alongside a diet and lifestyle questionnaire to help optimise brain health. Parents can also access a home test kit for homocysteine levels, providing valuable insight into potential nutritional deficiencies that may affect brain function.

The Smart Kids conference will provide further guidance on evidence-based interventions, bringing together researchers, clinicians, and parents seeking practical solutions to support children’s cognitive development.

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“People come in assorted shapes and sizes, with brains that are unique,” says Dr Rona Tutt, OBE, a trustee of Food for the Brain and past President of the National Association of Head Teachers. “A significant minority who are neurodivergent need to be recognised, valued, and supported to maximise their strengths and overcome challenges. Understanding the factors driving the rise in neurodivergence is key to ensuring the best outcomes for future generations.”

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For more information on all the events relating to Smart Kids – visit foodforthebrain.org/smartkids.

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Food for the Brain is a not-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 https://www.cdc.gov/mmwr/volumes/72/ss/ss7202a1.htm?s_cid=ss7202a1_w

² https://researchbriefings.files.parliament.uk/documents/POST-PN-0612/POST-PN-0612.pdf; see also Russell G, Stapley S, Newlove-Delgado T, Salmon A, White R, Warren F, Pearson A, Ford T. Time trends in autism diagnosis over 20 years: a UK population-based cohort study. J Child Psychol Psychiatry. 2022 Jun;63(6):674-682. doi: 10.1111/jcpp.13505

³ https://www.gov.scot/publications/pupil-census-supplementary-statistics/

⁴ https://www.health-ni.gov.uk/news/publication-prevalence-autism-including-aspergers-syndrome-school-age-children-northern-ireland-a nnual-report-2023

⁵ D’Adamo C et al., Reversal of Autism Symptoms among Dizygotic Twins through a Personalized Lifestyle and Environmental Modification Approach: A Case Report and Review of the Literature. J Pers Med. 2024 Jun 15;14(6):641. doi: 10.3390/jpm14060641

⁶ Survey conducted in collaboration with the charity Thinking Autism. The full survey results will be shown at the Smart Kids conference, April 24^th 20025.

⁷ https://www.nhs.uk/conditions/autism/autism-and-everyday-life/treatments-that-are-not-recommended-for-autism/

⁸  https://www.nice.org.uk/guidance/cg142/chapter/Recommendations#interventions-for-autism-2

⁹ Roigé-Castellví J, Murphy M, Fernández-Ballart J, Canals J. Moderately elevated preconception fasting plasma total homocysteine is a risk factor for psychological problems in childhood. Public Health Nutr. 2019 Jun;22(9):1615-1623. doi: 10.1017/S1368980018003610; see also Murphy MM, Fernandez-Ballart JD, Molloy AM, Canals J. Moderately elevated maternal homocysteine at preconception is inversely associated with cognitive performance in children 4 months and 6 years after birth. Matern Child Nutr 2017;13,e12289 . doi: 10.1111/mcn.12289

¹0 Hasler M, Fideli ÜS, Susi A, Hisle-Gorman E. Examining the relationship between autism spectrum disorder and neural tube defects. Congenit Anom (Kyoto). 2023 Jul;63(4):100-108. doi: 10.1111/cga.12516. Epub 2023 Apr 18. PMID: 37073427.¹1 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

by Patrick Holford

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Neurodivergence refers to differences in mental or neurological function from what is considered typical. This concept encompasses conditions such as autism spectrum disorder (ASD), ADHD, Tourette’s syndrome, dyspraxia, synaesthesia, dyscalculia, Down syndrome, epilepsy, and chronic mental health conditions like bipolar disorder, OCD, borderline personality disorder, anxiety, and depression. The overlap of traits in ASD and ADHD has led to the term AuDHD, recognising their frequent co-occurrence [1].

The term ‘neurodiversity’ refers to the natural variations in how human brains function, emphasising that every individual is unique [2]. While some neurodivergent individuals face challenges in communication, information processing, and social integration, others exhibit remarkable creativity and intelligence. The former president of the National Association of Head Teachers, Dr Rona Tutt, highlights that neurodevelopmental disorders often co-occur, challenging outdated beliefs that conditions exist in isolation [3].

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The Environmental Influence on Neurodivergence

While genetics may contribute to neurodivergence, environmental factors play a significant role. The rise in neurodevelopmental diagnoses cannot be solely attributed to better awareness and diagnosis . Factors such as air pollution, processed food consumption, chemical exposure, and modern technology use are increasingly considered potential contributors [3]. Many characteristics of neurodivergence appear within families, often assumed to be genetic. However, shared environmental influences—nutritional deficiencies, exposure to toxins, and psychosocial stressors—may drive this heritability rather than genes alone [3].

The increase in neurodevelopmental diagnoses is particularly striking in children. In the US, one in six children is classified as neurodivergent, and autism diagnoses have risen fourfold in two decades [1]. A practical measure of this shift is the number of children classified as having special educational needs (SEN). These classifications are often made reluctantly by parents and educators, underscoring the genuine increase in neurodivergence rather than mere overdiagnosis.

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The Role of Nutrition in Brain Development

Nutrition plays a crucial role in cognitive development and mental health. Dr Carl Pfeiffer, a pioneering physician, identified zinc deficiency and pyroluria as biological imbalances linked to sensory overload and neurodevelopmental difficulties [4].

Nutrient deficiencies can contribute to key symptoms of ASD and ADHD. The following table is adapted from data provided by the US Centers for Disease Control and Prevention (CDC) on common ASD characteristics and their potential nutritional correlations. Research has linked the following deficiencies to common neurodivergent traits:

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The Critical Window of Pregnancy and Early Childhood

The foundation of brain health is laid during pregnancy. By birth, 70% of brain cells are already formed, making prenatal and early childhood nutrition crucial [5]. Deficiencies during this period can have long-term consequences.

For example, studies have shown:

Low seafood consumption during pregnancy is linked to poorer social behaviour, fine motor skills, and verbal IQ in children [6].
Vitamin A deficiency affects brain development, leading to cognitive impairment [7].
Low maternal folate intake is associated with poorer cognitive outcomes in children [8].
Higher B-vitamin levels in infancy predict better cognitive function in adulthood [5].
Supplementing with folic acid (400mcg/day) during pregnancy improves cognitive outcomes at ages three and seven [5].
Elevated homocysteine levels during pregnancy are linked to higher risks of anxiety, depression, and social difficulties in children [9].

Optimising Brain Health Through Diet

Given the strong link between nutrition and brain function, proactive dietary changes can support neurodevelopment and alleviate symptoms of neurodivergence. Key recommendations include:

Avoid alcohol and smoking, especially during pregnancy and breastfeeding.
Limit or avoid foods with added sugar and follow a low-GL diet.
Avoid artificial colourings and flavour additives, such as MSG.
Optimise omega-3 intake from seafood and eggs, and supplement with omega-3 DHA and EPA.
Ensure adequate vitamin A and D intake, with sufficient sun exposure to support vitamin D levels.
Support healthy methylation with B vitamins, especially vitamin B12 for vegans and those on a predominantly plant-based diet.
Check for food intolerances, including gluten, if digestive symptoms are present.

It is also important to note that the DRIfT test can be administered to any child over the age of two. Also note you can do the DRIfT test on any child over 2 years old. Find out more about the DRIfT test here

The Future of Neurodivergence: Prevention and Support

While some neurodevelopmental conditions may not be entirely preventable, improving prenatal and childhood nutrition can help reduce risks and alleviate symptoms. The rising prevalence of neurodivergence suggests an urgent need to address environmental and dietary factors [10]. Rather than normalising suboptimal brain development, prioritising nutrition and early intervention can improve outcomes for neurodivergent individuals.

By fostering a deeper understanding of how environmental and nutritional factors influence neurodivergence, we can better support individuals in reaching their full potential while reducing unnecessary suffering.

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Join us in our Smart Kids Campaign!

How to get involved:

Attend the Optimising Neurodivergence Webinar – happening on 24th April at 6:30 PM – sign up here
Register for the Smart Kids Conference – an all-day event for health professionals and practitioners on 24th April, 2025. – sign up here
Donate to the Smart Kids Programme – help support neurodivergent children – find out more here

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Food for the Brain is a not-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.Centers for Disease Control and Prevention (CDC). Autism Data. Available at: https://www.cdc.gov/autism/data-research/?CDC_AAref_Val=https://www.cdc.gov/ncbddd/autism/data.html

2. Psychology Today. “What Is Neurodiversity?”. Available at: https://www.psychologytoday.com/gb/basics/neurodiversity

3. Tutt, R. Neurodiversity insights. Trustee and Scientific Advisor, Food for the Brain.

4. Pfeiffer, C. Nutritional insights. Pfeiffer Treatment Center.

5. McNulty, H., et al. (2019). Effect of continued folic acid supplementation beyond the first trimester of pregnancy on cognitive performance in the child: a follow-up study from a randomized controlled trial (FASSTT Offspring Trial). BMC Medicine, 17(1), 196. doi:10.1186/s12916-019-1432-4.

6. Hibbeln, J.R., et al. (2007). Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study). Lancet, 369(9561), 578–585. doi:10.1016/S0140-6736(07)60277-3.

7. Liu, Z. (2021). The Impact of Vitamin A on Cognitive Functions. Behavioral Neurology, 2021:5417497. doi:10.1155/2021/5417497.

8. Veena, S.R., et al. (2010). Higher maternal plasma folate but not vitamin B-12 concentrations during pregnancy are associated with better cognitive function scores in 9- to 10-year-old children in South India. Journal of Nutrition, 140(5), 1014–1022. doi:10.3945/jn.109.118075.

9. Roigé-Castellví, J., Murphy, M., Fernández-Ballart, J., & Canals, J. (2019). Moderately elevated preconception fasting plasma total homocysteine is a risk factor for psychological problems in childhood. Public Health Nutrition, 22(9), 1615–1623. doi:10.1017/S1368980018003610.

10. Kranz, S., Jones, N.R.V., & Monsivais, P. (2017). Intake Levels of Fish in the UK Paediatric Population. Nutrients, 9(4), 392. doi:10.3390/nu9040392.

by Cath Verner

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A landmark study from the Centre for Healthy Brain Ageing (CHeBA) at the University of New South Wales (Sydney, Australia) has provided compelling evidence that targeted diet and lifestyle changes can improve cognitive function in older adults. 

Or put simply, what we teach and promote at Food for the Brain works when it comes to promoting brain health.

Raising awareness and providing tools to support the critical role of diet and lifestyle in long-term cognitive health is both essential and part of the solution.

This recent study affirms our approach: sustained step-by-step adjustments to diet, exercise, sleep, and social engagement significantly reduces the risk of dementia as well as maintaining – and even enhancing – cognitive function.

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Study shows a holistic approach to brain health works

The CHeBA study recruited over 6000 adults aged 55 to 77, dividing them into two groups, one participating in an online lifestyle intervention programme and the other serving as a control group.

Physical activity (strength and balance training), 
Brain training (three weekly cognitive training sessions), 
Mediterranean diet (rich in plant foods and healthy fats with limited meat and dairy), 
Mental well-being (a digital anxiety and depression reduction program).

While both groups showed some cognitive improvements, those in the intervention group experienced significantly greater gains, demonstrating the added value of a structured, multi-domain approach.

Professor Brodaty, one of the study’s research team, stated:

“Participants aged 55-65 showed greater improvement than those aged 66-77, suggesting that prevention programmes should start earlier.”

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Why a Multi-Domain Approach Works!

Unlike traditional approaches that focus on just one or two factors, the COGNITION® Programme, which you get access to when you become a FRIEND of Food for the Brain, is similarly built on eight interwoven pillars—including diet, physical exercise, sleep, social involvement, and even the gut microbiome—to provide a comprehensive brain health plan.

The study’s ‘Maintain Your Brain’ trial further supports this, showing that targeting multiple lifestyle domains simultaneously – including physical activity, nutrition, brain training, and mental well-being – leads to greater cognitive benefits, rather than focusing on a single risk factor.

And, as we always say, the earlier you start, the better!

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Your Roadmap to the 8 Pillars of Cognitive Health

In line with this study, we focus on 8 key domains that influence brain health. These areas provide strategies to help individuals reduce their risk of cognitive decline and support long-term brain health:

Domain 1: Low Glycemic Load (GL) Diet – Managing blood sugar levels is crucial for brain function. High-sugar diets contribute to inflammation and insulin resistance, impairing cognitive performance. A low-GL diet helps stabilise energy levels and protects brain cells from damage

Domain 2: B Vitamins & Homocysteine Levels – High homocysteine levels, a by-product of metabolism, are linked to cognitive decline. Ensuring adequate B vitamins (B6, B12, and folate) supports brain function and lowers homocysteine levels.

Domain 3: Brain-Boosting Fats – Healthy fats like omega-3s (found in fish, flaxseeds, and walnuts) are essential for brain cell structure and function. They help reduce inflammation, enhance memory, and support cognition.

Domain 4: Antioxidants & Polyphenols – Free radicals damage brain cells, but antioxidants (from colourful fruits, vegetables, green tea, and dark chocolate) help combat oxidative stress and keep your brain young.

Domain 5: Healthy Gut & Microbiome – The gut-brain connection is vital for mental clarity and mood. A diverse microbiome (supported by fibre-rich foods, fermented foods, and probiotics) can reduce inflammation and improve neurotransmitter function, supporting memory and mental health.

Domain 6: Active Body (Exercise & Movement) – Regular physical activity boosts blood flow to the brain, supports neuroplasticity, and reduces the risk of dementia. Both aerobic exercise (like walking and cycling) and strength training play a role in maintaining cognitive health.

Domain 7: Active Mind – The brain thrives on challenge! Lifelong learning, problem-solving activities, and hobbies stimulate new neural connections and help build cognitive resilience.

Domain 8: Sleep & Stress Resilience Management – Poor sleep and chronic stress are major contributors to cognitive decline. Deep, restorative sleep allows the brain to clear toxins, while mindfulness, relaxation techniques, and breathing exercises help reduce stress hormones that damage brain cells.

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We know that these 8 domains can help you protect your brain and prevent cognitive decline – but most of us need support, accountability, motivation and structure to be able to implement the necessary changes consistently.

That is why the  COGNITION® Programme exists.

It’s designed to make implementing the above easier and simpler, one step at a time. By providing tailored advice and guidance on all eight areas, the programme offers tangible, practical steps that members can take to enhance brain function, reduce dementia risk, and improve overall cognitive well-being.

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Real-Life Results…

As a research charity with a stellar scientific advisory board, we care about excellent research being carried out. 

Yet the most important thing is that ‘the science’ helps to transform lives, families and communities. Citizen science in action!

Here is what can happen when you join COGNITION. One participant told us:

“I have taken the CFT for at least seven years now and find it very worthwhile.
By monitoring sensibly what I eat, as you advise and exercising within my limitations, I have found that despite being 84, my results have improved.”

This experience is echoed by another participant who found benefit in making small, sustainable lifestyle changes every day:

“I’ve taken on board your recommendations and I’ve increased my vitamin B intake and started doing puzzle books every day to keep my brain active in different ways from before. I also do more exercise and yoga daily. I love the fact that I can make these small changes myself and hopefully reduce my chances of getting dementia.”

Another participant shared how working with Food for the Brain and starting with the COGNITION® Programme was a wake-up call that led to lasting changes:

“Since starting with Food for the Brain, I’ve completely reshaped my lifestyle. I now attend a weekly Pilates class, work on my allotment, swim regularly, and take longer evening walks. I’ve also cut down on alcohol and meat, increased my vitamin B intake, and started doing daily puzzles to challenge my brain in new ways. My sleep has improved and I feel more energetic with fewer foggy days.”

These testimonials show how small, targeted lifestyle changes can significantly enhance cognitive resilience and well-being. The COGNITION® Programme equips individuals with the necessary tools to take charge of their brain health, which leads to improved cognitive test scores, better mental clarity, and a greater sense of control over their future.

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Join the COGNITION® Programme today!

As a non-profit charity we aim to make resources affordable and accessible to all, while covering essential staff and research costs. Membership of the 8-domain COGNITION® Programme is just £50 per year or £5 per month, ensuring that everyone can benefit from the programme.

You get access to the programme when you become a FRIEND of Food for the Brain.

Members receive:

Guidance on which domains to target based on their test results.
Ongoing cognitive assessments to track progress.
Access to expert-backed articles for long-term brain health.
Access to regular group coaching and Q&A sessions.

How it works:

Become a FRIEND here
Complete the FREE Cognitive Function Test* to get personalised insights and The COGNITION Programme.
Pick one domain to work on each month for six months, attend live coaching calls and watch as your brain health improves!

*You do not need to be a FRIEND to do this test – you can access it for free here.

Start today!

Your brain health is in your hands.

Become a FRIEND from just  £5 per month or  £50 a year to get access to the COGNITION® Programme

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Food for the Brain is a not-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

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

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

By Patrick Holford

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At the end of 2024, as part of Food for the brain international expansion, I was honoured to attend and speak at a conference creating a task force to ‘popularise prevention’ in the ‘silver-haired’ economy. I’d like to share excerpts from the speech given by China’s Former Minister of Health, Gao Qiang.

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Speech by Gao Qiang -China’s Former Minister of Health

“Dear esteemed leaders, distinguished guests, and fellow advocates for the development of the silver economy. I am delighted to join you here in Nanjing to discuss the topic of high-quality development in the silver economy. In his earlier presentation, Mr Ai Bo, the General Manager of Xiangjia Group, categorised the living conditions of elderly individuals into four stages: early ageing, active ageing, semi-active ageing, and disabled ageing. I fully agree with Mr Ai’s perspective and commend his boldness, as a young entrepreneur, to invest in the silver industry. However, I have one small suggestion: the living conditions of elderly individuals should not be defined solely by age but rather by their actual health status. Take myself as an example—while my age has technically surpassed the “active” stage, I still feel full of energy”. 

Earlier, Patrick Holford also mentioned five criteria for optimal health, which align closely with the “Five Forces” standard I previously proposed for active seniors: physical strength, energy, intelligence, financial resources, and charisma. Physical and mental strength pertain to health, financial resources reflect economic stability, and charisma is the comprehensive result of personal influence. The above represents my personal understanding of health standards for the elderly population.

The most important issue at this stage in Asia and even globally…

This year, the State Council issued a key directive on the development of the Silver Economy. This is not the first time relevant Chinese authorities have introduced the concept. In 2021, the 14th Five-Year Plan for the Development of the Ageing Industry officially highlighted the importance of developing the silver economy. 

China’s neighbour, Japan, as the country with the most serious ageing population in the world, and one of the first countries to enter an ageing society, proposed the concept of the silver economy as early as the 1970s. In 2008, the European Union also introduced and actively promoted the development of the silver economy. It is not an exaggeration to say that the Silver Economy is the most important issue at this stage in Asia and even globally. It is closely related to the duration and extent of a country’s ageing population. The more severe the ageing process, the more prominent the role of developing the silver economy. And now, the time for the development of the Silver Economy is just right.

A person with health does not necessarily have everything, but when health is lost, everything else is inevitably lost. This is especially true for the elderly, whose demand for health is even stronger. The decline in physical strength and energy is a natural process, and we cannot resist ageing, nor can we stop it. What we can do is slow it down, as this is an inevitable part of human development. The goal is to minimise illness in old age, prevent serious diseases, and promote long-term health and longevity. This represents the highest pursuit of health. Professor Chen Xiaobing’s interpretation of health is correct in the first part—‘health benefits longevity.’ However, I don’t entirely agree with the second part: ‘longevity does not necessarily mean health.’ Longevity without health is meaningless

I was impressed by Mr Holford’s closing remarks, where he stated that Western health maintenance mainly relies on medicine, but he hopes that in China, the primary means of maintaining health would focus on prevention—avoiding illness or preventing serious disease. Having recognised this, we must work even harder to implement and integrate this into all aspects of our work, especially in meeting the basic needs of the elderly—such as clothing, food, housing, transportation, and daily necessities.

Which aspect—clothing, food, housing, transportation, or daily necessities—is more important? Which development direction has the most potential? 

I have conducted a systematic analysis on this, and the core lies in food and daily necessities. We have long passed the stage of food insecurity, and severe malnutrition resulting in physical damage is no longer a common issue. The focus now is on balance, even controlling nutritional excess and reducing obesity. Ensuring that the elderly eat nutritionally and beneficially is our primary goal. Achieving this requires collaborative research from multiple experts. Solely relying on doctors is not enough, as their advice is often limited to six simple words: ‘less salt, less oil, less sugar.’ But does reducing salt, oil, and sugar guarantee health? The answer is ‘no’; a balanced and reasonable diet is essential. Traditional Chinese medicine emphasises the idea that food and medicine come from the same source. In my discussions with related experts, I often stress that the concept of medicinal food is not enough on its own; it needs specific plans to support it. What kind of diet is beneficial for enhancing specific aspects of health? What kind of diet can enhance preventive effects? Only by addressing these questions can families across the country incorporate these dietary combinations and structures into their daily cooking.

Medications are not the primary means of healthy living

Most people are familiar with healthy living, but its scientific basis is not always well understood.Among the five major tasks within the five key elements of building a Healthy China, the primary task is to promote healthy living. This is a prerequisite for preventing various functional diseases and maintaining long-term health. However, whether this goal has been initiated, implemented, and started to produce benefits remains uncertain. Practitioners in relevant fields, including enterprises involved in the silver economy, need to promptly correct misconceptions—medications are not the primary means of promoting the widespread adoption of healthy living. What plays a larger role are nutritional supplements, health products, and adjunctive treatments.

Mastering these techniques would support health, prevent disease, and promote long-term well-being. ‘Daily necessities’ is the most promising area for development. It includes not just daily living products but also health supplements, entertainment products, and age-friendly items, among others.

In conclusion, I hope that the Silver Economy will become a new focal point in China’s economic development, not only serving the elderly population in China but also contributing to the global silver population, showcasing China’s wisdom and spirit of dedication to the world, bringing blessings to all.”

Speech by China’s Former Minister of Health, Gao Qiang.

Patrick Holford with President of the China National Health Association, Wu YingPing (to the left) , former Vice Minister of Health, Zhang Fenglou, and former Minister of Health, Gao Qiang (to the right)

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Wouldn’t it be refreshing if our health ministers were talking and thinking in this way? 

We are on the brink of shifting from a drug-focused model to one centered on true prevention through optimal nutrition It is an exciting time.

Will you join us in our mission of making prevention the primary focus?

This paradigm shift first needs to start in your own body and home, so here is how you can begin

Order your DRIfT 5 in 1 test here so you can join our research and find out what your unique body needs.
Take the Cognitive Function Test: Assess your brain health today and gain personalised insights. 
Want the campaign to launch in your country, translated into your language? Can you invest or help us raise the money to make that happen? Contact nigel@foodforthebrain.org to find out more.

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Food for the Brain is a not-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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Attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and other neurodevelopmental disorders, all classified as ‘neurodivergent’, have rocketed in both the UK and USA. 

One in six children is classified as neurodivergent or in need of special education and and one in 36 is diagnosed as autistic – a fourfold increase in 20 years. 

This cannot be explained away by genetics or better diagnosis.

On April 24^th, we are hosting a multi-disciplinary team of global experts – coming together for a virtual conference in London to explore what optimum nutrition and lifestyle choices are needed for smart, happy and healthy children and teens and what is driving this escalation of cognitive and behavioural problems.

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The conference starts at the beginning – with pregnancy. Professor Michelle Murphy from the University of Madrid has found that the B vitamin status in the first trimester of pregnancy, measured with a homocysteine blood test, predicts problems, specifically withdrawn behaviour, anxiety or depression, social problems and aggressive behaviour in the child at age 6. Folate is one of these vital B vitamins and nine out of ten obese women in the EU fail to meet basic guidelines for folic acid supplementation to prevent neurodevelopmental problems. 

At the Chelsea and Westminster campus of Imperial College London, Professor Michael Crawford’s team at the Institute of Brain Chemistry and Human Nutrition, based at the Chelsea and Westminster campus of Imperial College London, is discussing the importance of marine food in the maternal diet., They have identified which mothers are likely to have neurodevelopmentally impaired infants based on their blood fat levels,, with omega-3 DHA, found in oily fish, being a critical brain-building nutrient.

Professor Julia Rucklidge, Director of New Zealand’s Mental Health and Nutrition Research Lab at the University of Canterbury, will present evidence for the essential role of multivitamins and minerals both during pregnancy and in improving children’s mental health.

This kind of research is also helping to identify what the optimal intake of nutrients is to optimise children’s potential. Dr Alex Richardson from Oxford University is presenting her evidence for helping children with ADHD-like symptoms and paediatric endocrinologist Professor Robert Lustig from the University of California San Francisco is pioneering research showing the dangers of high-fructose diets. “Teenagers with blood sugar problems are showing early signs of the same kind of cognitive decline and shrinkage of the hippocampus that are seen in Alzheimer’s.” The youngest non-genetic Alzheimer’s diagnosis is age 19.

Two clinicians, assistant professor Dr Chris D’Adamo from the University of Maryland in the US and Dr Lorene Amet from France, will be presenting cases of children diagnosed with autism who no longer are diagnosable as such and discussing nutritional and other interventions that are helping autistic children lessen troubling symptoms. “We have over 200 cases of autistic children who have benefitted. The majority have shown significant improvements but not all respond.” Says Dr Amet.

Dr Tommy Wood, Associate Professor of Pediatrics and Neuroscience at the University of Washington, will address the role of an active lifestyle, backed up by a presentation on the dangers of early smartphone use by Dr Jonathan Haidt, author of the New York Times best-seller ‘The Anxious Generation’. “The changes in diet, less active lifestyles and early smart phone use have created a perfect storm, negatively impacting a child’s healthy brain development. These are issues we have to address urgently for the sake of our children”, says Dr Tommy Wood, who heads research at the foodforthebrain.org, the charity hosting the conference.

The conference is opened by Dr Rona Tutt, OBE, past president of the National Association of Head Teachers and an expert in special needs. “People come in assorted shapes and sizes with brains that are unique.  A significant minority who are neurodivergent, need to be recognised, valued and supported, so they can maximise their strengths and overcome their challenges. We need to understand what is driving this increase in neurodivergence and how to best support and optimise a child’s potential”, she says.

The conference, which is tailored for nutritionists, doctors, teachers, and health professionals, is also open to interested parents.

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We also have a webinar for everyone (parents, carers etc), where we will dive deeper into the topic of optimising neurodivergence. Find out more about the webinar here.

The conference coincides with the launch of COGNITION for Smart Kids & Teens, which offers a free online assessment to all parents and teenagers as part of a global research project aimed at optimising children’s intellectual and emotional development.

Please visit foodforthebrain.org/smartkids to find out more.

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Food for the Brain is a not-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 Roigé-Castellví J, Murphy M, Fernández-Ballart J, Canals J. Moderately elevated preconception fasting plasma total homocysteine is a risk factor for psychological problems in childhood. Public Health Nutr. 2019 Jun;22(9):1615-1623. doi: 10.1017/S1368980018003610. Epub 2019 Jan 14. PMID: 30636652; PMCID: PMC10261079.

² Loperfido, F., Sottotetti, F., Bianco, I. et al. Folic acid supplementation in European women of reproductive age and during pregnancy with excessive weight: a systematic review. Reprod Health 22, 13 (2025). https://doi.org/10.1186/s12978-025-01953-y

³ Yau PL, et al Obesity and metabolic syndrome and functional and structural brain impairments in adolescence. Pediatrics. 2012 

⁴ J. Jianping et al. ‘A 19-Year-Old Adolescent with probable Alzheimer’s Disease’ Journal of Alzheimer’s Disease 1 Jan 2023: 915-922

Recipe from the Upgrade Your Brain Cook App

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Last month we released the Upgrade Your Brain Cook App, to help you eat delicious food every day that supports your brain health.

Many of you have subscribed to the App and to celebrate we want to share a brain-friendly makeover of pancakes – so you can enjoy pancake day the right way.

These pancakes have low glycemic load (0.6 per portion) which means they will keep your insulin levels steady – a crucial part of supporting cognitive function as we outline in our COGNITION programme in more depth. 

They are high in healthy brain fats due to being nut-based, which also means they are high in fibre (a whopping 4.6g per portion!) something your gut microbiome will love. Plus, if you drizzle with Chicory Root Syrup rather than honey or maple syrup you can boost the fibre content by another 3g! (Save 10% off your chicory root here when you use the code FFB10.UK only)

If you pair it with some berries you will also get the benefits of vitamin C and lots of antioxidants, too, and for added protein simply serve with some natural or Greek yogurt.

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So, if you are struggling to turn all this brain health knowledge and research into practical meals, then subscribe to the Cook App today to get access to 100+ recipes for just £30 a year! We’re constantly adding new recipes and features.

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Almond Pancake Stack with Berries + Yoghurt

Serves: 3
Prep Time: 5 minutes
Cooking Time: 10 minutes

Ingredients

150 g ground almonds
4 tablespoons (60 g) Greek yoghurt plus extra to serve
1 large egg
1 teaspoon ground cinnamon
1 teaspoon bicarbonate of soda
20 g raspberries (approx. 10 berries)
20 g blueberries (approx. 10 berries)
1 tablespoon chicory root syrup to drizzle (optional – use code FFB10 to save 10% off syrup and low GL bread from Dillons)

Method

In a blender, blitz the ground almonds, Greek yoghurt, egg and cinnamon into a thick batter.
Heat a non-stick frying pan over medium heat. Scoop a small ladle (approx. 3 tablespoons) of batter into the pan for each pancake.
Cook for 2-3 minutes on one side until bubbles appear, then flip and cook for another 1-2 minutes until golden brown. Repeat with the remaining batter.
Serve the pancakes warm, topped with raspberries, blueberries and a dollop of Greek yoghurt. 
Drizzle with a little chicory root syrup (optional)

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Food for the Brain is a not-for-profit educational and research charity that offers a free Cognitive Function Test and assesses your Dementia Risk Index to be able to advise you on how to dementia-proof your diet and lifestyle.

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

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

by Patrick Holford

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Choline is an often-overlooked but vital nutrient for brain health.

A new study suggests the optimal intake is 400mg, yet there is no Recommended Daily Allowance or widespread promotion of this crucial nutrient. It is also notably low in vegetarian and especially vegan diets.

(We discuss this and more in our COGNITION 6-month brain upgrade programme – available when you become a FRIEND of Food for the Brain.)

A major study published this year found that higher choline intake lowers the risk of dementia, Alzheimer’s, and cognitive decline.

Researchers tracked 125,000 people from the UK Biobank for 12 years and the study was published in the American Journal of Clinical Nutrition. It showed that higher choline intake reduced risk, with the most benefit around 400mg per day.

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Why does it matter?

Brain cells are made of a membrane containing choline (and other phospholipids) attached to the omega-3 fat DHA. Without choline the omega-3 doesn’t work. The attaching of the two depends on methylation, a process that is dependent on B vitamins, especially B12, folate and B6. Choline helps methylation and healthy methylation, indicated by low homocysteine, helps synthesise choline.

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Also previous studies (2) have found remarkable effects supplementing 480-900mg of choline in pregnancy on promoting ‘smart’ babies with faster reflexes and cognitive processes. It’s important for all ages and a key topic in our Smart Kids & Teens Programme.

What should you do or eat?

Choline is essential for the body, especially the brain, yet it has no Recommended Daily Allowance.

Choline is abundant in eggs, fish, and meat. An egg provides about 120mg, while a 50g serving of beef or salmon contains around 50mg. Beef liver is the richest source, but eggs are the best overall because they contain phosphatidylcholine which is more easily absorbed by the body. Plant-based sources include soy, quinoa, nuts, seeds, beans, and broccoli. A 50g serving of almonds or broccoli provides about 25mg. Phosphatidylcholine, found in lecithin capsules and granules, is an easy supplement option for vegans and vegetarians.

We recommend eating two eggs most days, with a minimum of six per week. Include fish and some meat if you eat it, or soy, quinoa, broccoli, nuts, and seeds if you don’t. Supplementing is likely beneficial, especially for vegetarians. Taking two high-PC lecithin 1,200mg capsules daily provides 250mg of phosphatidylcholine (PC), the form used by the body. These supplements are available at your local health food store.

Remember, your brain is built from what you feed it – and how you use it (as covered in COGNITION). What choline-rich foods can you add to your diet this week?

If you’re unsure what to eat to support your brain or need inspiration, the Cook App is here to help! With over 100 recipes at your fingertips, eating delicious, brain-boosting foods has never been easier—all for just £30 a year.

Actions:

Take the Cognitive Function Test today – our validated online assessment – to find out exactly what you need to focus on.
Become a FRIEND and get access to your 6-month COGNITION programme so you know how to upgrade your brain.

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Food for the Brain is a not-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.

—Reference list

Reference

Niu YY, Yan HY, Zhong JF, Diao ZQ, Li J, Li CP, Chen LH, Huang WQ, Xu M, Xu ZT, Liang XF, Li ZH, Liu D. Association of dietary choline intake with incidence of dementia, Alzheimer disease, and mild cognitive impairment: a large population-based prospective cohort study. Am J Clin Nutr. 2025 Jan;121(1):5-13. doi: 10.1016/j.ajcnut.2024.11.001. Epub 2024 Nov 7. PMID: 39521435.
Caudill, M. et al, ‘Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study’ FASEB Journal (Apr 2018); 32(4): 2172-80. doi: 10.1096/fj.201700692RR.

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Homocysteine is a natural amino acid made in the body’s methylation process. It is becoming one of the key biomarkers for overall health – no matter your age.

High homocysteine levels don’t just show bad nutrition; they indicate poor methylation. This important process influences neurotransmitter production, gene expression, detoxification, and DNA repair.

It’s rarely discussed, and finding accurate and affordable testing has been tough. That’s why we made our own. Studies show that high homocysteine levels link to over 100 health problems. These include cardiovascular disease, depression, and neurodevelopmental delays in children (1, 2, 3).

Elevated homocysteine levels matter. Levels above approximately 10–11 µmol/L are a red flag – yet this is not uncommon. For example, studies in the United States have shown that 40% of adults over 60 may have levels exceeding 11 µmol/L (4).  In the UK, nearly 40% of older adults seem to have low B12 levels. This can lead to faster brain shrinkage (5).

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Homocysteine,  Methylation & B Vitamins

Methylation is a fundamental part of homocysteine conversion. The body uses this process to activate nutrients and manage many chemical reactions every minute.

For example, folate, also known as folic acid, needs to change into its active form, methylfolate. This change helps support cellular functions. Key enzymes that aid in methylation depend on vitamins B6, B12, and folate. They also need cofactors like zinc, riboflavin (B2), niacin (B3), and trimethylglycine (TMG).

 When nutrients are low or not absorbed well, methylation suffers, and homocysteine levels go up. This can happen with age or certain diets like veganism (3). Homocysteine is a “functional” test for your methylation status. It works like HbA1c, which shows average blood glucose over several months.

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Why does High Homocysteine matter?

So how much does this biomarker matter really? Here at Food for the Brain, we let the science lead – here are some of the ways it can impact your health:

Cardiovascular Disease and Stroke:

Elevated homocysteine damages the inner lining of blood vessels, promoting atherosclerosis. One study found that people with levels over 20 µmol/L have almost five times the risk of death. For every 5 µmol/L increase, the risk rises by about one-third (6).

. Another study, involving nearly three thousand cardiovascular patients, found that those in the highest homocysteine quartile had a threefold higher risk of death compared to those in the lowest quartile (7). Furthermore, other research shows that two-thirds of heart attacks and strokes in older adults could be predicted by homocysteine levels rather than by cholesterol (2).

Brain Shrinkage and Cognitive Decline:

High homocysteine levels are linked to faster brain shrinkage and p-tau buildup. P-tau is a protein involved in Alzheimer’s disease (8). Studies show that taking B vitamins to lower homocysteine can slow brain atrophy and reduce cognitive decline (1).

Pregnancy and Child Development:

Even small increases (above 9 µmol/L) in pregnant women can raise the risk of miscarriage and other issues. They may also affect child development. This can lead to issues like withdrawn behaviour, anxiety, and social difficulties later on (9, 10, 11).

Learn more about our Smart Kids & Teens Programme. Donate to support the next generation’s brain development. Help them reach their full potential.

Mental Health Disorders:

High homocysteine levels are linked to several conditions. These include autism, anxiety, and bipolar disorder. They also relate to children’s behavioural issues and cognitive decline in both kids and adults. Additionally, elevated homocysteine is tied to dementia, depression, and hearing loss. Other associations include migraines, multiple sclerosis, motor neuron disease, and neural tube defects. It also connects to obsessive-compulsive disorder, post-traumatic stress disorder, and schizophrenia (1).

So when it comes to mental health homocysteine is key!

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Fortunately, Hcy is easily lowered. 

The simplest and most effective way to do this is with B vitamin supplements at the right dosage. Click here to see not only how much to supplement but which supplements there are to provide these doses. 

Most critical is the amount of vitamin B12 they provide.

The basic Dietary Reference Value that you see on supplements is 2.5mcg. Few provide more than 10mcg, which is sufficient if you don’t have raised Hcy. This will do nothing to lower a high H score. Professors Smith and Refsum recommend 500mcg a day – that’s two hundred times higher. This is both safe and effective especially if taken alongside B6 (20mg) and methylfolate (400mcg). Also, it doesn’t take long to bring your level down.

In addition to these core nutrients, extra support from zinc, TMG (trimethylglycine), and N-acetyl cysteine (NAC) may be beneficial. NAC, for instance, helps channel homocysteine toward SAMe production by boosting the body’s antioxidant defences and glutathione production (1).

Other things you can do:

wise choices are to eat greens, beans, nuts and seeds which are high in folate
eat seafood and eggs, high in B12 and phospholipids as well as omega-3, which methylation helps bind together to make healthy cell membranes
don’t smoke or drink in excess (one 125ml of red wine doesn’t affect homocysteine levels)
don’t drink more than one coffee a day
reduce stress
quality sleep
stay active and keep fit.

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Want to learn more about homocysteine? There are two more things you can do:

1. Join us for the Homocysteine Unplugged webinar with Patrick Holford, where he’ll break down this key health marker and its impact on you

2. Join our research and order your homocysteine test to understand your body and take action.. Prevention is power and you can start today.

You can test your homocysteine in a single test or as part of our DRIfT 5 in 1 which also tests Vitamin D, HbA1c, Omega-3 status and Glutathione. 

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Food for the Brain is a not-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.

—

Reference list

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.
de Ruijter W, Westendorp RG, Assendelft WJ, et al. Use of Framingham risk score and new biomarkers to predict cardiovascular mortality in older people: population-based observational cohort study. BMJ. 2009 Jan;338:a3083. doi: 10.1136/bmj.a3083.
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.
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.
Vogiatzoglou A, Refsum H, Johnston C, Smith SM, Bradley KM, de Jager C, et al. Vitamin B12 status and rate of brain volume loss in community-dwelling elderly. Neurology. 2008 Sep 9;71(11):826-32. doi: 10.1212/01.wnl.0000325581.26991.f2. PMID: 18779510.
Fan R, Zhang A, Zhong F. Association between homocysteine levels and all-cause mortality: a dose-response meta-analysis of prospective studies. Sci Rep. 2017;7:4769. doi: 10.1038/s41598-017-05011-2. PMID: 28676687.
Pusceddu I, Herrmann W, Kleber ME, Scharnagl H, Hoffmann MM, Winklhofer-Roob BM, et al. Subclinical inflammation, telomere shortening, homocysteine, vitamin B6, and mortality: the Ludwigshafen Risk and Cardiovascular Health Study. Eur J Nutr. 2020;59:1399–411. doi: 10.1007/s00394-019-02018-x. PMID: 31392436.
Xia Y, Prokop S, Giasson BI. “Don’t Phos Over Tau”: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies. Mol Neurodegener. 2021;16(1):37. doi: 10.1186/s13024-021-00460-5. PMID: 34016169; PMCID: PMC8122932.
Li JG, Chu J, Barrero C, Merali S, Praticò D. Homocysteine exacerbates β-amyloid, tau pathology, and cognitive deficit in a mouse model of Alzheimer’s disease with plaques and tangles. Ann Neurol. 2014;75(6):851-63. doi: 10.1002/ana.24156. PMID: 24771537.
Shirafuji N, Hamano T, Yen SH, Kanaan NM, Hayashi K, Hashimoto T. 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.
Bossenmeyer-Pourié C, Kerek R, Martin N, Koziel V, Lidzborski E, Sargueil F, 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: 30734989.
Roigé-Castellví J, Murphy M, Fernández-Ballart J, Canals J. Moderately elevated preconception fasting plasma total homocysteine is a risk factor for psychological problems in childhood. Public Health Nutr. 2019 Jun;22(9):1615-1623. doi: 10.1017/S1368980018003610. Epub 2019 Jan 14. PMID: 30636652; PMCID: PMC10261079.
Li J, Feng D, He S, Wu Q, Su Z, Ye H. Meta-analysis: association of homocysteine with recurrent spontaneous abortion. Women Health. 2021 Aug;61(7):713-720. doi: 10.1080/03630242.2021.1957747. Epub 2021 Aug 1. PMID: 34334120.
Dai C, Fei Y, Li J, Shi Y, Yang X. A novel review of homocysteine and pregnancy complications. Biomed Res Int. 2021 May 6;2021:6652231. doi: 10.1155/2021/6652231. PMID: 34036101; PMCID: PMC8121575.

Dementia, including Alzheimer’s is not only the greatest cause of death entailing huge healthcare costs, it is the major fear for many about aging. The great news is that dementia and Alzheimer’s are preventable. Less than 1% of Alzheimer’s is caused by genes so for most of us, the risk for dementia and age-related cognitive decline relates to things we can easily change. 

At foodforthebrain.org we have tested (for free) almost half a million people with a validated Cognitive Function Test, followed by a questionnaire which calculates your future Dementia Risk Index and crucially, advises what to do about it. 

Your risk is divided into eight domains (see image), highlighting areas to focus on to enable brain and cognitive powers to stay intact. 

Here are 25 simple steps you can take to dementia-proof your diet and lifestyle taken from our advice and my recent book, Upgrade Your Brain, which gives more detail for those who want to dig deeper.

Brain Fats – Up your brain fats – omega-3, phospholipids and vitamin D 

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Get your omega-3 index above 8%

You can measure your omega-3 index with a home test kit. Psychologists at the Linda Loma University in California did this for a group of older people, publishing their results in the journal Brain Sciences (1). They found that the higher a person’s omega-3 index was, the more white matter there was in their brain and the better they performed in cognitive tests. 
Omega-3 index is part of the DRIfT home test kit from foodforthebrain.org/tests

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Eat oily fish three times a week or SMASH it

S for salmon, M for mackerel, A for anchovies, S for sardines, and H for herrings or kippers. Caviar has the highest known levels of omega-3 DHA, which  builds your brain. Even having one serving a week almost halves the risk of Alzheimer’s. (2, 3)(not sure what to actually eat? Subscribe to our Upgrade Your Brain Cook App. Get access to over 100 recipes, including many that are high in omega-3 options!

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Supplement omega-3 fish oils

Aim for any supplement that provides 500mg of omega-3 DHA. This may mean two capsules a day. See this recent study in the American Journal of Clinical Nutrition of over 100,000 people (4). If you’re vegan, supplement with algal omega-3 DHA. 
Read more about omega-3 supplementation here.

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Eat an egg and/or nuts and seeds every day 

Organic and free range are the preferred options.

Eating  two eggs a week halves future risk of Alzheimer’s (5). The best seeds are chia, flax, hemp and pumpkin. The best nuts are walnuts, pecans, and macadamia, but all nuts are a good source of protein and minerals.

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Exercise outdoors and supplement vitamin D

Low blood levels of vitamin D make cognitive decline 19 times more likely. If your vitamin D level is high, Alzheimer’s disease is 4 times less likely. People who take vitamin D, which is especially important in winter, have a one-third lower risk. 
A vitamin D test is part of the DRIfT test at foodforthebrain.org/tests

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Low Carb and GL – Eat a low-carb, low sugar, low GL diet

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Avoid sugar and don’t eat junk food

Avoid the white stuff – flour, sugar, rice and especially ultra-processed foods. Fructose and high fructose corn syrup are common sweeteners. They are especially harmful to the brain.

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Eat your fruit, don’t drink it

Stay away from fruit juices as they contain no fibre but lots of sugar. A glass of orange juice is worth three oranges’ worth of juice, but no fibre. Fibre fills you up.

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Limit your intake of bread, pasta, and potatoes

If you eat more than 100 to 150 g a day of grains or potatoes, which is one or two servings max, your risk of dementia goes up .

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Limit alcohol to a glass of wine a day or equivalent

Drinking alcohol, particularly red wine, can lower risk if done in moderation. However, the benefits are limited. . Abstinence increases risk, as does having more than 14 units of alcohol a week, according to a study in the British Medical Journal (6).

Add C8 oil to your coffee

The brain can run on either glucose or ketones, made in the liver from a ‘medium chain triglyceride’ called C8 oil. Two tablespoons of a C8-rich oil improve cognitive abilities and help provide the brain with energy (7).  Read more about MCT oil here.

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B vitamins – Keep your homocysteine low with B vitamins 

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Test your blood homocysteine level with a home test kit and supplement B vitamins if needed

A level above 10 mmol/l, which is extremely common in people over 60, is strongly associated with accelerated brain shrinkage and increases risk of Alzheimer’s ten-fold. Homocysteine is easily lowered by supplementing vitamin B6, B12 and folate but the amounts needed are much higher if your homocysteine level is high. We recommend everyone to supplement 10 mcg of B12, which is what you’ll find in a good multivitamin but if your homocysteine is raised, you’ll need 500 mcg a day to lower it. It’s completely safe so there’s no harm in taking this much.
It’s in the pin prick DRIfT test from foodforthebrain.org/tests

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Eat a serving a day of both greens and either beans, lentils, nuts or seeds

These are all high in the B vitamin folate as well as vitamin B6. A study in Holland gave 818 people aged 50 to 70 a folic acid supplement of 800mcg for three years, versus a placebo. At the end of the study, compared to those taking the placebo, those taking folic acid were functioning at the equivalent of being 5.5 years younger (8).

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Antioxidants – Eat and drink anti-ageing antioxidants and polyphenols [4]

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Eat lots of fresh fruit and veg

The more you eat, the better, though the benefits start to plateau at 500g a day, which is about five to six servings. People who ate the most greens had much less Alzheimer’s-related issues than those who ate the least.(9) . Berries are particularly protective, especially blueberries and strawberries.

Drink Tea

The more you drink, the better as confirmed by a recent study from Singapore (8). However, other studies are conflicting (9). My view is to drink tea, green over black, in preference to coffee, and limit your intake to one or two cups a day.

Eat dark (70%+) chocolate

The benefit peaks at 10g, or about 3 pieces. More recent studies on cocoa, a rich source of flavanols, have shown improved cognition, possibly by improving circulation (11).

Supplement vitamins C and E – and don’t smoke!

A study of 4,740 elderly people in Utah found that those taking both vitamin E and C reduced their risk of developing Alzheimer’s by 23%.

Taking either cut risk by a quarter (12).   Overall, a meta-analysis of vitamin C studies concludes thta supplementation lowers risk by about 26% (12). Smokers need at least twice as much vitamin C as non-smokers, just to have basic vitamin C levels in their blood. Smoking also raises homocysteine levels, another risk factor.

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Healthy Gut – A healthy gut is a healthy brain [5]

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Eat plenty of soluble fibre and prebiotic foods

Fibre from foods like oats, chia, and flax seeds benefits our gut microbiome. Prebiotic foods like garlic, artichoke, leeks, and onions nourish and support healthy gut bacteria.

When you eat potatoes or rice, cook them ahead of time. Then, store them in the fridge. Reheating food increases the amount of prebiotics, also known as resistant starch.

Supplementing vitamin C helps promote lactobacillus and bifidobacteria.

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Active Body – Exercise and keep physically active [6]

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Get active for 20 minutes … and build and maintain muscle 

Spend at least 20 minutes doing activities such as walking, gardening, housework or repairing things – anything that gets you moving. Don’t limit yourself to ‘exercise’– anything that gives you a faster heart rate and engages different sets of muscles is good. Muscle mass best predicts both your brain volume and risk of cognitive decline in later years (13).

Get balancing!

The brain works hard in exercise, especially if it involves complex movements and learning, such as learning to dance, or doing different movements in a yoga or t’ai chi class or running or walking on uneven surfaces. The brain is processing a lot of information, triggering patterns of muscle movement and keeping you in balance.

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Active Mind – Keep yourself socially and intellectually active [7] 

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Read, watch, or listen to stimulating content

A simple yardstick is to ask, ‘Am I learning anything? Am I using my mind?’ Reading books or listening to podcasts can be great ways to stimulate your mind, depending entirely on what you engage with.

Be social

Aim to spend at least two hours a week with other people in a social (not work) setting – groups, friends, family, etc.

Test your brain in the morning

Do Sudoku, the crossword or Wordle – check out this link. You may prefer an app; two that have high ratings are Brain HQ and Lumosity.

Learn something new and challenging

Learning a new language, sport or musical instrument are all good – anything that you keep practising. This fascinating study looked at the brains of musicians and showed that amateur musicians benefited most (14).

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Sleep and Calm – Sleep well, stay calm and live purposefully

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Avoid alcohol before bed and limit any caffeine intake after midday 

Caffeine suppresses melatonin, which helps you sleep, for up to 10 hours. 

Aim to follow a soothing bedtime routine

Ensure your bedroom is quiet and dark and you are comfortable. Turn off mobile phones and Wi-Fi connections at night.  Prioritise relaxing activities in the few hours before you go to bed.

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So, while you do not need to implement all 25 things this week, think about what 2-3 things you could focus on this month.

For further support, monthly coaching and detailed personalised email guidance make sure you join us as a FRIEND so you get access to COGNITION – your 6 month programme to help you upgrade your brain and improve your cognitive function. All for just 5 a month or 50 a year!

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Also, to accompany your 6-month programme we highly recommend completing the DRIfT at home blood test.

Not only will you be contributing to our research you will also get additional data so you know exactly what to do and what to supplement. 

Everyone is different but these tests help you know exactly what YOU need and are available worldwide, are done in the comfort of your own home and are suitable from age 2+!

Most of all – remember that Alzheimer’s and dementia is preventable and the best time to start is TODAY.

Food for the Brain is a not-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.

1 Hibbeln JR, Nieminen LR, Blasbalg TL, Riggs JA, Lands WE. Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity. Am J Clin Nutr. 2006 Jun;83(6 Suppl):1483S-1493S. doi: 10.1093/ajcn/83.6.1483S. PMID: 16841858.

2 Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Wilson RS, Aggarwal N, Schneider J. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol. 2003 Jul;60(7):940-6. doi: 10.1001/archneur.60.7.940. PMID: 12873849.

3 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.

4 Gong, Q., Xie, L., Bi, M., & Yu, L. (2021). A probability formula derived from serum indicators, age, and comorbidities as an early predictor of dementia in elderly Chinese people. Brain and Behavior 11, e2236. https://doi.org/10.1002/brb3.2236

5 Pan Y, Wallace TC, Karosas T, Bennett DA, Agarwal P, Chung M. Association of Egg Intake With Alzheimer’s Dementia Risk in Older Adults: The Rush Memory and Aging Project. J Nutr. 2024 Jul;154(7):2236-2243. doi: 10.1016/j.tjnut.2024.05.012. Epub 2024 May 22. PMID: 38782209; PMCID: PMC11347793.

6 Sabia S, Fayosse A, Dumurgier J, Dugravot A, Akbaraly T, Britton A, Kivimäki M, Singh-Manoux A. Alcohol consumption and risk of dementia: 23 year follow-up of Whitehall II cohort study. BMJ. 2018 Aug 1;362:k2927. doi: 10.1136/bmj.k2927. PMID: 30068508; PMCID: PMC6066998.

7 Croteau E, Castellano CA, Richard MA, Fortier M, Nugent S, Lepage M, Duchesne S, Whittingstall K, Turcotte ÉE, Bocti C, Fülöp T, Cunnane SC. Ketogenic Medium Chain Triglycerides Increase Brain Energy Metabolism in Alzheimer’s Disease. J Alzheimers Dis. 2018;64(2):551-561. doi: 10.3233/JAD-180202. PMID: 29914035.

8 Durga J, van Boxtel MP, Schouten EG, Kok FJ, Jolles J, Katan MB, Verhoef P. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. 2007 Jan 20;369(9557):208-16. doi: 10.1016/S0140-6736(07)60109-3. PMID: 17240287.

9 Devore E et al, ‘Dietary intakes of berries and flavonoids in relation to cognitive decline’, Annals of neurology 2012; 72: 135-43; see also Agarwal P, Holland TM, Wang Y, Bennett DA, Morris MC. Association of Strawberries and Anthocyanidin Intake with Alzheimer’s Dementia Risk. Nutrients. 2019 Dec 14;11(12):3060. doi: 10.3390/nu11123060. PMID: 31847371; PMCID: PMC6950087.

11 Lamport DJ, Pal D, Moutsiana C, Field DT, Williams CM, Spencer JP, Butler LT. The effect of flavanol-rich cocoa on cerebral perfusion in healthy older adults during conscious resting state: a placebo controlled, crossover, acute trial. Psychopharmacology (Berl). 2015 Sep;232(17):3227-34. doi: 10.1007/s00213-015-3972-4. Epub 2015 Jun 7. PMID: 26047963; PMCID: PMC4534492.

12 Basambombo LL, Carmichael PH, Côté S, Laurin D. Use of Vitamin E and C Supplements for the Prevention of Cognitive Decline. Ann Pharmacother. 2017 Feb;51(2):118-124. doi: 10.1177/1060028016673072. Epub 2016 Oct 5. PMID: 2770818; see also Yu JT, Xu W, Tan CC, Andrieu S, Suckling J, Evangelou E, Pan A, Zhang C, Jia J, Feng L, Kua EH, Wang YJ, Wang HF, Tan MS, Li JQ, Hou XH, Wan Y, Tan L, Mok V, Tan L, Dong Q, Touchon J, Gauthier S, Aisen PS, Vellas B. Evidence-based prevention of Alzheimer’s disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials. J Neurol Neurosurg Psychiatry. 2020;91(11):1201-9. Epub 2020/07/22. doi: 10.1136/jnnp-

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

14 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.