Nutrigenomics and Autism

When you consider that mental health problems affect around 1 in 4 people throughout the United Kingdom, it should come as no surprise that conditions that fall into that category such as anxiety, autism, schizophrenia, depression, ADHD and Alzheimer’s make up a significant proportion of people seeking complementary healthcare throughout the UK.

Our article this week is provided by Anne Pemberton, who is a recognised expert in the field of nutrigenomics. She trained at ION between 2003 and 2006 and later completed her MSc in Nutrition at NCA where she currently works part-time as Course Director for the MSc in Nutrition Science and practice.

In this article, Anne uses Autism as a framework for explaining how the genome, epigenome and the environment all contribute to the phenotype of every individual, and discusses why a condition that 30 years ago only affected 1 in 2500 children, now affects 1 in 84.

Anne will be speaking at our Seminar in July on the topic of Nutrigenomics and how to implement it into your health practice. To find out more about this event and to book tickets, please follow this link.

Nutrigenomics and Autism

Nutrigenomics has come to be almost a household name in the world of CAM practice and at the heart of this, DNA is recognised as the “code of life” by most of us (Morrow 2014)1.

So how and why does this “code of life” change so drastically that we see major shifts in human evolution? It may be many more years before we can attempt to answer this question but if we look at the most complex of conditions we can start to see a picture building up.

The focus to date has been set on methylation and with good reason. Methylation defects, in particular high levels of Homocysteine are being seen as one aspect of the top 5 killer diseases of our time according to Holford (2003)2. However we now know that we need to go beyond Homocysteine for a full understanding.

We know that epigenetic changes are linked to disease and whilst correlation does not prove causation we still have a duty to explore these changes. The genome, epigenome and the environment all contribute to the phenotype of the individual. I hope to demonstrate how this works by using Autism as a framework.


Autism as a diagnosis has been around since Kanner’s seminal paper in 19433 but it laid fairly dormant in the literature until the late 1980’s, when an explosion of cases and a spectrum of associated conditions began emerging. At this point Autism was also starting to be viewed as a biomedical condition, rather than resulting from parenting failures.  Autism manifests through an impairment of socialisation and repetitive behaviours and is the condition so closely identified with an epigenetic basis.

Today we have a UK estimated incidence of 1 in 84 children according to the National Autistic Society. This has risen from 1 in 2500 in 1985. It would be prudent to research for reasons for the increase in such a short timescale and the controversy continues as to why we might be seeing more cases.

Reasons / Rationale

With a 60-90% concordance between identical twins and less than 10% for fraternal twins5 we have a high heritable component. However that still leaves a significant environmental factor to consider. Interestingly typical regression cases have also climbed. These are cases where the child appears to develop normally until the age of 16-24 months then massively declines in function.

Environmental factors can switch genes on and off thereby changing their expression so we do need to be mindful of these when looking at specific polymorphisms associated with the disorder.

So what are those polymorphisms in question?

The one that seems to be on everyone’s mind is Methyltetrahydrofolate reductase (MTHFR). We all know this enzyme as being pivotal in methylation. After all, it is the enzyme that provides the final stage of six in the conversion of folic acid to 5-methylfolate, thereby aiding the conversion of Homocysteine back to methionine.

Interestingly in Autism Spectrum Disorders it has become quite centre stage and the two graphs below might shed light on why. It was known as early as 1965 that 400mcg of Folic acid could prevent neural tube defects (NTD’s) in the foetus6. In 1991 the Centre for Disease Control recommended all women with a history of NTDs take 400mcg Folic acid5 and the incidence was reduced by 70%.

However in a seminal 2016 paper14 this incidence was estimated at 49 to 71%. Other papers have shown varied results and perhaps this is because those with MTHFR polymorphisms can’t make use of Folic acid and are therefore at higher risk of NTDs15. The graph below demonstrates the success of the intervention. Many countries have subsequently introduced folic acid food fortification programmes and the topic rears its head in Europe every few years with a view to food fortifying in Europe.
Busby et al (2005)7

 However there may be some caveats to this approach..

If we look at the second graph from the Weintraub4 study we see a cross correlation in the rise of diagnoses with Autism Spectrum Disorders. Ok so correlation does not prove causation but we can see why MTFHR might be the big guy on the circuit.


(Weintraub, 2011)4

 When we look further we find studies such as Pu et al’s (2013)9 meta analysis of 8 case control studies, totalling 1672 cases with ASD and 6760 controls. Pu found that the C677T polymorphism was associated with a higher risk of ASD in countries with or without folic acid fortification.  Whereas the A1298C polymorphism was associated with lowered risk.

That’s really cool and really important BUT and there is a big but here.  It isn’t the only enzyme we need for methylation and giving it centre stage can detract from other important factors.

In the James et al (2006)9 paper other alleles have been identified that also play a role in Autism. The impact of the expression of some of these alleles may increase the incidence of oxidative stress due to decreased plasma levels of cysteine, glutathione, and the ratio of reduced to oxidised glutathione. In addition other alleles may impact on B12 metabolism and neurotransmitter balance.

Nutrient Imbalances and Pyrrole Disorder

If we look at the work of Walsh (2014)11 he talks a lot about abnormal biochemistry associated with nutrient imbalances such as zinc deficiency, copper overload, B-6 deficiency and elevated toxic metals.

I find zinc and B-6 deficiency interesting as many eminent scientists have identified this, Bernard Rimland being one of the first. Along with haem (the oxygen carrying compound in the blood), manganese and biotin; B-6 and zinc are excreted with HemokryptoPyrroles (HPU) in Pyrrole disorder.

Pyrrole disorder seems a little elusive right now. You may see it being called Pyrroluria, Haemokryptopyrroluria, mauve disease, haemepyrrole HPU and KPU. It can best be described as the abnormal synthesis and metabolism of the oxygen carrying molecule in the blood, called haemoglobin. The metabolic by-product of haemoglobin is hydroxyhaemopyrrolin-2-one (HPL) or Pyrrole.

Excessive amounts of pyrroles bind to and inhibit the nutrients vitamin B6, zinc, biotin and the omega 6 fatty acid GLA from reaching their target tissues in the body. As the levels of these nutrients drop, a myriad of symptoms may occur from learning and behaviour disorders, mood disorders, digestive and musculoskeletal and skin disorders. General health then proceeds in a downward spiral.

Abraham Hoffer linked elevated pyrroles to schizophrenia as a genetic disorder but Trudy Scott and Dietrich Kilnghardt now say it can be acquired. In addition, dysbiosis, leaky gut syndrome, alcohol and smoking can dramatically increase pyrroles. They are classed as nerve poisons because they can damage nerves, nerve cells and tissues, leading to loss of vital messaging, especially in the brain.

Where Pyrrole disorder exists we need to consider a number of enzymes that are dependent on these nutrients for full function. Haem dependent enzymes include the CYP450 family, which we know mostly for the part they play in phase one liver detoxification.

Secondly Phenylalanine Hydroxylase (PAH), Tyrosine Hydroxylase, (TH), Tryptophan Hydroxylase (TPH), Nitric Oxide Synthase (eNOS), Dopa Decarboxylase (DDC) and Ornithine Decarboxylase (ODC) which govern bioterin recycling; Phenylalanine to Tyrosine to Dopamine to Arginine and Nitric oxide and of course Tyrosine to 5-HTP and Serotonin. B-6 is a cofactor for Cystathione beta synthase (CBS), Cystathionine Gamma-Lyase (CTH) and Cysteine Sulfinic Acid Decarboxylase (CSAD) which govern the conversion of Homocysteine to Glutathione and Taurine in the transsulfuration cycle. Not to forget of course Serine Hydroxymethyltransferase (SHMT1) in the folate cycle.

Zinc on the other hand is a cofactor in 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), Betaine–Homocysteine S-Methyltransferase (BHMT), Adenosine Deaminase (ADA) and Superoxide Dismutase (SOD).

So when we put this all together we see abnormal biochemistry such as undermethylation, oxidative stress10, low levels of glutathione, copper overload and insufficient caeruloplasmin, depressed metallothionein levels, low levels of magnesium, selenium and cysteine deficiency, pyrroles and carboxyethylpyrroles11.

The latter has been associated with the consequence of a severe loss of high-acuity central vision12. Is this why some individuals with Autism look out of the corner of their eyes?


While MTHFR is still on the tips of tongues we need to be mindful that other polymorphisms have been associated with ASD’s13. Addressing MTHFR alone is not enough and may in fact be dangerous due to the impact of “pushing” methylation without a full understanding of the impact of polymorphisms within the Folate, Biopterin and Transsulfuration cycles.

There is also this aspect of Pyrrole disorder; if this exists what would be the plan of action given that polymorphisms are potentially expressing within all the above cycles. The answers to this lie in the teachings that follow (see References below).

anne-pembertonAnne Pemberton

Anne has a background of 26 years of intensive care cardiothoracic nursing and psychology, and is a recognised expert in the field of nutrigenomics. She trained at ION between 2003 and 2006 and later completed her MSc in Nutrition at NCA where she currently works part-time as Course Director for the MSc in Nutrition Science and practice.

Anne’s fascination with the area of nutrigenomics has led her to co-develop the first post graduate nutrigenomics CPD course. The course is delivered twice yearly in London and York.

With many thanks to Anne for this article, if you have any questions regarding the health topics that have been raised please don’t hesitate to get in touch with me via phone (01684 310099) or e-mail (

Amanda Williams and the Cytoplan Editorial Team: Clare Daley, Joseph Forsyth and Simon Holdcroft

A Cytoplan Education Event – Saturday 2nd July, 10.00am – 5.00pm.

CAM Conference Centre, 22 Duchess Mews, London, W1G 9DT

ad-headerAnne will be speaking at our Cytoplan Seminar in July on how to implement nutrigenomics into your health practice. To find out more about this event, and to book your place, please follow this link. 

Editor’s Note on Folic Acid:

Whilst folic acid supplementation has clearly reduced the incidence of NTDs, there are concerns over supplementation with folic acid, particularly in those with MTHFR mutations. This is because  MTHFR mutations can mean there is up to a 70% reduction in the functioning of this enzyme, resulting in reduced production of active 5-methyltetrahydrofolate (5-MTHF).

As folic acid is not efficiently converted it can build-up in the body resulting in high serum levels of ‘unmetabolised folic acid’ (UMFA) which is correlated with an increased risk of certain cancers (although causation has not been established).

In addition folic acid has a long half-life and can block folate receptors – further reducing conversion of folates to active 5-MTHF. An MTHFR mutation increases the risk of neural tube defects. We therefore include the active ‘methylfolate’ in our pregnancy supplement – Pregna-Plan.

None of our supplements contain isolated ‘folic acid’ which is a monoglutamate. Some of our multiformulae contain ‘methylfolate’ and others contain folates from a food source (these are polyglutamates but are labelled as folic acid).


  1. Morrow, K.J. (2014) Cancer, Autism and Their Epigenetic Roots. North Carolina, McFarland & Company
  2. Holford, P and Braley J (2003) The H Factor Homocysteine, the Biggest Health Breakthrough of the Century. London Piatkus
  3. Kanner L. (1946) Autistic disturbances of affective contact. Nervous Child 2, 217-250
  4. Weintraub K. (2011)The prevalence puzzle: Autism counts. Nov 2;479(7371):22-4. doi: 10.1038/479022a.
  5. Freitag, C.M. (2007) The genetics of autistic disorders and its clinical relevance: A review of the literature. Molecular Psychiatry, 12(1) 2-122
  6. Hibbard B.M., Hibbard E.D., Jeffcoate T.N. Folic acid and reproduction. Acta Obstet. Gynecol. Scand. 1965;44:375–400. [PubMed]
  7. (2005) Centers for Disease Control and Prevention, authors. Use of folic acid for prevention of spina bifida and other neural tube defects—1983–1991. MMWR Morb. Mortal. Wkly. Rep. 1991;40:513–516. [PubMed]
  8. Busby, A., Abramsky, L., Dolk, H., Armstrong, B., Addor, M.-C., Anneren, G., … Steinbicker, V. (2005). Preventing neural tube defects in Europe: a missed opportunity. Reproductive Toxicology (Elmsford, N.Y.), 20(3), 393–402.
  9. Pu, D., Shen, Y., & Wu, J. (2013). Association between MTHFR gene polymorphisms and the risk of autism spectrum disorders: a meta-analysis. Autism Research : Official Journal of the International Society for Autism Research, 6(5), 384–92.
  10. James, S. J., Melnyk, S., Jernigan, S., Cleves, M. A., Halsted, C. H., Wong, D. H., … Gaylor, D. W. (2006). Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : The Official Publication of the International Society of Psychiatric Genetics, 141B(8), 947–56.
  11. Walsh, W.J.(2014) Nutrient Power: Heal your biochemistry and heal your brain. New York Skyhorse.
  12. Ebrahem, Q., Renganathan, K., Sears, J., Vasanji, A., Gu, X., Lu, L., … Anand-Apte, B. (2006). Carboxyethylpyrrole oxidative protein modifications stimulate neovascularization: Implications for age-related macular degeneration. Proceedings of the National Academy of Sciences of the United States of America, 103(36), 13480–4.
  13. Mitchell, E. S., Conus, N., & Kaput, J. (2014). B vitamin polymorphisms and behavior: evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline. Neuroscience and Biobehavioral Reviews, 47, 307–20.
  14. Pre-conception Folic Acid and Multivitamin Supplementation for the Primary and Secondary Prevention of Neural Tube Defects and Other Folic Acid-Sensitive Congenital Anomalies. (2015). Journal of Obstetrics and Gynaecology Canada, 37(6), 534–549.
  15. Kirke, P. N., Mills, J. L., Molloy, A. M., Brody, L. C., O’Leary, V. B., Daly, L., … Scott, J. M. (2004). Impact of the MTHFR C677T polymorphism on risk of neural tube defects: case-control study. BMJ (Clinical Research Ed.), 328(7455), 1535–6.

Last updated on 10th March 2016 by cytoffice


One thought on “Nutrigenomics and Autism

  1. Interesting article, and I do firmly believe that our environment affects us more than anyone would care to admit. However, one needs to be very careful with citing links with autism. It seems instances are increasing but this may also be down to better education and knowledge, and therefore more people receiving early diagnosis. I have been diagnosed with Asperger Syndrome at age 56; clearly I have had it all my life and environmental factors were perhaps not as affective as they are now. It seems my sibling may also have the condition, and that my father almost certainly had it, so we are also talking genetics here with such neurological conditions.

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