Methyl B12: Shown to reduce autism symptoms


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If you are a nutrition practicing health professional you’ve likely heard of methyl B12. If you’re a patient or this is new to you as a practitioner, you will enjoy learning about this important subject.

An exciting study indicates that supplementation with methyl B12 (the coenzyme or active form of vitamin B12 which is also known as methylcobalamin) could lead to an overall amelioration of autism symptoms by improving DNA methylation [1]. You see, not all genes are active at all times: it is the role of DNA methylation, an epigenetic mechanism, to turn a cell’s genes on and off at the appropriate time – this process appears to be impaired in many individuals with autism [2].

methyl-B12-autismWhat exactly is methylation?

It seems that methylation has become the latest buzzword in the health world and for good reason: methylation is an essential biochemical process that occurs over a billion times per second in every single cell of our body. To keep things simple (and avoid putting you to sleep), methylation occurs when a methyl group (a carbon atom linked to three hydrogen atoms) is passed to another molecule.

So why should you care about methylation?

Listing all the roles of methylation is beyond the scope of this article but, in a nutshell, methylation is a necessary process used by cells to control gene expression – this type of methylation, known as DNA methylation, is vital for healthy growth and development. DNA methylation also enables suppression of retroviral genes as well as other potentially hazardous sequences of DNA that may impair a person’s health.

Methylation is also involved in:

  • The production of vital substances such as glutathione which controls oxidative stress or melatonin, a hormone involved in sleep regulation.
  • The body’s optimal use of nutrients.
  • The body’s production of energy (ATP).
  • Immune function.
  • Natural detoxification pathways.
  • The brain’s activities and the production of neurotransmitters – defects in the methylation cycle have been linked to various cognitive behavioral issues and may contribute to the development of autism [3]. Moreover, children with autism also experience higher oxidative stress levels and have lower levels of biotin, vitamins B5 and E and total carotenoids [4]. These vitamins are involved in energy production in the body and also possess antioxidant properties. Put simply, children with autism have a decreased capacity for methylation which makes them more vulnerable to depression, infections, brain fogs, irritability and fatigue. Now that you have the basics, let’s go back to the methyl B12 study.

The study protocol

A total of 50 children with autism spectrum disorder completed this 8-week study – they were either given subcutaneous injections of methyl B12 (75μg/kg) or saline placebo (the control group) every three days. Neither the researchers nor the participants knew who was receiving the methyl B12 and who was getting the placebo until after the study. To determine the efficacy of the treatment, the researchers utilized the Clinical Global Impressions Improvement (CGI-I) scale after the 8-week study period. In this study, this scale was used to assess overall improvement of autism symptoms by evaluating the severity of the symptoms from 1 (very much improved) to 7 (very much worse). The researchers also used the Aberrant Behavior Checklist and the Social Responsiveness Scale during their assessment. Laboratory assessments were also conducted to evaluate methionine methylation and antioxidant glutathione metabolism.

Study findings

Compared to the children who received the saline injections, those who were treated with methyl B12 showed considerable improvements in overall symptoms as shown by the CGI-I scale results. However, no significant difference was found between the two groups regarding the two other measures which assessed the severity of specific autism symptoms.

Why did the researchers use methyl B12 (and not another member of the B12 family)?

Previous research indicates that individuals with autism have low levels of vitamin B12 in their brain which could explain why neurological and neuropsychiatric symptoms are common in this population [5]. To understand why methyl B12 was used in this study, it can help to understand that out of the vitamin B12 family, only methyl B12 is able to directly activate the methionine/homocysteine pathway which is involved in fueling the brain, metabolism and muscle growth. If this pathway is not activated (that is homocysteine is not re-methylated and converted back to methionine, homocysteine will build up in the blood where it can cause numerous health issues).

In a nutshell, here’s how the remethylation of homocysteine to methionine occurs: initially, methionine synthase catalyzes this remethylation reaction by using a methyl (CH3) group from 5-methyltetrahydrofolate (5-MTHF). This methyl group is then transferred to the reduced form of cobalamin to generate methylcobalamin (methyl B12) and tetrahydrofolate. Next, the methyl group is transferred from methyl B12 to homocysteine – this generates methionine. As you can see, for methylation to be effective, the body needs both folate and methyl B12.

What this means for a client/patient:

  • Keep in mind that there are many forms of vitamin B12 on the market. As a nutrition or health care professional, you want to ensure that you recommend a quality methylcobalamin supplement and not cyanocobalamin which is a cheap, dangerous synthetic form of the vitamin.
  • Note that folic acid is also the synthetic version of folate – in other words, they are totally different. Everybody should steer clear of folic acid, not only those individuals with autism or methylation issues.

I always recommend individuals work with a good integrative physician or nutrition professional.  They can test B12 status, most often with an organic acid urine test looking at MMA levels (methylmalonic acid), rather than blood levels which can be deceiving. If you are a nutrition professional you will want to  recommend the proper dose and form. Most often that will be methylcobalamin as the study highlights, but there are also adenosyl- and hydroxy- forms, as well as sublingual, injections, and other methods of administration. Other articles in the future (and our BioIndividual Nutrition Training), address these other forms; however, since the focus of this study was on methyl B12, we’ll save the others for another day.


1. Hendren, R. L., James, S. J., Widjaja, F., Lawton, B., Rosenblatt, A., & Bent, S. (2016). Randomized, placebo-controlled trial of methyl B12 for children with autism. Journal of child and adolescent psychopharmacology. [Access the original article here.]

2. Menezo, Y. J., Elder, K., & Dale, B. (2015). Link between Increased Prevalence of Autism Spectrum Disorder Syndromes and Oxidative Stress, DNA Methylation, and Imprinting: The Impact of the Environment. JAMA pediatrics169(11), 1066-1067.

3. James, S. J., Cutler, P., Melnyk, S., Jernigan, S., Janak, L., Gaylor, D. W., & Neubrander, J. A. (2004). Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. The American journal of clinical nutrition80(6), 1611-1617.

4. Adams, J. B., Audhya, T., McDonough-Means, S., Rubin, R. A., Quig, D., Geis, E., … & Barnhouse, S. (2011). Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity. Nutrition & metabolism8(1), 1.

5. Zhang, Y., Hodgson, N. W., Trivedi, M. S., Abdolmaleky, H. M., Fournier, M., Cuenod, M., … & Deth, R. C. (2015). Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia. PloS one11(1), e0146797-e0146797.

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