Methyl- B12 + Autism
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder typified by limited social interaction skills and repetitive behaviours. Although approximately 25% of ASD is believed to be attributable to a genetic defect, recent studies have demonstrated that environmental influences contribute more than genetic factors in the etiology of autism. (1)
ASD and Metabolic Processes
Children with ASD have been shown to have specific deficits in important metabolic processes, include cellular methylation, and glutathione-mediated antioxidant defense.
A 2006 study of 80 children with ASD and 73 controls showed that the children with ASD had reduced methylation capacity and increased oxidative stress. (2)
In 2012, a study examined 68 children with ASD, 40 unaffected siblings, and 54 unrelated, unaffected, age-matched controls. The children with ASD again exhibited reduced methylation capacity compared to their unaffected siblings and the control group, which was associated with DNA hypomethylation and reduced glutathione antioxidant defense. (3) Increased DNA oxidative damage and markers of protein in the children with ASD also suggest functional consequences. (3)
Vitamin B12 and Methylation
Vitamin B12 is an essential factor in methionine transmethylation capacity, meaning that if there is a B12 deficiency, this important biological process will be negatively impacted.
Dietary sources of vitamin B12 are found only in animal products such as meat, fish, poultry, dairy foods, and eggs, or fortified products. This means that vegans and some vegetarians have a higher risk of deficiency and should speak to their healthcare professionals.
Trials have shown various benefits to supplementing vitamin B12 in children with ASD.
One 2009 study of 40 children with ASD found that supplementing with vitamin B12 and folinic acid significantly increased cysteine and glutathione, whilst decreasing the oxidised inactive form of glutathione. (1) Both of these reactions reliably improve antioxidant capacity.
Importantly, 37 of the 40 children from this study showed improvements in all measurements of the Vineland Adaptive Behaviour Scale. (1, 4) This study found a strong relationship between improved plasma glutathione levels and improvements in expressive communication, personal and domestic daily living skills, and socials skills for the children with ASD. (4)
One randomised controlled trial (RCT) compared the results of methyl B12 injections versus a placebo for 57 children with ASD. (1) The study found a statistically significant improvement in overall clinician-rated symptoms compared with children treated with placebo injections. (1) All improvements reported were correlated with changes in three metabolites; methionine, SAH, and the SAM/SAH ratio, which all also indicated an improvement in methylation capacity.
Importantly, in this study, children with ASD who responded the best to methyl B12 injections had much lower levels of methionine prior to commencing the study, which suggests that treatment with B12 might be particularly relevant to this subset of children with ASD. (1)
Promisingly, the small number of side effects noted in these studies were similar for the placebo group and the methyl B12 group. (5)
The results of these studies are promising, but the number of participants for both was quite low, warranting larger scale RCTs for further supportive evidence.
Methyl B12 supplementation does show potential for improving clinician-rated symptoms of ASD in children, especially for those who may have lower levels of methionine. This treatment may be a viable and low risk option for healthcare professionals to consider for patients with ASD.
Hendren RL, James SJ, Widjaja F, Lawton B, Rosenblatt A, Bent S. Randomized placebo-controlled trial of methyl B12 for children with autism. Journal of child and adolescent psychopharmacology. 2016 Nov 1;26(9):774-83.
James SJ, Melnyk S, Jernigan S, Cleves MA, Halsted CH, Wong, DH, Cutler P, Bock K, Boris M, Bradstreet JJ, Baker SM, Gaylor DW: Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet 141B:947–956, 2006.
Melnyk S, Fuchs GJ, Schulz E, Lopez M, Kahler SG, Fussell JJ, Bellando J, Pavliv O, Rose S, Seidel L, Gaylor DW, James SJ: Metabolic imbalance associated with methylation dysregulation and oxidative damage in children with autism. J Autism Dev Disord 42:367–377, 2012.
Frye RE, Melnyk S, Fuchs G, Reid T, Jernigan S, Pavliv O, Hubanks A, Gaylor DW, Walters L, James SJ: Effectiveness of methylcobalamin and folinic acid treatment on adaptive behavior in children with autistic disorder is related to glutathione redox status. Autism Res Treat 2013:609705, 2013.
Li YJ, Li YM, Xiang DX. Supplement intervention associated with nutritional deficiencies in autism spectrum disorders: a systematic review. European journal of nutrition. 2018 Oct;57(7):2571-82.
Written By Brittany Darling
NUTRITIONIST (BHSC), WESTERN HERBAL MEDICINE (ADV DIP),
CERT. PAEDIATRIC NUTRITION