Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism

Sj, James; Melnyk, Stepan; Fuchs, George J.; Reid, Tyra; Jernigan, Stefanie; Pavliv, Oleksandra; Hubanks, Amanda; Dw, Gaylor

doi:10.3945/ajcn.2008.26615

Cited by 221 publications

(249 citation statements)

References 39 publications

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“…The interdependence among folate, B12, and SAM and the importance of normal levels for optimal brain functioning has been discussed previously (Bottiglieri 2013). A 3 month open-label trial of injectable methyl B12 combined with folinic acid in 2009 in 40 children with ASD partially confirmed this hypothesis ( James et al 2009). Children supplemented with methyl B12 and folinic acid demonstrated significant increases in cysteine and glutathione (GSH) while reducing the oxidized inactive form of glutathione (GSSG), both consistent with improved antioxidant capacity.…”

Section: Introductionsupporting

confidence: 54%

“…Interestingly, we did not find that methyl B12 improved measures of oxidative stress (GSH/GSSG), which was seen in a previous open-label trial of 40 children with ASD ( James et al 2009). In the previous study, James et al screened children for metabolic evidence of reduced methylation capacity (SAM/SAH) and reduced antioxidant capacity (GSH/GSSG) as an inclusion criterion to increase sensitivity, and included folinic acid as a combined treatment with the methyl B12.…”

Section: Methyl B12 For Autismmentioning

confidence: 56%

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Randomized, Placebo-Controlled Trial of Methyl B12 for Children with Autism

Widjaja

et al. 2016

Journal of Child and Adolescent Psychopharmacology

106

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Objective: Children with autism spectrum disorder (ASD) have been reported to have reduced ability to methylate DNA and elevated markers of oxidative stress. We sought to determine if methyl B12, a key metabolic cofactor for cellular methylation reactions and antioxidant defense, could improve symptoms of ASD. Methods: A total of 57 children with ASD were randomly assigned to 8 weeks of treatment with methyl B12 (75 lg/kg) or saline placebo every 3 days in a subcutaneous injection. The primary outcome measure was overall improvement in symptoms of ASD as measured by the Clinical Global Impressions-Improvement (CGI-I) score. Secondary outcome measures included changes in the Aberrant Behavior Checklist (ABC) and the Social Responsiveness Scale (SRS). Laboratory measures of methionine methylation and antioxidant glutathione metabolism were assessed at baseline and 8 weeks.Results: A total of 50 children (mean age 5.3 years, 79% male) completed the study. The primary outcome measure -the clinician rated CGI-I score -was statistically significantly better (lower) in the methyl B12 group (2.4) than in the placebo group (3.1) (0.7 greater improvement in the methyl B12 group, 95% CI 1.2-0.2, p = 0.005). Clinical improvement among children treated with methyl B12 was positively correlated with increases in plasma methionine ( p = 0.05), decreases in S-adenosyl-lhomocysteine (SAH) ( p = 0.007) and improvements in the ratio of S-adenosylmethionine (SAM) to SAH ( p = 0.007), indicating an improvement in cellular methylation capacity. No improvements were observed in the parent-rated ABC or SRS. Conclusions: Methyl B12 treatment improved clinician-rated symptoms of ASD that were correlated with improvements in measures of methionine metabolism and cellular methylation capacity. Clinical Trial Registry: Efficacy Study of Subcutaneous Methyl B12 in Children with Autism: NCT01039792 (clinical trials.gov1).

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Section: Introductionsupporting

confidence: 54%

Section: Methyl B12 For Autismmentioning

confidence: 56%

Randomized, Placebo-Controlled Trial of Methyl B12 for Children with Autism

Widjaja

et al. 2016

Journal of Child and Adolescent Psychopharmacology

106

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“…James et al 129 reported improvement in glutathione and S-adenosylhomocysteine levels following open-label administration of methylcobalamin (methyl B 12 ) and folinic acid; again, however, there was no clinical correlation. Two double-blind, placebo-controlled studies on dimethylglycine (a methyl donor with potential activity at NMDA receptors) showed no treatment effects on Vineland Adaptive Scores, Aberrant Behavior Checklist, or Children's Psychiatric Rating Scale scores.…”

Section: Biologically Based Practicesmentioning

confidence: 99%

Complementary and Alternative Medicine in Autism: An Evidence-Based Approach to Negotiating Safe and Efficacious Interventions with Families

2010

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Summary: This review focuses on helping clinicians identify resources and develop strategies they may use to effectively negotiate safe and effective use of complementary and alternative medicine (CAM) treatments with families of children with autism spectrum disorders (ASD), as well as other neurodevelopmental disorders. Since new types of CAM continue to be introduced into the autism community, emphasis is placed on providing clinicians with tools to help families negotiate the myriad of available treatments and make decisions based on current safety and efficacy data, while remaining mindful of the reasons families may be considering these treatments.We familiarize readers with high-quality, evidence-based resources that providers and families may use to ascertain current information about specific types of CAM, verify the content of biologically-based treatments, identify ongoing CAM research and obtain toolkits designed to help healthcare providers raise the topic of CAM usage and facilitate disclosure and discussion of CAM use with patients and their families. Key Words: Complementary and alternative medicine, autism, integrative medicine, gluten-free casein-free diet, melatonin, chelation, hyperbaric oxygen treatment, evidence-based medicine.

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“…Very early detection of Hcy metabolic problems and supplementation with these essential factors could be a positive step towards preventing autism spectrum disorders, and this is a strategy that might be considered in pediatric preventive medicine. Supplementation in older autistic children may help to re-establish a correct metabolic profile (20), but the development of the nervous system is already established and the brain is not able to reverse the damaging processes and recover.…”

mentioning

confidence: 99%

Autism, imprinting and epigenetic disorders: a metabolic syndrome linked to anomalies in homocysteine recycling starting in early life??

Ménézo¹,

Marès

Cohen³

et al. 2011

J Assist Reprod Genet

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An association between imprinting syndromes and ART is now common knowledge. Imprinting problems are roughly linked to DNA methylation disorders, and clinical reports of ART-linked imprinting syndromes have implicated hypomethylation of the maternal alleles (1). Kattari et al. (2), examining DNA methylation in 700 genes, observed different levels of methylation between children conceived in vitro and in vivo. They also found that the differences observed in DNA methylation in the children conceived in vitro involved differences in gene expression for both imprinted and non-imprinted genes. This effect is observed even when maternal age is taken into account. We recently pointed out some aspects of in vitro and in vivo parameters that could be responsible for impairment of methylation processes in ART patients (3), in particular an increased concentration of homocysteine (Hcy) in the oocyte environment.Further to these observations, two articles recently presented at the International meeting for autism research in Philadelphia pointed out a correlation between Assisted Reproductive Technology and Autism. 111 women who had a child with an autism spectrum disorder (ASD) took part in the Nurses' Health Study II, which revealed that about 4% of mothers who took fertility drugs had a child with an ASD, compared to about 2% who did not take fertility drugs. In a second study, an Israeli group also observed an increased frequency in babies with ASD after ART: 10.5% of 461 children diagnosed with a disorder on the autism spectrum were conceived using IVF, significantly higher than the 3.5% autism rate in the general Israeli population. Two major metabolic problems are commonly involved in Autism disorders: altered thiol metabolism and increased homocysteine levels, and oxidative stress including mitochondrial dysfunction (4-8) In many cases a correlation is found with alterations in the mothers of autistic children (9, 10).One mechanism that oxidative stress/thiol metabolism and methylation (imprinting) have in common is the recycling of homocysteine (see Fig. 1). Recycling of homocysteine is a Capsule Monitoring and early supplementation with parameters linked to homocysteine metabolism immediately before and during pregnancy, as well as during early infancy of the child, could limit the risks of developing autism spectrum and imprinting related disorders.

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Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism

Cited by 221 publications

References 39 publications

Randomized, Placebo-Controlled Trial of Methyl B12 for Children with Autism

Randomized, Placebo-Controlled Trial of Methyl B12 for Children with Autism

Complementary and Alternative Medicine in Autism: An Evidence-Based Approach to Negotiating Safe and Efficacious Interventions with Families

Autism, imprinting and epigenetic disorders: a metabolic syndrome linked to anomalies in homocysteine recycling starting in early life??

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