This topic is always near-and-dear to my heart, as my former spouse of 22-years and several of my children have some level of autistic spectrum disorder (ASD). There is little doubt that I have some level of ADHD (which is where gain some of my superpower strength) and we all have variations of the MTHFR variant so our relationship with vitamin B12 (and magnesium) is significant.
Previously I wrote a bit about vitamin B12 deficiency, how this is so easily overlooked by today's clinician, is often under-treated, and how I like to address this issue for clients. I even touched a bit on autism's relationship directly with vitamin B12, but again, because this is such an important topic to me and because I know so many mothers are seeking additional tools and better understanding on #autism, I wanted to discuss this issue a little more thoroughly. The reality, as well, is that vitamin and micronutrient deficiency is an important and frequent health problem in children and adolescents (Kazanci et al., 2016).
Vitamin B12 (methylcobalamin and adenocyanocobalamin) is vital for synthesis of DNA, neurotransmitters, and the methylation process. It plays a critical role in the growth and development of the brain and the neurological system. When our vitamin B12 is low, we often notice increased forgetfulness, paresthesia, fatigue, hypotonia, decreased appetite, diarrhea, depression, hair abnormalities, growth retardation, and megaloblastic anemia. Vitamin B12 deficiency can reportedly progress to brain atrophy, leading to Alzheimer's disease, so it's a significant contributor to optimal health, particularly brain health.
Autism is a neuro-developmental disorder characterized by significant impairment in social interaction and communication. These individuals also typically have restricted interests or one primary hyperfocus and repetitive behaviors. Although several genetic syndromes are associated with ASD or autism spectrum disorder, all of these genetic syndromes together only account for a minority of ASD cases.
Research into understanding autism largely focuses on systemic physiologic abnormalities such as mitochondrial dysfunction, oxidative stress, and inflammatory/immune dysregulation; all hot topics in functional medicine, so you can imagine my distress at not being able to better help my own children. This is a complex condition, with so many challenges and far more which is just not well understood, even among the experts.
Several lines of evidence support the notion of an ASD endophenotype which demonstrates abnormal redox and methylation metabolism. This is particularly intriguing to me, as I mentioned our family has significant history with #MTHFR and also autism, as many of you may as well. Two case-control studies have now evaluated this phenomenon, finding the mean ratio of plasma S-adenosyl methionine (SAM) to S-adenosyl homocysteine (SAH), which is a reflection of cellular methylation capacity, to be significantly reduced in those with autism.
Also, the mean concentration of free reduced glutathione (GSH), the major intracellular antioxidant and mechanism for detoxification, was also significantly decreased and the oxidized disulfide form of glutathione (GSSG) was significantly increased. Several precursors for methylation and glutathione synthesis were also lower in the autistic children suggesting an insufficiency in the production of methylation and glutathione metabolites, at least in a subgroup of ASD children. And, researchers have demonstrated that GSH is significantly reduced in the cytosol and isolated mitochondria from lymphoblastoid cell lines and fresh peripheral blood mononuclear cells derived from children with autistic disorder (AD).
Glutathione
The essential intracellular reducing environment required for normal function is created by #glutathione, as well as redox-sensitive enzyme activity, and membrane redox signaling. Oxidative stress occurs when antioxidant defense mechanisms, our free radical fighters, fail to counterbalance reactive oxygen species created from endogenous oxidative metabolism or from pro-oxidant environmental exposures (meaning, from either by-products from biological systems within our bodies or from toxic exposures within our environment).
This theory that glutathione metabolism is associated with oxidative cellular damage is consistent with previous studies which demonstrate an increase in oxidative damage to protein and DNA in peripheral blood mononuclear cells and postmortem brain derived from ASD individuals. There are also several studies to support the hypothesis that redox imbalance and oxidative stress may be a contributing factor to autism pathophysiology.
The importance here is that we can offer support to these mechanisms clinically. Glutathione is a tripeptide of cysteine, glycine, and glutamate that is synthesized in each of our cells. This is tightly connected to methylation metabolism where it derives its cysteine precursor and we know that methylation and glutathione metabolism are abnormal in children with ASD. We also know that abnormal methylation metabolism will result in a depletion of the precursors needed for glutathione production. The question then is if we supplement glutathione or even methylcobalamin and oral folate as these can improve glutathione synthesis, might this improve adaptive behaviors in individuals with autism?
One study provided children 75 mg/Kg of #methylcobalamin every third day for three months and 400 mg of folic acid was administered twice daily by mouth, as a powder mixed with convenient food, and significant increases were found in all behavioral areas evaluated, including receptive, expressive, and written communication skills, personal, domestic, and community daily living skills, and interpersonal, play-leisure, and coping social skills (Frye et al., 2013). To illustrate the grand improvements realized, researchers demonstrated the years gained in maturity of skills. Communication for example, advanced on average, by 6.0 to 8.3 months and social skills improved between 5.4 and 12.0 months over only three months of treatment. In fact, all areas measured were improved by several months.
The goal of this study, conducted by Frye, MeInyk, Fuchs, Reid, Jernigan, Pavliv, Hubanks, Gaylor, Walters, & James (2013) was to identify if nutritional support with precursors for the abnormal metabolic pathways could result in improvement in ASD associated behavior as measured by the VABS and overall, significant improvement was noted in all subscales of the evaluation during the three-months of intervention. The adverse events were minimal and overall, this study provided excellent evidence for support for targeted nutritional support in children with AD who have metabolic abnormalities in glutathione and methylation pathways. Another double-blind placebo controlled study demonstrated that N-acetylcysteine, a glutathione precursor, resulted in decreased irritability and improved social function.
Ultimately the body of science has supported that nutritional interventions for children with ASD that target oxidative stress are associated with improvements in core ASD symptoms, sleep and gastrointestinal symptoms, and hyperactivity, tantruming and parental impression of general functioning. Methylcobalamin and folate treatments have demonstrated beneficial effects on detox metabolism in children with ASD. Glutathione metabolism can be improved with vitamin and mineral supplementation, as well as with antioxidants, coenzyme Q10 and B vitamin supplementation, and sapropterin treatment. Vitamin B12 supplementation offers a number of benefits, but most significantly, it has been found to reduce anxiety and depression (Frye et al., 2013). In fact, in teens with signs of unhappiness, their vitamin B12 should be evaluated as this is so significantly associated with their health and happiness.
Low vitamin B12 is associated with headaches, even sinusitis and dizziness, and supplementation can help. These are easy to take as well, as they can be placed under the tongue and dissolved. While many clinicians aim for levels higher then 200pg/mL to even 300pg/mL, my preferences is a minimum of 500pg/mL because at the lower levels, we seem improved vascularity or less neuropathy, particularly in those with diabetes, but at the higher levels, we see improved brain health and these are the minimum standards for most European countries.
References
Frye, R. E., Melnyk, S., Fuchs, G., Reid, T., Jernigan, S., Pavliv, O., Hubanks, A., Gaylor, D. W., Walters, L., & James, S. J. (2013). Effectiveness of methylcobalamin and folinic acid treatment on adaptive behavior in children with autistic disorder is related to glutathione redox status. Autism Research & Treatment.
Kazanci, S. Y., Saglam, N. O., & Omar, R. H. (2017). Vitamin B12 < 300pg/mL in children and especially adolescents may predispose forgetfulness, anxiety, and unhappiness.
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