B12 in Autism |
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B12 levelsThen the quantity found in serum has not been adequately repeated such that we can see repeated information coming from the scientific results. B12 is present as a vitamin in the diet that requires cobalt in very small amounts to be present. It is best absorbed from the terminal areas of the ileum.
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Cobalamin |
Serum
levels found in autism
This has
not been measured and published by many
groups, despite the method being fully available by many medical groups throughout
the world. The suggestion is that it is
not so much a low level of B12 but rather of the methylated product of it. This also has no adequate data.
Paşca SP, Nemeş B, Vlase L, Gagyi CE, Dronca E, Miu AC, Dronca M. High levels of homocysteine and low serum paraoxonase 1 arylesterase activity in children with autism. Life Sci. 2006 Apr 4;78(19):2244-8. Epub 2005 Nov 17. (This measured also the B12 levels and found them to be low or low normal).
Methylcobalamin used as a potential treatment
The consideration has been that there has been inadequate methylation capacity and that the addition of the methyl format of vitamin B12 may actually cause this to be modified. The work by James indicated that many changes were seen in the oxidative stress pathways (and the formation of compounds to prevent it) should this be given as a treatment. Can I recommend going through this article to try to understand the change seen in the oxidative, transsulphuration and methylation pathways:
James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004 Dec;80(6):1611-7.
(“The addition of
injectible methylcobalamin to the protocol (intervention 2) was based on
empirical observations of clinical improvement in speech and cognition (by JAN)
and the possibility that it might enhance methionine synthase activity under
conditions of oxidative stress by replacing oxidized inactive coenzyme B-12
[cob(II)alamin] or by posttranslational upregulation of methionine synthase, or
both. One month after the addition of
methylcobalamin, the methionine concentrations were within the control range”)
Deth R, Muratore C, Benzecry J, Power-Charnitsky VA, Waly M. How environmental and genetic factors combine to cause autism: A redox/methylation hypothesis. Neurotoxicology. 2008 Jan;29(1):190-201. Epub 2007 Oct 13. Review.
Neurological rarity. Functional vitamin B12 deficiency M R Turner, K Talbot Practical Neurology 2009;9:37-45; doi:10.1136/jnnp.2008. They describe a case of functional vitamin B12 deficiency where the repeated measurement of a serum B12 level within the normal range led to delay in the diagnosis of subacute combined degeneration of the spinal cord, and possibly permanent neurological damage as a result. Failure of intracellular transport of B12 by transcobalamin-2 can lead to functional B12 deficiency but with apparently normal serum levels, and is suggested by raised levels of either serum methylmalonic acid or homocysteine, associated with low levels of transcobalamin-2. In which case they may find that high dose injection of B12 may actually get around the problem.
Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. James SJ, Melnyk S, Fuchs G, Reid T, Jernigan S, Pavliv O, Hubanks A, Gaylor DW. Am J Clin Nutr. 2009 Jan;89(1):425-30. The results indicated that pretreatment metabolite concentrations in autistic children were significantly different from values in the control children. The 3-mo intervention with methyl cobalamine and folinic acid resulted in significant increases in cysteine, cysteinylglycine, and glutathione concentrations (P < 0.001). The significant improvements observed in transmethylation metabolites and glutathione redox status after treatment suggest that targeted nutritional intervention with methylcobalamin and folinic acid may be of clinical benefit in some children who have autism.
Transmethylation pathway
This is a complex pathway (see below) in which methyl groups
are transferred to specific molecules.
Diagram
of tetrahydrofolate (THF)-dependent pathway of methionine transmethylation to
homocysteine and the transsulfuration pathway from homocysteine to GSH
synthesis. MS, methionine synthase; SAH, S-adenosylhomocysteine; SAHH,
SAH hydrolase; GSSG, oxidized glutathione disulfide; SAM, S-adenyosylmethionine;
MTase, methyltransferase. (taken from James SJ et all, Am J. Clin Nutr
2009;89:425-30, which should looked at for fuller explanation).
From what you can see redox potentions through GSH/GSSH
ratios can be measured, plasma levels of cysteine, homocysteine and methionine
may be of meaning, and the levels of purines in the blood may also be of
significance. What has been found is
that all are altered in autism.
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