Synthetic vs Natural B12: Why the quality of your multi-vitamin does matter

Synthetic vs Natural B12: Why the quality of your multi-vitamin does matter

By Cliff Harvey

B12 is an essential vitamin, collectively known as cobalamin. Cobalamin contributes significantly to haematopoiesis (creation of blood cells), myelin synthesis and synthesis of epithelial tissue. As a coenzyme, it is also a principal component of fatty acid, carbohydrate and nucleic acid metabolism. Vitamin B12 and/or folic acid deficiency is one of the most common causes of hyperhomocysteinaemia (high homocysteine levels – a marker of cardiometabolic dysfunction).

The common form added to supplements cyanocobalamin is a synthetic form not found in foods in nature. The metabolism of cyanocobalamin leaves behind a cyanide residue that the body must then excrete. This is unlikely to cause problems for most people as the amount of cyanide left is extremely small, however it has been suggested that those with pre-existing kidney problems may have trouble excreting even these small amounts and that a methylcobalamin form is preferred (3) and it has been suggested for decades that cyanocobalamin should be replaced with a non-cyanide form of B12 (4) for general safety.
An alternative to synthetic vitamin B12 is a natural co-factor of B12 methylcobalamin.Vitamin B12 regulates, together with 5-methyl-tetrahydrofolic acid (folate), the remethylation of homocysteine to l-methionine and the subsequent formation of S-adenosylmethionine (SAMe). SAMe is essential to most biological methylation reactions including the methylation of myelin, neurotransmitters, and phospholipids (e.g., phosphatidylcholine). Methylcobalamin, having a methyl group is able to act as a methyl donor for these reactions (5), whereas the synthetic forms need to themselves be methylated in order to do this. This step may be limited in some people and even in healthy people taxes methylation pathways unnecessarily.
Naturally occurring cobalamins (like methylcobalamin) in food appear to be absorbed at a better rate than synthetic B12 (cyanocobalamin) (6). In dialysis patients a ‘remarkable’ homocysteine reducing effect was observed when methylcobalamin was added to high-dose folic acid supplementation (7). Although it has been suggested that there is an extremely rare genetic disorder for which cyanocobalamin may be effective (8) for almost all others for prudence it appears that methylcobalamin is a better, more effective and safer supplemental choice. 
1. Gröber, U., K. Kisters, and J. Schmidt, Neuroenhancement with Vitamin B12—Underestimated Neurological Significance. Nutrients, 2013. 5(12): p. 5031-5045.
2. Eussen, S.M., et al., Oral cyanocobalamin supplementation in older people with vitamin b12 deficiency: A dose-finding trial. Archives of Internal Medicine, 2005. 165(10): p. 1167-1172.
3. Vitamin B12 Deficiency. New England Journal of Medicine, 2013. 368(21): p. 2040-2042.
4. Freeman, A.G., Cyanocobalamin--a case for withdrawal: discussion paper. Journal of the Royal Society of Medicine, 1992. 85(11): p. 686-687.
5. Pfohl-Leszkowicz, A., G. Keith, and G. Dirheimer, Effect of cobalamin derivatives on in vitro enzymic DNA methylation: methylcobalamin can act as a methyl donor. Biochemistry, 1991.30(32): p. 8045-8051.
6. Matte, J.J., F. Guay, and C.L. Girard, Bioavailability of vitamin B12 in cows' milk. British Journal of Nutrition, 2012. 107(01): p. 61-66.
7.Koyama, K., et al., Efficacy of methylcobalamin on lowering total homocysteine plasma concentrations in haemodialysis patients receiving high‐dose folic acid supplementation.Nephrology Dialysis Transplantation, 2002. 17(5): p. 916-922.
8.Gherasim, C., et al., Pathogenic Mutations Differentially Affect the Catalytic Activities of the Human B12-processing Chaperone CblC and Increase Futile Redox Cycling. Journal of Biological Chemistry, 2015. 290(18): p. 11393-11402.


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