Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms

Integr Med (Encinitas). 2017 Feb;16(1):42-49.


Context: Three natural forms of vitamin B12 are commercially available: methylcobalamin (MeCbl), adenosylcobalamin (AdCbl), and hydroxycobalamin (OHCbl), all of which have been shown in clinical studies to improve vitamin B12 status. They are bioidentical to the B12 forms occurring in human physiology and animal foods. In contrast, cyanocobalamin (CNCbl), a synthetic B12 compound used for food fortification and in some supplements, occurs only in trace amounts in human tissues as a result of cyanide intake from smoking or other sources.

Objective: This study had 3 objectives: (1) To summarize and compare assimilation pathways for 4 B12 forms; (2) to determine whether supplementation with a particular B12 form (or combination of forms) presents any advantages for the general population or for individuals with single nucleotide polymorphisms (SNPs) in B12-related pathways; and (3) to address misconceptions regarding B12 forms, methylation pathways, and various SNPs reported in commercially available tests.

Design: PubMed was systematically searched for articles published up to June 2016 using specific key words. Human, animal, and in vitro studies that were published in English, French, and German were included. Other studies considered were found by selecting in PubMed the suggested "related studies" and also some referenced studies.

Setting: The study occurred in Los Angeles, CA, USA.

Results: The studies reviewed provide evidence that all supplemental or food-derived B12 forms are reduced to a core cobalamin molecule, which converts to the intracellular active forms: MeCbl and AdCbl, in a ratio not influenced by the form of B12 ingested. The methyl and adenosyl components of supplemental MeCbl and AdCbl are cleaved inside cells and are not used in the synthesis of intracellular MeCbl and AdCbl, respectively. However, the overall bioavailability of each form of supplemental B12 may be influenced by many factors such as gastrointestinal pathologies, age, and genetics. Polymorphisms on B12-related pathways may affect the efficiency of absorption, blood transport, cellular uptake, and intracellular transformations.

Conclusions: Supplementing with any of the nature bioidentical forms of B12 (MeCbl, OHCbl, and/or AdCbl) is preferred instead of the use of CNCbl, owing to their superior bioavailability and safety. For the majority of the population, all B12 forms may likely have similar bioavailabilities and physiological effects; thus, it makes sense to employ the least-expensive form of B12, such as MeCbl. Individuals with particular single nucleotide polymorphisms (SNPs) affecting B12 assimilation may raise their B12 status more efficiently with 1 or more particular forms of vitamin B12. However, because those types of SNPs are not currently reported in commercial tests, individuals may require either a trial-and-error approach by supplementing with 1 particular form of B12 at a time, or they might simply use a supplement with a combination of all 3 naturally occurring forms of B12 that are commercially available for a better chance of achieving faster clinical results. That approach may or may not offset genetic polymorphisms involving B12 metabolism and related pathways.

Publication types

  • Review