B-12Forms

The Coenzyme Forms of Vitamin B12: Toward an Understanding of their Therapeutic Potential
Gregory Kelly, N.D.

Abstract

Although cyanocobalamin and hydroxycobalamin are the most commonly encountered supplemental forms of
vitamin B12, adenosyl- and methylcobalamin are the primary forms of vitamin B12 in the human body, and
are the metabolically active forms required for B12-dependent enzyme function. Evidence indicates these
coenzyme forms of vitamin B12, in addition to having a theoretical advantage over other forms of B12, actually
do have metabolic and therapeutic applications not shared by the other forms of vitamin B12. This article will
provide an overview of the metabolism and function of adenosyl- and methylcobalamin, and will discuss the
potential therapeutic relevance of the coenzyme forms of vitamin B12 in a variety of clinical conditions,
including anemia, anorexia, cancer, HIV, and liver and sleep disorders. (Alt Med Rev 1997;2(5):459-471)

Introduction

Cyanocobalamin (CN-Cbl) is the most commonly supplemented form of vitamin B12, but it is present in the
body in trace amounts and its biochemical significance remains uncertain. Although the amount of cyanide is
considered toxicologically insignificant, humans must remove and detoxify the cyanide molecule, reduce the
cobalamin to its usable +1 oxidation state, and then enzymatically convert the cobalamin into one of two
metabolically active coenzyme forms. Nutritional inadequacies, enzyme defects, and pathological changes to
tissues can all contribute to a reduced ability of the body to accomplish the synthesis of the active forms of
vitamin B12 from CN-Cbl.

The two forms of vitamin B12 having activity in B12-dependent enzymes within the human body are
adenosylcobalamin (AdeCbl) and methylcobalamin (MetCbl). AdeCbl is occasionally referred to as coenzyme
B12, cobamamide, cobinamide, or dibencozide. In some biochemical or therapeutic situations, the clinical
utilization of either AdeCbl or MetCbl (alone or in combination) can produce results not found with the
supplementation of either CN-Cbl or hydroxycobalamin (OH-Cbl).

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Conclusion

AdeCbl and MetCbl are the coenzyme forms of vitamin B12 utilized in the vitamin B12-dependent enzymes in
humans. Because the coenzyme forms bypass several of the enzymatic reactions required for the formation of
the functional forms of vitamin B12, they offer a theoretical advantage in cobalamin supplementation. Both
AdeCbl and MetCbl are retained in the body better and increase tissue concentrations of cobalamin better than
CN-Cbl. Additionally, the coenzyme forms of vitamin B12 demonstrate a range of activity and clinical results
not shown by the other supplemental forms of vitamin B12.

It is important to remember that circulating levels of vitamin B12 are not always a reflection of tissue levels,
and that even if an adequate supply of cobalamin appears in the circulation, a functional deficiency of the
coenzyme forms might coexist in tissues and other body fluids. Although CN-Cbl will usually increase
circulating levels of cobalamin, its ability to increase tissue levels of the active forms of vitamin B12 can be
limited in a range of sub-clinical and clinical conditions. Even in a best case scenario, the activation of CN-Cbl
to either AdeCbl or MetCbl does not occur instantly, possibly occurring over 1-2 months, and requires the
interaction of GSH, reducing agents, possibly alpha-tocopherol, and in the case of MetCbl, SAM and the active
form of folic acid.

The use of either AdeCbl and/or MetCbl offers a significant biochemical and therapeutic advantage over other
existing forms of vitamin B12, and should be considered as a first-line choice for correcting vitamin B12
deficiency and treating conditions shown to benefit from cobalamin administration.