Intended for healthcare professionals

Clinical Review

Vitamin B12 deficiency

BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g5226 (Published 04 September 2014) Cite this as: BMJ 2014;349:g5226

Active form of vitamin B12

In answer to Nicholas Nutt:

Strictly speaking, the term 'vitamin B12' has been defined as cyanocobalamin. This form does not occur in vivo. Nutt correctly states that cyanocobalamin releases a cyanide group for every molecule of B12 that is used. However, it is incorrect that hydroxocobalamin is the active form of the vitamin.

There are two active forms of the B12 enzyme in the human cell. First, Methylcobalamin acts as a co-enzyme for the conversion of homocysteine to methionine. Methionine then acts as a methyl-donor to a great number of reactions that need a methyl group, including the synthesis of myelin, serotonin, dopamine, noradrenalin, DNA and phospholipids.

Second, Adenosylcobalamin is a co-enzyme for the conversion of L-methylmalonyl-CoA into succinyl-CoA which feeds into the citric acid cycle.

Is it important which form is used in treatment? In most people, it does not matter. They can convert cyano- and hydroxo-cobalamin into the active forms needed. However, I have recently reported a case in which it did matter. The severe vitamin B12 deficiency, including dementia and psychosis, responded to treatment with high dose oral methylcobalamin, but not to equally high dose oral hydroxocobalamin. [1]

1. Rietsema WJ. Unexpected Recovery of Moderate Cognitive Impairment on Treatment with Oral Methylcobalamin. Journal of the American Geriatrics Society 2014;62(8):1611-12 doi: 10.1111/jgs.12966[published Online First: Epub Date]|.

Competing interests: No competing interests

12 September 2014
Wilhelmina J. Rietsema
GP
Nuffield Department of Primary Care Health Sciences, Radcliffe Observatory Quarter, Oxford OX2 6GG