Form Comparison

Hydroxocobalamin vs Methylcobalamin

How hydroxocobalamin and methylcobalamin differ in potency, absorption, tolerance, and cost.

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Quick verdict. Methylcobalamin is the oral choice of the two, widely sold as 500-1,000 mcg tablets and lozenges. Hydroxocobalamin is mainly an injectable, favored because it is retained longer than other forms, so intramuscular doses can be spaced further apart. Choose hydroxocobalamin for an injection regimen, and methylcobalamin or cheaper cyanocobalamin for daily oral use.

Side by Side

Hydroxocobalamin Methylcobalamin
Absorption High High
How it is absorbed Binds plasma proteins more tightly than cyanocobalamin, so injected doses are retained longer and need less frequent dosing. Same intrinsic factor and passive diffusion pathways as cyanocobalamin. Cofactor for methionine synthase in the cytosol.
Typical dose 1,000 mcg intramuscular per protocol; 1,000 mcg oral 500-1,000 mcg daily
Common uses injectable B12 (standard in the UK), cyanide poisoning antidote (high dose) general supplementation, neuropathy (limited evidence)
Side effects Injection site pain; red urine at antidote doses. Very well tolerated.
Cost Moderate Moderate
Also called hydroxycobalamin, vitamin B12a methyl B12, mecobalamin
Labels in index 65 848

When to Choose Hydroxocobalamin

Choose hydroxocobalamin when you are on an injection regimen and want longer intervals. The natural form produced by bacteria.

Hydroxocobalamin

Longer retention than cyanocobalamin, which is why it is the injection of choice in much of the world.

What to look for: Mainly relevant as a prescribed injection. Oral hydroxocobalamin offers no proven advantage.

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When to Choose Methylcobalamin

Choose methylcobalamin when you prefer a cyanide-free active form and accept a modest premium. Less stable to light. Cells strip the methyl group on uptake and rebuild both active cofactors, so the form taken matters less than the dose.

Methylcobalamin

Fine, but not superior. Cells rebuild the active cofactors regardless of the starting form.

What to look for: Light-protective packaging and the same microgram dose you would use for cyanocobalamin.

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Products on Titrate

In Titrate's index of NIH label data, 65 labels named as vitamin B12 products list hydroxocobalamin and 848 list methylcobalamin.

Open supplement search

Supplement Search loads one category at a time. Choose the B-Complex tab, then type a form such as "cyanocobalamin" under Must contain, or a form to avoid under Must not contain.

Related

References

NIH Office of Dietary Supplements. Vitamin B12: Fact Sheet for Health Professionals.

Berlin H, Berlin R, Brante G. Oral treatment of pernicious anemia with high doses of vitamin B12 without intrinsic factor. Acta Med Scand. 1968;184(4):247-258.

Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160.

Lam JR, et al. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442.

Aroda VR, et al. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754-1761.

Wang H, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev. 2018;3(3):CD004655.