Form Comparison

Cyanocobalamin vs Hydroxocobalamin

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

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Quick verdict. For oral supplements, cyanocobalamin is the cheaper, more stable, better-studied choice. Hydroxocobalamin earns its place by injection: it binds plasma proteins more tightly, so intramuscular doses last longer and can be given less often. Choose hydroxocobalamin if you are on an injection regimen and want longer intervals; for tablets, cyanocobalamin.

Side by Side

Cyanocobalamin Hydroxocobalamin
Absorption High High
How it is absorbed Bound by intrinsic factor and absorbed in the terminal ileum; this route saturates at about 1.5-2 mcg per dose. About 1% of a large oral dose also crosses by passive diffusion, which is why 1,000 mcg oral doses work even without intrinsic factor. Binds plasma proteins more tightly than cyanocobalamin, so injected doses are retained longer and need less frequent dosing.
Typical dose 25-1,000 mcg daily; 1,000-2,000 mcg for malabsorption 1,000 mcg intramuscular per protocol; 1,000 mcg oral
Common uses general supplementation, deficiency treatment, fortified foods injectable B12 (standard in the UK), cyanide poisoning antidote (high dose)
Side effects Very well tolerated. The cyanide content is toxicologically trivial. Injection site pain; red urine at antidote doses.
Cost Low Moderate
Also called vitamin B12 hydroxycobalamin, vitamin B12a
Labels in index 871 65

When to Choose Cyanocobalamin

Choose cyanocobalamin when you want the most studied, stable, and cheapest form. Synthetic and the most stable form. Converted in cells to methylcobalamin and adenosylcobalamin. Most clinical trials used it.

Cyanocobalamin

The best-studied oral form and the one used in the trials of high-dose oral therapy. Stable and inexpensive.

What to look for: 1,000 mcg tablets for malabsorption or treatment; 25-100 mcg daily for vegans with normal absorption.

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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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Products on Titrate

In Titrate's index of NIH label data, 871 labels named as vitamin B12 products list cyanocobalamin and 65 list hydroxocobalamin.

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.