Methyl vs. Cyano B12

Special note: A study was just released suggesting that the algae chlorella has vitamin B12 activity. I will be reporting on that as soon as I get the paper.

A paper was published in the July edition of Molecular Nutrition and Food Research reviewing the four different forms of vitamin B12 (1). The four forms are cyanocobalamin (CNCbl), hydroxocobalamin (HOCbl), methylcobalamin (MeCbl), and adenosylcobalamin (AdoCbl).

A quick summary is that MeCbl and AdoCbl are the two forms of vitamin B12 that are co-enzymes–the body actually uses these forms and needs both of them. But CNCbl is the form most commonly found in supplements and fortified foods while HOCbl is the form usually contained in B12 shots.

There has been a debate for about the last 10 years as to whether supplementing with the co-enzyme forms is better than supplementing with CNCbl or HOCbl. The paper by Obeid et al. suggests that people do not benefit more from the co-enzyme forms. Even for people with genetic defects of vitamin B12 metabolism, injections with HOCbl are preferable to supplementing with the co-enzyme forms.


Currently, we do not have sufficient evidence to suggest that the benefits of using MeCbl or AdoCbl override that of using CNCbl or HOCbl in terms of bioavailability, biochemical effects, or clinical efficacy. There is uncertainty regarding the claimed superior role of Cbl coenzyme forms for prevention and treatment of Cbl deficiency. However, HOCbl may be an advantageous precursor of the cofactors, particularly in the inherited disorders of metabolic Cbl processing. CNCbl is a more stable and inexpensive form that appears to be best suited for oral supplementation and parenteral [intravenous] treatment as well.



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1. Obeid R, Fedosov SN, Nexo E. Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency. Mol Nutr Food Res. 2015 Jul;59(7):1364-72. | link

7 Responses to “Methyl vs. Cyano B12”

  1. Tammy Schauf Says:

    I recently found out I have the MTHFR genetic mutation, homozygous C677T. Where can I get more info about the hydroxocobalamin injections and where I can get one without any unsafe preservatives? Thanks for all you do!

  2. Jack Norris RD Says:


    I have no inside info on that.

  3. Leonid Kalichkin Says:

    > The exceptions are those with rare genetic defects in vitamin B12 metabolism

    How does a person know if they has this genetic defect? Supplement with CNCbl until they realise they have developed B12 deficiency with elevated homocysteine or uMMA? Or do an expensive genetic test?

    Isn’t it rational to advise for three options: 1) supplementing with cheap CNCbl and keeping an eye on homocysteine and uMMA; 2) doing a genetic test and supplementing accordingly; 3) taking supplements that include co-enzyme forms?

  4. Jack Norris RD Says:


    Genetic defects in B12 metabolism are very rare and if you don’t suspect that you have one, you most likely don’t. But this has nothing to do with being vegan and since most of the general population doesn’t worry about this, there’s no reason for vegans to do so.

    According to the Obeid et al. report, taking the co-enzyme forms of the supplement probably won’t overcome the genetic defects because all the forms of B12 are stripped of their side group in the cell and then they’re added back. Hydroxocobalamin is recommended for people with genetic defects because it’s able to bypass the process to at least some extent.

  5. Jack Norris RD Says:

    After rereading the paper and my post, I realized that my sentence suggesting that people with genetic defects of B12 metabolism might benefit from the co-enzyme forms wasn’t accurate. That idea was so ingrained in me from my past assumptions, that I didn’t fully question it when writing the post. I’ve now changed it to reflect my best understanding of the research presented in the paper: “Even for people with genetic defects of vitamin B12 metabolism, injections with HOCbl are preferable to supplementing with the co-enzyme forms.”

  6. Sally-Anne Wilkinson Says:

    Hi Jack,

    I’m interested in your thoughts about the cyanide byproduct in cyanocobalamin? Do you think this would be detrimental to health at all?


  7. Jack Norris RD Says:


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