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Vegan For Life
by Jack Norris, RD &
Ginny Messina, MPH, RD
Updates: |   JackNorrisRD.com

Methylcobalamin & Adenosylcobalamin



The typical non-cyanocobalamin forms of vitamin B12 in supplemental forms are methylcobalamin and adenosylcobalamin (also known as 5'-deoxyadenosylcobalamin, dibencozide, coenzyme B12, cobamamide, and cobinamide). Calling adenosylcobalamin "co-enzyme B12" is somewhat misleading because methylcobalamin is also a co-enzyme form of B12. Hydroxocobalamin is the form typically used in B12 injections.

Some researchers question whether these non-cyanocobalamin supplements are stable in their oral form. For this reason, much larger amounts are typically used with the hope that at least some is absorbed intact. One study suggests that once absorbed, methylcobalamin may be retained in the body better than cyanocobalamin (1).

I am unaware of any clinical trials testing the various forms of vitamin B12 against each other among the general population and most people seem to do well using cyanocobalamin. But some people with chronic fatigue report getting more relief from adenosylcobalamin than either methylcobalamin or cyanocobalamin (more info), while other people report feeling better only when taking both co-enzyme forms (adenosyl- and methyl-).

I received the following anecdotal report (2011):

I'd been taking 500 mcg of methylcobalamin for years, not knowing that the B12 dosages so often cited (daily 25 - 100 mcg) are just for cyanocobalamin. So, about a week ago I started taking 1000-2000 mcg of methylcobalamin instead of just 500 mcg, and I feel a difference!

A 2011 clinical trial from Korea found that 1,500 µg/day of methylcobalamin was effective at raising vitamin B12 levels, reducing or eliminating neurological symptoms of B12 deficiency, and lowering homocysteine levels (5). This trial was done on people who had a gastrectomy and, therefore, had vitamin B12 malabsorption, indicating that for most people 1,500 µg/day would be more than enough.

Methylcobalamin in a Small Sample of Vegans

Donaldson (2) (2000, USA) studied 3 vegans with elevated uMMA levels who were treated with 1/2 to 1 sublingual methylcobalamin tablet, 2 times/day for 3 weeks. Correspondence with the author (March 21, 2002) verified that these tablets contain 1,000 µg methylcobalamin each.

Two of the subjects' urinary MMA normalized while the remaining subject's stayed slightly elevated at 4.1 µg/mg creatinine (normal is < 4.0 µg/mg creatinine). Thus, at a rate of 1-2,000 µg/day, methylcobalamin appears to be absorbed at a high enough rate to improve B12 status in some vegans. Additionally, this indicates that the methylcobalamin was able to improve the MMA pathway which requires adenosylcobalamin (in other words, methylcobalamin was apparently converted into adenosylcobalamin in these people).

Therapeutic Use of Coenzyme Forms of B12

The coenzyme forms of B12 appear to be more effective in treating certain conditions than is cyanocobalamin (though they are often injected rather than taken orally). Kelly (3) (1997) reviewed the research on supplementing with the coenzyme forms of B12 (methylcobalamin and adenosylcobalamin). Results of studies performed on humans are listed here:

Table 1. Conditions Reported to Improve by Coenzyme Forms of B12
  Therapeutic dose recommended by Kelly3 Conditions reported to improve from treatment3,A
Methylcobalamin 1500-6000 µg/day Diabetic neuropathy
Hyperhomocysteinemia in diabetes
Sleep disordersB
Bell's Palsy
Adenosylcobalamin, aka:
5'-deoxyadenosylcobalamin, dibencozide, coenzyme B12, cobamamide, and cobinamide
1000-6000 µg/day Neurological problems secondary to anorexia
Hepatitis A
Viral hepatitisB
A - In many cases, treatment was not compared to cyanocobalamin
B - More effective than cyanocobalamin


Hydroxocobalamin is the form of B12 typically found in food. There are not many oral forms for people to take; it is normally injected. One study suggests that after injections, hydroxocobalamin is retained in the body better than cyanocobalamin (4).


1. Okuda K, Yashima K, Kitazaki T, Takara I. Intestinal absorption and concurrent chemical changes of methylcobalamin. J Lab Clin Med. 1973 Apr;81(4):557-67.

2. Donaldson MS. Metabolic vitamin B12 status on a mostly raw vegan diet with follow-up using tablets, nutritional yeast, or probiotic supplements. Ann Nutr Metab. 2000;44(5-6):229-34. The subjects receiving methylcobalamin was only a small part of this paper, mentioned on p. 232.

3. Kelly G. The co-enzyme forms of vitamin B12: Toward an understanding of their therapeutic potential. Alt Med Rev. 1997;2(6):459-471.

4. Tudhope GR, Swan HT, Spray GH. Patient variation in pernicious anaemia, as shown in a clinical trial of cyanocobalamin, hydroxocobalamin and cyanocobalamin-zinc tannate. Br J Haematol. 1967 Mar;13(2):216-28.

5. Kim HI, Hyung WJ, Song KJ, Choi SH, Kim CB, Noh SH. Oral vitamin B12 replacement: an effective treatment for vitamin B12 deficiency after total gastrectomy in gastric cancer patients. Ann Surg Oncol. 2011 Dec;18(13):3711-7. | link