Vegan For Life
by Jack Norris, RD &
Ginny Messina, MPH, RD
Methylcobalamin & Adenosylcobalamin
The absorption of supplemental vitamin B12 in the forms of methylcobalamin and adenosylcobalamin has not been fully elucidated. Common recommendations are to not rely on less than 1,000 µg/day. While there is some evidence that this amount might not be necessary, it would be prudent to use such an amount until more is known. For most people, cyanocobalamin is a less expensive, more reliable form of vitamin B12 to rely on.
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 and usually much higher doses of methylcobalamin are used–typically 1,000 µg/day.
A 1971 study found that at doses of 1 µg, 5 µg, and 25 µg, cyanocobalamin, hydroxocobalamin, methylcobalamin, and adenosylcobalamin were all absorbed at about the same rate (6). However, the researches suggested, based on other research, that at higher doses, cyanocobalamin is better absorbed. They theorized that this could be because absorption of methylcobalamin by way of intrinsic factor is efficient while cyanocobalamin is better absorbed through passive diffusion.
Here's a table of the absorption rates:
A 1973 study suggests that once absorbed, methylcobalamin may be retained in the body better than cyanocobalamin (1).
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. There was no comparison group receiving cyanocobalamin.
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-).
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).
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).
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.
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
6. Adams JF, Ross SK, Mervyn L, Boddy K, King P. Absorption of cyanocobalamin, coenzyme B 12 , methylcobalamin, and hydroxocobalamin at different dose levels. Scand J Gastroenterol. 1971;6(3):249-52. | link