Adenosylcobalamin

About six weeks ago, just for kicks, I bought a bottle of adenosylcobalamin which is one of the co-enzyme forms of vitamin B12 (the other one being methylcobalamin). I have previously bought methylcobalamin and experimented with it (finding no effects). But in my 25 years of being vegan, I had never tried adenosylcobalamin. So for the last six weeks, I’ve been taking 3,000 µg per day on most days. If I have experienced any health changes from them, I haven’t noticed it.

But during this time, I have also been corresponding with someone who has been struggling with fatigue on a vegan diet and he claims that adenosylcobalamin has been helping him. I checked out some of the links he provided of other people who claim the same thing and added this paragraph to Alternatives to Cyanocobalamin: Methylcobalamin & Adenosylcobalamin:

“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 am not necessarily convinced that adenosylcobalamin was the reason for any of these people’s improvements as they are typically trying other things as well and there is also the placebo effect to consider, but the claim has become common enough that until more research is done, it is worth considering.

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22 Responses to “Adenosylcobalamin”

  1. Matt Says:

    Don’t knock the placebo effect!!

  2. M. Grey Says:

    W00t! Two of my favorite authors together! I didn’t realize you ate more processed foods than you let on here…makes me feel better about my own indulgences! 😉

  3. Jack Norris RD Says:

    M.,

    I haven’t tried to hide it! http://jacknorrisrd.com/how-much-processed-food-is-healthy/

  4. Miriam Says:

    Hello Jack,

    People at University of West London, UK, are currently conducting a study to see how effective is methylcobalamin on reducing homocysteine levels in vegetarians. I wanted to take part (they are recruiting volunteers now) but I didn’t qualify because they are looking for vegetarians/vegans who are not taking B12 supplements and who have plasma homocysteine levels > 10 micromol/l.

    (By the way, when I became vegan two years ago (after 20 years of being vegetarian) my B12 was 350 pg/ml and my homocysteine 10 micromol/l. After one year of being vegan and following your recommendations about B12 supplements, my B12 was 580 pg/ml and my homocysteine 7.3 micromol/l. I’m taking normal cyanocobalamin).

    I don’t think they are comparing methylcobalamin with other forms of B12, which is a shame. If you are interested, there is more information about the study here:
    http://clinicaltrials.gov/show/NCT01661309

  5. Jack Norris RD Says:

    Miriam,

    Yes, it’s too bad they aren’t comparing other forms of B12. It’s also too bad they aren’t measuring MMA levels — maybe they intend to but just didn’t include in the write-up. I also thought it was odd that their secondary outcomes are blood pressure and body weight. And 16 weeks? That seems like an unnecessarily long time. Hopefully they’ll take intermediate measurements. Should be interesting to see what they find.

  6. Richard Says:

    Hi Jack,

    I tried the adenosylcobalamin on its own but noticed no real changes from when I had been taking methylcobalamin. I decided, then, to take both together to see how that worked. I was wondering: Is this safe?

    According to the labels, these are the combined quantities of the various vitamins in the B12 supplements I’m now taking:

    Adenosylcobalamin: 3000 µg
    Methylcobalamin: 1000 µg
    Vitamin B6: 2 mg
    Folic acid: 600 µg

    (Note: This doesn’t include the B12 or other vitamins that I get in fortified foods like soymilk, nutritional yeast, etc.)

    My biggest worry is about the folic acid because I’d heard that it’s one of those vitamins that can be dangerous in too high of quantities. I tried looking online to see whether the same was true for B12, but I couldn’t find anything. Is there any information out there that indicates that the levels of vitamin intake that I’m describing can be harmful?

    Thanks,
    Richard

  7. Jack Norris RD Says:

    Richard,

    Do you think you are suffering from vitamin B12 deficiency?

    Side effects: http://veganhealth.org/b12/toxicity

    There are no known long-term chronic diseases known to be caused by too much B12.

    A recent meta-analysis of clinical trails also cast doubt on the concern regarding folic acid supplements causing cancer.

  8. Jack Norris RD Says:

    Here is that study:

    http://www.ncbi.nlm.nih.gov/pubmed/23440809

  9. Richard Says:

    Jack,

    One never knows of course (without the aid of medical tests), but I don’t think I have a B12 deficiency. I decided to combine the two B12 forms because of a line in the original post: “‘…other people report feeling better [from fatigue] only when taking both co-enzyme forms (adenosyl- and methyl-).'”

    I’m suffering from CFS and am looking for anything that can provide relief from my fatigue symptoms. (You may recall our having discussed this in email correspondence a week or two ago.) When I read this original post, I thought I’d give the adenosylcobalamin a try to see if it would help, but I didn’t notice any effects from it, good or bad. Remembering the line I quoted above about combining adenosyl- and methyl- B12, I thought I’d give that a try and take both varieties. It could easily have been the placebo effect, but I seemed to feel something definite.

    Thanks for the information about B12 and folic acid; it really sets my mind at ease. I think I’ll continue with both forms of B12 for a while and see if that continues to have positive effects for me.

  10. Jack Norris RD Says:

    Richard,

    Yes, now I remember. Good luck! Let us know how it goes.

  11. Dan Says:

    Jack, is there any physiological explanation that people who use both forms (methyl- and adenosyl-) would benefit in terms of fatigue or B12 deficiency than just using good old cyanacobalamin?

    I understand there are effects of B12 deficiency that go way beyond homocysteine elevation (for example the bone and CNS side effects of B12 deficiency), but if B12 is being repleted, what is the mechanism by which combined methyl/adenosylcobalamin supplementation would ameliorate fatigue (or any other bodily condition)?

    I’m just asking, not from skepticism, but I think I share some of Richard’s symptoms, although I do not qualify for a diagnosis of CFS according to the 1994 CDA criteria. I am also interested in going to pubmed myself to see if there are any trials on various B12 analogues in treating fatigue (whether CFS or idiopathic chronic fatigue).

  12. Jack Norris RD Says:

    Dan,

    I don’t know of any solid research suggesting that people need the co-enzyme forms of vitamin B12 (except possibly people who smoke heavily, have cyanide poisoning, or kidney problems and can’t clear cyanide efficiently). However, there might be some other people who have rare conditions that prevent the conversion of cyano to methyl and/or adenosyl.

  13. Dan Says:

    Jack,
    Thanks for that explanation. I went to PubMed and I found two interesting trials with contradictory results. In 1971, researchers in England did a double-blind randomized crossover trial of daily i.m. hydroxocobalamin vs placebo and found major improvements in self-reported happiness and some other parameters in tired patients who got the injection of B12 first. However, in 1989, no effects were seen in CFS patients who got a bovine liver extract injected which was rich in B12 (in its native form) and folate. I’ve posted the URL’s here:

    http://www.ncbi.nlm.nih.gov/pubmed/2684076

    http://www.ncbi.nlm.nih.gov/pubmed/4583554 [this one is free if you click on the link to go to the Br J Nutr website]

  14. Jack Norris RD Says:

    Dan,

    The second study indicates that the people were possibly B12-deficient, but doesn’t address the different forms of vitamin B12.

  15. Dan Says:

    Jack, I’ve ordered the first study from the library. You’re right in that both studies deal with hydroxocobalamin (the parenteral form) and not the oral forms. But it is interesting that there is so little evidence to suggest that B12 works for CFS. If anything, I would have expected that the I.M. form would work, since it’s been the standard for years and years for pernicious anemia, and clearly works for that disease. So if CFS is related to subclinical B12 deficiency, one would have expected to see something in the liver extract study. I’ll share any details that may interest your readers once I’ve gotten the full report.

  16. Jack Norris RD Says:

    Dan,

    I don’t see why most cases of CFS would be related to vitamin B12. Most people shouldn’t be vitamin B12 deficient.

  17. Dan Says:

    By definition, CFS is a diagnosis of exclusion. In other words, B12 levels would need to be normal (as well as TSH, ferritin, hemoglobin, and a few other laboratory values). Thus I should not have said “if CFS is related to subclinical B12 deficiency”.

    On the other hand, I saw one study from Scandinavia which looked at cerebrospinal fluid levels of homocysteine in patients with fibromylagia and chronic fatigue syndrome and found high levels — http://www.ncbi.nlm.nih.gov/pubmed/?term=9310111%5Buid%5D — “The most obvious finding was that, in all the patients, the homocysteine (HCY) levels were increased in the cerebrospinal fluid (CSF). There was a significant positive correlation between CSF-HCY levels and fatiguability, and the levels of CSF-B12 correlated significantly with the item of fatiguability and with CPRS-15. ”

    However, it was based on only 12 patients. I will try to get the full PDF.

  18. Richard Says:

    A small update:

    On the first day that I took the methyl and the adenosyl together, I felt a vague but definite sensation, something akin but not identical to a caffeine zing. (What I felt could have been psychosomatic; one never knows.) In any case, on the second day that I took both together, I felt that same sensation again, only in a muted form; and on the third day, and on every day after, I felt nothing at all.

    As far as anything more substantive than that, I can’t say that I felt any improvement in my CFS symptoms. For the first couple of days I felt pretty good, fairly fresh and energetic, but I had been feeling that way before taking the adenosyl. Somewhere around the third or fourth day I actually had a fairly significant recurrence of CFS symptoms, such as headache, mental “fogginess,” and of course debilitating fatigue. So I’m inclined to doubt that the adenosyl is providing any appreciable benefit to my health.

    So far I haven’t removed the adenosyl from my daily vitamin regimen, but given its apparent ineffectiveness I’m considering it.

  19. Jack Norris RD Says:

    Richard,

    Thanks for the update. I’m sorry it didn’t work, I wish it had, but I can’t say I’m surprised.

  20. Dan Says:

    RIchard,

    There is an interesting anecdote by someone named “Adam” getting major improvement in fatigue symptoms by taking methylcobalamin — http://nutritionfacts.org/questions/which-type-of-b12-is-best/ (scroll down to “Adam”)

    But he did not say he has CFS.

    My understanding is that the greatest body of evidence in the literature is on cyanacobalamin (oral) and hydroxocobalamin (intramuscular injections), with far less evidence on methyl- or adenosyl-. The two repletion studies in fatigue that I found were with the former two analogues, not the latter two analogues. However, since it takes time to replete yourself orally with any form of B12, I would not give up after only 2 weeks (or however long you have been going) – you may as well finish the bottles while you are at it. And any effect in days 1-3 is probably a “placebo” effect, either way. Lastly, if there is a possibility you are either B12-deficient or B12-resistant, the only way to know is to get an MMA done (serum B12 or homocysteine are much less helpful, in my experience). I think there are some individuals with pernicious anemia or other malabsorption syndromes (e.g. due to common drugs – metformin, nexium, prilosec) that would benefit more from intramuscular therapy than oral therapy. It’s unlikely but possible.

  21. Julie Says:

    It is NOT a placebo effect at all, and Jack Norris, you have not done your research!

    Please refer to both:

    This site & post regarding some very well regarded research:

    http://forums.phoenixrising.me/index.php?threads/adenosylcobalamin-the-very-large-gorilla-in-the-room.20229/

    As well as the metabolic effects of this co-factor of B-12 … of which there are two- Methylcobalamin and adenosylcobalamin. Adenosylcobalamin is necessary for the Citric Acid, or Krebs Cycle, which creates ATP or cellular energy. All very likely if one is suffering from Chronic Fatigue, Fibromyalgia, or similar disorders.

    It would be a shame not to at least offer all the information which is available to those who need it the most!

  22. Jack Norris RD Says:

    Julie,

    If you can show me a peer-reviewed study that shows adenosylcobalamin to be effective where cyanocobalamin fails in improving vitamin B12 status in the general population, I’ll be happy to reconsider my view that cyanocobalamin is an adequate source of B12 for most people.

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