Clinical Trial of Methylcobalamin

I’m taking another break from vitamin K2 to report on a study that a reader passed on regarding methylcobalamin (1).

There has been very little testing of methylcobalamin and so I normally recommend taking cyanocobalamin because it is a more stable form of vitamin B12 and there are anecdotal reports of people needing large doses of methylcobalamin to achieve results.

A 2011 clinical trial from Korea sheds some light on this issue. The study was done with people who had their stomachs removed (gastrectomy) due to cancer. Patients who have had a gastrectomy can no longer produce intrinsic factor, a molecule required for efficient B12 absorption, and they are typically given B12 injections.

In this trial, patients took 1,500 µg of methylcobalamin each day.

At baseline, their B12 levels were an average of 170 pg/ml and 24 out of 30 had tingling in their hands and feet, the traditional sign of vitamin B12 deficiency. Many had other indicators as well, including elevated homocysteine (an average of 17.5 µg/l). Over the course of the 3 month trial, vitamin B12 levels steadily increased to an average of 810 pg/ml, homocysteine steadily decreased to 11.4 µg/l, 28 patients experienced symptom relief, and 16 patients were free of all symptoms.

A drawback to this trial is that it did not have a placebo group; all the patients knew they were receiving vitamin B12. But these results are, in my opinion, too impressive to be due simply to placebo and based on the homocysteine and symptom improvement, it appears safe to say that 1,500 µg per day of methylcobalamin should be enough for just about anyone.

I have added a paragraph about this study to the Methylcobalamin & Adenosylcobalamin page at


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1. 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

7 Responses to “Clinical Trial of Methylcobalamin”

  1. Dan Says:

    What is amazing to me is that you can remove 95%+ of someone’s stomach and still achieve physiological levels of B12 in the human body using the oral route. I guess the less efficient downstream site of absorption becomes the major prevailing mechanism, if you give very large oral amounts. I have a semi-vegan patient (not gastrectomized) with documented B12 deficiency which has not responded to sublingual B12 drops. Her naturopath recommended that she start injections but she does not know the dose of what was in those drops. I told her to consider increasing her oral dose to a much higher, prescribed level AND combine these with shots her naturopath recommended (though of course, just doing shots alone should be adequate, but at least this way, she has a back-up route of protection if she misses a shot).

  2. Humprey Says:

    Hello again Dr. Jack!

    I want to ask for your thought about RDA of Methylcobalamin? Although your seem to say 1.5mg may be ok for everyone, it seems the Methylcobalamin RDAs I’ve read here so far are all for treatment purposes. What about supplimentary purpose?

    Since, if I’m not mistaken, your RDA for Cyanocobalamin can be 1mg 2x/week, it seems to me a high difference for Methylcobalamin to be 1.5mg/day, but of course they are different elements.

    Thanks for any suggestion!

  3. Jack Norris RD Says:


    I don’t understand your question, but maybe this will help: It appears to require much larger doses of methylcobalamin to achieve the same results as cyanocobalamin. There is anecdotal evidence to think that 1,000 µg per day of methyl is enough for most people, but the study above is evidence that 1,500 µg is most definitely enough.

  4. Humprey Says:

    Dr. Jack,

    Allow me to clarify. It seems to me in this page, as well as this - – , which suggested Methylcobalamin of at least 1,000ug are for treatment purposes, namely, having deficiencies (in this page they don’t have “intrinsic factors” anymore due to gastrectomy, and on the link’s case they have “elevated uMMA levels who were treated”). These makes me think that those cases requires more than those who don’t have deficiencies (what I called “supplimentary purposes”).

    Nevertheless, your response clarify one of my inquiries, that is, Methylcobalamin seem to require larger dose to match the effect of Cyanocobalamin. So perhaps, that dose which I called for “treatment purposes” would be just the same for “supplimentary purposes”.

    Thanks for your response!

  5. Konstantinos Says:

    Hi Jack,

    I would like to ask you about MMA test. Is it better the urine measurement or serum to check for B12 deficiency. You give here the B12 values:

    Today, I read that urine measurement is the better test.

    Is it possible someone who has normal serum MMA values, to have B12 deficiency?

    And if you choose serum MMA or urine MMA, how many days ago, you should stop taking supplements?

    Thank you!

  6. Jack Norris RD Says:


    Dr. Greger isn’t saying that a urine MMA test is better than a serum MMA; rather, he’s saying that a urine MMA is better than a serum B12 test. My article, Should I Get My B12 Status Tested?, should answer the rest of your questions:

  7. Konstantinos Says:

    Thank you Jack,

    I misunderstood what Dr Greger is saying.

    I tried to compare them and i found opposite information.

    For example in page 171 of this article says:

    “Serum MMA is more sensitive and reliable than urine MMA because the urine level can be affected by diet and sample collection. However, renal insufficiency can falsely raise serum MMA but not urine MMA results.”

    On the other hand, in the introduction of this article
    “MMA is biochemically more stable in urine than in serum and has a 40-fold greater concentration in urine [10]. Urinary methylmalonic acid (uMMA) concentration offers a potentially useful functional marker of Vit B12 status.”

    Thank you again!

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