The clinical review by Milly Ryan-Harshman and Walid Aldoori in the April 2008 issue of Canadian Family Physician requires comment.1 While I appreciate the efforts of the authors to review such a huge, unwieldy topic, I think one of the several dangers in doing so is that certain key elements are not covered. I refer in particular to the section on B12 and mental health. It appears that there is a huge volume of literature that has not been researched by the authors regarding this topic, and I note that prolific authors (such as Coppen and Bottiglieri, for example) are not even mentioned in the bibliography. Yet their contributions to the literature on vitamin B12, folic acid, S-adenosylmethionine, homocysteine, and depression are of paramount importance. Therefore, I think that Ryan-Harshman and Aldoori’s conclusion that B12 is “unlikely to substantially alter cognitive function or depression” is both inaccurate and unfair.
The other issue I have with review articles such as this one is the attempt to single out one particular element as having a beneficial effect. This attempt is inappropriate and unlikely to produce valid results, especially regarding vitamins and minerals. Vitamins and minerals work in concert; they work synergistically. Nowhere is this more evident and important than in the 1-carbon methylation cycle, which involves folic acid, vitamin B12, and homocysteine. This cycle, in and of itself, requires no less than 6 or 7 cofactors that must work together, in concert, for appropriate methylation of neurotransmitters and other important intermediates, as well as to remove toxic by-products. In fact, I would suggest that it is impossible to even consider vitamin B12 in relation to the treatment of depression without considering folic acid, S-adenosylmethionine, and vitamin B6, as well as tetrahydrobiopterin. This is notwithstanding the contribution that the methylene-tetrahydrofolate reductase polymorphism would make.
For future clinical reviews in which nutrients are being considered, I think it would be worthwhile for both the editors and the authors to consider the synergistic aspects of medicine and direct themselves away from the outdated concept that there is one specific treatment for one disease.
For an excellent recent review of depression, folic acid, and vitamin B12, I would refer the readers to the paper by Coppen and Bolander-Gouaille entitled “Treatment of depression: time to consider folic acid and vitamin B12.”2
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