How we wish to be cited:
Norberg B. Folate and cobalamin deficiency – depressive and cognitive symptoms [debate]. Rondellen 2004; 20. URL: http://www.rondellen.net

Among hematologists of the past, 1960-80, it was a credo that cobalamin - and presumably folate - affects mood and mind. This conviction was based on observations of individual patients recovering from deep deficiency by adequate therapy. Thus, it is a logical step that current epidemiologists have developed a renewed interest in the monocarbon metabolism and its role in depressive disorders (1-3).

It is evident from Table 1 that the association (correlation) between deficiency of cobalamin/folate and depressive disorders might be complex; disturbances of the monocarbon metabolism could create mental disorders. On the other hand, the apathy associated with depressive disorders could lead to malnutrition and disturbed monocarbon metabolism. The results of the studies are weakened by lack of longitudinal design, small sample size, selection bias, and lack of adequate control groups (4-9). However, S-adenosylmethionine (SAM) was reported to be equivalent with imipramine as antidepressive therapy (10); SAM i the main methyl donator of the human body, the crucial metabolite for the nerve cells of the methionine cycle, fuelled by folate and kindled by cobalamin.

In order to elucidate the role of folate and cobalamin in depressive disorders, it is desirable to perform randomized and controlled trials. One prerequisite of such a trial is that both bobalamin and folate are used in combination, since these substances are coupled by a series of reactions in the methionine cycle (11); lack of one micronutrient will block the function of the other and make the trial inconclusive. Another prerequisite is adequate doses of cobalaamin and folate. It is suggested that oral cyanocobalamin, 1 mg daily, and folic acid, 5 mg daily, are used, since these doses have proved efficient in a previous trial on cognitive functions in demented patients (12).

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10. Chiaie RD, Poncheri P, Scapicchio P. Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine- 1.4-butanedisulfonate (SAMe)in the treatment of major depression: comparison with imipramine in two multicenter studies. Am J Clin Nutr 2002; 76 (suppl):1172S-6S.
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Published December 31, 2004