B12 Deficiency and Depression
Clinical Abstracts
With Comments by Adriane Fugh-Berman, MD
B12 Deficiency and Depression
November 2000; Volume 2; 86
Source: Penninx BW, et al. Vitamin B (12) deficiency and depression in physically disabled older women: Epidemiologic evidence from the Women’s Health and Aging Study. Am J Psychiatry 2000;157:715-721.
Design/Setting/Subjects: Cross-sectional study in 700 disabled, non-demented community dwelling women over 65 years old (a subset of the Women’s Health and Aging Study, a prospective cohort study of the causes and course of physical disability in a sample of physically disabled older women.) The mean age of participants was 77.3 years. Twenty-eight percent were African-American. Serum levels of vitamin B12, folate, methylmalonic acid, and total homocysteine were assayed.
Results: Depressed women were more likely to be less educated, more likely to be white, and had more chronic diseases and disability in activities of daily living. Depressed subjects had significantly higher serum methylmalonic acid levels. Metabolically significant vitamin B12 deficiency was present in 14.9% of the 478 nondepressed subjects, 17% of the 100 mildly depressed subjects, and 27% of the 122 severely depressed women; the difference between depressed and nondepressed women was significant. Homocysteine, folate, anemia, and serum vitamin B12 were not associated with depression status. The authors conclude that metabolically significant vitamin B12 deficiency was associated with a doubled risk of severe depression.
Funding: National Institute on Aging.
Comments: Of course, correlation does not prove causation, but there are several plausible explanations for why low levels of B12 might predispose one to depression. The authors point out that vitamin B12 deficiency affects serotonin and catecholamine synthesis, and that vitamin B12 is required for the synthesis of S-adenosylmethionine (SAM-e, currently a popular dietary supplement for which there is some evidence of efficacy for depression). However, in this study methionine levels were normal in severely depressed women and were not significantly different from subjects who were not depressed. Another explanation for the link is that depression could cause low vitamin B12 levels through decreased food intake; this was judged unlikely as serum folate levels (sensitive to food intake) were not different across groups, nor was the number of subjects who reported weight loss during the previous year. Severe B12 deficiency can cause a variety of psychiatric manifestations including depression, and lesser states of deficiency may also be implicated. Cobalamin is nontoxic even in high doses and should be tested as a treatment for depression.
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