Just as low folate levels promote depression, high levels seem to deter it (26). Recovered depressives (and manic depressives, perhaps) who have very high folate levels from diet or supplements are much less vulnerable to relapse, some (26,27), but not all (28) studies indicate. And in three recent clinical trials, megadoses of methylfolate (5-methyltetrahydrofolate) -- a more potent, "bioconverted" form of the vitamin -- have displayed significant antidepressant effects (26,29). In one double-blind study, methylfolate equalled a popular antidepressant drug (26).

This will come as no surprise to orthomolecular psychiatrists. For years they've claimed megadoses of folate can be a mood-lifting stimulant (6).

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3. I. R. Bell et al., "B Complex Vitamin Patterns in Geriatric and Young Adult Inpatients with Major Depression," Journal of the American Geriatric Society, 39 (March 1991): 252-257.

6. H. L. Newbold, Mega-Nutrients for Your Nerves (New York: Berkley Books, 1975).

25. M. T. Abou-Saleh and A. Coppen, "The Biology of Folate in Depression: Implications for Nutritional Hypotheses of the Psychoses," Journal of Psychiatric Research, 20(2): 91-101, 1986.

26. R. Crellin et al., "Folates and Psychiatric Disorders: Clinical Potential," Drugs, 45 (May 1993): 623-636.

27. Sing Lee et al., "Folate Concentration in Chinese Psychiatric Outpatients on Long-Term Lithium Treatment," Journal of Affective Disorders, 24 (April 1992): 265-270.

28. P. McKeon et al., "Serum and Red Cell Folate and Affective Morbidity in Lithium Prophylaxis," Acta Psychiatrica Scandinavica, 83 (March 1991): 199-201.

29. G. P. Guaraldi et al., "An Open Trial of Methyltetrahydrofolate in Elderly Depressed Patients," Annals of Clinical Psychiatry, 5 (June 1993): 101-105.