Vitamins in mood disorders
Vitamins B and D, folate, and trace elements are essential for the functioning of neurons, and have been shown to afford protection against certain types of mental disorders, particularly depression.101 These nutrients become depleted in the body for many reasons, including poor nutrition, chronic disease, old age, stress, and polymorphism. Low vitamin B12, vitamin D, and folate levels are also associated with poor memory and cognitive dysfunction.102,103 Folic acid and folate from the diet are converted into L-methylfolate in the body. In a randomized, double-blind, placebo-controlled trial, 123 patients with major depression and schizophrenia maintained on standard psychotropic medications were given augmentation therapy of methylfolate 15 mg/day or placebo. The investigators reported significant improvement in clinical and social symptoms with methylfolate compared with placebo.104 However, treatment with folate or vitamin B12 alone has been associated with mixed results in depression. Geriatric patients with depression and cognitive dysfunction showed benefit when tricyclic antidepressants were augmented with vitamin B complex (B1, B6, and B12) and folate.105 Nonresponse to antidepressants has been linked with low levels of folate. A study of 127 patients on fluoxetine supplemented with folate 400 mg/day or placebo reported a 94% response rate to fluoxetine plus folate compared with a 61% response to fluoxetine plus placebo.106 However, a recent placebo-controlled study found little support for B12 (100 μg/day) with folate (400 μg/day) supplementation in community-dwelling adults already taking conventional antidepressants.107 Another placebo-controlled trial of folate plus vitamin B12 supplementation given to older patients with depression also yielded negative results.108
In summary, clinical trials of vitamin B and folate have yielded equivocal results in patients with major depression. Although methylfolate and vitamin B have favorable safety profiles, allergic reactions may occur using these substances. Folate and vitamin B reduce homocysteine levels, so may be cardioprotective. However, combination of these vitamins may cause restenosis of stents in men by stimulating endothelial proliferation, although this effect has not been seen in women.109
Low levels of vitamin D have been identified in patients with major depressive and other mood disorders, but vitamin D supplementation in these patients has produced inconsistent results.110 Supplemental use of vitamin D (800 International Units; IU) produced no positive results in a study of prevention of winter-time blues in elderly women.111 In a placebo-controlled study, obese men and women with major depressive disorder were given high doses of vitamin D (20,000 or 40,000 IU) or placebo per week for one year. Depression scores were higher in patients with low serum 25-hydroxyvitamin D (<40 nmol L) levels than in those with normal levels of 25-hydroxyvitamin D (≥40 nmol L), and participants given the vitamin D supplement showed significant improvement in depression compared with those in the placebo group.112 However, a recent placebo-controlled study of vitamin D3 supplementation in patients with low or high levels of 25-hydroxyvitamin D found that levels of 25-hydroxyvitamin D was significantly lower in patients with depression and that supplementation with vitamin D3 was not associated with improvement in symptoms compared with placebo.113 Similarly negative results were reported for another placebo-controlled trial in elderly women with symptoms of depression given vitamin D3 supplementation at 400 IU/day and calcium.114 However, a recent review suggests that the suicide risk associated with vitamin D deficiency might be reduced by supplementation with vitamin D.115
Other nutrients commonly used in CAM include omega-3 fatty acids, choline, 5-hydroxy-L-tryptophan, inositol, and N-acetylcysteine. These substances are important in functioning of the neural networks involved in mood regulation.