Background: Pharmacotherapy is the first line of treatment for bipolar disorder, but many patients continue to experience persistent subthreshold symptoms. Alternative adjunct treatments, including nutritional therapies, may have the potential to alleviate residual symptoms and improve the outcomes of standard pharmacotherapy. The aim of this paper is to critically review the current clinical evidence and mechanisms of action of nutrient-based therapies alone or in combination with commonly used pharmacotherapies for mania and bipolar depression. Methods: We conducted a Medline search for clinical trials conducted with humans, published in English from 1960 to 2012 using nutritional supplements such as n–3, chromium, inositol, choline, magnesium, folate and tryptophan alone or in combination with pharmacotherapies for the treatment of bipolar disorder. Results: Preliminary data yields conflicting but mainly positive evidence for the use of n–3 fatty acids and chromium in the treatment of bipolar depression. Limited evidence found that inositol may be helpful for bipolar depression, but larger sample sizes are needed. Preliminary randomized, controlled trials suggest that choline, magnesium, folate and tryptophan may be beneficial for reducing symptoms of mania. Conclusions: Given the potential public health impact of identifying adjunct treatments that improve psychiatric as well as physical health outcomes, nutritional treatments appear promising for the management of bipolar disorder but require further study.

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