Fifteen patients with bipolar disorder consumed a diet that contained less than 10% of the usual amount of inositol. Six of the patients were rapid cyclers who had responded inadequately to lithium or valproate in different phases of illness; two were lithium-treated outpatients with residual symptoms, and seven were lithium-treated inpatients with acute mania who had not responded to treatment. A marked reduction in the severity of the disease was seen in 10 of the 15 patients within the first 7-14 days of treatment, including five of six rapid cyclers, four of seven non-responding acute manic patients, and one of two outpatients with residual symptoms.

Comment: One theory to explain the beneficial effect of lithium in the treatment of mania is that the drug depletes inositol by inhibiting inositol monophosphatase. If that theory is correct, than consumption of a low-inositol diet might also be beneficial. Wheat contains large amounts of inositol, so a low-inositol diet would presumably be wheat-free, and also free of other common allergens such as legumes and nuts. It is possible that some of the improvement observed in this study was due to the avoidance of allergenic foods, rather than to inositol depletion. I have worked with several bipolar patients in whom consumption of allergenic foods was a clear trigger for their psychiatric symptoms.

In a previous study, supplementation with 6 g/day of inositol improved lithium-induced psoriasis without apparently interfering with the beneficial effects of lithium. In another study of 14 patients with various lithium-related side effects, administration of 3 g/day of inositol relieved the side effects in the majority of cases, while appearing to aggravate psychiatric symptoms in only one of the 14 patients. Thus, it is not clear to what extent inositol exacerbates the symptoms of bipolar disorder. Whether the improvement observed in the present study is due to inositol depletion or to the avoidance of allergenic foods, the results suggest that some patients with bipolar disorder respond to dietary modifications.

Shaldubina A, et al. Inositol deficiency diet and lithium effects. Bipolar Disord. 2006;8:152-159.