- Background An elevated homocysteine level is reported to be a risk factor for several diseases, including Alzheimer’s and cerebrovascular disease. Recently, several studies have reported that homocysteine levels are elevated in many schizophrenic patients. Homocysteine levels can be lowered by oral folic acid, B-12, and pyridoxine. Methods Forty-two schizophrenic patients with plasma homocysteine levels >15 μmol/L were treated with these vitamins for 3 months and placebo for 3 months in a study with a randomized, double-blind, placebo-controlled, crossover design. Results Homocysteine levels declined with vitamin therapy compared with placebo in all patients except for one noncompliant subject. Clinical symptoms of schizophrenia as measured by the Positive and Negative Syndrome Scale declined significantly with active treatment compared with placebo. Neuropsychological test results overall, and Wisconsin Card Sort (Categories Completed) test results in particular, were significantly better after vitamin treatment than after placebo. Conclusions A subgroup of schizophrenic patients with hyperhomocysteinemia might benefit from the simple addition of B vitamins.