In clinical studies, individuals with Parkinson's disease have had higher concentrations of plasma homocysteine than did controls, and experimental evidence suggests that folate deficiency or focal administration of homocysteine sensitizes dopaminergic neurons to the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The authors thus prospectively investigated whether higher intake of folate, vitamin B(6), or vitamin B(12) was related to a lower risk of Parkinson's disease in the Health Professionals Follow-up Study (1986-2000) and the Nurses' Health Study (1980-1998). They documented Parkinson's disease diagnoses in 248 men and 167 women during the follow-up. Folate intake was not associated with the risk of Parkinson's disease; the relative risks for the highest compared with the lowest quintiles were 1.0 (95% confidence interval: 0.7, 1.5) in men and 1.3 (95% confidence interval: 0.8, 2.3) in women. Neither did they find significant associations in analyses stratified by age, smoking, alcohol consumption, or lactose intake. Intake of vitamin B(6) or vitamin B(12) also was not related to the risk of Parkinson's disease. The current study does not support the hypothesis that higher intake of folate or related B vitamins lowers the risk of Parkinson's disease.