Objective: To investigate the association of dietary folate, vitamin B(6) (VB(6)) and vitamin B(12) (VB(12)) with the risk of coronary heart disease among middle-aged persons.

Methods: A total of 40,803 subjects aged 40-59 years living in the community who were free of prior diagnoses of cardiovascular disease and cancer and who completed a food frequency questionnaire were followed from 1990-1992 to the end of 2001 in the Japan Public Health Center-based Prospective Study.

Results: After 468,472 person-years of follow-up, 251 coronary heart disease incidents were documented. Coronary heart disease and definite myocardial infarction were inversely associated with dietary intake of folate, VB(6) and VB(12) after adjustment for age and sex, but the associations were attenuated after further adjustment for smoking, dietary and other cardiovascular risk factors. However, among non-multivitamin supplement users, multivariable hazard ratios (95% confidence intervals) in the highest vs. lowest quintiles of VB(6) intake were 0.60 (0.37-0.97) for total coronary heart disease and 0.52 (0.29-0.91) for definite myocardial infarction, and the inverse associations with VB(12) were marginally significant. The combination of below-median intake of three vitamins or of only B(6) conferred a twice excess risk of total coronary heart disease.

Conclusions: Dietary intake of VB(6) was associated with a reduced risk of coronary heart disease among middle-aged non-multivitamin supplement users. Dietary folate and VB(12) were also suggested to be protective factors for coronary heart disease.