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Nutritional Epidemiology

The Use of B Vitamin Supplements and Peripheral Arterial Disease Risk in Men Are Inversely Related¹

Anwar T. Merchant^*,,2, Frank B. Hu^*,**, Donna Spiegelman^**,, Walter C. Willett^*,**,, Eric B. Rimm^*,**, and Alberto Ascherio^*,**,

^* Department of Nutrition, Harvard School of Public Health; Department of Oral Health Policy and Epidemiology, Harvard School of Dental Medicine; Departments of ^** Epidemiology and Biostatistics, Harvard School of Public Health; and The Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115

²To whom correspondence should be addressed. E-mail: amerchan{at}hsph.harvard.edu.

Peripheral arterial disease (PAD) causes morbidity and is associated with mortality. B vitamin intake has been inversely associated with coronary heart disease, but their effects on PAD are not known. We examined prospectively the relationships between dietary folate, vitamin B-6 and B-12 and PAD risk in 51,529 male U.S. health professionals, aged 40 to 75 y, who answered a detailed 131-item questionnaire to assess diet and vitamin supplement use. The study population consisted of 46,036 men free of PAD, cardiovascular disease and diabetes at baseline followed for 12 y during which we documented 308 incident PAD cases. For every 400 µg/d increment of folate intake, the multivariate adjusted PAD risk decreased by 21% [relative risk (RR) = 0.79, 95% CI 0.64–0.96]. Men in the top category of folate intake (median = 840 µg) were at 33% lower risk of PAD than men in the bottom category (median = 244 µg) (RR = 0.67, 95% CI 0.45–0.96, P-value, test for trend = 0.03) after multivariate adjustment. There were weak inverse associations between intake of vitamin B-6 and PAD risk (RR = 0.70, 95% CI 0.48–1.02, P-value, test for trend = 0.06) and B-12 (RR = 0.77, 95% CI 0.54–1.11, P-value, test for trend = 0.12). These results suggest that higher consumption of folate may contribute to the prevention of PAD.

KEY WORDS: • folate • peripheral arterial disease • vitamin B-6 • vitamin B-12 • homocysteine