Intake of B Vitamins and their Circulating levels in Relation to Incident Stroke in Women and Men: Findings from Two National Prospective Cohorts in the United States

Evidence linking different B vitamins to stroke risk remains sparse, particularly regarding long-term intake and dose-response thresholds in populations fortified with folic acids. To prospectively investigate the associations of long-term intake of B vitamins and their circulating levels with incident stroke. Using a validated food frequency questionnaire, we assessed intake of B vitamins among 121,565 participants in the Women's Health Initiative (WHI). We also examined circulating levels of B vitamins in relation to stroke risk among 99,667 All of Us Research Program (AoU) participants. Multivariable Cox models estimated hazard ratios (HRs) and their 95% confidence intervals (CIs). In WHI (6,803 incident stroke cases; median follow-up: 18.4 years), higher long-term intakes of thiamin, riboflavin, niacin, pyridoxine, and folate were significantly associated with lower stroke risk, with HRs (95% CI) of 0.84 (0.76, 0.92), 0.90 (0.81, 0.99), 0.80 (0.72, 0.88), 0.88 (0.80, 0.96), and 0.88 (0.80, 0.97) comparing the highest to the lowest quintiles, respectively. Most B vitamins exhibited reverse J-shaped associations, whereas folate showed a linear inverse relationship up to at least 2,000 dietary folate equivalent (DFE)/day. In AoU (5,163 incident stroke cases; median follow-up: 5.7 years), higher plasma folate and pyridoxine were associated with lower risk (HRs: 0.86 and 0.50, respectively). In two large prospective cohorts of US adults, higher intake of thiamin, riboflavin, niacin, pyridoxine, and folate, as well as higher circulating concentrations of pyridoxine and folate, were associated with a lower risk of stroke, even after folic acid fortification.