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

Xinge Zhang; Bo Yang; Bernadette Boden-Albala; Hoda Anton-Culver; Matthew Allison; Linda Van Horn; Tracy E Madsen; Shaista Malik; JoAnn E Manson; Marian L Neuhouser; Alexander P Reiner; Nathan D Wong; Simin Liu

doi:10.1016/j.ajpc.2026.101534

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

Am J Prev Cardiol. 2026 Mar 12:28:101534. doi: 10.1016/j.ajpc.2026.101534. eCollection 2026 Aug.

Authors

Xinge Zhang^{1

2

3}, Bo Yang^{1

2

3}, Bernadette Boden-Albala^{1

2}, Hoda Anton-Culver⁴, Matthew Allison⁵, Linda Van Horn⁶, Tracy E Madsen⁷, Shaista Malik^{8

3}, JoAnn E Manson^{9

10

11}, Marian L Neuhouser¹², Alexander P Reiner^{12

13}, Nathan D Wong^{1

2

3}, Simin Liu^{1

2

3}

Affiliations

¹ Department of Epidemiology & Biostatistics, Joe C. Wen School of Population and Public Health, University of California, Irvine, CA, USA.
² Center for Global Cardiometabolic Health & Nutrition, University of California, Irvine, CA, USA.
³ Mary and Steve Wen Cardiovascular Division, Department of Medicine, School of Medicine, University of California, Irvine, CA, USA.
⁴ Genetic Epidemiology Institute, Department of Medicine, University of California, Irvine, CA, USA.
⁵ Department of Family Medicine, University of California, San Diego, La Jolla, CA, USA.
⁶ Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
⁷ Department of Emergency Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA.
⁸ Susan Samueli Integrative Health Institute, Mary and Steve Wen Cardiovascular Division, Department of Medicine, University of California, Irvine, CA, USA.
⁹ Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
¹⁰ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹¹ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹² Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹³ Department of Epidemiology, University of Washington, Seattle, WA, USA.

Abstract

Background: 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.

Objective: To prospectively investigate the associations of long-term intake of B vitamins and their circulating levels with incident stroke.

Methods: 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 99,660 All of Us Research Program (AoU) participants. Multivariable Cox models estimated hazard ratios (HRs) and their 95 % confidence intervals (CIs).

Results: In WHI (6803 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 2000 dietary folate equivalent (DFE)/day. In AoU (5163 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).

Conclusions: 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.

Keywords: B vitamin; Folate; Niacin; Riboflavin; Stroke; Thiamin.