Dietary Intake of Homocysteine Metabolism-Related B-Vitamins and the Risk of Stroke: A Dose-Response Meta-Analysis of Prospective Studies

Adv Nutr. 2020 Nov 16;11(6):1510-1528. doi: 10.1093/advances/nmaa061.


Observational studies regarding the putative associations between dietary intake of homocysteine metabolism-related B-vitamins (vitamin B-6, folate, and vitamin B-12) and stroke risk have yielded inconsistent results. Thus, we conducted a systematic meta-analysis of prospective studies in order to examine the relation between the dietary (from diet and supplements) intake of these B-vitamins and the risk of stroke. PubMed and Web of Science were searched for relevant articles published through to 25 February, 2020, and RR of stroke in relation to dietary intake of vitamin B-6, folate, and vitamin B-12 were pooled using a random-effects model. Eleven publications of 12 prospective studies comprising 389,938 participants and 10,749 cases were included in the final analysis. We found that dietary intake of vitamin B-6 and folate were associated with a reduced risk of stroke, and this inverse association remained significant in studies with >10 y of follow-up periods and among participants without a pre-existing stroke event. A dose-response analysis revealed a linear inverse association between folate and vitamin B-6 intake and the risk of stroke, with a pooled RR of 0.94 (95% CI: 0.90-0.98) and 0.94 (95% CI: 0.89-0.99) for each 100 μg/d increment in folate intake and 0.5 mg/d increment in vitamin B-6 intake, respectively. In contrast, we found no significant association between dietary vitamin B-12 intake and the risk of stroke, with an RR of 1.01 (95% CI: 0.97-1.06) per 3 μg/d increase. In conclusion, our findings suggest that increased intake of vitamin B-6 and folate is associated with a reduced risk of stroke, supporting the notion that increasing habitual folate and vitamin B-6 intake may provide a small but beneficial effect with respect to stroke.

Keywords: B-vitamins; dietary intake; dose-response; meta-analysis; stroke.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • China
  • Eating
  • Female
  • Folic Acid
  • Follow-Up Studies
  • Homocysteine
  • Humans
  • Male
  • Middle Aged
  • Nutrition Surveys
  • Prospective Studies
  • Risk Factors
  • Stroke* / epidemiology
  • Vitamins


  • Vitamins
  • Homocysteine
  • Folic Acid