Intake of vitamin B6, folate, and vitamin B12 and risk of coronary heart disease: a systematic review and dose-response meta-analysis of prospective cohort studies

Crit Rev Food Sci Nutr. 2019;59(16):2697-2707. doi: 10.1080/10408398.2018.1511967. Epub 2018 Nov 15.


The objective of this study was to quantify the association of B-vitamins intake with the future risk of coronary heart disease (CHD). A systematic search was performed with the use of PubMed and Scopus from inception to April 30, 2018. Prospective cohort studies evaluating the association of intake of folate, vitamin B6, and vitamin B12 with risk of CHD in the general population were included. A random-effects meta-analysis was performed. Eleven prospective cohort studies (total n = 369,746) with 5133 cases of CHD were included in the analyses. The relative risks were: 0.79 (95%CI: 0.69, 0.89; I2 = 67%) for a 250 µg/d increment in folate intake; 0.87 (95%CI: 0.78, 0.96; I2 = 80%) for a 0.5 mg/d increment in vitamin B6 intake; and 0.97 (95%CI: 0.80, 1.14: I2 = 67%) for a 3 µg/d increment in vitamin B12 intake. The results did not change materially when the analyses were restricted only to dietary vitamins intake. A nonlinear dose-response meta-analysis demonstrated a linear inverse association between folate and vitamin B6 intake and risk of CHD. In conclusion, higher intake of folate and vitamin B6 is associated with a lower risk of CHD in the general population.

Keywords: Coronary heart disease; folic acid; meta-analysis; vitamin B6.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Cohort Studies
  • Coronary Disease / prevention & control*
  • Diet*
  • Dose-Response Relationship, Drug
  • Folic Acid / administration & dosage*
  • Humans
  • Vitamin B 12 / administration & dosage*
  • Vitamin B 6 / administration & dosage*


  • Vitamin B 6
  • Folic Acid
  • Vitamin B 12