Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease

Atherosclerosis. 2014 Jul;235(1):94-101. doi: 10.1016/j.atherosclerosis.2014.04.010. Epub 2014 Apr 28.


Objective: Few studies have examined the roles of homocysteine and related nutrients in the development of peripheral artery disease (PAD). We examined the associations between plasma homocysteine, dietary B vitamins, betaine, choline, and supplemental folic acid use and incidence of PAD.

Methods: We used two cohort studies of 72,348 women in the Nurses' Health Study (NHS, 1990-2010) and 44,504 men in the Health Professionals Follow-up Study (HPFS, 1986-2010). We measured plasma homocysteine in nested matched case-control studies of clinically recognized PAD within both cohorts, including 143 PAD cases and 424 controls within the NHS (1990-2010) and 143 PAD cases and 428 controls within the HPFS (1994-2008). We examined the association between diet and risk of incident PAD in the cohorts using a food frequency questionnaire and 790 cases of PAD over 3.1 million person-years of follow-up.

Results: Higher homocysteine levels were positively associated with risk of PAD in men (adjusted IRR 2.17; 95% CI, 1.08-4.38 for tertile 3 vs. 1). There was no evidence of an association in women (adjusted IRR 1.14; 95% CI, 0.61-2.12). Similarly, higher folate intake, including supplements, was inversely associated with risk of PAD in men (adjusted HR 0.90; 95% CI, 0.82-0.98 for each 250 μg increase) but not women (HR 1.01, 95% CI, 0.88-1.15). Intakes of the other B vitamins, betaine, and choline were not consistently associated with risk of PAD in men or women.

Conclusion: Homocysteine levels were positively associated and dietary folate intake was inversely associated with risk of PAD in men but not in women.

Keywords: Betaine; Choline; Folate; Homocysteine; Peripheral artery disease; Riboflavin; Vitamin B12; Vitamin B6.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Betaine / therapeutic use*
  • Case-Control Studies
  • Choline / therapeutic use*
  • Cohort Studies
  • Diet
  • Dietary Supplements
  • Female
  • Folic Acid / chemistry
  • Follow-Up Studies
  • Homocysteine / blood*
  • Humans
  • Male
  • Middle Aged
  • Peripheral Arterial Disease / epidemiology*
  • Peripheral Arterial Disease / prevention & control*
  • Proportional Hazards Models
  • Riboflavin / therapeutic use
  • Risk Factors
  • Surveys and Questionnaires
  • Vitamin B Complex / therapeutic use*


  • Homocysteine
  • Vitamin B Complex
  • Betaine
  • Folic Acid
  • Choline
  • Riboflavin