Effect of 3 y of folic acid supplementation on the progression of carotid intima-media thickness and carotid arterial stiffness in older adults

J. Durga, M.L. Bots, E.G. Schouten, D.E. Grobbee, F.J. Kok, P. Verhoef

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28 Citations (Scopus)


Background: Observational studies have shown that low folate and elevated homocysteine concentrations are risk factors for vascular disease in the general population. Randomized controlled trials in vascular patients have failed to show that folic acid reduces the risk of recurrent vascular disease, whereas such trials are lacking in the general population. Objective: The objective was to determine whether folic acid supplementation reduces the progression of atherosclerosis as measured by common carotid intima-media thickness (CIMT) a validated marker of atherosclerosis and predictor of vascular disease risk. Design: A randomized, double-blind, placebo-controlled study in 819 men and postmenopausal women aged 50-70 y, free-living in the Netherlands, and with a total homocysteine concentration >= 13 mu mol/L at screening was conducted. Participants received either 800 mu g folic acid or placebo daily for 3 y. Rate of change in CIMT and arterial distensibility were the primary and secondary outcomes, respectively. Results: Compared with placebo, serum folate increased by 577% and plasma total homocysteine concentrations decreased by 26% after 3 y of folic acid supplementation. The mean (+/- SE) rate of change in CIMT was 1.9 +/- 0.9 mu m/y in the folic acid arm and 1.3 +/- 0.8 mu m/y in the placebo arm (mean difference: 0.7 mu m/y; 95% CI: -1.8, 3.1 mu m/y; P = 0.59). No difference was observed (P = 0.23) between the rates of change in distensibility in the folic acid arm (-0.53 +/- 0.06 x 10(-3) kPa(-1)) and in the placebo arm (-0.62 +/- 0.06 x 10(-3) kPa(-1)). Conclusion: Despite a considerable increase in folate concentrations and a reduction in total homocysteine concentrations, 3-y folic acid supplementation did not slow down atherosclerotic progression or arterial stiffening. This trial was registered at clinicaltrials.gov as NCT00110604. Am J Clin Nutr 2011;93:941-9.
Original languageEnglish
Pages (from-to)941-949
JournalAmerican Journal of Clinical Nutrition
Issue number5
Publication statusPublished - 2011


  • randomized controlled-trial
  • cardiovascular-disease
  • homocysteine levels
  • subclinical atherosclerosis
  • familial hypercholesterolemia
  • risk
  • hyperhomocysteinemia
  • metaanalysis
  • coronary
  • torcetrapib

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