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

FACIT was an interventional study in 819 men and postmenopausal women aged 50 to 70 years from the Gelderland region of the Netherlands with elevated total homocysteine at screening. The folic acid arm included 406 participants.

The active regimen was oral folic acid 800 micrograms daily for 3 years, compared with placebo. Outcomes were assessed at baseline and after 36 months.

Three years of daily folic acid did not slow progression of carotid intima-media thickness or improve carotid arterial stiffness, despite increasing folate levels and lowering homocysteine. In the folic acid arm, the rate of change in CIMT was 1.9 ± 0.9 lm/y versus 1.3 ± 0.8 lm/y with placebo; the mean difference was 0.7 lm/y (95% CI -1.8 to 3.1), P = 0.59. Carotid distensibility also did not differ significantly (P = 0.23). Twelve participants reported side effects attributed to treatment, 5 in the folic acid group and 7 in the placebo group.

The active intervention arm was modest in size (n = 406), and follow-up was limited to 3 years, which may not capture slower vascular effects. The findings are based on older Dutch adults with elevated homocysteine and surrogate vascular endpoints, limiting generalizability to other populations and to clinical cardiovascular outcomes. Some contextual variables, including ethnicity, BMI, and physical activity, were not reported.