Background: This study was carried out to evaluate the effects of folate supplementation on carotid intima-media thickness (CIMT) and metabolic status among patients with metabolic syndrome (MetS). Methods: This randomized, double-blind, placebo-controlled trial was conducted among 60 patients with type 2 diabetes mellitus and coronary heart disease. They were all overweight in the age range 40-85 years. Participants were randomly divided into 2 groups: group A (n = 30) received 5 mg folate supplements and group B (n = 30) received placebo for 12 weeks. Results: Folate supplementation resulted in a significant reduction in maximum levels of left CIMT (-0.05 ± 0.13 vs. +0.02 ± 0.11 mm, p = 0.01) compared with the placebo. Changes in fasting plasma glucose (-2.2 ± 37.5 vs. +30.2 ± 65.8 mg/dl, p = 0.02), serum insulin concentration (-2.0 ± 10.7 vs. +3.0 ± 7.6 µIU/ml, p = 0.04) and homeostasis of assessment-estimated insulin resistance (-0.6 ± 2.3 vs. +0.9 ± 2.3, p = 0.01) in supplemented patients were significantly different from those of patients in the placebo group. Changes in serum triglycerides (p = 0.04), high-density lipoprotein-cholesterol (p = 0.001), high sensitivity C-reactive protein (p = 0.01) and plasma nitric oxide concentrations (p < 0.001) were significantly different between the supplemented patients and placebo group. Conclusions: Overall, 5 mg/day folate supplementation for 12 weeks among patients with MetS had beneficial effects on CIMT and the metabolic status.

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