Melatonin administration lowers biomarkers of oxidative stress and cardio-metabolic risk in type 2 diabetic patients with coronary heart disease: A randomized, double-blind, placebo-controlled trial.

Background & Aims: Melatonin may benefit diabetic people with coronary heart disease (CHD) through its beneficial effects on biomarkers of oxidative stress and cardio-metabolic risk. This investigation evaluated the effects of melatonin administration on metabolic status in diabetic patients with CHD.

Methods: This randomized, double-blind, placebo-controlled trial was conducted and involved 60 diabetic patients with CHD. Subjects were randomly allocated into two groups to receive either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 30) or placebo (n = 30) once a day for 12 weeks.

Results: Compared with the placebo, melatonin supplementation resulted in significant increases in plasma glutathione (GSH) (+64.7 ± 105.7 vs. -11.1 ± 137.6 μmol/L, P = 0.02) and nitric oxide (NO) (+0.9 ± 4.7 vs. -3.3 ± 9.6 μmol/L, P = 0.03), and significant decreases in malondialdehyde (MDA) (-0.2 ± 0.3 vs. +0.1 ± 0.5 μmol/L, P = 0.007), protein carbonyl (PCO) (-0.12 ± 0.08 vs. +0.03 ± 0.07 mmol/mg protein, P < 0.001) and serum high sensitivity C-reactive protein (hs-CRP) levels (-1463.3 ± 2153.8 vs. +122.9 ± 1230.4 ng/mL, P = 0.001). In addition, taking melatonin, compared with the placebo, significantly reduced fasting plasma glucose (-29.4 ± 49.0 vs. -5.5 ± 32.4 mg/dL, P = 0.03), serum insulin concentrations (-2.2 ± 4.1 vs. +0.7 ± 4.2 μIU/mL, P = 0.008), homeostasis model of assessment-estimated insulin resistance (-1.0 ± 2.2 vs. +0.01 ± 1.6, P = 0.04), total-/HDL-cholesterol ratio (-0.18 ± 0.38 vs. +0.03 ± 0.35, P = 0.02) and systolic (-4.3 ± 9.6 vs. +1.0 ± 7.5 mmHg, P = 0.01) and diastolic blood pressure (-2.8 ± 7.3 vs. +0.1 ± 3.6 mmHg, P = 0.04). Melatonin treatment also significantly increased quantitative insulin sensitivity check index (+0.006 ± 0.01 vs. -0.004 ± 0.01, P = 0.01) and serum HDL-cholesterol (+2.6 ± 5.5 vs. -0.01 ± 4.4 mg/dL, P = 0.04). Supplementation with melatonin had no significant effect on other metabolic parameters.

Conclusions: Overall, melatonin intake for 12 weeks to diabetic patients with CHD had beneficial effects on plasma GSH, NO, MDA, PCO, serum hs-CRP levels, glycemic control, HDL-cholesterol, total-/HDL-cholesterol ratio, blood pressures and parameters of mental health. Registered under ClinicalTrials.gov Identifier no. http://www.irct.ir: IRCT2017051333941N1.