Controlled‐release oral melatonin supplementation for hypertension and nocturnal hypertension: A systematic review and meta‐analysis

Systematic review and meta-analysis of 4 randomized controlled trials in adults with hypertension or nocturnal hypertension. Participants were mostly middle-aged adults on antihypertensive therapy; trials were conducted in Israel, Italy, the Netherlands, and the USA using parallel or crossover designs with short-term follow-up and ambulatory blood pressure monitoring.

Oral melatonin was studied mainly as controlled-release formulations, with one immediate-release trial. Doses ranged from 2 mg to 24 mg taken in the evening or at bedtime for 3 to 4 weeks, compared with placebo or no treatment.

Controlled-release melatonin may modestly lower asleep blood pressure, but the overall antihypertensive effect was inconsistent and evidence certainty was low to very low. In pooled analyses of controlled-release melatonin, asleep SBP fell by -4.67 mm Hg (95% CI: -8.79 to -.55) and asleep DBP by -2.39 mm Hg (95% CI: -5.01 to .23), while daytime SBP and DBP were not significantly changed. Immediate-release melatonin increased 24-h SBP by 6.5 mm Hg (95% CI: 2.3 to 10.7; p < .001) and 24-h DBP by 4.9 mm Hg (95% CI: 1.2 to 8.4; p < .001). Sleep outcomes showed small, non-significant improvements, and melatonin appeared generally safe and well tolerated, although no cardiovascular outcomes were reported.

Evidence was based on only 4 short-term trials with 137 participants total, limiting precision and generalizability. Formulation-specific effects differed between controlled-release and immediate-release melatonin, and several outcomes had wide confidence intervals or substantial heterogeneity. No cardiovascular events or long-term clinical outcomes were reported, and overall certainty was low to very low.