Can melatonin (melatonin) increase blood pressure (hypertension)?

Melatonin Does Not Raise Blood Pressure—It Lowers It

Melatonin supplementation, particularly controlled-release formulations taken at bedtime, reduces blood pressure rather than increasing it, with the most pronounced effects on nocturnal systolic and diastolic blood pressure in patients with hypertension. 1, 2

Evidence for Blood Pressure Reduction

Nocturnal Blood Pressure Effects

• Repeated daily melatonin intake (2.5 mg taken 1 hour before sleep for 3 weeks) reduced nocturnal systolic blood pressure by 6 mm Hg and diastolic blood pressure by 4 mm Hg in men with untreated essential hypertension. 1
• The day-night amplitudes of blood pressure rhythms increased by 15% for systolic and 25% for diastolic pressures, indicating improved circadian blood pressure regulation. 1
• A single acute dose of melatonin had no effect on blood pressure—only repeated daily administration produced blood pressure reduction. 1

Controlled-Release Formulation Superiority

• Controlled-release melatonin (not immediate-release) reduced asleep systolic blood pressure by 3.57 mm Hg in a meta-analysis of hypertensive patients. 2
• Controlled-release melatonin also reduced asleep and awake diastolic blood pressure, though these reductions did not reach statistical significance. 2
• Immediate-release preparations did not demonstrate significant blood pressure-lowering effects in the meta-analysis. 2

Dose-Response Relationship

• Higher doses (10 mg) of melatonin taken at bedtime for 7 days lowered both systolic (from 108.4 to 104.0 mm Hg) and diastolic (from 59.3 to 57.1 mm Hg) blood pressure during sleep in adolescents with type 1 diabetes. 3
• The blood pressure-lowering effect was independent of sleep duration or number of awakenings. 3

Mechanisms of Blood Pressure Reduction

Multiple Pathways Involved

• Melatonin improves endothelial function through its antioxidant properties, increasing nitric oxide availability and producing vasodilatory and hypotensive effects. 4
• Melatonin interferes with peripheral and central autonomic systems, decreasing adrenergic tone while increasing cholinergic system activity. 4
• Melatonin acts via specific melatonin receptors located in peripheral vessels and central nervous system regions involved in blood pressure control. 4
• Animal studies demonstrate direct antihypertensive action with gradual cardiovascular effects and trends toward decreased plasma renin concentration. 5

Clinical Implications

Patient Selection

• Patients with non-dipping nocturnal blood pressure patterns (disturbed circadian blood pressure rhythm) show the most promising results from melatonin treatment. 4
• Patients with essential hypertension who have reduced nighttime melatonin production are ideal candidates. 4
• Adolescents with type 1 diabetes may benefit from melatonin for prevention of hypertension and cardiovascular complications. 3

Dosing Strategy

• Start with 2.5-3 mg of controlled-release melatonin taken 1-1.5 hours before bedtime. 1, 6
• If inadequate response after 1-2 weeks, increase to 5-10 mg. 3, 6
• Avoid immediate-release formulations for blood pressure management—controlled-release is superior. 2

Important Caveats

Medication Interactions

• Beta-blockers suppress endogenous melatonin production, which may explain some of their cardiovascular effects and suggests potential benefit from melatonin supplementation in patients taking beta-blockers. 7
• Use caution with warfarin due to potential interactions. 8
• NSAIDs suppress melatonin and should be avoided for 72 hours before assessing melatonin effects. 7

Quality Concerns

• Melatonin is regulated as a dietary supplement in the U.S., raising concerns about purity and reliability of stated doses. 6
• Choose United States Pharmacopeial Convention Verified formulations for reliable dosing. 6, 8

Monitoring Considerations

• Blood pressure effects develop gradually over days to weeks, not acutely. 1, 5
• Monitor for impaired glucose tolerance, as melatonin has been associated with this in healthy individuals after acute administration. 8
• The blood pressure-lowering effect is statistically unrelated to improvements in sleep quality. 1