Cerebrovascular response to acute melatonin supplementation at rest and during small muscle exercise in young healthy adults

Melatonin is a vasoactive hormone that has been shown to have a negative correlation with cardiovascular disease risk. However, effects of acute melatonin supplementation on the cerebral vasculature in humans is under-investigated. Purpose: To determine if acute melatonin supplementation affects the cerebrovascular response and autoregulation during rest and during small muscle exercise. Methods: 14 healthy young adults (6 females testing only during the first 5 days of their menstrual cycle) completed a familiarization preceding 2 experimental visits separated by ≥48hrs. Participants received either 5mg of sublingual melatonin (MEL, mint flavored) or a placebo (PLA, mint extract mixed with filtered water) in a single-blind, randomized, crossover design. Following dosing, participants rested for 30 minutes in a supine position to allow melatonin levels to reach peak blood concentration (Bartoli et al., 2013). Next, middle cerebral artery velocity (MCAv, cm/s, Transcranial Doppler) and mean arterial pressure (MAP, mmHg, finger photoplethysmography) were measured continuously for 5 minutes of supine rest followed by 5 minutes of dynamic hand grip exercise (contraction/relaxation cycle 1:2 seconds) at heart level with a resistance of 20% of their maximal voluntary contraction. Cerebrovascular conductance index was calculated as CVCi = MCAv/MAP (cm/s/mmHg). Gain, phase, and coherence of the MCAv and MAP data were also determined using transfer function analysis (TFA) in the low frequency domain at rest (n=10). Results: Data presented as change (∆) from rest to exercise or compared between treatments, reported as means ± SD. No values were different between treatments when comparing ∆ from rest to exercise (MCAv PLA ∆1.43±4.34 vs. MEL ∆1.52±6.59 cm/s, p = 0.95, MAP PLA ∆7.84±5.16 vs. MEL ∆6.71±4.37 mmHg, p = 0.30, CVCi PLA ∆-0.03±0.06 vs. MEL ∆-0.03±0.06 cm/s/mmHg, p = 0.87). TFA analysis revealed differences in Gain (Gain PLA 1.10±0.79 vs. MEL 0.62±0.45, p = 0.047, d = 0.73) between treatments at rest with no differences in coherence and phase (Coherence PLA 0.44±0.16 vs. MEL 0.53±0.23, p = 0.16, Phase PLA -0.16±1.89 vs. MEL -0.84±1.74, p = 0.22). Conclusion: In line with previous research, our data indicates that acute melatonin supplementation does not affect MCAv, MAP, or CVCi at rest or during small muscle exercise. However, acute melatonin did reduce the gain of a transfer function analysis indicating that melatonin improves cerebral autoregulation efficiency at rest, thereby warranting further investigation into melatonin supplementation in clinical populations characterized by poor cerebral autoregulation. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.