Does Acute Melatonin Supplementation Affect Cerebrovascular Reactivity in Healthy Young Adults?

Abstract

Melatonin receptors have been found in the cerebrovasculature in animal models, and melatonin has been shown to improve systemic vascular control. While there is a correlation between low melatonin production and cardiovascular disease, the effect of acute melatonin supplementation on the cerebrovasculature, and more specifically, cerebrovascular reactivity (CVR), is unknown. PURPOSE: To determine if acute melatonin supplementation alters CVR via CO2 rebreathing in healthy, young adults. METHODS: 14 healthy young adults (Age 23.7±4.39, 7 females tested during the first 5 days of their menstrual cycle) participated in a familiarization visit followed by 2 experimental visits separated by ³48hrs. Participants received a sublingual dose of either a placebo (PLA, mixture of mint extract and filtered water, to mimic taste of melatonin) or 5mg of melatonin (MEL, mint flavor) in a single-blind, randomized, crossover design. After ingestion, participants rested for 30 minutes prior to the experiment to allow for melatonin levels to reach peak concentration in the blood (Bartoli et al., 2013). After which, mean arterial pressure (MAP, mmHg, finger photoplethysmography), middle cerebral artery velocity (MCAv, cm/s, Transcranial Doppler), and end-tidal CO2 concentration (PetCO2, mmHg, Gas Analyzer) were measured continuously for 5 minutes of supine rest while breathing atmospheric air followed by a CO2 rebreathing challenge (CO2=3%, O2=40%, balanced N2) until the participant displayed a PetCO2 increase of ³10mmHg. Cerebrovascular conductance index was calculated as CVCi = MCAv/MAP (cm/s/mmHg). CVR was calculated in absolute ∆MCAv/∆PetCO2, ∆CVCi/∆PetCO2, and percent change from resting values. RESULTS: Data presented as change (Δ) from rest to CO2 rebreathing, as mean ± SD. All values were not different between treatments during rest. No value was significantly different between treatments when comparing ∆ from rest to CO2 rebreathing (MCAv PLA ∆13.35±5.1 vs. MEL ∆11.62±6.03, p = 0.31, d = 0.28, MAP PLA ∆1.75±3.91 vs. MEL ∆-0.55±4.49, p = 0.20, d = 0.34, CVCi PLA ∆0.11±0.04 vs. MEL ∆0.11±0.05, p = 0.55, r = 0.16, CVRMCAv PLA ∆2.75±1.30 vs. MEL ∆3.54±2.57, p = 0.92, r = 0.03, %CVRMCAv PLA ∆18.41±7.07 vs. MEL ∆16.12±10.00, p = 0.36, r = 0.24, CVRCVCi PLA ∆0.02±0.03 vs. MEL ∆0.02±0.02, d = 0.28, p = 0.31, %CVRCVCi PLA ∆2.32±2.58 vs. MEL ∆1.52±1.83, d = 0.28, p = 0.31). CONCLUSION: Our results indicate that melatonin does not affect MCAv, CVCi, MAP, or CVR during rest or CO2 rebreathing. Reactivity was variable individually and did not trend in any direction when comparing PLA treatment to MEL treatment. Thus, melatonin supplementation does not improve cerebrovascular function indicating melatonin supplementation may have differential responses between the cerebral and peripheral vasculature in humans.