The Effects of Acute Melatonin Supplementation on Microvascular Function in Healthy Young Adults

Reactive hyperemia is a noninvasive tool to assess microvascular function and cardiovascular risk. Although melatonin shows vascular protective effects in animals, its impact on human microvascular function is unclear. Methods: Twenty-two healthy young adults (9 females; tested during days 1–7 of the menstrual cycle) completed a randomized, double-blind, counterbalanced protocol. Thirty minutes prior to testing, participants ingested either 5 mg of melatonin (MEL, mint-flavored) or a placebo (PLA, mint extract in water) via sublingual spray. Following 5 minutes of supine rest, forearm blood flow was occluded (230mmHg, 5 min) using a rapid cuff inflation/deflation system (Hokanson). A frequency-domain near-infrared spectroscopy (NIRS) probe was placed over the flexor digitorum profundus muscle to continuously measure oxy-, deoxy-, and total hemoglobin Hb + myoglobin Mb. Tissue saturation index (TSI%) was calculated as oxyHb+Mb÷totalHb+Mb. Desaturation rate (%·s - ¹) was calculated as a linear slope over the first 60 seconds of occlusion, O 2 deficit was the area above this curve (area above the curve). Resaturation rate (%·s - ¹) was determined as the slope over the first 10s of reperfusion and normalized to O 2 deficit Results: Data are means ± SD. Baseline TSI was lower in MEL compared to PLA, with no effect of sex or condition-by-sex interaction (PLA M: 81.6 ± 5.0%; PLA F: 78.1 ± 4.0% vs. MEL M: 78.6 ± 5.3%; MEL F: 77.5 ± 4.35%; Condition: p = 0.05, ηₚ 2 = 0.18; Sex: p = 0.22, ηₚ 2 = 0.07; Interaction: p = 0.23, ηₚ 2 = 0.07). Desaturation rate was not influenced by melatonin but was faster in males (PLA M: 0.23 ± 0.06%·s - ¹; PLA F: 0.15 ± 0.04%·s - ¹ vs. MEL M: 0.26 ± 0.14%·s - ¹; MEL F: 0.17 ± 0.08%·s - ¹; Condition: p = 0.23, ηₚ 2 = 0.06; Sex: p = 0.02, ηₚ 2 = 0.24; Interaction: p = 0.86, ηₚ 2 = 0.00). O 2 deficit was not influenced by melatonin but was greater in males (PLA M: 7766 ± 1496 %·s - ¹; PLA F: 4766 ± 1117 %·s - ¹ vs. MEL M: 8102 ± 2868 %·s - ¹; MEL F: 5049 ± 1619 %·s - ¹; Condition: p = 0.50, ηₚ 2 = 0.02; Sex: p < 0.001, ηₚ 2 = 0.47; Interaction: p = 0.95, ηₚ 2 = 0.00). Resaturation rate was unaffected by melatonin and did not differ between sexes (PLA M: 2.70 ± 1.06 %·s - ¹; PLA F: 1.83 ± 0.89 %·s - ¹ vs. MEL M: 2.26 ± 1.24 %·s - ¹; MEL F: 1.59 ± 0.47 %·s - ¹; Condition: p = 0.09, ηₚ 2 = 0.14; Sex: p = 0.06, ηₚ 2 = 0.17; Interaction: p = 0.64, ηₚ 2 = 0.01). However, when the resaturation rate was normalized to O 2 deficit, melatonin slowed the normalized rate, with no sex differences observed (PLA M: .00034 ± .00012 s - ¹; PLA F: .00038 ± .00016 s - ¹ vs. MEL M: .00028 ± .00011 s - ¹; MEL F: .00033 ± .00011 s - ¹; Condition: p < 0.001, ηₚ 2 = 0.33; Sex: p = 0.44, ηₚ 2 = 0.03; Interaction: p = 0.61, ηₚ 2 = 0.01). Conclusion: Acute 5 mg melatonin supplementation did not improve microvascular function in healthy young adults. This may reflect receptor oversaturation, region-specific vascular responses, or the lack of effect from acute versus chronic or circadian-timed administration. This abstract was presented at the American Physiology Summit 2026 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.