Does menthol independently modify thermoregulatory control during passive heat stress in humans?
Authors: Nelson Mackenzie , Newhouse Douglas , Lefebvre KarLee , Ravanelli Nicholas 
Published: May 2024

Introduction: Physical cooling within the gastrointestinal (GI) tract attenuates sudomotor activity likely by activation of the cold-sensitive transient receptor potential melastatin 8 (TRPM8). In the absence of physical cooling, it remains unknown whether stimulation of TRPM8 receptors within the GI tract during heat stress alters sudomotor control. Objective and Hypothesis: The purpose of this study is to assess whether a TRPM8 agonist (e.g., menthol) independently modulates the sudomotor response during heat stress. Relative to 37°C water, It was hypothesized that menthol would i) delay the sweating onset, and ii) attenuate the sweating response during heat stress. Methods: To date, a total of 9 participants (5 females; 22±5 y; 72.7±10.5 kg; 1.8±0.1 m) have completed three passive heating protocols on separate days. The participant’s rectal temperature was increased by 1.0°C above baseline using a water perfused suit circulating 49°C water. Participants consumed 3.2 ml per kg of body mass of either: i) 37°C water (37C), ii) 1.5°C water (1.5C), or iii) 37°C menthol solution (0.05%, 37M), 5 minutes before passive heating, and following a 0.5°C and 1.0°C increase in rectal temperature. Mean skin temperature (4 sites) and local sweat rate of the forearm and forehead were recorded during the baseline period and passive heating protocol. Mean body temperature was calculated as the weighted average between skin (20%) and rectal (80%) temperature, and whole-body sweat rate expressed as the net difference in body mass relative to heating time (in g/h). Results: Mean body temperature at baseline was not different between the three conditions (37C: 36.21±0.41˚C, 1.5C: 36.24±0.38˚C, and 37M: 36.30±0.43˚C, P=0.32). Forearm sweating onset was attenuated with 37M (36.97±0.42˚C, P=0.04), and trending to be attenuated with 1.5C (36.96±0.26˚C, P=0.07) relative to 37C (36.69±0.40˚C). Similarly, forehead sweating onset was attenuated with 37M (36.95±0.44˚C, P=0.02), and trending to be attenuated with 1.5C (36.84±0.35˚C, P=0.09), relative to 37C (36.70±0.43˚C). Thermosensitivity was not different between all three fluid conditions for the arm (37C: 1.4±0.7 mg/cm2/min/˚C; 1.5C: 1.7±1.0 mg/cm2/min/˚C; 37M: 1.5±1.0 mg/cm2/min/˚C, P=0.59) and head (37C: 1.7±0.9 mg/cm2/min/˚C; 1.5C: 1.6±1.2 mg/cm2/min/˚C; 37M: 1.7±1.1 mg/cm2/min/˚C, P=0.88). Lastly, whole-body sweat rate was not significantly different between all three conditions (37C: 631±288 g/h; 1.5C: 580±270 g/h; 37M: 635±440 g/h, P=0.63). Conclusion: Preliminary results suggest that consumption of a TRPM8 agonist in advance of passive heat stress may attenuate the sudomotor onset similarly to 1.5˚C water relative to 37˚C. However, the sweating response remains largely unaffected during passive heat stress between all three fluids assessed. Funding: This research was supported by Dr. Nicholas Ravanelli’s Natural Sciences and Engineering Research Council of Canada Discovery Grant (PIN#2022-05096). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.