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Updated: Jun 17, 2025

A Preclinical Model of Exertional Heat Stroke in Mice
Published on: July 1, 2021
Thermal and Cardiovascular Responses during Exertional Heat Stress after Diphenhydramine Use: A Randomized Crossover
Douglas Newhouse, Emily Mihalcin1, Karlee Lefebvre1
1School of Kinesiology, Lakehead University, Thunder Bay, Ontario, CANADA.
Introduction:
Despite sparse systematic evidence, current exercise heat safety recommendations suggest that antihistamines blunt sweating and increase the risk for heat-related injury during exertional heat stress. The primary purpose of the present study was to examine whether diphenhydramine hydrochloride (DPH), a first-generation antihistamine, affects the sweating, core temperature, and heart rate (HR) response during exertional heat stress using a double-blind randomized crossover design.
Methods:
On two occasions separated by >48 h, 20 healthy adults (10 females, 23 ± 3 yr, body surface area: 1.9 ± 0.2 m 2 , body mass index: 23.7 ± 2.2 kg·m -2 ) orally consumed either 50 mg of DPH or placebo (PLA), and then rested for 2 h in a climate-controlled room maintained at 30°C and 35% relative humidity (heat index of ~29°C), followed by a 60-min fixed-heat production treadmill walk (6.3 ± 1.0 W·kg -1 ). Whole-body sweat loss, local sweat rate, rectal temperature ( Trec ), and HR were measured.
Results:
Whole-body sweat loss was not different between conditions (PLA: 406 ± 78 g, DPH: 396 ± 75 g; P = 0.26, treatment effect: -10 g; 95% confidence interval, -28 to 8). No differences were observed for the onset of sweating (PLA: 13.5 ± 2.4 min, DPH: 13.3 ± 2.7 min; P = 0.79) and steady-state local sweat rate (PLA: 0.83 ± 0.26 mg·cm -2 ·min -1 , DPH: 0.82 ± 0.27 mg·cm -2 ·min -1 ; P = 0.99). No difference in baseline Trec was observed (PLA: 37.09°C ± 0.35°C, DPH: 37.13°C ± 0.33°C; P = 0.68), and the 60-min Δ Trec was not different ( P = 0.99) between PLA (0.83°C ± 0.29°C) and DPH (0.81°C ± 0.30°C). HR was similar at baseline (PLA: 86 ± 13 bpm, DPH: 84 ± 11 bpm; P = 0.30) and end-exercise (PLA: 134 ± 28 bpm, DPH: 132 ± 26 bpm; P = 0.90).
Conclusions:
Fifty milligrams of DPH does not modify the sweating, core temperature, and HR response during exertional heat stress in young healthy adults.
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