Menthol - Clinical Research
Menthol: The Science Behind the Relief
Menthol has been used for centuries to cool, soothe, and relieve pain. Modern science has uncovered its molecular mechanism — activating TRPM8 cold receptors, increasing blood flow, and modulating inflammatory pathways — making it a cornerstone in natural, topical pain relief.
Clinical & Mechanistic Evidence
1. The Role and Mechanism of Action of Menthol in Topical Analgesic Products
Pergolizzi JV Jr, Taylor R Jr, LeQuang J-A, Raffa RB; NEMA Research Group. J Clin Pharm Ther. 2018;43(6):880-885.
Menthol selectively activates TRPM8 receptors, providing a cooling counter-irritant effect while desensitizing nociceptors. It also engages central analgesic pathways, supporting its use as a safe, non-opioid topical analgesic.
🔗 Read full study on Wiley Online Library
2. T-2 Toxin Induces Dermal Inflammation and Toxicity in Mice: The Healing Potential of Menthol
Rachitha P, Krupashree K, Jayashree GV, et al. Environ Res. 2023;115838.
Topical menthol (0.25–0.5%) demonstrated strong anti-inflammatory effects, suppressing oxidative stress and down-regulating i-NOS gene expression. This study highlights menthol’s ability to repair toxin-induced skin inflammation.
🔗 Read full study on ScienceDirect
3. Mud Pack With Menthol and Arnica Montana Accelerates Recovery Following a High-Volume Resistance Training Session
Bartolomei S, Nigro F, D’Amico A, Cortesi M, Di Michele R. J Strength Cond Res. 2022;36(7):1909-1915.
In trained men, a mud pack containing menthol and arnica significantly reduced muscle soreness and improved strength recovery after intense lower-body training compared with placebo.
🔗 Read full study on PubMed Central
4. Influence of Menthol on Recovery From Exercise-Induced Muscle Damage
Gillis DJ, Vellante A, Gallo JA, D’Amico AP. J Strength Cond Res. 2020;34(2):451-462.
Menthol gel preserved lower-body power and reduced soreness following sprint-induced muscle damage, suggesting enhanced neuromuscular recovery potential.
🔗 Read full study on PubMed
5. Cold Stimuli, Hot Topic: An Updated Review on the Biological Activity of Menthol in Relation to Inflammation
Cheng H, An X. Front Immunol. 2022;13:1023746.
Comprehensive review summarizing menthol’s down-regulation of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and antioxidant benefits in both acute and chronic inflammation models.
🔗 Read full paper on Frontiers in Immunology
6. More Than Cool: Promiscuous Relationships of Menthol and Other Sensory Compounds
Macpherson LJ, Hwang SW, Miyamoto T, et al. Mol Cell Neurosci. 2006;32(4):335-343.
Identified menthol’s multi-receptor interactions — activating TRPM8 and TRPV3 while inhibiting TRPA1 — explaining its dual cool–warm modulation and analgesic versatility.
🔗 Read full paper on ScienceDirect
7. Menthol-Induced Activation of TRPM8 Receptors Increases Cutaneous Blood Flow Across the Dermatome
Dillon GA, Lichter ZS, Alexander LM. Microvasc Res. 2021;104271.
Topical 5% menthol gel increased blood flow locally and across the same dermatome via TRPM8-mediated spinal reflexes, supporting its role in circulation enhancement and pain relief.
🔗 Read full study on PubMed Central
8. Topical Menthol Increases Cutaneous Blood Flow
Craighead DH, Alexander LM. Microvasc Res. 2016;104:81-86.
Menthol dose-dependently increased microvascular blood flow in human skin through sensory nerve and endothelial mechanisms.
🔗 Read full paper on PubMed Central
9. The Use of Menthol in Skin Wound Healing – Anti-Inflammatory Potential, Antioxidant Defense System Stimulation and Increased Epithelialization
Rozza AL, Beserra FP, Vieira AJ, et al. Pharmaceutics. 2021;13(11):1902.
Menthol (0.5%) cream accelerated wound healing in rats by lowering pro-inflammatory cytokines and enhancing antioxidant enzyme activity and epithelial regeneration.
🔗 Read full paper on MDPI Pharmaceutics