Feel Cool, Lose Weight: TRPM8 Activation

Transient receptor potential melastatin 8 (TRPM8) is known as the cold and menthol receptor, where it is activated by changes in temperature and cooling agents. Once activated, the TRPM8 receptor allows Na+ and Ca2+ to enter the cell, causing depolarization and action potential generation.

Menthol is an organic compound that elicits a cooling sensation when an interaction has occurred with the skin or a mucosal surface, without affecting core body temperature. It is responsible for the ‘cooling’ sensation presented in mint flavoured foods. Conversely, the non-thermal chemical, capsaicin, is responsible for the warm sensation present in chili.

The original cooling compounds were created by a shaving product company, Wilkinson Sword. These compounds provide a non-thermal cooling sensation without the minty effect associated with menthol. These compounds were created in hope to provide after shave cream users the cooling sensation without the volatile, negative effect of menthol. Over the years, some of these compounds have been commercialized for both topical and oral use.

·      WS-23

·      WS-3

·      WS-5

·      WS-12

·      WS-27

·      WS-116

Menthol and exercise performance

In response to exercise, the body’s temperature rises, particular in warm climates, which can be an uncomfortable feeling and lead to undesirable performance outcomes. Thermal cooling strategies including cold water immersion and cooling garments have been used in attempt to recover increased body temperature. Menthol is a non-thermal cooling strategy that has been observed to provide sensations of coolness, without reducing body temperature, to reduce perceived exertion, enhancing performance.

Menthol can be applied topically through the skin in creams or gels, however oral ingestion of menthol solutions has shown to provide greater effects. Compared to thermal and topical non-thermal practices, non-thermal delivery through ingestion provides a reduced-burden method to improve performance. It is important to note, menthol toxicity can occur with high or prolonged use.

TRPM8 activation and weight loss

One mechanism of weight loss that has received attention is the ability to modify resting energy expenditure. Adipose tissue non-shivering thermogenesis is an action that ultimately dissipates energy as heat, leading to increased basal energy expenditure which can cause a reduction in weight when paired with appropriate diet and exercise strategies.

At The Protein Factory, we use a range of WS cooling compounds as ingredients that act on the TRMP8 receptor to stimulate the cooling sensation without the volatile, negative effect of menthol. Thermostim, Bitter Cold GH, MetaslimB2 Preworkout, SR900Prime flavour oil, and wS-23 flavour oil all incorporate these unique WS compounds.

Sanders OD, Rajagopal JA, Rajagopal L. Menthol to induce non-shivering thermogenesis via trpm8/pka signaling for treatment of obesity. Journal of Obesity and Metabolic Syndrome. 2021;30(1): 4–11. Available from: https://doi.org/10.7570/jomes20038

Jeffries O, Waldron M. The effects of menthol on exercise performance and thermal sensation: A meta-analysis. Journal of Science and Medicine in Sport. 2019;22(6):707-715. Available from: https://doi.org/10.1016/j.jsams.2018.12.002

John C. Leffingwell, Ph.D. Cool without menthol & cooler than menthol and cooling compounds as insect repellents