Topical application of menthol enhances brown adipose tissue thermogenesis and fat oxidation in humans

This study examined the relationship between human brown adipose tissue (BAT) activity and thermogenesis in response to topical menthol application, which activates the transient receptor potential melastatin-8 in individuals with various BAT activity. Thirteen healthy male participants were separated into high (n = 6) and low (n = 7) BAT groups based on BAT activity (SUV_max). They were placed in a supine position at 27°C for 120 min with 4% l-menthol or a control solution applied to their abdomen and lower limbs. Expired gas was measured to calculate energy expenditure (EE) and substrate oxidation. Menthol application increased EE at 60-120 min, with no effect in the controls. Changes in EE adjusted for free fat mass (ΔEE/FFM) were significantly higher following menthol treatment compared with the control application at 60-120 min in the high BAT group (P < 0.05), but not in the low BAT group. A significant positive correlation was observed between SUV_max and EE/FFM averaged over 60-120 min with menthol treatment (r = 0.57, P < 0.05), but not in the controls. Fat oxidation averaged over 60-120 min was significantly greater with menthol in the high BAT group (P < 0.05) compared with the low BAT group. Rectal temperature at 120 min was significantly higher with menthol treatment in the high BAT groups (P < 0.05); however, menthol showed a minor effect on vasomotor responses, with no effect from BAT activity. Taken together, topical menthol application enhances thermogenesis and fat oxidation, which depends, in part, on BAT activity.NEW & NOTEWORTHY This study examined the relationship between human brown adipose tissue (BAT) activity and thermogenesis in response to topical menthol application, which activates transient receptor potential melastatin-8. A significant positive correlation was observed between BAT activity and energy expenditure. Fat oxidation was significantly greater with menthol application in the individuals with high BAT activity. Taken together, topical menthol application enhances thermogenesis and fat oxidation, which depends, in part, on BAT activity in humans.