Ibuprofen inhibits human sweet taste and glucose detection implicating an additional mechanism of metabolic disease risk reduction.

BACKGROUND AND PURPOSE

The human sweet taste receptor, TAS1R2-TAS1R3, conveys sweet taste in the mouth and may help regulate glucose metabolism throughout the body. Ibuprofen and naproxen are structurally similar to known inhibitors of TAS1R2-TAS1R3 and have been associated with metabolic benefits. Here, we determined if ibuprofen and naproxen inhibited TAS1R2-TAS1R3 responses to sugars in vitro and their elicited sweet taste in vivo, in humans under normal physiological conditions, with implications for effects on glucose metabolism.

EXPERIMENTAL APPROACH

Human psychophysical taste testing and in vitro cellular calcium assays in HEK293 cells were performed to determine the effects of ibuprofen and naproxen on sugar taste signalling.

KEY RESULTS

Ibuprofen and naproxen inhibited the sweet taste of sugars and non-nutritive sweeteners in humans, dose-dependently. Ibuprofen reduced cellular signalling of sucrose and sucralose in vitro with heterologously expressed human TAS1R2 (hTAS1R2)-TAS1R3 in human kidney cells. To mirror internal physiology, low concentrations of ibuprofen, which represent human plasma levels after a typical dose, inhibit the sweet taste and oral detection of glucose at concentrations nearing post-prandial plasma glucose levels.

CONCLUSION AND IMPLICATIONS

Ibuprofen and naproxen inhibit activation of TAS1R2-TAS1R3 by sugar in humans. Long-term ibuprofen intake is associated with preserved metabolic function and reduced risk of metabolic diseases such as Alzheimer's, diabetes and colon cancer. In addition to its anti-inflammatory properties, we present here a novel pathway that could help explain the associations between metabolic function and chronic ibuprofen use.