Ibuprofen, a Phenylpropanoic Acid Nonsteroidal Anti-inflammatory Drug, Inhibits Human Sweet Taste and Glucose Detection

The sweet taste receptor, TAS1R2-TAS1R3, is expressed both orally, where it signals sweet taste, and extraorally in the intestine and pancreas, where it may affect glucose absorption and metabolism. Lactisole is a well characterized negative allosteric modulator of the transmembrane domain of T1R3. Lactisole binds with a phenylpropionic acid moiety. More recently, ibuprofen and naproxen, which are similar to lactisole in structure, have been identified to inhibit human T1R3 when heterologously expressed in cells. In the present study, the initial objective was to determine if ibuprofen and naproxen inhibit interactions of sugars with human sweet taste receptor under normal, physiological conditions. Ten healthy participants were asked to rate sweetness intensity for a range of sweet stimuli (sucrose, fructose, sucralose) after a prerinse of ibuprofen, naproxen or water. Both ibuprofen and naproxen inhibited sweet taste intensity in a dose-dependent manner. The experiment was repeated in vitro with TAS1R2-TAS1R3 expressing human cells, with ibuprofen reducing signaling of sucrose and sucralose. To explore ibuprofen's potential connection with glucose signaling and metabolism, the investigators next tested whether prerinses of lower concentrations of ibuprofen including a typical peak plasma concentrations (0.18 mM, 0.57 mM and 5.7 mM), would affect sweet taste intensity ratings of lower levels of glucose. Ibuprofen inhibited glucose sweetness in a dose dependent manner. Finally, the investigators tested whether prerinses of 0.12 mM and 0.24 mM ibuprofen (resulting from ingestion of two or three 200 mg pills respectively) affects detection thresholds of glucose, which are concentrations nearing post-prandial plasma glucose levels. Detection thresholds were significantly higher after rinsing with 0.24 mM ibuprofen compared to water rinses (p<0.01, n=12). In association studies, ibuprofen use has been linked to preserved metabolic function, as its use is correlated with lower rates of Alzheimer's disease, diabetes and colon cancer. Here the investigators present a potential novel pathway for systemic ibuprofen to impact these metabolic diseases.