{"doi":"10.1111/bph.70004","title":"Ibuprofen inhibits human sweet taste and glucose detection implicating an additional mechanism of metabolic disease risk reduction","abstract":"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.","journal":"British Journal of Pharmacology","year":2025,"id":538896,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.964,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":661816,"name":"Caroline P Harmon","orcid":"0000-0003-4803-1984","position":1,"is_corresponding":false},{"id":661817,"name":"Daiyong Deng","orcid":"0000-0001-5899-9177","position":2,"is_corresponding":false},{"id":1407328,"name":"Sarah M. Sywanycz","orcid":"0009-0005-7853-3696","position":3,"is_corresponding":false},{"id":1238781,"name":"Lauren Caronia","orcid":null,"position":4,"is_corresponding":false},{"id":393021,"name":"Peihua Jiang","orcid":"0000-0001-6705-8248","position":5,"is_corresponding":false},{"id":429745,"name":"Paul Breslin","orcid":"0000-0001-5988-8401","position":6,"is_corresponding":false},{"id":759791,"name":"Emily C Hanselman","orcid":"0000-0003-0778-7881","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T02:52:25.799399Z","pmid":"39999478","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}