Ibuprofen Inhibits Human Sweet Taste

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. Recently, ibuprofen and naproxen 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. 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.

Study Overview

• Status: Completed
• Conditions: Treatment of Sweet Taste Receptors Without or With an Oral Rinse of Ibuprofen Solution in Healthy Participants; Treatment of Sweet Taste Receptors Without or With an Oral Rinse of Naproxen Solution in Healthy Participants
• Intervention / Treatment: Drug: Inhibition of Sweet Taste by Ibuprofen Oral Rinses; Drug: Inhibition of Sweet Taste by Naproxen Oral Rinses

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Food Science and Nutritional Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participant must be able to taste sugars as sweet
• Participant must be able to make ratings on a scale and follow instructions

Exclusion Criteria:

• Participant must not be on any medications that would preclude exposure to NSAIDS
• Participant must not be on any medications that are know to alter taste perception

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment of sweet taste receptors with Ibuprofen oral rinse; Participants were tested for sweetness perception without and with an oral rinse of ibuprofen.	Drug: Inhibition of Sweet Taste by Ibuprofen Oral Rinses; Participants rinse the mouth with ibuprofen and the impact on perceived sweet taste elicited by sugar solutions in the mouth was assessed
Experimental: Treatment of sweet taste receptors with naproxen oral rinse; Participants were tested for sweetness perception without and with an oral rinse of naproxen.	Drug: Inhibition of Sweet Taste by Naproxen Oral Rinses; Participants rinse the mouth with naproxen and the impact on perceived sweet taste elicited by sugar solutions in the mouth was assessed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sweet taste ratings	The impact of oral rinses with NSAIDS on sweet taste ratings of sugars on a labeled magnitude scale was assessed. The numeric outcome is the value of sweetness intensity provided by the participant from the labeled magnitude scale with each sweetener oral rinse.	6 months
Sugar detection thresholds	The impact of oral rinses with NSAIDS on detection thresholds for sugars was assessed. The detection threshold is the lowest concentration of the sweetener solution that can be distinguished from water. The numeric outcome is the concentration of sweetener solution that can be distinguished from water.	6 months

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: Monell Chemical Senses Center
• Investigators: Principal Investigator: Paul A Breslin, Ph.D., Rutgers University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): September 1, 2023
• Study Completion (Actual): September 30, 2023

Study Registration Dates

• First Submitted: February 15, 2024
• First Submitted That Met QC Criteria: February 26, 2024
• First Posted (Estimated): March 4, 2024

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Sensation Disorders; Taste Disorders; Dysgeusia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gout Suppressants; Ibuprofen; Naproxen
• Other Study ID Numbers: Pro2019001483; 10-204Mc (Other Identifier: Rutgers IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the trial, after de-identification.
• IPD Sharing Time Frame: Immediately following publication and ending 7 years following article publication.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal. Proposals should be directed to breslin@monell.org to request data to achieve aims of the proposal. Data are available for 7 years at a third party website:
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No