Ibuprofen Inhibits Human Sweet Taste

Not Applicable

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
• Interventions: Drug: Inhibition of Sweet Taste by Naproxen Oral Rinses; Drug: Inhibition of Sweet Taste by Ibuprofen Oral Rinses

• Registration Number: NCT06291337
• Lead Sponsor: Rutgers, The State University of New Jersey

Brief Summary

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.

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 Timeline

• Study Start: 2020-06-01
• Primary Completion: 2023-09-01
• Study Completion: 2023-09-30
• Status Verified: 2024-02
• Study First Submitted: 2024-02-15
• Study First Submitted QC: 2024-02-26
• Last Update Submitted: 2024-02-26
• Study First Posted: 2024-03-04
• Last Update Posted: 2024-03-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment of sweet taste receptors with naproxen oral rinse	Inhibition of Sweet Taste by Naproxen Oral Rinses	Participants were tested for sweetness perception without and with an oral rinse of naproxen.
Treatment of sweet taste receptors with Ibuprofen oral rinse	Inhibition of Sweet Taste by Ibuprofen Oral Rinses	Participants were tested for sweetness perception without and with an oral rinse of ibuprofen.

Primary Outcome Measures

Name	Time	Method
Sweet taste ratings	6 months	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.
Sugar detection thresholds	6 months	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.

Trial Locations

Locations (1)

Food Science and Nutritional Sciences; 🇺🇸 New Brunswick, New Jersey, United States