Ibuprofen suppresses sweet taste perception

By Dr. Liji Thomas, MDReviewed by Benedette Cuffari, M.Sc.Mar 31 2025

New research suggests that common NSAIDs like ibuprofen may blunt sweet taste perception by inhibiting key taste receptors—raising questions about their potential impact on metabolism and glucose regulation.

Study: Ibuprofen inhibits human sweet taste and glucose detection implicating an additional mechanism of metabolic disease risk reduction. Image Credit: Kmpzzz / Shutterstock.com

A recent study published in the British Journal of Pharmacology explores how taste receptors react to sweet stimuli following exposure to ibuprofen.

The role of taste receptors throughout the body

In humans, sweetness is detected by taste receptor class 1, receptor number 2 (TAS1R2)–TAS1R3, which are G protein-coupled receptors expressed on taste bud cells. Exposure to substrates like sugars, certain amino acids, non-nutritive sweeteners (NNS), and metal salts activate these receptors and trigger neural signals that result in the sensation of sweetness.

Taste receptors are expressed in a wide range of tissues including the gastrointestinal tract, pancreas, skeletal muscle, fat, brain, and testes. In addition to taste perception, these receptors support the absorption of dietary sugars, insulin secretion, lipid metabolism, bone formation, and reproductive function.

Gymnemic acid, zinc salts, sodium lactisole, as well as phenoxy herbicides and fibrates can inhibit the activity of TAS1R2-TAS1R3. To date, it remains unclear whether non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen, both of which share the phenylpropionic acid moiety of lactisole, similarly inhibit TAS1R2-TAS1R3 activity. The widespread use of NSAIDs, particularly ibuprofen, necessitates additional clarification to identify any potential off-target metabolic effects associated with this drug.

About the study

The researchers of the current study investigated whether exposure to ibuprofen inhibits TAS1R2-TAS1R3 signaling in vitro and in vivo. To this end, a total of 32 study participants, 15 of whom were male and 17 female, between 18 and 58 years of age performed an oral rinse with or without ibuprofen or naproxen. A cohort of hyperglycemic patients with equal gender representation were also included in the analysis.

After the oral rinse, study participants rated the sweetness of sucrose, sucralose, or fructose solutions. Sweetness intensity, which was measured using a general labelled magnitude scale (gLMS), was described as barely detectable, weak, moderate, strong, very strong, and strongest imaginable.

The researchers also determined the effects of physiologically relevant levels of ibuprofen on TAS1R2-TAS1R3 signaling in vitro using human emnbryonic kidney 293 (HEK 293) cells.

Study findings

To replicate physiologically relevant ibuprofen concentrations in vitro, the researchers selected 0.12 and 0.24 mM doses of ibuprofen, which are equivalent to plasma levels after an oral dose of 400 or 600 mg of ibuprofen, respectively. In HEK293 cells genetically engineered express human TAS1R2-TAS1R3 (hTAS1R2-TAS1R3), both ibuprofen doses prevented receptor activation induced by 25, 50, and 75 mM sucrose, as well as 0.1 mM sucralose.

Ibuprofen and naproxen rinses at concentrations of 13.5 mM and 57 mM, respectively, significantly reduced sweetness perception of sucrose, sucralose, and fructose in a dose-dependent manner. Notably, ibuprofen oral rinses did not significantly impact intensity ratings for salty, bitter, savory, or sour tastes, thus suggesting that ibuprofen specifically targets sweet taste.

Ibuprofen concentrations of 0.18, 0.57, and 5.7 mM were also used in an oral rinse to determine the impact of ibuprofen exposure on glucose sweetness perception. Whereas 0.18 and 0.57 mM ibuprofen reflect physiologically relevant plasma serum levels after an oral dose of 400 and 600 mg, respectively, 5.7 mM plasma levels are achieved following an intravenous dose of 800 mg. At all concentrations, ibuprofen suppressed the intensity sweetness perception with sucrose, sucralose, and fructose in a dose-dependent manner.

Low physiological ibuprofen levels are effects inhibitors of TAS1R2-TAS1R3 responses to physiological post-prandial plasma levels of glucose.”

Conclusions

Both ibuprofen and naproxen potently inhibit hTAS1R2–TAS1R3 receptors that sense sweetness in a dose-dependent manner. The suppression of sugar signaling by ibuprofen and naproxen at physiological concentrations suggests a potentially profound effect of these NSAIDs on carbohydrate absorption and metabolism.

NSAIDs like ibuprofen and naproxen are frequently used, with current estimates indicating that 17% of the United States population uses ibuprofen more than once a week, whereas 3.5% use naproxen weekly. The off-target effects of ibuprofen and naproxen emphasize the importance of conducting additional human clinical trials to confirm that these NSAIDs inhibit TAS1R2-TAS1R3 and whether these effects may support metabolic health.