Ibuprofen suppresses the perception of sweet taste

Ibuprofen suppresses the perception of sweet taste

New research suggests that common NSAIDs such as ibuprofen may impair the perception of sweet tastes by inhibiting key taste receptors - raising questions about their possible effects on metabolism and glucose regulation.

A recently published study in theBritish Journal of PharmacologyExplores how taste receptors respond to sweet stimuli after 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 such as sugars, certain amino acids, non-nutritive sweet stones (NNs), and metal salts activate these receptors and trigger neural signals that lead to the sensation of sweetness.

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

Gymnemianic acid, zinc salts, sodium lactisol, as well as phenoxyherbicides and fibrates can inhibit the activity of Tas1r2-Tas1R3. To date, it remains unclear whether nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen, both of which share the phenylpropionic acid moiety of lactisol, similarly inhibit Tas1R2-Tas1R3 activity. The widespread use of NSAIDs, particularly ibuprofen, requires additional clarification to identify potential off-target metabolic effects associated with this drug.

About the study

Researchers in the current study examined whether exposure to ibuprofen inhibits TAS1R2-TAS1R3 signalingin vitroAndIn vivo.For this purpose, a total of 32 study participants, 15 of whom were male and 17 of whom were women, between 18 and 58 years of age, performed an oral rinse with or without ibuprofen or naproxen. A sex-matched cohort of hyperglycemic patients was also included in the analysis.

After oral rinsing, study participants rated the sweetness of sucrose, sucralose, or fructose solutions. Candy intensity, measured using a general marked size scale (GLMS), was described as barely detectable, weak, moderate, strong, very strong, and strongest imaginable.

The researchers also determined the effects of physiologically relevant ibuprofen levels on TAS1R2-TAS1R3 signalingin vitroUsing human embryonic kidney 293 (HEK 293) cells.

Study results

Replicate physiologically relevant ibuprofen concentrationsin vitro,The researchers selected 0.12 and 0.24 mm doses of ibuprofen, which correspond to plasma levels after an oral dose of 400 and 600 mg of ibuprofen, respectively. In HEK293 cells genetically engineered to 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 m m sucralose.

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

Ibuprofen concentrations of 0.18, 0.57, and 5.7 mM were also used in an oral rinse to determine the influence of ibuprofen exposure on glucose sweetness perception. While ibuprofen 0.18 and 0.57 mM reflect physiologically relevant plasma serum levels after an oral dose of 400 and 600 mg, respectively, 5.7 mM plasma levels are achieved after 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 effect inhibitors of the Tas1r2-Tas1R3 responses on physiological postprandial plasma levels of glucose. “

Conclusions

Both ibuprofen and naproxen potently inhibit htas1r2-tas1r3 receptors, which detect sweetness in a dose-dependent manner. The suppression of glucose signaling by ibuprofen and naproxen at physiological concentrations suggests a potentially profound effect of these NSAIDs on carbohydrate absorption and metabolism.

NSAIDs such as ibuprofen and naproxen are commonly used, with current estimates using ibuprofen more than once per week while 3.5% use naproxen weekly. The effects of ibuprofen and naproxen highlight the importance of conducting additional clinical trials to confirm that these NSAIDs inhibit Tas1r2-Tas1R3 and whether these effects can support metabolic health.

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