Protein intake counteracts alcohol intake in the regulation of postprandial FGF21 secretion in humans.

FGF21 is a hormone secreted from the liver in response to various nutritional stressors, suggested to act to balance dietary intake through negative feedback regulation. This meal study aimed to investigate two different potential nutrient interactions on postprandial FGF21 secretion in healthy human participants: 1) between intake of alcohol and protein, and 2) between intake of alcohol and vitamin A (retinol). In a 4-arm, randomized, double-blinded, cross-over meal study (NCT06105476), postprandial circulating concentrations of FGF21, glucose, insulin, ethanol, and acetate were compared after intake of four different test drinks containing alcohol, alcohol + protein, alcohol + retinol, or retinol in 27 healthy humans. The postprandial FGF21 response to the alcohol + protein drink was severely attenuated compared with the alcohol drink. The FGF21 response to the alcohol + retinol drink was similar to the alcohol drink, whereas there was no FGF21 response to the drink with retinol only. In conclusion, intake of protein inhibited the secretory FGF21 response to alcohol intake, whereas retinol intake did not appear to influence FGF21 secretion.NEW & NOTEWORTHY The hepatic hormone FGF21 is regulated by dietary intake. The results of this human meal study suggest that coconsumption of protein inhibits alcohol-induced FGF21 secretion in humans, similar to how protein intake previously has been shown to inhibit sugar-induced FGF21 secretion. This indicates that dietary protein is a consistent downregulator of FGF21. We found no indication that intake of retinol influences FGF21 regulation.