Fibroblast Growth Factor 21 And Fructose Dynamics In Humans

ObjectiveFructose consumption is a risk factor for metabolic disease. We recently demonstrated that fibroblast growth factor 21 (FGF21), a metabolic hormone involved in lipid and glucose metabolism, is acutely stimulated in humans by 75g oral fructose, with peak levels occurring 2h after consumption. This study reports on the dose dependency and reproducibility of the FGF21 response to fructose.MethodsLean, healthy adults drank either five different doses of fructose dissolved in water, each separated by 2weeks, or the same dose on three occasions, each separated by 1week.ResultsFibroblast growth factor 21 levels peaked at 2h in a dose-dependent manner. No significant increase in FGF21 was seen after consumption of 10g fructose, while robust increases were seen after drinking solutions containing 30, 50 and 75g. At 2h, the minimal fold change of FGF21 was highest following a 75g fructose drink, and all subjects demonstrated at least a doubling of FGF21 levels following consumption of this dose.ConclusionsThe increase in FGF21 following an oral fructose challenge is dose dependent, with levels peaking at 2h independent of dose. The FGF21 response to 75g fructose is also highly reproducible within individuals.Clinical ImplicationsBy demonstrating that the FGF21 response to fructose is dose dependent and reproducible, this study deepens current understanding of FGF21 fructose dynamics and physiology in humans. This is an important area of clinical interest given associations between fructose intake and a wide variety of metabolic derangements.