Objective  Fibroblast growth factor (FGF21) is a potent regulator of glucose and lipid metabolism. In rodents, the hepatic expression of FGF21 is controlled by fasting and a circadian regulation, but the physiological role and regulation of FGF21 in humans is not well established. Therefore, the objective of this study was to elucidate the 24‐h profiling of plasma FGF21 during a 72‐h fast.

Study design  After an initial 12‐h overnight fast, plasma levels of FGF21 together with circulating levels of glucose, insulin, glucagon and free fatty acids (FFA) were measured every 6 h during a 72‐h fast in healthy female volunteers (n = 14).

Results  During the fast, plasma glucose and serum insulin gradually decreased whilst glucagon and FFA levels increased. Mean 24‐h plasma FGF21 levels did not increase during the 72‐h fast, but, despite large inter‐individually variations, a significant circadian rhythm was observed. Thus, during the first day, plasma FGF21 increased from 125 pg/ml (16–142) at 8.30 a.m to peak levels of 224 pg/ml (88–326) at 2.30 a.m (P = 0·0215), the second day from 60 pg/ml (7–74) at 8.30 a.m to 268 pg/ml (103–410) at 2.30 a.m. (P = 0·0010) and the third day from 94 pg/ml (9–146) to 151 pg/ml (87–207) at 2.30 a.m. (P = 0·0049). Cortisol also showed circadian regulation and peaked at 8.30 a.m every day, 6 h after the observed FGF21 peak.

Conclusion  Plasma FGF21 follows a circadian rhythm during a 72‐h fast in healthy female subjects. The circadian regulation has a stronger impact on plasma FGF21 than the fasting status over 72‐h period.