Endocrine Abstracts

Background: Fibroblast growth factor 21 (FGF21) is a hormone induced in the liver by metabolic stressors including starvation, sugars, and ethanol. Alcohol consumption increases endogenous FGF21 levels in humans while administration of FGF21 has been shown to reduce alcohol consumption in non-human primates. The effect of acute moderate alcohol consumption and long-term alcohol cessation on FGF21 levels in humans is controversial. We hypothesize that even moderate alcohol consumption increases FGF21 levels and that reduced long-term alcohol consumption lowers FGF21 levels.

Methods: We included data from two prospective intervention studies: first, a randomized, crossover design with 10 healthy men consuming beer (goal blood alcohol concentration of 0.8‰) or water. Blood samples were collected at six time points over the observation period of 720 minutes. The primary endpoint was difference in FGF-21 levels following both interventions. Second, 147 alcohol-drinking individuals participating in a randomized, placebo-controlled trial investigating the effect of glucagon-like peptide 1 (GLP-1) receptor agonist dulaglutide on smoking cessation. Alcohol consumption was assessed at baseline and after 12 weeks of treatment. The primary endpoint was change in FGF21 levels in persistent drinkers and those who had stopped drinking.

Results: In healthy volunteers, blood alcohol concentration peaked at 90 min and FGF21 levels increased from 125.5 pg/ml to 3149.6 pg/ml at 240 min after beer intake and from 142.0 pg/ml to 184.8 pg/ml after water intake (estimated difference 1386.0 (95% CI 934.55, 1837.44), P<0.001). FGF21 levels remained elevated at 720 min after beer intake (525.3 pg/ml vs 302.7 pg/ml, P=0.028). In the individuals striving for smoking cessation, median (IQR) baseline alcohol consumption was 3 glasses/week (2, 7) and median (IQR) FGF21 levels were 458.87 pg/ml (278.81, 779.81). At 12 weeks, 27 had stopped drinking alcohol which correlated with lower FGF21 levels (356.18 pg/ml (228.17, 720.75) vs 413.07 pg/ml (223.58, 717.83), estimated difference 228.65 pg/ml (95% CI 14.57, 440.35), P=0.03). The results were independent of age, sex, BMI, or smoking status. There was no difference in FGF21 levels between intervention (P=0.3) or smoking status (P=0.1).

Conclusions: Our findings suggest a dynamic response in FGF21 levels, with moderate acute alcohol consumption inducing elevated FGF21 levels, reflecting metabolic liver stress. In contrast, the reduction in long-term moderate alcohol consumption was associated with lower FGF21 levels, indicative of potential liver recovery These insights contribute to our understanding of the interplay between alcohol consumption and FGF21 dynamics, emphasizing the importance of both short and long-term considerations in liver health.