Effects of short-term fasting and different overfeeding diets on thyroid hormones in healthy humans

Background Greater decrease in 24-h energy expenditure (EE) during fasting and smaller increase in 24-h EE during low-protein overfeeding (metabolic "thrifty" phenotype) predict weight gain. As thyroid hormones (TH) are implicated in energy intake and metabolism, we assessed whether: 1) TH concentrations are altered by 24-h fasting or overfeeding diets with varying protein content; 2) diet-related changes in TH correlate with concomitant changes in EE. Methods Fifty-eight euthyroid, healthy subjects with normal glucose regulation underwent 24-h dietary interventions including fasting, eucaloric feeding, and five overfeeding diets in a crossover design within a whole-room indirect calorimeter to measure 24-h EE. Overfeeding diets (200% of energy requirements) included three diets with 20%-protein, one diet with 3%-protein (LPF: 46%-fat), and a diet with 30%-protein (HPF: 44%-fat, n=51). Plasma free thyroxine (FT4), triiodothyronine (FT3), and fibroblast growth factor 21 (FGF21) concentrations were measured after overnight fast the morning of and after each diet. Results On average, FT4 increased by 8% (+0.09 ng/dL, 95% CI: 0.06-0.13, p<0.001) while FT3 decreased by 6% (-0.17 pg/mL, CI: -0.27 to -0.07, p=0.001) after 24-h fasting, whereas both FT4 and FT3 decreased by 5% (-0.08 ng/dL, CI: -0.11 to -0.04, p<0.0001) and 4% (-0.14 pg/mL, CI: -0.24 to -0.04, p=0.008) following HPF, respectively. Greater decreases in FT3 after HPF associated with larger decreases in FGF21 (r=0.40, p=0.005). Following LPF, mean FT3 increased by 6% (+0.14 pg/mL, CI:0.05-0.2, p=0.003) with no change in FT4 (p=0.7). No changes in TH were observed after normal-protein overfeeding diets (all p>0.1). No associations were observed between TH concentrations and diet-related changes in 24-h EE during any diet (all p>0.07). Conclusion Acute (200%), short-term (24h) changes in food intake induce small changes in TH concentrations only after diets with low (0%-fasting and 3%-protein overfeeding) or high (30%-protein overfeeding) protein content. The FT3-FGF21 association after high-protein overfeeding suggests a role for TH in inhibiting FGF21 secretion by the liver during protein excess. These results indicate that TH are involved in protein metabolism; however, they do not mediate the short-term EE response to diets that characterize the metabolic phenotypes and determine the individual susceptibility to weight gain.