Systemic metabolic, hormonal, and glycomic remodeling during a 72-hour fast in healthy adults: a pilot study

To investigate integrated biochemical and glycomic signatures in humans related to coordinated metabolic and endocrine adaptations during prolonged fasting, which are essential for maintaining systemic homeostasis.

This single-arm longitudinal interventional study enrolled five healthy adults who underwent a 72-hour water-only fast. Blood samples were collected at baseline (T0), immediately after fasting (T1), and after 11 days of refeeding (T2). A broad panel of biochemical, hormonal, inflammatory, and glycomic parameters was determined. Time-dependent differences were evaluated using the Friedman test.

Fasting induced a distinct biphasic response across multiple circulating markers, with significant alterations in total cholesterol, C-reactive protein, thyroid-stimulating hormone, and free triiodothyronine at T1 followed by recovery toward baseline at T2. Insulin and glucose concentrations declined during fasting and increased after refeeding, although these changes did not reach statistical significance. Plasma, immunoglobulin G (IgG), and IgA N-glycosylation profiles were extensively remodeled, which indicated dynamic metabolic and immune system adaptation. Liver enzymes, electrolytes, and most lipid fractions exhibited only minor and reversible fluctuations.

A 72-hour fast was associated with metabolic and hormonal changes consistent with an environment conducive to autophagy, although autophagy was not measured directly. The protocol appeared feasible and well tolerated in a small cohort of healthy adults. Given the limited sample size, these findings should be considered preliminary and require confirmation in larger studies incorporating direct autophagy markers and additional time points.