Excessive weight loss during alternate day modified fasting increases the risk of hyperuricemia and muscle loss

Obesity has become a significant contributor to non-communicable diseases worldwide, making it imperative to explore effective weight-loss methods. Alternate day modified fasting (ADMF) has emerged as a popular approach, but its effects on uric acid (UA) dynamics and body composition in Chinese populations remain unclear. This study aimed to investigate whether ADMF could change body composition and cardiometabolic parameters in individuals with obesity, and to analyze the correlation between changes in body composition indices and UA levels.

A total of 35 adults were recruited and completed a 62-day trial, which consisted of a 32-day high-controlled fasting phase (HCFP) and a 30-day low-controlled fasting phase (LCFP). Body composition was measured by bioelectrical impedance analysis, and blood pressure (BP) and metabolic parameters were assessed at baseline, day 16, day 32, and day 62.

Of the 35 participants (20 males, 15 females; mean age 36.23 ± 8.98 years; baseline body weight 100.02 ± 16.89 kg; baseline BMI 35.47 ± 4.15 kg/m²), body weight decreased significantly over the entire 62-day ADMF intervention (absolute loss: -6.83 ± 4.26 kg; -7.02%, P < 0.001). The proportion of total weight loss attributable to fat free mass (FFM) was 22.68%. During HCFP, weight decreased by -6.38% (absolute loss: -6.29 ± 3.11 kg, P < 0.001), with significant reductions in body fat mass (BFM, -11.14%, P < 0.001), FFM (-3.32 %, P < 0.001), visceral fat area (VFA, -13.10%, P < 0.001), and waist circumference (WC, -5.35%, P < 0.001). However, significant losses in soft lean mass (SLM; -3.40%, P < 0.001) and fat free mass (FFM; -3.32%, P < 0.001) were observed during HCFP, with partial improvement during LCFP (SLM: +0.73%, P = 0.031; FFM: +0.78%, P = 0.022). A transient but significant increase in UA occurred during HCFP (+27.30 ± 79.60 umol/L, +8.85% from baseline, P = 0.047), which subsequently decreased during LCFP (-33.70 ± 72.48 μmol/L, -6.67% from Day 32 to Day 62, P = 0.012). This UA elevation was correlated with concurrent loss of SLM (r = -0.340, P = 0.025).

A phased ADMF intervention was associated with effective reduction in adiposity and improvement in cardiometabolic risk factors. However, the transient hyperuricemia and lean muscle loss during the intensive phase suggest that UA monitoring and muscle-preserving strategies may be considered to optimize the safety and efficacy of ADMF protocols.