Alternate-day fasting induces short-term weight loss but is associated with lean mass reduction, study reports

A recent study published in Nutrients raises important concerns regarding the effects of alternate-day fasting (ADF) on body composition, particularly skeletal muscle mass. While ADF resulted in significant short-term reductions in body weight and fat mass over four weeks, it was also associated with a concurrent loss of fat-free mass, suggesting clinically relevant muscle loss. Protein supplementation on fasting days did not reduce this decline. 

The findings are particularly relevant given the escalating global prevalence of obesity. Current estimates indicate that approximately 44% of adults worldwide are overweight and 16% are obese. Similar trends are observed in Singapore, where 41% of adults are overweight and 14% are obese. In this context, intermittent fasting strategies, including ADF, have gained prominence due to reported benefits on metabolic parameters, cardiovascular risk factors, and lipid profiles. 

Alternate-day fasting differs from other intermittent fasting regimens by alternating 24-hour fasting periods with ad libitum feeding days. On fasting days, caloric intake is typically restricted to 400–600 kcal, consisting primarily of non-caloric fluids and a single small meal. Although previous studies have demonstrated improvements in body weight, fat mass, blood pressure, and triglyceride levels with ADF, its impact on lean body mass has remained inadequately characterized. 

To evaluate this, investigators conducted two related studies involving Asian men aged 21–35 years with body mass index (BMI) >23 kg/m², a cutoff associated with increased metabolic risk in Asian populations. Participants were non-smokers and free of comorbidities that could be adversely affected by fasting. One study assessed the effects of four weeks of ADF alone, while the second incorporated protein supplementation. Body composition was measured using bioelectrical impedance analysis at baseline and post-intervention, with serial monitoring of blood pressure and fasting glucose. 

In the protein supplementation study, participants were randomized to receive either standard ADF or ADF plus a 25-g whey protein supplement (125 kcal) on fasting days. Across both studies, 37 participants completed the intervention. Mean caloric intake on fasting days ranged from 495 to 533 kcal. Protein accounted for approximately 25% of fasting-day calories in the non-supplemented group and increased to about 40% in the supplemented group; however, total daily protein intake remained below recommended levels. 

The results demonstrated significant reductions in body weight and fat mass across both cohorts, accompanied by a parallel decrease in fat-free mass. Hydration status remained stable, indicating that reductions in lean mass were unlikely to be due to fluid shifts. The addition of whey protein supplementation did not prevent lean mass loss. The authors attribute this to the relatively modest increase in protein intake, lack of standardized protein intake on feeding days, and overall caloric restriction during fasting periods. 

Participants also reported reduced physical activity levels during weeks two and three, a factor that may have contributed to muscle catabolism. Minor, transient changes in diastolic blood pressure and fasting glucose were observed, while systolic blood pressure remained unchanged throughout the study. 

These findings contrast with earlier evidence suggesting that ADF is a metabolically advantageous intervention. Previous work by Nawaz et al. demonstrated that ADF enhances ketogenesis and lipolysis more effectively than pair-fed caloric restriction. However, the current data underscore the potential musculoskeletal consequences of ADF when implemented without adequate nutritional and exercise support. 

The authors conclude that while alternate-day fasting may be effective for short-term fat loss, it may adversely affect muscle mass, an outcome with implications for metabolic health, physical function, and long-term disease prevention. They recommend future studies examining higher protein dosing strategies, leucine-enriched supplementation, and the integration of resistance training to reduce lean mass loss during ADF. 

From a clinical perspective, these findings suggest that ADF should be prescribed with caution, particularly in populations where preservation of muscle mass is critical, and should ideally be combined with strategies aimed at maintaining or enhancing lean tissue. 

 

Reference 

  1. Pang BWJ, Yang Y, Rashiqah N, Huang CB, Sim DW. Effects of Four Weeks of Alternate-Day Fasting with or Without Protein Supplementation—A Randomized Controlled Trial. Nutrients. 2025 Jan;17(23):3691. 
  2. Nawaz H, Lee H, Kang S, Kim H, Kim W, Go GW. Alternate-day fasting enhanced weight loss and metabolic benefits over pair-fed calorie restriction in obese mice. Obesity (Silver Spring). 2025 Mar;33(3):512-521. 

 

 

 

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