Daniele Cannavaro

Background/Objectives: Clinically meaningful weight loss reduces fat mass but is commonly accompanied by loss of fat-free mass (FFM). Ketogenic diets are of interest because ketone bodies have plausible anabolic and anti-catabolic actions. This narrative review examined whether these mechanisms translate into preservation of lean compartments or skeletal muscle during weight loss in clinical studies. Methods: MEDLINE was searched via PubMed from database inception to 14 August 2026 using terms related to ketogenic exposure, body composition, muscle metabolism, and weight loss. Evidence was synthesised according to dietary context, energy and protein intake, population, exercise exposure, measurement modality, and timing relative to carbohydrate restriction or reintroduction. Results: Acute human studies demonstrate biological effects of ketone bodies on muscle protein turnover and signalling, but these findings do not establish long-term tissue preservation during ketogenic weight-loss diets. Supervised very-low-energy ketogenic diets generally produce weight loss composed predominantly of fat mass; however, comparative meta-analyses report small yet larger reductions in FFM or lean body mass than non-ketogenic regimens. Because most studies used hydration-sensitive compartment methods rather than direct anatomical imaging of skeletal muscle, the contributions of glycogen, water, and non-muscle lean tissues remain uncertain. Energy deficit, protein intake, resistance exercise, baseline adiposity, age, metabolic health, and training status may modify the observed response. Conclusions: Current evidence is insufficient to determine whether ketosis itself has either a protective or harmful effect on contractile skeletal muscle during weight loss. Ketogenic diets may be effective short-term options for selected adults with obesity, particularly within supervised protocols, but adequate protein, resistance exercise, and monitoring of strength and physical function remain the best-supported muscle-preserving strategies.

Background/Objectives: Weight loss interventions in individuals with overweight or obesity result in reductions in both fat mass and lean body mass (LBM). While fat loss is the primary therapeutic target, preserving LBM may have favorable health implications. This narrative review evaluates the role of amino acid supplementation, including essential amino acids (EAAs) and branched-chain amino acids (BCAAs), in supporting the preservation of LBM during weight loss induced by lifestyle interventions, pharmacotherapy, or bariatric surgery. Methods: This is a narrative review of preclinical and clinical studies examining the effects of amino acid supplementation during calorie restriction on body composition and, when available, functional outcomes. A comprehensive search was conducted in the PubMed, Scopus, and Web of Science databases. Results: Evidence suggests that EAA and peptide-based supplementation may help preserve LBM during periods of reduced energy intake, particularly when protein intake from whole foods is limited. Benefits appear more consistent when supplementation is combined with resistance exercise. BCAA supplementation alone has shown variable effects, especially in sedentary individuals or when total protein intake is already sufficient. Anabolic resistance associated with obesity may attenuate the muscle protein synthesis response to dietary amino acids. Conclusions: Amino acid supplementation may support the maintenance of LBM during weight loss, particularly under conditions of low protein intake or in conjunction with exercise. Further research is needed to determine the clinical significance of LBM changes and identify optimal supplementation strategies.