Abstract
BACKGROUND AND OBJECTIVE: Resistance training is the cornerstone of sarcopenia management. However, whether combining it with amino acid-based supplementation, including essential amino acids, branched-chain amino acids, leucine, and derivatives such as HMB, provides additional benefits remains unclear. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials until February 2025. Meta- and subgroup analyses were performed using a random-effects model. The Cochrane ROB2 tool and GRADE framework were used to assess the risk of bias and evidence certainty. RESULTS: We included nine randomized controlled trials involving 496 participants with sarcopenia. Evidence rated as low to very low certainty indicated that, compared with resistance training alone, combined amino acid supplementation and resistance training significantly improved handgrip strength (SMD = 0.69, 95% CI: 0.04 to 1.35), gait speed (SMD = 0.64, 95% CI: 0.02 to 1.25), Short Physical Performance Battery scores (SMD = 1.69, 95% CI: 0.81 to 2.57), and Five Times Sit-to-Stand Test performance (SMD = -1.42, 95% CI: -2.68 to -0.16). No significant effects were observed for skeletal muscle mass index or appendicular skeletal muscle mass. Subgroup analyses showed that baseline protein intake, intervention setting, amino acid supplement type, resistance-training frequency, and whether the supplement contained co-nutrients were significant effect modifiers. CONCLUSION: Resistance training combined with amino acid supplementation may improve muscle strength and physical function in older adults with sarcopenia, although effects on muscle mass remain limited. Responsiveness to the intervention may vary by baseline protein intake, training frequency, setting, type of amino acid supplementation, and whether the supplement includes co-nutrients, all of which should be considered when designing sarcopenia management strategies.