Nutrition as a Therapeutic Strategy to Counteract Age-Related Skeletal Muscle Decline and Metabolic Dysfunction in Older Adults: A Systematic Review

Age-related decline in skeletal muscle mass and function (sarcopenia) is a major contributor to frailty, disability, falls, hospitalization, metabolic dysfunction, and mortality among older adults. With global population aging accelerating, sarcopenia represents an urgent public health and clinical priority. Muscle anabolic resistance, chronic low-grade inflammation, mitochondrial dysfunction, and inadequate dietary protein intake are key biological drivers of age-related muscle loss. Nutritional strategies—including protein supplementation, leucine-enriched formulations, essential amino acids, β-hydroxy-β-methylbutyrate (HMB), vitamin D, omega-3 fatty acids, collagen peptides, and multi-ingredient supplements—have been proposed to counteract anabolic resistance and stimulate muscle protein synthesis. However, evidence across randomized controlled trials (RCTs) remains heterogeneous in terms of intervention composition, dosage, duration, and target population. Furthermore, whole-diet approaches such as Mediterranean-style dietary patterns may exert additional anti-inflammatory and metabolic benefits relevant to muscle health. A comprehensive synthesis of high-quality randomized trials is therefore necessary to clarify the comparative effectiveness of these nutritional strategies in older adults. Objectives The primary objective of this systematic review is to evaluate the effectiveness of oral nutritional interventions on: Skeletal muscle mass (e.g., DXA-derived lean mass, appendicular lean mass) Muscle strength (e.g., handgrip strength, knee extension strength) Physical performance (e.g., gait speed, SPPB, chair stand test) Secondary objectives include evaluating the effects on: Metabolic parameters (fasting glucose, insulin sensitivity, HOMA-IR) Inflammatory markers (CRP, IL-6) Body composition changes Functional frailty indicators