The Role of Omega-3 Polyunsaturated Fatty Acids on Sarcopenia and Aging Muscle

Sarcopenia, characterized by the progressive loss of skeletal muscle mass, strength, and function, represents a major public health challenge in aging populations. This condition affects approximately 10–16% of community-dwelling older adults and is associated with increased risks of falls, frailty, functional decline, and mortality. The pathogenesis of sarcopenia involves chronic low-grade inflammation (inflammaging), oxidative stress, mitochondrial dysfunction, and anabolic resistance. Omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have emerged as promising nutritional interventions due to their anti-inflammatory properties and potential anabolic effects on skeletal muscle. This comprehensive review evaluates the current evidence on omega-3 PUFA supplementation for the attenuation and management of sarcopenia. Mechanistically, omega-3 PUFAs appear to enhance muscle protein synthesis through activation of the mTOR-p70S6K signaling pathway, reduce inflammation via specialized pro-resolving mediators (SPMs), improve mitochondrial bioenergetics, and attenuate muscle disuse atrophy. Clinical trials demonstrate that omega-3 supplementation, particularly at doses exceeding 2 g/day of combined EPA and DHA, can increase thigh muscle volume, handgrip strength, and one-repetition maximum strength in older adults. When combined with resistance exercise training, the benefits appear more pronounced, especially in women. However, heterogeneity in study designs, intervention durations, dosages, and outcome measures has produced some conflicting results. Large-scale trials, such as the MAPT study, have shown null findings for long-term supplementation alone, suggesting that omega-3s may be most effective as part of multimodal interventions. The evidence also supports benefits in clinical populations at risk for muscle wasting, including cancer patients experiencing cachexia and individuals with neuromuscular disorders. Future research should focus on identifying optimal dosing strategies, understanding sex-specific responses, and elucidating the mechanisms underlying the synergistic effects of omega-3s with exercise. Overall, omega-3 PUFA supplementation represents a safe, accessible, and potentially effective nutritional strategy for attenuating muscle decline in aging and clinical populations, though its benefits appear most pronounced when combined with resistance exercise as part of a multimodal approach.