Omega-3 PUFAs in musculoskeletal health and sports medicine: from molecular pathways to precision nutrition strategies

The imbalance in the dietary ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratio contributes to chronic low-grade inflammation, a key pathological basis for degenerative musculoskeletal conditions such as osteoporosis and osteoarthritis. While individual reviews have explored aspects of ω-3 PUFAs in bone or muscle, a comprehensive narrative review integrating their multidimensional mechanisms with translational evidence across orthopedics and sports medicine is less common. This review consolidates evidence from fundamental science, clinical trials, and translational research, employing an interdisciplinary approach to systematically elucidate their mechanisms and application values. ω-3 PUFAs exert multi-layered anti-inflammatory and pro-repair effects through mechanisms including cell membrane remodeling, reprogramming of lipid mediator profiles (promoting the generation of specialized pro-resolving mediators), and inhibition of key pathways such as NF-κB and the NLRP3 inflammasome. Clinical studies indicate that ω-3 PUFA supplementation can improve bone metabolic markers, alleviate pain in osteoarthritis, and reduce inflammation and muscle loss in the perioperative period. In sports medicine, ω-3 PUFAs enhance muscle anabolic metabolism, optimize energy utilization, promote recovery, and demonstrate neuroprotective potential. Their extended application value lies in regulating the "bone-muscle axis," providing targeted nutritional support for athletes, and serving as a nutritional countermeasure in extreme environment medicine. Statement of Significance: This review constructs an integrative framework linking molecular mechanisms to clinical translation, positioning ω-3 PUFAs as key physiological modulators for musculoskeletal health and delineating future directions for precision nutrition-based intervention strategies.