Muscles have a variety of important functions in the body. They create force and movement, support bones to maintain posture, contribute to energy metabolism and storage, and regulate endocrine function. Several health conditions result from muscle mass loss, including sarcopenia, cachexia, and muscle disuse atrophy. Muscle wasting diseases are linked to chronic, low-grade inflammation with elevated concentrations of pro-inflammatory cytokines, such as interleukin (IL)-6, tumor necrosis factor-alpha, and IL-1 beta. 

Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to possess anti-inflammatory properties. EPA and DHA are present in fish oil, krill oil, and algae. EPA and DHA can be synthesized endogenously from the essential fatty acid alpha-linolenic acid (ALA), but this conversion can be limited. After ingestion, EPA and DHA are incorporated into cell membranes, including sarcolemma of skeletal muscle fibers and inflammatory immune cells. The n-3 PUFAs in cell membranes can potentially reduce the production of pro-inflammatory molecules and act as substrates for anti-inflammatory chemical mediators, such as resolvins, protectins, and maresins. 

Research suggests that n-3 PUFA supplementation has the potential to support muscle health and function. The anti-inflammatory properties of n-3 PUFAs were shown to counteract muscle loss by reducing toxic lipid mediators that induce muscle metabolism disorders, such as ceramides and diglycerides. Intake of n-3 PUFAs may also promote muscle protein turnover through mammalian target of rapamycin (mTOR) activation by P13K/Akt and mitogen-activated protein kinase pathways. 

Furthermore, n-3 PUFAs may support proper insulin response in skeletal muscles. Insulin-like growth factor-1 (IGF-1) and insulin are the main anabolic signaling molecules for muscle synthesis, playing a crucial role in the initiation of protein translation and activation of the mTOR protein. The n-3 PUFAs may attenuate insulin resistance and decrease IGF-1 levels linked to diminished muscle protein synthesis and induced muscle atrophy. 

One meta-analysis found that increased n-3 PUFA supplementation (2 g daily) may have the potential to lower the loss of muscle mass in the elderly. A systematic review and meta-analysis inferred a positive effect of n-3 PUFA supplementation on overall body muscle mass and strength, particularly in individuals at risk of sarcopenia. Additionally, research suggests supplementation of n-3 PUFAs could reduce lipotoxicity in muscles and limit insulin and anabolic resistance in those with rheumatoid arthritis. 

Many Americans fail to meet n-3 PUFA dietary recommendations (1.6 g daily for men and 1.1 g daily for women ≥14 years old) while concurrently consuming large amounts of omega-6 (n-6) PUFAs, arachidonic acid, a precursor to pro-inflammatory mediators. The n-6 PUFAs compete with EPA and DHA for biosynthesis and cell membrane incorporation, making their ratio of utmost importance. Further research is necessary to determine the role of n-3 PUFAs in musculoskeletal health for different muscle-wasting disorders. However, considering the high ratio of n-6 to n-3 PUFAs in a typical Western diet, increasing n-3 PUFA intake may have clinically relevant benefits in promoting muscle health and function. 

By Danielle Moyer, MS, CNS, LDN