Omega-3 polyunsatured fatty acids and physical performance across the lifespan: a narrative review

Abstract

Background and aims: Physical performance is a major contributor of mobility and independence during older life. Despite a progressive decline in musculoskeletal function starts from middle age, several factors acting during the life-course can negatively influence musculoskeletal functional capacities. Lifestyle interventions incorporating nutrition and physical exercise can help maximizing the muscle functional capacities in early life as well as preserving them later in life. Among various dietary compounds, omega-3 polyunsaturated fatty acids (PUFAs) are gaining growing attention for their potential effects on muscle membrane composition and muscle function. Indeed, several pathways are enhanced, such as an attenuation of pro-inflammatory oxidative stress, mitochondrial function, activation of the mammalian target of rapamycin (mTOR) signaling and reduction of insulin resistance.

Methods: We performed a narrative review to explore the existing literature on the relationship between omega-3 PUFAs and physical performance across the life-course.

Results: Growing evidence from randomized controlled trials (RCTs) suggests beneficial effects of omega-3 PUFAs on muscle function, including physical performance parameters in mid to later life. On the other hand, despite a direct association in early life is not available in literature, some mechanisms by which omega-3 PUFAs may contribute to improved adult physical performance could be hypothesized.

Conclusion: Omega-3 PUFAs are gaining growing attention for their positive effect on muscle function parameters. The integration of physical function measures in future studies would be of great interest to explore whether omega-3 PUFAs could contribute to improved muscle function, starting from early life and extending throughout the lifespan. However, larger and high-quality RCTs are needed to fully elucidate the beneficial effects of omega-3 PUFAs supplementation on muscle mass and function.

Keywords: aging; frailty; life course; nutrition; omega-3 PUFAs; sarcopenia.

Figure 1

Muscle strength across the life course. Modified from Cruz-Jentoft et al. (3), licensed under CC BY-NC 4.0. The rate of decline in muscle strength is reflected by the peak attained during early life. Maximizing the peak of muscle strength in early life as well as maintaining this peak during adult life is pivotal to minimize losses during older life.

Figure 2

Overview of polyunsaturated fatty acids metabolism in mammals. Schematic metabolic pathways of the two families of polyunsaturated fatty acids in mammals, omega-3 and omega-6, from the precursors α-linolenic acid and linoleic acid, respectively. In this figure are represented all the consecutive desaturation and elongation steps and the names of major eicosanoids derived. ALA, α-linolenic acid; LA, linoleic acid; EPA, eicosapentaenoic acid; DPA, docosapentaenoic acid; DHA, docosahexaenoic acid; AA, arachidonic acid.

Figure 3

Overview of the main mechanisms by which Omega-3 PUFAs can influence muscle parameters. Modified from Therdyothin et al. (47), licensed under CC BY 4.0. Omega-3 PUFAs, incorporated into the cell membrane, modulate neuromuscular transmission and seem to directly stimulate mTORC1, both as stand-alone and synergically with amino acids ingestion thus enhancing muscle protein synthesis. Omega-3 PUFAs also counteract inflammatory processes through less production of inflammatory mediators as well as by the release of pro-resolution mediators and by reducing ROS production at the mitochondrial level, thus decreasing muscle protein breakdown. Omega-3 PUFAs also act as ligands for G-protein coupled receptors (GPCRs) and induce the activation of the peroxisome proliferator-activated receptors (PPARs), with the consequent inhibition of nuclear factor kappa B (NFκB). In turn, the inhibition of NFκB leads to a reduced cyclooxygenase production resulting in a decreased inflammatory response finally reducing muscle protein breakdown. The inhibition of NF-κB also leads to the downregulation of the muscle ring finger-1 (MuRF-1) gene counteracting the ubiquitin-proteasome system and thus reducing muscle protein breakdown. n-3 PUFA, omega-3 polyunsaturated fatty acid; mTORC1, mammalian target of rapamycin complex; NFκB, nuclear factor kappa B; MuRF-1, muscle ring finger-1; PPARs, peroxisome proliferator-activated receptors.

Figure 4

Possible mechanisms mediating the associations between low omega-3 status during early life and physical performance decline later in life. Decreased omega-3 status has been associated with low birth weight, altered growth and development parameters in early life and decreased immune function, augmented inflammation and oxidative stress across the lifespan. In turn, all these mechanisms have been largely associated with poor physical performance during older life. ↓, decreased; ↑, increased.