In my last post I talked about how omega-3 fish oil can improve blood flow to the muscles during exercise thereby increasing performance. This post is on the key role omega-3 can play in promoting new muscle growth and strength increases, and also how it helps to prevent muscle loss or wasting due to injury, illness, ageing or when otherwise taking a break from training.
Several studies have shown growth of muscle protein after omega-3 fish oil supplementation, firstly in animals [1-3], and then in humans [4-9]. It seems that this omega-3 muscle growth occurs for 2 reasons, the first is that omega-3 fatty acids, and specifically EPA and DHA, stimulate an anabolic response. The second is that as the omega-3 fatty acids are incorporated into cell membranes in the body, the greater fluidity and insulin sensitivity that they create allow more anabolic nutrients and amino acids to enter the muscle cells from the circulation, which naturally leads to greater muscle growth.
Omega-3’s muscle building or anabolic effects come from it’s ability to switch on the mTOR signalling pathway [6-10]. mTOR is effectively the body’s protein sensing system. It controls cell growth, metabolism, protein synthesis and DNA transcription based on the environment it senses in the body. This means it can get turned on, or off, depending on different physiological factors, such as the availability of nutrients, the body’s biochemistry, stress, as well as hormone, cellular energy and oxygen levels. Because of this, mTOR acts like a master switch for skeletal muscle growth [11-12]. So, if we can turn on mTOR, we can grow more muscle and develop greater strength [13-15].
However, other research has shown omega-3’s influence on the cell membrane of muscle cells may have a much bigger impact on muscle growth than it’s ability to turn on the mTor system. Omega-3’s are preferentially taken up into the membrane of the cell and increase membrane fluidity. This means cell membranes become more permeable so they are better able to transmit nutrients, hormones and chemical and electrical signals into and out of the cell. This means the more permeable they become, the more nutrients, amino acids and anabolic hormones can enter the cell, and the more the cell can synthesise proteins .
One of the key ways omega-3 fluidity seems to effect muscle synthesis is by increasing insulin sensitivity. Most people think of the role of insulin as a hormone that regulates blood sugar, however, insulin’s effect on blood sugar is actually a secondary role, it’s primary purpose is for nutrient storage. Insulin allows our cells absorb the nutrients and energy from our diets that enter our blood stream through the digestive system. How well our cells can absorb the nutrients and energy depends on the sensitivity of the insulin receptors in our cell membranes.
Several studies have shown that omega-3 fish oil has a direct effect on protein synthesis and muscle growth as a result of increased insulin sensitivity , and that omega 3 can help prevent the muscle loss associated with ageing that is due to a loss of insulin sensitivity (known as sarcopenia) [10-17]. The studies all used both men and women with a 4g daily dose of fish oil, with 1.86g of EPA and 1.5g of DHA, although it was in the ethyl ester form which is less well absorbed than natural triglycerides, which suggest supplementation with a natural triglyceride omega-3 can be even more effective.
It’s also an interesting prospect that insulin sensitivity, rather than diet or strength training, could actually be a limiting factor in muscle growth and strength development. Known as ‘Anabolic Resistance’ the muscle cells are simply not being able to access enough amino acids and nutrients to keep making muscle gains, regardless of training, diet or hormone levels. This could be especially relevant for athletes who require massive calorie intakes, including high level of carbohydrates, to maintain huge muscle mass. For example, powerlifters often have this type of diet and can carry significant levels of excess body fat, factors that are known to reduce insulin sensitivity.
Omega-3 Prevents Muscle Breakdown
Muscle is in a constant state of change, and is being continually being broken down, repaired, and new muscle cells being synthesised. This process of ‘anabolism’ and ‘catabolism’ is generally balanced. However, when we focus on building strength through training and increasing our protein intake, we’re trying to create a net positive synthesis balance, where more protein is made than is broken down. Of course during times of injury, illness and prolonged inactivity, catabolism is often greater than anabolism, and we can lose muscle mass.
The system for catabolism, or breaking down of proteins, is governed by the ubiquitin proteasome system. This systems seeks out and breaks down faulty and damaged proteins, or other proteins that are not needed, or are otherwise surplus to requirements. It maintains homeostasis, by ensuring we have the right levels of proteins, in the right amounts, at the right time.
When we take a break from training, or generally become more inactive, our need for muscle mass decreases, and so the ubiquitin proteasome pathway is ‘turned up’ and we tend to lose muscle mass. Also, the system can start to malfunction and become more active due to ageing, infectious diseases, cancers, as well as degenerative and inflammatory conditions like alzheimers, arthritis, diabetes as well as other wasting conditions. However, omega-3 supplementation, and specifically the omega-3 fatty acid EPA, has been shown to turn down or down regulate the ubiquitin proteasome pathway, so there is less muscle wasting  .
Another way omega-3 may have anti-catabolic effects is through it’s effects on stress hormones. Elevated stress hormones such as cortisol, adrenaline and noradrenaline can cause muscle breakdown , and Omega-3 supplementation has been shown to reduce cortisol, catecholamine and adrenal activation  .
Omega-3 fish oil can form an important part of a strength and muscle building program, and can also form an important part of the treatment and care for muscle wasting conditions and muscle loss due to ageing, illness and injury. This is in addition to all of the other health benefits deleted to omega-3 supplementation including better brain function and cognition, improved CV health, improved fat burning and lipid profiles.
The studies suggest aiming for 4g of fish oil per day, however these studies were conducted with the less well absorbed ethyl ester omega fish oil rather than natural triglycerides. I’ve written previously on why this makes a difference and how natural triglycerides are around 70% better absorbed, and triglycerides are also more effective in the body once they have been absorbed. We always recommend supplementing with the best quality triglyceride fish oil you can afford. At Intelligent Labs we only sell the highest quality natural triglyceride oil, and recommend supplementing with 3 capsules per day which is 3 grams of fish oil for maximum muscle gains.
 Alexander J.W., H.Saito, O.Trocki, C.K.Ogle (1986) The importance of lipid type in the diet after burn injury. Ann.Surg. 204:1-8.
 Bergeron K., P.Julien, T.A.Davis, A.Myre, M.C.Thivierge (2007). Long-chain n-3 fatty acids enhance neonatal insulinregulated protein metabolism in piglets by differentially altering muscle lipid composition. J.Lipid.Res. 48:2396-2410.
 Gingras A.A., P.J.White, P.Y.Chouinard, P.Julien, T.A. Davis, L.Dombrowski, Y.Couture, P.Dubreuil, A.Myre, K.Bergeron, A.Marette, M.C.Thivierge (2007) Long-chain omega-3 fatty acids regulate bovine whole-body protein metabolism by promoting muscle insulin signalling to the Akt-mTOR-S6K1 pathway and insulin sensitivity. J.Physiol. 579:269-284.
 Noreen E.E., M.J.Sass, M.L.Crowe, V.A.Pabon, J.Brandauer, L.K.Averill (2010) Effects of supplemental fish oil on resting metabolic rate, body composition, and salivary cortisol in healthy adults. J.Int.Soc.Sports Nutr. 8:7-31.
 Ryan A.M., J.V.Reynolds, L.Healy, M.Byrne, J.Moore, N.Brannelly, A.McHug, D.McCormack, P.Flood (2009) Enteral nutrition enriched with eicosapentaenoic acid (EPA) preserves lean body mass following esophageal cancer surgery: results of a double-blinded randomized controlled trial. Ann. Surg. 249:355-363.
 Smith G.I., P.Atherton, D.N.Reeds, B.S.Mohammed, D.Rankin, M.J.Rennie, B.Mittendorfer (2010) Dietary omega- 3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial. Am.J.Clin.Nutr.
 Gordon I. Smith, Philip Atherton, Dominic N. Reeds, B. Selma Mohammed, Debbie Rankin, Michael J. Rennie, and Bettina Mittendorfer. Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperaminoacidemia-hyperinsulinemia in healthy young and middle aged men and women. Clin Sci (Lond). 2011 Sep; 121(6): 267–278.
 Di Girolamo FG1, Situlin R, Mazzucco S, Valentini R, Toigo G, Biolo G. Omega-3 fatty acids and protein metabolism: enhancement of anabolic interventions for sarcopenia. Curr Opin Clin Nutr Metab Care. 2014 Mar;17(2):145-50.
 McDonald C1, Bauer J, Capra S. Omega-3 fatty acids and changes in LBM: alone or in synergy for better muscle health? Can J Physiol Pharmacol 2013 Jun;91(6):459-68.
 Smith, G.I., et al., Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperinsulinaemia-hyperaminoacidaemia in healthy young and middle-aged men and women. Clin Sci (Lond), 2011. 121(6): p. 267-78.
 Bodine, S.C., T.N.Stitt, M.Gonzalez, W.O.Kline, G.L. Stover, R.Bauerlein, E.Zlotchenko, A.Scrimgeour, J.C.Lawrence, D.J.Glass, G.D.Yancopoulos (2001) Akt/mTOR pathway is acrucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat.Cell.Biol. 3:1014–1019
 Thomas, G., M.N.Hall (1997) TOR signaling and control of cell growth. Curr.Opin.Cell Biol. 9:782-787.
 Bodine, S.C., et al., Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol, 2001. 3(11): p. 1014-9.
 Rommel, C., et al., Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol, 2001. 3(11): p. 1009-13.
 Baar, K. and K. Esser, Phosphorylation of p70(S6k) correlates with increased skeletal muscle mass following resistance exercise. Am J Physiol, 1999. 276(1 Pt 1): p. C120-7.
 Kummerow F.A. (1983) Modification of cell membrane composition by dietary lipids and its implications for atherosclerosis. Ann.NY.Acad.Sci. 414:29-43.
 Guillet, C., et al., Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans. FASEB J, 2004. 18(13): p. 1586-7.
 Rasmussen, B.B., et al., Insulin resistance of muscle protein metabolism in aging. FASEB J, 2006. 20(6): p. 768-9.
 Cuthbertson, D., et al., Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J, 2005. 19(3): p. 422-4.
 Whitehouse A.S., H.J.Smith, J.L.Drake, M.J.Tisdale (2001) Mechanism of attenuation of skeletal muscle protein catabolism in cancer cachexia by eicosapentaenoic acid. Cancer Res. 61:3604-3609.
 Whitehouse A.S., M.J.Tisdale (2001) Downregulation of ubiquitin-dependent proteolysis by eicosapentaenoic acid in acute starvation. Biochem.Biophys.Res. 285:598-602.
 Ross, J.A., A.G. Moses, and K.C. Fearon, The anti-catabolic effects of n-3 fatty acids. Curr Opin Clin Nutr Metab Care, 1999. 2(3): p. 219-26.
 Smith, H.J., J. Khal, and M.J. Tisdale, Downregulation of ubiquitin-dependent protein degradation in murine myotubes during hyperthermia by eicosapentaenoic acid. Biochem Biophys Res Commun, 2005. 332(1): p. 83-8.
 Rooyackers, O.E. and K.S. Nair, Hormonal regulation of human muscle protein metabolism. Annu Rev Nutr, 1997. 17: p. 457-85.
 Delarue J, Matzinger O, Binnert C, Schneiter P, Chioléro R, Tappy L. Fish oil prevents the adrenal activation elicited by mental stress in healthy men. Diabetes Metab. 2003 Jun;29(3):289-95.