Does fish oil build muscle?

Fish oil is one of the more popular supplements. Many athletes are taking it, often because it is believed to be healthy. However, fish oil also has a wide range of claims such as improved performance, improved oxygen efficiency, improved VO₂max, faster recovery and so on. There are mechanisms in the literature that explain it all the way from the food or capsule to function, but a mechanism and actual performance are not the same thing. In this blog we will explore the evidence that fish oil can help muscle building.

Fish oil and muscle building

When omega-3 fatty acids are incorporated into muscle membranes the signalling proteins that control muscle protein synthesis appear to work more readily. Another example is that the membranes of red blood cells become more fluid (more flexible), which has been proposed to help them travel more easily through capillaries and has been linked to oxygen delivery capacity. The theories are attractive, and the incorporation of omega-3 fatty acids into membranes is well documented.

However, not every proposed step has held up when tested in humans. In a dose-response study in healthy men, for example, red blood cell deformability was not affected in a dose-dependent way (we discuss this in the blog on the omega-3 index). But a mechanism is not an outcome. When the question is narrowed to whether adding fish oil puts more muscle on someone who already trains hard and eats enough protein, or whether it improves VO₂max in an already trained cyclist, the applied studies do not provide clear-cut answers. Fish oil is best known for its anti-inflammatory effects, and this stems mostly from studies in the general population. In previous blogs we discussed how reducing inflammation is not always what athletes need or want.

The evidence overall for fish oil in athletes is thin. That is the verdict, and the rest of this blog explains where it comes from and where the exceptions sit, because there are exceptions and they are the interesting part. In the next two blogs we will look at fish oil in injury and in endurance performance. The evidence from all trials of fish oil in athletes is summarised in do athletes need fish oil supplements?.

What omega-3s are, and how much is in a capsule

Omega-3 fatty acids are polyunsaturated fatty acids in which the first carbon double bond sits three carbons from the methyl end of the chain, which is where the name comes from. Three of them matter here: alpha-linolenic acid (ALA), which comes mainly from plant sources, and EPA and DHA, which come mainly from oily fish and from fish oil supplements. ALA can be converted to EPA and DHA inside the body, but the conversion rate is modest, so eating oily fish or supplementing EPA and DHA directly is the reliable way to change omega-3 status. For a fuller overview of where ALA, EPA and DHA come from, see our blog on omega-3 sources.

A fish oil capsule often contains 500 to 1000 mg of fish oil, and 1000 mg of a standard fish oil contains roughly 300 to 350 mg of omega-3 fatty acids. Almost all of this is eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This is important because not all fish oil is equal, and the doses that are commonly taken are smaller than the doses used in the studies that show effects.

Two mechanisms, and only one of them seems to matter for muscle

The first proposed mechanism is the anti-inflammatory action of omega-3s, which is the one most practitioners already know about. We will not focus on this here, but will refer the reader to our blogs on inflammation, which explain why reducing inflammation is not always a good thing or necessary. The second is less familiar and is the anabolic effect. EPA and DHA are readily incorporated into the phospholipid membrane of many cell types, including the red blood cell, cardiac tissue, adipose tissue and skeletal muscle. Once incorporated they change the fluidity and the integrity of that membrane, and this appears to upregulate the activity of the proteins that sit within it.

In skeletal muscle two of those proteins are directly relevant. Focal adhesion kinase (FAK) responds to muscle contraction, and the mechanistic target of rapamycin (mTOR) responds to nutrient provision. Both control muscle protein synthesis, which is the incorporation of amino acids into bound muscle proteins. In the human study described below (3), the increase in muscle protein synthesis after supplementation was not accompanied by any change in inflammatory markers, so the anti-inflammatory route does not appear to be doing this particular job.

It takes weeks, not days

McGlory and colleagues measured how quickly EPA and DHA appear in the membrane during supplementation with 5 g of fish oil per day in 10 healthy men (1). In the blood, the omega-3 content had increased within one week and stayed elevated. In skeletal muscle the increase was slower: it was measurable after two weeks and was still rising at four weeks, when the study ended.

This time course has practical implications. Taking fish oil in the week before a training block or a competition changes little in the muscle membrane. If fish oil is going to be used for a muscle-related reason, the decision has to be made weeks before the effect is wanted, and the supplement has to be taken every day in between.

“If fish oil is going to be used for a muscle-related reason, the decision has to be made weeks before the effect is wanted.”

Is it the EPA or the DHA?

Fish oil has many components, and the most important ones are the omega-3 fatty acids DHA and EPA. One of the questions is whether DHA and EPA have similar functions, or whether a fish oil with a higher DHA or a higher EPA content would be more effective. In one study (2) the effects of DHA and EPA were separated using a cell model. Cultured muscle cells (C2C12 myotubes) were incubated with ethanol as a control, with EPA alone, or with DHA alone, and all of them were then stimulated with leucine to trigger an anabolic response. EPA increased protein synthesis by 25% and reduced protein breakdown by 22%. DHA had no effect on either compared with the ethanol control.

Of course, these are cultured cells rather than people, and a cell in a dish does not have a circulation, a training history or a protein intake. But the result is one reason why later human studies, including the study in trained men described below, used EPA-rich preparations rather than the balanced EPA and DHA formulations sold on most shelves, and it is also the first hint that the two omega-3 fatty acids have different jobs. That point returns in the blog on fish oil and injury and in the blog on the omega-3 index and endurance performance.

The study that got the field interested

The work that opened this area up came from Gordon Smith and colleagues (3), in nine healthy men and women aged 25 to 45 who did not exercise regularly. They supplemented for eight weeks with 4 g of fish oil per day, split fairly evenly between the two fatty acids at 1.86 g of EPA and 1.5 g of DHA. Muscle protein synthesis was measured under basal conditions and under simulated feeding, where amino acids and insulin were infused rather than eaten.

Under basal conditions the eight weeks of supplementation changed nothing. Under simulated feeding the increase in muscle protein synthesis was about 50% larger after supplementation than before it, and the activation of mTOR and p70S6 kinase, another protein upstream of muscle protein synthesis, increased in parallel. Inflammatory markers did not change. So the effect appeared to run through the membrane and the signalling proteins.

Three features of that design limit how much we can extrapolate from this study. The obvious one is that the amino acids were infused into a vein rather than eaten, so they bypassed digestion and absorption entirely. There was no exercise in the protocol, and the participants did not exercise regularly, which matters because trained muscle is already exposed to a large anabolic stimulus several times a week.

What happened when the same question was asked in trained lifters

The follow-up study (4) addressed all three. Resistance-trained young men supplemented for eight weeks, this time with an EPA-weighted preparation providing 3.5 g of EPA and 0.9 g of DHA per day, against a coconut oil control. After the eight weeks they performed a single bout of leg press and leg extension with one leg, and biopsies were taken from both the exercised leg and the rested leg, so that the response to 30 g of whey protein alone could be compared with the response to protein plus muscle contraction in the same person.

There was no difference between the fish oil and coconut oil groups under basal conditions, which matches the earlier work. There was also no statistically significant potentiation of muscle protein synthesis with fish oil when the rested muscle was given protein, and none when the exercised muscle was given protein contraction, even though the omega-3 content of the muscle had doubled. The activity of p70S6 kinase 3 hours after exercise and protein was in fact increased only in the coconut oil group. The hypothesis was not supported, and the authors reported it that way.

It is worth converting these doses into something an athlete can picture. A daily intake of 3.5 g of EPA plus 0.9 g of DHA is about 4.4 g of omega-3, which at 300 mg per capsule is roughly fifteen standard fish oil capsules a day (the study used 5 g of a concentrated fish oil). This is a proof-of-concept dose, chosen to give the mechanism every chance to show itself. Even with that dose it did not, in trained men who were already getting 30 g of whey protein after exercise.

“A daily intake of 3.5 g of EPA plus 0.9 g of DHA is roughly fifteen standard fish oil capsules a day. That dose did not add anything in trained men who were already eating 30 g of protein after training.”

Where the picture changes: a weaker stimulus, or a catabolic one

Those studies asked what fish oil adds to an already optimal anabolic environment. They do not answer the question of what it does when the environment is not optimal, either because the protein dose is suboptimal or because the athlete is in an energy deficit.

In an energy restriction study, Philpott and colleagues (5) restricted 20 resistance-trained young men to 60 per cent of their habitual energy intake for two weeks, and compared fish oil with a control supplement. Body mass fell in both groups, as did lean mass and fat mass, with no difference between the two. So on the primary outcome, fish oil did not spare muscle during a substantial energy deficit. The strength results were mixed: one-repetition maximum (1RM) leg extension of the non-dominant leg increased by about 6% in the fish oil group and did not change in the control group, whereas leg press 1RM, maximal voluntary contraction and muscular endurance changed similarly in both groups. It has been suggested that effects of omega-3s on strength without changes in muscle size reflect effects on neuromuscular function.

Older adults and the masters athlete

The decline in skeletal muscle mass that begins around the age of 50 is a gradual one under normal circumstances, and a much steeper one when a period of disuse is imposed on top of it, whether that is a broken leg, orthopaedic surgery or a spell of bed rest.

Here, unlike in young trained men, fish oil does appear to add something. In a trial in 16 healthy older women who did 6 weeks of resistance training with either a placebo or a high-dose omega-3 supplement, only the omega-3 group increased thigh fat-free mass, and the gain was driven by the cross-sectional area of the type 2 fibres (6). Muscle protein synthesis, measured over several days with deuterium oxide as a tracer, was not significantly higher with omega-3 (there was only a trend), but activation of the signalling protein 4E-BP1 after exercise was greater. Strength outcomes are the more meaningful outcome for older adults. In a larger trial, 50 older men and women did 18 weeks of resistance training with 3 g of fish oil or a placebo per day (7). Maximal isometric strength increased more with fish oil in the women (34% versus 16%) but not in the men, and muscle size did not differ between the groups.

Practical takeaways

• For a resistance-trained athlete who is already eating around 30 g of high-quality protein after training, eight weeks of fish oil at a high dose did not increase muscle protein synthesis, and there is currently insufficient evidence to recommend it as a way to build muscle.

• In cultured muscle cells, EPA but not DHA stimulated protein synthesis. This is cell-culture evidence and has not been shown to translate to people. In the human study in which supplementation augmented the response to feeding, inflammatory markers did not change.

• Incorporation into the muscle membrane takes weeks and was still increasing after four weeks of daily supplementation, so there is no acute or short-term use for this purpose.

• The scenarios where a benefit is more plausible are those where the anabolic stimulus is suboptimal: a low protein dose, a period of energy restriction, or older age. During two weeks at 60 per cent of habitual energy intake, fish oil did not preserve lean mass, and only one of several strength measures improved.

• In older women, omega-3 supplementation alongside resistance training increased thigh fat-free mass and type 2 fibre size in one study and strength in another, but did not significantly increase muscle protein synthesis. In older men, strength did not improve more than with placebo.

References

1. McGlory C, Galloway SDR, Hamilton DL, McClintock C, Breen L, Dick JR, Bell JG, Tipton KD. Temporal changes in human skeletal muscle and blood lipid composition with fish oil supplementation. Prostaglandins Leukot Essent Fatty Acids 90(6) 199-206, 2014.

2. Kamolrat T, Gray SR. The effect of eicosapentaenoic and docosahexaenoic acid on protein synthesis and breakdown in murine C2C12 myotubes. Biochem Biophys Res Commun 432(4) 593-598, 2013.

3. Smith GI, Atherton P, Reeds DN, Mohammed BS, Rankin D, Rennie MJ, Mittendorfer B. 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) 121(6) 267-278, 2011.

4. McGlory C, Wardle SL, Macnaughton LS, Witard OC, Scott F, Dick J, Bell JG, Phillips SM, Galloway SDR, Hamilton DL, Tipton KD. Fish oil supplementation suppresses resistance exercise and feeding-induced increases in anabolic signaling without affecting myofibrillar protein synthesis in young men. Physiol Rep 4(6) e12715, 2016.

5. Philpott JD, Bootsma NJ, Rodriguez-Sanchez N, Hamilton DL, MacKinlay E, Dick J, Mettler S, Galloway SDR, Tipton KD, Witard OC. Influence of fish oil-derived n-3 fatty acid supplementation on changes in body composition and muscle strength during short-term weight loss in resistance-trained men. Front Nutr 6 102, 2019.

6. Brook MS, Din U, Tarum J, Selby A, Quinlan J, Bass JJ, Gharahdaghi N, Boereboom C, Abdulla H, Franchi MV, Narici MV, Phillips BE, Williams JW, Kadi F, Wilkinson DJ, Atherton PJ, Smith K. Omega-3 supplementation during unilateral resistance exercise training in older women: a within subject and double-blind placebo-controlled trial. Clin Nutr ESPEN 46 394-404, 2021.

7. Da Boit M, Sibson R, Sivasubramaniam S, Meakin JR, Greig CA, Aspden RM, Thies F, Jeromson S, Hamilton DL, Speakman JR, Hambly C, Mangoni AA, Preston T, Gray SR. Sex differences in the effect of fish-oil supplementation on the adaptive response to resistance exercise training in older people: a randomized controlled trial. Am J Clin Nutr 105(1) 151-158, 2017.