Omega-3 PUFAs Augment the Muscle Protein Anabolic Response to Hyperinsulinaemia-Hyperaminoacidaemia
Long-chain n-3 fatty acids, more commonly referred to as Omega-3 polyunsaturated fats, are unsaturated fatty acids that cannot be synthesized by the human body; intake of these “essential fatty acids” is vital for normal metabolism. In the last 20 years, Omega-3 polyunsaturated fats (or PUFAs, for short) have been the subject of an abundance of research, mostly touting their many potential pathways for improving health.
Some of the better-established benefits include a reduction in risk for cancer and CVD, improved immunological and neurological function, and an anti-inflammatory cascade initiated through the activation of G protein-coupled receptor 120 – GPR120 Study While the list above would create a strong pedigree for any compound, researchers at the prestigious Washington University School of Medicine are attempting to extend that scope to increased muscle protein anabolism as well.
It has been demonstrated that Omega-3 PUFA supplementation aids in maintaining muscle mass in individuals experiencing atrophy due to aging or cancer cachexia. Could these benefits extend to a “healthy” individual by augmenting anabolic signaling and muscle protein synthesis?
**Editors note – In the interest of full disclosure, I now carry and sell my own Fish Oil product, but regardless of whether you buy it from me, use another brand, or try to consume enough food to meet the requirements, Fish Oil has a wide range of benefits and this is an interesting piece of research that I felt would benefit the readers of this site. I did not ask Eric to endorse, or reference my own brand and he was not compensated in any way for doing so. **
The researchers chose a sample of nine middle-aged men and women, all of whom were deemed “healthy” after a comprehensive medical examination. Note: while these subjects may have been titled healthy by virtue of their blood constituents and a physical evaluation, they were by no means trained. All individuals studied reported less than an hour and a half of moderate physical activity per week.
In order to induce an anabolic environment in the research participants, they were injected with a potent insulin-amino acid solution. Prior to that injection, they consumed two tracer isotopes to assess potential changes in metabolism – a phenylalanine tracer to measure the rate of protein synthesis and a glucose tracer to track glucose metabolism. The researchers used tracer activity as well as two muscle biopsies to evaluate any changes in intracellular signaling and muscle protein anabolism.
As far as the experimental protocol, baseline data was attained on all dependent variables – these included RNA/DNA concentrations, the fractional rate of protein synthesis, cell-signaling activation of the anabolic pathways, and markers of systemic inflammation (CRP, IL-6, TNF-a), among others.
Then, the subjects were instructed to consume 4g/day of the fish oil supplement Lovaza® for 8 weeks consecutively, upon which they would be retested. (Lovaza® contains 1.86g of EPA and 1.50g of DHA in their ethyl ester forms.)
Upon re-testing the subjects at the end of the 8 weeks, here are some of the researchers significant findings:
- Both muscle protein concentration and cell size increased
- No change in insulin/glucose kinetics
- Increased anabolic response of ~50% post insulin-amino acid infusion, compared to basal values
- Significantly increased mTOR and p70 s6 kinase activation
- No change in the basal rate of protein synthesis
The researchers concluded that while Omega-3 PUFA supplementation alone is insufficient to create increases in muscle protein anabolism, it can create considerable increases in anabolic intracellular signaling sensitivity and protein synthesis in the presence of a suitable anabolic stimulus.
Implications & Limitations
While the structure of this study was well-conducted, three words highlight one of the study’s greatest shortcomings – small sample bias.
My work in the neuromuscular physiology lab at the University of Georgia allows me to personally relate to such a difficult reality – amassing the industry standard of 30 subjects per group can sometimes seem impossible. Even so, it must be mentioned that a nine-participant study is always open to bias due to its small sample size.
And, though it’s no fault of the researchers, the subjects chosen would most likely constitute an absolute beginner if compared alongside you or your athletes. The intracellular signaling pathways of a beginner may respond differently to varying stimuli relative to a more advanced trainee – this fact must be considered when interpreting the results of the above study.
However, even with these two potential limitations under consideration, the Washington University researchers present a compelling case for Omega-3 supplementation as it relates to improved anabolic signaling in the presence of nutritional stimuli. For more information regarding Omega-3 PUFAs and their effects on intracellular anabolic signaling, check out this 2007 bovine study
For those interested, my previous research review provides a very general overview of the anabolic signaling cascade.
The researchers concluded that it was the sensitivity of the mTOR/p70 s6k signaling cascade that was most affected by the Omega-3 supplementation. Presumably, one could take advantage of this increased sensitivity by introducing any anabolic stimulus (like strength training), not exclusively nutritional stimuli. A similar study involving trained individuals with the addition of a strength training condition on top of the insulin-amino acid infusion condition would be an excellent progression in this line of research.
The participants in this study received 3.36 g/day of combined EPA/DHA in the Lovaza® supplement. Given this experiment protocol, there’s really no way to know if a lower dose would have produced a similar positive effect. By the standards set in most research concerning Omega-3 dosages, the amount used in this study seems high.
As discussed in an outstanding Weston A Price Foundation review on EFAs, high concentrations of PUFAs can be harmful because they oxidize so easily in the body. This occurs as a result of PUFAs’ molecular structure, containing two or more double bonds – the carbon that lies between those double bonds is susceptible to oxidation.
When these molecules oxidize, they can break down into smaller particles, such as malondialdehyde, which can damage structures at the cellular level. I won’t dig much more into the biochemistry than that, but it’s certainly something worth considering when choosing a supplementation dosage.
How much fish oil should a person consume?
As is often the case with any nutritional or training recommendation, it honestly depends on the individual in question. I can make the educated guess that I’m writing to a diverse audience – some of you have probably taken fish oil for years while others may have never used it.
One important factor to determining a recommended dosage might be how long a person has been supplementing fish oil already. The only long-term RCT performed on Omega-3 supplementation, the DART-2 study actually showed an increase in risk for heart disease and sudden cardiac death after four years.
Omega-3s appear to exert their initial benefits (as described above) through the displacement of intramembranous Omega-6 PUFAs – once a person reaches some saturation point, more is not necessarily better. Most RCTs cite a reduction in Omega-6 intake as most beneficial, so maybe we should look to the ratio of Omega-3:Omega-6 PUFAs instead of an absolute dosage.
Nutritionists John Berardi and Robb Wolf both prescribe a high dose initially – this presumes that a person may be overweight and in need of decreased systemic inflammation. They then taper this dosage toward a maintenance level as the person’s health improves and the Omega-3 “saturation point” is reached. Obviously, the best option would be to directly test a person’s Omega-3:Omega-6 ratio to determine a precise dosage, but this is not always ideal for the average coach/trainee.
Even though the mantra “If you’re not assessing, you’re guessing” applies here, it’s safe to assume that most Americans are not consuming enough Omega-3 PUFAs. Lyle McDonald has stated that the absolute bare minimum dosage that he would recommend would be 500mg of combined EPA/DHA. Literature describing intakes in the range of double or triple that value show mostly positive benefits without some of the negative ramifications described above. For that reason, I’d shoot for about 1-1.5g/day of combined EPA/DHA as a general recommendation.
Whole food is king when it comes to meeting your Omega-3 needs – consuming a nutrient-dense, whole-foods based diet that includes fatty fish, shellfish, and organ meats should suffice in meeting the recommended amount. If that were unavailable, I’d advise choosing a high-quality liquid fish oil supplement to fill in the gap.
While I like both Nordic Naturals and Carlson’s, Joel’s own Omega-3 Fish Oil from his BioForce supplement line is the best I’ve used. The nutrient profile fits perfectly with the dosage recommended above and, of the three I mentioned, it wins out on both taste and texture.
As I stated above, there’s no way to tell if a lowered dosage from what was used in the study would provide the same benefits of an increased muscle protein anabolic response. This issue alone proves the need for continued research on this topic.