Friday, February 20, 2015

More Evidence of a Ceiling Effect for Protein Synthesis at ~30g of Whey and/or 23g of Whey + 5g of Leucine in Young (and Old?) | Plus: mTOR is no Reliable Marker of MPS

There are two things you need to build muscle: Iron - to lift it and protein to drink it... for both, it appears, though, as if there was a definitive ceiling effect. For iron, too much can even be a bad thing. For protein, however, consuming too much after a workout is for most uf us only waste of resources and money. 
"More does not help more!" As a SuppVersity reader you know that this is not just the case for money, where studies indicate that once a certain wealth-threshold is achieved, more money won't make you any happier. It's also the case for protein and allegedly most anabolic of all all amino acids: leucine!

In their latest study, scientists from the Massey University, the Victoria University and the McMaster University were able to confirm previous results from rodent studies (e.g. Norton. 2009) which suggested that there is a distinct threshold level of maximal fractional protein synthesis in response to exercise + protein / amino acid supplementation that cannot be surpassed even if you "spike" your protein supplements with extra leucine.
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To be precise, the purpose of the study was to determine if a reduced dose of protein and leucine ingested following endurance exercise resulted in a similar anabolic signal impulse for the stimulation of skeletal muscle myofibrillar protein FSR, relative to a higher protein-leucine dose associated previously with improved recovery of performance in a study by Jasmine Thomson et al. (2011). In the corresponding paper in Medicine & Science in Sports & Exercise, the scientists add:
"We also examined the phosphorylation (as a surrogate marker of activity) of signaling proteins within the mammalian target of rapamycin complex 1 (mTORC1) pathway to study the associations between plasma amino acids, translational signaling and myofibrillar FSR. We hypothesized that the lower ingested quantity of protein (23 g) plus leucine (5 g) would be sufficient to stimulate myofibrillar FSR to an equivalent magnitude to a 3-fold higher amount. Accordingly, a secondary hypothesis was that mTORC1 pathway phosphorylation would be similar between the two protein-leucine fed doses" (Rowlands. 2014).
For us (and the researchers, obviously) the most relevant study outcomes are thus the actual fractional protein synthesis and its faulty proxy, the increase in mTOR phosphorylation of which recent studies clearly indicate that it is no accurate measure of the real influx of protein, let alone the 24h protein balance (Atherton. 2015).
Figure 1: Myofibrillar fractional protein synthesis (left) and anabolic signalling proteins after the ingestion of different amounts of protein + leucine mixtures immediately after 90 minutes of aerobic exercise (Rowlands. 2014).
In view of the fact that I know that many of you are interested only in the results, I have put together the most important study outcomes in Figure 1. What you see is that ...

  • the addition of an extra of 47g of milk + whey protein (2:1 ratio) and 10g of leucine (15LEU) to the baseline dose of 23g of milk + whey protein (2:1 ratio) + 5g of leucine (5LEU) did not lead to a physiologically relevant extra-increase in protein synthesis
  • what the addition of protein did, though was to fool anyone who tries to judge the real-world protein synthesis by measuring m-TOR phosphorylation, as the latter increased by more than 100%
While we have to be careful not to overgeneralize results that have been observed in a group of young, endurance trained cyclists after a standardized 90 minute bout of cycling consisting of a warm up of
"10 min at 30% (Wmax), 8 min at 40%, 2 min at 50%, then intervals (4 x 5 min at 70%) interspersed with three blocks of 3 x 2-min intervals at 85%, 80%, and 75%, respectively, interspersed with 2-min periods at 50%, followed by 5 min at 40%," (Rowlands. 2014)
The results clearly add to the existing evidence that there is a limit to post-exercise protein synthesis that cannot be overcome by the provision of extra protein and or anabolic amino acids.
Please note: This is not the first study to show that measuring only mTOR after a workout and/or taking a supplement is not enough to estimate the real world protein synthetic response. And what's more: Measuring the fractional myofibrillar protein synthesis may give you an idea of whether / how anabolic a workout or supplement may be, but it cannot be used to predict the actual lean mass gains you would see in an 8-12 week study.
In 2009, for example, Daniel Moore et al. presented the results of a very simlar study which compared the protein synthetic effects 20g and 40g of  0, 5, 10, 20, or 40 g egg protein (=relatively low leucine) consumed after a standardized resistance training protocol.
Figure 2: Comparison of the myofibrillar fractional protein synthesis in response to different doses and types of protein / amino acids after aerobic training (Rowlands. 2014, left) and resistance training (Moore. 2009, left) - both in young previously trained subjects.
Just like Rowlands et al. in the study at hand, the scientists from the McMaster University found that a ceiling effect (more does not help more) occurred with "only" 20g of protein in their young, male subjects with only 4-8 months of previous resistance training experience.
Bottom line: The results of the Rowlands study add to the existing evidence that 20-30g of high EAA (and high leucine) protein sources consumed immediately after the workout maximize are sufficient to maximize the protein synthetic response after exercise - independent of whether the workout was of aerobic or anaerobic nature.  One thing that may matter, though, is the age of the subjects, studies like Paddon-Jones, et al. (2006) for example indicate a blunted increase in protein synthesis in response to rather low doses of EAAs and / or protein compared to younger individuals.

Koopman et al. found no difference in FSR between young and old men w/ boluses of 0.16g/kg/h whey + 0.03g/kg/h after the workout (Koopman. 2006).
In view of the fact that other studies found no significant difference (Symonsi. 2011) with a high protein meal (60g) and considering the results of a 2006 study by Koopman et al. which found that beverage containing 12g of a whey protein hydrolysate (0.16g/kg) and ~2.4 g leucine (0.03g/kg) that's consumed in boluses every 60 minutes in the post-workout period will lead to identical protein synthesis rates in young and elderly men, the longstanding SuppVersity recommendation still holds: 30g of whey which naturally contain ~2.5g of leucine consumed immediately after your workout and a high protein meal ~60min after the shake are probably enough to maximize the protein synthesis irrespective of how old you are.

I must admit though, if anyone will actually benefit from additional leucine, it's the elderly in whom the exercise induced increase in protein synthesis is blunted (Kumar. 2009) so that they depend to a much larger degree on the nutrition component | Comment on Facebook
  • Atherton, Philip J., Et Al. "Commentaries On Viewpoint: What Is The Relationship Between Acute Measure Of Muscle Protein Synthesis And Changes In Muscle Mass? Commentary Response To Viewpoint:“What Is The Relationship Between Acute Measures Of Muscle Protein Synthesis And Changes In Muscle Mass?” Comment Viewpoint:“What Is The Relationship Between Acute Measures Of Muscle Protein Synthesis And Changes In Muscle Mass?” The Postexercise Increase In Muscle Protein Synthesis Rate Is Indicative Of Skeletal Muscle Reconditioning Rather ...." Journal Of Applied Physiology 118.4 (2015): 498-503.
  • Koopman, RenĂ©, et al. "Co-ingestion of protein and leucine stimulates muscle protein synthesis rates to the same extent in young and elderly lean men." The American journal of clinical nutrition 84.3 (2006): 623-632.
  • Kumar, Vinod, et al. "Age‐related differences in the dose–response relationship of muscle protein synthesis to resistance exercise in young and old men." The Journal of physiology 587.1 (2009): 211-217.
  • Moore, Daniel R., et al. "Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men." The American journal of clinical nutrition 89.1 (2009): 161-168.
  • Norton, L., and Gabriel J. Wilson. "Optimal protein intake to maximize muscle protein synthesis." AgroFood industry hi-tech 20 (2009): 54-57.
  • Paddon-Jones, Douglas, et al. "Differential stimulation of muscle protein synthesis in elderly humans following isocaloric ingestion of amino acids or whey protein." Experimental gerontology 41.2 (2006): 215-219.
  • Rowlands, David S., et al. "Protein-Leucine Fed Dose Effects on Muscle Protein Synthesis After Endurance Exercise." Med Sci Sports Exerc (2014).
  • Symonsi, T. B., et al. "The anabolic response to resistance exercise and a protein-rich meal is not diminished by age." The journal of nutrition, health & aging 15.5 (2011): 376-381.
  • Thomson, Jasmine S., Ajmol Ali, and David S. Rowlands. "Leucine-protein supplemented recovery feeding enhances subsequent cycling performance in well-trained men." Applied Physiology, Nutrition, and Metabolism 36.2 (2011): 242-253.