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A Detailed Look into Protein Synthesis!Leave a Reply

It is understood that if you want to build muscle, one of your primary concerns should be the ability to maintain an anabolic state. When I started out back in the day (1980), this meant promoting a positive nitrogen balance by ingesting enough protein throughout the day to stay in a positive anabolic environment. In fact, I can remember several years later Weider – who was THE guru at the time (at least the self-proclaimed guru) came out with Nitrogen Test Strips so you could test your personal nitrogen balance. The idea didn’t really take off, and they didn’t make much of a dent in the marketplace. Back in those days, you didn’t hear much about protein synthesis. It should be noted that, back in 1980, as well as before that, the only sources of information were magazines, training books, and possibly “experts” at the local gym. There was no internet and there wasn’t a personal trainer on every corner like there is today, so in comparison to today you really had little to go by.

For me, one of the most exciting recent advances in supplementation was the discovery of the relationship between BCAAs and protein synthesis. BCAAs have a long history in bodybuilding, in fact, I can again think back to the early 80’s and Weider’s attempt to replace steroids (which had hardly been mentioned in the magazines before that, especially his) with a product stack that included “Dynamic Life Essence”, Weider’s BCAA-based formula. That didn’t work out too well for him as the FTC came knocking soon after. Understand that for the most part, he dominated the marketplace back then, in fact, my first exposure to professional bodybuilding came from seeing a Muscle and Fitness at the local store – I bought it and the rest, as they say, is history. So, despite the extended history of BCAAs, they became relatively unimportant until it became known that Leucine was clinically studied and shown to be directly tied into protein synthesis stimulation.

I first heard the terms “protein synthesis” and “mTOR” probably around 2008-2010 and I was intrigued from the second I read about it. In this article, we will cover basic science and definitions as well as look at ways we can maximize protein synthesis.

Protein Synthesis and Bodybuilding – The Mechanisms of Protein Synthesis

The term “protein synthesis” has become commonplace in bodybuilding – yet not everyone may completely understand what it is and how it applies to muscle growth. Protein synthesis is, briefly, a fundamental biological process by which individual cells build their specific proteins (1). Within the process are involved both DNA (deoxyribonucleic acid) and RNA (ribonucleic acids). The process is initiated in the cell’s nucleus, where specific enzymes unwind the needed section of DNA, which makes the DNA in this region accessible and a RNA copy can be made. This RNA molecule then moves from the nucleus to the cell cytoplasm, where the actual process of protein synthesis takes place (2).

Admittingly, this is a very brief explanation, but I do not want the science to be overwhelming. If we understand that protein synthesis is a biological process that basically replaces proteins in the body, how does this apply to muscle growth?

To understand this, we need to understand the concept and function of “signaling pathways”, the primary pathway is known as “mTOR”, which originally stood for “mammalian target of rapamycin”, it has also been defined as “mechanistic target of rapamycin”. mTOR is a type of protein that is considered a master growth regulator that “senses” nutritional and environmental (such as intense exercise) signals and utilizes these signals to increase the potential of the anabolic processes of the body, which includes muscle growth, in fact, it’s considered to be the primary regulator of protein synthesis. (3,4,5).

Now, the key point of this article is not to get deeply into the science of what happens in the body, although for those readers that enjoy that, it can be very detailed but very enlightening, but rather to look at what we can do optimize the natural processes that result in muscle growth. mTOR is one of the more important cell signaling pathways for muscle growth, as seen above, it's the master regulator of protein synthesis (among other anabolic functions) in the cell. The good news is, you can directly affect muscle growth by activating mTOR, and it’s activated by three things:

• Mechanical stress (from heavy training loads)
• Growth factors (IGF, growth hormone, insulin, etc.)
• Amino acids (particularly leucine)

Resistance exercise increases protein synthesis (6). This means you have to train hard enough for growth to occur. How do I define training hard? By using progressively heavier training loads, the use of basic exercises as well as moderate rep ranges (6-8), the use of an explosive up/slow and controlled down rep method and either a full-body routine or 3-day split routine. As far as training frequency, as long as recovery as occurred, you can get back to the gym in 48 hours, so this means a basic full body can be done 3 times a week, and by “basic” I mean you have to keep total sets in a reasonable range if you want to be recovered and back in the gym within 2 days. In an article that I wrote on Full Body Training, I advocated 4-6 total exercises done for 3-4 sets each. None of this 30-50 set stuff! If you’re training hard, you shouldn’t be able to do 30-50 sets! Or, for those prefer a split, how about the classic Push, Pull, Legs 3-day split? Most lifters will do this split twice in one week, with a day off in-between.
What About Other Factors?

The ATP system of energy, which is the primary energy system your muscles use, require two things to operate at peak efficiency – carbs and creatine. As it turns out, mTOR activation is affected by high levels of ATP, so if ATP levels drop, mTOR activation also drops (7).

BCAAs - Leucine, isoleucine, and valine – the BCAAs are highly effective for stimulating protein synthesis, especially leucine, which seems to have the greatest effect of any amino acid in terms of stimulating protein synthesis through the mTOR pathway (8,9). In fact, mTOR seems to be sensitive to concentrations of leucine in the same way it’s sensitive to ATP levels – as leucine levels decline in the body, mTOR is signaled that there's not enough dietary protein present to synthesize new skeletal muscle protein, therefore turning mTOR off. Once you take in more BCAAs (leucine, primarily), the elevated amino acid levels signal mTOR that there is now sufficient dietary protein, and switches protein synthesis back on. It should be noted that all the EAAs, which include the BCAAs, are involved in protein synthesis, however, the key is leucine.

If you consider that once you’ve worked out – and insured you’ve worked out with heavy weights and trained hard enough to stimulate growth – what the entire concept of protein synthesis comes down to is the ingestion of protein and allowing proper recovery to take place – which, really, can be defined as the timeframe required for new muscle growth to occur.


If we take a look at insulin, one of the three primary anabolic hormones produced by the body, we see that it’s a protein hormone released by the pancreas when levels of glucose increase above normal. Now, it seems apparent that carb consumption in the timeframe leading up to and surrounding the workout is important as far as energy and mTOR activation is concerned. Simple carbs taken in during the hours surrounding your workout cause insulin spikes, which means: glucose absorption, utilization, ATP production, amino acid absorption and protein synthesis are all enhanced. (10).

Protein/BCAA Timing

Ingesting consistently timed protein sources and/or BCAA-EAA sources is important to stay in an anabolic state and set yourself up for growth. It’s a good idea to take in a protein shake about an hour before your workout, you should make sure it consists of 30-50 grams of fast digesting whey protein with some simple carbs, about 30 grams. I also advocate a BCAA-Creatine intra-workout drink, and a pre-workout that has a good pump complex that includes Citrulline because increased blood flow means enhanced nutrient delivery. If you do not use a pre, then add a stim-free pump formula to your intra.

Once you are done with your workout, take in a whey protein shake consisting of 30-50 grams and include some carbs – base the amount on your goals, but about 30 grams regardless. Even if fat loss is your primary goal, limited carb intake will have a positive effect on muscle growth. Of course, most lifters eat a whole food meal not long after their shake, as well you should. The recovery process begins at the end of the final set of your workout, allow time for adequate nutrition and rest before you hit the gym again, even if it seems ideal to hit it again in 48 hours, if you are not recovered, take one more day – recovery is where growth happens, something I’ve said in almost every article I’ve ever written, and you will not grow if you are in an over-trained state.

Protein Synthesis Rates

Two researchers, Bohe and Anthony, demonstrated that amino acids with extra leucine increased the rate of protein synthesis for 30-60 minutes after a workout with a return to normal after about 120 minutes (11, 12).
It would therefore be a good idea to take in a BCAA or protein shake that has 3-4 grams of Leucine every 2-4 hours since Bohe demonstrated that amino acid pool levels remain high 4 hours after ingesting amino acids (11).

Based upon the research of Bohe, Paddon-Jones, Norton, and Anthony, it would be a good idea to take in protein – be it a protein meal, protein shake and/or BCAA drink – every 2-4 hours (12,13,14). With that in mind, despite some recent trends to the contrary, it seems the old standard of protein timing isn’t so wrong after all, and the idea of carrying around a BCAA drink or protein shake in a water bottle makes a lot of sense, that stupid Planet Fitness ad mocking a gallon-jug carrying bodybuilder notwithstanding!

So, in recap, to optimally stimulate protein synthesis, which leads to new muscle growth, we need to maintain a consistent protein intake with an emphasis on the BCAAs (especially leucine) as well as include simple carb sources (30-40grams) in the hours surrounding our workouts (16), as well as maintaining optimal protein intake daily – a good point here is to know how much of the BCAAs are supplied in your protein powder, especially leucine, which should be 3-4 grams per serving (17, 18). Whey protein and quality animal protein sources such as chicken, turkey and lean beef are the best choices. Slower digesting milk protein makes sense at bedtime or during the day if your obligations keep you from getting in a planned meal or shake. It should also be noted that you can use a BCAA drink or BCAA/EAA drink if you wish, besides being part of your intra, as you go about your day, although I would also use a protein powder, primarily when I was at home. Additionally, planning your pre, intra and post workout shakes is important, make sure that, along with whatever else you take, you’re getting in BCAAs, a pump complex and creatine – and this nonsense of all these pre-workouts or intra-workouts avoiding creatine is just that, nonsense. Add in your own if your favorite products do not contain it, I suggest 5 grams of the proven creatine monohydrate, I also suggest the micronized version.

Along with these tips, make sure your workouts are hard and heavy, and that you allow yourself to recover – let me say that again and end with – allow yourself to recover so you can allow yourself to grow!


  1. What Is Protein Synthesis. (2015, December 27). Retrieved May 02, 2017, from
  2. Protein synthesis. (n.d.). Retrieved May 02, 2017, from synthesis
  3. Laplante, M., & Sabatini, D. M. (2009, October 15). MTOR signaling at a glance. Retrieved May 02, 2017, from
  4. Norton, L.E. & Layman, D.K. Leucine Regulates Translation Initiation of Protein Synthesis in Skeletal Muscle after Exercise. J. Nutr., 136:533S-537S, February 2006.
  5. 5. Laplante, M., & Sabatini, D. M. (2009, October 15). MTOR signaling at a glance. Retrieved May 02, 2017, from
  6. Phillips, S., M, Tipton, K. D., Aarsland, A., Wolf, S. E., & Wolfe, R. R. Mixed muscle protein synthesis and breakdown after resistance exercise in humans. (1997) Am. J. Physiol. 273(1 Pt 1): E99-107.
  7. Home - PMC - NCBI. (n.d.). Retrieved May 02, 2017, from
  8. Charlebois, D. B. (2017, February 09). BCAA Part 2: What To Stack With BCAA For Enhanced Results! Retrieved May 02, 2017, from
  9. Anthony JC, Yoshizawa F, Anthony TG, Vary TC, Jefferson LS, Kimball SR. Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway. J Nutr. 2000;130(10):2413-2419.
  10. Fryburg DA, Jahn LA, Hill SA, Oliveras DM, Barrett EJ. Insulin and insulin-like growth factor-I enhance human skeletal muscle protein anabolism during hyperaminoacidemia by different mechanisms. J Clin Invest 1995;96:1722-9.
  11. Bolster DR, Crozier SJ, Kimball SR, Jefferson LS. AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. J Biol Chem. 2002;277(27):23977-23980.
  12. Bohe, J., Low, J.F.A., Wolfe, R.R. & Rennie, M.J. Latency and duration of stimulation of human muscle protein synthesis during continuous infusion of amino acids. J Physiol., 532(Pt 2): 575-579. April 2001.
  13. Anthony, J.C., Lang, C.H., Crozier, S.J., Anthony, T.G., MacLean, D.A., Kimball, S.R. & Jefferson, L.S. Contribution of insulin to the translational control of protein synthesis in skeletal muscle by leucine. Am J Physiol Endocrinol Metab., 282: E1092-E1101, May 2002.
  14. Norton L.E., Layman D.K., Bunpo P., Anthony T.G., Brana D.V. & Garlick P.J. The Leucine Content of a Complete Meal Directs Peak Activation but Not Duration of Skeletal Muscle Protein Synthesis and Mammalian Target of Rapamycin Signaling in Rats. J. Nutr., [Epub ahead of print] April 2009.
  15. Paddon-Jones D., Sheffield-Moore M., Aarsland A., Wolfe R.R. & Ferrando A.A. Exogenous amino acids stimulate human muscle anabolism without interfering with the response to mixed meal ingestion. Am J Physiol Endocrinol Metab., 288: E761-E767, April 2005.
  16. Wolfe, R. R. (2006, February 01). Skeletal Muscle Protein Metabolism and Resistance Exercise1–3. Retrieved May 02, 2017, from
  17. Tipton, K.D., Ferrando, A.A., Phillips, S.M., Doyle Jr., D. & Wolfe, R.R. Postexercise net protein synthesis in human muscle from orally administered amino acids. Am J Physiol Endocrinol Metab., 276: E628-E634, April 1999.
  18. Bohe, J., Low, J.F.A., Wolfe, R.R. & Rennie, M.J. Latency and duration of stimulation of human muscle protein synthesis during continuous infusion of amino acids. J Physiol., 532(Pt 2): 575-579. April 2001.

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