A Detailed Look At Protein Synthesis!

A Detailed Look At Protein Synthesis – Updated for 2020 by Jim Brewster

In the last several years, the term “protein synthesis” has become common in sports nutrition. As exciting as this concept is, there may be athletes that do not completely understand what protein synthesis is and how it applies to muscle growth. Since building muscle mass is crucial to your bodybuilding goals, and important in many sports, understanding this concept is one of the keys to your athletic success. Protein synthesis can be defined as a fundamental biological process by which individual cells build their specific proteins (1,2). You can think of this as the synthesis of new skeletal muscle proteins. When this occurs because of intense resistance exercise and correct nutrition, it’s the trigger for muscle growth. The process itself is a little complicated. However, there’s no need to make it more complicated than it needs to be. If we understand that protein synthesis is a biological process that replaces proteins in the body, we can explore how this relates to muscle growth.

Net Protein Balance

The term “anabolic environment” is one you frequently hear in sports nutrition. Put simply, it means keeping the body in a state of positive protein balance. Protein synthesis occurs if you have ingested more protein than what’s required to cover the basic functions of the body, thereby maintaining positive protein balance. The human body is made of protein (after water, the dry weight of your body is about 75% protein). Protein in the form of amino acids is required to perform the hundreds of processes needed to keep you alive and functioning. This means that your body demands sufficient protein intake every single day. Despite a daily protein intake, there may not be enough left over for muscle growth to occur. Therefore, bodybuilders and athletes need to ingest more than is typically suggested by mainstream sources. A good rule of thumb is at least 1g per pound of bodyweight.

Another reason adequate protein intake is important is that If the body needs more protein than what is available, it will break down muscle tissue to compensate. This is referred to as muscle protein breakdown. Protein breakdown and protein synthesis occur simultaneously throughout the day. When you wake up in the morning, you’re in a fasted state because you have not eaten for 6-9 hours, so the rate of protein breakdown will increase. That’s why it’s important to ingest a fast-digesting protein source such as a whey protein shake first thing in the morning. If the rate of breakdown exceeds the rate of protein synthesis, you lose muscle, this is also known as a state of negative protein balance. Your body fluctuates between these anabolic and catabolic states based on when you eat and how much quality protein you take in.

So, muscle growth, then, can be defined as the rate of protein synthesis exceeding the rate of protein breakdown over time. (3) Therefore, understanding protein synthesis contributes to your ability to stay in an anabolic environment.

The mTOR Pathway

The first step in understanding protein synthesis is to understand “signaling pathways”. The primary signaling pathway is called “mTOR”, which originally stood for “mammalian target of rapamycin”, it has been more recently defined as “mechanistic target of rapamycin”. mTOR is a type of protein that is considered a master growth regulator that “senses” nutritional and environmental signals including intense exercise. These signals are used to increase the potential of the anabolic processes of the body, which includes muscle growth. mTOR is considered to be the primary regulator of protein synthesis. (4,5,6).

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 (Testosterone, IGF, growth hormone, insulin, etc.)
  • Amino acids (particularly leucine)

Not surprisingly, resistance exercise increases protein synthesis (7). This means you have to train hard enough for growth to occur. The type of training that seems to be most effective is the use of progressively heavier training loads on basic exercises with reps in the 6-8 range. Furthermore, the use of an explosive up/slow and controlled down rep performance is considered effective. Whether you use a full-body routine or split routine does not appear to make a difference. Also, training frequency is important, but it’s tied to recovery. As long as recovery as occurred, you can get back to the gym in 48 hours, so this means a basic full body could be done 3 times a week. For those bodybuilders and athletes that use a split routine, a 3 or 4-day split works great.

Factors That Affect Protein Synthesis

BCAAs/EAAs – One of the more recent developments in sports nutrition supplementation was the discovery of the relationship between EAAs (with a focus on BCAAs) and protein synthesis. There are nine Essential Amino Acids, including the three BCAAs. The EAAs cannot be made by the body, they must be supplied through diet and supplements. The BCAAs, especially leucine, are known to be extremely effective for stimulating protein synthesis. Leucine has the greatest impact of any amino acid in terms of protein synthesis stimulation via the mTOR pathway (8,9). mTOR appears to be sensitive to levels of leucine because as leucine levels decline in the body, mTOR is signaled that there's not enough dietary protein present to synthesize new skeletal muscle protein. This effectively turns protein synthesis off. As soon as you ingest more BCAAs/EAAs (leucine, primarily), the elevated amino acid levels signal mTOR that there is now sufficient dietary protein, and protein synthesis turns back on. It’s now understood that all the EAAs are involved in protein synthesis. However, it’s also understood that leucine is still the most anabolic of all amino acids. (9)

Protein/BCAA/EAA Timing

Ingesting consistently timed whole food protein, the protein powder of your choice, and/or a good BCAA-EAA formula is important to stay in an anabolic state to stimulate muscle growth. It makes sense to take in a protein source with some simple carbs about an hour before you train. A good starting point is 30-50 grams each of fast-digesting whey protein and simple carbs. If you want, a good BCAA/EAA formula can be used as an intra-workout drink. Most of us use a pre-workout, a good pre-workout that contains a pump complex that includes Citrulline is also important. This is because increased blood flow means enhanced nutrient/amino acid delivery.

Once your workout is over, take in a post-workout shake with 20-30 grams of fast-digesting whey protein as well as fast and slow-digesting carbs. Most bodybuilders/athletes eat a whole food meal within 2 hours after their shake. The recovery process begins as soon as your workout ends, and correct nutrition/supplementation is key to full recovery. It should be noted that full recovery includes a consistently good night’s sleep of at least 7 hours. It’s critical to understand this as short-changing your sleep means you’re short-changing your goals.


Insulin is one of the three primary anabolic hormones produced by the body. 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 is concerned. It may also be important as far as mTOR activation is concerned. Simple carbs that are taken in during the hours surrounding your workout cause insulin spikes, which means that glucose absorption, utilization, ATP production, amino acid absorption, and protein synthesis are all enhanced. (10).


Testosterone is frequently considered to be the most powerful anabolic hormone produced by the body. That’s for good reason as it directly affects muscle growth by binding to receptors on the muscle cell surface and magnifying the signals in muscle tissue that stimulate protein synthesis. Additionally, testosterone increases GH (growth hormone), another of the body’s primary anabolic hormones, and released in response to exercise. Like testosterone, growth hormone also increases protein synthesis. By stimulating the release of GH, testosterone also supports the process of protein synthesis in general. (11)

Protein Synthesis Rates

There’s a current trend among some athletes and informational websites that seem to believe that protein timing does not matter. When it comes to maintaining an anabolic environment in the body as well as optimal protein synthesis, it definitely matters.

Regarding the rate of protein synthesis, clinical studies have 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 (12, 13). This means that if you want to keep protein synthesis going, you have to ingest more protein.

Based on this research, for those athletes that are serious about protein synthesis, it’s a good idea to take in a protein shake, protein meal or even a BCAA/EAA drink every 3-4 hours since research indicates that amino acid pool levels remain high 4 hours after ingesting amino acids (12, 13,14,15). It would seem the old bodybuilding standard of protein timing isn’t so wrong after all.


To recap, if you want to optimally stimulate protein synthesis, you will need to maintain a consistent protein intake with an emphasis on the BCAAs/EAAs (especially leucine). You will also want to ingest simple carb sources (30-40 grams) in the hours surrounding your workouts (16). Additionally, you will want to maintain an optimal daily protein intake – a good point to be made here is to know how much of the /EAAs is in your protein powder, especially leucine, which should be 3-4 grams per serving (17, 18). As far as protein sources are concerned, quality whole food protein sources such as chicken, turkey, and lean beef are the best choices with whey protein and casein protein as the best powder choices. A protein blend of whey and casein makes sense because casein is slower digesting than whey and will stay in your system longer. It should also be noted that you can use a BCAA/EAA drink as you go about your day. Additionally, planning your pre, intra, and post-workout shakes is important. Make sure you’re getting in BCAAs/EAAs, a pump complex for enhanced nutrient delivery and creatine for enhanced endurance and performance along with whatever else you take. BTW, this nonsense of all these current pre-workouts or intra-workouts avoiding creatine is just that, nonsense. Creatine is one of the most proven-effective supplements on the market and has a positive impact on protein synthesis. (19) Unless you take it at a separate time of the day, it should be in your pre or intra. Along with these tips, make sure your training is intense and that you allow yourself to recover to become the best bodybuilder or athlete you can be!


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Protein synthesis. (n.d.). Retrieved May 02, 2017, from http://medical-dictionary.thefreedictionary.com/protein synthesis

Tipton, K. D., & Wolfe, R. R. (2001, March). Exercise, protein metabolism, and muscle growth. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11255140

Laplante, M., & Sabatini, D. M. (2009, October 15). MTOR signaling at a glance. Retrieved May 02, 2017, from http://jcs.biologists.org/content/122/20/3589

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.

Laplante, M., & Sabatini, D. M. (2009, October 15). MTOR signaling at a glance. Retrieved May 02, 2017, from http://jcs.biologists.org/content/122/20/3589

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.

Jackman SR, Witard OC, Philp A, Wallis GA, Baar K, Tipton KD. Branched-Chain Amino Acid Ingestion Stimulates Muscle Myofibrillar Protein Synthesis following Resistance Exercise in Humans. Frontiers in Physiology. 2017;8:390. doi:10.3389/fphys.2017.00390.

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.

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.


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.

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.

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.

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.

Wolfe, R. R. (2006, February 01). Skeletal Muscle Protein Metabolism and Resistance Exercise1–3. Retrieved May 02, 2017, from http://jn.nutrition.org/content/136/2/525S.long

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.

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