Muscle Protein Synthesis: Quantity, Timing, Digestion And Enhancement

[01dragonslayer]

Everything you need to know about protein intake and consumption, including discussions on protein timing, and the improvement of protein synthesis rates.

What is it? How does it work? Why is it important?​

The science of digestion and utilization has always been confusing—not just for the layperson, but for scientists as well. Some things you consume digest perfectly, instantly, and do what you want them to.
Other stuff just sits there, does nothing, or worse, turns to fat…or so it seems. So what gives? Why the unpredictability? And what can we do to at least make sure the foods we eat and supplements we take will do their job?
Given the issues with general nutrition consumption and digestion, it seems that making sure protein synthesis occurs is even that much harder. The truth is, yes, there are uncertainties when it comes to the bioavailability of the necessary components, but we are getting better at understanding when and how to make it happen. To begin to get a handle on the entire process, we need to go back to the beginning and see how food makes it from your mouth to your muscles.

Ready, Set, Eat!​

As I am writing this article, I am eating a 3/4-pound hunk of turkey breast (roughly 350 grams). No, seriously, I am. By gram weight, give or take some math, I will consume almost 80 grams of protein. And while turkey is considered one of the higher protein-containing foods (as well as being a lean meat), it still only has about 22% of its weight in protein.
That means 78% of my lunch contains nothing I really want. Ok, maybe that is a bit of an exaggeration, but I still need to break it down to get to my protein. While you may eat for other reasons, I am eating this to get a huge protein fix while filling up my belly (especially since it has nowhere near the taste of family-sized bag of Lays Potato Chips).
If you are wondering where this is going, my point will be made clear soon. I hope…

The turkey starts out being chewed and partially digested in my mouth by enzymes. As it makes its way down to my stomach, it is further digested by those enzymes and others being activated along the way. When it hits my gut, the real chomping action begins, and more powerful digestive juices (acids) jump in to help out.
The smaller fragments are continually separated as the now turkey puree makes it way in to the digestive tract where it continues to break down into manageable pieces. And this is where the fun, or not so fun, begins. What happens next is anyone’s guess (ok, again, I poke fun). Some of the stuff just sits there and waits until it is needed.
This is one of the great, and not so great, aspects of protein—but more on that in a bit. The rest gets converted to sugars and fats (or their constituents). Oh and yes, some of it actually gets shuffled off as waste—but unfortunately, that is not the stuff that could potentially prevent you from getting fatter.
From there, the now digested fragments enter the bloodstream as amino acids, sugars, and fats. And thus, like a white-water raft ride, the journey of each molecule either finds itself safe at the end of a friendly binding site and gets a chance to penetrate the target tissue and do something useful, or it finds mayhem and becomes piled up along with all the other molecules that didn’t make it. Of course, the latter is referring to the hoarding of like molecules to make a bigger, more complex substance known as either glycogen (if you are lucky) or fat (as most-often is the case).

Getting Protein to Its Target​

So let’s get back to the protein issue and try to understand what my previous paragraph has to do with protein synthesis.
First, in the above scenario, time never became an issue, but if you consider the process, the hope for needed molecules to penetrate target tissue is both time-dependent and need-specific. If those two do not match, well, you are back on the white-water raft ride again, but your fate, the ill-fated part actually, is much clearer now.
For protein, fortunately, its destiny is slightly different. Protein will hang around the digestive tract longer than most other components of food before it is completely digested. This means it does have a better chance of being used. And no, even if it is not used, it will not turn to fat (at least not without going through several different processes first), as it will eventually be taken up and used by the body for something else. But this is where the issues lie for determining timing and quantity of protein consumption.
It should be clear from the analogies above that the more pure the protein form is, the less breaking down needs to occur. So rather than chomp down on a boring, dry, sinewy chunk of turkey, perhaps consuming some faster digesting protein would be a better alternative. At least by doing that, we can estimate that absorption would occur in 30 to 45 minutes or less, and we now have a known window of opportunity.
However, it should be noted that the body can only maximally process 10 grams of protein per hour. So, additional protein could hang-out, like that annoying, hairy, beer-gut, tank-top-wearing guy in your small intestine for a bit if you consume too much.

This poses two problems. The first is that if protein sits around for a long time (several hours), it can become very uncomfortable (think tank-top dude) by causing gas and bloating. The second is that it could be further digested, moved to the liver, and converted to glucose, rendering the protein-effect for building muscle virtually useless.
Your take-home message here is, consume smaller quantities (not more than 30 grams or so) of protein more often, rather than sitting down to a heaping mess of protein-rich foods in a single setting.
Additionally, if you can take faster digesting proteins and time consumption around a need, you will likely see better benefits from it.

Muscle Protein Synthesis​

All the protein needed by muscle is extracted through the intestinal tract into the bloodstream as individual amino acids. Those amino acids will either be used individually or combined to form some kind of peptide chain (multiple amino acids strung together) that has a specific function.
Again, this is where more issues lie. The exact peptide combination needed for protein synthesis to occur means the individual amino acids must join together and create an active binding portion that would connect with a specific target receptor, and then the function will occur. In the case of Muscle Protein Synthesis (MPS), the hope is to first stimulate the need for it to occur and then provide the right combination of amino acids to make it happen. The process itself is understood, but whether it can happen or not is still a bit of a mystery.
Let’s suppose the proteins you need have made their way to their target. What if they are not in the right form? What if they have the wrong combination? In either case, MPS does not occur. So again, timing becomes a critical link in the success rate of MPS.
The details and true process of MPS are quite complicated. There are some definite known issues such as that if we can increase MTORC1 and ATK pathway activity levels, we will get better MPS. Don’t worry if you don’t know what those acronyms mean or how they work—most people don’t—but there is some adequate information looming about for those who are really curious.
We also know certain substances pass through the cell membranes, while others are required to activate another peptide to do the job. There are some factors that are contingent upon one another, but we are still learning how they integrate and differentiate. Interestingly, if you try to call up a search on how MPS occurs at the cellular level, you will get several different variations although all contain the same components.
So what that means to me is we have some unknowns, but overall, Cytokines and Growth Factors are needed to start the process across the membrane and their specific target receptors are ready for them. Once the passage is open, various pathways fire, and cellular rebuilding occurs. In all cases, having protein, amino acids, and the activator constituents available are a must. And finally, supplement science will continue to try to determine which is the best combination to effectively enhance MPS.

The Importance of Timing​

I have mentioned timing on a few occasions throughout this diatribe. It is an essential component of muscle development, training, healthy eating, and a number of other human-type processes. In the case of building muscle, wouldn’t it be nice to know when the best time for MPS to occur is? Well guess what? Of the few things we know, this happens to be one of them!
First MPS occurs as a result of muscle tissue being destroyed, broken down, or stressed. Any form of “out-of-the-normal” muscle contracting causes stress (actually normal muscle contractions do as well, albeit it to a much lesser extent). By “not normal,” I am referring to exercise versus that of everyday life activities. Second, training pushes tissues to contract at higher, stronger, and faster rates than normal, thus causing the protein structures within the muscle to break down.

So, we now know, for certain, when MPS could take place. And last, if we have some protein available at the muscle, it will likely be used in MPS to begin repairs. Thus, for certain, a good time to ensure you have protein (and amino acids) in your blood is right around your workout either before, during, immediately after, or all three.
We also know having extra protein in the blood throughout the 24-hour period following your exercise is also beneficial as MPS continues to occur until the process is complete. Oh, and what that means for those of you who exercise daily—well, you need to always be consuming protein whether it be by whole foods or supplementation.
Don’t miss your window of opportunity by not being prepared. Again, with so many unknowns in exercise, when you get a “for sure” for sure, you should jump on it!

Part 1 Summary​

While this look at protein synthesis is not complete nor is it detailed into the science, it does give a solid overview of the process and, at the very least, should get you thinking about ways to improve your ability to synthesize protein and use it specifically to enhance athletic performance and muscle size.
In the next section, we will discuss some methods of enhancing MPS and training strategies to ensure you maximize your results while minimizing all that difficult food processing.

Muscle Protein Synthesis—Applying Practice to Theory​

Can we enhance protein synthesis? Can we improve amino acid utilization?​

Muscle protein synthesis, to an athlete, especially a bodybuilder or someone trying to enhance his or her physique, is about the most important thing the human body can do toward ensuring goals are met and performances are surpassed.
Imagine if you were able to take control of the process and affect the rate and frequency of protein synthesis? Well, guess what? By understanding some of the unique properties of this phenomenon, while I can’t guarantee miracles, I will promise you will see results happen faster than ever before. But I do throw some caution in that statement—don’t come crying to me when shirts get tight around the chest and arms, and people start staring at you in the gym.
If you perused the first section of this series, you should have a layman’s understanding of what it takes to get the body to process proteins and use it for repairing damaged muscle and rebuilding new. If you didn’t see part 1, no worries, you will still get the gist of this, just without the precursory information—besides, this is the fun stuff anyway.
In part 1, we spoke about the process and claimed we still have a lot of investigating to go to truly understand the details. Well, we know that must be the case because if it were that easy to predict when and how protein synthesis truly works, researchers wouldn’t continually be going to great lengths to try to find the very best formula to make things work better and faster.

In Theory​

The idea of improving or increasing the ability for muscle to synthesize protein has been part of supplementation research for decades. While only recently have we been able to gain a clearer picture of some of the possibilities, the attempt to create novel products has never had a bigger presence than it does now.
Can it be done? We believe so, but honestly, I think we are still going to need a little time to really connect the dots. But we do know a few things that can certainly help. So let’s identify some of the key players on the field and their specific roles. Then we will come back to the question of how to make them work together as a team.

The Key Players in Muscle Protein Synthesis​

Muscle Protein Synthesis (MPS) is initiated by the demand for rebuilding worn down proteins. While there are several mechanisms that are part of the signaling process, the continual demand for “help” comes from cytokines. These are specific molecules similar to hormones but initiated by a different system, with the intent of repairing or combating issues within a cell that have caused disruption such as the case in muscle damage.
Next, pathways such as MTOR and AKT are stimulated to begin the protein synthesis process. MTOR, which is short for the Mammalian Target of Rapamyacin (which still doesn’t mean much to me either, so don’t worry) is the functioning unit that senses nutrient and oxygen levels in cells but also integrates the effect of growth factors and amino acids. The MTOR pathway has garnered much attention lately as its effect on MPS is critical, but more importantly, it may be controlled to some extent, especially through supplementation.
AKT is named such for a reason that has nothing to do with its name, so we will just look at its function. Really, it’s not worth getting into. (No seriously, look it up for yourself, and you will see.) But functionally, it is the main signaling pathway for transcription and cell proliferation, which is the actual protein development, so it is the key factor that induces MPS to increase muscle size and strength.
Thus, the AKT pathway has profound effects on adaptations specific to training. The building process begins, and the muscle’s overall structure and architecture change in accordance to the demands last placed on it. While this discussion is not about training adaptations, it should be noted, again, that since you control the type of training you perform, you also control the adaptations that your muscles undergo.
So if you are looking to increase muscle size, then you need to train accordingly. And if you are looking for speed, power, or even endurance, again, the choice is up to you to provide the stimulus that will make your muscles respond favorably.

Possible Ways to Improve Processes​

We’ve isolated some of the moving parts that are responsible for MPS. It would seem prudent to explore the possibilities of how to get those components to connect, fire, and improve pathway activity. We know there are constituents which can affect the process positively, and that is where this discussion will begin. However, one caveat: the research is still incomplete, so what we say today may change tomorrow.
Of mainstream interest has been the seemingly powerful effects of leucine on MTOR function. It is not fully understood whether leucine has a direct effect (although many people suggest it does) on MTOR or if it is mediated by some other factor first. However, leucine also appears to have a secondary method through a peptide connector called eIF4G which directly affects MPS but not through MTOR.
Which then begs the question that if leucine has multiple functions, can other amino acids play a specific role in aiding MPS? My gut instinct says yes, but again, time will tell. For now, supplementing with leucine can’t be bad, but how much and what other combinations of aminos might be effective is still a matter of debate.
Of course the MTOR pathway is inside the cell, where amino acids can gather as they can freely pass across the cell membrane to their target. Yet, simply having a high level of amino acids in the cell doesn’t mean MPS will be optimal. Furthermore, MTOR is only one of the pathways involved in MPS; there are other ways to excite MPS.
Many of the key players in MPS still need to get inside the cell and require passage through the membrane channels. These activators bind with their target receptor RTK (receptor tyrosine kinase) that resides in the cell wall and, when properly connected, open up a pathway that directly affects AKT, MTOR, and other pathways by triggering PI3K (phosphatidylinositol 3-kinase) to do its thing.
PI3K plays a vital role that affects many of the pathways responsible for cell proliferation, growth, and function. PI3K itself is primarily activated by Growth Factors but regulated by signaling mechanisms known as Cytokines and G-Protein Coupled Receptors. Additionally, insulin plays a role in receptor activation and especially the influence of Insulin-Like Growth Factor (IGF1). In all, there are several different external mechanisms that have to be triggered for optimal MPS to occur.
Are you confused? We all are. This is a complicated process that requires precise sequencing, which itself is a bit of a misnomer since we still are uncertain of all of the sequences that may be involved. MPS is timing specific as well, and thus, having all of the players lined up and ready is still part of the challenge.
But, we also believe there may be ways to enhance these sequences by ingesting bioactive peptides (smaller functional units within protein) such as the growth factors and proline-rich peptides (a type of cytokine) themselves, which can be extracted from the larger proteins by special processing. In fact, processing the finer bioactive peptides is not new as it has been done for decades to build-out infant formulas and immune-function-improving products. It is only now the powerful constituents have been considered for muscle-building and exercise applications.
The good news is: if you consume proteins and/or amino acids and/or bioactive peptides along with solid, consistent exercise, you may positively influence MPS. As science continues to understand the processes and practice continues to show positive results, one can expect an explosion of both products and research relating to bioactive peptides and how one can fine tune MPS.