Muscle Protein Synthesis and the Anabolic Window

TAGS: Rasmussen, Myofibrillar Protein Synthesis, MPS and the Anabolic Window, MPS, Muscle Protein Synthesis, macronutrients, research, brandon patterson, Nutrition

The concept of the anabolic window—an all-important slice of time where muscles are seemingly primed for nutrient-enhanced growth—is ubiquitous, now, thanks to aggressive marketing strategies. If you don’t follow the protocols yourself, you probably have seen lifters lugging around bottles of fluorescent fluids at your local gym, ads for a dozen different workout-nutrition supplements plastered on the walls at GNC and Vitamin World, and even products designed for the anabolic window lining your grocer’s juice aisle.

The post-workout shakes, the different blends of protein, the carb-cycling, and the myriad of amino-acid formulations all exist because of the anabolic window. Its popularity makes sense: it promises a once-secret path to gains, is legal and relatively inexpensive, and requires only that you chug a shake right around the time you lift. For a lifter, that’s a lot easier than an insane “mass-builder” program, and for the manufacturers, it’s as simple as reformulating (or just rebranding) products they already have established supply lines for.

But have we really figured this all out....Or did we unintentionally defenestrate ourselves?

The key concept in the theory is Muscle Protein Synthesis (MPS). MPS, also called Myofibrillar Protein Synthesis, is the basic process by which muscle tissue is grown. Muscle cells undergo constant damage and repair. MPS, on the other hand, is the process by which muscle is repaired, and therefore is likewise a constant activity in the body. MPS creates extra tissue that is added to muscle. Other processes can increase a muscle’s cross-section or its number of cells, but only MPS increases your mass of actual contractile elements.

MPS can be detected as it’s actually happening, and well before visible changes in hypertrophy appear. In the past 15 years, many studies examining MPS in subjects after lifting and ingesting various concoctions of nutrients have shown that MPS seems to spike within an hour or two when exercise and the right nutrients combine. This spike is why Gatorade now buys discarded whey from cheese factories.

Unfortunately for the athletes standing to benefit from an improved understanding of the anabolic window, nearly two decades of incomplete research and overzealous promotion have created a mess.

brandon patterson MPS david allen preworkout 082714

How It Began

Oddly enough, the most exciting part of “anabolic window” is the word “window” and its resulting implication that trainees have a very limited time in which to optimally grow their muscle. The general importance of calories, protein, carbs, etc., was old hat in the late '90s when American researchers began narrowing their work. They concentrated temporally on the lifting period and on very basic nutrients, particularly amino acids and simple carbs. Writers and supplement companies jumped on the resulting publications to push a new category of post-workout shakes, pills, and powders.

One of the most cited of these papers was Rasmussen’s paper, “An oral essential amino acid-carbohydrate supplement enhances muscle protein anabolism after resistance exercise,” published in the Journal of Applied Physiology in 2000. You might recognize Rasmussen and his colleagues Tipton, Miller, Wolf, and Wolfe from a ton of workout nutrition studies they performed at the University of Texas Medical Branch at Galveston. For this particular study, however, the team gave two groups of fasted subjects a pre-workout drink, led them through some leg presses and leg extensions, and collected blood and biopsy data. The exercise protocols were identical; however, the experimental group received Essential Amino Acid and sucrose beverages after the workout, while the control group got water sweetened with zero-cal aspartame. The blood and tissue samples show pretty conclusively that MPS was jacked up in the experimental group.

Nearly every such paper released during the first few years of workout nutrition studies looked like Rasmussen’s research. On the one hand, they were critical in shining a light on how amino acids, carbohydrates, hormones, and other factors combined to create new muscle. On the other hand, they were entirely inappropriate for use as the foundation of a new supplementation model. Let’s use Rasmussen as a guide for exploring these limitations.

The Limitations

If you’ve read my series on reading research, you’ll be familiar with many of the topics here. The first issue, naturally, is that these studies weren’t conducted in order to discover new elixirs for meatheads. Remember that Rasmussen’s team worked at the UT Medical Branch. Their focus was on discovering ways to counteract sarcopenia, atrophy, and other causes of muscle wasting. Any discoveries of relevance to gym rats would be tangential or even coincidental.

More specifically, even if these groups had been trying to create a new workout nutrition protocol, their studies were far too preliminary to spark anything more than ideas. All of these early studies demanded their subjects to be “clean slates” so that the results wouldn't be contaminated by activities outside of the lab environment. For a nutrition study, this meant relying on fasted subjects.

brandon patterson MPS matt wenning forearm HOOGE 082714

Remember that these studies were used to justify complex workout nutrition protocols prescribed to a population that not only made a habit of avoiding fasted states, but also consumed calories with more regularity and in greater quantity than the general populace. Even before the advent of workout nutrition prescriptions, the average lifter ate a protein-containing meal no more than several hours before or after hitting the iron (often both) in order to meet increased calorie demand or as part of high-frequency eating diets. These lifters had a robust mixture of amino acids, carbohydrates, lipids, and hormones ready to respond to any training stimulus. Put another way, an average meal consumed before lifting would, by its very nature, fall into the workout nutrition paradigm because its digested macronutrients would be circulating through the body during the entire workout.

Now, compare these lifters to individuals who have fasted overnight. Not only are their blood sugar, glycogen, and hormone levels depressed, but their bodies are also caught in an absolutely minimal state of blood-amino acid levels. The protein these people consumed had long since emptied from the blood stream and metabolized, though they hadn't been without food long enough for existing skeletal muscle to have been catabolized. In short, while these fasted subjects are set for a lousy, maybe even self-defeating day at the gym, they’re positively primed to blow up some muscle blots. And that’s exactly what happened.

A second issue that prevents many studies from being translated directly into dietary protocols is the use of “apples and oranges” comparisons in terms of drink formulations. Rasmussen’s paper is useful as a concept, but just knowing that consuming amino acids after training is better than drinking flavored water isn’t especially helpful. Even research that would at first glance seem more useful runs into problems by failing to match caloric and/or protein content between the administered supplements. Just in terms of protein matching alone, Schoenfeld’s meta-analysis of nutrient timing research reviewed 23 published papers, and out of all of those papers, only three gave their control and experimental groups the same amount of protein during their respective studies.

Finally, there’s been a paucity of outcome-oriented studies. It’s one thing to measure MPS, but it’s another to detect actual differences in hypertrophy after a few weeks or months of a given protocol. Given the way most research on workout nutrition has progressed, it’s been hard to discern if there’s a benefit to slamming your shakes right after lifting. There are two major questions: 1) is the short-term boost in MPS derived from workout-timed nutrition tangible over a longer time frame, and 2) if so, does it translate into honest muscle, especially to gains that outpace one’s genetic limitations?

Rethinking the Window

Let’s start with the first question. It may well be that just because a protein shake taken around the right time revs up MPS, but it doesn’t mean that it stays that way. It’s possible that MPS (or tangible hypertrophy) might drop below baseline after administering PWO nutrition. For the ease of demonstration, imagine a two-group workout nutrition study. The experimental group receives a dose of amino acids and carbs right before lifting while the control group receives the same quantity of extra nutrients, but spaced out hours after lifting. A short-term study wouldn’t be able to ferret out MPS activity such as the following:


As you might expect, there’s little in the way of fine-grained studies, and they aren’t ironclad by any stretch. Hoffman ran a 10-week trial that compared a pre- and post-workout supplement group with a morning and evening supplement group and turned up no significant findings. On the other hand, Cribb’s similar 10-week study showed demonstrative body composition changes, though their work was muddled by using a supplement that contained creatine. Being small-scale hypertrophy studies, neither could afford anything more complicated than dietary self-reporting.

Areta’s 2013 study is perhaps the most interesting of the bunch. This international team was one of the first to look at our question in the manner of the above table. They tested the difference between two large, 40-gram doses taken immediately post-workout and shortly afterwards, and ranges of smaller doses that in total were equal to the two large doses. The team’s results showed that regular 20-gram doses of protein taken every three hours were most effective. Coupled with other studies, and it’s like the Kool-Aid Man walked through the anabolic window and left behind a gaping hole. (Areta’s work also helped launch a thousand “pulse” feeding programs.)

But this all assumes that lab-defined MPS has a direct relationship to actual hypertrophy. If you’re familiar with my past articles, then you already know that I have my doubts in this regard. Here’s why:

Mayhew’s 2009 study accidentally found a disconnect between MPS and hypertrophy in fasted subjects of varying ages. Mitchell’s work in 2014 purposefully looked to see if MPS correlated with hypertrophy in subjects receiving a post-workout protein blend, and likewise found a disconnect. To quote the paper itself, “[A]cute early measures of MPS are not proxy measures for hypertrophy or hypertrophic potential within the same individual.”

So what’s going on? Mitchell takes a few stabs, but it’s guesswork. We just don’t know. Maybe there’s a transient bump in sarcoplasm, later changes in how subjects responded to the exercise/nutrition protocols, or even different responses to MPS itself. My bet is that it’ll be a little while before this is sorted out.

Even if workout nutrition leads to benefits that are tangible, permanent, and standalone, they may be extremely minor. To quote Tipton and Wolfe, “Calculations based on metabolic studies from our laboratory suggest that if one used typical body composition techniques to measure changes in lean body mass, it would take approximately 1 year before any effect of a dietary supplement plus resistance exercise training could be distinguished from the resistance training alone.”

They go on to say that meaningful studies might be impossible to properly conduct due to the logistical and procedural issues inherent in a complicated, year-long statement. They also note that if the benefits are physiologically important, then it’ll be for people suffering from wasting disease. And these are two of the guys who started this entire trend in the first place.

brandon patterson MPS david allen bicep pose 082714

I do think there’s anecdotal evidence that points to workout nutrition being overrated. First, there hasn’t been a wave of body recomposition reports. If there were a tangible, short-lived anabolic window, then it should be much easier to simultaneously lose fat and gain muscle. The burst of MPS during the anabolic window would add muscle, the following fast would reduce overall calories, and the next training session would maintain the gains. That hasn’t happened though, even in the professional bodybuilding community.

In my personal experience, the people who respond best to workout nutrition are the same people who don’t have their daily calories and macros dialed in. With that in mind, it’d make sense for someone who isn’t getting enough calories, protein, and/or carbs to benefit from the inclusion of a pre-workout shake of some sort. The current formulation of one of the first supplement powders specifically designed for workout nutrition comes in at 330 calories and 24 grams of protein per serving, which isn’t exactly a zero-calorie mouth rinse by any standard.

Admittedly, this body of research is seen in the eye of its beholder, but my takeaway is that, at the very least, the idea of a tiny, anabolic window is tenuous. I also think that spending good money on exotic circa-workout protein, amino, and carb blends is probably a waste, given both the tenuous nature of the window concept and the fact that the most-engineered products are generally the least validated.

I don’t think the book is necessarily closed on workout nutrition, but it’s perhaps not as lengthy as we assumed. And even if there’s nothing to the concept of the anabolic window, workout nutrition can be advantageous in terms of helping energy levels during exercise (especially pre-workout nutrition following a fasted state,) and helping hard gainers squeeze in extra meals during the day.


  • Areta, et al. “Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesis.” J Physiol 591.9 (2013) pp 2319–2331.
  • Cribb and Hayes. “Effects of Supplement Timing and Resistance Exercise on Skeletal Muscle Hypertrophy.” Med Sci Sports Exercise 38 no11 N 2006.
  • Hoffman, et al. “Effect of Protein Supplement Timing on Strength, Power and Body Compositional Changes in Resistance-Trained Men.” Int J Sport Nutr Exerc Metab. 2009 Apr;19(2):172-85.
  • Mayhew, et al. “Translational signaling responses preceding resistance training-mediated myofiber hypertrophy in young and old humans.” J Appl Physiol (1985). Nov 2009; 107(5): 1655–1662.
  • Mitchell, et al. “Acute Post-Exercise Myofibrillar Protein Synthesis Is Not Correlated with Resistance Training-Induced Muscle Hypertrophy in Young Men.” PLoS One. 2014; 9(2): e89431.
  • Rasmussen, et al. “An oral essential amino acid-carbohydrate supplement enhances muscle protein anabolism after resistance exercise.” J Appl Physiol (1985). 2000 Feb;88(2):386-92.
  • Schoenfeld, et al. “The effect of protein timing on muscle strength and hypertrophy: a meta-analysis.” J Int Soc Sports Nutr. 2013 Dec 3;10(1):53. doi: 10.1186/1550-2783-10-53.
  • Tipton and Wolfe. “Exercise, Protein Metabolism, and Muscle Growth.” Int J Sport Nutr Exerc Metab, 2001, 11, 1 09-1 32



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