Should You Vary Protein Sources To Maximize Muscle Building?

Leucine, mTor, and muscle protein synthesis (MPS). Find out how the protein foods you eat impact the muscle growth process for the better - and for the worse.

Proteins are often put upon a pedestal by gym-goers and for good reason. Aside from the myriad of functions proteins play in vivo, they’re also a key regulator/substrate for muscular (and other tissue) hypertrophy. Obviously if you’re putting in endless hours training and beating your body to a pulp you’re going to want to maximize your output with proper nutrition, and specifically, proper protein intake.

Not surprisingly, the health and fitness industry has a propensity to dichotomize subtopics into polar extremes. Many bodybuilders/physique competitors search tirelessly for the optimal way of doing things and with this comes tendency to adhere rigidly to extreme measures.  It’s only natural then that the topic of protein sources would fall victim to this trend.

This isn’t to say that a middle-road approach is always superior to extreme protocols, because that isn’t the reality of things either (and quite frankly, more often than not people use “moderation” as a copout for laziness/lack of discipline).

So what really is best (optimal) when it comes to different protein sources (such as whey, casein, egg, animal, etc.)? Moreover, is there a necessity to vary between these sources to sort of “cover all the bases” or could we achieve optimal results subsisting on a lone, “ideal” protein source? This article will take a look at what the literature says about these queries and form some conclusions for you to draw from on your quest to improving your health and body.

The physiology of muscular hypertrophy

Many readers likely have a rudimentary understanding of what muscle hypertrophy is/means, but for those who don’t (or those who need a bit of refreshment) we will take a truncated look at the physiological basis of how muscles grow. Before we move on, be sure not to confuse the terms anabolism and hypertrophy with one another; anabolism simply refers to any process that results in synthesis of substrates and/or tissues (e.g. the formation of ATP from ADP and phosphate is an anabolic reaction).

Hypertrophy, on the other hand, is used to denote the growth of tissue. So while you could theoretically say muscle hypertrophy is an anabolic process, you wouldn’t want to say the formation of ATP from ADP and phosphate is a hypertrophic reaction because it makes no sense.

Beef and iron

Muscle hypertrophy (or atrophy) is ultimately determined by the net protein turnover ratio. The protein turnover ratio is a quantitative measurement of the rate of muscle protein synthesis (MPS) and muscle protein breakdown (MPB).  Thus, when the MPS rate is greater than the rate of MPB, the protein turnover ratio is in favor of muscle growth. It should be noted that we are looking specifically at skeletal muscle protein turnover, not the whole-body protein turnover (e.g. hypertrophy of gut tissue, for example. isn’t indicative of muscle growth).

A plethora of factors influence the net protein turnover ratio, such as exercise, nutrient intake, disease/immune conditions, gene expression, pharmaceutical agents, over-the-counter supplements, etc.  Intuitively, we want to maintain a high rate of MPS and a low rate of MPB (thus the muscle protein turnover ratio is in favor of hypertrophy/growth).  But like most physiological pathways, muscle protein synthesis is tightly regulated, in this case via a protein encoded by the FRAP1 gene in humans called the mammalian target of rapamycin (mTOR). (1)

The mTOR protein is the backbone to mTOR protein complexes (such as mTORC1 and mTORC2) that activate protein synthesis when suitable cell conditions are met (and ultimately result in cellular growth and proliferation). (2) The activity of mTOR protein complexes are controlled by the cell’s energetic state, circulating growth factors and hormones (especially insulin), nutrient availability, and oxidative stress. Naturally then, our goal is to bolster these signals in a manner that is conducive to up-regulating MPS.

Alas, the entire regulation of protein synthesis pathways is highly complex (and would only convolute this article), it’s still useful to have this elementary knowledge of how muscle cells actually grow.

Do different protein sources differentially stimulate mTOR?

Naturally, those looking to get the most out of their diet are seeking for the protein sources that maximize MPS in response to feeding.  Much of the research thus far has uncovered that a key substrate in the activation of mTOR is the amino acid L-leucine. Moreover, studies corroborate that the proportion of leucine in a given protein source has direct effect on the peak MPS rate attained in the postprandial state. (3,4)

What this tells us, then, is that protein source does indeed matter, but only in the sense that we are ingesting sufficient essential amino acids (and a nominal amount of leucine). Remember, essential amino acids (EAAs) are those which we must obtain from exogenous sources (e.g. diet, supplementation, etc.)  since we don’t synthesize them endogenously. Lo and behold, whey protein, the acclaimed gold standard of supplementation for many gym-goers, is one of the best sources of these essential amino acids, and more importantly of L-leucine.

Getting the most out of your protein

As aforementioned, protein source matters since MPS is differentially stimulated in proportion to the EAA content (and specifically L-leucine) of each meal. A conservative estimate, based on extrapolations, is that 30+ grams of a leucine-rich protein source (such as most animal proteins and whey protein) is plenty to sufficiently elevate MPS for a good 3-4 hours. (5) Again, this is just a starting point (read: baseline) for active individuals but is by no means a strict rule.

Furthermore, you can obtain the EAAs (and l-leucine) from various sources in a single meal so long as still reach the overall quota for protein needed to maximize MPS. So for example, if you’re a vegetarian, you would likely want to supplement with whey protein since vegetable sources of protein (like soy) are lacking in leucine content. Contrarily, carnivores/omnivores may not need as much (or any) supplemental protein as animal proteins are generally rich in the necessary EAAs for maximal MPS response to a feeding.

For your reference, the table belows provides a few supplemental and food-source proteins, respectively, with their inherent L-leucine content:

Branched-Chain Amino Acid and Leucine Content of Food Ingredients
Type of Protein BCAAs Leucine
Whey protein isolate 26% 14%
Casein 23% 10%
Egg protein 20% 9%
Soy protein isolate 18% 8%
Wheat protein 15% 7%

Adapted from: Layman DK, USDA Food Composition Tables. J Nutr 133:261S-267S, 2003.

BCAA Content


1. Tokunaga C, Yoshino K, Yonezawa K (2004). "mTOR integrates amino acid- and energy-sensing pathways". Biochem Biophys Res Commun 313 (2): 443–6. doi:10.1016/j.bbrc.2003.07.019. PMID 14684182.

2. Wullschleger S, Loewith R, Hall MN (February 2006). "TOR signaling in growth and metabolism". Cell 124 (3): 471–84. doi:10.1016/j.cell.2006.01.016. PMID 16469695.

3. Katsanos CS, Kobayashi H, Sheffield-Moore M, Aarsland A, Wolfe RR. A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E381-7. Epub 2006 Feb 28. PubMed PMID: 16507602.

4. Norton LE, Wilson GJ, Layman DK, Moulton CJ, Garlick PJ. Leucine content of dietary proteins is a determinant of postprandial skeletal muscle protein synthesis in adult rats. Nutr Metab (Lond). 2012 Jul 20;9(1):67. doi: 10.1186/1743-7075-9-67. PubMed PMID: 22818257; PubMed Central PMCID: PMC3488566.

5. Areta JL, Burke LM, Ross ML, Camera DM, West DW, Broad EM, Jeacocke NA, Moore DR, Stellingwerff T, Phillips SM, Hawley JA, Coffey VG. Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesis. J Physiol. 2013 May 1;591(Pt 9):2319-31. doi: 10.1113/jphysiol.2012.244897. Epub 2013 Mar 4.