Is Whey The Way?

By: Cody Haun, PhD(c), MA, CSCS

This is a short and sweet post on some of the scientific research related to supplemental whey protein of relevance to fitness-related endeavors. For a more extensive discussion, please see Hulmi et al. Proteins are composed of amino acids linked by peptide bonds. Amino acids contain the chemical element nitrogen. This makes proteins unique to carbohydrates and fats. A typical human body consists primarily of protein and water, where proteins are critical in providing structure to tissues and support a host of physiological processes necessary for health and performance. In relation to human physiology, amino acids are categorized as essential (EAA) or non-essential (NAA) to attain through the diet. This is because our cells cannot manufacture the amino acids characterized as EAA, whereas the NAA can be synthesized.























Importantly, ~80-90% of the dry weight of skeletal muscle is comprised of protein (dry weight refers to the weight of skeletal muscle tissue when water is removed). Muscle proteins are constantly being turned over at various rates; meaning that proteins are continually being synthesized and broken down. Therefore, significant alterations in skeletal muscle size over time are due in large part to acute and chronic alterations in muscle protein synthesis (MPS) and muscle protein breakdown (MPB) rates. The difference between MPS and MPB rates results in a positive or negative muscle protein balance (MPBAL) at a given time, visualized by the equation: MPS – MPB = MPBAL.

Once structural proteins are synthesized and folded in skeletal muscle cells, they can be transported and deposited at specific loci of the cell. If synthesis rates and the deposition of structural proteins outpace breakdown rates for a sufficient amount of time, measurable increases in muscle cell size can occur. Below is a microscopic image from our lab showing this from an immunohistochemical stain of skeletal muscle cells sampled from the vastus lateralis muscle of the quadricep from the same subject before 12 weeks of RT and after.

In addition to resistance training (RT), ingestion of EAA can increase MPS acutely. Combining RT with ingestion of EAA pre- and/or post-RT has been shown to result in higher MPBAL measures than RT or EAA ingestion alone. Various dietary proteins have different proportions of EAA, affecting their effectiveness to increase MPS upon ingestion. Although a variety of calculations and terms have been proposed to describe the quality of a dietary protein source, the Protein Digestibility Corrected Amino Acid Score (PDCAAS) has been adopted as the preferred method of calculating protein quality for human nutrition. Casein, egg, milk, soy, and whey PDCAAS are among the highest, as shown in the table from Hoffman et al.

Although other proteins exhibit similar PDCAAS to whey protein, ingestion of whey protein has been shown to result in comparatively higher MPS responses at rest and post-RT versus other types of protein with similar PDCAAS. Data from Tang et al demonstrates this point nicely in the figure below.

Whey proteins are derived from milk. Whey is defined as the liquid portion of milk remaining after the formation of curds (i.e., solid or semi-solid coagulate of milk) during the process of making cheese. Bovine (i.e., cow) milk is most commonly used for the production of commercial whey protein powders. However, not all whey protein powders are the same. Commercially, whey protein powders are typically characterized as: whey protein concentrate (WPC), whey protein hydrolysate (WPH), or whey protein isolate (WPI). This nomenclature is associated with how whey protein is manufactured. Consequently, each type of whey protein supplement can contain different amounts of EAA, and exhibit different properties pertinent to the effectiveness of the whey protein supplement.

Depending on the manufacturing process, WPC can contain anywhere between ~30% – ~80% protein by volume. Commonly, commercial WPC powders contain ~70-80% protein concentrations by volume. Conversely, WPI contains ≥~90% protein concentrations by volume. WPH is produced by hydrolyzing (i.e., breaking down) whey proteins via enzymatic digestion and/or mild acid based techniques typically involving warm temperatures. This technique is utilized to break whey proteins down into smaller peptides. This can potentially increase the rate of digestion and absorption of amino acids. However, various manufacturing processes can affect the degree of hydrolysis making specific effects of WPH difficult to study. Albeit, as noted by Hulmi et al, select evidence has demonstrated a higher insulin response to WPH ingestion and augmented recovery from exercise in humans compared to WPC or WPI. With these points in mind, it is important to consider the quality of the whey protein supplement you’re thinking of purchasing by studying the manufacturing process utilized and your intention of consumption. Briefly, it seems that, by volume, one can attain a higher proportion of whey protein through consumption of a WPI in comparison to a WPC supplement. Although intriguing, WPH deserves further research before confident comparisons to WPC and WPI can be made since little evidence is available on specific types of WPH utilizing different manufacturing techniques. For example, the manufacturing process utilized could affect the number of specific bioactive peptides present in a WPH supplement potentially altering the physiological consequences.

Notwithstanding, whey protein is enriched with EAA, and particularly the amino acid leucine. As shown in the table above, whey protein tends to contain higher amounts of leucine compared to other common sources of protein. I think a short snippet from my dissertation is useful here to provide some clarity regarding why this is important at the molecular level in skeletal muscle. In skeletal muscle cells, significant increases in leucine concentrations tend to result in the activation or increased activity of a signaling protein complex called mammalian target of rapamycin complex 1 (mTORc1), whereas other amino acids do not seem to exert this effect. mTORc1 activation seems to be required for the hypertrophic response to RE in humans. Leucine seems to enhance the activation of mTORc1 by first binding to the leucyl-transfer RNA synthetase (LRS). LRS facilitates the hydrolysis of a molecule called guanosine triphosphate (GTP) bound to a small G-protein (RagD), allowing the interaction of various other Rag proteins which eventually direct mTORc1 to an organelle in the cell called a lysosome. A molecule located at the lysosome called Rheb (Rag homolog enriched in brain) is a critical activator of mTOR and, therefore, the ultimate effect of leucine on muscle protein synthesis seems to result from the direction of mTOR to interact with Rheb at the lysosome. Upon mTOR-Rheb interaction, downstream targets of mTORc1 involved in the translation of mRNA into proteins (e.g., contractile proteins) are activated thereby increasing the rates of MPS.

Beyond these interesting properties of whey, my good friend Dr. Brooks Mobley did some very cool work in our lab showing the presence of nanosized membrane vesicles called exosomes in whey protein. Exosomes can contain various bioactive components including peptides, mRNA, and microRNA that can affect the processes of MPB and MPS. Dr. Mobley then treated cultured skeletal muscle cells with these whey-derived exosomes and the cells grew! Furthermore, Dr. Mobley and Dr. Roberts performed an experiment in our lab where rodents were fed WPH and responses were compared to a control group provided water only. Interestingly, various responses related to increased lipolysis (i.e., fat breakdown) were significantly greater in the group fed WPH. This data suggests that the observed positive effects of whey protein consumption observed in other studies may extend beyond the amino acid profile alone. Additionally, the latter experiment indicates an acute lipolytic effect of whey protein consumption. For these reasons, on a per-serving basis, whey protein seems to be a wiser choice compared to other types of protein supplements for those interested in maximizing RT adaptations. The favorable EAA profile and unique bioactive properties point to whey as a superior protein source to many other options, by comparison. I hope you enjoyed the read and feel free to reach out with any questions you may have.

Until the next time,
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Cody Haun, PhD(c), MA, CSCS
-APLYFT Science Consultant