[Editor's Note: Here at ProSource, we virtually invented the modern era of whey protein supplementation with the introduction of our super-premium NytroWhey line of 100% whey protein isolate formulations over a decade ago. And, of course, we've been leading the way ever since, incorporating every new advance in protein science into a NytroWhey line that has always been the industry's gold standard. Today, the newest ultra-advanced super-protein in the line, NytroWhey Ultra Elite, is the most anabolically powerful NytroWhey yet. Unsurpassed in both its extreme muscle-mass-generating power and its smooth, luscious flavor, NytroWhey Ultra Elite contains an elite-quality, growth-factor-rich CFM whey isolate paired with a premium, ultra-rapid action super whey hydrolysate (WPH), plus Leuvon 590, all sourced from Glanbia, America's premier protein manufacturer. The Leuvon content is especially exciting, in that it contains a highly bioavailable Leucine- Bound Leucine Peptide with a remarkable capacity to help switch on anabolism.

At any rate, based on our long history of pushing the scientific envelope with regard to protein science, we're always keeping tabs on new studies that impact this all-important supplementation category. And we're committed to communicating those details to you, the members of the ProSource family. This month, we've got exciting news from a study just completed by a research team in Connecticut of which our long-time friend and ProSource writer Jeff Volek, PhD, RD was a member. This could very well be the definitive study in the field of whey protein research. Take it away, Jeff!]

There are literally thousands of different supplements you could experiment with; in the end some will work while others will be a waste of time and money.  Categorizing supplements into worthwhile versus junk is no easy task.  That's because scientific evidence is often lacking or imperfect, and the truth is people vary quite a bit in their response to supplements.  What works for one person may not work for you, and vice versa.  However there are a few supplements that consistently work well in just about everyone.  One that has received significant attention among researchers around the world over the last decade is whey protein.  The cumulative results of that work provide a strong basis for its recommended use among serious athletes.  A research team (of which point I was a part) at the University of Connecticut recently completed the largest study to date examining the muscle building effects of whey protein, and I'll share those results with you at the end of this article.  

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Basics on Whey Protein

Whey is a protein derived from milk. It actually makes up less than a quarter of the protein in milk, taking second place to the predominant protein casein.  When whey is isolated from milk and studied separately from casein, it is clear these two high quality proteins have very different amino acid compositions and biological effects.  A distinguishing feature of whey is that it has a high prevalence of essential amino acids (EAA), crucial for stimulating skeletal muscle protein synthesis and muscle gains to resistance training.  Compared to soy protein, whey contains a higher proportion of EAA, especially branched chain amino acids (BCAA) leucine, isoleucine, and valine.  For example in the same amount of total protein, whey has greater than 50% more BCAA than soy protein.  Whey is specifically the richest source of leucine, an essential amino acid that activates contractile muscle protein synthesis by activating the mammalian target of rapamycin (mTOR) signaling pathway (1,2). Another important and unique feature of whey is its rapid digestion and absorption.  Studies indicate that the availability of essential amino acids in the blood, especially leucine, is the principle driver of muscle protein synthesis.

The Importance of Leucine

The importance of leucine was showcased in recent work that examined the impact of meals containing different amounts of leucine on the time course and magnitude of muscle protein synthesis (3). In the first set of experiments, it was shown that ingestion of a meal containing 20% protein (in the form of whey protein) resulted in peak blood leucine levels after 45 min and they stayed elevated for 180 min after ingestion. Leucine levels in the blood were correlated with activation of key elements in muscle that stimulate protein synthesis. When leucine was highest, muscle protein synthesis peaked, and when leucine dropped to normal levels protein synthesis decreased as well. In a second series of experiments, whey protein was compared to wheat protein at varying levels of total protein intake. Regardless of background protein intake, whey protein resulted in greater increases in blood leucine and greater increases in muscle protein synthesis.  Again, the increases in muscle protein synthesis were associated with the levels of leucine in the blood. The bottom line from these experiments is that blood levels of leucine are a key factor in turning on protein synthesis. In addition to delivering leucine and other EAA rapidly to muscle, whey may work through other mechanisms as well.

Whey's Antioxidant Capacity

Several lines of evidence point to whey's antioxidant effects.  Exercise causes an increase in the generation of reactive oxygen species (ROS) that if not balanced appropriately by antioxidant defense systems contributes to fatigue and impaired responses to training.  Whey is a rich source of cysteine and thiol groups (3-4 times higher than soy) that are rate-limiting for synthesis of glutathione (GSH), one of the most important endogenous nonenzymatic antioxidant defense systems. Suboptimal cellular levels of GSH contribute to excessive oxidative stress that can amplify the biochemical stress response to exercise and impair recovery. Supplementation with whey protein is an effective cysteine delivery vehicle as shown by increased GSH in immune deficiency states, and chronic intense exercise training. Increased GSH translates into better antioxidant capacity, reduced oxidative stress and increased exercise performance.

Reviews addressing the immunoregulatory activities of whey in animals and humans have revealed widespread immunotropic functions that could be attributed to a variety of whey fractions such as lactoferrin, glutamine, immunoglobulins, and other peptides (e.g., lysozome, B-lactoglobulin, and B-lactalbumin).  Lactoferrin is an iron-binding glycoprotein with known immunological functions  that has been shown to be absorbed intact in adult humans.  Its anti-microbial activity is due to its ability to chelate iron, an essential element for many microorganisms. This same property may contribute to its ability to reduce oxidative stress.  Whey also contains immunoglobulins and is rich in the amino acid glutamine; both can decrease with intense exercise and therefore are important for a healthy immune system which is vital for optimal health.

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Whey Delivers a Big Anabolic Bang for the Buck

The combination of high levels of BCAA and quick absorption produces a larger and faster anabolic response than any other protein source.  Consuming whey protein at rest stimulates muscle protein synthesis (4,5), and this effect is amplified when provided before or after exercise (6,7).  In a unique and informative study, researchers performed a head-to-head comparison of whey, casein and soy on their ability to promote muscle protein synthesis after exercise (8). Trained men consumed 22 grams of hydrolyzed whey isolate, miscellar casein, or soy isolate following a bout of resistance exercise. The results were clear that whey rates of muscle protein synthesis over the 3 hour post-exercise period were about 2-fold higher after whey than casein, whereas soy was intermediate in between whey and casein. The authors attributed the superiority of whey to its greater content of leucine (2.3 grams) compared to 1.8 grams in casein and soy. Leucine levels in the blood over the 3 hour period were 73% greater than soy and 200% greater than casein.

Whey and Body Composition

Acute increases in mTOR signaling and skeletal muscle protein synthesis should logically translate into chronic increases in lean body mass, yet few studies have rigorously tested this theory directly. There is evidence that supplementation with whey protein alone (9) or a combination of whey and casein (10,11) are more effective than a carbohydrate supplement at augmenting lean body mass responses to resistance training. In comparison to casein, ingestion of whey protein during resistance training has been shown to promote greater increases in lean body mass and reductions in body fat (12).

Whey protein is particularly effective at preserving lean tissue during weight loss.  Overweight women participating in a 6 month weight loss intervention were prescribed diets consisting of 1400 kcal/day and protein at the recommended dietary allowance of 0.8 gram per kilogram body weight (13). In addition one group received 50 grams whey protein two times per day, and another group received an equal amount of carbohydrate supplement. After 6 months the whey protein group lost almost twice as much body weight (-8%) than the carbohydrate group (-4.1%).  In order to examine changes in the composition of thigh in greater detail, magnetic resonance imaging was conducted. Results revealed greater loss of adipose tissue in the whey group. As a percentage of the total muscle volume, there was a greater amount of muscle tissue present in the whey group after loss. These results indicate that a higher protein intake by way of whey protein supplementation helps maintain muscle relative to changes in body weight and body fat during calorie reduced diets.

A recent clinical study in 90 overweight men and women tracked body weight and composition over a 23 week period during which they supplemented twice per day with beverages containing whey protein, soy protein, or carbohydrate while following their normal diet (14). The supplements were consumed two times per day around breakfast and dinner and contained 200 kcal per serving. The whey and soy supplements contained 28 grams protein per serving. Subjects were not provided specific instructions to make dietary alterations during the study other than consume the supplements twice per day. The group supplementing with whey showed the greatest loss in body weight, body fat, and waist circumference. Compared to the carbohydrate group, the whey group lost 4 more pounds body weight and 5 more pounds of fat mass. The differences became apparent especially after the 4th month of supplementation.

UCONN Whey Study

My laboratory group at the University of Connecticut (UCONN) recently presented results of a large intervention study comparing whey to soy protein at the American College of Sports Medicine Annual Meeting (16).  This study involved 9 months of resistance training and protein supplementation.  Healthy men and women were randomly assigned in a double-blind manner to supplement daily with whey protein, soy protein, or carbohydrate while performing supervised resistance training. A battery of tests were performed at baseline (T0) and after 32 (T3), 64 (T6), and 96 (T9) workouts (i.e., every 3 months).  Subjects were untrained (defined as not participating in a systematic, high-intensity resistance program within 1 yr of participation) men and women 18-35 years of age.

In order to complete this work, more than 335 prospective volunteers attended an informational session and completed screening forms.  Nearly 150 subjects were enrolled, completed baseline testing and were randomly assigned into the whey protein, soy protein or carbohydrate group. Over the 9 months they were prescribed a specific diet including a constant protein intake of 1.0 g/kg body weight (not including supplementation).  For the whey and soy protein groups, the addition of the daily protein supplement (~22 g/day) increased protein intake to 1.4 grams protein per kilogram body weight.  The carbohydrate, whey, and soy powdered supplements were provided in individualized packets.  They were all isocaloric, and the whey and soy supplements contained equal amounts of protein. Subjects consumed the supplement in the morning with breakfast on non-training days and immediately after exercise on training days.

The resistance training program consisted of a non-linear, periodized program characterized by with-in week variation of the acute program variables. The goal was to promote changes in body composition, strength, power, and local muscular endurance. Four styles of workout were utilized:  light (12-15 repetitions, short rest period, lighter intensity); medium (8-10 repetitions, moderate intensity); heavy (3-6 repetitions, long rest periods, high intensity); and power (whole body exercises using 30-45% of the estimated 1 RM).  The program utilized free-weight (barbell and dumbbell), machine, bodyweight exercises, and limited use of plyometrics (i.e., medicine ball throws in various planes of movement).

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In the presentation at the American College of Sports Medicine meeting, we reported lean body mass responses between the whey and soy protein groups.  Body composition was determined using state of the art dual energy X-ray absorptiometry (DXA).  We also measured blood levels of amino acids, and as expected regular consumption of whey protein significantly increased plasma levels of leucine and other BCAA.  Despite consuming similar calories and protein during the intervention, gains in lean body mass were significantly greater in the whey protein group (7.3 pounds) than the soy protein (3.9 pounds) group.  Thus, whey protein supplementation was more effective than soy protein in promoting gains in lean body mass in response to chronic resistance training.  Stay tuned for further results from this ground breaking study where we will present findings on other aspects of performance and recovery.

Bottom Line

Previously regarded as a waste product of cheese making, whey protein is now highly valued with a solid foundation of good science behind it.  Much of this comes from the known composition of whey and acute feeding studies that have undeniably shown positive anabolic effects.  A growing number of studies now link the acute benefits of whey protein to long-term improvements in muscle mass.  

1.    Kimball SR, Jefferson LS: Signaling pathways and molecular mechanisms through which branched-chain amino acids mediate translational control of protein synthesis. J Nutr 2006, 136(1 Suppl):227S-231S.
2.    Anthony JC, Anthony TG, Kimball SR, Jefferson LS: Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine. J Nutr 2001, 131(3):856S-860S.
3.    Norton LE, Layman DK, Bunpo P, Anthony TG, Brana DV, Garlick PJ. 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. 2009 Jun;139(6):1103-9. Epub 2009 Apr 29.
4.    Boirie Y, Dangin M, Gachon P, Vasson MP, Maubois JL, Beaufrere B: Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci U S A 1997, 94(26):14930-14935.
5.    Dangin M, Boirie Y, Garcia-Rodenas C, Gachon P, Fauquant J, Callier P, Ballevre O, Beaufrere B: The digestion rate of protein is an independent regulating factor of postprandial protein retention. Am J Physiol Endocrinol Metab 2001, 280(2):E340-348.
6.    Tipton KD, Elliott TA, Cree MG, Aarsland AA, Sanford AP, Wolfe RR: Stimulation of net muscle protein synthesis by whey protein ingestion before and after exercise. Am J Physiol Endocrinol Metab 2007, 292(1):E71-76.
7.    Tipton KD, Elliott TA, Cree MG, Wolf SE, Sanford AP, Wolfe RR: Ingestion of casein and whey proteins result in muscle anabolism after resistance exercise. Med Sci Sports Exerc 2004, 36(12):2073-2081.
8.    Tang JE, Moore DR, Kujbida GW, Tarnopolsky MA, Phillips SM. Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men. J Appl Physiol. 2009 Sep;107(3):987-92. Epub 2009 Jul 9.
9.    Burke DG, Chilibeck PD, Davidson KS, Candow DG, Farthing J, Smith-Palmer T: The effect of whey protein supplementation with and without creatine monohydrate combined with resistance training on lean tissue mass and muscle strength. Int J Sport Nutr Exerc Metab 2001, 11(3):349-364.
10.    Kerksick CM, Rasmussen CJ, Lancaster SL, Magu B, Smith P, Melton C, Greenwood M, Almada AL, Earnest CP, Kreider RB: The effects of protein and amino acid supplementation on performance and training adaptations during ten weeks of resistance training. J Strength Cond Res 2006, 20(3):643-653.
11.    Willoughby DS, Stout JR, Wilborn CD: Effects of resistance training and protein plus amino acid supplementation on muscle anabolism, mass, and strength. Amino Acids 2006.
12.    Cribb PJ, Williams AD, Carey MF, Hayes A: The effect of whey isolate and resistance training on strength, body composition, and plasma glutamine. Int J Sport Nutr Exerc Metab 2006, 16(5):494-509.
13.    Mojtahedi MC, Thorpe MP, Karampinos DC, Johnson CL, Layman DK, Georgiadis JG, Evans EM. The Effects of a higher protein intake during energy restriction on changes in body composition and physical function in older women. J Gerontol A Biol Sci Med Sci. 2011 Jul 27.
14.    Baer DJ, Stote KS, Paul DR, Harris GK, Rumpler WV, Clevidence BA. Whey Protein but Not Soy Protein Supplementation Alters Body Weight and Composition in Free-Living Overweight and Obese Adults. J Nutr. 2011 Jun 15.
15.    Candow DG, Burke NC, Smith-Palmer T, Burke DG: Effect of whey and soy protein supplementation combined with resistance training in young adults. Int J Sport Nutr Exerc Metab 2006, 16(3):233-244.
16.    Volk BM, Quann EE, Ballard KD, Kupchak BR, Gomez AL, Kraemer WJ, Volek JS.  Whey protein supplementation results in greater gains in lean body mass compared to soy protein during a progressive 9-month resistance training program. American College of Sports Medicine Annual Meeting, Program #4916, May, 2012.

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