Whey Protein Research Update: Fat Loss, Myostatin-Binding Proteins And Androgen Receptors!
by Robbie J. Durand, MA

Whey Protein Enhances Fat Loss

Whey proteins modulate several hormones that are conducive for weight loss. Acute studies have reported that whey protein isolate (60 grams per day) evaluated over six months resulted in significantly lower hyperinsulinemia (less fat storage potential), lower cortisol levels (lean muscle preservation) and increased ghrelin release (satiety enhancement). A new study released in Nutrition & Metabolism reported that people on whey protein supplementation lost more weight than a control group receiving maltrodextrins in conjunction with a calorie-restricted diet. Each subject was instructed to consume one supplement 20 minutes before breakfast and one supplement 20 minutes before dinner. The whey protein supplement contained 10 grams of protein per serving as a combination of intact whey protein and peptides. It also contained minerals that were purified from milk. The control group received an isocaloric beverage containing maltodextrin. After 12 weeks, weight loss was consistently higher in the whey protein subjects, primarily the result of losing body fat (subjects taking whey protein lost 6.1 percent of their body fat mass). The whey protein group subjects also lost significantly less lean muscle mass compared to control subjects. Whey protein may be the perfect fat-loss supplement when dieting for an important event or for targeting fat loss while maintaining lean muscle.7

Whey Protein And Androgen Receptors

The physiological importance of the androgen receptor increasing muscle hypertrophy has been demonstrated, as animal studies that administer androgen receptor antagonists during muscle overload have suppressed muscle hypertrophy.1 This suggests that the androgen pathway has a significant effect in exercise-induced muscle hypertrophy and emphasizes the importance of the increase in the number of androgen receptors in exercised muscle. Elevated levels of testosterone that occur after heavy resistance exercise are important, however, if androgen receptor levels are low, then the increased testosterone would be of less anabolic value than if receptor levels were unchanged or increased. Intense exercise can induce transient increases in circulating testosterone that corresponds with an increase in skeletal muscle androgen receptor-binding.4 Only one supplement has been shown to enhance androgen receptors in response to resistance exercise and that is L-Carnitine L-Tartrate. In a previous study in Medicine & Science in Sports and Exercise, it was reported that the use of L-Carnitine L-Tartrate (500mg a day— twice at breakfast and twice at lunch…the total dose for the training study was 2 grams per day for 21 days) caused a significant increase in resting androgen concentration compared to the placebo group.2 Exciting new research has recently been released in the Journal of Steroid Biochemistry and Molecular Biology that pre- and post-exercise whey protein supplementation tended to cause small increases in androgen receptor regulation compared to the control group. Although it was not a large effect (findings did not reach statistical significance), even small increases in androgen receptors are beneficial in the long term, which means that testosterone has more binding sites. This study is similar to a previous study in which men were given a meal after exercise that resulted in an increase in androgen receptors.2

Study Breakdown

The study investigated elderly men (57-72 years of age) who are not the typical weight-training age, but the findings are interesting nonetheless. The subjects trained for five months, twice per week. The subjects were randomized to either a whey protein isolate group (15g of whey protein) or a placebo. The subjects consumed the whey protein isolate both before and after exercise. The heavy resistance exercise bout included the leg press machine. The total set number in the leg press was 5 sets (5×10-repetition maximums), with a 2-minute recovery between the sets. The loads were adjusted during the course of the session so that each subject would be able to perform 10 repetitions per set. If the load was too heavy, the subject was assisted slightly during the last repetitions of the set. Muscle biopsies were taken from the leg both before and after exercise. The group who consumed the 15g of whey protein isolate before and after exercise had a small trend toward an increase in androgen receptors, but this effect was not large.

The question that I wondered was, “If there was a small trend toward an increase in androgen receptor upregulation in older men consuming whey protein, what about a younger man performing high-intensity exercise?” Younger men tend to have more androgen receptors than older men, which may have resulted in different responses. Additionally, older men tend to have a blunted androgen receptor response after resistance exercise compared to younger men. Another issue is that the subjects were exercising twice a week and performed only 5 sets of leg presses, which is low volume compared to a some more intense workouts. Could more frequent workouts with whey protein isolates enhance the effect long term? Based on previous research, it seems that the more frequently a muscle is trained, the greater the increases in androgen content.

For example, subjects performed three lower body resistance exercise bouts, each separated by 48 hours. The subjects performed 3 sets of 8-10 repetitions at 75 percent to 80 percent one-repetition maximum (1 RM) using the squat, leg press and leg extension exercises, respectively. Muscle biopsies were obtained immediately before the first exercise bout and 48 hours after each of the three bouts, whereas blood samples were obtained immediately before, immediately after and 30 minutes after each bout. At the end of the study, the researchers reported that the androgen receptor mRNA and protein were significantly increased after the first session (40 percent increase), second session (~100 percent increase) and third session (~202 percent increase in androgen receptor concentration) exercise bouts, respectively, and were significantly correlated to serum testosterone increases during exercise.13 The study suggests that greater training frequency increased androgen receptors. Another problem is that the older men have a blunted response of growth factors (MGF, myostatin) compared to younger men. Even though the effect in older men was small, a slight increase in androgen receptors can lead to substantial gains over the long run.

Other Interesting Findings…

The researchers also reported that the increases in testosterone that occurred during the exercise protocol were correlated with the significant upregulation of the androgen receptor at 1 hour post-exercise. Once again, the study highlights the importance of high-intensity exercise and that increases in testosterone are associated with the degree in which the androgen receptor is increased. Once again, shorter rest periods (that result in enhanced testosterone production) may enhance androgen receptor concentration compared to longer rest protocols. 2cul48if600r4r7

Low-Dose Testosterone And GH Increase Androgen Receptors

Testosterone by itself increases androgen receptors; however, combining testosterone with resistance exercise has a greater effect than either one alone. For example, it was reported that during aging, an increase in androgen receptor content was induced by exercise and also administration of nandrolone decanoate, but combining the two had the greatest impact on increasing androgen receptor content in muscle.5 The problem with using testosterone is there is a large increase in testosterone which results in a dip below baseline, so scientists are looking for a way to have steady testosterone levels.

In the Journal of Clinical Endocrinology and Metabolism, researchers reported that a combination of GH and 5mg transdermal patch resulted in an increase in muscle thigh cross-sectional area, but also an increase in androgen receptor content in muscle. The combination of GH and transdermal patches resulted in greater effects compared to either treatment alone.6 The dose of testosterone was physiological, not supraphysiological; this means that even small increases in testosterone can result in increases in the androgen receptor and enhance lean muscle mass.

Whey Protein Increases Myostatin-Binding Protein

The same study group who examined androgen receptors in men also looked at the myostatin-binding proteins FLRG (follistatin-related gene.) FLRG has been shown to inhibit myostatin activity in a concentration-dependent manner and it has been shown to circulate in human blood and expressed in human skeletal muscle. Increasing FLGR reduces myostatin; mice that overexpress FLRG have increased muscle mass and lowered myostatin in a dose-dependent manner. Interestingly, the older men who consumed whey protein before and after exercise had an increase in FLGR, while the control group had no change in FLGR.8 This suggests that whey protein may suppress myostatin levels by increasing FLGR, but more research needs to be conducted.

• Whey protein has a nutrient-partitioning effect (enhances fat loss while sparing lean muscle.)
• The acute increases in testosterone were associated with greater androgen receptor concentration post-exercise.
• Whey protein may increase androgen receptors post-exercise.
• Whey protein increased myostatin-binding proteins.

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1. Inoue K, Yamasaki S, Fushiki T, Okada Y, Sugimoto E. Androgen receptor antagonist suppresses exercise-induced hypertrophy of skeletal muscle. Eur J Appl Physiol Occup Physiol, 1994;69(1):88-91.
2. Kraemer WJ, Spiering BA, Volek JS, Ratamess NA, Sharman MJ, Rubin MR, French DN, Silvestre R, Hatfield DL, VAN Heest JL, Vingren JL, Judelson DA, Deschenes MR, Maresh CM. Androgenic Responses to Resistance Exercise: Effects of Feeding and L-Carnitine. Med Sci Sports Exerc, 2006 Jul;38(7):1288-1296.
3. Bamman MM, Shipp JR, Jiang J, Gower BA, Hunter GR, Goodman A, McLafferty CL Jr, Urban RJ. Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans. Am J Physiol Endocrinol Metab, 2001 Mar;280(3):E383-90.
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6. Giannoulis MG, Jackson N, Shojaee-Moradie F, Nair KS, Sonksen PH, Martin F, Umpleby AM. The Effects of Growth Hormone and/or Testosterone on Whole Body Protein Kinetics and Skeletal Muscle Gene Expression in Healthy Elderly Men: A Randomized Controlled Trial. J Clin Endocrinol Metab, 2008 May 13.
7. Frestedt JL, Zenk JL, Kuskowski MA, Ward LS, Bastian ED. A whey-protein supplement increases fat loss and spares lean muscle in obese subjects: a randomized human clinical study. Nutr Metab, (Lond). 2008 Mar 27;5:8.
8. Hulmi JJ, Kovanen V, Lisko I, Selänne H, Mero AA. The effects of whey protein on myostatin and cell cycle-related gene expression responses to a single heavy resistance exercise bout in trained older men. Eur J Appl Physiol, 2008 Jan;102(2):205-13.