Tuesday, October 14, 2014

Low Testosterone ⇨ No Muscle Repair & Long-Term Gains: Testosterone's Effects on Satellite Cells & Myonuclei. Plus: Paradoxical 19% Drop in T W/ Whey + CHO Shake in Boys

Studies show that "women demonstrate significantly larger satellite cell and satellite cell nucleus areas than men" (Roth. 2000) - an effect that could be mediated by the effects of estrogen, not testosterone on satellite cells.
As a SuppVersity reader you will know that satellite cells are the "muscle reserve" that's "cooking" between the basal lamina and sarcolemma of your muscles. They are the cells your body needs to (a) repair damaged muscle cell nuclei (myonuclei) and (b) generate new myonuclei. As a SuppVersity reader you will also know that these new myonuclei are necessary to "Grow Beyond Temporary Physiological Limits" (learn more) that are imposed to your muscle by the myostatin increase that occurs, when the domain size, i.e. the volume of your muscle that's controlled by a single myonucleus, becomes too large.

To make a long story short: Without satellite cells, your muscle repair and growth will be impaired, which is why the results Thue Kvorning and Danish colleagues present in a soon-to-be-published paper in Acta Physiologica are relevant for everyone who want to gain or simply maintain maximal / optimal muscle mass.
You can learn more about satellice cells & co at the SuppVersity

Acc. Satellite Cell Growth

Training in Hypoxia

Epicatechin as a Muscle Builder

Intracrine Effects of Anabolics

NAC Impairs Sa- tellite Cell Act.

Understanding Muscle Growth
In the corresponding experiment, the Danish researchers treated 22 moderately trained young men with a GnHR analogue called goserelin that will dock to the gonadotropin receptors in the brain without stimulating the production of testosterone.
Figure 1: Graphical overview of the procedures (Kvorning. 2014)
Needless to say that the testosterone levels of the study participants were significantly reduced after 4 weeks, when the actual resistance training study began - see Figure 1 for an overview.
In obese boys whey + cho shakes lead to sign. T-reductions (Schwartz. 2014)
Speaking of ways to reduce testosterone: A recent study in obese pubertal boys showed - much to my own astonishment - that having 30 whey isolate + 30g glucose will significantly reduce the testosterone levels (19%) of the young subjects.

Don't ask me what exactly it is that causes this effect, but I suspect it may be related to the huge insulin spike (+410% - no typo!) the subjects experienced. From studies in women with polycystic ovary syndrome we know that insulin which will usually augment the release of sex hormones loses its function in vivo (Willis. 1996).

A similar temporary suppression of the pulsatile luteinizing hormone release and subsequent acute redutions in testosterone has been observed in adults in response to glucose alone (Iranmanesh. 2012). No reason to avoid carbs, though. In a study by Volek et al. the consumption of a high fat diet lead to a persistent 22% and 23% reduction in total and free testosterone (Volek. 2001).
A standardized training program which didn't look much different from what some of you may be doing at the gym (both the guys in the active and the placebo group had to perform, by the way):
"A standardized warm-up was performed before training consisting of 4 sets of squats with 20 repetitions without load and with 1 min rest between sets. Subjects from both groups trained using the same progressive strength training program. The programs were performed 3 times a week for 8 weeks and consisted of leg press, knee extension, leg curl, bench press, lat pull down, biceps curl, and elbow extension. Subjects did 4 sets of each exercise for the lower body and 3 sets of each exercise for the upper body. The strength training period consisted of 24 training sessions periodized in 3 cycles of 8 training sessions with changing training loads (6 RM – 10 RM). The goserelin group and the placebo group increased training loads to the same extent and underwent the same training volume." (Kvorning. 2014)
In contrast to the training stimulus, which was identical for both groups, the intra-muscular response to the workout differed significantly between the young men in the goserelin group (10-20x reduced testosterone levels) and their peers in the placebo group:
Figure 2: This is one of the cases, where having more is not better. Having more free satellite cells and fewer myonuclei is certainly not a good thing for someone striving to build maximal muscle mass.
In spite of the fact that in both, the placebo and goserelin groups, training lead to a signficant increase in the number of satellite cells in fast twitch type II fibers by 20 % in placebo and by 52 % in goserelin (p<0.01), the number of myonuclei, which is the one that's important with respect to future growth remained unchanged in the goserelin (p<0.05) group. In the placebo group, on the other hand, the myonuclear number increased significantly by 12 %.

In view of the resistance training focus of the workouts, it's not really surprising that on such changes were observed in the slow-twitch, endurance-type type I fibers in either group.
Can't believe estrogen is required for muscle building, check out the previous evidence in this SuppVersity article!
Bottom line: In view of preceding evidence that it's not testosterone, but estrogen that's required for proper satellite cell function (see "Estrogen, Friend or Foe of Skeletal Muscle Hypertrophy? Plus: Hey, Bro! Are You 'SERMing' Away Your Satellite Cells?" | learn more), it's a pity Kvorning et al. didn't measure the estrogen levels as well.

In view of the fact that men produce their estrogen via aromatization from testosterone, it's yet very likely that not just the T, but also the E2 levels of the men in the goserelin group were significantly suppressed. The association between estrogen and bone health and the distinctive changes in bone morphogenetic proteins signaling the researchers observed would actually support this hypothesis, which should remind you of the fallacy of abusing SERMs and / or aromatase inhibitors longer than it would be necessary to normalize your estrogen levels, guys.

And I mean, if you have enough testosterone, you'll have enough estrogen, as well, right? Comment on Facebook!

PS: I am fully aware that the necessity of satellite cell recruitment for muscle gains (and by some scientists even repair) is still debated (cf. Pallafacchina. 2013), but up to now, I still have to see the counter-evidence that is not based on mere short-term muscle protein synthesis studies. If you look at the mechanism, it should be obvious that satellite cell activity becomes important only, when the natural upper limit for functional domain sizes is reached and that was certainly not the case in any of the commonly cited rodent studies. Plus: There is evidence in favor of the important role of satellite cells in skeletal muscle hypertrophy from other studies (Appell. 1988; Schultz. 1989; Rosenblatt. 1994;  Barton-Davis. 1999; Mitchell. 2001).
  • Appell, H-J., S. Forsberg, and W. Hollmann. "Satellite cell activation in human skeletal muscle after training: evidence for muscle fiber neoformation." International journal of sports medicine 9.04 (1988): 297-299.
  • Barton-Davis, E. R., D. I. Shoturma, and H. L. Sweeney. "Contribution of satellite cells to IGF-I induced hypertrophy of skeletal muscle." Acta physiologica scandinavica 167.4 (1999): 301-305. 
  • Iranmanesh, Ali, Donna Lawson, and Johannes D. Veldhuis. "Glucose ingestion acutely lowers pulsatile LH and basal testosterone secretion in men." American Journal of Physiology-Endocrinology and Metabolism 302.6 (2012): E724-E730.
  • Kvorning, Thue, et al. "The activity of satellite cells and myonuclei following 8 weeks of strength training in young men with suppressed testosterone levels." Acta Physiologica (2014). 
  • Mitchell, Patrick O., and Grace K. Pavlath. "A muscle precursor cell-dependent pathway contributes to muscle growth after atrophy." American Journal of Physiology-Cell Physiology 281.5 (2001): C1706-C1715. 
  • Pallafacchina, G., B. Blaauw, and S. Schiaffino. "Role of satellite cells in muscle growth and maintenance of muscle mass." Nutrition, Metabolism and Cardiovascular Diseases 23 (2013): S12-S18.
  • Rosenblatt, J. David, David Yong, and David J. Parry. "Satellite cell activity is required for hypertrophy of overloaded adult rat muscle." Muscle & nerve 17.6 (1994): 608-613. 
  • Schultz, E. D. W. A. R. D. "Satellite cell behavior during skeletal muscle growth and regeneration." Medicine and science in sports and exercise 21.5 Suppl (1989): S181-6.
  • Schwartz et al. "Acute decrease in serum testosterone after a mixed glucose and protein beverage in obese peripubertal boys." Clinical Endocrinology (2014). Accepted Article. 
  • Volek, Jeff S., et al. "Effects of a high-fat diet on postabsorptive and postprandial testosterone responses to a fat-rich meal." Metabolism 50.11 (2001): 1351-1355.
  • Willis, D. E. B. B. I. E., et al. "Modulation by insulin of follicle-stimulating hormone and luteinizing hormone actions in human granulosa cells of normal and polycystic ovaries." The Journal of Clinical Endocrinology & Metabolism 81.1 (1996): 302-309.