Monday, August 8, 2011

Well-Stocked Muscle Glycogen Stores Not Necessary For Exercise Induced Muscle Anabolic Response. Additional 5x Increment by Post(!)-Workout Whey + Cho Supplement.

Image 1: Glycogen depleted or not,
post-workout protein, preferably from a 
leucine-rich, fast digesting and nutritionally
complete source such as whey, is a must.
It is one thing that many trainees feel they perform better, train harder or have better endurance, when they (over-)"load" their muscle glycogen stores pre-workout. And as long as their need for carbohydrates is not merely imaginary, i.e. they feel sluggish and their gym performance sucks, whenever they are training on empty glycogen stores, I am quite sure that they will also make better gains. This mechanism would yet be completely different from any immediate, yet hitherto scientifically not validated, facilitative biomolecular effect of well-stocked glycogen stores on muscular hypertrophy, as it is proposed by many advocates of preworkout or even 24/7 carbohydrate (re-)feeding.

Dr. Connelly, who talked about this issue at length in the past installments of the BodyRX Show, was kind enough to remind me that back in 2007 Coffey et al. from Stuart Phillips' group at McMaster University, in Hamilton, Ontario (Canada), conducted a study that was based on an antithetical hypothesis, i.e. whether or not commencing resistance exercise with low muscle glycogen would enhance the encoding of genes implicated in muscular hypertrophy (Coffey. 2007). Yet, while there were significant differences at rest for the glycogen depleted vs. the normal leg of the subjects, both the increased GLUT4-MRNA expression, which is a sign of an increased capacity for glucose uptake, as well as the reduced expression of atrophic atrogenes (responsible for proteolysis, i.e. protein degradation) were overridden by exercise. Now, four years later Donny Camera from the University of Melbourne presented the results of a recent colloberation with the scientists from McMaster at the American College of Sports Medicine Conference in Denver, this year (Camera. 2011). The intention of this 2nd study was to elucidate the "effect of divergent glycogen content and subsequent post-exercise nutrition on anabolic signaling target p70S6 kinase during the early recovery period" after the completion of a standardized resistance training protocol.
Illustration 1: Very simplified illustration
of the role of mTOR and p90S6K
in protein synthesis.
Did you know that p70S6 kinase is a key component of the mTOR (the mammalian target of rapamycin) signaling cascade? The activation of mTOR via branched chain amino acids (leucine in particular) has been shown to increase p70S6K phosphorylation (the phosphorylation is equivalent to 'switching' it on). In a similar vein, physical exercise can activate protein synthesis via phosphorylation (activation) of p70S6K. The degree / increase / decrease of p70S6K kinase phosphorylation is thus considered a reliable indicator of the protein anabolic response to supplement and exercise protocols.
The evening before the actual experiment was conducted, the 16 resistance-trained male subjects (~23y) who participated in the study, reported to the laboratory in order to perform a single-legged cycling exercise to fatigue. In order not to upset the thusly established difference in glyocogen content between the trained (LOW) and the untrained leg (NORMAL), the subjects consumed an identical low carbohydrate meal after the workout and had to abstain from foods until the subsequent day, when they performed 5 unilateral leg press repetitions at 80% of their personal 1RM (one-repetition-max) with both their normal, as well as the glycogen depleted (LOW) leg. Muscle biopsies were taken 1h post exercise, and subjects consumed either a 0.5l post-workout shake that consisted of 20g whey + 40g maltodextrin or placebo immediately post and 2h after the exercise regimen.
Figure 1: Increase in  p70S6K phosphorylation in 16 resistance trained males after unilateral leg press exercise in normal and glycogen depleted leg relative to baseline (data adapted from Camera. 2011)
Although the muscle glycogen content increased exclusively in the nutrient (20g whey + 40g maltodextrin) group, significant increases of phosphorylation of p70S6K one of the key regulators of protein synthesis were seen in both legs of the subjects. As my plot of the restricted data I could extract from the abstract in the conference protocol (a paper obviously has not been published, yet) indicates, this increase was augmented up to 5x in the 1-4h hour post workout window in the glycogen depleted leg. While there was still a 8x increase in p70S6K phosphorylation in the glycogen-depleted leg even in the absence of post-workout nutrient repletion, post-workout nutrient (re-)feeding turned out to be necessary to illicit any increase in p70S6K phosphorylation over baseline in the normal leg.
Note that the baseline levels of the LOW and the NORMAL leg were probably different and the 8x increase could thus have lead to an absolute level of p70S6K phosphorylation that was still lower than in the NORMAL leg..
These results do not only contradict the initially raised hypothesis that well-stocked glycogen stores would be a necessary or at least facilitative prerequisite for the muscle anabolic response to exercise to take place, they also (re-)raise the question whether "training on empty" may not after all be advantageous if ...
  1. the training performance is not effected by the lack of muscle glycogen and
  2. the muscle anabolic response is augmented via appropriate post-workout nutrient-replenishment
Since this conjecture is yet solely based on the relative increases in phosphorylation, the scientists cite in their abstract, it is far from being a valid scientific hypothesis. We will probably have to wait for the publication of a respective paper (or ask someone who was lucky enough to attend the presentation for the absolute values; cf. "Note...", above), to get a preliminary answer on any beneficial effect exercising in a glycogen depleted state could have. In that, I would like to add that its artificial incarnation, i.e. the induction of local glycogen depletion, as it was practiced in the study at hand, has no significance with regard to the whole body (including liver) glycogen depletion some trainees experience as a result of (over-)training and no-carb (over-)dieting. In case of the latter, it does not take a rocket scientist to be able to tell that this won't have any beneficial effect on the gains people are making in the gym.