3 Tips for Muscle Hypertrophy (Bigger Muscles): Research Review for November 2009

Jack Leon[between 1910 and 1915]

Just a few very cool studies this month and see my comments on how you can apply these for increased athletic performance on the field and in the gym!  Let’s roll

Local NSAID infusion inhibits satellite cell proliferation in human skeletal muscle after eccentric exercise

Despite the widespread consumption of nonsteroidal anti-inflammatory drugs (NSAIDs), the influence of these drugs on muscle satellite cells is not fully understood. The aim of the present study was to investigate the effect of a local NSAID infusion on satellite cells after unaccustomed eccentric exercise in vivo in human skeletal muscle. Eight young healthy males performed 200 maximal eccentric contractions with each leg. An NSAID was infused via a microdialysis catheter into the vastus lateralis muscle of one leg (NSAID leg) before, during, and for 4.5 h after exercise, with the other leg working as a control (unblocked leg). Muscle biopsies were collected before and 8 days after exercise. Changes in satellite cells and inflammatory cell numbers were investigated by immunohistochemistry. Satellite cells were identified using antibodies against neural cell adhesion molecule and Pax7. The number of Pax7+ cells per myofiber was increased by 96% on day 8 after exercise in the unblocked leg (0.14 ± 0.04, mean ± SE) compared with the prevalue (0.07 ± 0.02, P < 0.05), whereas the number of Pax7+ cells was unchanged in the leg muscles exposed to the NSAID (0.07 ± 0.01). The number of inflammatory cells (CD68+ or CD16+ cells) was not significantly increased in either of the legs 8 days after exercise and was unaffected by the NSAID. The main finding in the present study was that the NSAID infusion for 7.5 h during the exercise day suppressed the exercise-induced increase in the number of satellite cells 8 days after exercise. These results suggest that NSAIDs negatively affect satellite cell activity after unaccustomed eccentric exercise.

My thoughts

Very interesting study, but I am not convinced that NSAIDs are actually bad for muscle growth.  The data about 2-3 years ago, said that they were bad for muscle hypertrophy; but newer data is not pointing that way.     The eagle observer would notice that this study showed a negative effect on satellite cells, which would say that it is bad for muscle growth.  The downside is that muscle growth was not measured in this study.  Muscle can get bigger by various mechanisms, and while satellite cells is one way, it is not the only way.  Satellite cells are the little guys that hang out at the end of the muscle fibers and work to repair them from damage.   So for now I would not automatically reach for NSAIDs if you have muscle soreness, but if you have to, it is probably not affecting growth too much.  If people are interested, drop a note in the comments and I will do a blog post just on this.

Working around the clock: circadian rhythms and skeletal muscle

The study of the circadian molecular clock in skeletal muscle is in the very early stages. Initial research has demonstrated the presence of the molecular clock in skeletal muscle and that skeletal muscle of a clock-compromised mouse, Clock mutant, exhibits significant disruption in normal expression of many genes required for adult muscle structure and metabolism. In light of the growing association between the molecular clock, metabolism, and metabolic disease, it will also be important to understand the contribution of circadian factors to normal metabolism, metabolic responses to muscle training, and contribution of the molecular clock in muscle-to-muscle disease (e.g., insulin resistance). Consistent with the potential for the skeletal muscle molecular clock modulating skeletal muscle physiology, there are findings in the literature that there is significant time-of-day effects for strength and metabolism. Additionally, there is some recent evidence that temporal specificity is important for optimizing training for muscular performance. While these studies do not prove that the molecular clock in skeletal muscle is important, they are suggestive of a circadian contribution to skeletal muscle function. The application of well-established models of skeletal muscle research in function and metabolism with available genetic models of molecular clock disruption will allow for more mechanistic understanding of potential relationships.

My thoughts

Very cool study and the first I have seen in this area.  The age old question of what is the perfect time to lift has been around for a long time.   From what I have seen, there does not seem to be a perfect time.  The perfect time is when you can get to the gym and seems to be highly individual.  First priority is to get there, lift the weights and then later worry about finding the best time.  If I could set up my perfect schedule it would be to lift at 3pm in the afternoon.   Keep in mind that if you have a contest, say a powerlifting meet that start at 9am, you may want to do some lifts at that time in practice just to see how your body reacts.

For now, get to the gym first.

Translational signaling responses preceding resistance training-mediated myofiber hypertrophy in young and old humans

While skeletal muscle protein accretion during resistance training (RT)-mediated myofiber hypertrophy is thought to result from upregulated translation initiation signaling, this concept is based on responses to a single bout of unaccustomed resistance exercise (RE) with no measure of hypertrophy across RT. Further, aging appears to affect acute responses to RE, but whether age differences in responsiveness persist during RT leading to impaired RT adaptation is unclear. We therefore tested whether muscle protein fractional synthesis rate (FSR) and Akt/mammalian target of rapamycin (mTOR) signaling in response to unaccustomed RE differed in old vs. young adults, and whether age differences in acute responsiveness were associated with differences in muscle hypertrophy after 16 wk of RT. Fifteen old and 21 young adult subjects completed the 16-wk study. The phosphorylation states of Akt, S6K1, ribosomal protein S6 (RPS6), eukaryotic initiation factor 4E (eIF4E) binding protein (4EBP1), eIF4E, and eIF4G were all elevated (23–199%) 24 h after a bout of unaccustomed RE. A concomitant 62% increase in FSR was found in a subset (6 old, 8 young). Age x time interaction was found only for RPS6 phosphorylation (+335% in old subjects only), while there was an interaction trend (P = 0.084) for FSR (+96% in young subjects only). After 16 wk of RT, gains in muscle mass, type II myofiber size, and voluntary strength were similar in young and old subjects. In conclusion, at the level of translational signaling, we found no evidence of impaired responsiveness among older adults, and for the first time, we show that changes in translational signaling after unaccustomed RE were associated with substantial muscle protein accretion (hypertrophy) during continued RT.

My thoughts

There is more and more research coming out on hypertrophy in older folks.  My good buddy Carl Lanore likes to say “muscle is metabolic currency, so go to the gym and make a deposit today,’ and I totally agree.   It appears that muscle size is harder to come by as we age; but how much harder is still not clear.  Early studies showed that it was difficult, but recent data like the one above show that maybe there is not much difference.  Again, this is a 16 week study (which is pretty good for most studies) and note that they used NOVEL exercises.  I think this is a key point.  You need to give the body a REASON to adapt.  It also showed that strength increased, so the old people in the study were not all show and no go!

What 3 Tips Did We Learn Today?

1. NSAIDs may not be as bad for muscle hypertrophy as we once thought

2. Timing may become a bigger issue in the future, but for now get to the gym first

3. If hypertrophy is your goal, you need to “surprise” the muscles.  Now don’t go all crazy with the Weirder “confusion” principle, as plain old overload (doing more work over time) is a very powerful stimulus as the work load is novel.  I am a big fan of adding volume since it allows you to manage fatigue (Charles Staley’s ears are burning) and keep doing perfect reps.

Any questions/thoughts, let me have it in the comments

Rock on

Mike T Nelson

PS

You will have to come back here on Monday as you will have to see what I am posting.  The feedback on it so far has been crazy (both good and bad crazy),  Stay tuned!

So I am a few months behind on research updates, but have no fear as more good stuff is coming. For June some great studies on pre and post protein and carbohydrate beverages, NSAIDs (like Advil) and their effects on muscle growth, and some molecular mechanisms in action.

Be sure to check out my previous post HERE on protein synthesis (adding muscle) and what you can do to maximize it based on bleeding edge research.

If all this crazy research makes your head spin back like a Pez dispenser and just want to get the plan and get started today, check out Jimmy Smith’s Physique Formula.

Let’s get to it

Differential effects of resistance and endurance exercise in the fed state on signaling molecule phosphorylation and protein synthesis in human muscle.

Wilkinson SB, Phillips SM, Atherton PJ, Patel R, Yarasheski KE, Tarnopolsky MA, Rennie MJ. McMaster University.

Resistance (RE) and endurance (EE) exercise stimulate mixed skeletal muscle protein synthesis. The phenotypes induced by RE (myofibrillar protein accretion) and EE (mitochondrial expansion) training must result from differential stimulation of myofibrillar and mitochondrial protein synthesis. We measured the synthetic rates of myofibrillar and mitochondrial proteins and the activation of signaling proteins (Akt-mTOR-p70S6K) at rest and after an acute bout of RE or EE in the untrained state and after 10 wk of RE or EE training in young healthy men. While untrained, RE stimulated both myofibrillar and mitochondrial protein synthesis, 67% and 69% (P

Conclusion: Chronic resistance exercise (wt training) or endurance exercise training modifies the protein synthetic response of functional protein fractions, with a shift toward exercise phenotype-specific responses, without an obvious explanatory change in the phosphorylation of regulatory signaling pathway proteins.

My notes: sounds like the SAID principle in action! The body is adapting specifically to the stimulus (exercise)

Essential amino acid and carbohydrate ingestion prior to resistance exercise does not enhance post-exercise muscle protein synthesis.

Fujita S, Dreyer HC, Drummond MJ, Glynn EL, Volpi E, Rasmussen BB.University of Tokyo. Ingestion of an essential amino acid-carbohydrate (EAA+CHO) solution following resistance exercise enhances muscle protein synthesis during post-exercise recovery. It is unclear whether EAA+CHO ingestion prior to resistance exercise can improve direct measures of post-exercise muscle protein synthesis (FSR; fractional synthetic rate). We hypothesized that EAA+CHO ingestion prior to a bout of resistance exercise would prevent the exercise-induced decrease in muscle FSR and would result in an enhanced rate of muscle FSR during post-exercise recovery. We studied 22 young healthy subjects before, during, and for 2 hr following a bout of high-intensity leg resistance exercise. The Fasting control group (N=11) did not ingest nutrients and the EAA+CHO group (N=11) ingested a solution of EAA+CHO 1 hr prior to beginning the exercise bout. Stable isotopic methods were used in combination with muscle biopsies to determine FSR. Immunoblotting procedures were utilized to assess cell signaling proteins associated with the regulation of FSR. We found that muscle FSR increased in the EAA+CHO group immediately following EAA+CHO ingestion (P0.05). Eukaryotic elongation factor 2 phosphorylation was reduced in both groups at 2 hr post-exercise (EAA+CHO: 39+/-7%; Fasting: 47+/-9%; P

Conclusion: We conclude that essential amino acids and carbs (EAA+CHO) ingestion prior to resistance exercise does not enhance post-exercise fractional synthesis rate (FSR–Fractional Synthetic Rate–aka rate of adding protein to muscles) as compared to exercise without nutrients.

My note–while this interesting, I would not dump your protein carb drink before lifting just yet. Based on info from Dave Barr (source, AI and personal conversation) moving it to 15 minutes before training may be more ideal. Stay tuned!

Gene expression profiling in human skeletal muscle during recovery from eccentric exercise.

Mahoney DJ, Safdar A, Parise G, Melov S, Fu M, MacNeil L, Kaczor J, Payne ET, Tarnopolsky MA. Department of Medical Sciences, McMaster University Medical Center, 1200 Main Street W., Hamilton, Ontario, Canada. We used cDNA microarrays to screen for differentially expressed genes during recovery from exercise-induced muscle damage in humans. Male subjects (n = 4) performed 300 maximal eccentric contractions, and skeletal muscle biopsy samples were analyzed at 3 h and 48 h after exercise. In total, 113 genes increased 3 h postexercise, and 34 decreased. At 48 h postexercise, 59 genes increased and 29 decreased. On the basis of these data, we chose 19 gene changes and conducted secondary analyses using real-time RT-PCR from muscle biopsy samples taken from 11 additional subjects who performed an identical bout of exercise.
Real-time RT-PCR analyses confirmed that exercise-induced muscle damage led to a rapid (3 h) increase in sterol response element binding protein 2 (SREBP-2), followed by a delayed (48 h) increase in the SREBP-2 gene targets Acyl CoA:cholesterol acyltransferase (ACAT)-2 and insulin-induced gene 1 (insig-1). The expression of the IL-1 receptor, a known regulator of SREBP-2, was also elevated after exercise. Taken together, these expression changes suggest a transcriptional program for increasing cholesterol and lipid synthesis and/or modification. Additionally, damaging exercise induced the expression of protein kinase H11, capping protein Z alpha (capZalpha), and modulatory calcineurin-interacting protein 1 (MCIP1), as well as cardiac ankryin repeat protein 1 (CARP1), DNAJB2, c-myc, and junD, each of which are likely involved in skeletal muscle growth, remodeling, and stress management.

Conclusion: In summary, using DNA microarrays and RT-PCR, we have identified novel genes that respond to skeletal muscle damage, which, given the known biological functions, are likely involved in recovery from and/or adaptation to damaging exercise.

My notes: I wonder why all this muscle physiology stuff is so elusive, to quote the authors “In total, 113 genes increased 3 h postexercise, and 34 decreased.” That is a lot of stuff going on! Still wondering if you need to damage the muscle for it to increase in size?

Post exercise carbohydrate-protein supplementation: phosphorylation of muscle proteins i
nvolved in glycogen synthesis and protein translation.

Ivy JL, Ding Z, Hwang H, Cialdella-Kam LC, Morrison PJ.Exercise Physiology and Metabolism Laboratory, Department of Kinesiology and Health Education, The University of Texas, Austin, Texas 78712-0360, USA. johnivy@mail.utexas.edu The enzymes Akt, mTOR, p70(S6K), rpS6, GSK3, and glycogen synthase interact in the control of protein and/or glycogen synthesis in skeletal muscle, and each has been found to respond to exercise and nutrient supplementation. In the present study, we tested the hypothesis that nutrient supplementation post exercise, in the form of a carbohydrate-protein (CHO-PRO) supplement, would alter the phosphorylation state of these enzymes in a manner that should increase muscle protein and glycogen synthesis above that produced by exercise alone. After a 45 min cycling session followed by sprints and again 15 min later, the subjects (n = ingested 400 ml of a CHO-PRO drink (7.8% dextrose and 1.8% protein-electrolyte) or a placebo drink, as assigned using a randomized, counter-balanced design with repeated measures. Biopsies of the vastus lateralis were taken before exercise and at 45 min of recovery.
At 45 min after supplementation, CHO-PRO treatment yielded greater phosphorylation of Akt (65%), mTOR (86%), rpS6 (85-fold), and GSK3alpha/beta (57%) than pre-exercise levels (p

Conclusion: These results suggest that a post exercise carb and protein (CHO-PRO) supplement alters the phosporylation levels of the enzymes tested in a manner that should accelerate muscle glycogen synthesis and protein initiation during recovery from cycling exercise.

My notes: cool info, but I would like to see this carried out in the future to any performance changes. This would say that it should help. I am sure that is in the pipeline and there is some data already out in that area

The effects of ibuprofen on muscle hypertrophy, strength, and soreness during resistance training.

Krentz JR, Quest B, Farthing JP, Quest DW, Chilibeck PD. High doses of ibuprofen have been shown to inhibit muscle protein synthesis after a bout of resistance exercise. We determined the effect of a moderate dose of ibuprofen (400 mg.d-1) consumed on a daily basis after resistance training on muscle hypertrophy and strength. Twelve males and 6 females (~24 years of age) trained their right and left biceps on alternate days (6 sets of 4-10 repetitions), 5 d.week-1, for 6 weeks.
In a counter-balanced, double-blind design, they were randomized to receive 400 mg.d-1 ibuprofen immediately after training their left or right arm, and a placebo after training the opposite arm the following day. Before- and after-training muscle thickness of both biceps was measured using ultrasound and 1 repetition maximum (1 RM) arm curl strength was determined on both arms.
Subjects rated their muscle soreness daily. There were time main effects for muscle thickness and strength (p

Conclusion: We conclude that a moderate dose of ibuprofen ingested after repeated resistance training sessions does not impair muscle hypertrophy or strength and does not affect ratings of muscle soreness.

My Notes: If you would have asked me even a few months ago, I would have said that the use of NSAIDs (like Advil) is not a good idea as it may limit muscle growth (hypertrophy). After talking to some at ACSM, looking at some newer litature, I am thinking it will probably be ok. It may even be beneficial after an acute injury to keep your movement quality better and limit pain, thus reducing the chance on longer term chronic pain ala the neuromatrix of pain. See the following posts on that below

Pain Perception and the Neuromatrix–Guest Blog by Katelin Bigelow

Pre-emptive Analgescis–what is he talking about now?

Cellular and molecular events controlling skeletal muscle mass in response to altered use.

Favier FB, Benoit H, Freyssenet D.Unité Physiologie et Physiopathologie de l’Exercice et Handicap, IFR143, Université Jean Monnet, 15 rue Ambroise Paré, 42023, Saint Etienne, cedex 2, France.
Gain or loss of skeletal muscle mass occurs in situations of altered use such as strength training, aging, denervation, or immobilization. This review examines our current understanding of the cellular and molecular events involved in the control of muscle mass under conditions of muscle use and disuse, with particular attention to the effects of resistance exercise/training. The DNA content, which is a critical determinant of protein synthesis by providing the amount of DNA necessary to sustain gene transcription, can be either increased (activation of satellite cells) or decreased (apoptosis) depending on muscle activity and ongoing physiological processes. In addition, several transcription factors are sensitive to functional demand and may control muscle-specific protein expression to promote or repress myofiber enlargement. The control of skeletal muscle mass is also markedly mediated by the regulation of transduction pathways that promote the synthesis and/or the degradation of proteins. Insulin-like growth factor-I plays a key role in this balance by activating the Akt/tuberous sclerosis complex 2/mammalian target of rapamycin pathway.

Conclusion: Stimulation of this pathway leads to the concomitant activation of initiation and elongation factors resulting in the elevation of protein translation and the downregulation of ubiquitin proteasome components through Forkhead-box O transcription factors.

My Notes: Good review (with lots of big words), but the take away is still the same–USE IT OR LOSE IT!

Rock on
Mike N