3 Tips for Muscle Hypertrophy (Bigger Muscles): Research Review for Novemember 2009
November 6th, 2009
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by Mike T Nelson · Filed Under: athletic performance
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?
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NSAIDs may not be as bad for muscle hypertrophy as we once thought
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Timing may become a bigger issue in the future, but for now get to the gym first
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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
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!




















Mike–like your site, came across it when I was researching z-health (which I recently stumbled upon (now I have the R phase, Neural warmup and quick start dvds). Keep up the good work.
I subscribe to the Crossfit Journal, which is an awesome online resource. The following information is from a discussion about NSAIDs and injury healing. The comments are from Kelly Starrett, DPT, a brilliant physical therapist, athlete, and owner of Crossfit San Fransisco. It is a little long, but cites many studies and medical journal articles.
“2) The technical evidence about NSAID’s affecting tissue healing IS what I’m basing my discussion on. My friends know that I was all about the Ibu until I began working as a physical therapist in a world class Sports Medicine clinic where:
Minimizing NSAID’s use was the clinical standard for care (ligament ruptures, tendon ruptures, tendonopathies, surgical reconstruction, etc). This is directly in response to the literature (best practice) and the clinical experience of nearly 20 years of treating high level sports injuries. (About a billion famous high end athletes were treated there as well as normal folks). This clinical experience coincides with the literature: For example, the following is a study that reports faster return to duty with the use of NSAID’s in a good study.
But reports (even in the abstract) that quote: “Interestingly, subjects treated with piroxi cam showed some evidence of local abnormalities such as instability and reduced range of movement.”
A Randomized Controlled Trial of Piroxicam in the Management of Acute Ankle Sprain in Australian Regular Army Recruits
The Kapooka Ankle Sprain Study
Mark A. Slatyer, BMedSci, BMed, PhD, FAFPHM
3) Tylenol is horrible stuff. So dangerous in fact that the FDA changed the dosages because it is the number one way to kill your liver. No question here.
Again, the best practice in the clinical setting in which I was part was to treat swelling with ice, and tylenol (under an Md’s guidance) for pain. Never, never drink and take tylenol.
4)You bring up an excellent point about the “other issues” of taking anything for pain. Ibuprofen has been shown across the board to be murder on the stomach and be the number one cause of bleeding stomach ulcers. I have personally witnessed several athletes in the clinic taking hidden ibu (not cleared with their doc and not cases of poly-pharmy) end up in stomach surgery after becoming anemic secondary to GI bleeds.
5) There is good evidence that Ibu/nsaids mess with renal function and may lead to hyponatremia.
NSAID use increases the risk of developing hyponatremia during an ironman triathlon
WHARAM Paul
(1) ; SPEEDY Dale B. (1) ; NOAKES Timothy D. (2) ; THOMPSON John M. D. (3) ; REID Stephen A. (4) ; HOLTZHAUSEN Lucy-May
Medicine and science in sports and exercise 2006, vol. 38, no4, pp. 618-622
Additionally, the evidence is strong that NSAID’s like ibu put significant downstream load on the kidneys. Since many of us are running around with high CPK levels secondary to our hard training, taxing kidney function probably isn’t necessary.
6.) My doctoral training includes courses in pharmacology and histopathology. The mechanisms of prostaglandin suppression and the subsequent halting of the inflammation cycle are well known. What is not well known, because the long term longitudinal studies in humans are hard to come by, is what the long term effects of nsaid use are. Clinically, first hand, I’ve seen stress fractures, heal cord ruptures, rotator cuff tears that existed in the presence of athlete typical self-medicating nsaid dosages. (I know it’s only “black box” clinical experience and not and RCT.
7) Are other alternatives to nsaids suggested in the this CLIP of a 7 hour lecture? No. In the other parts of the lecture, yes. Of course.
Feeling No Pain
Bruce Reider, MD
Am J Sports Med February 2009 vol. 37 no. 2 243-245
–Nsaid use is extremely widespread
–Nsaid use should be used cautiously because of potential downstream effects.
9) Where the “hell” this advice comes from: Kelly Starrett DPT, formerly a full time sports medicine practicing therapist a world class sports medicine clinic called The Stone Clinic. Now in private practice. Everyone in that lecture knew this. I’m sorry it’s not clear. I can certainly see that it would be even more disconcerting if this was just coming from Kelly Starrett Crossfit Coach.
10) Good point about hand ripping and liver failure.
11) This video tells you several other factors that affect tissues healing times.
Again, it is the opinion of the practice group (MD’s) of which I’m part that due to the scientific literature and long/vast clinical experience, NSAIDS affect tissue healing.
Effect of ibuprofen and diclofenac sodium on experimental would healing.
Dvivedi S, Tiwari SM, Sharma A.
Indian J Exp Biol. 1997 Nov;35(11):1243-5.Links
The Role of Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Acute Soft Tissue Injuries
Jay Hertel, MEd, ATC
J Athl Train. 1997 Oct–Dec; 32(4): 350–358.
Indomethacin and Celecoxib Impair Rotator Cuff Tendon-to-Bone Healing
David B. Cohen, MD*, Sumito Kawamura, MD§, John R. Ehteshami, MD|| and Scott A. Rodeo, MD
The American Journal of Sports Medicine 34:362-369 (2006)
Effect of ibuprofen on the healing and remodeling of bone and articular cartilage in the rabbit temporomandibular joint.
Obeid G, Zhang X, Wang X.
J Oral Maxillofac Surg. 1992 Aug;50(8):843-9
Anti-inflammatory treatment of muscular injuries in sport. An update of recent studies.
Almekinders LC.
Sports Med. 1999 Dec;28(6):383-8.
Inhibition of tendon cell proliferation and matrix glycosaminoglycan synthesis by non-steroidal anti-inflammatory drugs in vitro.
Riley GP, Cox M, Harrall RL, Clements S, Hazleman BL.
J Hand Surg Br. 2001 Jun;26(3):224-8.
The Mechanisms of the Inhibitory Effects of Nonsteroidal Anti-Inflammatory Drugs…
Harder and An J Clin Pharmacol .2003; 43: 807-815
And:
Comprehensive Sports Injury Management
By Jim Taylor, Kevin R. Stone, Michael Mullin, Todd Ellenbecker, Ann Walgenbach
Pg.s 77-85
Isbn 0-89079-891-5″
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Hi there Tom! Glad you like the site and anything that I can do to make it better, please let me know.
Glad you are loving the R Phase! Nice! Are you going to the R Phase Cert? It is a blast and let me know if you have any questions on it.
Thanks for the great NSAID info! I actually agree with about 95% of it. I am not personally a big fan of them for many of the reasons listed above. Although I think that acutely they may serve a use to keep people from associated pain from certain movements (again, be VERY careful during this time if you still lift or play) while not affecting hypertrophy perhaps.
I personally like to use other options such as turmeric, cat’s claw, fish oil and proteolytic enzymes at high doses between meals.
Rock on and thanks again
Mike T Nelson
Mike, I do want to pursue Z-Health cert as soon as I can afford to do so. I used to consume a lot of turmeric, can’t say I noticed a difference. I do take 3200 mg EPA/2000 mg DHA of fish oil per day (Carlson liquid–good stuff, way more pleasant for me than gel caps). Funny thing, just read your latest post on foam rolling, and your Jan 08 post/comments. I am a big foam “roller”, but understand the limitation of moving into pain.
thanks/ts
Thanks for the info Tom! Any R Phase cert questions, hit me up or call the Z office and tell them I sent ya. It is great stuff.
Turmeric seems to be hit or miss. Helps some and indifferent with others.
My whole point the foam roller is that it is not the be all and end all and don’t do it in pain. Glad you understand the limitations!
rock on and thanks for the comments!
Mike T Nelson
That’s why it is better for beginners to learn from those who have walked the path already, not those who have only theoretically walked the path whose knowledge consists of what “should” be.