Build Size & Strength With Isometric Co-Contractions: 4% Increase in Arm Circumference and ~20% More Strength With Less Than 10 Minutes of "Flexing" Per Week

Big guns without weights? True - the question yet remains: "How big?"

I am psyched and the reason is the advanced access publication of the results of the latest study from the Department of Sports and Life Science at the National Institute of Fitness and Sports in Kanoya, Japan (Maeo. 2013b).

Why? Well, it claims to solve two of the most urgent issues that keep our sedentary fellow men (and women ;-) from working out: The lack of equipment and the lack of time, exactly those two factors the average American and European slacker pleads as an excuse for not making the necessary, since potentially life-saving physical investments into "metabolic currency" (this is a term my good friend Carl Lanore uses to refer functional muscle mass).

"Big guns without weights? You're kiddin', bro!"

Actually the idea of using simultaneous voluntary contractions of antagonistic muscle pairs (aka co-contraction) to improve muscle strength in the absence of external apparatuses is not new. The voluntary co-con traction of elbow flexors and extensors you can see in the photo in the red "This is how it's done" box, for example, may look ludacris (imagine doing that at the gym), its efficacy is however backed by previous research and its working principle is as simple as ingenious: Biceps and triceps, i.e. elbow flexor and extensor, produce resistive forces that act against each other (Tyler. 1986), so that one muscle actually "trains" the other.

You can learn more about training biceps & triceps at the SuppVersity

Training the Individual Parts of the Triceps

Find the Best Triceps Exercises (EMG Data)

Explore the Best Biceps Exercises (EMG Data)

Train Bis + Tris on a Single Day & Grow!

Add 0.5 Inch To Your Arms in 5 Minutes

Disproportionate Triceps Growth? Is It Real?

In their initial investigation into the effects of muscular co-contraction, the results of which have been published in the International Journal of Sports Medicine in July 2013 (Maeo. 2013b), the researchers have been able to confirm that the muscular activity that occurs during the voluntary co-contractions is a sufficient training stimulus for improving the strength capability of both muscles (Maeo et al. 2013a).

"In fact, previous studies that adopted co-contraction training for elbow flexors and extensors (Driss et al. 2013; MacKenzie et al. 2010; Maeo et al. 2013) found significant increases in the strength capability, as well as agonist electromyographic (EMG) activity during isometric maximal voluntary contraction (MVV) (MacKenzie et al. 2010; Maeo et al. 2013), of the two muscle groups. the previous findings cited above support the idea that co-contraction can be an effective training modality, which does not require any external apparatus, for increasing muscle strength." (Maeo. 2013b)

So, while we are pretty certain that "standing there and contracting your bis and tris" can increase muscle strength (learn how to build strength), there is a scarcity of evidence that would allow us to make reliable statements about the effects of voluntary muscular cocontractions on muscle size (learn how to build muscle). It is thus only logical that the intention of Sumiaki Maeo's, Yasuhide Yoshitake's, Yohei Takai's, Tetsuo Fukunaga's and Hiroaki Kanehisa's follow up study was "to clarify neuromuscular adaptations following 12-week maximal voluntary co-contraction training" (Maeo. 2013b). In that, the researchers hypothesized that

• 

  If you feel like a shadow of yourself, betaine may help | learn more

  the training modality with maximal voluntary co-contraction would increase both size and strength capability of the exercised muscles, and
• training unsing co-contractions does not change involuntary coactivation level during MVC of the agonist alone

In other words: The researchers wanted to make sure that (a) this form of training builds strength and muscle and (b) that it does not have lasting potentially performance decreasing effects on the co-activation of the triceps / biceps, when you actually want to use only one of them (imagine you want to curl the weight up and your triceps works against you).

The study protocol

To satisfy their research interest, the researchers from the Department of Sports and Life Science at the Japanese National Institute of Fitness and Sports in Kanoya recruited 16 healthy young men.

Don't neglect the proven benefits of periodization: "Six Weeks On + Three Weeks Off" Macrocycle Yields Identical Gains Strength and Size Gains as Continuous Training | more

The guys, who were in their early twenties, lean, healthy and habitually active, but not involved in regular exercise programs with a duration and frequency of more than two 30 minute exercise sessions per week, were then randomly assigned to two groups: A training group (T) with 9 participants and an inactive control group (C) with 7 participants. It goes without saying that all participants had to abstain from additional physical activity over the course of the whole study period during.

In those 12 weeks the subjects in the the subjects in T group participated in a 12-week training program with maximal voluntary co-contraction of the elbow flexors and extensors of the right arm 3 times per week.

Usually this would be the paragraph of this SuppVersity article, where I would give you a concise summary of the exercise protocol. In view of the fact that I doubt that many of you are actually familiar with muscular co-contractions, I decided to use a somewhat abridged quote of  the scientists' lengthy, but comprehensive explanation of the procedure (see red box).

This is how it's done: In a standing position with the feet shoulder width apart, upper arm vertical to the ground, the elbow joint at 90° (full extension = 180°), forearm in a neutral (middle of supinated and pronated) position you will perform a 4-s muscle isometric co-contraction followed by 4-s muscle relaxation (total volume: 10 times per set, 5 sets per session; rest: 2 min between sets). Make sure to perform each voluntary co-contraction as rapidly as possible and sustain maximal effort for full 4s!

Basically what the subjects were doing could be summarize as 10x4s maximal isometric muscle contractions with 4s break between each contraction for one set and 5 of these sets with an interim of 2 minutes between each of them three times per week.

Now for those surprisingly impressive results

If you do the math and add up the actual time under tension for this 12-week experimental intervention, you will get 10 × 4s isometric contractions × 5 sets × 3 / week × 12 weeks = 7200s or 2h. That's not really much considering the fact that it lead to strength and size increases of +15% / +27% and 4% / 4% in the elbow flexors (biceps) and extensors (triceps) of the previously more or less untrained, but no necessarily sedentary subjects.

Figure 1: Pre vs. post measures of muscle thickness, MVC torque and coactivation level (Maeo. 2013b)

As you can read in the small box in Figure 1 the increases in size and strength did not occur rapidly after two or three weeks and were then followed by a plateau.In fact, the researchers recorded statistically significant strength and measurable, but statistically not yet significant size gains after 4 weeks.

Probably effective for increases in dynamic performance, as well

Now, brute strength and a huge muscle mass are by no means what all athletes are striving for. For many athletes improving their dynamic performance and strength, which would have required the measurement of changes in isokinetic torques for elbow flexors and extensors in both eccentric and concentric conditions, is at least as important. It is thus more than noteworthy that data from Maoe et al.'s previous 4-week study (Maeo. 2013a),

"[...]in which untrained individuals conducted 4-week co-contraction training, showed that the co-contraction training significantly increased isokinetic torques for elbow flexors and extensors in both eccentric and concentric conditions." (Maeo. 2013b)

As the researchers rightly point out, we do thus have reason to believe that "contraction training is also effective for improving dynamic performance, at least for untrained individuals" (Maeo. 2013b). With respect to trained athletes, the reaserchers do yet argue that they'd require higher exercise intensities to achieve additional improvement in muscle strength than non-athletes (Alway. 1992; Cormie. 2011). This, as well as the emphasis sports specific training puts on ballistic, plyometric, and weightlifting exercises involving sports-specific and/or multi-joint movements (Cormie. 2011), make it difficult to believe that similar training results could be achieved by performing maximal voluntary co-contraction.

Suggested read: "Advanced Trainees Benefit from Increased Training Volume!" | more

Great! But nothing a trained individual can benefit from? It's obvious that someone with a 50cm biceps is not going to add another 2cm in 12 weeks in the course of which he lies around on the sofy and performs 5 sets of voluntary maximal co-contructions thrice a week.

This does yet not mean that this relatively unknown training stimulus cannot make a valuable addition to his training regimen... and let's be honest, haven't we all had a pro-bodybuilder give us a bro-scientific lecture on how flexing, in and out of itself nothing, but a voluntary maximal contraction (albeit not necessarily with antagonistic co-contractions for every muscle part) is a vital part of any hypertrophy oriented strength training routine?

References:

• Alway, S. E., Grumbt, W. H., Stray-Gundersen, J. & Gonyea, W. J. (1992). Effects of resistance training on elbow flexors of highly competitive bodybuilders. Journal of Applied Physiology, 72(4), 1512-1521.
• Cormie, P., McGuigan, M. R., & Newton, R. U. (2011). Developing maximal neuromuscular power. Sports medicine, 41(1), 17-38.
• Maeo, S., Yoshitake, Y., Takai, Y., Fukunaga, T., & Kanehisa, H. (2013). Neuromuscular adaptations following 12-week maximal voluntary co-contraction training. European Journal of Applied Physiology, 1-11.
• Maeo, S., Yoshitake, Y., Takai, Y., Fukunaga, T., & Kanehisa, H. (2013). Effect of short-term maximal voluntary co-contraction training on neuromuscular function. International journal of sports medicine, (EFirst). 
• Tyler, A. E., & Hutton, R. S. (1986). Was Sherrington right about co-contractions?. Brain research, 370(1), 171-175.

Leucine, Citrulline or a Non-Essential Amino Acid Mix - Which Amino Acid(s) are Most Effective in Preventing Muscle Loss During an 18h (Intermittent) Fast?

Image 1: If Chris, "the Techician", Aceto's usually well-informed sources are right and the former Mr Olympia Jay Cutler is currently trying to lose muscle (I heard him say that on Heavy Muscle Radio), Cutler would be ill advised if he ingested ~20g of non-essential amino acids during and / or in-between extended fasts and hours of arduous low-intensity cardio sessions (img  MuscleTech)

Those of you who followed the "Amino Acids for Super Humans" series I did earlier this year on Carl Lanore's Super Human Radio may remember the arginine < > citrulline < > ornitine cycle and how I tried to explain that, from a physiological perspective, arginine's role in ammonia detox is probably as, if not more important than its role in the production of nitric oxide. What most of you will probably have overheard, or, in the respective shownotes, over-read, was my reference to a 2006 study from the University of Paris, which was - at least to my knowledge - the first study to show that citrulline (much like leucine) increases protein synthesis and thusly reduces the loss of muscle protein in old malnourished rats (Osowska. 2006). As it is often the case with isolated study results like that, these observations have not gotten much attention within the research community, so that it is not very surprising that the latest information on citrulline's putative role in whole body protein homeostasis come from the same laboratory at the Sorbonne, as the previously cited ones.

Citrulline vs. Leucine, and non-essential aminos as a control!?

What is particularly interesting about these results, the scientists from the Département Biologie Expérimentale, Métabolique et Clinique at the Pharmaceutical Faculty of the venerable Université Paris Descartes published in the (btw. highly recommendable) Journal Amino Acids, is that they allow for a direct comparison of the magnitude and the mechanism the ingestion of citrulline, leucine or a mix of other non-essential amino acids has on the fractional protein synthesis in skeletal muscle tissue (Tibialis anterior) in a fasted state (18h food deprivation).

Figure 1: Fractional protein synthesis (in %/h) in tibialis anterior muscle of fasted rats 50 minutes after administration of leucine, l-citrulline or isonitrogenous (to leucine) non-essential amino acids (data adapted from Plenier. 2011)

To my own surprise the winner of the battle of the "protein anabolic amino acids" is neither the usual (leucine), nor the unusual suspect (citrulline), but rather the non-essential amino acid combo which consisted of 1.35g/kg of alanine, glycine, proline, histidine, asparagine and serine.

Alanine, glycine, proline, histidine, asparagine, serine - Non-essential high potentials?

Let's briefly put this surprising result into (a human) perspective: If we assume that you are on an extended intermittent fast, traveling or had - for whatever other reason - no access to food for 18h, then the ingestion of 0.22g/kg of a non-essential amino acid mixture (if you weigh 80kg that would be 17.5g), would induce a 9.37% greater increase in muscle protein synthesis than the same amount of leucine and a 16.67% greater increase than 23g of l-citrulline.

Figure 1: Phosphorylation of Akt, s6K, 4EBP1 (left) and AMPK (right) 60min after administration of leucine, l-citrulline or isonitrogenous (to leucine) non-essential amino acids (data adapted from Plenier. 2011)

If we combine the previous calculations with the data from the Western blot analyses of the PI3K/Akt, mTORC1, ERK1/2/MAPK pathways and AMP kinase component, it becomes even more obvious that this study provides further evidence against the current over-emphasis of l-leucine which is so prevalaent especially among the bodybuilding-oriented physical culturists. As I have pointed out in previous posts, here at the SuppVersity, pushing the "protein-anabolic gas-pedal" through the floor (=ingesting huge amounts of leucine on its own) makes no sense if your car has long run out of fuel (=there are no amino acids to synthesize).

Against that background it is actually not very surprising that the protein synthesis in the fasted leucine group was reduced, although the phosphorylation of  p70S6K was identical and the one of 4EBP1 even greater (both indicate that the protein synthetic machinery was set into gear) than in the fed control. What is surprising, though, is the fact that the actual protein synthetic response in the leucine group fell 10% short of the one that was observed in the tibialis muscle of the rodents which receive an isonutrogenous amount of non-essential amino acids. After all, previous studies have suggested that the induction of measurable increases in protein synthesis was an exclusive property only branched chain (BCAA) or essential (EAA) amino acid mixtures would posses. Methodological differences in the design of respective studies aside, Servane Lé Plenier and his colleagues suggest the following two possible explanations for the surprising effects the alanine, glycine, proline, histidin, asparagine and serine combo exhibited on skeletal muscle protein synthesis in the fasted state:

[firstly,] in the fasted state, NEAA homeostasis is maintained by catabolism of essential amino acids (EAA) - alanine, for example, is produced in muscle from LEU and pyruvate - and limited EAA availability affects MPS since it is well known that a deficiency in one amino acids may be a limiting step for protein synthesis. Hence, in the fasted state, NEAA administration could spare EAA utilization and thereby preserve MPS.

[secondly,] one or more amino acids in the NEAA mixture could display specific anabolic properties. For example, alanine has been shown to stimulate liver protein synthesis in starved rats (Perez-Sala. 1987), but to the best of our knowledge this effect has not been shown in muscle. Similarly, proline and glycine may possess pharmacological properties that could indirectly modulate protein synthesis.

Personally, I don't believe that any of the non-essential amino acids (NE-AA) in the NE-AA formula actually had an individual effect on protein synthesis beyond its ability to spare essential amino acids and its availability as a substrate for inter-organ amino acid transfer (especially for alanine and asparagine, which are transaminated in the liver, this could be an important factor). So that the practical implications of this study should be clear: if you want to minimize muscle loss during a(n) (intermittent) fast, you better have some non-essential amino acids with your leucine!

One question answered, 999 new ones raised

Image 2: If you have read all Intermittent Thoughts articles which dealt with the AMPK/mTOR Metabolic Seesaw and the respective follow-ups, you will probably already have noticed that the ingestion of non-essential amino acids had the least impact on the fasting-induced increase in AMPK-phosphorylation of all three treatments. And I guess I don't have to tell you that this is good news for all intermittent fasters out there - spare the muscle, improve your health and burn the fat, what more can you as for?

Unfortunately, this study leaves us with way more questions than answers. I personally, for example would venture the guess that the ingestion of a complete EAA product would result in an even more profound amelioration of the fasting induced reduction in fractional protein synthesis. That being said, the latter could also compromise another advantage of the non-essential amino acids, I have not even mentioned, yet: their almost non-existent effect on intra-muscular AMPK-expression (cf. figure 2, right). If you read all Intermittent Thoughts articles which dealt with the AMPK/mTOR Metabolic Seesaw and the respective follow-ups, you will be familiar with notion that the fasting-induced phosphorylation of intra-muscular AMPK is responsible for the majority of the health, as well as the closely related fat-burning effects of (intermittent) fasting. Now, if the ingestion of a ~20g bolus of alanine, glycine, proline, histidine, asparagine and serine could increase your skeletal muscle protein synthesis back to almost normal levels (NE-AA -12.5% vs. leucine-only -20%), while keeping the AMPK-alpha levels maxed out (cf. figure 2, right), it would at least warrant an experiment before we totally discard the possibility that, under certain circumstances, such as the fasting window of an intermittent fast, the oftentimes disregarded "non-essential amino acids" could perhaps be more than just a band-aid when you have run out of essential ones.

Whether there will be a place for citrulline in particular is questionable, though. With the least effect on protein synthesis and the greatest impact on AMPK, it would de facto be a "band-aid" solution, for everyone who fasts, deliberately. In other contexts, however, l-citrulline supplementation could well have its merits. In cancer patients it could for example be used to ameliorate muscle loss without triggering the pro-carcinogenic (Garcia-Maceira. 2009), but I guess this would be the topic of another study and another blogpost, here at the SuppVersity ;-)

Will 2015 Be the Year You Pick up The Kettlebells? Find Out If Your Strength, Fitness & Physique Would Benefit

2015 may offer a chance to get spice up your routine with kettlebells.

"Moderate evidence indicates that kettlebell training may be safe and effective for increasing certain functional strength and power measures and may show positive results with postural control in young, healthy populations," says a recent review of the literature in Physical Therapy Reviews (Girard. 2014) and does thus sound positively optimistic, but by far not as euphoric as some kettlebell warriors on the Internet.

Those of you who know me are probably aware that I am not a fan of kettle bells, but I am true to the motto of being open to good scientific evidence, like the one from the previously cited review by Girard et al. (2014).

I won't lie to you: I believe there are better muscle builders than kettlebells

Tri- or Multi-Set Training for Body Recomp.?

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Full ROM ➯ Full Gains - Form Counts!

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Study Indicates Cut the Volume Make the Gains!

Speaking of which, the previously cited review found only five studies satisfied the eligibility criteria and were included in this review. The populations studied age range was 18–72 years old. Methodological scores based on the PEDro scale ranged from 3 to 7 out of 10. In those studies, ...

[k]ettlebell training demonstrated improvements for a number of strength measures: time 6 group for bench press ( P < 0.05) and back extension (P = 0.053), main effect for clean and jerk (P < 0.05) and certain power measures such as improved explosive strength comparable to a jump squat control (19.8% increase). Improved postural control was demonstrated in one study (P = 0.04)" (Girard. 2014).

What the kettlebells did not do in any of the five studies by Otto et al. (2012), Manoccia et al. (2013), Lake et al. (2012) and Jay et al. (2011 & 2013) was to have an effect on aerobic endurance as measured by VO2 Max.

Original photos from the study by McGill et al. (2014).

Isn't Kettlebell training bad for your back? No, it isn't. According to data from a 2012 study by McGill, kettlebell training rather than being bad for the back provides unique muscular pulses to the abdominals which, "[t]ogether with the muscle bracing associated with carries create kettlebell-specific training opportunities" makes McGill et al. conclude that the "unique loading patterns discovered during the kettlebell swing [...] which is opposite in polarity to a traditional lift" may in fact be the reason why "many individuals credit kettlebell swings with restoring and enhancing back health and function, although a few find that they irritate tissues" (McGill. 2014).

According to McGill et al. (2014) the "message for coaches is" that the kettlebell offers "several unique training opportunities", for example (a) the opportunity to train rapid muscle contraction-relaxation cycles emphasizing posterior chain power development about the hip. However, the large shear to compression load ratio on the lumbar spine created during swing exercises suggests that this training approach may be contraindicated for some individuals with spine shear load intolerance and (b) enhanced activation of the core musculature during the bottoms-up carry.

The non-significance of the oxygen uptake and thus the non-existence of conditioning effects may come as a surprise for those of you have already done kettlebell swings. Rightly so, as I would argue, because this result of the review is based mainly on the results of Jay et al. (2011) who invited 57 employees of a large pharmaceutical company for a physical examination. Of those only 43 showed up (motivation to work their assess off ↓) of whom 40 men and women in their mid-forties then trained for 20 minutes included a 5 –10 minute warm up and a 10–15 minute interval training consisting of 10 intervals of 30 seconds with rest period of 30–60 seconds which began with ZERO workload and was progressively intensified by the participants choice!

Kettlebell, weights, or ergometer, you have to work your ass off to make progress!

That's much in contrast to Fortner et al. (2014) who had their 14 young (18-25y), non-obese volunteers train three times a week for 8 weeks with 4.5kg and 8kg kettlebells for the female and male subjects, respectively in a "tabata style", i.e. at a twenty-second work to ten-second rest ratio and compared the VO2 response to a traditional protocol, consisting of four sets of work separated by ninety seconds of rest.

Figure 1: Subjective Borg RPE response to Tabata versus traditional kettlebell swing protocols in healthy, young adults. TAB- Tabata, TRADtraditional (left). % of peak VO2 value achieved during Tabata and traditional kettlebell swing protocols in healthy, young adults (right | Fortner. 2014).

As you can see in Figure 1 the response to the two different workouts was very different - despite the fact that the total number of swings from each individual's "tabata condition" (TBA) was equally divided into four sets for their "tradititional condition" (TRAD). From non-kettlebell studies, we know that training at an intensity like this, even if it's done for only a few minutes, will just as Fortner et al. say "safely and effectively provide multi-faceted exercise adaptations with a relatively short time investment" (Fortner. 2014) - an assumption that's backed by a 2011 study by Falatic et al. that used a 15s/15s protocol and elicited significant increases in VO2max in seventeen female NCAA Division I collegiate soccer players.

Figure 2: Energy expenditure during two-hand kettlebell exercise and graded treadmill walking (Thomas. 2014).

Furthermore, James et al.  (2014) were recently able to show that a KB routine consisting of 2-hand swings and sumo deadlifts with 3-minute rest periods produces similar metabolic responses to those of a moderate-intensity treadmill walking protocol designed for the improvement of aerobic fitness in 5 women, 5 men between 21 and 31 years of age - and, as you can see in Figure 2, it also burned a few extra calories.

A comparison with treadmill walking is yet not enough to confirm that kettlebell training is also superior to "regular" HIIT training. Personally, I suspect it isn't but it's at least a good way to diversify your training routines and create a new exercise stimulus that may even help you break through a plateau.

You're not interested in fitness? What about improve- ments in glucose tolerance, then? Samantha Leigh Greenwald found in her master thesis that kettlebell training can improve glucose clea- rance in young sedentary men" and concludes that the results of her study "suggest that kettlebell training may provide an inexpen- sive home-based approach for prevention or management of type 2 diabetes" (Greenwald. 2014).

Speaking of diversification: Another recent study by Budnar Jr, et al. who investigated the testosterone, GH and cortisol response to kettlebell training, indicates that "the kettlebell swing exercise might [in fact] provide a good supplement to resistance training programs" (Budnar Jr. 2014).

So, in case you are just working on your 2015 workout routine, you may want to give kettlebells a chance. In that you may, for example, replace one of your regular HIIT training sessions with a brief, but intense tabata-style kettle bell workout as it was described by James et al. (2014): 2-hand swings and sumo deadlifts with 3-minute | Comment on Facebook!

References:

• Falatic, Jonathan Asher. "The effects of kettlebell training on aerobic capacity." San José state University (2011).
• Fortner, Howard A., et al. "Cardiovascular and metabolic demands of the kettlebell swing using a Tabata interval versus a traditional resistance protocol." International Journal of Exercise Science 7.3 (2014): 2. 
• Greenwald, Samantha Leigh. The impact of an acute bout of kettlebell exercise on glucose tolerance in sedentary males. Diss. State University of New York at Buffalo, 2014.
• Jay, Kenneth, et al. "Kettlebell training for musculoskeletal and cardiovascular health: a randomized controlled trial." Scandinavian journal of work, environment & health (2011): 196-203.
• Jay, Kenneth, et al. "Effects of kettlebell training on postural coordination and jump performance: a randomized controlled trial." The Journal of Strength & Conditioning Research 27.5 (2013): 1202-1209.
• Lake, Jason P., and Mike A. Lauder. "Mechanical demands of kettlebell swing exercise." The Journal of Strength & Conditioning Research 26.12 (2012): 3209-3216.
• Manocchia, Pasquale, et al. "Transference of kettlebell training to strength, power, and endurance." The Journal of Strength & Conditioning Research 27.2 (2013): 477-484.
• McGill, Stuart M., and Leigh W. Marshall. "Kettlebell swing, snatch, and bottoms-up carry: back and hip muscle activation, motion, and low back loads." The Journal of Strength & Conditioning Research 26.1 (2012): 16-27. 
• Otto III, William H., et al. "Effects of weightlifting vs. kettlebell training on vertical jump, strength, and body composition." The Journal of Strength & Conditioning Research 26.5 (2012): 1199-1202.
• Thomas, James F., et al. "Comparison of Two-Hand Kettlebell Exercise and Graded Treadmill Walking: Effectiveness as a Stimulus for Cardiorespiratory Fitness." The Journal of Strength & Conditioning Research 28.4 (2014): 998-1006.

Glycerol, An Overlooked Ergogenic Supplement? 10-12g of Glycerol May Increase Lean Mass Without Training. Plus: Effects on Adrenals & AST + Lactate Response to Exercise

Interestingly, the study at hand suggests that glycerol may make you more musclar, even if you don't life. Crazy, but true (photo by awesomebody).

As a SuppVersity reader the potential ergogenic effect of the backbone of triglycerides are no news to you. The number of studies investigating the effects of glycerol on exercise performance and/or the adaptive response to exercise is yet low. Against that background, even a rodent study like the one by Eric Francelino Andrade from the Federal University of Lavras is worth its own SuppVersity article, I guess.

In said study, the Brazilian researchers evaluated the training adaptation and physical performance parameters in rats orally supplemented with glycerol,glucose, or saline, and submitted to moderate aerobic exercise.

Glycerol can be used in conjunction with creatine to hyperhydrate (Easton. 2007).

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Thirty male rats were trained for 6 weeks and administered the supplements during the last 4 weeks of the experiment. Animals were distributed in a completely randomized factorial 2 × 3 design (with or without exercise and 3 substrates) and received 864 mg/kg body of either glucose or glycerol in solution.

For human beings this equals human equivalents of 140mg/kg or ~10-12g of both, glucose and glycerol, for an adult. If this amount of glycerol had the same effects on humans at it did on the rodents in the study at hand, this would mean that it would lead to non-significant increases in lean body mass, even if the men and women who take it, were not working out.

Figure 1: Overview of the study design (top) and changes in protein content (~lean mass) and fat content of the carcass of trained and untrained rodents in the glycerol, glucose and saline groups at the end of the study period (Andrade. 2014)

The data from the rodent study at hand does yet also suggest that glycerol may at the same time non-significantly inhibit the lean mass gains that occur in response to aerobic training.

Glycerol as an adrenal supplement?

In contrast to the previously cited changes in lean body mass, which are not the result of a simple increase in body water (that's the beauty of actually cutting your "hairy subjects" open - you don't have to use BIA or DEXA scans to measure their lean mass), the effects on the weight of the adrenals of the animals was statistically significant in both, the trained and the non-trained rodents.

Figure 2: Organ weights (top row) and lactate (middle row) and aspartate aminotransferase (AST | lower row) levels at the end of the study period and after workouts, respectively (Andrade. 2014)

In the exercise trained rodents, there was also a significant reduction in the protein oxidation marker AST in both, the glucose and glycerol group. An obvious sign that both, pure glucose and the polyol (sugar alcohol) compound were used as alternative fuel during the exhaustive workouts, with the latter providing greater reductions in lactate build-up than the former.

What do previous studies say? Previous studies suggests that both glycerol, as well as combined creatine and glycerol can be used to hyperhydrate before exercise and thus to reduce the thermal and cardiovascular strain (Easton. 2007). This practice can also increase the exercise performance of endurance athletes like cyclists (Montner. 1996). Consumed in large amounts of 80g and in conjunction with 2L water, glycerol has also been shown to decreases body weight in athletes & increase overall performance in sedentary subjects, as previously reported at in a previous article of mine.

What do we make of these results? The increased lean mass in the non-trained rats is good news for every couch potato. The non-significance of the difference in trained rats is good news for athletes. The same goes for the reduced AST and lactate levels which suggest that glycerol is effectively used as alternative fuel and thus a candidate for pre- and intra-workout supplements for low-carbers.

Both the increases in heart and adrenal weight are physiological responses to exercise. In that, it is good news that the heart weight did not increase more in the glycerol group, despite the increased adrenal weight in these rats (otherwise, this may be interpreted as a result of pathological stress). The possible mechanisms for the increased adrenal weight are thus not of sympathetic (stressful) nature. Rather than that, the increased adrenal weight "may be related to an increase in body fluid volume caused by glycerol, decreasing relative sodium concentration (hyponatremia) (Von Duvillard. 2004), and increasing mineralocorticoid (aldosterone) secretion and adrenal gland mass (Decaux. 2003)" (Andrade. 2014). Overall, the results of the study still confirm that the ergogenic effects of glycerol are beyond the well-known hyperhydration properties caused by this substance | Comment on Facebook!

References:

• Andrade, Eric Francelino, et al. "Adaptation to physical training in rats orally supplemented with glycerol." Canadian journal of physiology and pharmacology 93.999 (2014): 1-7.
• Decaux, Guy, et al. "Low plasma bicarbonate level in hyponatremia related to adrenocorticotropin deficiency." The Journal of Clinical Endocrinology & Metabolism 88.11 (2003): 5255-5257.
• Easton, Chris, Stephen Turner, and Yannis P. Pitsiladis. "Creatine and glycerol hyperhydration in trained subjects prior to exercise in the heat." International journal of sport nutrition and exercise metabolism 17.1 (2007): 70-91.
• Montner, P., et al. "Pre-exercise glycerol hydration improves cycling endurance time." International Journal of Sports Medicine 17.01 (1996): 27-33. 
• Von Duvillard, Serge P., et al. "Fluids and hydration in prolonged endurance performance." Nutrition 20.7 (2004): 651-656.

The Latest on Combined Training: 15% Increase in Muscle Size in 24 Weeks in Healthy Moderately Active Young Men Regardless of "Cardio First" or "Weights First" Training

If you think even non-significant differences in "lean gains" are significant, "weights first" is for you.

If you are about to embark on a combined strength + endurance training regimen in 2015, it does not matter if you do "cardio first" or "strength first"... well, almost. If you stick to the traditional exercise order, you may gain a non-significant 2% extra on your vastus lateralis (some people would wrongly say "quads") size.

You've read evidence for both, the superiority of "cardio first" and "strength first" on the SuppVersity before and it may in fact be a matter of personal preference, whether you do your cardio or strength training first.

You can learn more about the optimal exercise order at the SuppVersity

Before, After or In-Between?

Exercise Order & Leptin

Cardio First for Anabolism?

Large Muscle Groups First?

How to Combine Cardio & Strength?

Exercise Order Reloaded

The latest study from the University of Jyväskylä and the Edith Cowan University actually appears to confirm just that. In their 24-week study Schumann et al. had 34 physically active and healthy young men performed a combined strength and endurance exercise program with 16 subjects performing the endurance and 18 subjects performing the resistance training exercise first, 2-3 times a week for 24 weeks. Or, more precisely, ...

"[d]uring the first 12 wk, the subjects performed according to their corresponding training group two times 1E+1S or two times 1S+1E per week. The frequency was then increased during the second 12 wk so that two combined training sessions were performed in every first and fourth week and three combined training sessions in every second and third week (i.e., two times 1E+1S or two times 1S+1E or three times 1E+1S or three times 1S+1E, respectively)" (Schumann. 2014)

To reflect tapering before testing, both week 12 and week 24 were conducted by maintaining the training frequency but reducing training volume and intensity by reducing the number of sets, lowering the loads during the strength loading, and reducing both the total duration and time spent at high intensity (i.e., above the anaerobic threshold) during endurance cycling.

Dietary control: To control nutritional intake, food diaries were collected for 3 days including one weekend day at weeks 0, 12, and 24. Subjects received both verbal and written nutritional recommendations and were instructed on how to report nutritional intake in the diaries. The food diaries were analyzed by a nutrient analysis software (Nutri-Flow; Flow-team Oy, Oulu, Finland). Subjects were asked to maintain constant dietary intake throughout the study period. In preparation for all testing, subjects were instructed to consume a light meal 2–3 h before the start of each test and were asked to maintain similar nutritional intake before the measurements at weeks 0, 12, and 24. During each training session, a standardized low dose of glucose was provided at the midpoint of each combined exercise session (after E or S, respectively) whereas water was allowed whenever the subjects felt thirsty.

The intensity of the endurance training was controlled by HR (Polar S410; Polar Electro Oy, Kempele, Finland) associated with subject’s individual aerobic and anaerobic threshold determined during measurements at weeks 0 and 12, respectively. Subjects were instructed to maintain a constant pedaling frequency of approximately 70 rpm during each training session while the magnetic resistance of the ergometer was adjusted to achieve the required exercise intensity.

Concomitant Training: Cardio Before or After Weights? Cardio First Triggers 916% Increase in Growth Hormone. Plus: 7x Higher Testosterone & 3x Higher IGFBP-3 Peaks | read more.

"During weeks 1–7, steady-state cycling of low-to-moderate intensity (below and above the aerobic threshold) was performed, and during the remaining weeks, additional high intensity interval sessions (below and above the anaerobic threshold) were incorporated into the training program. The duration of endurance cycling progressively increased throughout the 12 wk of training from 30 to 50 min. During the second 12-wk period, the major endurance program structure was maintained whereas both training volume and intensity were further increased. The aerobic threshold represented intensities (% HRmax) of 65% T 5% and 67% T 6% in E+S and 68% T 8% and 67% T 6% in S+E at weeks 0 and 12, respectively. The anaerobic threshold represented intensities of 85% T 5% and 86% T 5% in E+S and 82% T 8% and 86% T 5% in S + E at weeks 0 and 12, respectively. The loads used during the strength training were determined by the number of repetitions and execution velocity and progressively increased throughout the two 12-wk periods" (Schumann. 2014)

Exercises for the lower body were bilateral dynamic leg press and bilateral (weeks 1–7 and 13–18) and unilateral (weeks 8–12 and 19–24) dynamic knee extension and flexion. Additional exercises for the upper body included dynamic seated vertical press, lat pulldown, and exercises commonly used to improve trunk stability (crunches, torso rotation, and lower back extension).

• During the first 2 wk, training was performed as a circuit using 2–4 sets of 15–20 repetitions at an intensity of 40%–60% of 1RM. 
• Thereafter, protocols aiming for muscle hypertrophy (2–5 sets of 8–10 repetitions at 80%–85% of 1RM, 1.5- to 2-min interset rest) and maximal strength (2–5 sets of 3–5 repetitions at 85%–95% of 1RM, 3- to 4-min interset rest) and, during the last 2 wk, protocols targeting explosive strength (two sets of 8–10 repetitions at 40% of 1RM with maximal velocity, 3- to 4-min interset rest) were performed. 
• During the second 12-wk period, the major strength program structure was maintained whereas both training volume and frequency were slightly increased to maximize fitness and health outcomes and to avoid a training plateau. 

The overall duration of the strength protocol within each combined training session was 30–50 min, resulting in a total duration of approximately 60–100 min for each combined training session (i.e., E+S and S+E, respectively)

Figure 1: Changes in leg press strength (left), time to exhaustion and aerobic power (right | Schumann. 2014).

Similar to the muscle size, the strength (Figure 1 | left) endurance performance (Figure 1 | right) increased non-significantly more in the "weights first" (S+E) group. In that, it is interesting to observe that the discrepancy between the "endurance first" (E+S) and "weigths first" (S+E) group increase over time. A fact that may suggest that after another four weeks the already measurable difference would have become significant.

Figure 2: Changes in vastus lateralis muscle cross sectional area (CSA, left) and lean mass (right | Schumann. 2014).

This is yet as speculative as the corresponding assumption that the inter-group difference in increase in lean muscle mass and vastus lateralis cross sectional area (CSA) would have achieved statistical significance if the study duration had been longer. On the other hand, that would probably imply that the "strength first group" would have ended up with significantly larger increases in upper body muscle mass.

You know what? Who cares! If there is a bottom line to this article it is the same, I used for previous articles discussing the question whether you "should" do your cardio training before or after your weight training: Do whatever works for you!

Beware of the "training frency" - Chronic Resistance Training Reduces the Anabolic Signaling in Response to Exercise - 12 Days of Detraining Restore It | read more.

And in the unfortunate case that neither "weights first" nor "cardio first" works for you, you can still do cardio and weights on separate occasions. Either on a single day with AM and PM sessions, or on separate days, which is what I would suggest to all of you who are aiming for maximal effects on their physique: Three resistance training workouts and two cardio sessions of which at least one should be a high intensity interval workout on five days of the week. If you stick to a whole-food based higher protein diet (30g of high quality = high EAA protein with every meal), that's going make a difference in the mirror... promise! Comment on Facebook!

References:

• Schumann, Moritz, et al. "Fitness and lean mass increases during combined training independent of loading order." Medicine and science in sports and exercise (2014).

Intermittent Thoughts on Building Muscle: IGF-1, TNF-α, IL-15 & Co and the Emerging Role of an Auto-/Endocrine-Immune Axis in Skeletal Muscle Hypertrophy

Image 1: The word "inflammation" triggers associations which hinder a appropriate understanding of the complexities of the "inflammatory" immune response that is vitally important for (re-)building muscle tissue.

Just to make sure that I do not get off another tangent, again, I will start right off, where I left you in the last installment of the Intermittent Thoughts and that was with the promise to have a closer look at the intricate relationship of (exercise-induced) inflammation and the increases in muscle-specific insulin-like growth factor 1 (IGF-1) and its splice variants, above all the muscle (re-)building mechano-growth factor 1 (MGF-1). Before we are looking how one influences the other, we will yet have to establish a consistent understanding of "inflammation", which, despite being in on everyone's lips these days is commonly (mis-)understood and / or confused with "oxidation", as in the oxidation of "inflammable" substances, you have encountered innumerable times in the form of fire or rust.

What is inflammation? And is it good or bad?

If we simply rely on our everyday understanding of inflammation, we are totally missing the boat on the true significance of a very complex net of biological processes some scientists quite blunderingly labeled "inflammation", which is not the "fire", i.e. the damaging (in many, but by no means all cases oxidative) process, itself, but the appropriate, or, as in the case of auto-immune reactions, inappropriate physiological reaction to it. Whether this misleadingly termed reaction of your immune cells is "appropriate" and thusly healthy or "inappropriate" and thusly detrimental, depends on a whole host of factors, among which the distinction between subclinical chronic inflammation and acute inflammatory responses probably is the most important one.

Illustration 1: The theoretical relationship between the biphasic hormetic curve and exercise salience (Nunn. 2010. Fig. 1)

While scientists believe that a chronic low, yet elevated level of inflammation is the root cause of almost all modern disease, the acute inflammatory response to real threads is the driving force behind those hormetic adaptation processes about which Alistair V. Nunn and his colleagues from Imperial College in London write that their "decline [...] in our daily life may be leading to increased systemic sub-clinical inflammatory tone, decreased metabolic flexibility and suppression of exercise salience" and thusly set the stage for "obesity, the metabolic syndrome, diabetes, vascular disease and even cancer" (Nunn. 2010). It is thusly only consistent of the researchers to demand:

Whether we like it or not, a long and healthy life needs to include regular exposure to occasional doses of environmental stressors, including fasting, natural temperature changes, polyphenols and exercise. Although human intelligence has enabled us to remove most stressors from the environment, common sense may be required to re-introduce some of them.

And while I could unquestionable go into much more detail on the concept of hormesis and its fundamental importance to our health, I am determined not to lose sight of the real intention of this installment of the Intermittent Thoughts, which is to elucidate the intricate relationship between the local inflammatory response to exercise, the intramuscular expression of IGF-1 and its splice variants and the exercise-induced increases in skeletal muscle mass and strength.

The IGF-1 response to acute inflammation

Contrary to what you may have gathered from a cursory read of the literature on the "dangers" of the "growth promoting" and thusly potentially carcinogenic insulin-like growth factor, neither the mature 70 amino acid polypeptide IGF-1 nor any of its splice variants are in and out of themselves carcinogenic. It is the (not even indiscriminate, cf. red box) growth promoting effect they exert on target tissues via interactions with the respective IGF-1 receptors which will promote the growth and proliferation of all sorts of cells, including cancer cells that is responsible for their bad reputation.

Image 2: IGF-1 per se is not fattening,
if anything it is "IGF-resistance"

Did you know that a 2008 study by a group of scientists from the University of Leipzig, in Germany, found that the "growth promoting" effect of IGF-1 on adipocytes is negligable, the effect of the latter on systemic IGF-1 expression via negative feedback, on the other hand pretty profound (Klöting. 2008)? As it turned out, not IGF-1, but its absence, or I should say, its inability to activate the receptor in the IGF-R knock-out mice that were used in the study were the underlying cause of both statistically significant increases in body, fat and organ weight, as well as ~20% elevated serum IGF-1 levels. Similar to the fattening effects of insulin, its structural cousin (cf. insulin vs. insulin-like growth factor discussion in the previous installment), it is thusly not the physiological expression of IGF-1, but its inability to trigger necessary cellular signaling cascades and negative feedback that could be at the heart of the metabolic derrangements that oftentimes go hand in hand with elevated levels of circulating IGF-1.

In this context an important result of a meta-study by Claudio Franceschi and his colleagueson genes involved in the etiology of longevity, comes to mind (Franceschi. 2005):

In a longitudinal survey it has recently been shown that older women having low serum levels of IGF-I and high serum levels of IL-6 have the highest risk of disability and mortality, in comparison with women who have low levels of IL-6 and high levels of IGF-1 (Cappola et al., 2003). Such a beneficial effect of high IGF-1 serum level in the elderly is in apparent contrast with the above reported data showing that reduced IGF-I plasma levels are associated with longevity (Bonafè et al., 2003b). In order to reconcile this apparent discrepancy, it can be hypothesised that the decrease in plasma IGF-1 observed in nonagenarians and centenarians might minimise the risk of cancer in these subjects by decreasing a generalised mitogenic stimulation. The price to pay is frailty and massive reduction of muscle strength, two characteristics of such very old people.

With this connection between overexpression of the inflammatory cytokine interleukine 6 (IL-6) and the low, or as we will see insufficient IGF-1 expression in elderly people, we have come full-circle and back to our initial question: How do "inflammation" and IGF-1 expression go together?

Image 3: Unlike Hermes, the Greek messenger of the Gods, cytokines have no intrinsically mischievous side and their vilification is unjust.

Although it was certainly not a good idea to summarize such a complex phenomenon as the release of signaling molecules and the consequent reponse of the immune system under the term "inflammation", the name "cytokine" is actually quite fitting, because the combination of the Greek words -cyto, for "cell", and -kinos, for "movement", denote the exact consequences the release of respective signaling molecules has: it induces the movement of cells, which, in the case of "inflammatory cytokines", obviously are immune cells. The contemporary vilification of all "inflammatory" cytokines in the lay-press is however unwarranted - or would you hold the guy who takes the calls on the emergency line responsible for either the outbreak of the fire (=immune reaction necessary) or another nuisance alarm (unwanted auto-immune reaction)?

A very important clue that points us into the right direction comes from a 2007 study by Pelosi et al. (Pelosi. 2007), who analyzed the regenerative process skeletal muscle tissue undergoes subsequent to injuries. The scientists analyzed the differential expression of the two major inflammatory cytokines TNF-alpha and IL-1-beta, which in turn triggers the release of the aforementioned (and much better known) IL-6 in skeletal muscle (Luo. 2003), in response to cartiotoxin (CTX) injection in normal (wild-type) mice and mice who were genetically engineered to over-express mIGF-1 specifically in differentiated myofibres (MLC/mIGF-1).

Figure 1: Differential expression (relative to maximum) of TNF-alpha and IL-1b in CTX-injected muscle of wild-type and MLC/IGF-1 mice during the 10 days of recovery (data adapted from Pelosi. 2007)

As the data in figure 1 goes to show, the higher mIGF-1 expression (the "m-" indicates autocrine production, i.e. IGF-1 that is produced right at the target tissue, in this case skeletal muscle) in the genetically engineered mice led to a statistically significant amelioration in the expression of pro-inflammatory cytokines, which are involved in the recruitment of monocytes and macrophages.

An "anomaly" you will probably have noticed is the sudden increase of both inflammatory marker on day 5 post injury. I don't know if you are familiar with the term "deep onset muscle soreness", but the "onset" increase in inflammation certainly reminds me of the feeling I tend to have whenever I have gone overboard on squatting. Do you know what I am talking about? This awkward feeling of cramping pain in the quads that tends to appear right then, when you thought that the soreness was abating? Interestingly enough, this sudden onset of inflammation, which is completely absent in the MLC/mIGF1 mice, goes hand in hand with a the peak of  another, less well-known cytokine that goes by the (telling) name of macrophage migration inhibition factor, or MIF. This stands in contrast to the MIF response in the MLC/mIGF-1 mice, where

the significant down-regulation of MIF at 5 days post-CTX injection in MLC/mIGF-1 injured muscle may facilitate the emigration of infiltrating cell pools, leading to a rapid resolution of the inflammatory response.

These facilitatory, or rather dis-inhibiting effects IGF-1 seems to exert with respect to the MIF-driven "lockout" of the macrophages, allows for a "rapid restoration of injured mIGF-1 transgenic muscle", of which Pelosi et al found that it...

was also associated with connective tissue remodeling and a rapid recovery of functional properties.

Show that autocrine mIGF1 via its modulating effect on the inflammatory response and its (related) ability to reduce the formation of fibrotic muscle tissue "creates a qualitatively different environment for sustaining more efficient muscle regeneration and repair" (Pelosi. 2007).

Image 4: The local administration of platelet (and growth factor) rich plasma is about to become a recognized treatment strategy for muscular injuries and chronic degenerative joint diseases such as tendinopathy.

Did you know that a 2006 study from the University of Melbourne showed that both, IGF-1 gene transfer to the injured muscle (which would be comparable to the autocrine mIGF-1 expression discussed in the previous paragraph), as well as systemic IGF-1 administration via mini-osmotic pump at 1.5 mg/kg/day "hastened functional recovery" in artificially injured tibialis anterior muscles of mice? The injection of platelet rich plasma, which contains various growth factors, into injured muscle tissue is already practiced by many physicians working with competitive athletes (Creany. 2007) and appears to be a promising treatment strategy for other (non-muscular) pathologies such as chronic degenerative tendinopathy, as well (Vos. 2010).

If we set these results into a somewhat broader context, it becoms clear that the inflammatory cytokines that are released as a result of muscular damage, summon macrophages and other immune cells to the injured tissue. The concomitant production of local mIGF-1 facilitates their migration into the muscle where they increase the proliferation of satellite cells (Merly. 1999) and help (re-)building (new) muscle tissue (Chazaud. 2003). The "ameliorative" effect of IGF-1 on inflammation is thusly by no means comparable to the "ameliorative" effect firefighters exert on a fire. IGF-1 does not work against the inflammatory response (remember: in 99% of all cases the latter is a completely healthy and beneficial physiological reaction to an external assault on your body!), it works hand in hand with the driving forces of "inflammation", the monocytes, by "opening the door to the muscle" and rejuvenating the satellite cell pool from which, in turn, relies on the immune cells during the incorporation of these progenitor cells into the existing muscle tissue.

The emerging importance of an endocrine-immune-axis in skeletal muscle hypertrophy

Image 5: Control (A) and IL-15 treated (B) myotubes; nuclei are stained yellow; note the wide myotubes in the IL-15 treated muscle (img. from Quinn. 2002)

This intricate interplay of the endocrine (IGF) and the immune (monocytes) system, which is so characteristic for our emerging understand of the true complexity of the mammalian physiology, reminds me of the question Trevor's Facebook question from last week. Trevor, who has obviously done his homework on the "IGF-1 / cytokine connection" wanted to know my thoughts on interleukin-15, one of the less-researched "inflammatory" cytokines, which appears to play a central role in the accrual of myosin heavy chain (MHC) motor proteins (if you have not done so, already you can read more about the role of the motor proteins in Part II of the Hypertrophy 101). Back in 1995, already, a group of scientists from the American Lake VA Medical Center published a ground-breaking (yet hitherto unfortunately largely overlooked) paper on the role of interleukin-15 in skeletal muscle myogenesis (Quinn. 1995). Quinn et al. were for the first time able to show that

IL-15 used at concentrations of 10 or 100 ng/ml increased MHC accumulation five-fold in C2 myoblast cultures and 2.5-fold in primary bovine myogenic cultures. Moreover, C2 myotubes formed in the presence of IL-15 appeared larger than controls.

Interestingly, the researchers must have apprehended the existence of the previously discussed intreaction of the endocrine and the immune system and tested whether this effect depended on the presence of IGF-1:

Figure 2: Moysin heavy chain expression (arbitrary units) in in bovine muscle cultures after incubation with IL-15 (dose in ng/ml), IGF-1 (dose in ng/ml) or both (data adapted from Quinn. 1995).

From the data in figure 2 it becomes quite obvious that IL-15 has more than a facilitative effect on the IGF-1 induced accrual of motor proteins. A 2002 follow up study on mice myocytes (Quinn. 2002) and a 2003 study using human skeletal muscle myogenic cultures (Quinn. 2003) confirmed the validity of these initial findings.

Figure 3: Myosin heavy chain expression, protein synthesis and protein degradation in rodent muscle in response to IL-15 treatment at different basal levels of IGF-1 (data adapted from Quinn. 2002)

Interestingly, the synergistic effect of IL-15 and IGF-1 appears to be restricted to the accrual of motor proteins (cf. figure 3) and has only marginal effects on protein synthesis and degradation.

mTOR & Co, IGF-1, inflammation ... what's next?

Image 6: Is the role of naturally achievable testosterone levels in the accrual of lean muscle tissue overrated, or not? What exactly does the principal male androgen do on a tissue level and why did your OTC test booster only increase your libido and not the size of your sleeves?  Come back on 01.01.2012 to learn more ;-)

With protein synthesis and degradation, we have come back to one of the initial discussed cornerstones of skeletal muscle hypertrophy (cf. What is Hypertrophy?), of which you should have learned in the previous installment of this series that is a necessary, yet not sufficient prerequisite of sustainable muscle growth. Without the IGF-1 mediated and, as you have learned in this installment, monocyte-driven (re-)construction (increase in myonuclei + accumulation of motor proteins) of the underlying structure of the muscle, however, neither the repair of damaged, nor the accrual new, functional (cf. Hypertophy 101: Part II) muscle tissue would be possible.

The question we still have to answer before we can eventually integrate all those different pathways into a model which would allow us to develop a "hypertrophy-optimized" training, nutrition and supplementation regimen, we do yet still have to shed some light on the role of the legendary "big T": Testosterone! So stick with me and come back next week, or next year, whatever you like better, to learn more about the actual role of the principal male sex in the complex process of skeletal muscle growth.