D-Finitively Relevant News: Vitamin D Supplementation Speeds Up Strength Recovery and Lowers Markers of Muscle Damage in Vitamin D-Sufficient Young Subjects

If we were all training at "Muscle Beach", we would probably not need any vitamin D3 caps to get our 25(OH)D levels into the recovery friendly 50ng/ml zone. They would already be there!

Ok, I know this looks odd, but it's really total coincidence that all the interesting vitamin D research is published in the last weeks of the year. Unlike the latest vitamin D articles, i.e.

• "Vitamin D Builds Muscle: 70% Reduction in Myostatin, 45% Increase in Myotube Size in 10 Days" |  learn more
• "Leucine, Insulin & Vitamin D*: A Hypertrophy Boosting Triplet That Does Not Make It From the Dish to the Gym?" | read more

today's SuppVersity article does yet leave little room for speculations about it's real-world significance. I mean, how could it, if the paper it discusses is titled "Supplemental vitamin D enhances the recovery in peak isometric force shortly after intense exercise" (Barker. 2013).

You can learn more about vitamin D at the SuppVersity

Vitamin D Builds Muscle

Leucine, Insulin & Vitamin D

Vitamin D = Fat Synthesizer

Overlooked D-Sources

Vitamin D For Athletes!

Vitamin D Helps Store Fat

The title does yet not "say it all". Moreover, what it doesn't tell you is the most important piece of information. The study period was short (35 days) the dose of vitamin D was relatively high (4,000IU) was conducted with "reportedly healthy and modestly active (30 minute of continuous physical activity at least 3 time/week) adult men with low, albeit normal vitamin D levels (25(OH)D ~ 30ng/ml)! The otherwise almost obligatory question about the potential relevance in "normal" human beings does thus become superfluous - and this is true for all the observations the scientists made, i.e.

• ... the linear relationship between baseline 25(OH)D levels and the increase in serum vitamin D in response to the with an up to 150% increase in subjects in the deficiency zone and less than 50% increases in subjects in the >40ng/ml range, ...
• ... the steady serum calcium levels, which make concerns about potentially kidney damaging increases in calcium from vitamin D3 supplementation obsolete, ...

... and, not to forget, the enhanced recovery in peak isometric force the researchers observed in their subjects after these had performed 10 sets of 10 repetitive eccentric-concentric jumps with a load of 75% of their respective body mass on their shoulders and a 20 sec rest period between each set.

For the researchers this is a model of a "muscle damaging event" (P< 0.05; ≈8% at 24-h), which was, as it was to be expected, associated with an increase in the circulating levels of the "liver enzymes"  alanine (ALT) and aspartate (AST) aminotransferase, of which many medical textbook will tell incorrectly tell you that they would indicate a strain on the liver / liver damage, when they are actually only markers of increase amino acid catabolism. The attenuation (P< 0.05) of the immediate and delayed (48-h, 72-h, or 168-h) increase in these enzymes in the vitamin D supplemented group  is thus an indicator of "muscle protective" or at least general protein sparing effects of supplementally increased vitamin D levels.

Figure 1: Strength recovery (%) from immediately post to 24 post workout, left; serum ALT values immediately after, 24h, 72h, and 168h after the exercise test (Barker. 2013).

The fact that the alleged decrease in muscle damage did not correlate with a decrease in muscle soreness does or doesn't negate the purported muscle protective effects of vitamin D. There is, as you should remember from Alex' excellent articles about DOMS, after all no direct link between ALT, AST, muscle damage and delayed onset muscle soreness, aka DOMS (learn more about DOMS). What is clear, though is that there was no consistent trend in the subjective measures of muscle soreness in the study at hand, so that Barker et al. are right, when they state that "[s]upplemental vitamin D was ineffective at abrogating muscle soreness in the SSC leg" (Barker. 2013). If it's an improvement in pain you are looking for, you'd be better off with one of the techniques Alex' discussed in part I of his article series.

Figure 2: It looks boring, but the linear association between the subjects baseline levels and the change in 25(OH)D and the ceiling effect at ~50ng/ml are also important results of the study at hand (Barker. 2013).

Bottom line: I guess you can't have it all, so I would not mourn over the lack of effect on muscle soreness. I mean, come on (!), this is one out of thousand (literally!) vitamin D studies with real-world relevance for you and me. A study that confirms that getting your 25(OH)D levels into the 50ng/ml range can actually have small, but stat. significant beneficial effects on your exercise performance (without negative effects on calcium, btw).

Furthermore, the fact that this increase to the 50ng/ml+ was achieved in all subjects with "only" 4,000IU D3 within only 35 days and was directly associated to their respective baseline level is an intruiging result on its own (see Figure 2). It does after all provide you with a rough guideline of what you have to do if your next 25(OH)D blood test comes back way below the 50ng/ml margin.

Against that background, there is no reason to frown about the fact that we still don't really know what vitamin D actually does to elicit its ameliorative effects on the performance decline in response to potentially muscle damaging stretch-shortening contraction. This was beyond the scope of the study at hand and cannot be investigated in isolated muscle cells... much contrary to the previously reported anabolic effects in the Petri dish, by the way, which may be exciting, but more or less irrelevant, if we can't observe corresponding increases in muscle hypertrophy in the real world.

References:

• Barker, T., Schneider, E. D., Dixon, B. M., Henriksen, V. T., & Weaver, L. K. (2013). Supplemental vitamin D enhances the recovery in peak isometric force shortly after intense exercise. Nutrition & Metabolism, 10(1), 69.

"10x3 = 3x10 < 20x3"? The Mathematics of Optimal Set and Rep Ranges for Maximal Increases in Sleeve Size

Image 1: Going for the pump was Arnold's way
to biceps peak and size, but is that "optimal"?

How many sets do you do, when you are at the gym? How many repetitions (reps) each? And are you sure that this is the "right" way to train? No? Well I guess then you will be interested in the results of a study from the School of Exercise, Biomedical and Health Sciences at the Edith Cowan University in Joondalup, Western Australia ( Chan. 2011), for which Roy Yang Han Chan (I hope I did not mix up name and surname, here ;-) recruited 10 non-resistance trained men to investigate the effects of different set/rep schemes on muscle strength, range of motion  (ROM),  muscle  cross  sectional  area  (CSA),  muscle  soreness  and  plasma  creatine kinase  (CK)  activity after two bouts of eccentric biceps curls (see illustration 1 for exact study setup).

Illustration 1: Setup of the 4 training bouts the 10 subjects of the study participated in (according to Chan. 2011)

Now, "non-resistance trained" subjects (mean ± SD age: 26.1 ± 4.1 y, height: 173.1 ± 6.1 cm, body weight: 72.4 ± 9.1 kg)  and training on just two occasions, are not exactly constituents of a highly significant study protocol. In view of the scarcity of data on what some trainers consider the holy grail of training theory, the finding that

Maximal  voluntary  contraction  strength,  ROM,  biceps  brachii  CSA [cross sectional area],  muscle soreness and plasma CK [creatine kinase - leakage of this enzyme from the muscle is a measure of muscle damage] activity changed significantly after the first bouts without significant differences  between  3x10  and  10x3,  and  changes  in  the  measures  following  20x3  were similar  between  arms.  No  significant  differences  in  the  changes  of  the  criterion  measures were  evident  between  bouts.the  set-repetition  configuration  had little effect on muscle damage, which was likely to be due to similar peak torques produced during  exercise  between  the  3x10  and  10x3  bouts.

The question we have to answer now, is "How representative is this data?" In the previous paragraph I already mentioned the first fundamental flaw of the study: the subject selection. "Why on earth", you may be asking yourself rightly, "Why did this Australian exclude resistance trained subjects from his study and chose subjects with 4.5inch arms? Isn't it obvious that these bonsai-guns will grow no-matter what those guys would do in the gym?" And, yes that is exactly the case and, at the same time though, also the reason why, time-and-again, we see those studies done with "resistance training virgins" - due to the completely novel stimulus their muscle simply grow like crazy, no matter how short your study period, how flawed your exercise program or how useless your supplement may be - and that, in turn, reduces your costs and the threat of observing a null-result dramatically. You better keep these general objections in mind, especially if you look at absolute values of studies like this one.

Figure 1: Relative increase in biceps cross sectional area [CSA] of 3 sets a 10 reps (3x10) and 10 sets a 3 reps (10x3) compared to 20 sets of 3 reps (data calculated based on Chan. 2011)

With the afore-made objections in mind, the relative results depicted in figure 1, do still provide some insight into the differential time-course of the effects of a high intensity training with 10 sets a 3 reps (10x3) and a classic hypertrophy regimen with 3 sets a 10 reps. The greater increase in muscle CSA on the first day (both are expressed relative to the 20x3 regimen that both group A and group B performed) in what I would like to call the hypertrophy group (3x10), as well as the delayed response in the high intensity 10x3 group appear to support the commonly cited hypothesis that due to the greater myofibrilar damage the high intensity 10x3 protocol would inflict, it takes longer for the muscles to recover and thus grow.

Figure 2: Relative elevation of creatine kinase over baseline in group A (3x10 vs. 20x3) and group B (10x3 vs. 20x3) 4 days after eccentric biceps training (data calculated based on Chan. 2011)

The creatine kinase [CK values are generally accepted as markers of muscular damage] values in figure 2 suggest another conclusion, though. While the CK values in what I labeled the hypertrophy group were still +60% elevated over baseline, they had returned to normal (+8%) in the HIT group already. While this would go against the idea that a 10x3 training regimen requires longer recuperation times than a rather hypertrophy oriented regimen of 3x10 sets, these results would obviously warrant longer term studies in well-trained athletes to be of reasonable significance for any bodybuilder or fitness athlete - especially in view of the marginal and statistical non-significant difference in overall strength and size gains I already cited at the beginning of this post.

For the time being you could however try to switch things up for a week or two and see whether and how a rather unorthodox 10x3 regimen impacts your sleeve size, since even if it may not be the "optimal" training regimen, changing the training stimulus from time to time is always a good idea... ah, and if you wake up four days later with an +2inch increase in your biceps size, please let me know ;-)

Supramaximal Eccentrics (+38%) on Leg Presses & Calf Raises Pay Off in Form of Extra Strength and Significantly Higher Lean Mass Gains of the Trained Muscles

It goes without saying that you need someone to help you to do eccentric leg presses... well, unless you use one leg to help with the concentric part of the exercise, obviously.

Training techniques have long been heralded as the single best way to increase your gains. These days, however, the discussion on bodybuilding and fitness boards has evolved away from talking about drop sets, singles, staggering and forced reps and towards BCAAs, whey, herbs and antioxidants - in short: People believe they could buy results, they would otherwise have to work for.

Apropos work, the amount of work the subjects in a recent study from the JES Tech, Ilc., Wyle Science and the NASA Johnson Space Center in Houston had to perform was not even overtly demanding.

Learn more about the best muscle builders at the SuppVersity

Optimizing Rest for Size and Strength Gains

Alternating Squat & BP - Productive?

Farmer's Walk or Squat? Is Strong- men T. For You?

Full ROM ➯ Full Gains - Form Counts!

Battle the Rope to Get Ripped & Strong

Up Your Squat by 25% With Sodium Bicarbonate

The study, which was conducted by Kirk L. English, James A. Loehr, Stuart M. C. Lee,
Scott M. Smith and published in the European Journal of Physiology, required the 40 male subjects (34.9  ±  7  years, 80.9  ±  9.8  kg, 178.2 ± 7.1 cm; mean ± SD), who were  free from any orthopedic or other medical conditions, but had not participated in a strength training program for at least 6 months prior to entering the study (only five subjects had any history of strength training), performed a supine leg press and calf press training program 3 days per week for a total study duration of 8 weeks. 

Table 1:  Warm-up and training volume and concentric training intensity (% pre-training 1-rM) during 8 weeks of resistance exercise (Smith. 2014); (a)  the number of warm-up and training sets × repetitions performed was the same for all 3 days of each training week; (b) Warm-up intensity (not shown) progressed in a graded fashion from 50 % 1-rM to the prescribed training intensity (e.g., week 1 high intesity day: warm-up at 50 and 60 % followed by training sets at 64 % 1-rM). Warm-up repetitions decreased with each successive set as intensity increased (e.g., week 8 high intensity day: 8, 6, 6, and 4 repetitions at 50, 64, 73, and 82 % 1-rM, respectively, followed by training sets at 96 %1-rM); (c) rest periods between sets were 1 min (50–70 % 1-rM), 1.5 min (70–80 % 1-rM), 2 min (80–90 % 1-rM), and 2–3 min (90–100 % 1-rM)

The subjects were matched for pre-training leg press (1-rM) and randomly assigned to one of five training groups. concentric training load (% 1-rM) was constant across groups, but within groups, eccentric load was 0, 33, 66, 100, or 138 % of concentric load.  Muscle mass (dual energy X-ray absorptiometry; DXA), strength (1-rM), and BMD (DXA) were measured pre- and post-training. Markers of bone metabolism were assessed pre-, mid- and post-training.

The idea was to analyze the adaptive responses to a uniquely broad range of eccentric to concentric loading "to inform the development of appropriate exercise prescriptions for a range of populations and to guide resistance exercise hardware requirements for exploration spaceflight." (Smith. 2014)... needless to say that you don't have to be an astronaut to benefit from Smith's findings.

Figure 1: Individual and mean (±SE) leg press (left) and calf press (right) strength before and after  8 weeks of training. Asterisk significant difference from pre-  to post-training (P < 0.05); hash significantly different from 0,  33, and 66 % training groups (Smith. 2014)

As you can see in Figure 1, the increase in leg press 1-RM in the 138 % (highest resistance) group (20 ± 4 %) was significantly greater (P < 0.05) than the 0 % (8 ± 3 %), 33 % (8 ± 5 %) and 66 % (8 ± 4 %) groups.

Compared to the 100 % group, on the other hand, using supramaximal weights did not yield a statistically significant advantage (13 ± 6 %; P = 0.15). Still, while all groups, except the 0 % group, increased their 1-RMs (P < 0.05) on the calf press, only the supramaximal training elicited statistically significant leg lean mass gains! So, even if there was only a non-significant strength advantage we are still dealing with an intriguing "mass advantage" of supramaximal eccentrics - an observation that could refuel the debate about the role of muscle damage as a trigger of skeletal muscle hypertrophy.

Figure 2: Changes in body composition, i.e. total body mass, lean mass and leg lean mass, sign. increases only in the 138% group (Smith. 2014)

Bottom line: Statistics inform us that strength-wise (only!) it wouldn't be necessary to use supramaximal weights on the eccentric part of an exercise. Common sense and the exclusive increase in lean leg mass in the 138% group, on the other hand, indicate that it would very well make sense to have a partner assist you during the concentric phase of your leg workouts, in order to torture your self on the eccentric portion. The results, a statistically significant lean mass and a visible strength advantage are unquestionably worth it and certainly more pronounced than the effects of many of the dubious supplements people prefer to talk about on the fitness and bodybuilding boards all over the Internet, these days (discuss the results on Facebook).

References:

• Smith et al. "Early‑phase musculoskeletal adaptations to different levels of eccentric resistance after 8 weeks of lower body training." European Journal of Physiology (2014). Accepted Manuscript.

Fast & Slow, Heavy & Light, Eccentric & Concentric: Do All These Fancy Training Variables Really Matter? Probably For Power. Not So Much for Size, Though.

Image 1: According to Sakamoto, 2011, EMG
activation during the bench press increases
with rep-speed & weight (pic from mylot.com)

"Go heavy or go home!" You probably have heard this advice time and again and, after all, two recent studies appear to suggest that, when all is set and done, ah... I mean all sets are done, the thing your muscles seem to care most about is workload. While the study by More et al. (Moore. 2011) does not tell us anything about the effectiveness of training with different rep speeds, it goes to show that concentric and eccentric training are similarly effective, when it comes to building sleeve bursting biceps. Sakamoto et al. (Sakamato. 2011), on the other hand, found that EMG activity of the pectoralis major increases with rep speed and (readers of the SuppVersity EMG Series know that already) weight. Now, before we jump to any preliminary conclusions, let's tackle the studies in some more detail...

The nine healthy, but previously not weight-training average Joes (mean age: 22yr; height: 1.75m; weight:78.3kg) from the Moore study (Moor. 2011) performed single arm biceps curls on a dynamometer twice per week. The volume increased from week one to week five from 2 to 6 sets and was cut back again in the last (ninth) week before the final testing session. Other than in similar studies on the effectiveness of eccentric vs. concentric training, the subjects did not perform their dynamometer curls either concentrically or eccentrically, but were instructed to perform concentric curls with one arm and eccentric curls with the other. Right and left arm had previously been randomly assigned to either the maximal lengthening (eccentric) or shortening (concentric) condition, so that limb dominance (n=5 dominant; n=4 non-dominant) was adequately counterbalanced. Moreover, the subjects had to perform ~40% more repetitions on the concentrically trained arm, to ensure total work was equal, or, put differently, to make up for the greater muscle force generation (+60% total work per repetition in eccentric vs. concentric) during eccentric dynamometer curls. Thusly, the participants performed the same 51.8MJ of work with each of their arms in the course of the 9-week training program.

Under these equalizing conditions, workoutput for both conditions rose similarly over the 9-week training program:

Total work per repetition increased from week 1 to week 9 for both LC and SC (main effect for time, P = 0.001) with no difference between conditions (time by condition interaction, P = 0.63). The average increase in work per repetition was similar between LC and SC (17.2 ± 6.3 vs. 22.1 ± 8.9%, respectively; P = 0.69). There were increases (at least P<0.05) in peak torque for all velocities tested (*8–20%) with no significant difference between conditions.

The scientists also found similar results for the muscle crossectional area (CSA), which had been "virtually identical (P = 0.99) before training" (48.5mm² vs. 48.4mm², for the ecc. and con. trained arm) and "increased similarly between conditions" (ecc. 6.5 ± 0.6% vs. con. 4.6 ± 0.4%, respectively; interaction, P = 0.37). What may initially sound like one of those statistically induced geeky underestimations of real world effects, i.e. calling 6.5% vs. 4.6% increases in muscle CSA "similar", turns out to be actually negligible if you calculate the respective absolute difference in CSA increase which is less than 1mm², or an area with the size of a pinhead.

Figure 1: Other than total work per repetition, the respective peak torque development did vary significantly (+8.9% vs. +13.5% for con vs. ecc) between the concentrically and the eccentrically trained arm (data adapted from Moor. 2011)

If, however, you plot the peak torque data from table 1 from the Moore study (I did that for you in figure 1), you will realize that, after all, there is more of a difference between the two training regimens than Moore and his colleagues dissertations would make you think. In fact, their assertion that "there was a main effect for condition for peak torque measured at 0.79 rad/s [slow concentric] in that LC [eccentrical training] was *8% greater than SC [concentric training]" is simply not consistent with the data they provide.

Note: A comment by "anoymous" (guys give me at least a pseudonym!) reminded me that in yesterday's hurry I forgot to mention a major caveat to the study. The latter is directly related to the unilateral training protocol which could potentially (or rather certainly) lead to cross-over effects from one arm (probably the eccentrically trained one) to the other. Similar effects have been observed in e.g. Adamson et al., 2008, where rate of force development and maximal isometric contraction (37% vs. 35%) in 10 adult females increased similarly in both arms, although the ladies had trained only one arm. It is yet notable that the 1RM increased almost exclusively in the trained arm and that the strength increases in the Adamson study occurred in the absence of muscular hypertrophy and are thus attributed by the authors to neurological addaptions of which obviously both arms benefited to a similar degree.

As far as peak torques are concerned the available data (with reservations that the data the authors provide in table 1 of their paper is correct) would suggest that the peak torque increments in the concentrically trained arm for different repetition tempos were on average 4.6% greater than those for the eccentrically trained arm, or, in other words, the higher rep lower weight concentric training resulted in greater strength improvements than the higher weight, lower rep eccentric training, which is so contrary to what you see in similar studies that I would assume that the authors just got the captions wrong and the data in figure 1 would have been reversed, i.e. what now is red should be blue and what now is blue should be red... but who cares, anyway? Focus on getting a good contraction on both the con- and the eccentric phase of your curls, do the exercises described in the SuppVersity EMG series and grow ;-)!

Figure 2: The time [in s] to "speed failure" (i.e. not being able to complete another rep at the given tempo / slow: 5.6s; medium: 2.8s; fast: 1.9s) increases with increasing tempo and load expressed in % of 1 repetition max, 1RM (data adapted from Sakamato. 2011)

Fortunately, the Sakamato study does not contain similarly confusing results. In essence the study, which investigated muscle activations under varying speeds and intensities during bench press using surface electromyography (EMG) found that in the 13 weight-trained men (21.7 ± 3.6-year-old) who performed bench press until fatigue under five intensities (40–80% 1RM), and four speeds (slow 5.6-s/repetition, medium 2.8-s/repetition, fast 1.9-s/repetition, and ballistic maximum speed), found that ...

...faster conditions [...] produced a significant fall in amplitude during the final concentric phase compared to slower movements [while at the same time] after fatigue, EMG amplitude increased, with the speed effect being maintained. 

This means that in the rested state at the beginning of the training you still have the explosiveness to really "pump" the weight up and thus pump out more reps. On the othrt hand, maximum muscle stimulation does not occur before your pectoralis major brgins to fatigue later in the exercise session (cf. figure 3).

Figure 3: Normalized EMG activity at five time points for a given rep tempo / slow: 5.6s; medium: 2.8s; fast: 1.9s / in the rested and fatigued state (data adapted from Sakamato. 2011)

According to the EMG data in figure 3, it does make sense to start (after an appropriate warm up) with heavy and explosive sets / movements and to switch to medium weights and tempo later in a training session. But wait, isn't that exactly what generations of successful trainees have been doing already? Well, I guess this is then another case, where practical training experience beat exercise science by decades and thus further evidence that much more than in the case of nutrition & supplements most of the research that is put into specific exercise programs does little more than reproduce pieces of the knowledge that has accumulated in the heads of trainers and trainees all around the globe ever since the earliest days of physical culture.

Taurine Pumps Up Strength & Recovery in Response to Eccentric Curls. NAC Decreases Peformance & Boosts Fat Oxidation!? Exercise Reduces, Caloric Restriction Increases Inflammation. Carnitine Rescues Fast Twitch Muscle

Blood glucose alone would not last for 90s of running up the stairs.

80 minutes! That's the SuppVersity Figure of the Week and the impressive timespan you could (theoretically) fuel your energy demands during exercise at 70% of your VO2max from your muscle glycogen stores.

The latter hold the energetic equivalent of ~1,500kcal and are thus an almost 40x larger reservoir of energy than the tiny amounts of glucose that's floating around in your bloodstream (data based on Gleeson. 2008).

If you had to rely on that alone, you would pass out after 2 mins of the previously mentioned exercise at 70% VO2max.

Obviously no workout is going to be fueled 100% exclusively by glucose/glycogen, so that you can still use the amount of energy your body stores in the fat cells (~93,000kcal) and in form of tissue proteins (~49,000kcal) and keep running for another 7,400 minutes or 5.13 days... theoretically

Enough of the figures let's get to some recent research results

• 

  You want the boost without the buzz? Hit the right taurine / caffeine ratio to avoid the stim crash & sleeplessness (learn how)

  Taurine for increased strength and recovery during and after eccentric biceps curls (Acordi da Silva. 2013) In a recent study researchers were able to show that the provision of taurine for 14 days before a standardized eccentric exercise regimen comprising 3 sets of eccentric biceps curls on the Scott bench that were performed at  80% of the 1-RM to total failure resulted in significant increases in strength levels and thiol total content of the muscle, as well as a decrease in muscle soreness, lactate dehydrogenase level, creatine kinase activity and oxidative damage (xylenol and protein carbonyl) after the workouts.
  
  Since the activity of the antioxidant enzymes (superoxide dismutase, catalase, and gluthatione peroxidase) and inflammatory markers (tumor necrosis factor, interleukin (IL) -1 beta, and IL10) in the blood of the twenty-one participants (mean age of 21 ± 6 years, weight of 78.2 ± 5 kg) were not altered, decreases in muscle growth as they have been reported for NAC, only recently are not likely to occur. 

• 

  CLA in pomegranate? Not really, but the CLnA in the seeds of the fruit may be even more potent (learn more)

  NAC increases fat oxidation, but compromises performance during HIIT cycling (Trewin. 2013) Talking about NAC another recent study conducted by Adam J. Trewin, Aaron C. Petersen, Francois Billaut, Leon R. McQuade, Bernie V. McInerney, Nigel K. Stepto found that the provision of N-acetylcysteine (NAC) before a HIIT cycling exercise (6x5min HIIE bouts at 82 % PPO (316 ± 40 W) ) separated by 1min at 100W, then after 2min recovery at 100W) elevated the fat oxidation yet only during the last two bouts by 150%. It also reduced the makers of lipid oxidation (these are cell lipids not stored fat) and lactate levels after the time trial. However, the mean EMG activity was -7% and the mean power output 4.9% lower during the NAC trial.
  
  Now, whether that's a good or bad thing actually depends on your goals. If you are glucose tolerant and train to burn fat, it's a good thing. If you want to empty your glycogen stores to promote GLUT-4 or are a competing athlete whose main interest is maximal performance, though the changes would be detrimental.

• Exercise training vs. dieting - anti- vs. pro-inflammation (Auerbach. 2013) In a soon-to-be-published paper in the American journal of physiology. Regulatory, integrative and comparative physiology scientists from the University of Copenhagen report that contrary to their own expectations, the adherence to an endurance exercise program that would burn ~600kcal /day (LISS training of 65% of the heart rate reserve) that was interspersed by 3-4 days of high intensity workouts at 85% of the heart rate reserve ...
  

  "[...] increased the number of anti-inflammatory CD163⁺ macrophages (from 12.7 [2.1] (mean [SE]) to 16.1 [3.1] CD163⁺ cells/100 adipocytes, P=0.013), whereas diet-induced weight loss tended to decrease CD68⁺ macrophages in subcutaneous abdominal adipose tissue" (Auerbach. 2013)

  In that it is interesting to note that the most beneficial changes were observed in the group that compensated for the 600kcal extra energy expenditure per week.

  

  Figure 1: Effects of the 12 week diet + exercise / diet only / exercise only interventions on the body composition of caucasian overweight men aged 20-40 yrs w/ body fat >25% (Auerbach. 2013)

  Compared to the exercise + baseline diet and diet only (-600kcal energy reduction) group, they had a highly significant decrease in the TNF-alpha in the femoral adipose tissue ended and the greatest increase in anti-inflammatory CD163⁺ macrophage. 

• Carnitine rescues fast-twitch glycolytic macrofibers in a rodent study (Couturier. 2013) According to a recently published paper in Nutrition & Metabolism, the provision of carnitine as part of the diet did prevent the type-II-diabetes-induced transition of glycolytic to oxidative muscle fibers in obese Zucker rats.
  
  Now while you can never be sure if things that happen in a rodent model will also happen in man, it is not totally unlikely that these effects could be observed in human beings as well.
  

  

  Carnitine to prevent sugary fat gain

  "The results demonstrate that carnitine supplementation to obese Zucker a rat counteracts the obesity-induced muscle fiber transition and restores the muscle oxidative metabolic phenotype. Carnitine supplementation is supposed to be beneficial for the treatment of elevated levels of plasma lipids during obesity or diabetes. " (Couturier. 2013)

  The corresponding human equivalent dose to the 3g/kg of carnitine in the rodent chow would be would be roughly 16mg/kg or something between 1-2g per day for an adult human being (learn how to calculate HEDs). This is actually not really much and may well be worth a try, assuming that your own or your relatives' glucose burning, weight lifting musculature is endangered by diabetes.  

That's it for the short news!

In case you still have enough glycogen left in any of your major "tanks", or, alternatively, are depleted enough to have your body produce tons of ketones to fuel your brain for another 3-5 minutes you may yet want to take a brief look at the latest SuppVersity Facebook News...

• 

  With the relation of fish oil to prostate cancer (see facebook news) being based on high serum levels, I suggest you (re-)read this post about why fish oil supplements may fail to increase tissue levels, of way which previous studies have shown that they may protect against prostate cancer (read more).

  High or low fat for blood lipids? - Recent meta-analysis says: "The jury is still out there." The same appears to be the case for the type of fat, by the way | read more...
• Fish oil is bad for your prostate! - That's at least what the latest spin-off of the SELECT study (the one with selenium and vitamin E, you know?) says | read more...
• Green tea, butter and bread - Neither the most nutritious, nor the most yummy breakfast one can thing of, but way better for your triglyceride levels than water, butter and bread | learn why....
• Fat gains with saturated fats? Not if you pick the right ones - Study identifies interestification of saturated fat as a main determinant of its obesogenic effect. Regular palm oil, for example leads to lower fat gains than soy oil | read more...

... before you either eat, train sleep or have fun on the best day of the weekend: Saturday! ... What's so special about Saturday? Well easy, you can sleep late, shop, work out, party and whatever you like and sleep all the exertions and occasional "spiritual diversions" off on Sunday ;-)


References:

• Acordi da Silva et al. Effects of taurine supplementation following eccentric exercise in young adults. Applied Physiology, Nutrition, and Metabolism. 2013
• Auerbach P, Nordby P, Bendtsen LQ, Mehlsen JL, Basnet SK, Vestergaard H, Ploug T, Stallknecht BM. Differential effects of endurance training and weight loss on plasma adiponectin multimers and adipose tissue macrophages in younger, moderately overweight men. Am J Physiol Regul Integr Comp Physiol. 2013 Jul 10. [Epub ahead of print]
• Couturier A, Ringseis R, Mooren FC, Krüger K, Most E, Eder K. Carnitine supplementation to obese Zucker rats prevents obesity-induced type II to type I muscle fiber transition and favors an oxidative phenotype of skeletal muscle. Nutr Metab (Lond). 2013 Jul 10;10(1):48.
• Trewin et al. N-acetylcysteine alters substrate metabolism during high-intensity cycle exercise in well-trained humans. Applied Physiology, Nutrition, and Metabolism. 2013
• Gleeson, M. Biochemestry of Exercise in Maughan, Ronald J., ed. The Encyclopaedia of Sports Medicine An IOC Medical Commission Publication, Nutrition in Sport. Vol. 7. Wiley.com. 2008.

Science Round-Up Seconds: NAC Reduces Inflammation, Muscle Injury & Cytokine Expression, but Impairs Anabolic Signaling, Satellite Cell Activity and Recovery

Inflammatory cytokines won't build muscle, but without them your body won't notice that it's time to adapt.

As a SuppVersity student and listener of the SuppVersity Science Round-Up on Super Human Radio, you will be well aware of the fact that "inflammation" is a pretty loosely - or, I should say, lousily - defined and largely misunderstood term. What most people think of, when they hear the word has little to do with our bodies cytokine reponse (which is "inflammation") and is all about oxidative stress, which is one of the triggers of the release of cytokine. This is a process of which you've already learned that it plays a vitally important role in our bodies' ability to appropriately react to the wear and tear each and every of our cells is exposed to day by day, month by month and year by year. In fact, the misunderstood "inflammation" is a vital necessity to avoid the development of cancer. After all, it is the inflammatory response to the presence of degenerate cells that is what kills them before they can start to proliferate an turn into a systemic problem.

In this context, the feared "inflammatory" markers, IL-6 (interleukin 6) and TNF-alpha (tumor necrosis factor alpha) are of paramount importance as they are part of the singaling cascade that will have our bodies' own defenses target and cull the said degenerate cells before they become "immortal" cancer cells.

Inflammation and the adaptive response to exercise - the hormesis hypothesis

Figure 1: Health and longevity as a function of mitochondrial reactive oxygen species (ROS) formation (learn more)

That being said, previous studies in healthy human beings have yielded conflicting results as far as the effect of normal-to-large doses of exogenous anti-oxidants are concerned. According to scientists like Ristow and Schmeisser from the Department of Clinical Nutrition at the German Institute of Human Nutrition in Nuthetal, Germany, the suppression of the natural / normal cytokine response to the wear and tear of exercise will blunt the hormetic (=everything that does not kill you makes you stronger) response of which they believe that it drives the beneficial effects of working out.

Yet, while there are studies that would confirm this notion, the available data is by no means conclusive and a recent close review of the literature reveals that the consumption of "passive" anti-oxidants (e.g. vitamin C, vitamin E & co, i.e. molecules that simply eradicate reactive oxygen species and will thus blunt not regulate the cytokine response) appears to have either no, or detrimental effects in younger, relatively healthy individuals, the majority of the currently available data in older and sick individuals points to benefits of modest anti-oxidant supplementation.

We know that we know too little...

In short, we are still in the limbo as far as the "to use or not to use antioxidant supplements" question is concerned. Against that background I am grateful for every study that may help us solve this "mystery" and further our understanding of when a perfectly healthy and normal physiological response becomes pathologic and whether, when and for whom the use of specific anti-oxidants may be beneficial.

If you want to hear and learn more about the study at hand, the effects of other anti-oxidants and NSAIDs, and have not had the chance to listen live to yesterday's installment of the Science Round-Up on the Super Human Radio Network I suggest you download the show before you go on reading (click here to download).

Now without taking away too much in advance the latest of theses studies, I can already tell you that the actual outcomes of the latest study from the Democritus University of Thrace in Komotini and a couple of other European institutes, could confirm the scientists' hypotheses that the use of NAC [N-acetyl-cysteine; one of the most potent anti-oxidant supplements] during an 8-day eccentric and thus particularly "muscle damaging" exercise intervention would lead to an increase in GSH availability that would [...]

• ameliorate skeletal muscle performance by reducing inflammatory processes and exercise-induced muscle injury 
• attenuate intracellular redox dependent signaling pathways

and does nevertheless raise the question whether this really is something the average, healthy athlete should be looking for.

Figure 2: Allegedly beneficial effects on the irrelevant markers of inflammation, negative effects on what you are training for - the exercise induced increase in muscle protein synthesis (as evidenced by AKT, mTOR) and satellite cell incorporation (as evidenced by MyoD; adapted from Michailidis. 2013)

If you take look at the data I plotted in figure 2 it is quite obvious that the beneficial effects the participants, 10 healthy male volunteers with at least one month of thrice weekly strength training experience who consumed 20 mg NAC/kg per day (spread in three equal doses) dissolved in a 500-mL drink that contained water (375 mL), a sugar-free cordial (125 mL), and a 2-g low-calorie glucose/dextrose powder to improve palatability, experienced, namely ...

• an attenuation of the exercise induced elevation of inflammatory markers of muscle damage (creatine kinase activity, C-reactive protein, proinflammatory cytokines), nuclear factorkB phosphorylation, and 
• an amelioration of the damage-induced strength decrease during the first 2 d of recovery,

were  accompanied by a blunted increase in phosphorylation of protein kinase B, mammalian target of rapamycin (mTOR), p70 ribosomal S6 kinase, ribosomal protein S6, and mitogenactivated protein kinase p38 (MAPK) 2d and 8days after the workout.

Now, you could well argue that this is simply a result of less damage, right?

Was it mitohormesis that helped Walter Breuning live to the biblical age of 114 (learn more)?

It would at least seem logical that reductions in structural damage and (potentially - this was not accessed) loss of muscle protein in response to the 300 eccentric unilateral repetitions (20 sets, 15 repetitions/set, 30-s rest between sets) of leg extensions at a speed of 30°/s, the participants performed on an Isoforce (TUR Gmbh) isokinetic dynamometer, would entail a recuduction in compensatory protein synthetic response. In other words, with less damage the same amount of protein (re)synthesis that's insufficient to produce gains or at least restore the baseline protein content in the non-supplemented group could  well suffice to do just that in the NAC group.

(Unfortunately?) this is nothing but a neat hypothesis - one that is not supported by the results of the study at hand, in which the scientists also observed

• a blunted increase in myogenic (=satellite cell replenishing / recruiting and muscle repairing and building) factors and
• the failure to fully recover from eccentric exercise

in the supplement group. It goes without saying that the opposite should have been the case, if our neat hypothesis in defense of NAC supplementation as a means to increase athletic performance and muscle gains by buffering the exercise induced muscle damage, were true.

---

It's only logical that you wouldn't want to suppress the reactive oxygen species (green-yellow) too much, as their presence in the vicinity of muscle cells (blue) is not just a "stressor", but also important signal that will trigger and regulate the adaptive response to exercise (learn more)

Bottom line: NAC turns out to be an excellent example that well-meant interventions with outcomes that have classically been associated with positive health / performance effects (reduced CK, increased GSH, etc.) do not necessarily translate into beneficial real-world effects. In fact, the long(er)-term consequences of the attenuated cytokine (I am deliberately not using the term "inflammatory", here) response to exercise will probably be rather detrimental than beneficial for the more experienced healthy (young) physical culturist.

For other individuals which have to re-establish a healthy baseline level of glutathione and cut back on non-exercise induced oxidative damage (elderly, obese, diabetics, etc.), it may yet well be the other way around. These people may only be able to benefit from the exercise-induced cytokine response, if it is not drowned by an over-abundant amount of "pro-inflammatory" cytokines from other stressors.

References:

• Michailidis Y, Karagounis LG, Terzis G, Jamurtas AZ, Spengos K, Tsoukas D, Chatzinikolaou A, Mandalidis D, Stefanetti RJ, Papassotiriou I, Athanasopoulos S, Hawley JA, Russell AP, Fatouros IG. Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise. Am J Clin Nutr. 2013 May 29.

Speed Up Your Regeneration and Propel Your Gains by Taking a HOT Bath Bath 2-Days Before Arduous Workouts

Image 1: Are women tougher than men, because bathe more often? If you define toughness by your muscles resistance to eccentric exercise damage, the answer could be "YES!"

If you listened to Brooks, Carl and me on Super Human Radio, yesterday (download the podcast), you may remember me stating that 48h appears to be a good rule of thumb, as far as the rest periods between workouts for individual body parts are concerned (this assumes that you are young, healthy, reasonably conditioned and lift heavy). A recently published paper by Chad D. Touchberry  does now suggest that there may be another 48h window before your workout (Touchberry. 2012). One you would use a priori to improve your recovery a posteriori - preconditioning in a hot bath for 20 min at 41°C, 48h before a hard workout or competition!

Eccentric treadmill running = maximum muscle damage

At least in a rodent model, those 20 min of heat exposure in 41°C warm water lead to statistically highly significant decreases in exercise induced muscle damage, improved and accelerated the recovery process and, contrary to what could be assumed based on previous research on the expression of heat proteins (Frier. 2007), did not hamper, but promote muscle gains in response to an exercise protocol consisting that consisted of running at 18m/min down a -16% grade for 5 min. This protocol has been used as a model for injurious exercise repeatedly in the past and constitutes one of the standard tests in rodent, but also in human studies (e.g. Pumpa. 2011).

Figure 1: Creatine kinase (CK) activity and immune cell infiltration after eccentric exercise with (EE+HS) and without (EE) preconditioning via hot bath 48h before (data calculated based on Touchberry. 2012)

As the data in figure 1 goes to show, the hot bath (EE+HS) had significant ameliorative effects on both the muscle damage (indicated by CK and the black sections in the H&E-stained soleus muscle cross-sections in figure 1, right), of which the researchers state that, despite the fact that "the mechanism by which heat shock protects skeletal muscle from damage is currently unknown", the protection of skeletal muscle against damage in mice overexpresssing HSP70 (McArdle. 2004a) as well as the differential HSP72 elevation in the HS group 2h and 48 h following exercise collectively

[...] suggest that HSP72 or another heat sensitive protein (i.e.,alphaB-crystallin) may play a role in mediating cytoprotection of skeletal muscle cells.

Moreover, Touchberry et al. explain the existing discrepancies between their own results and previous results by Mc.Ardle et al. (Mc. Ardle. 2004b), who did not find reduced muscle damage after pre-treatment with hsp-inducing concentric exercise 10h prior to the (in my humble opinion questionable) in-vitro application of eccentric strain to skeletal muscle tissue, with the "greater time for HSP accumulation prior to the exercise stressor" in their (48h) vs. the Mc.Ardle study (10h), which is obviously yet another indicator that rest is one of the most under-appreciated determiners of workout efficiency (cf. my words on SHR ;-)

Regeneration is one thing, but are muscle gains another?

Now, I am well aware that one of the main reasons regeneration isn't sexy, is that it does not trigger the phosphorylation of Akt, m-TOR and all the rest of the sciency terms with which laymen are bombarded by the supplement industry these days.

Figure 2: Total protein, new myosin heavy chain (MHCNEO) content and p-Akt expression in soleus muscle 2h and 48h after the eccentric exercise bout (data calculated based on Touchberry. 2012)

The study at hand does even show that heat pre-treatment will actually reduce, not promote the phosphorylation of AKT 48h after the exercise bout (cf. figure 2). If you do yet take into account that the total protein concentration and MHCneo (novel myosin-heavy-chain motor proteins) content in the soleus muscle of the rodents was increased profoundly, I guess you will have to agree that it is unlikely that less damage, a faster regeneration, and as a consequence less need for protein to be recruited via p-AKT only to repair the damage is going to propel, not diminish your gains!

Practical implications & open questions

Once again, the obvious message of this study is: Not he who trains the most, but he who regenerates and rebuilds the best, gains the most! And adequate rest aside, preconditioning in a hot (not a "cold thermogenic" bath ;-) can help dampen the exercise induced damage and accelerate your recovery.

Note: In February 2012, Bayley et al. published a paper that shows that the application of passive heat in form of a 42°C hot water bath for 40min immediately prior to a bout of HIT leg extensor exercises reduced the time to fatigue in seven healthy men by a whopping -36%  (Bayley. 2012). Impatience, or rather the unwillingness to grant your body the time it needs to recover is thus detrimental even if the stressor is "just" a hot bath!

Whether the same would be true if you train today and do the hot water immersion immediately, 2h, 10h or 12h post and thus 48h, 46h, 38h or 36h before your next workout is yet about as questionable, as whether or not similar effects could be elicited by switching back and forth between light and heavy days every 48h.  Both may appear likely, but aside form the fact that the optimal timing or workout intensity will still have to be elucidated, are still in the state of an interesting research hypothesis, not more, but also not less.

Update - Suggested reading: Since there have been questions pertaining to the usefulness of hydrotherapy post-workout, i.e. as a means of "classic" re- and not "precovery", I thought I rather refer you directly to my buddy Sean's E-book on the issue. Here is a snippet from the book

Image 2: Don't miss Sean's free e-book on classic hydrotherapy

Quick Hit Summary Water therapy is a common modality to enhance muscle recovery post workout. Sitting in chest high thermoneutral water for 20-30 minutes may accelerate waste removal while increasing blood flow to working muscles. Cold, hot and contrast water temps are also commonly used to assist recovery. The goal of cold water therapy is to reduce inflammation whereas hot water purportedly increases muscle blood flow. Contrast water therapy involves alternating between hot and cold water baths to induce a vaso-pumping effect. Current evidence does not support the theory behind these latter 2 therapies simply because the heat (from the water) is incapable of penetrating more than a couple centimeters into the skin. Thus, there is no stimulus to increase muscle blood flow

You can get this e-book alongside two other books for free if you register for Sean's newsletter, which is, take my word on it (!), not a weekly advertisement piece!
 
References:

1. Bailey SJ, Wilkerson DP, Fulford J, Jones AM. Influence of passive lower-body heating on muscle metabolic perturbation and high-intensity exercise tolerance in humans. Eur J Appl Physiol. 2012 Feb 10.
2. Briese E. Normal body temperature of rats: the setpoint controversy. Neurosci Biobehav Rev. 1998 May;22(3):427-36. Review. 
3. Frier BC, Locke M. Heat stress inhibits skeletal muscle hypertrophy. Cell Stress Chaperones. 2007 Summer;12(2):132-41. 
4. McArdle A, Dillmann WH, Mestril R, Faulkner JA, Jackson MJ. Overexpression of HSP70 in mouse skeletal muscle protects against muscle damage and age-related muscle dysfunction. FASEB J. 2004a Feb;18(2):355-7.
5. McArdle F, Spiers S, Aldemir H, Vasilaki A, Beaver A, Iwanejko L, McArdle A, Jackson MJ. Preconditioning of skeletal muscle against contraction-induced damage: the role of adaptations to oxidants in mice. J Physiol. 2004b Nov 15;561(Pt 1):233-44. Epub 2004 Aug 26.
6. Pumpa KL, Fallon KE, Bensoussan A, Papalia S. The effects of Lyprinol(®) on delayed onset muscle soreness and muscle damage in well trained athletes: a double-blind randomised controlled trial. Complement Ther Med. 2011 Dec;19(6):311-8.
7. Touchberry CD, Gupte AA, Bomhoff GL, Graham ZA, Geiger PC, Gallagher PM. Acute heat stress prior to downhill running may enhance skeletal muscle remodeling. Cell Stress Chaperones. 2012 May 17. [Epub ahead of print]

Exercise Velocity Does not Determine Hypertrophy Signaling in Eccentric Exercises: Akt, mTOR, P70s6k Protein Phosphorylation Identical for Fast and Slow Movements

Finally, a study (Roschel. 2011) related not only to nutrition and supplementation for exercise, but to exercise itself! The respective paper was published in the Applied Physiology, Nutrition, and Metabolism on April, 13th, and reports the results of a study on the effects of exercise velocity on markers of muscle hypertrophy, specifically, Akt/mTOR/p70^s6k.

Figure 1: Schematic illustration of the mTOR signaling cascade (Betz, Charles. Wikipedia)

Roschel, et al. had 20 subjects, "not enrolled in any form of strength training for at least 6 months prior to the
study and without any history of musculoskeletal disorders" perform 5 sets of 8 repetitions of an eccentric knee extension exercise at either a slow (20°·s^–1; ES) or fast execution speed (210°·s^–1; EF). After the workout, biopsies were taken from vastus lateralis at three timepoints: baseline (B), immediately after (T1), and 2 h after (T2). The results did not confirm the scientists' working hypothesis that execution velocity (and thus muscle tension) would have a direct influence on Akt, mTOR, and p70^S6K expression in the trained muscles:

Akt, mTOR, and p70^S6K total protein were similar between groups, and did not change postintervention. Further, Akt and p70^S6K protein phosphorylation were higher at T2 than at B for ES and EF. MGF messenger RNA was similar between groups, and only significantly higher at T2 than at B in ES.

So, with respect to the measured variables and in the confounding case of eccentric exercises, it does not matter whether you whack your reps out at maximum speed (assuming you still maintain adequate form) or try to slow the movement down deliberately. I guess this, aside from their (ab-)use certain "supplements", is why Coleman and Co. grew monstrous muscles despite training with the worst form you could probably think of.

Remember though, the results could be completely different for concentric exercises, like pressing movements or for equal times under tension, meaning 10x more repetitions in the EF group to make up for the total time difference. Results from previous studies, such as Farthing and Chilibeck (2003) and Shepstone et al., for example suggest that compared to slow training a faster (yet still controlled) exercise execution is linked to greater hypertrophy of the elbow flexor, in general, and the biceps' type IIa (+16%) and type IIx (+18%), in particular. I guess future studies will further elucidate the exact mechanisms and guess what: the SuppVersity is where you will read about them, first!

Beyond Satellite Cells: Eccentric Training Bullies Bystanding Stem Cells, Destined to Become Bone, Cartilage, Adipose or Nerve Tissue into Contributing to Skeletal Muscle Growth

Image 1: Apart from their epistemic value, these stained tissue samples from the Valero study are actually pretty aesthetic.The arrows, by the way, mark NG2 monocytes, which "coerce" the non-myogenic stem cells (perycites) to get going ;-)

I guess, the term "satellite cells" has been mentioned so often in the course of the past couple of weeks that it actually would not be necessary to tell you (once again) that these myogenic precursor cells are a necessary prerequisite for the repair and long-term growth of your pecs, legs, back, biceps, triceps, delts and the rest of the skeletal muscle tissue in your body. Those of you, who have read all the latest installments of the Intermittent Thougths will also be familiar with the notion that both the local expression of MGF-1 and inflammatory cytokines, as well as systemic hormones, such as testosterone and estrogen play an important role not only in the recruitement and migration of satellite cells into the muscle, but also in their regeneration and maintenance (cf. "Are You Serming Away Your Growth Potential"). A group of scientists from the University of Illinois must however have figured that this is not yet complicated enough and began digging even deeper into the (re-)generation of (new) muscle tissue... and let me tell you, what they found is intriguing.

Eccentric training is "numero uno" for satellite cell recruitment

I guess you will be aware that it is a relatively well-established fact that of all real-world physical activities eccentric, or lengthening, contractions of skeletal muscle appears to constitute the most potent inducer of both "productive" exercise induced muscle damage, as well as subsequent increases in satellite cell recruitment.

Figure 1: Changes in intramuscular architecture in young and old subjects in response to 6 sets of eccentric leg extensions (data calculated based on Dreyer. 2006)

Back in 2006 Dreyer et al. published the results of a study which compared the satellite cell response to an eccentric exercise regimen (1x12 + 5x16 eccentric-only reps on leg-extension machine) in young and old subjects (Dreyer. 2006). As the data in figure 1 goes to show, this unquestionably exhaustive bout of exercise produced a quite remarkable (>150%) increase in satellite cell volume per muscle fiber and a likewise highly significant (>100%) increase in the number of satellite cells compared to the total number of cells in the sublaminar compartment. It is also evident from the data in figure 1 that the preparatory accumulation of satellite cells 24h after the eccentric exercise-bout was profoundly blunted in the older subjects.

Figure 2: Satellite cell count per myonucleus before and 8d after 100reps of eccentric leg extensions in untrained young subjects (data adapted from Mikkelson. 2009)

Note: As you can see in figure 2, age is yet not the only factor that can compromise the adaptive response to eccentric lengthening contraction of skeletal muscle. Mikkelson et al. who had the (young) participants of their study perform 100 eccentric reps on a similar leg-extension machine (Mikkelson. 2009), for example, found that an indomethacin (NSAID; COX-inhibitor) infusion for 7.5 h during the exercise day did not only blunt the increase in pax-7+/myonuclei, or in "layman's terms", satellite cells 8 days after the exercise session, the combination of exercise and NSAID actually led to a slight and statistically obviously non-significant reduction in satellite cells per myonucleus. This does support the findings, I discussed in one of the previous installments of the Intermittent Thoughts, which dealt with the importance of "inflammation" as a vital constituent of both the repair and hypertrophy response to exercise induced muscle-damage (cf. "IGF-1, IL-15 & Co").

The age-related decline in satellite cell activity unquestionably raises a question Lerner addressed in one of his insightful comments on my post on the important role of estrogen for the maintenance of the satellite cell pool, which is whether or not the latter would be limited... I mean, when the whole craze about stem-cell therapy began, the general accepted notion appeared to be that the average adult human being has a very limited / if any of those "super cells".

If you have been following recent publications, you will yet be aware that as of late researchers (interestingly also from the University, I work at ;-) have made quite some progress in "producing" and "reprogramming" stem cells from all sorts of human and animal tissue. Assuming that you have also read everything about how testosterone works its "muscle building and fat burning magic" (cf. "Understanding the Big T"), you should also be aware that the latter, i.e. the "fat burning" effect is at least partly mediated by the reprogramming of stem cells which are actually supposed to become fat cells into "satellite cells". All that being said, it should actually not surprise you that the main finding of the initially mentioned study is that eccentric contractions of skeletal muscle have a very similar effect on "non-myogenic" stem cells, which "happen to be in the vicinity of the exercised muscle fibers".

A study on You, Wolverine and the Ultimate Hard Gainer

Unfortunately, the design of the study by M. Carmen Valero and her colleagues from the Department of Kinesiology and Community Health at the University of Illinois is... well, let's say not exactly straight-forward, or easy to understand (Valero. 2012). Basically, the scientists took 3 types of muscle fibers from rodents,

Figure 3: Localization of stem cell antigen-1 (Sca-1) (arrows, TRITC-red) positive mononuclear cells and a-7 integrin (FITC-green) in the different muscle tissue before (SED) or 24 hr post-exercise (Ex) at 20x magnification (adapted from Valero. 2012)

• wild type, as a normal control (that would be your muscle ;-)
   
• alpha-7 integrin transgenic (a7TG), which is resistant to injury, but still responsive to strain (I guess that is either the "Wolverine" or "Unbreakable" type of muscle tissue ;-), and
   
• alpha-7 (-/-), which is the "ultimate hard gainer muscle" that does not respond with alpha-7 integrin expression to overload

Now, even if you don't understand a word of what I am talking about here, I guess that you will be able to see the significant color-differences in the immuno-stained (=marked by antibodies) tissue samples in figure 3. If you just focus on the arrows, the red and green areas, that should suffice to grasp the idea that the both the stretch induced alpha-7 integrin response, as well as the number (arrows) and area (red staining) of stem cells in are maximal in the Wolverines, "normal" in guys and gals like you and minimal to non-existant in the "ultimate hard gainer".

The first take-home message of this study is thusly that the strain that is induced by eccentric training activates "dormant" stem cells via alpha-7 integrin. Why this is the case, becomes clear when you look at the structure of those heterodimers, which transverse the cell membranes of regular muscles and adhere the extracellular matrix to the cytoskeletal network. If you strain the muscle, this will obviously affect the integrin system, which thusly functions as a "sensor" for mechanical signals.

"No satellite cell available? Well I guess we just take this one, then..."

Upon closer analysis of the "satellite cells" that actually responded to the alpha-7 integrin signals, the scientists did yet realize that the resource from which the majority of the new muscle cells were recruited were actually mesenchymal stem cells, which are usually destined to become osteoblasts (bone), chrondocytes (cartilage) and adipocytes (fat cells):

In this study, we provide the first demonstration that muscle resident mesenchymal-like stem cells (mMSCs), predominantly pericytes, are increased in muscle in an a-7 integrin dependent
manner following an acute bout of eccentric exercise. mMSCs maximally appeared in a7BX2 transgenic muscle resistant to injury following eccentric exercise and were rarely present in
muscle lacking the a-7 integrin, suggesting that factors other than injury or inflammation are primary regulators of mMSC accumulation in skeletal muscle.

In view of the fact that a preliminary experiment in which the scientists transplanted exogenous mMSCs into the muscle of living mice, led to a very localized, but distinctly measurable increase in new fibers opens a whole new venue for research into the artificial enhancement of skeletal muscle hypertrophy... for you as an avid (and probably "natural") trainee, however, the main take home message is that exercise, in this case, the strain (not the damage!) that is induced by eccentric lengthening contractions of your muscles still appears to be the major determinant of all aspects of skeletal muscle hypertrophy. Don't forget that, when you are about to invest the next few hundred bucks into whatever "myogenic" supplement the guy at GNC is trying to persuade you into buying... without hard and consistent work at the gym those powders and caps are pretty useless.