Upper Body Workout Doesn't Impair 48h Leg-Day Recovery, Lactobacillus for Immunity & Alcohol Impairs Your Gains

PWO alcohol is not for male athletes. But before you rejoice, ladies. The ill health effects of a given amount of alcohol are more severe for the fairer sex.

It's Christmas! And you can almost smell the new year with its smell of alcohol approach... and that's bad news for your gains, as a recent study in the latest issue of the Journal of Strength and Conditioning Research shows. With a study on the possible interference of upper body training on your leg-day recovery (Abaïdia. 2017), and the purported benefits of lactic acid bacteria for athletes' immunity (Michalickova. 2017), Duplanty's study, which shows that alcohol will impair the adaptation to resistance training in previously resistance trained men, but not female trainees w/ RT experience (Duplanty. 2017), constitutes what's probably going to be the last SuppVersity Science Update for 2016.

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• Doing an upper body workout after muscle damaging "leg day" won't impair your recovery, study shows (Abaïdia. 2017) -- The purpose of this study was to investigate the effects of an upper-limb strength training session the day after an exercise inducing muscle damage on recovery of performance.
  
  

  

  Figure 1: Creatine kinase (CK) and muscle force recovery ofter the 48h period w/ and w/out upper body exercise on the day after the leg workout (Abaïdia. 2017).

  In a randomized crossover design, subjects performed the day after the exercise, on 2 separate occasions (passive vs. active recovery conditions) a single-leg exercise (dominant in one condition and nondominant in the other condition) consisting of 5 sets of 15 eccentric contractions of the knee flexors. Active recovery consisted of performing an upper-body strength training session the day after the exercise. Creatine kinase, hamstring strength, and muscle soreness were assessed immediately and 20, 24, and 48 hours after exercise-induced muscle damage.
  
  The upper-body strength session, after muscle-damaging exercise accelerated the recovery of slow concentric force (effect size = 0.65; 90% confidence interval = −0.06 to 1.32), but did not affect the recovery kinetics for the other outcomes. The addition of an upper-body strength training session the day after muscle-damaging activity does not negatively affect the recovery kinetics.
  
  "Upper-body strength training may be programmed the day after a competition," the authors conclude and rightly so, after all their efforts to measure Creatine kinase, hamstring strength, and muscle soreness does indeed provide reliable information about the subjects' recovery.
• Lactobacillus helveticus Lafti L10 as an immune booster for elite athletes (Michalickova. 2017) -- To test the influence of probiotic supplementation on humoral immune response, a double-blind, placebo-controlled trial was conducted. Thirty athletes (24 males and 6 females, females: V_O2max 38.2 ± 4.9 ml·kg−1·min−1, age 23.2 ± 1.4 years; males: V_O2max 57.5 ± 9.2 ml·kg−1·min−1, age 24.0 ± 2.4 years, mean ± SD) were randomized either to the probiotic group (Lactobacillus helveticus Lafti L10, 2 × 1010 colony-forming units) or to the placebo group. Serum and saliva samples were collected at the baseline and after 14 weeks. Total and specific antibacterial antibody levels of IgM, IgG, and IgA classes were determined for different bacteria in the serum, and in saliva, total and specific antibacterial IgA levels were examined.
  
  

  

  Teddy bears are like vitamin C and zinc. They can help you when you are already sick, but what are supplements athletes and gymrats take in advance to survive the flu season without getting sick at all?

  The scientists' analyses showed: Total IgM was elevated in both probiotic (18%, 15–20%; mean, 90% confidence interval; p = 0.02) and placebo group (35%, 22–47%; p = 0.02), without observed differences in changes between the groups. No significant changes in IgM levels specific for tested bacteria were found. Total IgG level was constant in both groups. A significant (16%, −2.8 to 35%, p = 0.04) reduction of anti–Enterococcus faecalis IgG was noted in the placebo group, in comparison with the probiotic group.
  
  There was a substantial decrease in total IgA level in the placebo group, when measured either in serum (15%, 12–18%, p = 0.04) or in saliva (35%, −1.4 to 53%, p = 0.03).
  
  Significantly reduced levels of serum anti–lactic acid bacteria IgA antibodies in the placebo group compared with the probiotic group were detected for Lactobacillus rhamnosus LA68 (24%, 5.8–42%, p = 0.02) and for L. rhamnosus LB64 (15%, 2.7–27%, p = 0.02).
  
  Nice? Well, there's one word in the scientists' conlusion I want you to pay specific attention to the small word "could" in "Probiotic administration could have beneficial effects on systemic humoral and mucosal immune responses" (Michalickova. 2017).
• Alcohol post-workout = impaired gains, at least in men (Duplanty. 2017) -- If this is not surprising to you, you must be unaware of the mixed evidence from previous studies on the impact of alcohol on post-workout protein synthesis.
  
  

  

  Figure 2: Bar graphs represent the quantification of western blot images for proteins (phosphorylated proteins relative to total proteins and normalized to a-tubulin | Duplanty. 2017).

  The purpose of the latest study on this subject was to further elucidate the effects postexercise alcohol ingestion.
  
  In that, the study had many novel aspects including using a resistance exercise (RE) only exercise design and the inclusion of women. Ten resistance-trained males and 9 resistance-trained females completed 2 identical acute heavy RE trials (6 sets of Smith machine squats) followed by ingestion of either alcohol or placebo.
  
  All participants completed both conditions. Before exercise (PRE) and 3 (+3 hours) and 5 (+5 hours) hours postexercise, muscle tissue samples were obtained from the vastus lateralis by biopsies. Muscle samples were analyzed for phosphorylated mTOR, S6K1, and 4E-BP1.
  
  For men, there was a significant interaction effect for mTOR and S6K1 phosphorylation. At +3 hours, mTOR and S6K1 phosphorylation (unlike mTOR S6K1 is usually a reliable marker of protein synthesis) was higher for placebo than for alcohol.
  
  For women, there was a significant main effect for time. mTOR phosphorylation was higher at +3 hours than at PRE and at +5 hours.  There were no significant effects found for 4E-BP1 phosphorylation in men or women.

  "The major findings of this study was that although RE elicited similar mTORC1 signaling both in men and in women, alcohol ingestion seemed to only attenuate RE-induced phosphorylation of the mTORC1 signaling pathway in men" (Duplanty. 2017)

  Yes, guys, that's right: alcohol should not be ingested after RE as this ingestion could potentially hamper the desired muscular adaptations to RE by reducing anabolic signaling. The one thing that's still necessary, now, is a study investigating the dose-response effect and whether it takes vodka (40% vol/vol alcohol; Smirnoff Co., Norwalk, CT, USA) diluted in water at a concentration of 15% vol/vol absolute alcohol and thus a dose of 1.09 g of alcohol per kg of fat-free body mass to do the ergolytic trick.

Health food for sick people - Much better than cholesterol supplements ;-) -- Cholesterol Boosts Your Immune Defenses: Infections Can Lower Cholesterol, Extra-Chol. Will Help You Battle Them | Learn more

So, here's what you should remember: (1) You can do upper body workouts the day after hitting your legs without compromising your muscular recovery, but you must not forget that your central nervous system needs time to recover, too. Accordingly, the long-term performance effects of doing this regularly may differ significantly with the CNS beating taking it's toll after a certain number of back to back workouts. (2) Your immunity could benefit from lactobacillus supplements, but don't dare paying for these supps before you don't get at least enough cholesterol to fuel your immune function. (3) As a man, you want to pay particular attention not to go overboard on alcohol, as it appears to have sign. more pronounced effects on you compared to your significant other | Comment! 

References:

• Abaïdia, A-E, Delecroix, B, Leduc, C, Lamblin, J, McCall, A, Baquet, G, and Dupont, G. Effects of a strength training session after an exercise inducing muscle damage on recovery kinetics. J Strength Cond Res 31(1): 115–125, 2017.
• Duplanty, AA, Budnar, RG, Luk, HY, Levitt, DE, Hill, DW, McFarlin, BK, Huggett, DB, and Vingren, JL. Effect of acute alcohol ingestion on resistance exercise–induced mTORC1 signaling in human muscle. J Strength Cond Res 31(1): 54–61, 2017
• Michalickova, DM, Kostic-Vucicevic, MM, Vukasinovic-Vesic, MD, Stojmenovic, TB, Dikic, NV, Andjelkovic, MS, Djordjevic, BI, Tanaskovic, BP, and Minic, RD. Lactobacillus helveticus Lafti L10 supplementation modulates mucosal and humoral immunity in elite athletes: a randomized, double-blind, placebo-controlled trial. J Strength Cond Res 31(1): 62–70, 2017.

Panaxatriol - Ginseng Constituent Has Protein-Anabolic Effects When It's Administered After Resistance Training

Warning: It's too early to stockpile ginseng or ginseng capsules, yet... the independent jury is still out there.

Ginseng is not exactly the agent you will think about when you hear the word "natural anabolic". And in fact, previous studies using whole ginseng or extracts that were usually standardized for ginsenosides shown to help with dementia in athletes were not exactly encouraging.

Against that background, I have to warn you right away (I will repeat my warning in the conclusion) that you should not rush to the next best supermarket or supplement store to get a bag of ginseng roots or pills.

Why's that? Well, you cannot be sure that they contain enough of Panaxatriol, which is the active ginseng saponoid that worked the muscle building magic in the latest sponsored proof-of-concept study from Japan. A rodent study (another reason not to literally buy into the hype, yet), yes, albeit one with results I consider worth reporting... if nothing else, because I expect this agent to be part of yet another kitchen-sink "natural anabolic" supplement in the near future.

In contrast to PT, a high protein intake has been proven to be sign. protein anabolic

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So what do you have to know? Well, it has long been known that the anti-hyperglycemic mechanism of ginseng involves upregulation of Akt signaling and that it owes its nerve-regenerating effects to an upregulation of ERK1/2 signaling. Since these proteins also figure in skeletal muscle protein synthesis, it was only logical for Takamura et al. to assume that "ginseng could increase muscle protein synthesis via the Akt-mTORC1 or ERK1/2-mTORC1" (Takamura. 2016).

Since previous studies suggested that the Panaxatriol saponins are responsible for the effects on Akt and ERK1/2, it was only logical for the Japanese researchers to use isolated panaxatriol saponins, which have an excellent bioavailability, because the interaction with the gastric acid and the enzymes of intestinal bacteria cleaves the branched-chain sugars from the saponins and turns them into active Panaxatriol (PT), in their study. A study on Sprague-Dawley rats, whose legs were divided into control, PT-only, exercise-only, and exercise + PT groups. As the authors explain, "[t]he right legs were subjected to isometric resistance exercise using percutaneous electrical stimulation, while the left legs were used as controls" (Takamura. 2016).

Figure 1: Effects of PT on rpS6 phosphorylation at Ser240/244 0.5 h (A) and 3 h (B) after resistance exercise (Takamura. 2016); Con, control; EX, exercise; PT, panaxatriol; A.U., arbitrary unit

Interestingly enough, the isolated PT was administered only once and after the "workout" at a dose of 0.2 g/kg - 30 mg/kg for a human being (so ~1.8 - 3g of Panaxatriol) and yet it had the effects the scientists had expected: the treatment did not just elevate the Akt and ERK1/2 phosphorylation in the PT treated animals significantly over the exercise-only group, it also triggered highly significant elevations of the downstream controller of muscle protein synthesis, p70S6K, which was significantly increased at both 0.5 h and 3 h after exercise.

Figure 2: Effects of PT on muscle protein synthesis 3 h after resistance exercise. Representative images of western blot analysis with anti-puromycin (Takamura. 2016).

Now you may rightly be arguing that this is all nice, but irrelevant. After all, it's the actual protein synthesis that counts, not the elevation of regulatory proteins. Indeed, you're right, but by the means of the relatively new, but tested SUnSET method (Goodman. 2013), Takamura et al. were able to detect a significant increase in protein synthesis in the rodents that received the PT supplement immediately after their "workout".

The extent of the increase, however, cannot be accurately quantified by this method. Accordingly, we know that the increase in the protein synthesis gauge p70S6K actually triggered increases in protein synthesis, but we don't know if the effect size of this increase was practically relevant.

Yes, you're right, ginseng was also on the list of 20 that may help you stay lean after you lost weight | more.

Beware! Don't buy the next best ginseng supplement! Even though panaxatriol saponins are abundant in ginseng, you can hardly tell how much you had to ingest to arrive at the human equivalent of the effective dose, i.e. 30 mg/kg.

And even if you got the dosage right, you do not know how practically significant and sustainable (maybe that's a one-time thing, or one will become resistant over time) the increase in protein synthesis the authors didn't quantify will actually be. Ah, ... and yes: the fact that this is a sponsored rodent study, obviously doesn't make its results more reliable, either | Comment on Facebook!

References:

• Goodman, Craig A., and Troy A. Hornberger. "Measuring protein synthesis with SUnSET: a valid alternative to traditional techniques?." Exercise and sport sciences reviews 41.2 (2013): 107.
• Takamura, Yusuke, et al. "Panaxatriol derived from ginseng augments resistance exercised–induced protein synthesis via mTORC1 signaling in rat skeletal muscle." Nutrition Research (2016).

Maximal Protein Synthesis in the Elderly: How Much Protein Does it Take? Another Study to Suggest More is Better!

Maximal protein synthesis requires protein, but how much exactly you need will depend on your age - the older you are the more PWO protein you'll need.

Scientists from the University of Auckland were fed up with the lack of information about the differential response in protein synthesis in response to the ingestion of various amounts of protein. Accordingly, Randall F. D’Souza et al. conducted a study to characterize the changes in intramuscular levels of EAAs and BCAAs and the expression of the "protein pump" p70S6K at Thr389, a marker of protein synthesis, in response to resistance exercise and graded ingestion of whey protein in older men.

As a regular SuppVersity reader you will probably already think: "Where is the actual measurement of the fractional protein synthesis?" The unfortunate answer: It's not there.

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Previous research had show that the ingestion of graded amounts of high-quality protein such as whey after resistance will maximize with "only" 20g of egg protein (Moore. 2009) or whey (Witard. 2014) in young men. Multiple studies in older adults (>60 years), on the other hand, suggest that they exhibit a lower anabolic signaling and MPS response to protein feeding, resistance exercise, and the combination of feeding and exercise when compared to young men (Cuthbertson. 2005; Fry. 2011; Burd. 2013). Scientists call this phenomenon age-related "anabolic resistance" (Yang. 2012b).

Figure 1: In contrast to the fractional protein synthesis in the elderly, which increases with increasing amounts of protein, the FSR of young men shows a ceiling effect at 20g+ whey protein (Yang. 2012a; Moore. 2009)

As you can see in Figure 1 from a 2012 study by Yang, the same 20g of extra-whey (total dose 40g) that was useless in young men, lead to a significant increase in protein anabolism in elderly men. Compared to young men, the MPS response to feeding 40 g of protein was yet still slightly lower in older vs. count men (Yang. 2012a; Churchward Venne. 2013b).

What is particularly relevant for the study at hand, and the previously criticized absence of actual MPS measurements is the fact that deficits in feeding induced p70S6K phosphorylation may at least partially underpin anabolic resistance in aged skeletal muscle (Cuthbertson. 2005), which is why measuring the p70S6K phosphorylation in older human subjects (mean age 71 years) in response to the graded ingestion of whey protein after a leg workout consisting of three sets of 8–10 repetitions of bilateral barbell smith rack squat, 45°leg press, and seated knee extensions at 80% of the subjects' predetermined 1R is not as irrelevant at it may initially have seemed.

Workout + supplements, that's the "whey to go" ;-)

The exercises were performed in a circuit manner with 1 min rest between each exercise and 3 min rest between subsequent sets, the exercise protocol took approximately 20 min to complete. Following completion of the exercise protocol, subjects were immediately provided with a fixed-volume (350 mL) beverage, containing a flavored noncaloric placebo, or oneof the four doses of whey protein concentrate (10 g, 20 g, 30 g, or 40 g).

Figure 2: Intramuscular amino acids. This figure is a heat map which shows groups means fold changes from the resting fasted condition. Green represents a decrease in amino acid content, white represents no change, and red represents an increase in amino acid content (D’Souza. 2014)

Subjects were instructed to ingest the beverage within 2 min and were required to ingest the total volume provided. Following consumption of the supplements, subjects rested in a supine position throughout the 4 h of post-exercise recovery with additional muscle biopsy samples collected at 2 and 4 h post exercise.

Figure 3: Higher protein intake = higher increase in p70S6K phosphorylation (left graph). This increase is linearly associated with intramuscular leucine levels (right graph | both from D’Souza. 2014)

As you can see in Figure 3, there was a similar dose-dependent increase in p70S6K as it was observed previously for MPS in skeletal muscle of elderly subjects by Yang et al. (2012b). In fact, the fold change in the phosphorylation of p70S6K (Thr389) at 2 h post exercise was correlated with the dose of whey protein consumed (r =0.51,P<001) and was found to be significantly correlated with intramuscular leucine content (r =0.32,P=0.026).

Moreover, the intramuscular BCAAs, and leucine in particular, appear to be important regulators of anabolic signaling in aged human muscle during post-exercise recovery via reversal of exercise-induced declines in intramuscular BCAAs.

Suggested Read: "Protein Timing Does Matter! Yet Only in Trained Men. More Than 2x Higher Relative Protein Retention W/ Immediate vs. 6h Post Whey Consumption in Bodybuilders vs. Rookies" | read more.

Bottom line: In the absence of a young control group and actual muscle protein synthesis (MPS) measurement, the study at hand cannot finally answer the question, whether older men require higher amounts of protein than young ones to achieve maximal increases in post-workout protein synthesis, but it is at least another piece of evidence that "more helps more" - at least in the elderly.

As mentioned in other recent posts, there are yet still many confounding variables that would have to be controlled and modified as well to answer the important (?) question: "How much protein does it take to achieve maximal post-workout protein synthesis?" Which confounding factors that would be? Well, what about the training experience? The baseline muscle mass? The protein content of the diet? And so on and so forth || Comment on Facebook!

References:

• Burd, N. A., S. H. Gorissen, and L. J. van Loon. 2013.  Anabolic resistance of muscle protein synthesis with aging. Exerc. Sport Sci. Rev. 41:169–173.
• Churchward-Venne, T. A., N. A. Burd, C. J. Mitchell, D. W. West, A. Philp, G. R. Marcotte, et al. 2012. Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men. J. Physiol. 590:2751–2765.
• D'Souza, Randall F., et al. 2014. Dose‐dependent increases in p70S6K phosphorylation and intramuscular branched‐chain amino acids in older men following resistance exercise and protein intake. Physiological Reports 2.8: e12112.
• Churchward-Venne, T. A., L. Breen, and S. M. Phillips. 2013a. Alterations in human muscle protein metabolism with aging: protein and exercise as countermeasures to offset sarcopenia. BioFactors 40:199–205.
• Churchward-Venne, T. A., C. H. Murphy, T. M. Longland, and S. M. Phillips. 2013b. Role of protein and amino acids in promoting lean mass accretion with resistance exercise
  and attenuating lean mass loss during energy deficit in humans. Amino Acids 45:231–240.
• Churchward-Venne, T. A., L. Breen, D. M. Di Donato, A. J. Hector, C. J. Mitchell, D. R. Moore, et al. 2014. Leucine supplementation of a low-protein mixed macronutrient beverage enhances myofibrillar protein synthesis in young men: a double-blind, randomized trial.
  Am. J. Clin. Nutr. 99:276–286.
• Cuthbertson, D., K. Smith, J. Babraj, G. Leese, T. Waddell, P. Atherton, et al. 2005. Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J. 19:422–424.
• Moore, D. R., M. J. Robinson, J. L. Fry, J. E. Tang, E. I. Glover, S. B. Wilkinson, et al. 2009. Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men. Am. J. Clin. Nutr. 89:161–168.
• West, D. W., and K. Baar. 2013. May the Force move you: TSC-ing the mechanical activation of mTOR. J. Physiol. 591:4369–4370.
• West, D. W., N. A. Burd, J. E. Tang, D. R. Moore, A. W. Staples, A. M. Holwerda, et al. 2009a. Elevations in ostensibly anabolic hormones with resistance exercise enhance neither training-induced muscle hypertrophy nor strength of the elbow flexors. J. Appl. Physiol. 108:60–67 .
• West, D. W., G. W. Kujbida, D. R. Moore, P. Atherton, N. A. Burd, J. P. Padzik, et al. 2009b. Resistance exercise-induced increases in putative anabolic hormones do not enhance muscle protein synthesis or intracellular signalling in young men. J. Physiol. 587:5239–5247.
• Witard, O. C., S. R. Jackman, L. Breen, K. Smith, A. Selby, and K. D. Tipton. 2014. Myofibrillar muscle protein synthesis rates subsequent to a meal in response to increasing doses of whey protein at rest and after resistance exercise. Am. J. Clin. Nutr. 99:86–95
• Yang, Y., L. Breen, N. A. Burd, A. J. Hector, T. A. Churchward-Venne, A. R. Josse, et al. 2012a. Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. Br. J. Nutr. 108:1780–1788.
• Yang, Y., T. A. Churchward-Venne, N. A. Burd, L. Breen, M. A. Tarnopolsky, and S. M. Phillips. 2012b. Myofibrillar protein synthesis following ingestion of soy protein isolate at rest and after resistance exercise in elderly men. Nutr. Metab. 9:57.

Can You Build Muscle By Depriving it of Glucose? Muscle Cells Increase Protein Synthesis After Only 3 Minutes of Running on Empty, But Beware of Jumping to Conclusions

Unless you're already infected with carbophobia and the "oh god, I got to not eat after a workout to maximize growth hormone"-bullshit-viruses, it sounds awkward that glucose deprivation should increase protein synthesis, but in the end, it all depends on the right circumstances

It may sound stupid and certainly not like something you would read on the SuppVersity, one of the few places on the Internet that has not been infected with "carbophobia", yet, but it's actually exactly what a recent study from the , University of Napoli "Federico II" suggests: Muscular glucose deprivation promotes the activation of mTOR signaling pathway and will thus increase protein synthesis!

And no, we are not talking about even more cognitive masturbation and theoretical considerations, here. The conclusions Maria Concetta Miniaci and her colleagues present in the latest issue of Pflugers Arch - Eur J Physiol are in fact based on experimental evidence - experimental evidence that is, if you think it through - not contradicting its practical counterpart!

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Evidence from a rodent in vitro study, but evidence of which not just Miniaci et al. (2014) but also I am confirmed that it is relevant for humans, as well.

In a way you may say that Miniaci et al. were inspired by the increased interest in the pro-anabolic effects of blood flow restriction. Corresponding studies using aterial and venous compression, induced by either muscle contraction at high intensity or by pressure cuff will, as the scientists point out, induced "short reduction of blood flow and therefore a reduced delivery of nutrients to the muscle" (Barcroft. 1939; Schwartz. 2000).

"Since glucose is an important energy substrate for skeletal muscle, we presumed that a brief period of glucose deprivation may trigger, as metabolic stress, the anabolic signaling cascade leading to an increased rate of protein synthesis when blood flow recovers and all nutrients are again available (Holloszy. 1996)." (Miniaci. 2014)

To test this hypothesis, the scientists investigated the effect of glucose deprivation on mTOR signaling and protein translation in L6 cell line, "a well established in vitro model system for studying skeletal muscle physiology" (Miniaci. 2014); and their results demonstrate that glucose deprivation upregulates mTOR and its downstream target the ribosomal S6 kinase (p70S6K), through the activation of NO/PI3K/Akt/mTOR/p70S6K signaling pathway.

Figure 1: Glucose deprived and thus stressed muscle cells increase mTOR and p70S6K and show an increase in protein synthesis after only a short time of "running on empty" (Miniaci. 2014)

Now, the interesting thing is that the observed results are pretty similar to what we see in response to regular resistance training, as well. The "pump induced" occlusion of the regular nutrient flow, as well as the acute (!) glucose deprivation in response to exercise could thus be more than casually related to the post-workout increase in protein synthesis. They could, and this is also what the scientists believe, actually be mechanistically involved in the post-workout increase in protein transport into the skeletal muscle.

mTOR, AMPK, NOS and good (=EU-)stress

In that, auxiliary data from the study at hand showed that the post-workout increase in protein synthesis is directly related to an increase in (surpris!) nitric oxide synthesase activtiy (this is the stuff that is not increased by the mere provision of the NOS substrate arginine, so that corresponding pump-supplements pretty useless). As the Italian researchers point out, NOS is activated in L6 cells exposed to glucose deprivation. Why this is the case, however is still unclear.

"[It] is likely that an increase in AMPK activity, in response to energy depletion, can account for activation of NOS. Indeed, NOS and AMPK can interact through a positive feedback loop. In particular, AMPK has been found to phosphorylate and activate skeletal muscle NOS inducing an increase in glucose uptake." (Miniaci. 2014)

If AMPK is in fact the main link, here, the findings of the study at hand, would - just like previous studies on exercise induced increases in glucose uptake lead us back to one surprisingly positive mechanism, which triggers both, glucose uptake and protein synthesis: Metabolic stress! In this case, glucose starvation and susequent acute increases in AMPK expression during exercise.

Figure 2: Urine urea levels after working out in a glycogen replete (CHOH) vs. depleted (CHOD) state (Mullin. 1980)

What is important, though, is that you understand that this is an acute phenomenon - a beneficial effect of short-term glucose deprivation and not a result of running around glycogen depleted 24/7. The latter would not just decrease your training performance significantly. Studies by Lemon & Mullin (1980), for example, show that working out in a glycogen depleted state is associated with an almost 3x increase in markers of protein loss (urea; see Figure 2) compared to the same workout in a glycogen replete state.

More recent studies by Howarth et al. which measured the rate of leucine oxidation and other markers of protein catabolism confirm these results (Howarth. 2009), where the net amino acid loss doubled and underline that the last thing you want is to do if you're training for size gains and/or lean mass retention is to train in a glycogen depleted state.

Rather than that, I suggest you take another look at my glyocogen repletion recommendation from a previous article, hit the gym with full glycogen stores and see as the AMPK and NOS expression increases to trigger an increase in glucose uptake and protein synthesis while the glycogen stores are fading during your workout. Remember: It's about cycling high and low levels of energy availability and you certainly don't want to stay on the low end side for more than the few minutes it may take to trigger increases in protein synthesis.

Reference:

• Barcroft H, Millen JL (1939) The blood flow through muscle during sustained contraction. J Physiol 97:17–3.
• Holloszy JO, Kohrt WM (1996) Regulation of carbohydrate and fat metabolism during and after exercise. Annu Rev Nutr 16:121–138 
• Howarth K, et al (2009). Effect of glycogen availability on human skeletal muscle protein turnover during exercise and recovery. Journal of Applied Physiology 17:19.
• Lemon, PW, Mullin JP (1980) Effect of initial muscle glycogen levels on protein catabolism during exercise. Journal of Applied Physiology 48:624-629.
• Miniaci, M. C., Dattolo, M. G., Irace, C., Capuozzo, A., Santamaria, R., & Scotto, P. (2014). Glucose deprivation promotes activation of mTOR signaling pathway and protein synthesis in rat skeletal muscle cells. Pflügers Archiv-European Journal of Physiology, 1-10.
• Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404:661–671.

Chronic Resistance Training Reduces Anabolic Signaling in Response to Exercise - 12 Days of Detraining Restore It

This rodent obviously knows about the value of detraining as a means to restore the signaling protein response that gets blunted over weeks of continuous training (photo from livescience.com)

Ah, some really good stuff in the news, or rather in the journals as of late (for the news version of the articles, you obviously got to come here, to the SuppVersity ;-). So, let's skip any lengthy preludes and let's start with a simple question pertaining to the topic of the day: "When was the last time you took 2 weeks or more off?" What? Last year, when you were down with the flu? No, that does not count. I am talking about detraining, here; so only voluntary off-times will be reckoned as off time... I thought so, you haven't taken off in years, right? Well, what if I told you that this may be the reason your gains have not taken off either? Interested? Yeah, that's what I thought.

Chronic resistance training reduces its own anabolic effect, detraining restores it

I guess in the end, all of us knew this instinctively: The unbelievable gains you make as a rookie vs. the slow and arduous road you will be walking later in your "career" as a trainee are too obvious for anyone not to suspect that the marginal utility of exercise declines.

Learn more about domain sizes, protein synthesis and  "muscle bulding" in Part II of the Intermittent Thoughts on Building muscle.

Now, one of the most common and certainly accurate hypothesis to explain this phenomenon is that the restructuring processes that starts when you hit the early domain size limit is more time consuming than just "pumping more protein into the muscle" - a process, which happens more or less automatically, a previously sedentary individual picks up a dumb- or barbell ;-)

With the impending publication of a study by researchers from the Ritsumeikan University, the University of Tokyo, the Nippon Sport Science University and the  University of Mississippi we do now have evidence for another, yet probably not unrelated reason to the exponential decline in marginal utility: The amelioration of the exercise induced phosphorylation of signaling proteins, due to which the marginal utility of your workouts decreases over time.

What did the scientists do?

In the experiment, the results of which Riki Ogasawara and his colleagues summarized an discussed in their latest paper, the researchers randomized a group of male Sprague-Dawley rats (10 weeks of age, 356.1 ± 4.4 g body weight) to four groups (+control) performing either continuous training (1S, 12S, 18S), in the form of 1 exercise session (1S), 12 exercise sessions (12S), or 18 exercise sessions (18S) every other day (Mo, Tue, Wed, Fr, Su, Tue, ...), or continuous training + detraining (DT), in the form of 12 sessions of exercise every followed by 12 days of detraining.

Figure 1: The "muscle builder" mTOR and the pertaining signaling cascade(s); remember that the line with the bar at the end indicates an antagonism → higher mTOR = higher phosphorylation of p70SK and it's downstream target rpS6, but lower 4E-BP1 (my orange markups; original from ebiotrade.com).

The exercise itself was mimicking a leg-training regimen, in the course of which, the gastrocnemius muscle was trained by stimulating 5 contractions, with a 5-s interval between contractions, per set for 5 sets (5-min rest intervals in-between the sets).

"The voltage (~30 V) and stimulation frequency (60 Hz) were adjusted to produce maximal isometric tension. Before every exercise session, peak twitch torque was measured. Torque signals were collected continuously at a sampling rate of 1024 Hz using a 16-bit analog-to-digital converter (PowerLab/16SP;AD Instruments, Japan) and analyzed using Power Lab Chart 5 software (AD Instruments, Japan). " (Ogasawara. 2013)

24h after the last exercise session, the rats were anesthetized and exsanguinated. The muscles were removed immediately after death and both muscle size, volume and weight, as well as the expression of the signaling proteins p70S6 kinase, p90RSK, 4E-BP1 and S6 ribosomal protein (rpS6) were measured.

So what's that all about? Did the rats become more muscular?

As you can see from  my plot of the protein responses on the left and the respective effects the different training (+detraining) protocols had on the muscle weight of the rodents on the right hand side of figure 2, the chronic resistance training protocols lead to statistically significant reductions in the post training p70S6K and rpS6 expression, which were restored in response to the detraining protocol.

Figure 2: Phosphorylation status of p70S6K (Thr389), p90RSK (Thr573), 4E-BP1 (total) an rpS6(Ser235/236) on the left and body weight, as well as muscle weight  in both exercised (RT ) and non-exercised (CON) rodents measured on the day after the last workout of the respective training group (Ogasawara. 2013).

Notwithstanding, the fact that the muscle gains were (expressed relative to the respective control group) statistically identical, shouldn't surprise you. After all, the growth benefits of the detraining protocol will show only in the weeks after your absence from the gym. The rodents in the study at hand, however, were subjected to only one training session after the detraining period and killed afterwards. Therefore, the main message the data on the increase in muscle weight in the DT compared to its control group is sending us is that short periods of detraining won't cost you precious muscle mass.

Don't hesitate, dare growing like a rookie again - dare taking a week off!

In a previous study, by Ogasawara et al. I have likewise discussed here at the SuppVersity, the researchers have already shown that a "6-weeks-on vs. 3-weeks off" training-detraining regimen produces identical gains in muscle growth as continuous training w/out  producing the logarithmic decline in marginal gains that brings skeletal muscle hypertrophy to a screetching halt over time (read more)

The novel information about the decline and restoration of the signaling proteins this study provides would support the longstanding hypothesis that continuous exercise blunts its own growth response. And what's more it's also supported by various human studies. In 2006, for example, Coffey et al. were able to show that the phosphorylation of p70S6K and rpS6 in response to resistance training was almost completely blunted in highly resistance-trained subjects (power lifters), while it did occur in the untrained controls (Coffey. 2006).Morever, Ogasawara et al. have shown last year already that an even longer detraining period of 3 weeks lead to much steeper inclines in muscle CSA in human subjects than continous training (see figure next to the paragraph below and read up all the details in the respective SuppVersity article from October 2012)

Collectively, these results clearly suggest that the notion of planned, regular detraining periods could have benefits that go way beyond the well-known ability to protect you from getting caught in the downward spiral of chronic overtraining, as it will also "reset" the anabolic response to a given workload.

And while you can hardly expect the results to be anywhere similar to those you've hopefully experienced, when you were still a scrawny beginner, the data from the study at hand does suggest that there will be an increase in the marginal utility of your workouts after one or two weeks of detraining. Moreover, there is no reason to be afraid that you could lose muscle within this short time period. Based on the absolute numbers in the study at hand (cf. figure 2), you could rather expect to see a non-significant increase in muscle mass that will occur during shorter (1-2 weeks) detraining phases.

If you have no idea what macro- and micro-cycles are or are clueless about how to incorporate phases of detraining and - as a possible alternative with potentially similar effects - tapering into your routine, I suggest you go back to part VI of the Step by Step Guide to Your Own Workout

Just don't forget, that just as it was the case in the previously mentioned 2012 human study by Ogasawara et al., you will see and feel the beneficial effects of the detraining period, not before you are back on the grind for 1-2 weeks. If you look back at the protocol, Ogasawara et al. used, the fact that the gains were "just" identical (even that would be a huge plus: after all you get the added bonus of reduced risk of injury, overtraining, etc. without missing out on a single additional mm on your arms, chest, shoulders, quads, hams, and what not) would actually support my gut feeling that a detraining period (= no training at all) of three weeks after "only" 6 weeks, could be a little too long. In the study at hand, which is obviously not a human stud and did not involve a regular full-body split routine, it did after all take no more than 12 days, i.e. 9 days less for the signaling responses to return to baseline.

Further speculations about optimal off-times and respective increases in muscle gains would be mere speculation, so that I would suggest, we will postpone more concrete suggestions until the next paper from Ogosawara's group at the Research Organization of Science and Technology to be published. If we assume that it will take another 3 months, which happens to be the interval between the aforementioned human study and the study at hand, you better mark the first two weeks of April 2013 in your calendar, if you don't want to miss the respective SuppVersity post on the matter ;-)

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Regular periods of detraining are not the only thing you should keep in mind, when you lay out your workout routine. A study I wrote about in June 2012, for example showed that appropriate periodization can help you "Cut 12% Body Fat in 12 Weeks, Get Stronger, Bigger and Better Conditioned" (read more)

In short, what is it, this paper brings to the table and what are the implications? The "new" information this paper has to offer pertains to the restorative effects of detraining n the exercise induced protein signaling cascade that will eventually result in skeletal muscle hypertrophy (=muscle gains). The differential protein expression in the different training groups tell us, that the 12 days of detraining effectively restored the p70S6K an  rpS96 that declines with each and every workout during periods of continuous training.

The practical implications of these findings, should actually be obvious: Incorporating regular periods of detraining in your macrocycles and most importantly sticking to the plan, will not just help you to avoid overtraining with all it's negative side effects, it will also prevent the hypertrophy response to your workouts from diminishing and thus propel your lean mass gains.

Update: Steven Acerra called my attention to an older study by Kadi et al. who report distinct effects of detraining on the satellite cell response to heavy resistance training (Kadi. 2004). According to the results of their study, the often overlooked contribution of the satellite cells to the structural underpinnings of skelatal muscle appears to peak early in the detraining phase with the maximal number of satellite cells per muscle fiber being achieved after 10 days of detraining and a return to pre-training levels after 90 days. Despite the fact that a straight forward extrapolation of practical recommendations based on these observations alone is not feasible, the researchers observations do confirm that there is a multilayered benefit to short (~14 day) detraining periods.

Whether 12 days is the "optimal" length for a detraining period, if this "optimum" depends on the length, intensity and type of the previous training period, whether it's body part specific (like stop training arms for two weeks to restore your growth response in the biceps and triceps) and whether or not the training status of an individual has any impact on the time that's necessary for the "reset" to take place, will have to be elucidated in previous studies. That the SuppVersity is going to be the place, where you will read about these first, is something I probably don't have to tell you, right?

References: 

• Coffey VG, Zhong Z, Shield A, Canny BJ, Chibalin AV, Zierath JR, and Hawley JA. Early signaling responses to divergent exercisestimuli in skeletal muscle from well-trained humans. FASEB J. 2006; 20: 190-192. 
• Kadi F, Schjerling P, Andersen LL, Charifi N, Madsen JL, Christensen LR, Andersen JL. The effects of heavy resistance training and detraining on satellite cells in human skeletal muscles. J Physiol. 2004 Aug 1;558(Pt 3):1005-12. Epub 2004 Jun 24.
• Ogasawara R, Yasuda T, Sakamaki M, Ozaki H, Abe T. Effects of periodic and continued resistance training on muscle CSA and strength in previously untrained men. Clin Physiol Funct Imaging. 2011 Sep;31(5):399-404.
• Ogasawara R, Kobayashi K, Tsutaki A, Lee K, Abe T, Fujita S, Nakazato K, Ishii N. mTOR signaling response to resistance exercise is altered by chronic resistance training and detraining in skeletal muscle. J Appl Physiol. 2013 Jan 31. [Epub ahead of print]

The Anabolic Effects of HIIT: 3x30s High Intensity Intervals Increase mTOR & Ramp Up Marker of Protein Synthesis by +43% in Men and +222% in Women - Even in a Fasted State!

Image 1: While the study at hand clearly shows that HIIT, even done on an empty stomach, is anabolic, not catabolic, it appears as if women respond better to sprint exercises than men. And this assumption is not based on gene-assays but dates back to the results of a 1999 study by Esbjörnsson which showed a more pronounced CSA increase in the leg muscles of female subjects.

Not all too long ago, the general accepted consensus was that anyone whose main interest is in building muscle must abstain from any strenuous cardiovascular exercise... running on a treadmill? God-forbid! You could lose muscle. Over the last two years or so, this paradigm has began to totter, though. And now, at the beginning of 2012 I would estimate that the number of (recognized) trainers and trainees who recommend doing high intensity interval training (HIIT), if not for general conditioning, then at least as a means to shed fat, initially surpasses the number of the conventionalists who maintain that "classic cardio" training in the "fat-burning zone" was the way to go. Now, if this is not your first visit here at the SuppVersity, you should be aware that the latest scientific research supports the arguments of the advocates of HIIT. And not so much to my, as to the surprise of some researchers, this holds true not only for already well-conditioned gymrats and athletes, who want to finally pass beyond the 10% body-fat barrier, but also for the obese and metabolically deranged diabetic, who is trying to get his blood sugar under control (cf. "Hitting Diabetes With A Hammer").

The advantages of HIIT reach well beyond fat loss, but...


Moreover, a 2011 study by Naito et al., the results of which I have discussed in November 2011, shortly after it was published in Acta Physiologica (cf. "HIT Your Satellite Cells to Increase Your Gains"), already hinted at the fact that the advantages of HIIT reach well beyond its fat-burning effects. Yet although the increase in both satellite cell count and incorporation into the muscle Naito et al. observed speak for themselves, there's still rumors going round that this training style could be catabolic. In that the argument usually revolves around the notion that muscle damage is a major driving force of satellite cell recruitement and that if the latter is a necessary consequence of HIIT it would counter your efforts to build muscle. Now, aside from the fact that this argument is intrinsically flawed (I mean, what to you do in the gym, when you weight train? You break down muscle tissue!), a recently published study from the famous Karolinska Institute in Stockholm, Sweden, attests to the fact that the exact opposite is the case.

... it appears as if women could derive even greater benefit from all-out sprinting than men

Image 2: The exercise stimulus in the study was a Wingate test, one of standard procedures in exercise science.

In an earlier study from 1999 Esbjörnsson and his / her colleagues had observed that the cross-sectional area of the leg muscles of women exhibited a more pronounced hypertrophy response to sprint training than those of their male peers (Esbjörnsson. 1999). With the advent of our advanced understanding of the underlying principles of skeletal muscle hypertrophy and the central, but as those of you who read the Hypertrophy 101 know, in the current discussion possibly overemphasized position of the mammalian target of rapamycin (mTOR), Esbjörnsson et al. did now set out to examine, whether a sex-specific response of mTOR and its downstream targets could explain their previous results (Esbjörnsson. 2012).

To this ends, the scientists recruited nine men and eight women who despite participating in leasure time sports were only "in good shape" and not considered to be athletes. For the experiment the subjects reported to the lab fasted and, after a brief 1min warm-up, performed the well-known Wingate-test, which consists of three consecutive 30s all-out sprints with 20min breaks between the intervals on a braked cycle ergometer (average peak power was ~645W and ~935W for women and men, respectively, on a per-lean body-mass base, the peak and mean power was yet identical)

Figure 1: Illustration of the experimental protocol used in the study.

Before the warm-up and 140min after the 3rd sprint, Esbjörnsson et al. took muscle biopsies from the quadriceps muscles of the subjects to assess the local expression of mTOR and its downstream targets.

Figure 2: Phosphorylated AKT, mTOR, p70S6K and rpS6 (a.u.) in male and female study participants before the first and 140min after the third sprint of the Wingate test (data adapted from Esbjörnsson. 2012)

If you are not well-versed in the the intricacies of the mTOR-cascade, it appears as if the data in figure 2 would disprove the scientists' research hypothesis that "mTOR signalling is more pronounced in women than in men". After all, the increase in phosphorylated mTOR (p-mTOR) and AKT (p-AKT) in response to the three 30s seconds sprints was obviously more pronounced in the male, than in the female participants (mTOR +26% and AKT +17% greater increases; a difference which did not reach statistical significance, though).

Do women just make better use of the same stimulus?

As far as the phosphorylation of p70S6K, of which the current scientific evidence suggests that is a more appropriate measure of the "real-world" protein synthetic effect of mTOR, a completely different picture emerges. While the +43% increase in the male subjects is just about statistically significant (p = 0.04), the +222% increase in p-p70S6K in the female subjects appears to confirm what Esbjörnsson et al. already  had suspected.

Figure 3: Serum leucine and growth hormone levels at rest and after the sprints (data adapted from Esbjörnsson. 2012)

The slightly greater disappearance of leucine from the skeletal muscle of the male subjects (cf. figure 3) is yet only one of three possible explanations (and one you could counter by ingesting BCAAs, for example) Esbjörnsson et al. come up with based on the results of previous studies:

Image 3: If you look at the leg muscles
of some of the female speed skaters,
it is quite obvious that the leg muscles
of women respond pretty well to short,
intense bouts of all-out sprinting.
(the image shows Claudia Pechstein)

1. Lower accumulation of lactate and ammonia and a faster recovery of ATP levels in type II fibers of women than men
    
2. Lower levels of plasma catecholamins (=stress hormones) in response to sprint exercises in women than in men
    
3. Slower disappearance of leucine and thusly more sustained elevation of protein synthesis in women than in men

Whether it is any of these, or a combination of all three factors which is responsible for the differential response to statistically (!) not significantly different activations of mTOR and p-AKT, cannot be decided based on the available data.

An alternative explanation, which would, by the way, have real-world implications for the training practice, is (and I prefer to cite this, to avoid being accused of sexism) that...

women do not exhaust themselves as much as men during each bout of exercise and thereby elicit a smaller activation of AMPK, resulting in less inhibition of mTOR.

In view of the fact that previous studies by Esbjörnsson et al. refute this hypothesis, it appears unlike that an "over-expression" of AMPK, of which I have discussed in one of the previous installments of the Intermittent Thoughts that its locally expressed alpha-2 isoform does not inhibit the exercise induced increase in protein synthesis, anyway, could explain why similar exercise stimuli (peak and mean power per fat-free mass were virtually identical for men and women) and within the statistical margin identical mTOR responses induce a more pronounced protein synthetic response in women than in men. And whether the early(-ier) rise in serum growth hormone, which is the last possible explanation the scientists mention, has anything to do with it appears questionably, as well. After all, the data in figure 3 shows quite clearly that the overall GH response was much more pronounced in the male than the female participants.

We don't know about aliens, but for earthlings HIIT is anabolic - regardless of their sex

In essence, it does not even really matter, what the underlying cause of the sex-specific response to sprint training is. As far as I am concerned, the most significant result of the study is not the gender-difference, but the simple, yet as the scientists point out "novel" finding that "repeated 30-s all-out bouts of sprint exercise, separated by 20 min of rest, increased Akt- mTOR signalling in skeletal muscle." And this effect was observed in both men and women. Now, this is allegedly not exactly your "usual" HIIT protocol, if you do yet take into consideration that it was performed after an overnight fast and went without BCAAs, protein shakes all the other "obligatory" anti-catabolics, the average gymrat uses to avoid the purported catabolic effects of high intensity conditioning work, I would dare to say that it HIITs another (if not a final) nail into the lid of the casket of the "HIIT = catabolic" myth.