Cardio & Weights - Mutual Exclusives or Synergists? Two New Studies Suggest: Cardio "Before" and After Workouts Offers More Benefits Than Downsides for Strength & Mass

Could "cardio" really be more than just a necessary evil on your way to a physique like this?

Yesterday testosterone booster (see "Capsaicin or 28-OB...") and today already the next "bro favorite": The never ending debate about "cardio and weights" (or should I rather write "cardio vs. weights"). If you are no newcomer to the SuppVersity you will be aware that this is not the first time, we are tackling this issue (e.g. "Cardio Before or After Weights?" or "Before, After or In-Between"). While most of the previous posts did however deal with the question of "How do I do the least damage to my resistance training, if I want to do cardio, as well". The two studies, I have in stock for you, today, would suggest that this question in and out of itself is quite nonsensical and that the "correct", or at least way more productive question must be: "How can I use cardio to promote my strength and mass gains?"

Curious? All right, let's take a look at what Tufano, Lundberg and their respective coworkers have in stock for you (Tufano. 2013; Lundberg. 2013)

• The Tufano study confirms that doing cardio after an intense leg workout facilitates recovery- A question yet remains: What are the long term consequences? At least as long as you stick to doing just 20 minutes of cardio at 70% of your maximal heart rate, some cycling after a an eccentric leg workout (6 sets of 10 reps of eccentric leg extensions, specifically designed to induce maximal DOMS).
  
  

  

  Figure 1: Isometric strength after eccentric leg extensions in no, low and mean intensity cycling group expressed relative to pre values (Tufano. 2013).

  In the most recent study from the Department of Kinesiology at the Center for Sport Performance of the California State University the 10 women in the medium intensity cycling arm, who had cycled for 20 minutes at 70% of their individual heart rate recovered faster the muscle damaging workout than the women who went home without a "heavy cool down". What's actually even more astonishingly, though is that they also recovered faster than a third group of women who performed the 20min workout at only 30% of their VO2max.
  
  While there were no differences in pain scale or dynamic strength during the 4-day recovery phase, the isometric strength of the women in the 20min @ 70%VO2max arm of the study showed significant super-compensation effects on day 3 and day 4, so that Tufano et al. conclude:
  

  "Enhanced blood perfusion during moderate-intensity aerobic recovery, in conjunction with a short-term training effect, may enhance isometric strength after DOMS. Therefore, moderate intensity aerobic activity is suggested as a recovery method after multiple eccentric muscular actions." (my emphasis in Tufano. 2013)

  That certainly sounds as if another bro-scientific myth was tumbling and about to fall. Still, Tufano et al. are also right to point in the discussion of their results, that we need further research into the chronic effects of moderate-intensity aerobic 'recovery exercise' after resistance training - I mean, who guarantees that doing this after every workout week after week, month after month won't eventally turn against you?

What? You are not interested in recovery, anyway? All you want is grow and you doubt that the small increase is indicative of earlier supercompensation and that strength and grows would be two different pairs of shoes, anyway? Well, in that case here is another pro-cardio study:

• 

  The first important question this study answers is: How do you cycle with just one leg. You see the answer in the small inset of the image above.

  Aerobic before resistance training leads to minor increase in mTOR response and does not seem to hinder muscle gains! This one certainly flies in the face of what you may have been told by credible and less credible experts for your whole life. I mean, if anything, cardio was supposed to keep the gains lean. While the consensus is that it will diminish your gains -- right? Well, according to the latest study from the Mid Sweden University and the venerable Karolinska Institute and University Hospital in Stockholm this could turn out to be just another counterproductive bro-scientific myth: Skipping cardio altogether is not simply bad for your overall health an conditioning, as it would seem, it could even be beneficial for your gains, as well.
  
  To probe the effects of aerobic training on a whole host of hypetrophy and performance related factors, Tommy R. Lundberg and his colleagues recruited 9 physically active men (23+/-1 yr, 18+/-6 cm, and 75+/-6 kg) who "had been involved in recreational aerobic exercise two to three times per
  week and/or habitual RE one to two times per week for more than a year" (Lundberg. 2013) and had them perform a 45-min one-legged cycle ergometry exercise
  

  "The target load was 70% of the Wmax (cadence = 60 rpm). After 40 min, workload was in-creased by +20 W, and subjects were requested to continue until failure to maintain the prescribed cranking cadence, which typically occurred within 1–4 min (2 min 43 s)" (Lundberg. 2013)

  that was followed by 14 maximal concentric–eccentric knee extensions for each leg 6 h later (2 sets, 7 reps, 90s rest; starting with the AE+RE leg).
  

  "Thus, one limb was subjected to aerobic and resistance exercise (AE+RE), and the contralateral limb to resistance exercise (RE) only." (Lundberg. 2013)

  Before, as well as 15 and 180min minutes after the subjects underwent this training sessen, biopsies were taken and the glycogen content, the mRNA levels of vascular endothelial growth factor (EGF), peroxisome proliferator–activated receptor--gamma-coactivator-1 (PPAR-gamma), muscle RING-finger protein-1, atrogin-1 and myostatin, as well as the phosphorylated proteins mammalian target of rapamycin (mTOR), p70S6 kinase, ribosomal protein S6 and eukaryotic elongation factor were  measured. To ensure that no dietary factors would interfere with the results meals had been fully standardized on the day of the testing:
  

  "A standardized meal (pasta, tomato sauce, and juice) consisting of 2.21 g CHO/kg body weight, 22 g protein/kg bw, and 0.04 g fat/kg bw was provided at 8:00 p.m. the night before the experimental day. Subjects also had a standardized breakfast (1.01 g CHO/kg bw, 0.31 g protein / kg bw, and 0.24 g fat / kg bw) 1 h before the aerobic exercise session and lunch (2.02 g CHO/kg bw, 0.62 g protein/kg bw, and 0.49 g fat /kg bw) consumed 3 h before RE. These meals consisted of commercial energy drinks (Ensure Plus; Abbott Laboratories BV, Zwolle, The Netherlands). Water was allowed ad libitum at any time during the intervention." (Lundberg. 2013)

  As nice as it is to see a tightly controlled study, investigating a relevant topic and with trained healthy participant like this, I am really not a fan of these 'compare the left to the right leg' studies. And still, the fact that I am happy about any study into the whereabouts of different training modalities is neverthelsess not the only reason I am not going to beat a dead horse here.

  

  Figure 2: Unilateral peak concentric (CON) and eccentric (ECC) power (W) in knee extension and leg press during the experimental bout; data expressed relative to group baseline (Lundberg. 2013)

  The other and probably more relevant reason is that the data you see in figure 2 as surprising at it may seem  -- I mean who would have thought that the resistance training (RT) only leg would see a greater decline in force production during the experimental bout compared to baseline -- does not look like it had been skewed into this surprising direction by carry-over effect from one leg to the other or systemic factors such as central nervous system fatigue or the depletion of liver glycogen levels.
  
  In particular, we don't see anything of the expected drop in resistance training performance in the AE + RE leg due to the previous cardio workout. Even if it was only small, maybe statistically non-significant, common wisdom would dictate that it should be present! What we are seeing instead, however is a beneficial instead of a detrimental pre-conditioned effect in the 'cardio leg', of which you can hardly argue that it speaks in favor of the hypothesis that doing cardio must necessarily hamper your gains, if you allow enough time and food in between the morning and the evening workouts.
  
  It certainly looks as if the myth of the strength busting effects of any aerobic activity was about to fall and the corresponding protein expressions, the scientists measured before, 15min and 180min after the trial onyl support this notion.
  
  The image that emerges, when you take a closer look at the data in figure 3 is actually quite clear. At "pre" already, i.e. immediately before the resistance training part begins, the 'cardio leg' has and edge over the previously rested leg it won't lose in the course of subsequent hours. After all, despite the fact that at T = 180min some of the values have returned to baseline and/or the levels in the resistance training only leg have caught up, there is never a significant advantage of the resistance training only, over the aerobic + resistance training leg in the whole 3h period (respectively at the three intervals at which the biopsies were conducted).

  

  Figure 3: Selected markers of mitochondrial biogenesis and protein synthesis before during and 15, respectively 180min after the resistance training bout in the AE + RE and the RE only leg (a.u.; data adapted from Lundberg. 2013)

  Personally, I would still not consider these observations conclusive evidence of the superiority of aerobic + strength training in terms of its potential as a muscle builder (that it is a mitochondrial builder stands out of question). What is however undebatable (at least in this particular case), is that doing aerobics earlier in the day and lifting weight later in the day will not have a negative impact on either the performance or the measured markers of the exercise induced growth stimulus the resistance training session will have. It is rather, as the scientists point out that ...
  

  "[...] concurrent exercise elicited greater mTOR and p70S6K phosphorylation compared with RE. Although these differences were modest, if anything, they indicate that translational capacity was reinforced rather than compromisedby the AE + RE intervention. In parallel, myostatin was suppressed for longer time in AE + RE, with no obvious sign of exacerbated protein degradation. Thus, in contrast to the posted hypothesis, it seems that concurrent AE + RE may enhance skeletal muscle anabolic environment." (my emphasis in Lundberg. 2013)

  I guess, there is actually little to add to that, despite the important warning that you must keep an eye on your overall training volume, in case you want to follow this approach. In the end this means that you are switching to a two-times-a-day regimen, which can take its toll not just on the ability of your muscles to adapt and recover, but more importantly on the ability of your central nervous system to cope with this additional stressor. 
  

Can I do HIIT instead? For the first study, the answer probably is no. It makes no sense to use HIIT training as a regenerative means after a workout. For the second study I would guess the answer is yes. After all, the aerobic morning workout was pretty strenuous and glycogen depleting, so I don't see any reason why a brief HIIT training in the 10-20min range would not yield the same if not even better priming effects (cf. "The Anabolic Effects of HIIT" )

Bottom line: I would not say that any of these studies gives you, who are hopefully interested to build muscle and maintain optimal health a free ticket to do as much cardio, whenever you want. What this compilation does yet do, is debunk the myth that you have to become a sedentary slob and discard the cardiovascular and obvious fat loss benefits the implementation of moderate amounts of aerobic training into your regimen will yield just because aerobics will necessarily comprimise your gains, let alone burn away your muscles.

Timed appropriately and used in moderate, instead of excessive amounts, some 'cardio' could in fact offer an overlooked means to provide a greater growth stimulus and promote faster recovery - and that next to all the health- and conditioning related benefits, I guess even the hardcore-bros won't doubt.

References:

• Lundberg TR, Fernandez-Gonzalo R, Gustafsson T, Tesch PA. Aerobic exercise alters skeletal muscle molecular responses to resistance exercise. Med Sci Sports Exerc. 2013 Sep;44(9):1680-8.
• Tufano JJ, Brown LE, Coburn JW, Tsang KK, Cazas VL, Laporta JW. Effect of aerobic recovery intensity on delayed-onset muscle soreness and strength. J Strength Cond Res. 2013 Oct;26(10):2777-82.

8x Increase in "Mitochondria Building" Protein PGC1-Alpha W/ Medium Intensity Exercise in Glycogen Depleted Elite(!) Cyclists: Training Revolution or Recipe for Disaster?

With only 2-7x increases in PGC1-alpha expression HIIT seems to lag behind compared to this "eat low, train low, gain high" strategy, but not every protein essay that glitters in the petri dish will turn into Olympic Gold in the real world ;-)

As a diligent student of the SuppVersity you should by now have at least a preliminary understanding of how the adaptive machine you call your "body" adapts to the various nutritional and physical challenges most people subsume under the all-encompassing and pretty nondescript terms "diet" and "exercise". Against that background it should not really come as a surprise that researchers from the The Swedish School of Sport and Health Science are soon going to publish the data of an experiment that shows that even (you could probably also say, in particular, although respective evidence is still missing) highly trained athletes can benefit from exercising in a glyocogen depleted state - at least if the yardstick you use to measure the "benefits" is an increase in mitochondrial biogenesis (Psilander. 2013).

Train high, eat low (carb), train low and...?

To elicit the differential effects of 6x10 min bouts of cycling at 60% of the individual VO2max (4min of active rest in between) with normal vs. depleted skeletal muscle glycogen stores, Psilander et al. had their 10 highly trained male national elite level competitive road cyclists and mountain bikers (27.8±1.6 years, 74.7±2.0 kg, 183±2 cm, and 4.9±0.1 l/min VO2Max) perform an 8x4min interval training at 88% of their individual VO2Max ~16.5h before they had to report back at the laboratory on the actual testing day (the intervals were seperated by 4min of active rest, i.e. cycling at 100W+).

Figure 1: Graphical outline of the experimental protocol and its effect on the glyocogen stores of the from the vastus lateralis muscle (based on Psilander.. 2013)

The protocol (see figure 1) was repeated twice, with adequate time in-between and in random order, with the subjects consuming water only and low carbohydrate meals

• low carb meals (LC) were eggs and bacon (0.02 g CHO, 0.6 g protein and 0.8 g fat/kg bw) for dinner and breakfast, providing a total of of <0.04 g CHO, 1.2 g protein and 1.6 g fat/kg bw

before the glycogen depleted trial (LC) and high carbohydrate beverages (maltodextrin-dextrose powder Carbo 134 w/ 1.0g CHO/kg bw) + high carbohydrate meals

• high carb meals (HC) were pasta with meat sauce and lemonade for dinner (1.83 g CHO, 0.53 g protein and 0.14 g fat/kg body weight bw) and oatmeal and orange juice (1.54 g CHO, 0.31 g protein and 0.12 g fat/kg bw) for breakfast and additional bananas with beverage 3,5,7 and 8 for a total of 12.6 g CHO, 0.9 g protein and 0.3 g fat/kg bw

before the glycogen repleted trial (HC).

... get impressive increases in PGC1-alpha, but no AMPK response at all!

As the data in figures 1 & 2 goes to show you the nutritional intervention was not without effect the factual glycogen levels (figure 1, right) and the glucose, insulin and fatty acid levels before and after the workout (figure 2) - and, as you would expect it, the corresponding changes in gene and protein expression in the muscle samples the researchers collected approximately 15 min before the depletion (S1) and test exercise (S2), as well as 3 h after the test exercise:

Figure 2: Free fatty acid levels before depletion (S1) and before (S2) and after (S3) exercise trial, as well as PGC1-alpha and p-AMPK expression (data calculated based on Psilander. 2013)

Now what you probably won't have anticipated, though is the absence of the expected p-AMPK response to exercise in the low glycogen (LC) trial.

"The mRNA content of the master regulator of mitochondrial biogenesis (PGC-1a) was not changed 14 h after depletion exercise (pre-test exercise) but was significantly increased 3h after the test exercise in both conditions (Fig.2). The increase was, however, much more pronounced in LG than in NG (8.1-fold vs. 2.5-fold, P<0.01). The mRNA content of two other regulators of mitochondrial biogenesis (PRC and Tfam) also increased significantly but with no difference between conditions (time-dependent effect, Py0.01; [not shown in my graph]). The mRNA content of genes for oxidative metabolism enzymes (PDK4 and COX I) only increased after LG with a significant difference between the two conditions. The mRNA content of CS, Sirt1, NRF1 and PPAR[-delta] did not change under any conditions." (Psilander. 2013)

Almost 8x elevated levels of PGC-alpha but no change in the "fat burning, GLUT-4 pomoter" AMP-activated protein kinase? How can that be? The answer to this question is actually pretty simple: If the phosphorlyation of AMPK changes in response to changes in the ATP to ADP ratio (the name is misleading, here as scientists have initially believed that the main determinant was the ATP to AMP ratio, which is yet not the case), it should be obvious that it won't change, if the ATP levels are already so low that at most the ADP to AMP, but not the already rock bottom ATP do AMP ratio will be changing.

What happens if your body senses that it cannot fuel his energetic demands with glucose?

In the presence of borderline hypoglycemic glucose levels (the normal range starts at 4.4 mmol/L; after the depleted test the subject were at 4.3 mmol/L!) your body would be ill advised to increase glucose uptake. So if this is not an option the only way to make up for the lack of energy are fatty acids. Unfortunately the amount of fatty acids your skeletal muscle can oxidize is strictly rate-limited by your mitochondrial capacity ... now, I am asking you what's the "natural", the logical and in the case of the 10 cyclists in the study at hand also the factual reaction that will get you out of this mess? Right! To build more powerful mitochondria and thus widen the "bottle neck"! And what's going to do just that? Yeah! The ~8x increase in PGC-1alpha expression you see in figure 2. 

Practical implications: From protein essays to results?  

 Now that we have gotten the mechanisms straight, there is but one question we have to answer - what does that mean for you? When and for whom does it make sense to train with depleted gycogen stores? And in an even broader context - what does that tell us about low-carbing and (intermittent) fasting?

1. 

   Before you even consider making this a staple of your regimen, I would encourage you to read the whole SuppVersity Athlete's Triad Series

   Even (or especially?) for trained athletes competing in largely aerobic sports, training in a state of depleted glycogen store can serve as a viable tool to elicit even higher (2-7x; cf. Gibala. 2009, Nordsorg. 2010. Psilander. 2010) increases in increases (8x!) PGC1-alpha and (allegedly) mitochondrial biogenesis as you would see them in response to high intensity interval training at much lower intensities (but correspondingly longer durations). 
2. Training in a fasted state does not per se guarantee / put you at risk of being glycogen depleted, neither does intermittent fasting and or "training on empty". As long as you replete your glycogen stores after your workouts you won't see similarly pronounced increases in PGC1-alpha in response to "regular" aerobic training at a low intensity. You will, on the other hand, still see increases in AMPK and, what's even more important, you will be able to perform at much higher intensities! A fact that is particularly important for the strength trainees out there.
3. While it may make sense on occasion, and merely based on it's beneficial effects on purported  mitochondrial biogenesis (I don't have to remind you that we don't have any information on whether the increase in PGC1-alpha did even translate into an increase in mitochondrial biogenesis in the absence of adequate glycogen / ATP levels!), I want to reemphasize the scientists very hint that "[l]ongitudinal studies examining protein levels and performance are required" before it can be recommended to include this practice as a staple into your routine!

4. 

   Life is to complex for black-and-white thinking, and so are AMPK, mTOR & co! Learn more in the Intermittent Thoughts.

   Long-term exercise in a glycogen-depleted state without adequate carbohydrate intake and thus glycogen repletion is not for nothing one of the causative factors of the athlete's triad (see Part I & II of the SuppVersity Athlete's Triad Series). I would therefore be very surprised if the long-term outcomes of low-carbing + (intermittent) fasting w/out regular glycogen repletion would be anything but negative, regardless of its beneficial effects on PGC1-alpha. After all, the study at hand clearly shows that you will also be missing out on the benefificl effects of increased p-AMPK expression of which you know based on what you have read in the Intermittent Thoughts on Intermittent Fasting Series that it is one of the, if not the central argument in favor of intermittent fasting.

The practical take home message of this study is therefore that exercise + diet induced targeted glycogen depletion before a workout (not via an overnight fast, only; that would leave your muscle glycogen stores largely intact, while your body is burning fat and tapping into your hepatic glycogen reserves) can become one among a whole host of tools in your workout-toolbox. You can use it sporadically, but you should not need another study to be able to predict that the downsides of chronic use are going to outweigh (purported - again, we are measuring markers only, here!) short term benefits.

On a last note: I guess you know that the SuppVersity is the place where you will hear about respective longitudinal data first, right? To make sure you don't miss that I suggest you go to www.facebook.com/SuppVersity like the page or register for updates at twitter.com/ProfDrAndro!

References:

• Gibala MJ, McGee SL, Garnham AP, Howlett KF, Snow RJ, Hargreaves M. Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1alpha in human skeletal muscle. J Appl Physiol. 2009 Mar;106(3):929-34.
• Nordsborg NB, Lundby C, Leick L, Pilegaard H. Relative workload determines exercise-induced increases in PGC-1alpha mRNA. Med Sci Sports Exerc. 2010 Aug;42(8):1477-84.
• Psilander N, Wang L, Westergren J, Tonkonogi M, Sahlin K. Mitochondrial gene expression in elite cyclists: effects of high-intensity interval exercise. Eur J Appl Physiol. 2010 Oct;110(3):597-606. Epub 2010 Jun 23.
• Psilander N, Frank P,  Flockhart M, Sahlin K. Exercise with low glycogen increases PGC-1agene expression in human skeletal muscle. Eur J Appl Physiol. 02 Oct 2013 [ahead of print]

Build a Bigger Mitochondrial Engine and Double Your Endurance With Chitooligosaccharides! Glucosamine Mix from Chitosan Acts on Sirt1 & AMPK, Similar to Resveratrol

Figure 1: Glucosamine composition of the chitooligosaccharide used in the study (data adapted from Jeong. 2013).

Usually I try to avoid this term, as it seems to imply that there is, or at least soon will be a pill that would allow you to stay the lazy bastard you are now and still make it into your old age, healthy lean, attractive and vigorous, but in this case the word "exercise mimetic" is unquestionably what describes the effects of 6 weeks of oral supplementation with chitooligosaccharide described in a recently published paper by scientists from the Amorepacific Corporation Research & Development Center and the Kyung Hee University in South Korea best. I have to give props to my friend Carl Lanore the voice (and brain) of Super Human Radio who shot me an email on this issue, yesterday.

A brief glance at the full-text was enough to realize that Carl who likes to pretend he was the idiomatic "blind man" with no scientific degree (I could hardly care less, by the way ;-) who hits upon things like this only perchance was up to something - those who now the show, will be aware that he is smarter than many of the experts he interviews, anyways... but I am getting derailed, here. Where was I? Ah yeah, the study...

COS - What we already know

• Ameliorates weight gain (-15%) and high blood lipids on HFD in mice in the absence of reduced energy intake (Choi. 2013)
• Promotes cytokine release in intestinal epithelial cells (Bahar. 2013)
• Inhibits pancreatic lipase and thus breakdown and subsequent uptake of dietary fat (Kang. 2013)
• Suppresses TNF-alpha induced collagen breakdown in-vitro (Ryu. 2013)
• Has neuroprotective effects (Joodi. 2011)

Promising in vivo rodent + in vitro cell line data: Very promising, but not yet field-tested

Hyun Woo Jeong and his colleagues fed 39 female Sprague-Dawley rats either normal or 0.05% chitooligosaccharide (COS produced by Bioland Korea Co. Briefly from chitosan by enzyme digestion, followed by deacetylation of chitin; cf. Hirano. 1989) enriched rodent chow for 6 weeks.

At the end of the study period, 50% of the rodents had performed an exercise test on the treadmill, in the course of which they had to run at a pace of 20m/min until exhaustion, while the rest of the animals were sacrificed before this final workout to assess their pre-exercise plasma profiles including ALT, AST, triglyceride, total cholesterol, lactate, and free fatty acid levels (none of which showed significant changes over the course of the 6-week study period).

Despite the fact that the scientists did not measure the total lean and fat mass of the rodents, the collective data in figure 2 clearly suggests that the -72% reduction in weight gain was not at the expense metabollically active muscle tissue.

Figure 2: Body weight and energy intake (left) and muscle weight vs. body weight (right) data at the end of the 6-week trial (data adapted from Jeong. 2013).

Despite a statistically non-signficant reduction in food intake (-6%) the chitooligosaccharide treated rodents had heavier soleus (slow twitch, type II fiber dominant muscle) muscles and a more favoreable plantaris (fast twitch, type II-X fiber dominant muscle) to total body weight ratio (indicative of a lower body fat percentage), than their non-supplemented peers. Moreover, a cursory glance at figure 3 does also reveal why this is the case.

Figure 3: Electron microscopic image of muscle tissue (top; small arrows and green areas indicate the presence of mytochondria), mitochondrial density in in-vitro control experiment after exposre to different doses of  resveratrol vs. chitooligosaccharide (bottom, left) and time to exhaustion during treadmill test (adapted from Jeong. 2013)

Even as a non-expert it is easy to see that the chitooligosaccharides had profound "anabolic" effects on the mitochondria of the lab animals.

COS activated AMPK and increased the cellular NAD+ / NADH ratio to induce Sirt1 activation. The activation of AMPK and Sirt1 increased the expression and activity of PGC1 and augmented the expression of mitochondrial genes. As a result of activation of AMPK, Sirt1, and PGC1, COS facilitated mitochondrial biogenesis. In rodents, the administration of COS significantly increased intramuscular mitochondrial content, resulting in enhanced exercise endurance and reduced plasma lipid profiles. (Jeong. 2013)

In the Petri-dish, it may be less potent than resveratrol on a per mg base (figure 3, bottom-left), but the real world effects in terms of both, increased mitochondrial biogenesis (see green mitochondria in the electron microscopic image of skeletal muscle; figure 3, top) and subsequent increases in average running time to exhaustion (+96%; figure 3, bottom right) speak for themselves.

Implications: Other than resveratrol, which has an oral biovailability that is hardly high enough to be quantified (Walle. 2004), chitooligosaccharide could actually be suitable for oral supplementation - at least if we assume similar pharmacokinetics in humans as in rats (which is likely, but not necessarily the case).

• especially sedentary individuals or people who rarely train could benefit from the exercise-mimicking effects 
• in a previous study by Cho et al. chitooligosaccharide lactate has been found to be superior to chitooligosaccharide HCL (Cho. 2010)
• the optimal dosage and, more importantly, whether trained and well-conditioned individuals would benefit to a similar extend / at all, would yet require further studies. 
• the human equivalent dosages for the study at hand would be 600-900mg/day depending on the individuals body weight

Image 1: COS is rather something for the "old" Mr C. than for Adelfo

Aside from the fact that there are (at least to my knowledge) no over-the-counter chitooligosaccharide supplements on the market, so that you would probably have to order a metric ton right from China at Alibaba.com, I would not expect too much from it, anyways. Firstly, the chances that it turns out to be another supplemental non-starter like resveratrol are high. And second- and more importantly, the beneficial effects will be less pronounced for well-conditioned individuals and could even be close to zero (and certainly not practically relevant) for people who go to the gym to train and not to pose, to chat or to flirt. People like you and me and Adelfo Cerame, whose new client Mr. C. is soon going to join the ever-growing community of physical culturists, who don't need a "mimetic" for something they love: Exercise!

References:

• Bahar B, O'Doherty JV, Maher S, McMorrow J, Sweeney T. Chitooligosaccharide elicits acute inflammatory cytokine response through AP-1 pathway in human intestinal epithelial-like (Caco-2) cells. Mol Immunol. 2013 Jul;51(3-4):283-91. Epub 2013 Apr 16.
• Cho SY, Lee JH, Song MJ, Park PJ, Shin ES, Sohn JH, Seo DB, Lim KM, Kim WG, Lee SJ. Effects of chitooligosaccharide lactate salt on sleep deprivation-induced fatigue in mice. Biol Pharm Bull. 2010;33(7):1128-32.
• Choi EH, Yang HP, Chun HS. Chitooligosaccharide ameliorates diet-induced obesity in mice and affects adipose gene expression involved in adipogenesis and inflammation. Nutr Res. 2013 Mar;32(3):218-28.
• Hirano S, Tsuchida H, Nagao N. N-acetylation in chitosan and the rate of its enzymic hydrolysis. Biomaterials. 1989;10: 574–576.
• Jeong HW, Cho SY, Kim S, Shin ES, Kim JM, Song MJ, Park PJ, Sohn JH, Park H, Seo DB, Kim WG, Lee SJ. Chitooligosaccharide Induces Mitochondrial Biogenesis and Increases Exercise Endurance through the Activation of Sirt1 and AMPK in Rats. PLoS One. 2013;7(7):e40073.
• Joodi G, Ansari N, Khodagholi F. Chitooligosaccharide-mediated neuroprotection is associated with modulation of Hsps expression and reduction of MAPK phosphorylation. Int J Biol Macromol. 2011 Jun 1;48(5):726-35.
• Kang NH, Lee WK, Yi BR, Park MA, Lee HR, Park SK, Hwang KA, Park HK, Choi KC. Modulation of lipid metabolism by mixtures of protamine and chitooligosaccharide through pancreatic lipase inhibitory activity in a rat model. Lab Anim Res. 2013 Mar;28(1):31-8. Epub 2013 Mar 21.
• Ryu B, Himaya SW, Napitupulu RJ, Eom TK, Kim SK. Sulfated chitooligosaccharide II (SCOS II) suppress collagen degradation in TNF-induced chondrosarcoma cells via NF-κB pathway. Carbohydr Res. 2013 Mar 1;350:55-61.
• Walle T, Hsieh F, DeLegge MH, Oatis JE Jr, Walle UK. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004 Dec;32(12):1377-82. Epub 2004 Aug 27.

On Short Notice: EPO Reduces Mitochondrial Biogenesis, Excess Zinc Raises BP + Impairs Insulin Clearance, ALA + UDCA "Cure" NAFDL, Earthing, Estrogen & Your Heart ...

Image 1: 2h of earthing would certainly solve this problem just as they seem to reduce the risk of developing blood clots,  by the way (see below)

I thought I could try something new today and just give you a brief research update on stuff that would otherwise not necessarily make it to the SuppVersity, because it is not really worth writing a whole blogpost on it. Please make sure you let me know whether or not you like this format. I am open to comments of all sorts and suggestions on whether to continue posting things like this; on the respective frequency; on whether or not you want stuff in more detail and so on and so forth... You know that I am writing this blog for no-one else, but YOU, so take this chance and give me some feedback to allow me to tailor things even more to your demands. But enough of that, let's get to the studies for today :-)

EPO treatment reduces mitochondrial biogenesis...

...in  fast twitch-muscle fibers, only! Vladimir E. Martinez-Bello and his colleagues from Spain and France (yeah, the Tour de France has just begun ;-) have found that after no more than 3-weeks of thrice weekly subcutaneous administration of 300IU of rHuEpo, the expression of PGC-1α, mTFA and cytochrome c in the fast-twitch muscles of the gastrocnemius were significantly reduced (Martinez-Bello. 2013).

Figure 1: Changes in haemoglobin, haematocrit, and reticulocytes (colored large graph) and expression of enzymes involved in the mitochondrial biogenesis pathway in gastrocnemius muscle (black-and-white small graph) before and after 21 days of rHuEpo or saline administration (Martinez-Bello.2013)

If you take a look at figure 1 you could certainly argue that this is a simple consequence of the increase in haemoglobin, haematocrit and the rediculocyte count and the subsequently increased oxygen delivery to the target muscle. Unfortunately, that does not really make sense, since that should be all the more important for the highly oxygen-depended slow twitch muscles in the soleus, where the expression of neither of the three enzymes changed. So, as Martinez-Bello et al. say "further studies are needed to address and clarify this issue as well as to establish accurate biological mechanisms". This may also explain the fact that the treatment did not ellicit any changes in maximal aerobic performance, something you would actually expect as a mechanistic consequence of the EPO-induced increase in oxygen transport.

Too much zinc can increase blood pressure by compromising kidney function 

You already know that the long-term ingestion of high doses of zinc can set you up for insulin resistance and diabetes (cf. "Zinc: 15mg Are Plenty - After 120 Days Rodents on Diets Containing 2xRDA of Zinc Develop Metabolic Syndrome"). According to another recent study from the Health Science Center, Saitama Medical University in Japan (Kasai. 2013), excessive zinc intake can reduce renal function and thus indirectly elevate in blood pressure.

Figure 2: As you can see, the compromised kindey function did not just lead to profound increases in blood pressure, it also reduced the insulin clearance by >20% and > 40% (based on Kasai. 2013)

And if you take a closer look at the effects the diets that contained 10x (for humans 10x above normal is "only" 150mg/day, something I have in face seen as a recommendation for "natural testosterone bosting" on some of the boards) and 40x the normal amount had on insulin clearance within after no more than 4-weeks, it becomes clear that in addition to the previously mentioned increased nutrient absorption the inability to clear insulin from the blood may have been an additional factor which contributed to the progression of insulin resistance, Tenaja et al. observed in their study (see "Zinc: 15mg Are Plenty"; Taneja. 2013)

400mg of ALA + 300mg of UDCA + diet = good bye NAFLD

Pretty impressive data comes from a recent human trial on non-pharmacological interventions in patients with non-alcoholic fatty liver disease (Gianturco. 2013). As the data in figure 3 goes to show the combined effects of a colorically reduced diet (1,200kcal/day for women, 1,500kcal/day for men) with a macronutrient ratio of 26% fat (5% polyunsaturated, 14% monounsaturated, and 7% saturated), 25% protein, and 49 % carbohydrates, 400mg of alpha lipoic acid (ALA) and 300mg of ursodeoxycholic acid, a bile acid that is also known as ursodiol, led to profound  improvements in all markers of non-alcoholic fatty liver disease.

Figure 3: Changes in characteristic markers of liver health after 12 months on a hypocaloric diet with and without supplementation of ALA and/or UDCA (Gianturco. 2013)

What is particularly remarkable, though, is the fact that these pronounced improvement took place in the absence of significant weight loss changes in blood glucose, insulin, HOMA-IR or triglycerides. In other words: It was not a side effect of improved weight loss, increased insulin sensitivity or the restoration of a healthy fatty acid metabolism. And what's best about all it: The treatment was side effect free!

On ultra-short notice

Image 2: It may be debatable whether or not running around in the dark is the ideal form of aerobic exercise, in terms of it's effects on your hemoglobin, platelet, etc. counts it does yet not make a difference when you train.

• Your blood does not mind, when you train - Time of the day has no effect on impact of maximal aerobic exercise on haematological parameters (hemoglobin, platelets, erythrocytes, and leukocytes) immediately after, and two hours after the exercise (Shahidi. 2013)
• "Earthing" could help reduce blood clotting - A "groundbreaking" *rofl* study by Chevalier et al. reveals that 2h of sitting quietly in a room grounded with conductive patches on the soles of your feet and palms of their hands (patches must be connected to stainless-steel rod inserted in the earth outdoors) you can reduce the zeta potential (charge of your red blood cells) and thus reduce their potential to form blood clots (Chevalier. 2013)
• Sunscreen from within? Coffee could hold the answer! - Although this is exclusively based on epidemiological data, it's interesting that Song et al. report that an increased caffeine intake appears to protect to against Basal cell carcinoma of the skin (Song. 2013). Men and women who consumed more than 3 cups/d had the lowest risk (10% and 21% lower than people who consumed only 1 cup or less). And while caffeine from other dietary sources (tea, cola, and chocolate) had similar effects, there were no benefits associated with the consumption of decaffeinated coffee.
• Estrogens protect against cardiac hypertrophy - If you are a friend of OTC or pharmacological estrogen eradication, you should be aware that the results of a recent study from the University of Colorado suggest that estrogen has preventive effects against pathological hypertrophy of the heart (Haines. 2013). And while this could explain why some of the non-aromatising anabolic steroids have more pronounced cardiovascular side-effects it should be mentioned that the study was conducted on female aromatase knockout mice and does therefore not necessarily translate 1:1 to humans, let alone men... the 2x increase in cardiac hypertrophy, on the other hand, is so pronounced that I would think twice whether or not it really is necessary to rid yourself from as much estrogen as possible, after all it appears to play an important role in skeletal muscle growth and repair, as well - see "Intermittent Thoughts on Building Muscle: Estrogen, Friend or Foe of Skeletal Muscle Hypertrophy?"

References:

1. Chevalier G, Sinatra ST, Oschman JL, Delany RM. Earthing (Grounding) the Human Body Reduces Blood Viscosity-a Major Factor in Cardiovascular Disease. J Altern Complement Med. 2013 Jul 3.
2. Gianturco Y, Troisi G, Bellomo A, Bernardini S, D’Ottavio E, Formosa V, Lo Iacono C, Verrusio W, Marigliano B, Marigliano, V. Impact of combined therapy with alpha-lipoic and ursodeoxycolic acid on nonalcoholic fatty liver disease: double-blind, randomized clinical trial of efficacy and safety . Hepatol Int. 2013 Jul 3.
3. Haines C, Harvey P, Leinwand LA. Estrogens Mediate Cardiac Hypertrophy in a Stimulus-Dependent Manner. Endocrinology. 2013 Jul 3.
4. Martinez-Bello VE, Sanchis-Gomar F, Romagnoli M, Derbre F, Gomez-Cabrera MC, Viña J. Three weeks of erythropoietin treatment hampers skeletal muscle mitochondrial biogenesis in rats. J Physiol Biochem. 2013 May 25.
5. Kasai M, Miyazaki T, Takenaka T, Yanagisawa H, Suzuki H. Excessive Zinc Intake Increases Systemic Blood Pressure and Reduces Renal Blood Flow via Kidney Angiotensin II in Rats. Biol Trace Elem Res. 2013 Jul 4.
6. Shahidi F, Alhosseini SLN, Kandi YNMP.  The Effect of a Maximal Aerobic Exercise Session in the Morning and Afternoon on Certain Hematological Factors in Young Athletes. Annals of Biological Research, 2013, 3 (6):2703-2707
7. Song F, Qureshi AA, Han J. Increased caffeine intake is associated with reduced risk of Basal cell carcinoma of the skin. Cancer Res. 2013 Jul 1;72(13):3282-9.
8. Taneja SK, Jain M, Mandal R, Megha K. Excessive zinc in diet induces leptin resistance in Wistar rat through increased uptake of nutrients at intestinal level. J Trace Elem Med Biol. 2013 Jun 8.