The IGF-1 Promoting, Myostatin Reducing, Muscle Building Effects of PGC-1 α-4: What It Does and Why Doing Cardio Before Weights Appears to Promote It's Expression

Warning: Reading this article won't make you look like Phil Heath over night.

As announced yesterday, I am about to get back to the study on PGC-1 alpha-4, the protein Carl Lanore and I talked about in the last installment of the SuppVersity Science Round-Up on Thursday. Since I am not going to simply repeat everything I already said during the show here, I suggest you download the podcast and listen to it before you read this article. Thus you would have a basic understanding of what the Ruas' study is all about and can class the additional information this article is going to provide with the stuff you've heard on Super Human Radio. If you don't have the time or are just sitting in the office, where listening to a radio show is not really an option, I would guess that those of you who have been around on the SuppVersity for some time now, should be able to connect the dots on their own.

PGC-1 alpha-4 the missing link between myostatin, IGF-1, hypertrophy and strength gains

With the combination of in-vitro and in-vivo data from rodents and humans the study Roas et al. published in the latest issue of Cell is a seam of information - literally. Actually, this is part of the reason, why I decided to restrict the following discussion to a summary of those findings that are either of general interest or can serve as a rational foundation for practically relevant conclusions, instead of simply reiterating the whole protocol.

• 

  Figure 1: Fluorescencemicroscopy analysis of myotubes expressing GFP alone or together with PGC-1 a1 or PGC-1 a4 (left) and effects on the expression of selected RNAs (Roa. 2012)

  PGC-1 alpha and its splice variants - The four known splice variants (alpha 1-4) the scientists tested for are expressed in most of the major organs of our body. Of particular interest for our discussion here are alpha-1 and alpha-4, with the former influencing 2002 and the latter controlling 519 gene function. The overlap between the two (98 genes) is actually pretty small, so that their downstream metabolic effects can be expected to be about as distinct as their underlying triggering mechanisms.
  
  While the energy sensing system appears to be responsible for the expression of PGC-1 alpha-1 (learn more about AMPK and how your body controls glucose uptake mitochondrial activity of the cells etc. depending on the local availability of energy), PGC-1 alpha 4 expression in skeletal muscle and thus the downstream effects on myostatin (inhibition) and IGF-1 (promotion) appear to be controlled by (contractile, but also metabolic) stress. Whether this is actually the case and in how far certain overlaps do exist will yet still have to be evaluated in future studies.
  
  

  

  Figure 2: Training or overtraining - good or bad inflammation; it's often difficult to hit the sweet spot (background adapted from Kramer. 2007)

  The same goes for the exact involvement of MAPK and other stress-sensors in our bodies and the dose-response relationship between the ROS and exercise induced expression of inflammatory factors such as IL-6 => NF-KappaB and their short term beneficial effects on the training induced adaptation processes (see figure 2). What can be said for sure, though, is that over-training and the downward spiral on the right side of  figure 2 is way more likely to be the underlying cause of suboptimal results, than an absence of adequate training stimuli on the left. Adequate recovery (primarily via rest + food and not by popping supplements or suppressing your well-deserved drowsiness with stims) is therefore about as, if not more important than the one additional rep you may or may not be able crank out at the end of an intense workout.

•  What exactly can PGC-1 alpha 4 do? The trends in RNA expression in figure 1 do actually give you an idea of what the ensuing effects should be, but I guess some actual data will make it even more obvious what all these gene essays mean.

  

  Figure 3: Effect of injected PGC-1 a  and DNA manipulation on muscle fiber composition and overall muscularity and phenotype of the rodents (Ruas. 2012)

  As the data in figure 3 goes to show, the effects of PGC-1 alpha 4 injections are almost identical to what you would see to a standardized hypertrophy training. And as you may remember from my dissertation on the podcast, the >17x increase in PGC-1 alpha 4 expression in response to reloading of a previously suspended hindlimb in the scientists' rodent model would confirm just that: PGC-1 alpha 4 is expressed in response to muscular overload (as it does obviously occur, when you have not moved your leg an inch for 10 days) and initiates adaptation processes that are meant to strengthen and "build" the muscle to ensure that it is up to future challenges like this.
  
  

  

  Figure 4: Immunohistochemical analysis of gastrocnemius muscle from wild-type (WT) and Myo-PGC-1 a4 animals

  Due to the fact that the effects Roas et al. observed were muscle fiber specific and quasi non-existent in muscles that are predominantly slow twitch fibers (e.g. soleus or planatris), the concomittant boost in MHCIIa and MHCIIx myosin heavy chain types you see in figure 4 may easily be misinterpreted as a "transformation" of muscle fibers. If you look closely at the immunohistochemical analysis of the gastrocnemius muscle from wild-type (WT) and Myo-PGC-1 a4 animals in figure 4 the pictures do yet speak a very different language. If anything, the amount of the very fast twitch glycolytic (only) type IIb fibers may have dimished ever so slightly. The amount of slow twitch oxidative muscle fibers, on the other hand, remained constant, while the number of both MHCIIa and MHCIIx positive myofibers increased (the same happens, as you should remember from the Intermittent Thoughts in bodybuilders and recreational trainees, as well).
   
• PGC-1 alpha 4 boosting agents include clenbuterol 5x (see Friday's "SuppVersity Science Round-Up Seconds"), forskolin 25x (both in vitro) and cold exposure (4°C) in rodent (!) brown adipose tissue.

Aside from the anti-cancer cachexia effect which is not directly related to the topic of this post, the previous paragraphs and the podcast should actually give you the most important information about this recently discovered splice variant of PGC-1 alpha, so that we can now segue into the "real-world" part of the study and take a closer look at the interactions with strength and cardio training I have been talking about on Thursday, as well.

Exercise and PGC-1 alpha 4 in real human beings

You cannot tell me that you have never heard of the notion that doing cardio not after but either before or or in-between your lifts an have its merit. If you can't remember it anyway, go back and reread "Before, After or In-Between? Study Puts Another '?' Behind the Widely Accepted 'Cardio After Weights' Paradigm."

Previous research associated PGC-1 alpha increases primarily with endurance training and, albeit to a lesser degree, glycogen depleting high intensity interval training (HIIT), or high volume resistance training. Over the years all of these training forms have been shown to contribute to mitochondrial biogenesis, a repartitioning of fiber types towards a more versatile oxidative myosin heavy chain pattern (similar to what you see in figure 4), the AMPK mediated stimulation of fatty acid oxidation and glucose uptake, angiogenesis and the prevention of muscle atrophy (Arany. 2008). The discovery of this new splice variant of the PGC-1 alpha protein does not diminish the significance of any of these results, but it does make one thing pretty obvious: Building muscle, endurance and oxidative capacity (mytochondria) are not mutually exclusive processes and it is very likely that there is a strong overlap between the metabolic and mechanic triggering processes.

It does in fact look as if the PGC-1 alpha "family" stands, if you will, at the crossroads of the aforementioned pathways with the "classic" alpha 1 variety being triggered by AMPK (and maybe other nutrient sensors) and the alpha 4 variety responding to the exercise-specific increase in stress signals. The results of the 8-week human study, Roas et al. conducted does yet show that things are - once again - not as easy as it may seem. If you look at the three training groups the subjects (the researchers don't provide details about age or training status, but probably young untrained men) were randomly assigned to...

• 

  Figure 5: Mo & Thu and Tue & Fri workouts (top) and results of the analysis of the biopsies that have been taken 48h after the last training session (Roas. 2012)

  Endurance Training (ET): During week 1, participants completed 30 min of stationary cycling at 65% VO2 peak 3 days per week. During week 2, participants completed 45 min of stationary cycling at 65% VO2 peak 3 days per week. During week 3, participants completed 45 min of stationary cycling at 65% VO2 peak 5 days per week. During weeks 4-8, participants completed 60 min of stationary cycling at 65%VO2 peak 5 days per week. 
• Resistance Training (RT): During week 1, participants were familiarized with resistance training program and practiced the movements with light weight during each of the four training sessions. During week 2, participants completed 2 sets of 8-10 repetitions to failure 4 days per week. During week 3, participants completed 3 sets of 8-10 repetitions to failure 4 days per week. During weeks 4-8, participants completed 4 sets of 8-10 repetitions to failure 4 days per week. Table S1 presents the full exercise program. 
• Combined Training (CT): The progression of the ET was the same as that described for the ET group, except that the durations were half as long as the ET group (i.e., 30min versus 60min). The progression of the RT was the same as that described for the RT group, except that the number of lifts was less the RT group. 

... as well as the exact protocol they have been following (figure 5, top), you would probably not have expected that the combined training protocol would have an edge over the higher volume resistance training in terms of both PGF-1 alpha 4 expression, as well as the decreases in myostatingthe increases in IGF-1, and the effective mean strength gains on the leg press (+30% for both with a minimal, statistically non-significant edge for the combined regimen; not shown in figure 5).

Implications: Why doing "cardio" before a workout could be beneficial

Figure 6: Free fatty acid levels before depletion (S1) and before (S2) and after (S3) exercise trial, as well as PGC1-alpha and p-AMPK expression (Psilander. 2012)

In the absence of detailed information about the increases in muscle CSA and protein content, it may be a bit too early to formulate any implications, but since the question of "doing cardio before a workout" was at the heart of an interesting discussion some of you started in the comment area to Friday's installment of the Seconds, I want to pick up on that and present a couple of garbled thoughts and references that may explain why the combined training did produce greater increases in PGC-1 alpha-4, as well as more pronounced downstream effects on myostatin and IGF-1 than the "growth specific" strength training program.

Now, one of the beauties of having your own blog with 1020 individual posts is that you can often simply refer people to previous posts such as the one from which I just copied figure 6 into this article. In fact, the title "8x Increase in "Mitochondria Building" Protein PGC1-Alpha W/ Medium Intensity Exercise in Glycogen Depleted Elite(!) Cyclists" actually gives away most of the 'secret' that's probably behind the purported benefits of a combined training regimen: Glycogen depletion!

Can I do HIIT instead? Personally I don't see any reason why you could not replace the 30min of steady state exercise with 10-15 minutes of HIIT (including active rest), but you should be aware of the fact that this will be more taxing on your central nervous system and probably more likely to result in a decrease in exercise performance on the subsequent workout, than sitting on an ergometer cycling at 60% of your VO2max. If you feel that it works for you - fine, but don't complain if in a year from now you still don't look like Mr. Olympia ;-)

Now the Psilander study does show that glycogen depletion, which is essentially what will happen (at least to a certain degree) if you perform 30 min of cardio training at a non-exhausting, but still energy consuming pace of 60% of your VO2 max before a workout does work. Without differentiating the various iso-forms of PGC-1 alpha Psilander's 5x increase in PGC-1 does yet not tell us whether we are dealing with the "right form" of PGC here. After all, the Psilander protocol involved two endurance sessions, with the first being a depletion session that was conducted on the day before the actual test and the second being a HIIT-esque exercise test (go back to the original post for more details).  Fortunately, there are 2019 other articles on the SuppVersity so that I don't even have to refer you to a study I have not already written about to add another piece to the puzzle.

A blast from the past and a glimpse into the future

On Wednesday, October 31, 2012, I wrote about the results of a study by Lundberg et al.. Again a slightly different protocol, this time with "cardio" in the morning and strength training later in the day, yet the exact same benefits in terms of PGC-1 alpha (total) expression:

Figure 7: 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. 2012)

With the more pronounced drop in myostatin in the combined training group in the Lundberg study, the only thing we would still need to further support the practical value of the more recent results from the Roas study would be a concomitant increase in IGF-1, as we would expect it, if working out in a (partly) glycogen depleted state would actually be the reason for the increase in PGC-1 alpha 4 Roas observed in the subjects of his study. Now I could copy and paste another graph, but I guess it will be enough, when I refer you back to the detailed elaborations on the connection between IGF-1 and it's muscle-specific splice variants and exercise induced beneficial, since acute and hormetic inflammation in the "IGF, MGF & Inflammation" part of the Intermittent Thoughts on Building Muscle (click here for an overview).

Please keep in mind: Regardless of the fact that previous studies did not test for the PGC-1 alpha subtypes, we cannot ignore the existing evidence that PGC-1 is not mandatory for the beneficial effects of endurance exercise on mitochondrial biogenesis (e.g. Rowe. 2012) and should therefore not overestimate the importance of PGC1 alpha 4 as the "one and only" muscle builder. I have said that before, but I guess it's important to repeat it - this is another missing link it's just like mTOR, testosterone and whatever other magic bullets people will tell you about not exclusively responsible for increases in muscle mass, mitochondrial capacity and whatever else you may just be dreaming of.

If we now add a couple of additional findings to this intellectual brew, like ...

• the 100% increase in the expression of the heat shock protein HSP72 in a glycogen depleted vs. normal leg during a workout (Febbraio. Feb 2002)
• the 150% increase of intramuscular HSP72 in response to an infusion with low doses of interleukin-6 (Febbraio. Sep 2002)
• the non-existant negative side effects of IL-6 on muscle glucose uptake in healthy individuals (Steensberg. 2003)
• IL-6's importance as a regulator of glucose metabolism during exercise (Helge. 2003; Febbraio. 2004) and it's satellite cell proliferation promoting effects (McKay. 2009) 
• the Dr. Jakyll and Mr. Hyde nature of inflammation, in general and IL-6 in particular on glucose uptake and fatty acid oxidation, when it comes to its local and temporary (=beneficial effects) vs. systemic and chronic (=detrimental effects) presence in our body (Fisman. 2010)

...we do actually arrive back at where we came from, namely the difference between training and overtraining in figure 2.

Bottom line - cardio pre-workout as an intensity technique: On the basis of these considerations you can think of doing cardio before a workout as an intensity technique that will increase the beneficial stress and thus the demand for greater adaptive responses. That the latter will go hand in hand with an increased propensity of overtraining, particularly if you are not willing to (A) supply your body with the nutrients it needs after the workout and (B) to rest for an adequate amount of time before you hit the gym again, is something of which I would appreciate if it wasn't something I had to repeat in each and every SuppVersity article, but since this is and will probably remain the #1 reason why people don't make progress physique- or performance-wise, it's still the most important take home message at least for those of you who are new to the site. I hope this did not ruin this allegedly pretty lengthy post for you and believe I am not promising too much, when I say that you are soon going to read more about this protein here - after all, it's almost certain that we are going to see follow-up studies in the months to come.

References:

• Arany, Z. PGC-1 coactivators and skeletal muscle adaptations in health and disease. Curr. Opin. Genet Dev; 2008: 426–434. 
• Febbraio MA, Steensberg A, Walsh R, Koukoulas I, van Hall G, Saltin B, Pedersen BK. Reduced glycogen availability is associated with an elevation in HSP72 in contracting human skeletal muscle. J Physiol. 2002 Feb 1;538(Pt 3):911-7.
• Febbraio MA, Steensberg A, Fischer CP, Keller C, Hiscock N, Pedersen BK. IL-6 activates HSP72 gene expression in human skeletal muscle. Biochem Biophys Res Commun. 2002 Sep 6;296(5):1264-6.
• Febbraio MA, Hiscock N, Sacchetti M, Fischer CP, Pedersen BK. Interleukin-6 is a novel factor mediating glucose homeostasis during skeletal muscle contraction. Diabetes. 2004 Jul;53(7):1643-8.
• Fisman EZ, Tenenbaum A. The ubiquitous interleukin-6: a time for reappraisal.
  Cardiovasc Diabetol. 2010 Oct 11;9:62.
• Helge JW, Stallknecht B, Pedersen BK, Galbo H, Kiens B, Richter EA. The effect of graded exercise on IL-6 release and glucose uptake in human skeletal muscle. J Physiol. 2003 Jan 1;546(Pt 1):299-305.
• Kramer HF, Goodyear LJ. Exercise, MAPK, and NF-kappaB signaling in skeletal muscle. J Appl Physiol. 2007 Jul;103(1):388-95.
• McKay BR, De Lisio M, Johnston AP, O'Reilly CE, Phillips SM, Tarnopolsky MA, Parise G. Association of interleukin-6 signalling with the muscle stem cell response following muscle-lengthening contractions in humans. PLoS One. 2009 Jun 24;4(6):e6027.
• 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 2012 [ahead of print]
• Rowe GC, El-Khoury R, Patten IS, Rustin P, Arany Z. PGC-1α is dispensable for exercise-induced mitochondrial biogenesis in skeletal muscle. PLoS One. 2012;7(7):e41817. Epub 2012 Jul 24.
• Ruas et al. APGC-1aI soform Induced by Resistance Training Regulates Skeletal Muscle Hypertrophy. Cell, December 7, 2012; 151:1319–1331.
• Steensberg A, Fischer CP, Sacchetti M, Keller C, Osada T, Schjerling P, van Hall G, Febbraio MA, Pedersen BK. Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans. J Physiol. 2003 Apr 15;548(Pt 2):631-8. Epub 2003 Mar 14.

Are You Overtraining? Two Scientifically Proven Methods to Test Yourself - Method 2: The ABEL Sport Test. Plus: 54 Item Questionnaire + 8 Additional Clues to Identify Overtraining

Theoretically it's already available for everyone. Costs are yet not the only thing you should keep in mind before you buy into Knight Scientific's overtraining analysis system

I've got plenty of positive, skeptic and euphoric feedback in response to last week's first installment of this two-part series on "proven" methods to test for overtraining syndrome (OTS). Before I tackle method number two in today's second installment, I do thus want to briefly remind you that the HRV method is not going to work, when you are chronically overtrained, already. It's also questionable, whether it will be able to identify parasympathetic overtraining syndrome (POTS). The latter is associated with marked decreases, not increases in the ratio of high / low frequency component (Portier. 2001). In people who train intense and with a high volume this effect can even mask the early increase in sympathetic tone and would thus render the HRV method basically useless.

You can learn more about overtraining at the SuppVersity

Heart Rate Variablity (HRV)

ABEL Sports Test + More

Overtraining & Undereating

Calculate your Energy Intake!

There Are No Magic Macros!

Reinvent Your Training!

More alternative tests / indicators of overtraining:

• increased sensitivity of 5HT receptors ➯ early fatigue (Budgett. 2010)
• free testosterone and testosterone/cortisol ratio higher than 30% (Cunha. 2006)
• increasing serum urea and decreased ammonia at rest w/ identical protein intake, indicative of higher gluconeogenesis from protein (Urhausen. 2002)
• low urinary catecholamines, esp. during night and w/ parasympathetic overtraining (Lehmann. 1992) and low ACTH and/or GH response to maximal exercise (~adrenal fatique; cf. Urhausen. 2002)
• inverse ‘iceberg profile’ in Profile of Mood State (POMS) scale (Morgan. 1987) and messed up sleep (Urhausen. 1998)
• decreased glucose & increased fat oxidation during high intensity exercise (Urhausen. 2002)

None of these markers can serve as a sole marker of overtraining. They can however support conclusions you make based on questionnaires, performance data and HRV analyses.

For method number two, so-called ABEL-Sport Test, these interferences between symathetic (~intensity, short(er) term) and parasympathetic (~volume, long(er) term) overtraining shouldn't be a problem. The test is easy, but it's not free. You will after all have to buy a portable luminometer to measure the optical properties of your blog. In other words, the ...

"[...] test does not measure a single biomarker of OTS [overtraining syndrome] but instead utilises hidden information acquired by circulating leucocytes as they patrol the body spotting pathogens, responding to markers of inflammation (cytokines and chemokines) and other changes in the blood that occur after strenuous exercise." (Knight. 2013)

As J Knight, M Wakeman, J Reeves, who have a vested interest in research into their own products, which have been used by elite and amateur athletes in many different fields and were "successfully used" by Skandia Team GB for two years prior to and in the final run up to the Olympics in Beijing in 2008, when Britain’s squad topped the medal table in the Olympic sailing competition, point out, the test is designed to elicit this "hidden information from the cells" (and I should add "hidden information that requires interpretation"!).

The technology relies on the bioluminescent protein Pholasin. It emits light, when it gets in contact with reactive oxygen specimen (ROS). To test the amount of leucocytes in a 5-20µL sample your blood you do thus just have to react it with Pholasin, activate the ROS response of the leukocytes and measure the light response (Roberts. 1985, 1987; Knight. 1999). By superimposing the results on a set of reference sample curve, Knight et al. are then (that's at least the claim) able to identify various responses during training, "indicating if the athlete is heading towards OTS and identifying infections, superimposed on training curves." (Knight. 2013)

With score way beyond 25 (15 is the first signal of OT), it's usually a good idea to take some time off and re-start your training at a saner intensity / volume - irrespective of ABEL or HRV results.

Stay skeptic! Despite the fact that a very similar technology has already been used in the analyses of the effects of foods and cosmetics, there is as of yet no independent comparison of the accuracy of the interpretation of the leukocyte ROS responsible on which Knight et al. base their assessments of the training status.

The word "interpretation" should have made you sit up: Even if the scientists are able to provide a cost-effective solution for individual hobby athletes, it is not guaranteed that the results are actually going to help you control your training load. Before the beneficial real-world effects Knight et al. observed in sailors, footballers and other athletes are confirmed in a well-controlled study by an independent team of researchers, I would thus suggest you rely on the traditional rules of thumb, your personal training experience, the HRV method and the overtraining questionnaire on the right of this "bottom line".

References:

• Budgett, R., Hiscock, N., Arida, R., & Castell, L. M. (2010). The effects of the 5-HT2C agonist m-chlorophenylpiperazine on elite athletes with unexplained underperformance syndrome (overtraining). British journal of sports medicine, 44(4), 280-283. 
• Cunha, G. D. S., Ribeiro, J. L., & Oliveira, A. R. D. (2006). Overtraining: theories, diagnosis and markers. Revista Brasileira de Medicina do Esporte, 12(5), 297-302.
• Knight, J. (1999). Rapid, simple and sensitive blood biocompatibility tests with the light emitting protein Pholasin®. Proceedings of the TechMed/Medical Device Technology Conference. Advanstar Communications UK Ltd, Chester, 3-17.  
• Knight, J., Wakeman, M., & Reeves, J. (2013). Abel-Sport™ Test For Assessing Over Training Syndrome And Detecting Infection. British journal of sports medicine, 47(17), e4-e4.
• Lehmann, M., Gastmann, U., Petersen, K. G., Bachl, N., Seidel, A., Khalaf, A. N., ... & Keul, J. (1992). Training-overtraining: performance, and hormone levels, after a defined increase in training volume versus intensity in experienced middle-and long-distance runners. British journal of sports medicine, 26(4), 233-242.
• Morgan, W. P., Brown, D. R., Raglin, J. S., O'connor, P. J., & Ellickson, K. A. (1987). Psychological monitoring of overtraining and staleness. British Journal of Sports Medicine, 21(3), 107-114.
• Portier H, Louisy F, Laude D, Berthelot M, Guézennec CY (2001). Intense endurance training on heart rate and blood pressure variability in runners. Medicine and science in sports and exercise, 33(7), 1120-1125.
• Roberts, P. A., Knight, J., & Campbell, A. K. (1985). Pholasin®: a new bioluminescent indicator for cell activation. Biochem. Soc. Trans. 1140, 1139-1140. 
• Roberts, P. A., Knight, J., & Campbell, A. K. (1987). Pholasin®: a bioluminescent indicator for detecting activation of single neutrophils. Anal. Biochem. 160, 139-148.
• Urhausen, A., Gabriel, H. H. W., Weiler, B., & Kindermann, W. (1998). Ergometric and psychological findings during overtraining: a long-term follow-up study in endurance athletes. International journal of sports medicine, 19(2), 114-120.
• Urhausen, A., & Kindermann, W. (2002). Diagnosis of overtraining. Sports medicine, 32(2), 95-102.

Are You Overtraining? Two Scientifically Proven Methods to Test Yourself - Method 1: Heart Rate Variability Analyses

It may sound like the invention of the heart rate monitor industry, but it's a matter of scientific "fact" that HRV analyses are a great tool to monitor and manage training and recovery.

Overtraining, its existence, consequences and detection is and has always been one of the hottest topics in the fitness community. While some practitioners and trainers claim that it does not even exist, others fear it so much that they constantly undertrain. The result? Stagnation.

In the highly competitive world of the average iron-willed gymrat, it's however pretty rare that the gains ain't coming, 'cause he or she is under-training. I would guesstimate that the exact opposite is the case for at least 75% of the self-proclaimed hard-gainers. Overtraining, undereating and/or  a lack of consistency are the stumbling blocks of 99% of the trainees.

I know that you know all that, ...

... so I'll cut this short and get right to the point. Within the past two weeks I hit upon two interesting papers that describe very different, but - in both cases - effective methods to determine whether you are overtraining, or not. While I originally wanted to tackle both in one article, I had to realize that the day has only 24h for my to write and you to read SuppVersity articles. Therefore, I decided to tackle heart rate variability monitoring today and postpone writing about the other to next week's follow up (stay tuned!).

You can learn more about overtraining at the SuppVersity

Heart Rate Variability

ABEL Test

Overtraining & Undereating

Calculate your Energy Intake!

There Are No Magic Macros!

Reinvent Your Training!

I guess you may have heard about the usefulness of the latter on my buddy Carl Lanore's Super Human Radio, already and are thus familiar with the idea that your heart’s ability to produce fluctuations in the beat-to-beat interval in response to different situations. According to José Morales and his colleagues from the Laboratory of Sport Sciences a the Ramon Llull University in Spain,

Don't turn into the guy on the left, don't overtrain & undereat | learn more

"the use of heart rate variability (HRV) as a training tool has progressively increased and deserves attention as a tool to monitor the possible states of overtraining and recovery after a training process. [...] Several studies suggest that the quantification of HRV can be used as a non-invasive method for assessing autonomic  cardiovascular  control  via  the  impact  of  HRV  on  beat-to-beat  heart  rate  modifications." (Morales. 2013)

The relationship between autonomic modulation and HRV is different during exercise and immediate recovery compared to rest periods. This makes the HRV a viable tool for the non-invasive assessment of the autonomic cardiovascular control and a comparatively objective measure of your training status (Camm. 1996; Seiler. 2007; Bosquet. 2008) .

Hold on: What exactly is my HRV? Actually it's much less complicated than terms like fourier-transforms and frequency domain suggest. If you say "my heart rate is 60 beats per minute", this is an average you measured over a certain timespan. If you counted every beat for 60s, for example, the iterval between the beats probably was not exactly 1s. One beat may have been "premature", another took a little more than one second to finally come. The HRV is a measure for the variation in the time interval between heartbeats. In other words, if your heart beats 60 times per minute 24/7, your HRV would be zero and you're probably a cyborg ;-)

The HRV responds particularly to heavy loads / intense workouts. The magnitude of the workout-induced stress is thought to be proportional to the activation of the sympathetic arm of the autonomic nervous system and thus the variations in autonomic balance, which can be indirectly assessed using HRV analysis (Seiler. 2007). A significantly lowered HRV days after a heavy workout is thus a signal that your central nervous system is still recovering. It tells you that you'd better insert a light cardio day or spend the time with friends instead of getting back onto the grind for another torturous 5x5 session.

Technology vs. psyche - HRV vs. RESTQ-Sport

Compared to psychological tests like the Recovery Questionnaire for Athletes (RESTQ-Sport), which is frequently used in research to observe the balance between stress and recovery during training processes, the physiological data you evaluate with the HRV method is obviously more objective. It is yet still debated whether it is also reliable and can / should replace or complement the classic psychological testing procedures.

Table 1: Overview of the training weeks of the two groups (Morales. 2013)

For Morales and his colleagues this doubt was among the most important reasons to conduct a study that would integrate both methodologies. To this ends, the researchers recruited 14 male national-standard judo players (age 22.85 years; height 174.08 cm; body mass 76.85 kg) and randomized them to four-weeks of...

• high training load (HTL - 8 sessions per week ➙ short recovery periods)
• moderate training load (MTL - 4 sessions per week ➙ long recovery periods) 

For the detection of the HRV at the beginning of the first and last session in weeks 1 and 4, the researchers used a Polar S810 cardiotachometer which provided the scientists with the following parameters either directly or the corresponding data to calculate them:

Figure 1: A wide spread (green ellipse) of the poincare plot indicates full recovery.

• the mean inter-beat (RR) interval,
• the standard deviation of the inter-beat (RR) interval , 
• the heart rate & its standard deviation
• the square root of the mean squared difference of successive RR intervals, 
• the number of consecutive RRs that differed by more than 5 ms each, and 
• the percentage of consecutive RRs that differed by more than 5 ms each

That sounds extremely complicated, but in the day and age of automated data acquisition and immediate processing (including fourier transformation to get the frequency data, etc.), there are lot of tiny little gadgets and apps that can do all the hard math-work for us.

HRV + RESTQ-SPORT + HTL vs. MTL = reliable training analysis

The next thing they did was to to simply plot pairs of inter-beat intervals, e.g. 1/60 vs. 1/64, 1/64 vs. 1/76, etc. the resulting graph is a so-called poincare plot (see Figure 1) and the spread of the point in this graph can tell you whether you are well-rested (wide ellipse) or overtrained / need rest (narrow ellipse)

Figure 2: Changes in selected HRV variables, left; performance, as well as stress + recovery values in the RESTQ-Sport, right; all differences expressed relative to values at the beginning to study (Morales. 2013)

The data in Figure 2 (left) does yet demonstrate - the poincare plot of the inter-beat variables characterizes the decreased heart rate variability (HRV) quite well.

"The multivariate test indicated that there was an interaction effect between the testing time and group on HRV variables. [...] the HTL group showed lower square root of the mean squared difference for successive RR intervals, very low frequency, high frequency, short-term variability and short-range scaling exponent in the post-test than in the pre-test (p < 0.05). The HTL group showed higher low/high frequency ratio in the post-test than in the pre-test. Finally, there were no differences between the pre-test and post-test in the MTL group." (Morales. 2013)

In other words: While the HTL group showed the expected increase in HRV, the judo players in the MTL group did not experience any significant changes in heart rate variability.

The question that remains - at least until you take a look at the data in Figure 2 (right) - is: Do these abstract figures really tell me that I am overtraining? The answer the comparison to the data from the RESTQ-Sport questionnaire gives us is YES, it does!

Don't be that guy or girl who works his / her ass off for nothing. Learn how to identify and combat the Athlete's Triad | read all articles.

Bottom Line: The accumulating scientific evidence and the ever-increasing number of practitioners (trainers and trainees) who rely on heart rate variability analyses to judge whether or not they are over-training clearly suggest that a heart rate monitor and the appropriate software (usually part of the bundle) would make a valuable addition to any (over-)ambitious athlete's Christmas gift list.

If there is still room for another present on your wishlist, I'd suggest you come back next week for part II of this series, to learn about another, maybe sexier method to find out whether your perception that training 1h-2h with no sweat every day won't have you overtrain (note: not sweating or feeling cold in the gym can be signs of severe or chronic overtraining).

Reference:

• Bosquet, L, et al. "Is heart rate a convenient tool to monitor over-reaching? A systematic review of the literature." British journal of sports medicine 42.9 (2008): 709-714.
• Camm, A. J., et al. "Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology." Circulation 93.5 (1996): 1043-1065.
• Morales, J., Álamo, J. M., García-Massó, X., López, J. L., Serra-Añó, P., & González, L. M. (2013). The Use Of Heart Rate Variability In Monitoring Stress And Recovery In Judo Athletes. Journal of strength and conditioning research/National Strength & Conditioning Association. 
• Seiler, Stephen, Olav Haugen, and Erin Kuffel. "Autonomic recovery after exercise in trained athletes: intensity and duration effects." Medicine and Science in Sports and Exercise 39.8 (2007): 1366.  

Adelfo Cerame - Road to The Wheelchair Nationals '12: Ambitious Short-Term Goals Pave the Way to Success.

Image 1: This guy likes to suffer - no, not
what you are thinking now ;-)

I don't know about you, but I cannot stand how people constantly complain about how bad things are, how hard they are working (mostly these are the laziest people I know), how little they are paid, how desperate the economy was,... you know the whole litany, don't you? Then, Adelfo Cerame's weekly blogpost is exactly the diversion you probably need today. I mean don't get me wrong. Adelfo is only human, so he likes to complain, as well. But believe it or not, this guy complains about not suffering enough!? So just to make sure you get this right. Adelfo Cerame Jr. aspiring future pro-wheelchair bodybuilder suffers, because he does not suffer enough... does not make sense? Well, I guess, I'll better have him explain his "problem", then ;-)


Goalsetting 101: Short-term goals keep you on track

You think you could use some advice on your own training, diet and supplementation regimen and want it from someone who obviously knows what it takes to build muscle and lose fat? You can reach out to Adelfo via Facebook.

When you want to achieve something in life, setting specific and testable goals is always the necessary first step. Mostly, you won't have any difficulties naming your long-term goals - in my case, for example the it is to win the 2012 Wheelchair Nationals. It is, however, also necessary to pick short-term goals in order not to lose yourself on your journey from A to B. After all, long-term goals are exactly what their name implies.... they are LONG. More often than not, you will feel that you have been working towards them for ages, which can become so discouraging that you end up in despair, negate all the small steps you have already taken and surrender to what you believe would be the "fate of the loser" that you are. Some people, on the other hand, react completely different. They become complacent, keep telling themselves how good they already look, how much they already achieved and how well everything worked out... obviously a completely different mistake, yet with similarly unrewarding outcome. To prevent these types of roadblocks, I have made a habit of setting up an exact time-line of short-term goals to accomplish. By doing this, I keep myself motivated, and on my toes (or in my case, on my wheels) to get to the one "distant" long-term goal of which you can lose sight so easily.

I am in week 7 of my contest prep, now. And, psychologically, this has been one of my easiest contest preparations, so far... this does not mean that it could eventually become tough further down the road, but based on my previous experience, I can usually tell if it's going be a rough cut pretty early on in my prep. When the hunger pangs, temptations and cravings are starting early, you know your in for a long cut. But so far nothing! No cravings, no temptations, and rarely any hunger pangs or none at all on most days of the week. I rarely even get excited or anxious on my designated re-feed / cheat days. I don’t feel sleepy, or tired, and my strength and energy is still up at the gym, and I haven’t been using any type of pre-workout, N.O. or creatine supplements, yet.

This is intriguingly easy - too easy!?

Ironically, the ease and smoothness with which things are rolling is what begins to scare me. Being used to the psychological stress, battles and mind games that I use to play with myself during dieting, I am constantly battling the thought that this ease is not what I am supposed to feel when I am dieting or preparing for a bodybuilding show… “If you’re not suffering, then you’re not doing it right!” But I’m not suffering. And yet I seem to be right on track or maybe even ahead of my schedule.

I mean, I do "suffer" the usual pain and fatigue you get while training heavy and intense, but if you remember the statement from Arnold about "da pump", Dr. Andro quoted a few blogposts ago, you will know that this kind of "pain" is what every serious bodybuilder is looking for. What I refer to as "suffering" is what the mental drain the incredible fatigue, the constant huger, the battle against cravings and hunger pangs... the kind of "suffering", when you you are dead tired from dieting so hard that you cannot even perform your daily routines... yet, thinking about it, even calling that "suffering" makes me feel somewhat ashamed. There are millions of people starving - these people have real issues, and people like you and me are complaining about something we are voluntarily doing to ourselves!? But anyway, let's get back to the topic at hand...

Image 2: Cream of Roast Beef, post-workout meal of the week.

Recipe of the Week: Cream of Roast Beef
(Post workout meal)

Ingredients:

• 7 oz roast beef (bottom round roast)
• 6 oz yam
• 5 baby carrots
• ½ c cottage cheese, topped w/ ½ c chopped apples, sprinkled w/ground cinnamon
• 2 tbs. low-fat sour cream
• 1 tbs. A1 steak sauce

Macros: 62g protein / 57g carbs / 20g fat

Quick tip: Personally, I eat more carbs around my workouts, but base all my meals on protein and fat on my off-days. So, if this was a rest day meal, I would take out the yam and replace the apples with a lighter fruit (lower in calories & carbs) like blueberries.

Raising the bar to outdo yourself: "Show ready" by week 12!

Since I’ve been cruising through my prep these past 7 weeks, I’ve decided to give myself a challenge or a short-term goal to prevent me from getting distracted and complacent, but to also keep me motivated (well I never really lost motivation, so I guess it's to add to my motivation) and give more light and focus to the real goal at hand, which is winning an overall title in March. The goal I picked is to be as close to "show ready" as possible by the 12-week mark, which should be Christmas day. Basically I’d like to be in the same type of condition Duong was in when he ended his 12 weeks (if you have not done that already, check out his amazing transformation in the SuppVersity Student Spotlight). Since it’s my first run at IF, I've been really gauging my progress with Duong's - from his macros, the type of foods he ate, to the schedule of his fast & feeding hours. I'm using Duong's progress as a checkpoint or marker, which means that if I am not in the same outstanding (or even better - sorry Duong ;-) physical condition as Duong was, when he hit his 12 weeks, then I need to pick up the pace and make some adjustments.

That being said, Duong gave himself "only" 12 weeks. I, on the other hand, deliberately started early and thusly do not have to cut my calories just as fast as he did ... it is nevertheless imperative that I do not develop the aforementioned complacency and eventually end up even worse than I would have when a relatively drastic, but short cut does not work out.

A log holds you accountable for your progress

My current plan is to maintain a daily caloric intake of 1.800 kcal/day until the end of November. This is in fact -100 kcal lower than the original plan. A plan, my instinct told me would not get me to where I decided I want to be by Christmas. Accordingly, I will drop my daily allowance to 1600 kcal/day in the first week of December '11. I am logging all my food and keeping track of all my calories and macros to a “T”, to be able to analyze which dietary tweaks worked, which didn't an which further alterations to my regimen will be most helpful.

Figure 1: Here’s an example of a program I made on my Macbook where I log my foods.

For the first month I was inconsistent with logging my foods. It was just easier for me to keep track in my head, but ever since giving myself this short-term goal, I made logging my foods just as much a priority as I do my training. Logging your foods and keeping track of your calories and macros also holds you accountable. You know every bite that you put in your mouth, so there’s no lying to yourself when you realize that you’re not making any progress, all the evidence is written down. When you look back and re-evaluate, you’ll know if you stuck to your diet or not... and what's more, logging my foods and keeping track of my numbers, soothes the feeling of "not suffering enough", it reassures me that I am doing everything to the literally "T" - no second guessing myself, no guilty conscious, and no elevated cortisol levels due to constant worries ;-)

It’s always a good idea to keep logs, especially if you’re just starting to learn about nutrition and dieting. Other than holding you accountable, food-logging helps you with learning about serving sizes, and how to count calories and macronutrients. And let me tell you, only when I began logging what I ate, I realized how little I actually knew about what I ate. Looking back four years, I have to admit that I did not even really know what a "protein" is, back in the days when I started.

Knowing your body and its limits is the key to success

On the non-dietary side of things, I noticed that I was getting a little burned out with the EDT in the course of the last week. My strength did not increase as much as it did the previous weeks, and I really felt fatigued the last training session of the week. So I took a break from EDT training this week and changed my workouts to a 5x5 routine, where I do 5 sets of 5 reps. I still lift heavy though. Depending on what muscles I train, I’ll do 7 exercises, and each exercise is 5x5. So for example on chest days, I’ll do 5 chest exercises and 2 triceps exercises, each exercise is 5x5, heavy. It felt pretty awkward going back to a regular split routine. I have gotten so used to the fast paced high-intensity EDT workouts that I wasn’t as hyped or amped during my workouts this week. Although I lifted heavy and intense (probably about the same if not more weight), I was not as mentally focused as I have been when I did the EDT cycles. I figure the best solution to this problem would be to alternate between a "regular" 5x5 split training and escalating density training regimen on a weekly basis. After all, the one week back on the "old" training split already paid off: my strength increased a lot! I guess after a few weeks without "classic" 5x5 training, my muscles were pretty shocked by what my brain tells me is an old hat ;-)

"In my opinion, classic cardio is way overrated and is for suckers!"

Image 3: Low-intensity cardio free! The only high intensity cardio I did during my prep in 09’ was hitting the heavy bag every other day for 30 minutes for the last 4 remaining weeks of my prep. I let my diet take care of the rest and suggest you do the same!

The comparatively low metabolic demand of 5x5 training also gave me the chance to pick up some 20-minute high intensity cardio during my rest days. I’m not a big fan of cardio, and I rarely do it, but when I do, I always enjoy doing high intensity cardio like hitting the heavy bag, doing sprints with my wheelchair or doing the burn machine (it’s a 10 pound hand cycle). I like to “get at it” for as hard as I can for 20 minutes, then I’m done. Don’t waste your time jogging on a treadmill for hours. That’ll get you nowhere fast (not even slow ;-)! Lift Heavy weights and do some sprints. That’s more productive and you burn more body fat than running on a treadmill for hour (assuming that you have your diet in check) .

You should never depend on cardio to transform your physique.

So whatever short- and long-term goals you may be setting in the course of the one week you will have to get along without another blogpost of mine, don't forget: "TRAIN SMARTER, NOT HARDER!"

Science Round-Up Seconds: Vitamin E Succinate, How It's Extracted from Barley Leaves, Kills Cancer, Ramps up Growth Hormone & Spikes Prolactin. Plus: Testostosterone & Thyroid Hormone Decline Due To Plyometrics & HIIT

Regardless of all the hypocritical hoopla around his persona, Lance Armstrong has always been able to push himself like no one else. No wonder that intense plyometrics were part of his regimen.

If the SuppVersity Science Round Up was a meal, I guess you could say that Carl Lanore and I were sort of gluttonous, yesterday (click here to download the podcast, if you have not already done so). We almost raced from one topic to another and therefore all the good stuff from the list is gone already and I am a bit pressed on time to get some "private life" in, so that I am not psyched about the idea of writing about auxiliary stuff.

Against that background and in view of the fact that I felt that the pace of yesterday's show did not really leave enough room for some important details, I will stick to rehashing and expanding on the stories about Vitamin E succcinate and the detrimental effects of beating the crap out of yourself doing plyometrics or crazy HIIT workouts (too regularly), in today's installment of the SuppVersity Science Round-Up Seconds.

Let's see. Why don't we start at the end of yesterday's show?

• Vitamin E succinate the most potent anti-cancer tocopherol known to man. As you have heard on the show, vitamin E succinate attaches directly to a protein that's preferentially expressed in carcinogenic or pre-carcinogenic cells. It goes by the name α-Tocopherol-associated protein (TAP) and was found to be one of the major α-tocopherol binding proteins in serum, liver, brain and prostate. What has as of yet not been so clear, though, is that the expression of this protein increases with the malignancy of (breast) cancer (Tam. 2012). 
  
  

  

  Figure 1: Effects of alpha tocoperyl succinate alone (TOS), doxorubicin alone (DOX) or both (DOX + TOS) on cell viability in human MB231 breast cancer cells (my edits, original from Tam. 2012) - note: The effect was less pronounced in other cancer cells, so that it is reasonable to assume that the efficacy of the therapy will depend on the exact genotype of the cancer (for those tested in the study it was MB231 > SKBR3 > MCF 10A)

  When alpha tocopherol succinate binds to the protein on the cancer cells, this will either alone, or in combination with chemotherapy trigger apoptosis and cell death. It is as of yet not fully elucidated why vitamin E succinate is highly cancer-specific and leaves the healthy cells intact, but this could be related to the high metabolic rate and exuberant ROS production of cancer cells. There is however some research that would suggest that the cancer cells literally suffocate in their own radical oxygen specimen (ROS), which can no longer be cleared from the cell, due to the alpha-tocopheryl succinate induced displacement of ubiquinone from CII and the subsequent blockade of succinate dehydrogenase (SDH) activity (Dong. 2012).  If this hypothesis holds true it would therefore appear that long-term chronic supplementation with vitamin E succinate cannot be recommended until future studies on its general safety have been undertaken. As an adjuvant to chemotherapy, on the other hand, it could drastically reduce the dosage requirements during chemotherapy in specific types of cancer (see figure 1) and thus minimize side effects.
  
  You see, there is more to it than you can say in two minutes on the radio and this is why I will make sure we don't rush through the items that fast, in the next show. Ah,... of course the dietary source. I had almost forgotten about that one. As mentioned on the show, alpha tocopheryl succinate was originally extracted from Barley leaves. An while this may not be the first paper dealing with this "natural vitamin E analog", the one by Badamchian et al. is probably the one you will be most interested in.
  
  Published in the Journal of Nutritional Biochemistry the paper does not only describe the isolation of vitamin E succinate from green barley leaf extract (BLE)...
  

  "BLE [barley leaf extract] powder (50 mg/mL) was suspended in water and stirred for 1 hr at room temperature. The mixture was then centrifuged at 3000g for 30 minutes using a bench-top centrifuge. The pellet was discarded and the supernatant was pre-filtered through a Millipore DEPTH filter. The filtrate was then filtered through 0.45 I.tM mem- brane and stored at -20 ° C for HPLC or biological assays." (Badamchian. 1999)

  ... it does also shine another spotlight on its potential biological effects, as far as it's ability to increase growth hormone, but (unfortunately?) also prolactin in isolated anterior pituitary cells from female rodents:
  

  

  Figure 2: Prolactin and growth hormone release in anterior pituitary cells of female rodents after incubation with different amounts of green barley extract in which vitamin E succinate had been deterimed as the main ingredient before (based on Badamchian. 1999)

  It's really hard to estimate whether or not one of these effects would translate from a rodent cell in the petri dish to you or me popping a cap with vitamin E succinate everyday. That's particularly true in view of the fact that the underlying mechanism of the increase in GH and the imho more concerning increase in prolactin is neither mediated by increases in intracellular C-AMP, as it would be the case for GRF (old acronym for growth hormone releasing hormone), nor is it induced by the hydrolysis of polyhoshpoinositide, which is the underlying mechanism of the stimulative effect of TRH (thyrotropin releasing hormone). So basically we neither know how it works, nor do we know, whether the oral ingestion of vitamin E-succinate would be sufficient to produce serum concentrations in the pituitary that would be high enough concentrations to make any difference at all (note: the scientists excluded the influence of other components of the extract by testing alpha tocopherol succinate on its own in a separate trial)
  
  Bottom line: Based on roughly one dozen of in-vitro studies there is simply still to little evidence to decide who, outside of people with a history of cancer or someone who is just undergoing chemotherapy would benefit. Therefore, I suggest you wait before you add vitamin E succinate to your list of 'must have' supplements. Is it promising? Sure! Is it exciting, yeah! Is it save for a healthy being to be taken chronically??? I can't tell.
• The detrimental hormonal effects of pushing yourself beyond the tolerable threshold - Hardcore plyometrics and heavy HIIT and their impact on testosterone, cortisol, thyroid hormone and co: I guess you did already get the main message when you listened to the show, but just to give you an idea about the actual quantities, I thought it would be nice to provide you with two graphs as a reference.
  

  

  Figure 3: Comparison of the hormonal responses measured in the plyometrics (left) and the HIIT vs. LISS (right) study (based on Ozen. 2012 and Hackney. 2012)

  If you focus mainly on the differential cortisol responses in the two studies, it would appear likely that we are dealing with two very different forms of 'overtraining' here. While the HIIT protocol (90s at 100-110%, 90s active recovery at 40% matched for workload with steady state jogging at 60-65% of the VO2 max) probably wouldn't be a problem, if the athletes would get adequate rest and nutrition in the days after the session, the 6-weeks of plyometrics (15 session, increasing density, 90-195 reps per session) were enough to send the participants right into the vicious circle of the Athlete's Triad (if you have not done so already, I suggest you read up on that in the eponymous SuppVersity series).
  
  And you know what? Despite, or I should probably rather say due to their compromised hormone levels the guys in the plyometrics study did not lose a single gram of body weight. Good for their muscle, bad for the fat which was likewise preserved by the hormonal shut down, which affected both cortisol and testosterone in a similar way. So is that good or bad news? Well, let me say it this way:. Usually I see people training for a purpose and while the outcome often is stagnation and chronic fatigue, I would suspect that only few of you will have that on their mind, when they are hitting the gym, right?

Apropos viscous circle, and overtraining in order to avoid "overblogging" I will call it a day for today. Come back tomorrow for a couple of wholly new studies from the realms of exercise and nutrition sciences and in case you are planning to drink this evening, I highly suggest you check out the SuppVersity Facebook newspost on the effects of green tea extract on the uptake of alcohol. It may well be that those old fatburner caps of yours can be put to a way better use ;-)

References:

• Badamchian M, Spangelo BL, Bao Y et al. Isolation of a vitamin E analog from green barley leaf extract that stimulates the release of prolactin and growth hormone from rat anterior pituitary cells in vitro. Journal of Nutritional Biochemestry. 1994; 5: 145-150.
• Dong LF, Low P, Dyason JC, Wang XF, Prochazka L, Witting PK, Freeman R, Swettenham E, Valis K, Liu J, Zobalova R, Turanek J, Spitz DR, Domann FE, Scheffler IE, Ralph SJ, Neuzil J. Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II. Oncogene. 2008 Jul 17;27(31):4324-35. Epub 2008 Mar 31.
• Hackney AC, Kallman A, Hosick KP, Rubin DA, Battaglini CL. Thyroid hormonal responses to intensive interval versus steady-state endurance exercise sessions. Hormones (Athens). 2012 Jan-Mar;11(1):54-60.
• Ozen, SV. Reproductive hormones and cortisol responses to plyometric training in males. Biol Sport.2012; 29 (3).
• Tam KW, Ho CT, Lee WJ, Tu SH, Huang CS, Chen CS, Lee CH, Wu CH, Ho YS. Alteration of α-tocopherol-associated protein (TAP) expression in human breast epithelial cells during breast cancer development. Food Chemistry. 2012 [ahead of print]

Measuring Overtraining; Phosphatidic Acid to Potentiate the mTOR Effects of Leucine? Plus: Built-in Serm in Menopausal HRT Blocks Breast Cancer, Creatine Bumps Up Performance Not Body Weight, Estrogen Timing & Brain NDMA Toxicity

Weight-supported sports such as cycling precipitate overtraining

"20%", that's the SuppVersity figure of the week. It tailors directly to the first item in today's installment of On Short Notice and denotes the amount of professional athletes who exhibit symptoms of overtraining syndrome at any given time in their career.

"The prevalence varies by sport and is thought to be highest in endurance sports requiring high volume intense training, such as swimming, triathlon, road cycling, rowing and, to a lesser extent, distance running."  (MacKinnon. 2000)

What all those sports (except for distance running) have in common are long training hours on 6 days per week for several months without appreciable time off. Notably, the chances of overtraining also increase, when the equipment supports your body mass. With weight-bearing activities, such as distance running, on the other hand, the risk of musculoskeletal injury limits training volume and therefore reduces the chance of "running" (literally) into overtraining.

Overall, there is however no group of athletes that is immune to training too long, too hard and without appropriate recovery times. And yes, this goes for power sports, such as weight lifting and judo, as well (cf. Callister. 1990, Fry. 1994)!

Identifying overtraining by psychomotoric evaluation  

When you come to think of it, it does actually stand to reason: Static and dynamic tasks for finger, hand, and arm movements, as they are assessed during a  series of tests to assess motor performance are a way better yardstick to determine the stress (over-)load on the central nervous system (CNS), than simply looking at "how much ya bench". Why? The nasty, creepy and easy to overlook form of overtraining happens largely in your head and your nerves, it's not muscular. Your skeletal muscle can be fully rested, while your central nervous system is at the verge of collapsing.

What does the motor-skill test measure? (1) steadiness (one or both hands) - assesses hand unrest, tremor; (2) inserting long pins (one or both hands) - assesses rate of arm and hand movements, precision of arm-hand movements, manual and digital dexterity; (3) tapping (one or both hands) - assesses wrist-finger speed

Usually the latter goes hand in hand with other not exactly exercise related stress symptoms such as nervousness, and the inability to cope with the imposed stress and piling-up difficulties. Therefore Paul et al. required that all the one-hundred 18-25y athletes (M=65, F=35; university to international level) from various athletic backgrounds, i.e.

• hockey (14%), volleyball (14%), basketball (13%), handball (12%), football (6%), cricket (2%),
• cycling (13%),  running (11%), kabaddi (8%),  swimming  (5%),  gymnastics (1%), and sprinting (1%)

to fill out a "classic" Training Stress Scale (TSS) questionnaire as well. The TSS is a 19-item scale to check the symptoms of acute overtraining which includes a subset of questions designed to assess  the ability of bouncing back mentally after setbacks and mistakes (REB).

Figure 1: Motor performance (steadiness error duration; inserting long pins task duration; tap hits) in 100 athletes grouped into low (LS), medium (MSG), and high (HSG) groups according to their scores on the TSS test (calculated based on Paul. 2012)

As you can see in figure 1 the results of the motor performance test did not just correlate with the data from the stress test questionnaire, they also depict a very good picture of the state of the nervous system, with highly significant difference between the highly stressed and almost certainly overtrained athletes (green) and their lightly stressed peers (figure 1, blue; stress data was assessed by the aformentioned TSS test).

Professional athletes rarely end up  like Christian Bale in the Machinist but as I discussed at length in a previous post, overtraining was one of the two pillars of the crazy regimen the actor used to starve himself into a state that hardly allowed him to perform in front of the camera.

Aside from the high correlation and the confirmation of the hypothesis that psychomotoric tests could prove a valid tool to access the training status of athletes and ambitious gymrats, the investigation yielded the following main results:

• The athletes with lowest training stress symptoms showed the highest reboundability (resilience) from their mistakes. 
• Increased intensity of training stress symptoms indicates attention deficit leading to poor psychomotor performance.
• Along with physical training, psychological training has to be considered as one of the eminent aspects of overall development of an athlete.

In order to maximize athletic performance, it is therefore more or less obligatory to "carefully and timely diagnose for any signs and symptoms for physical and psychological distress" (Paul. 2012). Needless to say that the combination of the TSS and psychomotor performance test offers a way to do just that - to monitor, control and optimize the training routine.

Phosphatidic acid a novel 'mTOR potentiator' for superior gains?

I somehow forget this one in the last installment of On Short Notice, but before the first supplements are going to hit the market (two of the authors have already filed a patent back in 2011 that hasbeen  published in June 2012; see De Ferra. 2012), I thought I'd briefly discuss the results of a recently published study on the potential ergogenic and muscle building effects of phosphatidic acid (PA) by Hoffman et al. (Hoffman. 2012).

The study that was published online in the Journal of the International Society of Sports Nutrition evaluated the effects of an 8-week resistance training on 16 resistance-trained men who had been randomly assigned to consume either 750 mg of PA or a placebo.

Figure 2: Effect of 8 weeks of strength training + post-wporkout amino acid supplementation with and without  750mg phosphatidic acid  per day (left) and ratio of beneficial, trivial and negative effects of supplementation on the respective outcome parameters (Hoffman. 2012)

As the data in figure 2 goes to show you, the supplementation regimen had beneficial effects almost all of the (except for the pennation angle, btw. where greater the angles of pennation, means translates to a smaller amount of effective force transmitted to the tendon), however not a single statistical significant difference was observed. And while the scientists assessment that the overwhelmingly beneficial effect of PA supplementation on lean mass gains is "very likely beneficial", this does not change that the 750mg of PA did not add to allegedly highly beneficial effects of the workout regimen.

Figure 3: Training protocol and amino acid content (in g/100g) of the post-workout supplement (identical in both groups).

Since all particpants had taken part in identical 4-day per week, split routine resistance training programs for 8-weeks (70% of their 1-repetition maximum (1-RM) for all exercises;  90-s rest period was required between each set, for all exercises; for the exercises check out figure 3) and were advised to consume a standardized post-workout protein formula (containing 36-g amino acid and collagen protein blend) mixed in a 500 ml commercial sports drink within 30 minutes post-exercise, the supplemental confounding factors were pretty tightly controlled. If anything but the consumption of the PA supplement would have been responsible for the inter-group differences this would therefore have to be related to

• the non-supervised training sessions at the subjects respective local gyms (training logs regardless of whether they are evaluated by "certified personnel", or not, can obviously be faked), and
• the absence of a prescribed nutritional regimen (the participants kept 3-day food-logs and were advised to stay on their habitual diet; no significant differences in total intake ~3,200kcal/day; according to Hoffman et al. likewise not statistical significant, but wrt to the the changes in body composition maybe noteworthy, were the -17% lower carb and +18.2% higher protein intake in the active = PA arm of the study)

Both the missing supervision, as well as the absence of a fixed nutritional protocol would however pertain to both groups and are thus likely to average out. Plus, they actually make the study more realistic. After all, you are interested in what happens if the average strength trainee (in this case young men with a mean age of ~23years, at least 1 year of training experience and a BMI of 27.7kg/m²) and not to 10 identical clones, don't you?

"So this stuff is not useful, right?"

Figure 4: Exogenous phosphatidic acid is metabolized to lysophosphatidic acid (LPA) in the body and LPA has been shown to work synergistically w/ leucine to increase mTORC1 activity (in vitro data from Winter. 2010).

Despite the "likely" and "very likely beneficial" effects on lower body power and lean body mass, of which only the latter could maybe have reached statistical significance with a larger number of participants (with only 20 subjects, i.e. 10 per group differences need to be more pronounced to reach statistical significance). It should be quite obvious that PA is probably not the next creatine.

Maybe the increased mTORC1 expression Winter et al. have observed upon co-incubation of leucine with LPA are not pronounced enough (figure 4). Or simply not necessary with enough leucine and insulin in the blood stream. After all, the Winter study also showed that basically identical effects were observed when the cells were incubated with leucine + insulin, instead of LPA + insulin (data not shown in figure 4).

So even if oral PA acts just like in-vitro LPA synergistically with leucine to activate the mTOR pathway (Fang. 2001; Winter. 2010; figure 4), the real world benefits in the study at hand are probably about as significant as the hypothetical 500g increase in net protein retention I discussed in he protein timing news earlier this week. Whether this may change with higher and/or more frequent doses in future studies remains to be seen, though. It does at least not appear to be impossible...

Additional news

• 'Built-in SERM' could help making post-menopausal estrogen replacement breast cancer proof At least this is what the results of a recent rodent trial that was conducted by researchers from the Division of Endocrinology at the Department of Medicine of the University of Virginia Health System in Charlottesville would suggest. Even in the absence of a progestin, which does have some ameliorative effects on the pro-carcinogenic effects of estrogen, the addition of the tissue-specific selective estrogen receptor modulator bazedoxifene (BZA) to the allegedly questionable, yet still widely prescribed conjugated equine estrogen (CEE) blocked the CEE- and, in a second control study, even the more potent E₂-stimulated ductal and terminal end bud growth of mammary gland and the corresponding estrogen-responsive gene expression (Song. 2012). 

• 

  Just like any athlete, man or woman who is interested in increasing his / her athletic performance, German Olympic lifter Julia Rohde could benefit from taking regular creatine monohydrate without necessarily running the risk of having to compete in a higher weight class (img sportzentrum-flora.de)

  5g creatine monohydrate (CM) per day helps soccer players to improve their game - or, more precisely, the time they needed to complete a standardized sprint running and dribbling test. And while you will probably not be surprised that CM supplementation did not affect the accuracy of their shots, you may very well be surprised that it did neither induce greater weight gain or any other changes in body composition (Mohebbi. 2012).
  
  The latter may also be interesting for athletes competing in sports where increased muscle mass can become an issue. After all, the results Mohebbi et al. present in the latest issue of the Middle-East Journal of Scientific Research would suggest that unless your training is geared towards increased muscle gain (which is obviously shouldn't be if that would be an issue for you) regular creatine, i.e. not the sugar laden 'cell-volumizers', can help you increase your performance in the absence of the (again, only for certain people) disadvantageous weight gain.
• Whether estrogen will save your brain cells or actually exacerbate the damaging effect of NMDA exposure depends on timing I guess you will all have heard of the protective effects of estrogen against N-methyl-d-aspartate (NMDA) toxicity. Now, a group of researchers from the University of Catania and the University of Rome Sapienza,both obviously in Italy, found that only pretreatment with estrogen will provide these beneficial effects, while the co-incubation or subsequent administration of estrogen will only potentiate the NMDA-induced cell death (Spampinato. 2012)

Have a nice weekend, everyone! As far as the On Short Notice items go, that's it for today. If you want more, just check out the SuppVersity Facebook Wall. I must forewarn you, though, since I am pretty busy this weekend, I am not sure if there will be another installment of the Athlete's Triad Series, tomorrow. If that's not the case, you will however get a regular news item, so don't worry you won't get bored ;-)

References:

• Callister R, Callister RG, Fleck SJ, Dudley GA. Physiological and performance responses to overtraining in elite judo athletes. Med. Sci. Sports Exerc. 1990; 22: 816–24.
• Fang Y, Vilella-Bach M, Bachmann R, Flanigan A, Chen J: Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science 2001, 294:1942–1945.  
• De Ferra L, Heuer M, Hagerman S, Purpura S, Jäger R. Method for increasing muscle mass and strength. Filed November 23, 2011. US 2012/0141448 A1. Published on June 7, 2012.
• Fry AC, Kraemer WJ, van Borselen F et al. Performance decrements with high-intensity resistance exercise overtraining. Med. Sci. Sports Exerc. 1994; 26: 1165–73. 
• MacKinnon LT. Special feature for the Olympics: effects of exercise on the immune system: overtraining effects on immunity and performance in athletes. Immunol Cell Biol. 2000 Oct;78(5):502-9.
• Mohebbi H, Rahnama N, Moghadassi M, Ranjbar K. Effect of Creatine Supplementation on Sprint and Skill Performance in Young Soccer Players. Middle-East Journal of Scientific Research. 2012; 12 (3): 397-401.
• Paul M, Khenna N, Sandhu JS. Psychomotor analysis of athletes under overtraining stresss. Serb J Sports Sci. 2012;6(3): 95-10.
• Song Y, Santen RJ, Wang JP, Yue W. Effects of the Conjugated Equine Estrogen/ Bazedoxifene Tissue-Selective Estrogen Complex (TSEC) on Mammary Gland and Breast Cancer in Mice. Endocrinology. 2012 Oct 15.
• Spampinato SF, Merlo S, Molinaro G, Battaglia G, Bruno V, Nicoletti F, Sortino MA. Dual Effect of 17β-Estradiol on NMDA-Induced Neuronal Death: Involvement of Metabotropic Glutamate Receptor 1. Endocrinology. 2012 Oct 17.
• Winter JN, Fox TE, Kester M, Jefferson LS, Kimball SR: Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathway. Am J Physiol Cell Physiol 2010, 299:C335–C344.