TReaTing Diabesity With Testosterone!? If You Keep DHT in Check + Stay Away From Aromatase Inhibitors, It May Work

It probably won't turn an overweight pre-diabetic into a fitness model, but a getting a TRT script has the potential of changing a man's physical and psychological health for the better.

Despite the fact that more and more men recognize the benefits of supervised testosterone replacement therapy (TRT) and the bodybuilding and fitness community cherishes 'their BIG T' as the be-all-and-end-all, many medical practitioners look at the administration of exogenous androgens as a potential health hazard. I would even bet that it won't be difficult to find one or two MDs who would say that Patricia S. Juang et al.'s idea to administer testosterone to obese men with normal, but low baseline testosterone levels to improve their body composition and insulin sensitivity borders physical injury - and that irrespective of adjuvant 5α-reductase (dutasteride) or aromatase (anastrazole) inhibitor administration.

TRT w/ or w/out aromatase or 5α-reductase inhibitor?

It goes without saying that the bodybuilding enthusiasts will think very differently about the usefulness of the 10 g testosterone gel (Testim) the fifty-seven 24–51-year old men with free testosterone levels in the lower 25% of normal range (<0.33 nmol/L) and a body mass index of ≥30.0 kg/m² in this recent  98-day randomized, double-blind, parallel group, placebo-controlled trial from the Universities of California and the Boston University Medical Center (Juang. 2013). In fact, I am pretty sure that, contrary to the scientists who put their subjects on either

• + subjects received a gonadotropin releasing-hormone antagonist to suppress endogenous T production
  10g Testim per day,
• 10g Testim + 1mg Arimidex (anastrazole) per day, or
• 10g Testim + 2.5 mg Avodart (dustasteride),

some of the physical culturists may even have suggested to use both, the aromatase inhibitor Arimidex and the 5α-reductase inhibitor Avodart to make absolutely sure that the T remains T and is not converted to estrogen or DHT.

Figure 1: Change in hormone levels (left) and body composition (right) after 98 days on 10g t-gel (Testim) with / without aromatase (Arimidex) or 5α-reductase (Avodart) inhibitor (Juang. 2013)

If they looked at the data in Figure 1, the estrogen-phobic bodybuilding enthusiasts would yet have to admit that the "bad estrogen" cannot be so bad as broscience would have it. Only minimal decreases in body fat, and significantly lower increases in fat free mass in the presence of a 5cm! (+4%) increase in waist circumference is certainly not what the bros are looking for.

Looking for natural ways to boost your testosterone levels? Look no further! You can learn about 10 ways to up your testosterone levels in my previous article "Natural Hormone Optimization Made Simple & Cheap: Avoid These 10 Anti-Androgens to Boost Testosterone & DHT" | read more

As surprising as the magnitude of the 'waist gain' may be, I personally have been more surprised by the effects the 10g of Testim had on the DHT levels of the overweight subjects. In both, the T-only and the T + Arimidex group the DHT level literally exploded and blunted the 25%, respectively 30% increase in glucose disposal during  minutes 120–180 and 240–300 of the euglycemic hyperinsulinemic glucose clamp test the scientists performed before and after the intervention period (Juang. 2013).

Despite a -40% decrease in PSA (vs. +9% in the T-only group), the 5α-reductase inhibitor dustasteride did not prevent the ~10% increase in prostate size that occurred in both the T-only (12%; +9% PSA) and T + Acodart (10%; -40% PSA) group. Other safety markers, such as AST (liver) or haemoglbin (iron overload) did not change.

The fact that dustasteride does not blunt testosterone induced lean mass gains is something you may have read in a previous article | more

Bottom line: I guess there are three things we can take away from this study:

1. TRT can help overweight men with impaired insulin resistance improve their body composition.
2. The administration of an aromatase inhibitor blunts the beneficial effects and causes a surprisingly pronounced increase in waist circumference.
3. The glucose sensitivity increases only, when the excessive reduction of testosterone to DHT is blocked by dustasteride.

In other words, if you want the T accept the E, but watch your DHT; but remember: Don't do it without blood work!

References:

• Juang, P. S., Peng, S., Allehmazedeh, K., Shah, A., Coviello, A. D. and Herbst, K. L. (2013), Testosterone with Dutasteride, but Not Anastrazole, Improves Insulin Sensitivity in Young Obese Men: A Randomized Controlled Trial. Journal of Sexual Medicine.

Creatine, DHT, Hair Loss & Prostate Cancer - Bro-Scientific Old Wives' Tales or Possible Side Effect? Plus: (Non-)Sense Creatine Loading, Exercise Induced 5-α Reduction & More

Poor guy! Must have taken too much creatine and treated his hair for muscle ;-) Ok, seriously, creatine may have helped a little that he was able to build this impressive physique, but the hair? Come on, seriously!?

If you have been around the bulletin boards of the fitness and bodybuilding community, I am pretty sure you will have heard about creatine induced increases in dehydrotestosterone (DHT). Probably you will also have had someone chime in who claimed that his hair started to fall out, when he started to use creatine supplements - right? Well, I guess in that case you will probably also remember how another guy chimed in and said: "Hold on does that mean that creatine will cause prostate cancer?"

Never heard something like that? I suggest you trust my word, then; and in case you want "scientific evidence" head over to www.pubmed.com and type in "creatine D" it will offer you "creatine DHT" as one of the typical search phrases people are looking for.

Cock-and-bull - right?

It is true that there is a study that supports the concept of increased DHT levels in athletes (20 collegiate rugby players to be precise) in response to 21 days of creatine supplementation. The athletes who participated in the said trial came from a Rugby Institute situated near Stellenbosch University in South Africa. None of the subjects had taken any supplements with their normal diet for 6 weeks before the trial in the course of which all had been randomized to one of the following groups:

• creatine: 25g creatine + 25g glucose for 7 days; 5g crea + 25g glucose for 14 days
• placebo: 50g glucose for 7 days; 30g glucose for 14 days
  

The subjects underwent standardized training, albeit for different player positions, during the whole study period. All subjects were residents at the institute and the ate the same food at the cafeteria. Moreover, all 20 were just coming back from a winter break and were "in similar condition as the start of the study and not fatigued from consecutive weeks of match play" (van der Merwe. 2009).

Instead of simply taking more you may rather want to "Super Charge Creatine W/ Baking Soda" | learn more

Creatine loading is neither necessary nor useful for the majority of athletes. Unless you have a meet close ahead there is no need to gobble down 25g+ doses of creatine - specifically not in one sitting. While the typical creatine supplementation protocol consists of a loading phase of 20 g creatine/d or 0.3 g creatine/kg/d that's followed by a 3-5 g/day (or 0.03g/kg) maintenance phase (Buford. 2007), it is also possible to use daily doses of ~3–6 g or between 0.03 to 0.1 g/kg per day (Willoughby. 2001; Hickner. 2010).

All subjects were lean (13-14% body fat and muscular 75kg muscle of 86-87kg total body weight) and thus way more representative of the average creatine guzzling gymrat than untrained average Joes whose beer bellies may well have messed up their endocrine system to an extend that could explain the DHT increases from 0.98 nmol/L to 1.53 nmol/L. The fact that the DHT levels in the control group did not change significantly in the course of the 7-day loading phase (in fact they dropped, but due to the high standard deviation the drop from 1.26 nmol/L to 1.09 nmol/L was non-significant), lends further support that the changes, the researchers observed must have been the result of the 25g of creatine the 10 subjects in the active arm of the trial had to swallow on during the first seven days of the study period.

Figure 1: Serum DHT levels total (left) and expressed relative to baseline levels in control group (right); data calculated based on van der Merwe et al. 2009

As you will probably already have read in-between the lines, I am not exactly impressed - let alone scared - by these results. Why? Well, the initial 56% increase in DHT was not only followed by a -10% decline during the maintenance phase, but this decline brought the DHT levels of the young men in the creatine group pretty close to where they had been in the placebo group at T0 (1.38nmol/L vs. 1.26 nmol/L for creatine vs. placebo, respectively).

The high DHT levels observed in the study at hand, were only midrange

If that does not comfort you, maybe it will help, if I tell you that the reference range for adult men ranges from 0.8-3.4 nmol/L (NHS Pathology. 2013 - please note that these reference ranges vary from lab to lab, in ng/dL the upper limit usually is 85ng/dL, which is 2.93nmol/L). Accordingly, the total DHT level of the subjects in the van der Merwe study did not even scratch the 50% mark on the reference range, when they maxed out at the end of the 7-day loading phase.

With a meager 9% difference to the baseline levels in the control group and a total DHT level of 1.38nmol/L in the "low DHT" zone of the reference range, I wouldn't say it is necessary (from a mere safety perspective) to investigate, as Green suggested it in a 2010 letter to the editor, whether the creatine supplement that has been used in the study may have been contaminated with androgenic compounds (Green. 2010). To answer the question about the why, i.e. "Why did the DHT levels in the creatine group go up, while those in the control group remained the same?",  it would yet in fact be nice to know if we were dealing with the side effects of androgenic compounds in the creatine supplement or the physiological effects of exercise, which has repeatedly been shown to be able to increase both intra-muscular and systemic DHT levels in men and rodent models (see the bottom line for selected references).

Want to learn how to modulate your DHT levels naturally? Rice, safflower, sorghum & Co. can help! learn more

In view of the fact that these increases are intensity dependent, but limited by the androgen suppressive effects of overtraining, The increased DHT levels may eventually have been a secondary response to increased training loads and the ameliorative effect creatine exerts on the androgen suppressive effects of overreaching (Volek. 2004).

And while I cannot tell you if this actually was the reason for the increase in DHT, I can tell you that the scientists assertion that what they observed was a "large increase in DHT rather than a marginal (possibly physiologically insignificant)"  (van de Merwe. 2009) is (at best) warranted if we look at the intra-group effect. In view of the broad "normal" range and the low baseline DHT levels in the creatine group, this relevance of this relative increase is yet more than questionable.

And the increasing DHT:Testosterone ratio?

Even at the risk of sounding like a smart ass, I do not want to forgot to mention that the "oh so dangerous" increase in DHT/T levels the scientists emphasize in their conclusion was found to be associated with a reduced risk of hair loss (-35% risk reduction) in 315 male subjects who were stratified with regard to age, race, and case-control (Demark-Wahnefried. 1997).

This and similar observations which have been made by Nomura et al. (1988), Hsing (1993) Shaneyfelt (2000) with respect to the non-significant impact of high(er) serum DHT levels on the occurance of prostate cancer and, more importantly, the increased risk that comes with higher T:DHT ratios, I seriously doubt that you have to be concerned about either your superb head of hair or your hitherto still pain and cancer free prostate when you are downing your daily dose of 3-5g creatine monohydrate.

No! Physical activity does not cause prostate cancer. I guess you will be surprised that I even address this issue, but due to several major shortcomings in previous prospective and epidemiological studies, you will easily find studies such as the one by Cerhan et al. which claims that men with a high physical activity have a 90%(!) increased risk of prostate cancer. What the abstract does not tell you, though, is that the researchers "forgot" to conduct a time lagged analysis to overcome the "I started to exercise yesterday, so I exercise vigorously every day" effect and did thus fail to measure consistent physical activity. Edward et al. did just that over a 4 year period and observed a -53% risk reduction for men aged 65+ to develop advanced prostate cancer.

Take home message: Despite being statistically relevant the absolute changes in the DHT levels van der Merwe et al. observed in the study at hand were neither physiologically relevant (DHT remained well within the reference range), nor totally inexplicable. Being afraid of hair loss, let alone prostate cancer, in response to the consumption of (untainted) creatine supplements is thus totally unwarranted.

And just in case you still want to freak out, I suggest you keep sitting on your ass for the rest of your life and refrain from ever playing football or any other sport again... why? Well according to Lupo et al., your DHT levels will double during a single football match. This and similar observations by Hawkins in a middle aged men on a 12-months aerobic exercise program (14.5% increase with moderate intensity cardio 6x per week; cf. Hawkins. 2008), as well as the results from Aizawa et al. who were able to demonstrate "that acute exercise enhances the local bioactive androgen metabolism in the skeletal muscle of both sexes" and not just men, do as bro-logic dictates suggest that any kind of physical activity will make you hair fall out and your prostate grow... now tell me how realistic is that?

References:

• Aizawa K, Iemitsu M, Maeda S, Otsuki T, Sato K, Ushida T, Mesaki N, Akimoto T. Acute exercise activates local bioactive androgen metabolism in skeletal muscle. Steroids. 2010 Mar;75(3):219-23.
• Buford T, Kreider R, Stout J, Greenwood M, Campbell B, Spano M, Ziegenfuss T, Lopez H, Landis J, Antonio J:International Society of Sports Nutrition position stand: creatine supplementation and exercise.J Int Soc Sports Nutr. 2007;4.
• Cerhan JR, Torner JC, Lynch CF, Rubenstein LM, Lemke JH, Cohen MB, Lubaroff DM, Wallace RB. Association of smoking, body mass, and physical activity with risk of prostate cancer in the Iowa 65+ Rural Health Study (United States). Cancer Causes Control. 1997 Mar;8(2):229-38. 
• Demark-Wahnefried W, Lesko SM, Conaway MR, Robertson CN, Clark RV, Lobaugh B,
  Mathias BJ, Strigo TS, Paulson DF. Serum androgens: associations with prostate
  cancer risk and hair patterning. J Androl. 1997 Sep-Oct;18(5):495-500. 
• Giovannucci EL, Liu Y, Leitzmann MF, Stampfer MJ, Willett WC. A prospective study of physical activity and incident and fatal prostate cancer. Arch Intern Med. 2005 May 9;165(9):1005-10.
• Hawkins VN, Foster-Schubert K, Chubak J, Sorensen B, Ulrich CM, Stancyzk FZ, Plymate S, Stanford J, White E, Potter JD, McTiernan A. Effect of exercise on serum sex hormones in men: a 12-month randomized clinical trial. Med Sci Sports Exerc. 2008 Feb;40(2):223-33
• Hickner R, Dyck D, Sklar J, Hatley H, Byrd P:Effect of 28 days of creatine ingestion on muscle metabolism and performance of a simulated cycling road race.J Int Soc Sports Nutr 2010;7:26.
• Hsing AW, Comstock GW. Serological precursors of cancer: serum hormones and risk of subsequent prostate cancer. Cancer Epidemiol Biomarkers Prev. 1993 Jan-Feb;2(1):27-32.
• van der Merwe J, Brooks NE, Myburgh KH. Three weeks of creatine monohydrate supplementation affects dihydrotestosterone to testosterone ratio in college-aged rugby players. Clin J Sport Med. 2009 Sep;19(5):399-404.
• Nomura A, Heilbrun LK, Stemmermann GN, Judd HL. Prediagnostic serum hormones and the risk of prostate cancer. Cancer Res. 1988 Jun 15;48(12):3515-7.
• Shaneyfelt T, Husein R, Bubley G, Mantzoros CS. Hormonal predictors of prostate cancer: a meta-analysis. J Clin Oncol. 2000 Feb;18(4):847-53.
• Van der Merwe J, Brooks NE, Myburgh KH. Three weeks of creatine monohydrate supplementation affects DHT to testosterone ratio in college-aged rugby players.Clin J Sports Med. 2009;19:399–404.
• Volek JS, Ratamess NA, Rubin MR, Gómez AL, French DN, McGuigan MM, Scheett TP, Sharman MJ, Häkkinen K, Kraemer WJ. The effects of creatine supplementation on muscular performance and body composition responses to short-term resistance training overreaching. Eur J Appl Physiol. 2004 May;91(5-6):628-37.
• Willoughby DS, Rosene J:Effects of oral creatine and resistance training on myosin heavy chain expression.Med Sci Sports Exerc2001,33:1674–1681.

Serum & Intramuscular Testosterone, DHT and Androgen Receptor Response to High vs. Low Volume Training

Another set for another ng of testosterone? Does it work that way and is it worth it - not just on paper, but in terms of real gains?

I know that we don't know! And among the many things we don't know the influence of the post-workout elevation in the long-thought "anabolic" hormones testosterone, growth hormone, and co. is unquestionably one of my personal favorites. You've read about it, here at the SuppVersity many times and I got to tell you in advance that the absence of convincing evidence for / against its importance will become a problem in the bottom line of today's SuppVersity article dealing with the intriguing results of an experiment that has been conducted by Lukas J. Farbiak as part of his Honors Thesis (Farbiak. 2013).

"Effects of Lower- and Higher-Volume Resistance Exercise on Serum Total and Free Testosterone, Skeletal Muscle Testosterone and Dihydrotestosterone Content, and Skeletal Muscle Androgen Receptor mRNA Expression and Protein Content"

That's quite a title for a thesis right? Well, one thing's for sure: Having the words, "high, "low", "training volume", "resistance exercise", "total and free testosterone", "dihydrotestostereone", etc. all in the headline is certainly an advantage when it comes to findability of a paper - or in this case - a thesis in a database. And in fact, it was really the title of the 91 page piece that has caught my eye, a couple of days ago - what peaked my interest, though were the research hypotheses Farbiak, whose thesis was by the way overseen by Darryn Willoughby, formulated:

• H1 : Following the HV [high volume] exercise bout involving both upper- and lower-body resistance exercise, a significant increase in serum testosterone will occur compared to the LV [low volume] exercise bout only involving lower-body resistance exercise. 
• H2 : Following the HV exercise bout involving both upper- and lower-body resistance exercise, a significant increase in muscle testosterone and DHT content will occur compared to the LV exercise bout only involving lower-body resistance exercise. 
• H3 : Following the HV exercise bout involving both upper- and lower-body resistance exercise, a significant increase in AR mRNA expression and protein content will occur compared to the LV exercise bout only involving lower-body resistance exercise.

I took the liberty of highlighting three things in Farbiak's hypotheses, which tell you why you want to know the outcome of the study, even if the current "state of the research" questions the significance of exercise-induced elevations of androgens in terms of their ability to elicit muscle growth.

What's special, here, is that we are not measuring serum levels exclusively, but get a much more detailed picture of the endocrine response to high vs. medium volume training.

Why would the internal androgen levels differ from those outside of the cell? The notion that this could and in fact is the case did not arise before Hammes et al. discovered that contrary to the previously heralded position that says that only free testosterone levels would matter and that the latter would be able to enter the cells via passive diffusion, the entrance of testosterone into the cell is actually governed by (attention please) megalin, a low density lipoprotein receptor (LDR) related  protein. According to Hammes, SHBG can bind to megalin can internalize the SHBG + androgen pair into the cytoplasm, where the binding globulin is degraded and the steroid will be released to the cellular environment.It goes without saying that this changes the interpretation of previous data and provides a whole new perspective on the androgen - muscle interaction with the formerly "passive" bound testosterone suddenly having the ability to promote hypertrophy.

In this context the relation of free androgens, androgen receptor expression and the presence and concentration of intra-muscular may well provide first insights into why previous studies, which have predominantly relied on the determination of serum levels without even checking,

• whether there were enough receptors to (this is an oversimplification) transduct the anabolic signal of workout induced increases in testosterone to the muscle cells, and
• to which extent the changes in extra-cellular androgen levels correlate with the amount of testosterone and DHT that's actually in the muscle.

Now that I have your full attention let's take a look at what kind of workout program we are dealing with in the study at hand, for which the researchers recruited 10 "apparently healthy resistance trained  [regular,  consistent  resistance  training (i.e. thrice weekly) for  at least 1 year prior to the onset of the study], men between the ages of 18-30" (Farbiak. 2013).

"In a randomized, cross-over design, participants visited the laboratory on 5 separate occasions in the following manner: visit 1 = entry/familiarization session, visit 2 = testing/resistance exercise session 1, visit 3 = 24 hour follow-up for session 1, visit 4 = testing/resistance exercise session 2, visit 5 = 24 hour follow-up for session 2. Relative to the testing sessions (visits 2 & 4), participants performed a resistance exercise session involving the knee extension exercise on two occasions separated by one week. One session constituted the control session and was preceded by rest and the other was preceded by the experimental session and preceded by a bout of high-volume, moderate-intensity upper-body resistance exercise using short rest periods." (Farbiak. 2013).

The dependent variables, i.e. serum free and total testosterone, intra-muscular testosterone, DHT and  AR  receptor mRNA, as well as protein expression were determined on all, but the initial entry/familiarization visit.

The workout itself (remember this is not a chronic resistance training study, as the one by West et al. (2012) which is - at least to my knowledge unique wrt to the real-world relevance of the data; learn more) consisted of

• LV - low volume: 5 sets of 5-RM (90%-95% 1-RM) of the bilateral knee extension exercise with 3 minutes of rest between sets.
• HV - high volume: Upper-body resistance exercise protocol of 4 sets of 10-RM each of the bench press, seated row, and overhead shoulder press exercises immediately prior to the knee extension protocol. 
• the initial load was set at 80% of the 1-RM for each participant. 
• if muscle fatigue/failure occurred during a set, a spotter provided assistance until the participant completed the remaining repetitions and resistance was reduced for subsequent sets

In all cases, 2 minutes of rest separated sets and exercises. All training sessions were conducted in
the Baylor Laboratories for Exercise Science & Technology (BLEST) and supervised by study personnel.

Figure 1: Sum total and free testosterone in response to high and low volume training (Farbiak. 2013)

Now, the data in figure 1 actually mirrors what we already know: The overall serum response to high volume training is more pronounced that that to playing around on a leg extension machine (which happens to be the favorite benchmark for the / I repeat myself / likewise not very useful studies on PWO protein synthesis).

"Several studies have shown that acute resistance exercise bouts elicit a testosterone response (Kraemer. 1990; Kraemer, Gordon et al., 1991; Kraemer, Hakkinen et al., 1999; Spiering, Kraemer. 2008; Roberts. 2009). Such exercise bouts shown to elicit a testosterone response need to consist of a high intensity (load) (85%-95%) of one repetition max and meet a minimum threshold, and moderate to high volume (set x number of reps x intensity). Exercises that utilize large muscle groups (i.e. power clean, squats, and dead lifts) as well as performing exercises involving large muscle groups first, with short rest periods (30-60 sec) have shown to elicit the greatest response (Kraemer, Marchitelli et al., 1990; Spiering, Kraemer et al., 2008; Vingren, Kraemer et al., 2010). [...] It is known that the testosterone response resistance exercise is highly variable (Kraemer, 1988). Thus, it is possible that after multiple years of resistance training, the initial phasic response of the hypothalamus gonadal axis (aka. testosterone axis) response elicited by resistance exercise bout un trained individuals has become blunted from habitual resistance exercise. However, it is necessary that further research be conducted to elucidate why this blunted response occurs." (Farbiak. 2013; my emphasis of the key points)

As far as the differential response of free and total testosterone is concerned the tendency for both to go hand in hand has been observed in previous studies, as well (Durand. 2003; Kraemer. 1990; Kraemer. 1991; Kraemer. 1999; Spiering. 2008; Roberts. 2009). What's "new" or let's say something we have much less reliable data on are the changes that take place within the muscle (see figure 2)

Figure 2: Intra-muscular androgen & -receptor mRNA & protein expression (Farbiak. 2013)

Interestingly, enough those potentially far more relevant changes take place on a very different time-scale. While we do see the touted increases in serum testosterone in the immediate vicinity of the workout, the corresponding intra-muscular levels are actually declining from pre to post (red vs. blue bars). As Farbiak points out, these changes were yet statistically non-significant and to thus correspond to previous results presented by Vingren & Kraemer et  al. in 2008 (Kraemer. 2008). The same goes for the DHT response that did not make it past the p > 0.05 mark of statistical significance (FYI: this means the chance that this is just a statistical artifice is >5% and thus "not significant").

As far as the androgen receptor mRNA expression is concerned a often-cited (also by me, here at the SuppVersity) by Kraemer et al. observed a reduction in response to a single bout of resistance exercise, (Kraemer. 2010). The latter does actually conflict with in-vitro studies that suggested that the presence of higher testosterone levels would lead to an increased expression of androgen receptor mRNA and proteins - an observation of which Farbiak points out that it does not only stand in line with a previous study by Willoughby  and  Taylor (Willoughby. 2004) who observed a

"+35% and +43% increases in AR mRNA expression 48 hours after the first and third resistance exercise bouts, with a peak increase of 68% in AR mRNA expression occurring 48 hours after the second resistance exercise bout within the resistance exercise group" (Farbriak. 2013)

which was ascribed to corresponding increases in serum testosterone levels. In view of the fact that the latter were absent in Farbiak's subjects, it is not surprising that the existing increases in AR receptor mRNA in the study at hand did not reach statistical significance. Similarly, Farbiak was not able to show significant alterations in androgen receptor protein content in response to either LV or HV bouts of resistance exercise, which leaves us with pretty much of a null result and raises the question...

What do we make of this null result?

I guess the first thing would be to take a look at the underlying "mathematical" reason for the non-significance of the results... standard deviations - HUGE standard deviations, indeed. So huge that I initially thought that this must be a mistake, I mean if you have a mean pre-testosterone level of 43.59 ng/dl and a standard devition of 43.03 ng/dl, i.e. 99%, what can you expect? Now this is an extreme example, but in view of the relative small number of participants it should suffice to tell you that - maybe - we should not focus that much on statistical significance, here?

Suggested read: "Advanced Trainees Benefit from Increased Training Volume! Greater & Steadier Strength Gains with 8 Sets of Squats. Plus: Over 6 Weeks, 1 Set and 4 Sets Equally (In-)Effective." If higher volume begets higher T-responses and the latter is blunted in advanced trainees, it would appear logical that they benefit from doing more (learn more)

Schoenfeld mentioned similar effects in a whole host of pertintent studies in his excellent review of the literature on the effects of the exercise induced hormonal changes on muscle hypertrophy (I mentioned this review before, e.g. March 2, 2013; March 4, 2013). So it could simply be inter-individual variability that skewed the results. If that was the case, it is however unlikely to assume a dose-response relationship between any (serum or intramuscular) changes in androgens / androgen receptor expression and skeletal muscle hypertrophy - I mean that would imply much more pronounced differences in muscle growth in response to a workout than the real world results do indicate.

Another factor that may have influenced the results is the high training experience (>8 years) of the participants in the Farbiak study, if the initially cited hypothesis that the androgen response to exercise declines in experienced athletes turns out to be true, the non-significance of the endo- and paracrine hormonal response in the study at hand could well be "normal" and no anomaly. And if that was the case, it would suggest that the changes that were observed in previous studies, many of which were conducted on rookies, do matter - at least to a certain degree.

To use this as the only explanation for the (comparatively) exorbitant gains training noobs experience once they pick up their first dumb- and barbells would yet be shortsighted. To add it as yet one of the many confounding factors, on the other hand, would make perfect sense, as it would stand in line with the (comparably) short-term detrimental effects chronic resistance training without off-times has on the protein synthetic mTOR response to exercise (learn more about exercise induced "mTOR resistance").

---

Bottom line: To sum it up, while we do now have another puzzle piece, it looks as if it only made us realize that our 1,000 piece puzzle is in fact a 10,000 piece puzzle and that it will probably require more than just a handful of follow up study to investigate the numerous factors "such as age, time of day [not all trainees trained at the same time, so the circadian rhythm may be an issue, in the study at hand], and training experience" (Farbiak. 2013) of which Farbiak speculates in the discussion of his honors thesis that they may account for the observed discrepancies and inconsistencies in testosterone response to acute resistance exercise... ah, and once we've done that, we would need more studies like the one by West et al. (2012) to see the real world implications. I guess, we better issue a bond to get those finance, right?

References:

• Farbiak, LJ. Effects of Lower- and Higher-Volume Resistance Exercise on Serum Total and Free Testosterone, Skeletal Muscle Testosterone and Dihydrotestosterone Content, and Skeletal Muscle Androgen Receptor mRNA Expression and Protein Content. A Thesis Submitted to the Faculty of Baylor University In Partial Fulfillment of the Requirements for the Honors Program. May 2013.
• Durand RJ, Castracane VD, Hollander DB, Tryniecki JL, Bamman MM, O'Neal S, Hebert EP, Kraemer RR. Hormonal responses from concentric and eccentric muscle contractions. Med Sci Sports Exerc. 2003 Jun;35(6):937-43.
• Hammes A, Andreassen TK, Spoelgen R, Raila J, Hubner N, Schulz H, Metzger J, Schweigert FJ, Luppa PB, Nykjaer A, Willnow TE. Role of endocytosis in cellular uptake of sex steroids. Cell. 2005 Sep 9;122(5):751-62. 
• Kraemer WJ, Marchitelli L, Gordon SE, Harman E, Dziados JE, Mello R, Frykman P, McCurry D, Fleck SJ. Hormonal and growth factor responses to heavy resistance exercise protocols. J Appl Physiol. 1990 Oct;69(4):1442-50.
• Kraemer WJ, Gordon SE, Fleck SJ, Marchitelli LJ, Mello R, Dziados JE, Friedl K, Harman E, Maresh C, Fry AC. Endogenous anabolic hormonal and growth factor responses to heavy resistance exercise in males and females. Int J Sports Med. 1991 Apr;12(2):228-35.
• Kraemer WJ, Häkkinen K, Newton RU, Nindl BC, Volek JS, McCormick M, Gotshalk LA, Gordon SE, Fleck SJ, Campbell WW, Putukian M, Evans WJ. Effects of heavy-resistance training on hormonal response patterns in younger vs. older men. J Appl Physiol. 1999 Sep;87(3):982-92.
• Kraemer WJ, Ratamess NA. Hormonal responses and adaptations to resistance exercise and training. Sports Med. 2005;35(4):339-61.
• Roberts MD, Dalbo VJ, Hassell SE, Kerksick CM. The expression of androgen-regulated genes before and after a resistance exercise bout in younger and older men. J Strength Cond Res. 2009 Jul;23(4):1060-7. 
• Schoenfeld BJ. Postexercise hypertrophic adaptations: a reexamination of the hormone hypothesis and its applicability to resistance training program design. J Strength Cond Res. 2013 Jun;27(6):1720-30.
• Spiering BA, Kraemer WJ, Anderson JM, Armstrong LE, Nindl BC, Volek JS, Maresh CM. Resistance exercise biology: manipulation of resistance exercise programme variables determines the responses of cellular and molecular signalling pathways. Sports Med. 2008;38(7):527-40.
• Spiering BA, Kraemer WJ, Vingren JL, Ratamess NA, Anderson JM, Armstrong LE, Nindl BC, Volek JS, Häkkinen K, Maresh CM. Elevated endogenous testosterone concentrations potentiate muscle androgen receptor responses to resistance exercise. J Steroid Biochem Mol Biol. 2009 Apr;114(3-5):195-9.
• West DW, Phillips SM. Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training. Eur J Appl Physiol. 2012 Jul;112(7):2693-702.
• Willoughby DS, Taylor L. Effects of sequential bouts of resistance exercise on androgen receptor expression. Med Sci Sports Exerc. 2004 Sep;36(9):1499-506.

Androgen 3-Some: BPA Exposure & Free Testosterone in Men. TRT Good For the Prostate. DHT, Alopecia (Hair Loss) & Monascus Fermentation. Plus: Mycotoxins in GCB Supps

Coffee and green coffee bean extracts are by no means the only way by which you are exposed to mycotoxins. Corn, for example, is likewise a favorite for the toxic mold. The same goes for almost all other grains. Common routes of exposure are, amongst others cereals, breads, wines, and even mils and meats (of swine ad turkey, not chicken; Duarte. 2010)

36%, 32%, 10%, and 16% these are the SuppVersity Figures of the week and the percentages of green coffee bean supplements (remember the chlorogenic acid news in Thursday's installment of the Science Round-Up) that were contaminated with Ochratoxin A, ochratoxin B, fumonisin B1 and mycophenolic acid, respectively.

"Mycotoxins occurred in the following concentration ranges: ochratoxin A: 2.7–136.9 µg/kg, ochratoxin B: 3.5–20.2 µg/kg, fumonisin B1: 110.0–415.0 µg/kg, mycophenolic acid: 43.1–395.0 µg/kg." (Vaclavi. 2013)

These poisonous substances are produced by fungi that form during (inproper) storage and are suspected to inhibit protein synthesis, damage macrophage systems, inhibit particle clearance of the lung, and increase sensitivity to bacterial endotoxins... ah, I almost forgot ochratoxins also wreak havoc on your hormones (Frizzell. 2013).

So far for the bad news, now the good one: According to the researchers calculations even with most contaminated of the 50 products they the average consumer who adheres to the suggested dosing protocol will still be well within the tolerable weekly intake (TWI) of 120 ng/kg body weight per week and tolerable daily intake (TDI) of 2000 ng/kg body weight per day for ochratoxin A and fumonisin B₁, respectively (these values were estimated by the EU Scientific Committee on Food (SCF) and the European Food Safety Authority (EFSA) - corresponding values of the "well-meaning" FDA or any other US government agencies are - as usual - not available).

Let's get to our androgen threesome

• 

  SuppVersity readers know: Tea is not only good for your prostate (learn more), it can also help you lose weight (read more)

  Testosterone replacement improves prostate issues (Ko. 2013) -- Contrary to what common "wisdom" will tell you scientists from the Yeungnam University College of Medicine in Korea can tell you that the 17 out of  46 patients who suffered from lower urinary tract symptom before they underwent TRT using intramuscular injection of 3 months bases injection of testosterone 1,000 mg undecanoate over a year achieved significant improvements (decrements) on the International Prostate Symptom Score (IPSS).
  
  Needless to say that "[d]uring the median follow up of 15.1 months, no patients experienced urinary retention, BPH-related surgery, or admission for urinary tract infection".

• BPA and low testosterone, you better know what to look at (Zhou. 2013) -- Talking about testosterone, there is finally some relatively reliable human data on the effects of BPA exposure on the hormone levels in men.

  

  Figure 1: Relative difference in free androgen index (FAI), androstenedione (AD), free testosterone (FT), SHBG, inhibin (INB), prolactin (PRL), follicle stimulating hormone (FSH), estrogen (E2) an total testosterone (T);  comparing the men with to the men without workplace exposure in the Zhou study

  As you can see in figure 1 the effects would go unnoticed, if you do not test for free hormones, but just checked the amount of total testosterone. How you can recognize that from the data? Well, the figures above the bars are the p-values. All that are >0.5 would suggest that this effect is statistically non-significant, so that every study not looking at things like the free androgen index (FAI) or the free testosterone levels (FT) will miss the 15% and 10% reduced levels of the latter and conclude: That it does not make a difference, if your serum contains 3.198 or 0.276mg/L as it was the case in the exposed and non-exposed subjects in this study from the Shanxi Medical University, because BPA won't harm you anyway.

• The fermented solution to all problems androgen?  (Chiu. 2013) Monascus bacteria that is used to ferment red mold rice, a traditional spice that is consumed throughout Asia could prevent androgenetic alopecia, benign prostate hyperplasia and prostate cancer.

  

  Figure 2: Changes in testosterone an DHT mice on TRT (control) w/w-out 0.2 & 0.5% Monascus extract in chow, corresponding images of the stained slices from the prostate and hair loss compared to standard treatment with finasteride (Chiu. 2013)

  The results of a recent study from the Department of Environmental and Occupational Health at the National Cheng Kung University Medical College clearly suggest that the way in which a monascus extract suppressed baldness in male B6CBAF1/j mice 

  

  Learn how to modulate DHT/T naturally.

  • decreased PSA levels  
  • decreased tumor volume and
  • decreased prostate cancer incidence, 
  • decreased dihydrotestosterone (DHT),
  • but left testosterone unchanged
  The effect was dose-dependent and was observed with 0.5-3% of the extract in the rodent diets. While it is not unlikely that the results will translate into human studies, it should be obvious that at least for the >0.5% doses, supplementation will be necessary.
  
  Irrespective of these latest study results, previous research indicates that Monascus-fermented products have many functional secondary metabolites, including monacolin K, citrinin, ankaflavin, and monascin and these have been shown to possess anti-inflammatory, antioxidative, cholesterol-lowering effect, and antitumor activities. Probably all of you will be familiar with at least one of them: Red Yeast Rice, the natural statin. And if you are not into spices or extracts, there are also other foods and even wines that are fermented with Monascus.

---

That's it for today: I know ladies, with today's focus on the male hormones, I owe you (big time?). But don't worry, there are also a couple of Facebook News, you may be interested in

• 

  Suggested read: "Carbohydrate Shortage in Paleo Land" (read more)

  "Oldie but goldie: T3, rt3 and carbohydrate intake in hyper- and eucaloric scenarios - Something worth considering for those constantly battling low T3 an high rT3 levels (read more)
• Omnipresence of "healthy" Subway sandwiches correlates w/ obesity rates - "Countries with the highest density of Subway restaurants such as the USA (7.52 per 100,000) and Canada (7.43 per 100,000) also tend to have a higher prevalence of obesity in both men (31.3% and 23.2%, respectively) and women (33.2% and 22.9%, respectively)." (read more)
• Understanding the neurological side effects of statin drugs - US scientists observed unusual swellings within neurons, which the team has termed the "beads-on-a-string" effect (read more)
• DHEA supplementation at 25gm/day to restore female fertility - A recent study from Turkey would suggest that this could actually work (read more)

If that's still not enough, come back tomorrow for another serving of the latest news from the realms of exercise, nutrition and health sciences, here at the SuppVersity! In the mean time, enjoy your weekend, everone!

References:

• Chiu HW, Chen MH, Fang WH, Hung CM, Chen YL, Wu MD, Yuan GF, Wu MJ, Wang YJ. Preventive effects of monascus on androgen-related diseases: androgenetic alopecia, benign prostatic hyperplasia, and prostate cancer. J Agric Food Chem. 2013 May 8;61(18):4379-86.  
• Duarte SC, Pena A, Lino CM. Ochratoxin a in Portugal: a review to assess human exposure. Toxins (Basel). 2010 Jun;2(6):1225-49. doi: 10.3390/toxins2061225. Epub 2010 Jun 1. Review. 
• Frizzell C, Verhaegen S, Ropstad E, Elliott CT, Connolly L. Endocrine disrupting effects of ochratoxin A at the level of nuclear receptor activation and steroidogenesis. Toxicol Lett. 2013 Mar 13;217(3):243-50.  
• Ko YH, Moon du G, Moon KH. Testosterone replacement alone for testosterone deficiency syndrome improves moderate lower urinary tract symptoms: one year follow-up. World J Mens Health. 2013 Apr;31(1):47-52.
• Vaclavik L, Vaclavikova M, Begley TH, Krynitsky AJ, Rader JI. Determination of Multiple Mycotoxins in Dietary Supplements Containing Green Coffee Bean Extracts Using Ultrahigh-Performance Liquid Chromatography–Tandem Mass Spectrometry (UHPLC-MS/MS). Journal of Agricultural and Food Chemistry. May 2013 [ahead of print].
• Zhou Q, Miao M, Ran M, Ding L, Bai L, Wu T, Yuan W, Gao E, Wang J, Li G, Li DK. Serum bisphenol-A concentration and sex hormone levels in men. Fertil Steril. 2013 May 4.

Exercise Research Quickie: HIIT vs. Steady State, More on the Hormonal Response. Light Training, High TUTs & Peak Contractions - Not Just for The Elderly. Train Your Left, Grow Your Right Leg - Contralateral Training Effects

The role of the innervations between our muscles as well as to our brain is often overlooked, when we are talking about size gains. The image shows stained nerve fascicles from the Song study, which brings this wiring back onto the radar.

I know that we have had the short news on Saturday only and that there are of course tons of short news on Facebook everyday, but the studies I am going to present you in this exercise research quickie were so in-between (meaning not really worth a full post, but still way too good to be wasted on facebook) that I decided to devote a post of its own to the research on the hormonal effects of interval vs. steady state training by Hackney et al. (Hackney. 2012b), the impressive and certainly not totally irrelevant effects of slow movement, low-intensity resistance training in the elderly Watanabe et al. describe in their latest paper and the surprising muscle building (Watanabe. 2013) and growth priming carry over effects Song et al. observed in response to unilateral electrical muscle stimulation (Song. 2012).

Although, the latter post is pretty theoretical I hope that all of you will find something that enlightens, amuses or entertains them in this "threesome" ;-)

More T, more DHT, more cortisol - that's the HIIT vs. LISS formula

(Hackney. 2012b) -- In fact the results of two subsequently published papers by Hackney et al. would suggest that it's about as easy. Work out hard and fast and see greater increases in testosterone levels, but also testosterone turnover (into DHT via 5-alpha reductase), but don't forget that aside from these (questionable) anabolic benefits, your thyroid hormone levels are going to take a dive (as reported previously), as well.

Figure 1: Comparison of the hormonal responses measured in the plyometrics (left) and the HIIT vs. LISS (right) study (based on Ozen. 2012 and Hackney. 2012)

The figure above is actually from a post where I discussed this before, so if you cannot remember all the details, briefly go back before you take a look at the summary of results of the more recent study by Hackney.

"Dihydrotestosterone (DHT) - Bigger, Stronger, Faster or just Balder, Fatter and Unhealthier?" That's the question I asked in one of the installments of the Intermittent thoughts on building muscle. A post I would highly suggest you read, by the way ;-)

In this 2nd paper that was published right before Christmas in the Journal of Endocrinological Investigations the researchers were able to show that repeated periods of 90-sec treadmill running at 100-110% maximal oxygen uptake (VO2max) and 90-sec active recovery at 40% VO2max for 42-47 min (which is obviously pretty long!) caused  just a significantly more pronounced increase not just in free testosterone, but also in its conversion to testosterone's big brother DHT (as indicated by statistically higher levels of the 5α-reductase marker 3-α Diol G at 12POST HIIT vs. LISS). This is interesting, as dihydrotestosterone (DHT) which is often falsely associated only with hair loss, prostate cancer and even obesity, does also play an important role in strength development (click here to learn more) and appears to do it's magic via the MAPK receptor. Now, MAPK in turn can activate PGC-alpha and that the latter is way more than just the endurance / mitochondria builder it was long thought to be is something you should still remember from the post on the"The IGF-1 Promoting, Myostatin Reducing, Muscle Building Effects of PGC-1 α-4" (read more).

Bottom line: It is becoming more and more clear that HIIT is in fact somewhat of a chimera that shares beneficial and detrimental effects of both classic cardio and classic strength training with mammoth sessions like the one performed in the studies at hand triggering similar hormonal cascades that will - despite probably causing beneficial adaptations - simply require longer rest times than a classic LISS regimen.

A  note of caution: Both these studies point to the highly questionable "value" of taking a bunch of people letting them do whatever type of training once, measure some stuff of which you do only have a very rough idea of what it's actually doing and then have a bunch of morons like myself try to come up with "practical implications"

So if you do HIIT, stick to the principles "short and hard" (I would never suggest doing the >40min interval sessions for anyone whose primary goal is to be healthy and look good naked, by the way; add a walk on the treadmill if you want to train longer like on a combined HIIT + LISS cardio only day. But most importantly don't forget to enjoy your well-deserved, highly productive off-time and remember that it's during those hours, when all the hard work is paying off... ah I almost forgot, this is a tried and proven way that happens to be confirmed by studies like Hackney's and not vice versa.

 Light training, high TUTs and peak contractions - not just for the elderly?!

You cannot only implement"light" training into your established routine (see last paragraph), but should also think of the often forgotten benefits of periodization, detraining & co (learn more), as well as times, when you may be injured or otherwise disabled and cannot lift heavy.

(Watanabe. 2013) -- It may sound like a study for the elderly, but just as the best-agers among the SuppVersity readers can learn something from studies done in the the younger fellows, the younger weightlifters may well get some intriguing insights from studies with older participants - studies like the one by Watanabe et al., for example.

When the researchers from the Department of Life Sciences at the University of Tokyo compared the hypertrophy and strength gains of two exercise regimen using a low resistance of 50% of the personal 1-RM max of their 59-76yr old subjects, the scientists found that slow movements with tonic force generation were superior to the regular 1s concentric vs. 1s eccentric reps I guess most of you will be employing in their training routines.

The subjects who had been randomized to the LST group and performed their reps with a 3s concentric, a 3s eccentric and phase and most importantly a peak contraction in-between did gain a similar amounts of strength as those subjects who performed the standard protocol for 10 weeks (the 12-week study had a 2-week familiarization phase), but contrary to they did also record statistically significant increases in muscle size.

Alternative exercises on which peak contractions work well, are the fly (preferably on a machine or using cables), the lat pulldown, cable crunches, all sorts of triceps extensions, the scott curl (where you would do them midrange), every form of calf raises. Always remember, though: A peak contraction is never done in the full stretch position, but always either midrange or as the name implies at the peak of the contraction, before the eccentric phase begins.

So what does that mean? Certainly not that all of you should stop lifting heavy weights, because 50% 1-RM was enough if not superior to the regular 70-90% that are recommended in most serious training regimen. Rather, these results should remind young and old trainees alike of keeping an eye on your form and making sure that you stimulate the muscle and don't just move whatever weight from place A to place B.

That said, try to incorporate peak contractions with every rep on the auxilliary movements of your next workout. Start your leg workout with regular squats, for example, 5x5 TUT 101 (meaning 1s eccentric, 0s rest at the bottom, 1s concentric), but instead of the 4x10 leg extensions you would usually do for your quads, you lower the weight somewhat and do them with a slower rep-speed (somewhere in between 1-3s) and a peak contraction (meaning you really squeeze the muscle in a position, where your knees are almost locked out). Done right, this is going to give the word DOMS (=deep onset muscle soreness) a whole new meaning + you will have to reduce your weights, anyways.

Train your left leg and your right one will grow as well

(Song. 2012) -- Do our bodies know something about aesthetics? Well, if that were the case, the legs of some of the gymbros who "don't train legs, because [they] play soccer" shouldn't look the way they do... but I am digressing here. According to the study by Yafeng Song et al. have just published in the open access journal Plos ONE, there appears to be a certain carry-over effect - at least if the growth stimulus is chronic and profound.

To achieve the latter, i.e. a chronic and profound training stimulus, the researchers from the Umea University in Sweden exposed the soleus and gatrocnemius muscles of rabbits to a 6-week electrical muscle stimulation + exercise protocol and measured muscle changes and inflammation on weeks 1, 3 and 6 of the study. Now, the clue of the study was that the unilateral "exercise" was actually mechanically and electrically enforced, so to say:

"The movements are produced by a pneumatic piston, in which the range of motion can be controlled. The range of movement was set to 9.5 cm, given a range of motion in the ankle of 55–65u of which 20–25u was dorsiflexion and 35–40u was plantarflexion. The right leg was attached to the piston and the pelvis/hip region was strapped down to restrict the motion in the left non-exercised leg. The left leg was unattached. During the plantar flexion of the right leg, an active contraction was induced by electrical muscle stimulation via surface electrodes placed 2 cm apart over the right triceps surae muscle. The stimulation was synchronized with the plantar flexion movement of the piston by a microswitch, which trigged the stimulator unit".

I will spare you the further details... just think of a modern rabbit torture machine that was designed to "work the rabbits right extremities out". As you would expect from any good torture machine this device brought about a significant amount of tissue damage and a corresponding increase in the number of necrotic fibers.

Figure 2: Variability in fiber size, fibers with internal nuclei, inflammation in soleus (left) and gastrocnemius muscle (right) in response to the exercise + electrostimulation program. Mind the similar responses in the exercised (E) and the non-exercised (NE) limb (Song. 2012)

Now what's surprising though is the fact that despite the local damage, the inflammation had a systemic component, which happened to be more pronounced in the untrained soleus vs. gastrocnemius muscle (slow vs. fast twitch, by the way).

Against that background it is still only a little less surprising that the variability in fiber size, the number of fibers with internal nuclei (=sign of restructuring process, cf. "The Skeletal Muscle Hypertrophy 101") and even the fiber splitting were virtually identical. After all, this would mean that systemic parameters do matter. But haven't we just discarded this notion yet another time in the first of the items in today's exercise research quickie? Yes we have, but in that case we were talking about the usual subjects, the "anabolic" and "catabolic" hormones, Song et al. on the other hand speculate that

"[t]he collateral muscle changes and inflammation after unilateral EMS/E observed in this study may be caused by [a] neuronal mechanism. Since there is some evidence for a commissural system in the spinal cord that mediates transmedian signaling with a fairly precise bilateral representation, nerve signals from the trained side may pass over to the contralateral muscles through commisural inter-neurons. If this is the case, unilateral injury caused by EMS/E may cause a cross-transfer up-regulation of neuropeptides that can be involved in the inflammatory response in the contralateral muscles." (Song. 2012)

The researchers indicate that their current, as well as previous results from their laboratory would support this hypothesis and that any systemic or circulatory effects must actually be excluded, because these would not have occurred only focally, but generally within all muscles. They also point towards previous studies in which the signalling between contralateral and ipsilateral limb was blocked and the observed cotralateral responses were abolished.

So what's the point? I will openly admit that the practical relevance of these results (esp. for you as a hopefully healthy trainee) is as of now still very questionable, but the fact alone that it brings the nervous system back on the "scientific" radar was certainly worth including it in this "threesome" - don't you think so? No, well... maybe you like the scientists own rational who argue that the findings are (a) important in the context of a wide range of musculoskeletal and neuromuscular disorders and (b) relevant for each and every unilateral exercise experiment, where the contraleteral limb is used as a control - and you know there are plenty of them!

References:

• Hackney AC, Kallman A, Hosick KP, Rubin DA, Battaglini CL. Thyroid hormonal responses to intensive interval versus steady-state endurance exercise sessions. Hormones (Athens). 2012a Jan-Mar;11(1):54-60.
• Hackney AC, Hosick KP, Myer A, Rubin DA, Battaglini CL. Testosterone responses to intensive interval versus steady-state endurance exercise. J Endocrinol Invest. 2012b Dec;35(11):947-50.
• Ozen, SV. Reproductive hormones and cortisol responses to plyometric training in males. Biol Sport.2012; 29 (3).
• Song Y, Forsgren S, Yu J, Lorentzon R, Stål PS. Effects on contralateral muscles after unilateral electrical muscle stimulation and exercise. PLoS One. 2012;7(12):e52230.
• Watanabe Y, Tanimoto M, Ohgane A, Sanada K, Miyachi M, Ishii N. Increased muscle size and strength from slow-movement, low-intensity resistance exercise and tonic force generation. J Aging Phys Act. 2013 Jan;21(1):71-84.

On Short Notice: Insanity vs. TurboFire - What's the Best HIIT Regimen? Plus: USA vs. China, Chews vs. Raisins, Epi-Sesamine vs. Body Fat, Exercise vs. Neurotoxins & More

Figure 1: The latest medal prognosis for Olympia 2012 by researchers at the Department of Economics at the Ruhr-Universität Bochum in Germany (Otten. 2012) - I must admit I am curious how accurate this prognosis will be... what's your take? The US or China? Who's going to take the lead?

The Queen has officially opened the Olympic Games 2012 and the games have their first doping case - those of you who followed yesterday's advice to subscribe to the SuppVersity Facebook page are already in the know... anyways, this is not the place for one of my hypocrisy rants, but for the weekly installment of "On Short Notice". Still, in the "honor" of the Olympics *rofl* and the spirit of the SuppVersity - which is, as you all know, the place you will get the news first! - I have compiled the TOP15 from the latest medal prognosis by Sebastian Otten, the chair of the Department of Economics at the Ruhr-Universität Bochum in Germany, for you as an appetizer (figure 1). Moreover, I picked more sports and less health, weight-loss, supplementation and nutrition related topics from my ever-growing collection of "On Short Notice" items, which is by the way already so exuberant that there will be another episode of this series either tomorrow or early next week, mostly because otherwise the latest news would come in late... so, let's go for it!

Insanity vs. TurboFire Interval - What's the optimal HIIT regimen?

As part of her recently published master thesis, Sarah A. McGlinchy investigated the differential effects two commercial fitness programs had on the heart rate pulmonary O2 uptake, CO2 output, caloric expenditure and substrate utilization during exercise and recovery, as well as the subjective satisfaction and physical exertion of trained individuals (N=15, four males and 11 females, aged 22.3 ± 1.6 years McGlinchy. 2012).

• 

  Image 1: Insanity (top) vs. Turbo Fire (bottom) - My HIIT workouts look profoundly different, but this does not mean that those workouts cannot be effective; specifically if you enjoy stuff like this and don't do it alone in front of your TV, but with friends & new friends at the gym. And trust me, I don't even need a study to be able to tell you that a workout you enjoy will be more productive than the "objectively" best workout you hate

  Insanity® Interval Training Protocol - A plyometric cardio circuit workout that is performed after a 9 min warum-up and followed by a 5 min stretch. It revolves around different drills (performed at progressively increasing intensity) that are separated by 30s water breaks, the drills last about 1 min each - the total length of the workout is 41 minutes and 35 seconds (click here to watch a promo video on YouTube)
• Turbo Fire® Interval Training Protocol - The HIIT 30 variety of a series of DVDs that comes from the same company that sells the P90X DVDs includes a 3 min warm-up, a 3 min cool down with stretching and slow movements to get the heart rate back to normal and a series of five drills of which the first four are repeated twice and the last one three times. Drills last about 1 min and are supposed to be performed with maximum effort each is followed by one minute of active recovery (walking, jogging in place, etc.). Water breaks are allowed during the active recovery. The total length of the workout is 30 minutes and 36 seconds (click here to watch a private workout video on YouTube).

I don't know about you, but based on the part of the videos I saw, before I felt I had seen enough, I would probably prefer the Insanity (Ins) over the Turbo Fire (TF) protocol; not so the study participants, though: After having performed both workouts in a randomized order, their "positive engagement" was slightly more pronounced after the TF protocol (see figure 2, left). It should however be mentioned that neither the the pre- to post- nor the inter-workout differences were statistically significant (with a total number of subjects of N=15, the difference could well have been 7/8, had the subjects been asked to pick one or the other).

Figure 2: Physical exhaustion, tranquility and pos. engagement after workouts (left), respiratory exchange ratio at rest and from min. 5-60 (middle), and time (in s) during the workout, when the heart rate was within the given percentages of the calculated personal HR_max(data adapted from McGlinchy. 2012)

My gut tells me that the part of the preference for the TurboFire (TF) protocol could be due to from a) the shorter overall duration and b) the greater exhaustion the subjects in experienced during the Insanity trial -I mean "insanity"? What else do you expect???

Ignore fatty acid oxidation and total calorie expenditure - pick the one you like!

The significantly less pronounced at the end of the TurboFire Intervals stand in contrast to the total the subjects were working out in the 81-90% HR_max, though. With 1000 seconds (vs. 580s) the latter was significantly longer during the Turbo Fire session. Accordingly, the subjects' respiratory exchange ratio (RER), a measure for the relation of glucose to fatty acid oxidation was significantly higher, as well.

SuppTensity Workout Perform 3 cycles of these 5 drills, each drill lasts 1 min, 45s active recovery  between drills, 2 min between cycles

• Squats*
• Push ups
• Lunges**
• Clean & press*
• Rope skipping

use adequately loaded *barbell or **dumbbell

While the former was to be expected, it may appear somewhat odd at first, though, is the higher and longer-lasting post-exercise energy expenditure in the Insanity group (p < 0.05), which could yet be explained by an overall slightly more demanding (figure 1, left > exhaustion) workout, which - and this is just based on what I saw in the videos - appears to have more "complete" drills - or did you see things like push-ups in the Turbo Fire workout? Against the background that the minimal differences in intra- and post-workout energy expenditure and substrate utilization won't have any noticeable effect on the desired outcome variable, i.e. a leaner, still muscular physique, and in view of the fact that"EPOC comprises only 6-15% of the net total oxygen cost of the exercise" (LaForgia. 2006), anyway, I would fully subscribe to Sarah McGlinchy's recommendation to simply pick the workout you like - based on McGlinchy's interpration of her subjects' feedback that would be the ...

• Turbo Fire® for people who are "looking for more variety of movements with fun music"
• Insanity® for people for whom "music isn’t a priority", but who look for "intense motivation"

Before I conclude this pretty longish and therefore single "on short notice" item with the implications and go ahead to the promised truckload of "on very short notice" items, I would yet like to add one thing to this recommendation: You don't actually need to buy a DVD to do HIIT. It's actually pretty straight forward to compile your own personal HIIT 1min on, 30s off (alternatively 1min active rest) workout by handcrafting your drills from from simple sprints on the grass or beach, intense rope skipping, push-ups, pull-ups, squats, kettlebell swings, stair climbers and everything else you can think of - if you are at a loss now, check out my botchy sample workout on the upper right - took me ~1min to put that together and I know that each one of you can do better!

Image 2: I am not saying everyone needs one of those workout DVDs, but for those of you (or friends of yours) who are not already fed up with "motivational pics + statements" like the one above, which are handed around on facebook like the WWF cards 20y ago on my schoolyard, it my be worth looking into either of these.

Implications: I don't care whether you like it or not (I don't like those workouts either), but I am 2x more inclined to believe the numerous success stories the producers of these workout DVDs use to plaster the Internet than any of the reports on how great supplement X is working for Mr. Y on bodybuilding.com and the like.

Do I suggest you buy a DVD or hop around like a jackass in the gym, let alone in front of your TV, when you prefer going to the next best park or beach doing sprints and combine those with your regular strength training program in the gym? Certainly not! Would I rather see you, your friends or family perform any of these workouts than doing exclusively strength training (let alone ultra low volume 1-rep max style) or hours of steady state aerobics if your goal is to get jacked? Abs(!)olutely ;-)

On very short notice

• 

  Image 3: Not everything that's golden is good - the "golden" raisins for example have been treated with sulfur dioxide, to prevent them from darkening. At least in susceptible persons SO2 can lead to serious allergic reactions, 4-8% of asthmatics are (also) allergic to dietary sulfites and its general safety is still a matter of constant debate - commonly associated health effects are Urticaria, angioedema, and IgE-mediated anaphylaxis (Rangan. 2009).

  Commercial carbohydrate chews not better than plain raisins - I guess this one falls into the "Olympia tribute" category, aside from Albanian weightlifters, wo obviously prefer Stanozolol, most of the athletes probably use carbohydrate supplements in one form or another. Whether anybody relies on resins as is intra-competition carbohydrate supplement is yet questionable and that despite the fact that the dried grapes can easily compete with the far more expensive Cliff blocks carbohydrate chews. Aside from nonsignificantly faster time-trial performances, the fourteen healthy competitive runners from the University of California who consumed raisins instead of chews, also felt slightly less sore after and had lower insulin levels and greater fatty acid oxidation rates during the run.
  Reason enough for Brandon W Too and his colleagues to conclude "that consuming a natural CHO source (raisins) [..] is well tolerated and maintains blood glucose levels and running performance similar to a commercial CHO product (sport chews)" (Too. 2012). Did you hear that Michael Phelps?
• Epi-sesamine from Lindera obtusiloba could be novel source for potent anti-obesity drug - This is at least what a recently published study that was conducted by scientists from the German Charité Universitätsklinikum in Berlin would suggest (Freise. 2012). In their in-vitro tests the active ingredient of the Japanese spice bush, which has traditionally been used for treatment of inflammation and the prevention of liver damage in Oriental Medicine, did not just prevent the accumulation of lipid droplets, it also activated the pro-apoptotic enzymes caspases-3/-7, which initiated programmed cell-death in the treated fat cells. In view of my recent blogpost on the nasty persistence of lower body fat, the latter could turn out to be of extreme importance - especially for those of you who have already lost a significant amount of body fat and are now suffering from "relative leptin deficiency" (see "Nasty Insights into the Yo-Yo-Effect" for more on how this relates to the YoYo-Effect and weight loss plateaus).

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  Figure 3: Mild exercise (5x 30 min / week, treadmill) boosts brain 5a- reductase and neurogenesis (Okamoto. 2012)

  Mild exercise and the brain: Is DHT what builds new neurons? If there was one hormone that really has gotten a bad rep over the past 50 years, it certainly is DHT: All of you who've read the respective installment of the Intermittent Thoughts (cf. "DHT - The All Things Male Hormone") or the latest news on the DHEA <> DHT muscle generation connection will be aware that the myth of the dangerous, carcinogenic bigger brother of testosterone is at least overtly simplistic if not totally devoid any scientific bases.
  Recently published data from the Laboratory of Exercise Biochemistry and Neuroendocrinology at the University of Tsukuba, in Japan does now add another piece to the "DHT is not bad" puzzle - one even women could come to appreciate (Okamoto. 2012): According to Masahiro Okamoto and colleagues, the exercise induced increase in 5-alpha reductase activity (5-ar converts testosterone to dihydrotestosterone) and the subsequent rise in neuronal DHT appears to be the driving force of neurogenesis (the generation of new neuronal networks / brain tissue and wiring).

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  Image 4: Those of you who have made the transition to physical culture too late or have friends or relatives who missed the boat completely may be interested to hear that researchers from the RIKEN Center for Developmental Biology successfully used stem cells to replete Purkinje neurons two years ago, already (Maguruma. 2010)

  Chronic exercise renders Purkinje neurons bullet proof - In a way unquestionably related to the previous "On Very Short Notice" item are the findings from Huang et al. have just published in Journal of Applied Physiology. In their paper the researchers describe the 8-weeks of moderate treadmill running had on the toxin resistance of 6-week old rodents. Specifically, Huang et al. observed that the "exercised rats not only performed better in the rotarod task [skilled behavior test, see video] but also showed finer Purkinje cell structure (higher dendritic volume and spine density)" (Huang. 2012). And while this is unquestionably reminiscent of the aforementioned neuron-building effects of DHT (which is, as you should know increased with aerobic / volume training; cf. "Intermittent Thoughts on DHT"), the big news is that the neurons of the exercised rodents were also protected against the immunotoxin OX7-saporin.
  If these results translate (I personally believe that this is not a question of yes or no, but only one of the extend to which these results translate) to any of the bazillion other toxins we are exposed to on a daily basis, this would imply that regular exercise may not just protect us from the "classic" neurodegenerative diseases such as Alzheimer's or Parkinson, but also from autoimmune diseases which have a neuronal component and often involve damage to the very Purkinje neurons the researchers found to be "bullet proof" in the study at hand.
• Children of diabetic parents benefit most from hitting the weights - "The offspring" of type II diabetics that's the somewhat surprising result of a 9-week training + 9-week detraining experiment Katherine Schofield and her colleagues from New Zealand and Denmark conducted respond particularly favorable to resistance training programs (Schofield. 2012). At the end of the initial 9 week training period, the insulin response of the children with diabetic parents was still worse than thatof their peers in the control group, but with improvements of roughly 30% they were already approaching what you may call the "normal zone", when the detraining phase begun. Contrary to the kids in the control group, whose insulin sensitivity did not change over the 9 weeks of laziness, the children of type II diabetics lost all their previously achieved improvements. Now, you could certainly argue how those poor kids are at such a disadvantage, but unless you want to feed them metformin for the rest of their lives, I suggest we should rather think of ways to teach them how to resist the bad eating habits of their parents and stick to a workout routine that will make the diabetes medication obsolete - don't you agree?

• 

  Suggested reads for everyone interested in some background info on nitrates: (1) Ask Dr. Andro: Is Creatine Nitrate Worth it? (2) Nitrates Work! First NO2 Victim in ER

  Nitrate supplements don't work for athletes and could mess with blood pressure regulation - At least if you are a trained athlete who wants to improve his/her performance, the use of sodium nitrate is a waste of time and money - this is at least what the soon to be published results of a randomized, double-blind cross-over study by Spanish scientists would suggest. For their experiment, Bescós et al. recruited 13 trained athletes and had them perform a 40-min ergometer distance-trial test after a 3-day supplementation regimen with either sodium nitrate (10mg/kg body weight) or placebo (Bescós. 2012).
  Contrary to earlier trials in non-trained subjects, the athletes' performance did not benefit from the supplemental nitrate - despite statistically significant increases in plasma nitrate (+17%) and nitrite (+56%), by the way. Moreover, the concommitant increase in endothelin-1, a protein that constricts blood vessels, raises blood pressure and thus counters the vasodilating effects of the nitrates raises concerns regarding potential side effects that could occur once you drop the supplement.

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  Image 5: Mineral supplements are usually not necessary, as long as you pick the right foods and drinks! What's much more likely in the Western hemisphere than deficiencies, though, are imbalances - and weekend warriors and gymbros are even more likely than your average obese pre-diabetic to run into oftentimes self-inflicted problems... there is going to be a Super Human University seminar Carl Lanore and I are currently working on - and let me tell you this, this is a topic that is literally very dear to Carl's heart.

  Decrease your risk of heart disease by 5% with each mg/L of Magnesium in your drinking water! - I am certainly not among the magnesium enthusiast who propose supplementation with whichever form of oral mg supplement (let alone the scientifically hitherto not verified use of oils) as the latest panacea, but as you may have heard on Super Human Radio on Wednesday, July 25, 2012 (click here for the podcast), I do believe in the overlooked importance of getting your ratios straight; and that, i.e. having the right ratio of Ca:Mg begins at the most fundamental level - with the mineral ratios in your drinking water! Finish scientists who recorded the mineral intake of 14,495 male subjects (aged 35-74), for example, found that with a constant and roughly two times too high mean Ca / Mg ratio of 5.39 / 1 in the drinking water of the area, every additional milligram of magnesium per liter drinking water (e.g. from 2.61mg/L to 3.61mg/L), would help to reduce the risk of acute myocardial infarction by 4.9% (Kousa. 2006)!
  This is an impressive figure and yet, the real beauty of this study is that it emphasizes the need to re-evaluate your nutritional mineral intake, instead / before considering using dietary (let alone oily ;-) supplements!

References:

• Bescós R, Ferrer-Roca V, Galilea PA, Roig A, Drobnic F, Sureda A, Martorell M, Cordova A, Tur JA, Pons A. Sodium Nitrate Supplementation Does Not Enhance Performance of Endurance Athletes. Med Sci Sports Exerc. 2012 Jul 17.
• Freise C, Trowitzsch-Kienast W, Erben U, Seehofer D, Kim KY, Zeitz M, Ruehl M, Somasundaram R. (+)-Episesamin inhibits adipogenesis and exerts anti-inflammatory effects in 3T3-L1 (pre)adipocytes by sustained Wnt signaling, down-regulation of PPARγ and induction of iNOS. J Nutr Biochem. 2012 Jul 18.
• Huang TY, Lin LS, Cho KC, Chen SJ, Kuo YM, Yu L, Wu FS, Chuang JI, Chen HI, Jen CJ. Chronic treadmill exercise in rats delicately alters the Purkinje cell structure to improve motor performance and toxin-resistance in the cerebellum. J Appl Physiol. 2012 Jul 26.
• Kousa A, Havulinna AS, Moltchanova E, Taskinen O, Nikkarinen M, Eriksson J, Karvonen M. Calcium:magnesium ratio in local groundwater and incidence of acute myocardial infarction among males in rural Finland. Environ Health Perspect. 2006 May;114(5):730-4.
• LaForgia J, Withers RT, Gore CJ. Effects of exercise intensity and duration on the excess post-exercise oxygen consumption. J Sports Sci. 2006 Dec;24(12):1247-64.
• Muguruma K, Nishiyama A, Ono Y, Miyawaki H, Mizuhara E, Hori S, Kakizuka A, Obata K, Yanagawa Y, Hirano T, Sasai Y. Ontogeny-recapitulating generation and tissue integration of ES cell-derived Purkinje cells. Nat Neurosci. 2010 Oct;13(10):1171-80.
• McGlinchy SA. The Effect of Two High Intensity Interval Training Protocols on Heart Rate, Caloric Expenditure, and Substrate Utilization During Exercise and Recovery. University of Toledo - Submitted to the Graduate Faculty as partial fulfillment of the requirements for The Master of Science Degree in Exercise Science. 2012.
• Okamoto M, Hojo Y, Inoue K, Matsui T, Kawato S, McEwen BS, Soya H. Mild exercise increases dihydrotestosterone in hippocampus providing evidence for androgenic mediation of neurogenesis. Proc Natl Acad Sci U S A. 2012 Jul 17.
• Schofield KL, Rehrer NJ, Perry TL, Ross A, Andersen JL, Osborne H. Insulin and Fiber Type in Offspring of T2DM with Resistance Training and Detraining. Med Sci Sports Exerc. 2012 Jul 17.
• Rangan C, Barceloux DG. Food additives and sensitivities. Dis Mon. 2009 May;55(5):292-311.
• Too BW, Cicai S, Hockett KR, Applegate E, Davis BA, Casazza GA. Natural versus Commercial Carbohydrate Supplementation and Endurance Running Performance. J Int Soc Sports Nutr. 2012 Jun 15;9(1):27.