Ecdysterone Beats Popular Anabolics!? Plus 75% Muscle Size in 21 Days in Rats - More Than DHT, IGF-1, Dianabol...

Ecdysterone Beats Popular Anabolics!? Plus 75% Muscle Size in 21 Days in Rats - More Than DHT, IGF-1, Dianabol...

anabolic anabolics build muscle DHT doping ecdysteroids ecdysterone estrogen receptor hypertrophy protein synthesis WADA

Parr et al. suggest that ecdysterone should be added to the WADA list.

Actually, I didn't plan to write a SuppVersity article about an agent of which everybody says that it's a waste of money, but I have to admit that the conclusion that "ecdysterone exhibited a strong hypertrophic effect on the fiber size of rat soleus muscle that was found even stronger compared to the test compounds metandienone (dianabol), estradienedione (trenbolox), and SARM S 1, all administered in the same dose (5 mg/kg body weight, for 21 days)" (Parr. 2015) in the abstract of a recent non-sponsored (no conflict of interest, either) study from the Freie Universität Berlin intrigued me.

In the corresponding study, Parr and colleagues had tested the effects of ecdysterones on the fiber sizes of the soleus muscle (that's mainly slow twitch muscle fibers) of rodents in vivo and in vitro.

If you want to build muscle forget T-booster and optimize your protein intake 

Protein Timing DOES Matter!

5x More Than the FDA Allows!

Protein requ. of athletes

High EAA protein for fat loss

Fast vs. slow protein

Whey vs. Pea Protein

In the less relevant in vitro study, the researchers incubated C2C12 derived myotubes with the test compounds and determination of diameters of 47 myotubes per group (mean of measurements every 10–20 µm along the myotube) by fixing the cells and using photographs of the stained cells to determine the myotube diameters of 50 myotubes every 10–20 µm along the length of the myotube (further details see Parr. 2014). As the authors point out, incubation with ecdysterone showed "sign. increased myotube diameters compared to vehicle treated control cells" (Parr. 2015 | see Figure 1).

Figure 1: Myotube diameter in the in vitro study after incubation with DHT, IGF-1 or Ecdysterone (Parr. 2015).

If you compare the effects of the Ecdy treatment with those of the endogenous anabolic androgenic steroid dihydrotestosterone at the same concentration and those of the anabolic growth factor IGF-1 (concentration for comparison was 1.3 nM) it is quite impressive to see that there was an (albeit non significant) advantage for an active phytoecdysteroid the Russians have supposedly used as early as in the 1980s for doping purposes.

How does ecdysterone work? Previous studies already confirmed the beneficial effects of ecdysterone on skeletal muscle protein synthesis. As early as in the year 2000, V.N. Syrov published a paper in the Pharmeceutical Chemistry Journal in which the beneficial effects ecdysterone and related agents on rodent muscles were documented. Later on, Gorelick-Feldman et al. proposed direct or indirect stimulation of the PI3K/Akt signaling pathway as mechanism for this increased protein synthesis (Gorelick-Feldman. 2008 & 2010). In the study at hand, Parr et al conducted molecular modeling experiments which appear to confirm that the effects of ecydesterone are mediated by estrogen-receptor-β (ERβ) binding, rather than via the androgen receptor which is the target of the many of the other drugs used. 

Obviously, the effects of bathing individual cells in concentrated ecdysterone cannot serve as a reliable litmus test for the anabolic prowess of an agent bodybuilders take as an oral supplement in dosages of usually no more than 1g per day. In this respect, the concomitantly conducted experiment with intact rodents is of much greater interest. In this part of study, the authors fed male Wistar rats (n = 42, Janvier, Le-Genest St-Isle, France) either 5 mg/kg body weight of ecdysterone, metandienone, estradienedione, or the selective androgen receptor modulatar (SARM) S-1, each diluted in a solution of 20% DMSO and 80% peanut oil daily. In that, it is unfortunately not 100% quite clear if the scientists used intraperitoneal or intra-muscular injections, but the composition of the "supplement" and the fact that a previous study (Syrov. 2000) used the same dosage orally, appear to suggest that Parr et al. refer to about IP injections, which mimic oral supplementation, but have the advantage of giving rodents no chance to regurgitate the drug, when they write that the rodents "received injections". What is pretty clear, though, is that the scientists used changes in muscle fiber size of the soleus muscle of male Wistar rats as measure of the anabolic potency of their test substances.

Figure 2: Anabolic effect of ecdysterone (Ecdy) expressed as fiber size of soleus muscle in intact rats (Parr. 2015).

The results of the comparison of ecdysterone to the anabolic androgenic steroids metandienone (dianabol) and estradienedione (trenbolox) as well as the selective androgen receptor modulator S-1 are plotted in Figure 2. Quite impressive , no? And this is not an outlier study. As Parr et al point out, their study is not the first to show that "ecdysterone induces hypertrophy of muscles with a comparable or even higher potency as shown for anabolic androgenic steroids, SARMs or IGF-1", as analogous findings have been reported in the previously cited study by Syrov back in 2000. Human data, as well as data that would confirm similar effects on muscles that are predominantly fast-twitch (the soleus which was examined in the study at hand is mostly slow twitch) are yet missing. The latter is of particular interest, because estrogen treatment appears to favor a more oxidative (=more slow vs. fast twitch) fiber muscle fiber composition (Suzuki. 1985).

Hormonal Response to Exercise, Revisited: A Consequence, not a Determinant of Your Mood, Effort & Performance | learn more

Bottom line: In spite of the fact that the study provides quite convincing evidence in favor of the unexpected potency of Ecdysterone, there is a problem with dosing. While the scientists say they used 5mg/kg body weight in order "mimic the situation in athletes", the correct rodent equivalent of the aforementioned dosages of up to 1g per day would be roughly 50-75mg/kg per day and thus far more than the meager 5mg/kg the researchers used.

In other words, if they didn't accidentally give us the human equivalen dose instead of the actual rodent dose, those 1g/day some bodybuilders may be taking should be way more than you'd need to see significant increases in muscle gains and that is a problem.

Why? Well, not because I'd believe that dosages as high may have toxic side effects, but rather in view of the fact that you can hardly imagine that a drug as effective as that wouldn't be all over the place in the discussions on pertinent bulletin boards. A 2006 study by Wilborn et al. even fuels the doubts, because it found no performance or hypertrophy effects in the 15 out of 45 subject of their 8-week training study who consumed 30 mg of 20-hydroxyecdysone per day from an allegedly standardized (but not tested) extract from Suma root. An even older study by Simakin et al. (1988), however, appears to confirm the existence of potent anabolic effects of ecdysterone in humans with significant increases in lean (6-7%) and reductions in fat mass (10%) in a 3-week study on 78 highly-trained male and female subjects. In view of the conflicting evidence, I am still very skeptical whether (a) the results translate to human beings, whether (b) the growth promoting effect is maybe restricted to slow twitch fibers and thus of little use to bodybuilders and whether (c) the supplements that are already being sold actually contain ecdysterones | Comment!

References:

• Gorelick-Feldman, Jonathan, et al. "Phytoecdysteroids increase protein synthesis in skeletal muscle cells." Journal of agricultural and food chemistry 56.10 (2008): 3532-3537.
• Gorelick-Feldman, Jonathan, Wendie Cohick, and Ilya Raskin. "Ecdysteroids elicit a rapid Ca 2+ flux leading to Akt activation and increased protein synthesis in skeletal muscle cells." Steroids 75.10 (2010): 632-637.
• Parr, Maria Kristina, et al. "Estrogen receptor beta is involved in skeletal muscle hypertrophy induced by the phytoecdysteroid ecdysterone." Molecular nutrition & food research 58.9 (2014): 1861-1872.
• Parr, M. K., et al. "Ecdysteroids: A novel class of anabolic agents?." Biology of sport 32.2 (2015): 169.
• Simakin, S. Yu. "The Combined Use of Ecdisten and the Product'Bodrost'during Training in Cyclical Types of Sport." Scientific Sports Bulletin 2 (1988).
• Suzuki, S., and T. Yamamuro. "Long-term effects of estrogen on rat skeletal muscle." Experimental neurology 87.2 (1985): 291-299.
• Syrov, V. N. "Comparative experimental investigation of the anabolic activity of phytoecdysteroids and steranabols." Pharmaceutical Chemistry Journal 34.4 (2000): 193-197.
• Wilborn, Colin D., et al. "Effects of methoxyisoflavone, ecdysterone, and sulfo-polysaccharide supplementation on training adaptations in resistance-trained males." Journal of the International Society of Sports Nutrition 3.2 (2006): 19-27.

Hormonal Response to Exercise, Revisited: A Consequence, not a Determinant of Your Mood, Effort & Performance

Hormonal Response to Exercise, Revisited: A Consequence, not a Determinant of Your Mood, Effort & Performance

build muscle DHT female GH growth hormone HIIT hormones performance resistance training testosterone women women strength

Studies in men suggest no effect of the hormonal response on training outcome - What about women? A news study provides insights that may be relevant for both female and male gymrats.

It has been a few years that I last wrote about the "hormonal ghost". Back in the day, Stuart M. Phillips published an excellent paper that debunked the myth of a mechanistic link of post-exercise increases in testosterone, growth hormone, IGF-1 and co., on the one hand, and exercise-induced strength and size gains, on the other hand. And for those for whom Phillip's review of the literature was not convincing enough, Daniel WD West's 2012, which showed none of the expected associations between exercise-induced hormone profiles (first and foremost higher post-workout testosterone levels) and the rate or significance of muscle strength and size gains in a large cohort of young men after weight training, should have been evidence enough to stop believing in "hormonal ghosts", but alas... you will probably know that "training for testosterone increases" is still en vogue.

Learn more about building muscle and strength at www.suppversity.com

Tri- or Multi-Set Training for Body Recomp.?

Alternating Squat & Blood Pressure - Productive?

Pre-Exhaustion Exhausts Your Growth Potential

Exercise not Intensity Variation for Max. Gains

Battle the Rope to Get Ripped & Strong

Study Indicates Cut the Volume Make the Gains!

That's stupid stubbornness, nothing else, right? Well, even though I don't believe in ghosts, I have to admit that a closer look at West's data will have you reject the hypothesis that the post-workout testosterone response would augment size gains, it does yet also show other hormonal changes do correlate with the changes in the study's subjects' lean mass (Figure 1, left) as well as type I (middle) and type II fiber size increases (Figure 1, middle & right).

Figure 1: Sign. associations between PWO hormone levels and lean mass, as well as fiber size increases (West. 2012).

As you can see in Figure 1, this was the case for the cortisol response and the lean mass gains and the growth hormone (GH) response and the increases in type I ('endurance') and type II ('strength') fiber size. Even though I don't believe that more than 1% of the gymrats world-wide who still believe that maximizing the post-workout "anabolic response" would help them to maximize their gains even know about these results, you could argue that these correlations fuel their beliefs - even if that's paradoxical, because - in bro-scientific terms - you'd have to maximize the catabolic response, i.e. the increase in cortisol (which could by the way simply be a measure of training intensity) in order to maximize the overall gains in muscle size, but alas...

Figure 2: Changes in anabolic and catabolic hormones in response to AM and PM HIIT and RT training (Toon. 2015).

In a series of experiments Rebecca Toone conducted for her thesis, she re-addressed the issue of the acute hormonal effects on performance with female study participants (yes, a long-term study was not part of her thesis, but I promise, the results are still noteworthy).

Higher sprint cadence (RPM) during HIIT, higher increase in DHT in the female study participants (Toon. 2015).

DHT another acute phase reactant? Even though the overall results of the study suggest that increased pre- vs. post workout changes in DHT as Toone observed the with higher RPM-numbers during HIIT sprints are not the reason, but rather the consequences of training at higher intensities, it is worth mentioning that this is the first study to observe the existence of an association between DHT and HIIT performance in women and that the results are in line with the results of previous research suggesting that DHT, not its precursor, testosterone, has a direct influence on skeletal muscle force production in vitro. 

After some preliminary testing, Toone began with another of the infamous "AM vs. PM" workout studies in which she unsurprisingly confirmed that...

"[...] it could be beneficial to perform resistance training in the afternoon preceded by interval exercise in the morning in order to stimulate a hormonal milieu that may be more conducive to stimulating muscle protein turnover" (Toon. 2015). 

If you scrutinize the data in Figure 2, you can see that this hypothesis is warranted, because of the differential response of the anabolic hormones, testosterone and IGF-1, and the stress / catabolic hormones, cortisol and prolactin, she observed in her young female subjects. Against that background it is quite interesting that Toone's last and most important experiment, in which she investigating the potential acute effects of hormones on performance, failed to demonstrate a direct correlation between changes in testosterone or other "anabolic" hormones and her subjects' performance.

"The trial consisted of a 20 min effort at a target power of 80% of the average power obtained during the maximal 20 min TT, followed by a 5 min break, before completion of a bout of repeated sprint interval cycle exercise consisting of 10 x 30 s sprinting, with 90 s recovery. The session was self-paced with real-time numerical feedback provided on elapsed time, cadence and power. Participants were given verbal encouragement at specific time-points throughout the trial. The same protocol was repeated for the second main trial one week later. Participants were permitted to drink water ad libitum throughout the trials. Trials were completed in a group setting as a group of six and a group of eight. A trial timeline schematic is displayed [in Figure 3]" (Toon. 2015).

Instead, the results of the previously described exercise test point towards affective variables, i.e. mood and effort, as the factors that mediate any link between hormonal changes and performance markers during an acute bout of high intensity cycling.

Figure 3: Design of the last and most important experiment of the study (Toone. 2015).

And guess what, the effort Toone's subjects invested into their workouts was not just a predictor of their performance, it was also positively associated with the percent change in testosterone concentration from post-sprint 4 to post-exercise (r = 0.449; P < 0.01).

Note: We are till talking about associations and correlations. That one of these, e.g. the one between the effort we put into our workouts and the preformance and hormonal response exists because of a causal link is thus in view of the results of the study at hand logical, but still hypothetical. As I am about to point out in the bottom line, future studies will have to investigate that - even though I have to admit that it will be difficult to develop an effective design for these studies.

In conjunction with the subjects' affect, which was inversely correlated with the rate of perceived exertion, which in turn showed positive correlations with cortisol, the results highlight a previously overlooked role of effort and affect when it comes to both, exercise performance and its effect on certain hormones.

Figure 4: The hormonal response is rather the consequence than the trigger of acute performance.

Or as Toone has it in her interpretation of these somewhat surprising results: The acute short-term effects of hormone concentrations on performance may be more related to mood and behaviour" than the actual type / time of exercise in the context of her study.

What does that mean? Practically speaking this would confirm what I have said about the initially cited West study in several previous SuppVersity articles. In said study, cortisol probably has no mechanistic effect on muscle size. Rather than that, the increase in cortisol could serve as a measure of how much effort the subjects put into their workouts; and this, in turn, determined their muscle gains (more effort = bigger growth stimulus = greater gains).

The meager and transient increase in testosterone after your workouts has none of the muscle building and fat shedding effects of exogenous testosterone. The latter however, can turn back the time and an aging pouch into a true best-ager | learn more.

In the study at hand, the situation appears to be similar. Mood and effort determine performance and hormonal response of the female study participants. Accordingly, there may be associations between exercise performance and certain hormones, but those are of corollary, not causative nature. In the absence of an additional experiment that would investigate the correlations and associations between mood, effort, RPE, hormones and the exercise-induced adaptation in the long run, we can still only speculate that making the workouts more fun and stimulating maximal effort would promote both, the adaptive response and the hormonal response and thus confirm that mood and effort are in fact the most relevant determinants of the outcome of your workouts | Comment!

References:

• Phillips, Stuart M. "Strength and hypertrophy with resistance training: chasing a hormonal ghost." European journal of applied physiology 112.5 (2012): 1981-1983.
• Toone, Rebecca. Assessing the Hormone Response to High Intensity Exercise and Identifying Associations with Performance. Diss. University of Bath, 2015.
• West, Daniel WD, and Stuart M. Phillips. "Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training." European journal of applied physiology 112.7 (2012): 2693-2702.