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

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.

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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).

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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.

Ecdysterone: Supplemental Non-Starter or Estrogen-Driven Muscle Builder? Phytoecdysteroid Builds Rodent Muscles, But the Devil's in the Details - "Growth" ≠ "Mass Gains"

Estrogens are not for women, only!?

If you asked me the above question a day ago, I would have answered "supplemental non-starter"; and while I still believe that the corresponding products are useless ripoffs, a recent study, Maria Kristina Parr and colleagues from the German Sport University, the Freie Universität Berlin, the , Beijing University of Chinese Medicine, the Central Institute of the Bundeswehr Medical Service, Bayer Pharma, the University of Veterinary Medicine Hannover, and the Nanchang University in China had me thinking: The results look impressive, at first sight, but there are strings attached - strings you'll see only if you look closely.

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Ok, we are talking about yet another rodent study with all the usual downsides and one major advantage - you can do a full analysis of all effects and possible underlying mechanisms! In the case of the study at hand this analysis included dissecting the prostate, weighing the muscles, and a lot of other stuff that would have required killing a human subject if it had been done in a human study.

Figure 1: Size of soleus muscle fibers in rodent study and effects of ecdysterone vs. dexamethasone, DHT, IGF1 in a previous in-vitro experiment (Parr. 2014)

Needless to say that this does not change the fact that we don't know if the human equivalent of the 5mg/kg the male rats in Parr's study received in an 20% ethanol + 80% corn oil dilution for 21 days would produce similarly impressive increases in soleus muscle fiber area and myotube diameter (see Figure 1) in a human being as it did in the male Wistar rats in the study at hand.

Beware of the details! The increases in muscle fiber size did not translate into increased muscle mass. In fact the soleus muscle from Figure 1 was lighter for the rodents in the ecdysterone: 0.16g in the control vs. 0.15g in the ecdysterone group - non-significant, obviously, but certainly not the impressive gains the various product descriptions of ECDY products promise, ha?

One thing that appears to be pretty certain, though, is the fact that ecdysterone will have some estrogenic activity in humans, as well. The latter, i.e. the ability of ecdysterone to bind to the both estrogen receptors quite potently, sounds like news right from nightmare of the bro next door. In the end, it does yet explain how Ecdy, the anabolic activity of which is believed to be androgen receptor independent (Grolick-Feldmann. 2008), could perform its muscle building job in humans, as well: via its estrogenic activity! And the fact that the levator ani muscle, which is plastered with androgen receptors (Joubert. 1994), did not react to the treatment only confirms this hypothesis.

Figure 2: Serum levels of cortisol, IGF-1 and 17b-estradiol (Parr. 2014)

And what's more, the decrease in cortisol, increase in IGF and reduction of real estradiol the scientist observed, when they analyzed the blood of their furry study subjects also look as if they were the objects of a bro's dreams - wet dreams, not nightmares.

If you want to optimize your androgen levels, avoid these 10 proven anti- androgenic agents in your diet and life and maximize your natural androgen production for free!

Bottom line: Overall the study at hand is unquestionably the most convincing evidence of the muscle building effects of ecdysterone I've seen. On the other hand, the mere fact that no one reports similar gains on any of the currently or previously available ecdysterone supplements should make you question, whether popping 60-75mg of >90% pure ecydesterone, which would be the human equivalent of the dosage the rodents received in the study at hand, will really make you big and strong. Why? Well because the fiber-size of the soleus increased without increases in soleus weight (control: 0.16g; ecy: 0.15g) -- If you expect internal changes in muscle structure, only, go for it, if you want gains, I stick to what I said before: Avoid ecdysterone supplements.

References:

• Gorelick-Feldmann, J., MacLean, D., Ilic, N., Poulev, A. et al., Phytoecdysteroids increase protein synthesis in skeletal muscle cells.J. Agric. Food Chem.2008,56, 3532–3537.
• Joubert, Y., Tobin, C., Lebart, M. C., Testosterone-induced masculinization of the rat levator ani muscle during puberty. Dev. Biol.1994,162, 104–110.
• Parr et al. Estrogen receptor beta is involved in skeletal muscle hypertrophy induced by the phytoecdysteroid ecdysterone. Mol. Nutr. Food Res.2014,00,1–12

Study Finds 17x Elevated Estrogen, High Progesterone + Reduced DHEA Levels in 65% of Ecdysteroid, Tribulus, Phytoestrogen, Phytosterol and / or Soy Protein Users!

Image 1 (Oliver Knöbel aka "Olivia Jones"): Not sure, but maybe the famous German drag artist Oilver Knöbel  aka "Olivia Jones" would be willing to buy some of your "all natural ergogenics"?

Tekin and Kravitz estimate the number of currently available "nutritional supplements" to be 30,000+ and if you want my personal estimate, roughly 30 of those are useful (Tekin. 2012). And while many of the other 29,970 supplements are often just dispensable, some are downright harmful or, as we have recently seen for alpha lipoic acid and zinc only beneficial for a certain, often sick, obese and diabetic part of the population (see "You are better of without alpha lipoic acid" and "Zinc supplements may cause insulin resistance & diabetes") and can - if taken in high doses or for long periods of time - become downright harmful for active physical culturists like you and me. The data Paolo Borrione and his colleagues from the Department of Health Sciences at the University of Rome present in a recently published paper does now confirm that ALA and zinc are probably still the most benign among the "potent ergogenics" and "all natural", "plant-derived nutritional supplements" that are specifically marketed to fitness enthusiasts all around the globe (Borrione. 2012).

Believe it or not: "Natural" and "non-hormonal" can be worse than synthetic and hormonal

Image 2: In view of the fact that ecdysteroids are meant to turn the guy on the left into the nasty bastard on the right, the guys in this study should be happy that they got away with hormonal imbalances ;-)

In their peer-reviewed observational pilot-study (I am already looking forward to the follow up ;-) the scientists queried 740 trained subjects (420 body builders, 70 cyclists, and 250 fitness athletes) over a 6-months period on their use of "commercially available plant-derived nutritional supplements", which contained any or several of the following ingredients

• ecdysteroids, 
• phytoestrogens, 
• phytosterols and/or
• tribulus terrestris

To my surprise only 26 of those 740 experienced trainees (all subjects have been training regularly for at least 1 year, 1–2 hours per day, 3–6 days per week) declared that they were currently using respective products, with

• In defense of at least some of the ingredients mentioned in this list to the left, it should be mentioned that it is not clear, if the observed effects were due to a single component of the supplements, due to several of the ingredients of an individual product or the highly undesirable and based on studies on isolated compounds non-predictable interactions. Personally, I would bet money that all three of these were involved, though.
  6 subjects consuming products that contained Caffeine, Citrus A., Zingiber, Guggul, Cacao, Naringine and Bioperine. 
• 6 subsect consuming products based on 5-Methyl-7Methoxyisoflavone, 7-Iso- propoxyisoflavone, 20-Hydroxyecdysone, Secretagogues, Triboxybol, Saw Palmetto extract, Beta Sitosterol, Pygeum extract, Guarana extract and Cordyceps extract. 
• 4 subjects consuming different dosages of a commercially available product containing Rhaponticum Carthamoides extract and (in one case) Ajuga Turkestanica and Rhaponticum Carthamoides root extract

for 6-12 months. The rest got at least a daily dose of phytoestrogens from soy protein products, some of which were enriched with Muira Puama and/or Guta Kola extracts - with highly detrimental consequences on the endocrine milieu for 15 (65%) of them.

Figure 1: Progesterone (ng/ml), estrogen (pg/ml) and DHEA (ng/ml) levels in users vs. non-users of "plant-derived nutritional supplements"; the bars for lower and upper indicate the lower and upper limit of the normal range, the figures on top of the blue bars are relative to the group average of the non-users (based on Borrione. 2012)

If your brain is not already malfunctioning due to too many "all natural ergogenics", it should be plain obvious that neither the 16x increase in estrogen, nor the 3x increase in progesterone are something you would be willing to pay money for. And that goes irrespective of whether you are a man or a women. After all,  these profound "hormonal alterations" (esp. the hyperestrogenism) could, as the scientists point out, lead to "severe health problems" such as

• gynecomastia, hypogonadism and reduced fertility in men, and 
• macromastia, enlarged uterus, menstrual irregularities and breast cancer in women.

In addition, hyperestrogenism represents a major risk factor for the female and male breast cancer (Heinig. 2002; Martin. 2003; Cederroth. 2010).

Taking DHEA or an "all natural" aromatase inhibitor will only exasperate the mess!

Image 2: Actually this post only confirms what I have been written in my previous post on "hormone optimization made simple and cheap". Avoiding all the natural and unnatural hormonal disruptors is the less expensive and healthiest way to optimize your endocrine system.

And while you could try to counter the reduced DHEA levels and the increase in estrogen by simply swallowing another pill (or a whole "stack"), I would suggest you better avoid all those totally natural, but by no means harmless test- or whatever boosters and suppressors of which Paolo Borrione et al. rightly state that they "have not been studied for long-term safety".

Contrary to the users in Berrione's study, of whom 45% did not even know all of the substances on the label of their supplement of choice you are now aware that the phytoestrogens, vegetal sterols and ecdysteroids are not simply not worth their money, they are more importantly not worth your health and should, just like the soy protein, which happens to be the one supplement that was on the list of every subject with abnormally elevated estrogen levels(!) never make it onto your supplement shopping list.

References:

1. Borrione P, Rizzo M, Quaranta F, Ciminelli E, Fagnani F, Parisi A, Pigozzi F. Consumption and biochemical impact of commercially available plant-derived nutritional supplements. An observational pilot-study on recreational athletes. J Int Soc Sports Nutr. 2012 Jun 19;9(1):28.
2. Cederroth CR, Auger J, Zimmermann C, Eustache F, Nef S: Soy, phyto-oestrogens and male reproductive function: a review. Int J Androl 2010, 33:304–316
3. Heinig J, Jackisch C, Rody A, Koch O, Buechter D, Schneider HP: Clinical management of breast concer in males: a report of four cases. Eur J Obstet Gynecol Reprod Biol 2002, 102:67–73.
4. Martin RM, Lin CJ, Nishi MY, Billerbeck AE, Latronico AC, Russell DW, Mendonca BB: Familial hyperestrogenism in both sexes: clinical, hormonal, and molecular studies of two siblings. J Clin Endocrinol Metab 2003, 88:3027–3034.
5. Tekin KA, Kravitz L: The growing trend of ergogenic drugs and supplements. ACSM’s Health Fitness J 2004, 8:15–18.