The All-Natural Muscle-Building Powers of Ecdysterone
By Robert Schinetsky
Individuals who take their fitness seriously are always looking for a way to improve their performance, size, and strength.
Proper diet, training, sleep, and stress-management will deliver the vast majority of results to fulfill most people’s wants and desires.
But, there are a select few amateur and professional athletes who want to eek out every last bit of performance and muscle gain from their bodies.
This is where supplementation comes into play.
A number of options (both legal and illegal) have been marketed to those to take their results to the next level.
While those “illegal” options (anabolic steroids) do provide benefits, they also come with a laundry list of side effects.
Today, we investigate an all natural anabolic that has been used by Russian athletes have used it for decades.
That anabolic is EsdySterone supplements containing beta-ecdysterone (20-hydroxyecdysone).
What is Beta-Ecdysterone (20-hydroxyecdysone)?
Ecdysterone (20-hydroxyecdysone) is a naturally occurring steroid belonging to a family of compounds called ecdysteroids.
Ecdysteroids are the androgens of insects that play a key role in both growth and reproduction.
They share structural similarities to testosterone and are viewed as the most similar “testosterone-like” compound active in arthropods.
Ecdysteroids can also be found naturally occurring in plants, such as Cyanotis Arachnoidea, where they serve as a deterrent to predators.
Ecdysterone Benefits and How it Works
Enhances Lean Mass Gains
The primary reason ecdysterone supplements (and ecdysteroids, in general) have received increasing amounts of interest in recent years is due to their anabolic (pro-muscle building properties).
Several studies have demonstrated that ecdysterone is able to significantly increase muscle hypertrophy both in vitro and in vivo.[1, 3,4]
In fact, some animal studies show that ecdysterone may be superior to anabolic androgenic steroids (such as metandienone or estradienedione) as well as the selective androgen receptor modulator (SARM) S-1 for enhancing anabolism when similarly dosed.
While cell cultures and animal models can certainly spark intrigue of ecdysterone benefits, it certainly helps to have some actual human research where a compound is orally ingested and shown to increase blood levels and produce a desired outcome, which in this case is muscle growth, and (more importantly) be safe when ingested.
Well, a new 10-week study involving 46 healthy, young, resistance-trained men was carried out testing the ergogenic and hypertrophic qualities of an ecdysterone-containing supplement.
While 46 individuals began the study, only 40 successfully completed the trial, according to the researchers.
At the start of the trial the 46 men were divided into four groups:
Placebo group (n = 12)
Control group (n=12)
Ecdysterone1 group (n = 12)
Ecdysterone2 group (n = 10)
All subjects, except for those placed in the control group, performed three resistance-training sessions per week using a two-day split (workout A and workout B) with each workout containing six barbell exercises that trained the whole body.
Subjects in the control group received the recommended serving of an ecdysterone-containing supplement supplying 100mg beta-ecdysterone (from spinach) alongside 100mg L-Leucine, but did not perform any resistance training.
Subjects in the Ecdysterone1 group received the suggested serving of the ecdysterone-containing supplement (100mg beta-ecdysterone + 100mg L-Leucine) in conjunction with their resistance training workouts.
Subjects in the Ecdysterone2 group took a “high dosage” of ecdysterone, which equated to consuming 4 times the suggested serving size. This delivered a daily total of 400mg ecdysterone and 400mg L-Leucine.
In addition to testing the supplement in healthy human subjects, researchers also performed an in vitro investigation to garner greater understanding of how ecdysterone may potentially enhance muscle hypertrophy and athletic performance.
C2C12-derived myotubes were incubated with one of three similar dosed treatments:
Ecdysterone (from the ecdysterone-containing supplement)
Ecdysterone control (procured from a nutraceutical lab)
Dihydrotestosterone (DHT) -- an endogenous anabolic androgenic steroid
The magnitude of growth (hypertrophy) was found to be similar across all treatments.
These findings are similar to previous in vitro ecdysterone studies which incubated C2C12-derived myotubes with one of the following:
Insulin-growth factor-1 -- an endogenous anabolic growth factor IGF-1
Now, here’s where things get a bit interesting regarding the study.
The researchers performed some QA/QC-testing on the supplement under investigation and found that although the product claimed to supply 100mg of ecdysteroids per capsule, it actually contained a mere 6mg per capsule!
Based on this, subjects in the Ecdysterone1 and Control groups only received 12mg of ecdysterone per day (plus any leucine contained in the capsule), and the “high-dose” Ecdysterone2 group only received a total of 48mg of ecdysterone per day, equivalent to 0.6 mg/kg BW in an 80-kg volunteer.
While this particular finding calls into question the quality of the products from the company that produces the particular ecdysterone-containing supplement used in the trial, the more noteworthy finding for individuals considering ecdysterone supplementation is that significant results may be able to be attained with very small doses.
Researchers performed extensive blood work on all subjects receiving ecdysterone to identify if ecdysterone was present in the blood as well as if it caused any adverse hormonal alterations.
Furthermore, researchers also tested the ecdysterone supplements for the presence of anabolic steroids (a common contaminant in “natural” muscle builders).
As we stated, this trial found significant increases in hypertrophy in both in vitro and in vivo models.
Researchers determined this by noting improvements in total bodyweight and muscle mass.
But that’s not all.
Both ecdysterone groups increased their performance significantly compared to the placebo group (the group that only performed resistance training but did not receive ecdysterone).
More specifically, both ecdysterone groups increased their 1-RM bench press.
And remember, these results occurred with subjects only receiving a mere 12mg or 48mg of ecdysterone per day, not 200mg or 800mg like the researchers originally thought the subjects were receiving!
This means that benefits from ecdysterone may be realized with doses as low as 0.15-0.6 mg/ kg BW!
During their blood tests, researchers noted a dose-dependent increase in ecdysterone, meaning the men who received the “high dose” ecdysterone treatment demonstrated higher blood levels of ecdysterone than either Ec1 and CO group (both administration of 2 capsules)
Furthermore, researchers detected no contaminants in the products used in the trial, nor did they find evidence of any significant change in urinary steroid hormones. This is particularly noteworthy as “muscle building” supplements by and large are notorious for being “spiked” with various illegal anabolic agents (steroids, prohormones, etc.).
They also found no increase in biomarkers that would indicate liver or kidney toxicity from ecdysterone supplementation, providing evidence that not only is ecdysterone effective, but SAFE!
Together, these findings suggest that the anabolic effect of ecdysterone is based on a different mechanism than that of testosterone, dihydrotestosterone, and synthetic anabolic androgenic steroids (more on this below).
Researchers concluded the paper stating:
“These data underline the effectivity of an ecdysterone supplementation with respect to sports performance. Our results strongly suggest the inclusion of ecdysterone in the list of prohibited substances and methods in sports in class S1.2 “other anabolic agents.”
In other words, the increase in muscle size and athletic performance accompanying ecdysterone supplementation was significant enough for the researchers to suggest that ecdysterone should be added to the list of WADA’s banned substances!
All too often when a supplement study is published showing significant results from a natural compound, it’s usually funded by the company that produces the supplement, which calls into question just how “reliable” the research and findings are.
However, this study wasn’t industry funded. It was funded by the World Anti-Doping Agency!
Obviously, this is just a single study, and while the results are remarkable, the researchers do state for the need for more studies to be carried out on the activity of ecdysterone.
Still, for those seeking an all natural compound that is safe and effective for increasing athletic performance, strength, and muscle mass, ecdysterone offers an alluring option.
So, How Does Ecdysterone Work?
Researchers have investigated how ecdysterone is able to promote anabolism while at the same time not significantly impacting hormone levels in the body.
Previous studies have shown that ecdysterone shows no significant binding at the androgen receptor or estrogen receptor-alpha (ERɑ).
As it turns out, ecdysterone’s induction of hypertrophy is mediated by estrogen receptor-beta (ERβ) activation.
This is noteworthy as ERβ signaling is involved in the regulation of skeletal muscle growth and regeneration by stimulating anabolic pathways, activating satellite cells and modulating immune function.
Ecdysterone has also been proposed to enhance muscle protein synthesis via direct or indirect stimulation of the PI3K/Akt signaling pathway.
Additional Potential Health Benefits
Ecdysteroids have also been shown to exert cholesterol-lowering (“hypocholesterolemic”) effects, via reduction of cholesterol production in the body and an increase of its catabolism (“breakdown”).[8,9]
Additional animal studies also find that ecdysterone may:
Improve kidney function
Improve heart and lung function
Enhance immune function
Improve CNS function
Aid antioxidant systems
Are Ecdysteroids Safe?
No matter how effective a supplement may be, if it’s carcinogenic, neurotoxic or hepatotoxic, it’s really not worth the risk of using.
A large part of what makes the class of ecdysteroids an intriguing option for individuals looking for a natural anabolic is that they have very low toxicity (LD50 > 6g/kg).
Furthermore, unlike anabolic steroids, ecdysteroids do not increase blood pressure, and despite their anabolic activities, they do not possess androgenic, estrogenic, or anti-estrogenic) effects.
Where to Find Ecdysterone
Advanced Molecular Labs Ecdy Sterone (20-hydroxyecdysone) is a natural anabolic support supplement supplying 500mg beta-ecdysterone per capsule (derived from Cyanotis Arachnoidea) of the highest quality (exceeding 95% purity) to aid muscle protein synthesis and lean mass gains.
Each capsule of AML Ecdy Sterone also includes 2,000IU Vitamin D3 (cholecalciferol).
Vitamin D3 is a fat-soluble vitamin that serves a number of roles in the body including cell growth, neuromuscular function, and immune function. It also helps combat inflammation, and most pertinent to our purposes here, supports the synthesis of numerous steroid hormones in the body, including testosterone.
EcdySterone Dosage and How to Take It
Take one capsule of Ecdy Sterone immediately following your workout.
For added benefit, Advanced Molecular Labs recommends consuming 1 capsule of Ecdy Sterone with 1 serving of AML Post Workout immediately after exercise on an empty stomach, before eating a post-workout meal.
AML PostWorkout contains 5 grams of pure leucine, 5 grams of creatine monohydrate and 2.5 grams of betaine.
The reason AML recommends stacking Ecdy Sterone with AML PostWorkout is that
leucine serves as an mTOR activator and creatine functions as a myostatin inhibitor.
Myostatin is a catabolic regulator of skeletal muscle mass that controls the proliferation of myoblasts (immature muscle cells) by downregulating myoblast determination protein 1 (MYOD1).
MYOD1 is a protein that plays a major role in regulating muscle differentiation.
Creatine supplementation in conjunction with resistance-training has been shown to lead to greater reductions in myostatin levels than resistance-training alone.
Let’s not forget about betaine.
Betaine is a metabolite of choline composed of a molecule of glycine surrounded by three methyl groups, hence its name -- trimethylglycine.
Betaine assists in methylation as well as cellular hydration, and it also supports endogenous creatine production in the body.
Research indicates it is beneficial for improving athletic performance as well as lean muscle mass.
Additional studies show betaine supplementation stimulates growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion. and subsequently improves the insulin IRS/AKT mTOR protein synthesis pathway.[14,16]
To top it off, a recently published meta-analysis also concluded that betaine supplementation might be an effective approach for reducing body fat, too!
- Lafont R, Dinan L. Practical uses for ecdysteroids in mammals including humans: an update. J Insect Sci. 2003;3:7. doi:10.1093/jis/3.1.7
- Dinan, L. (2001). Phytoecdysteroids: biological aspects. Phytochemistry, 57(3), 325–339. https://doi.org/10.1016/s0031-9422(01)00078-4
- Parr MK, Botrè F, Naß A, Hengevoss J, Diel P, Wolber G. Ecdysteroids: A novel class of anabolic agents?. Biol Sport. 2015;32(2):169–173. doi:10.5604/20831862.1144420
- Csábi, J., Rafai, T., Hunyadi, A., & Zádor, E. (2019). Poststerone increases muscle fibre size partly similar to its metabolically parent compound, 20-hydroxyecdysone. Fitoterapia, 134, 459-464. https://doi.org/10.1016/j.fitote.2019.03.017
- Isenmann, E., Ambrosio, G., Joseph, J. F., Mazzarino, M., de la Torre, X., Zimmer, P., Parr, M. K. (2019). Ecdysteroids as non-conventional anabolic agent: performance enhancement by ecdysterone supplementation in humans. Archives of Toxicology, 93(7), 1807–1816.doi:10.1007/s00204-019-02490-x
- Parr MK, Zhao P, Haupt O, Ngueu ST, Hengevoss J, Fritzemeier KH, Piechotta M, Schlörer N, Muhn P, Zheng WY, Xie MY, Diel P. Estrogen receptor beta is involved in skeletal muscle hypertrophy induced by the phytoecdysteroid ecdysterone. Mol Nutr Food Res. 2014;58:1861–1872
- Syrov VN. Comparative experimental investigation of the anabolic activity of phytoecdysteroids and steranabols. Pharm Chem J. 2000;34:193–197.
- Lupien, P. J., Hinse, C., & Chaudhary, K. D. (1969). Ecdysone as a hypocholesterolemic agent. Archives Internationales de Physiologie et de Biochimie, 77(2), 206–212. https://doi.org/10.3109/13813456909109700;
- Uchiyama M, Yoshida T. 1974 Effect of ecdysterone on carbohydrate and lipid metabolism. In Burdette WJ, editor. Invertebrate Endocrinology and Hormonal Heterophylly. 401–416.Springer-Verlag, Berlin.
- Velders, M., Schleipen, B., Fritzemeier, K. H., Zierau, O., & Diel, P. (2012). Selective estrogen receptor-beta activation stimulates skeletal muscle growth and regeneration. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 26(5), 1909–1920. https://doi.org/10.1096/fj.11-194779
- Saremi, A., Gharakhanloo, R., Sharghi, S., Gharaati, M. R., Larijani, B., & Omidfar, K. (2010). Effects of oral creatine and resistance training on serum myostatin and GASP-1. Molecular and Cellular Endocrinology, 317(1–2), 25–30. https://doi.org/10.1016/j.mce.2009.12.019
- Langley, Brett, et al. "Myostatin Inhibits Myoblast Differentiation by Down-regulating MyoD Expression." Journal of Biological Chemistry, vol. 277, no. 51, 2002, pp. 49831-49840.
- Cholewa JM, Wyszczelska-Rokiel M, Glowacki R, et al. Effects of betaine on body composition, performance, and homocysteine thiolactone. J Int Soc Sports Nutr. 2013;10(1):39. Published 2013 Aug 22. doi:10.1186/1550-2783-10-39
- Apicella, Jenna M., et al. "Betaine supplementation enhances anabolic endocrine and Akt signaling in response to acute bouts of exercise." European Journal of Applied Physiology, vol. 113, no. 3, 2012, pp. 793-802.
- Gao, Xiang, et al. "Effect of Betaine on Reducing Body Fat—A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Nutrients, vol. 11, no. 10, 2019, p. 2480.
- Senesi, P., Luzi, L., Montesano, A. et al. Betaine supplement enhances skeletal muscle differentiation in murine myoblasts via IGF-1 signaling activation. J Transl Med 11, 174 (2013) doi:10.1186/1479-5876-11-174