IngredientsPhytoecdysteroids (PEs) comprise a large group of biologically active plant steroids whose structures are similar to those of insect-molting hormones. Chemically, phytoecdysteroids are classed as triterpenoids, the group of compounds that includes triterpene saponins, phytosterols, and phytoecdysteroids. The term ecdysteroid derives from the Greek ecdysis, meaning "to shed the outer skin," a reference to their original identification as hormones governing insect molting and metamorphosis.
The carbon skeleton of ecdysteroids is termed cyclopentanoperhydrophenanthrene and has a β-side chain at carbon-17. The essential characteristics of ecdysteroids are their composition of a cis-(5β-H) junction of rings A and B, a 7-en-6-one chromophore, and a trans-(14α-OH) junction of rings C and D. The sterol structure is modified to produce ecdysteroids; the trans A/B ring juncture in sterols is converted to a cis A/B ring juncture in the ecdysteroids. Chemically, these are C27, C28, or C29 polyhydroxy steroids that have a 14α-hydroxy-7-en-6-one chromophore and A/B-cis ring fusion.
Chemically, ecdysteroids are polar steroids in nature; their solubility is almost identical to that of a sugar molecule. As a result, they are soluble in aqueous mediums and are also lipophilic. The mammalian steroid hormones have more variable structures and they generally lack the polyhydroxylated side chain characteristic of ecdysteroids; accordingly, they are quite nonpolar.
Depending on the natural source, ecdysteroids are subdivided into three groups: phytoecdysteroids (PEs), zooecdysteroids, and mycoecdysteroids. Some ecdysteroids, including ecdysone and 20-hydroxyecdysone (20E), are produced by both plants and arthropods. Besides those, over 250 ecdysteroid analogs have been identified so far in plants, and it has been theorized that there are over 1,000 possible structures that might occur in nature.
The most prominent and well-studied individual phytoecdysteroids include:
PEs are found in algae, fungi, ferns, gymnosperms, and angiosperms. More than 500 different PEs are found in over 100 terrestrial plants. PE distributions in plants vary from organ to organ and may change according to season or geographical area.
Plants, but not animals, synthesize phytoecdysteroids from mevalonic acid in the mevalonate pathway of the plant cell using acetyl-CoA as a precursor.
Major botanical sources include:
PEs are distributed in plants as secondary metabolites that offer protection against phytophagous (plant-eating) insects. When insects consume plants containing these chemicals, they promptly molt and undergo metabolic destruction; the insects eventually die.
Phytoecdysteroids are available in multiple commercial formats:
Label accuracy is a documented concern. A validated analytical method applied to 12 different dietary supplements labelled to contain ecdysterone showed an actual content generally much lower than the labelled one. Several products standardized to 80–95% ecdysterone contained substantially lower amounts than declared, with measured 20-hydroxyecdysone levels ranging from below the limit of detection to approximately 50 mg per capsule, whereas some non-standardized products exhibited moderate to high levels, reaching up to approximately 105 mg per capsule.
Among plant adaptogens, Rhaponticum carthamoides (Willd.) Iljin, known as maral root (Russian leuzea), holds a prominent place in Siberian traditional medicine. The root extract, abundant in bioactive compounds such as flavonoids and phytoecdysteroids, is reputed for reducing fatigue, boosting strength, and offering immunomodulatory benefits. The plant's folk name "maral root" derives from the observation of Siberian maral deer (red deer) reportedly digging up and eating the roots during the spring rutting season, leading local healers to adopt it.
In traditional medicine, R. carthamoides has been used to improve physical strength. Brekhman and Dardymov (1969) classified R. carthamoides as an adaptogen, a term currently used by herbalists to refer to a natural herb product which increases the body's resistance to stresses such as trauma, anxiety and bodily fatigue.
Rhaponticum is currently used in preparations such as dietary supplements for its adaptogenic and tonic properties that promote muscle growth and increase the body's resistance to stress, such as trauma and fatigue. In the last century, the muscle- and strength-building qualities of Rhaponticum have been largely investigated in Russia, where various preparations were commonly used by elite Soviet and Russian athletes who were exhausted by hard training to increase psychological and physical performance.
Ajuga turkestanica has long been employed in Central Asian ethnomedicine. Ecdysterone, cyasterone, ajugalactone, ajugasterone B, 22-acetylcyasterone, and turkesterone were isolated from leaves of Ajuga turkestanica (Labiatae). Traditional preparations included decoctions and infusions of aerial parts, used to support physical endurance and wound healing.
In traditional Brazilian medicine, Pfaffia glomerata roots are used as antioxidants and as a treatment in numerous physical and mental disorders; the adaptogenic effect of P. glomerata may be attributed to the phytosteroid 20-hydroxyecdysone (20E), a non-androgenic steroid.
Ecdysterone-containing plants have been used within Traditional Chinese Medicine frameworks. The compound has been linked to formulations that address fatigue and weakness; ecdysterone appears in the context of Traditional Chinese medicine as a keyword in the scientific classification of associated phytoecdysteroid research.
While phytoecdysteroids as a class encompass hundreds of distinct molecules, the following are the most pharmacologically studied:
A comprehensive review summarized the isolation and characteristics of 212 new PEs from different plant species, reported between 1999 and 2019. The diverse bioactivities reported for these PEs include antioxidant, anti-inflammatory, antimicrobial, analgesic, anabolic, adaptogenic, hepatoprotective, antidiabetic, and anticancer properties.
Contrary to anabolic-androgenic steroids (AAS) that increase muscle mass mainly through their binding to the androgen receptor (AR), no nuclear receptor homologous to the ecdysone nuclear receptor found in insects has yet been described in mammals. Only recently, binding of ecdysterone to the human ERβ (ED50 = 13 nM) could be shown in cell culture experiments, and induction of hypertrophy in C2C12 cells was shown to be mediated by ERβ activation. Unlike traditional anabolic steroids that act primarily via the androgen receptor (AR), ecdysterone's anabolic effects may be mediated through estrogen receptors (ERs), particularly estrogen receptor beta (ERβ).
In skeletal muscle cells, phytoecdysteroids increase protein synthesis. In mouse skeletal muscle cell line C2C12, 20-hydroxyecdysone (20HE) elicited a rapid elevation in intracellular calcium, followed by sustained Akt activation and increased protein synthesis. The effect was inhibited by a G-protein coupled receptor (GPCR) inhibitor, a phospholipase C (PLC) inhibitor, and a phosphoinositide kinase-3 (PI3K) inhibitor.
Murine C2C12 myotubes and human primary myotubes elevated protein synthesis by up to 20% when treated with 20E. 20-HE also increased the uptake of glucose, glycolysis, respiration, the production of ATP, and global protein biosynthesis in mouse myoblasts and fibroblasts. This phenomenon involves the PI3K/AKT/mTOR signaling pathway.
An extract from A. turkestanica decreased myostatin mRNA expression fourfold after treatment in myotubes in vitro. These data suggest that A. turkestanica may increase PI3K–Akt signaling and may inhibit the expression of myostatin, MAFbx, and MuRF-1 in vivo.
An intriguing mechanism of action involved increased heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf-2) production and mitigation of nuclear factor-kappa-light-chain-enhancer of activated B (NF-κB) activity, as well as a reduction in mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt) activation.
Some of the known PEs, such as paristerone, ecdysterone, and capitasterone isolated from the stems of Diploclisia glaucescens, have shown significant anti-inflammatory activity with IC50 values ranging from 1.5 to 11.6 μmol/L, as discovered by measuring the inhibitory ratios of β-glucuronidase release in rat polymorphonuclear leukocytes (PMNs) induced by platelet-activating factors.
PEs have anabolic modulatory activities that are used to treat diabetes, as they have blood-glucose-lowering properties by stimulating β-cells of the pancreas. In preclinical models, phytoecdysteroids from Dioscorea dumetorum have demonstrated α-glucosidase inhibitory activity: compounds isolated from that species display higher inhibitory activity against α-glucosidase than the positive control acarbose.
It has been suggested that the anabolic effects of 20E are mediated via a G-protein coupled cell surface receptor, as opposed to an intracellular androgen receptor. Thus, 20E is considered anabolic, but non-androgenic since it does not increase prostate or seminal vesicle mass in young castrated rats after 10 days of treatment.
Animal and in vitro evidence: In male rats, ecdysterone treatment increased muscle fiber size, serum IGF-1 increased, and corticosterone and 17β-estradiol (E2) decreased. Phytoecdysteroids, in particular 20-hydroxyecdysone (20E), increase protein synthesis in C2C12 skeletal muscle cells and muscle strength in young rats.
Human clinical evidence — Isenmann et al. (2019): The most prominently cited human trial to date was conducted at the German Sport University Cologne. Isenmann et al. conducted a 10-week randomized controlled trial involving strength training for young men (n=46). Various doses of ecdysterone-containing supplements were administered to assess their performance-enhancing effects. Notably, the research participants supplemented with high-dose ecdysterone (i.e., 48 mg of ecdysterone) showed a significant increase in muscle mass (2.0 kg delta). Significantly higher increases in muscle mass were observed in those participants who were dosed with ecdysterone. The same hypertrophic effects were also detected in vitro in C2C12 myotubes.
An important caveat was identified in subsequent analysis: the actual amount of ecdysterone in the capsule was only 6 mg, whereas the declared amount was 100 mg. This raises questions about the effective dose delivered and the reliability of the supplement label used in that study.
The results of Isenmann et al. strongly suggest the inclusion of ecdysterone in the list of prohibited substances and methods in sports in class S1.2 "other anabolic agents."
Conflicting evidence — asparagus-derived 20-HE study: A subsequent study that examined asparagus-derived 20-HE found different results: when comparing muscle mass development after the resistance training period, that study found no significant differences between the placebo and the 20E groups. These results contrast with those of Isenmann et al., who discovered differences between the groups receiving high doses (48 mg/day) of ecdysterone and a placebo group. The contrasting observations can be attributed to the varying concentrations of ecdysterone and leucine (100 mg per capsule) used.
Null result in sedentary aging mice: A study found no significant effects of acute or 28-day feeding of ATE and 20E to sedentary aging mice on muscle mass hypertrophy (mass and cross-sectional area), activation of the PI3K–Akt pathway, and attenuation of the expression of two E3 ligases regulated by Akt and myostatin. This indicates that beneficial effects may be context- and population-dependent, potentially requiring resistance training as a co-stimulus.
Earlier null RCT in resistance-trained men: A 2006 randomized controlled trial by Wilborn et al. examined the effects of ecdysterone among other supplements in resistance-trained males (J Int Soc Sports Nutr, 2006) and failed to show significant effects on training adaptations, highlighting the inconsistency of human data.
Evidence strength summary: Ecdysterone was found to be more effective than prohibited anabolic agents (e.g., metandienone and others) in a study performed in rats. However, scientific studies in humans are very rarely accessible. Overall, the human clinical evidence base remains limited in both quantity and methodological quality; results are inconsistent across trials and the field requires larger, better-controlled studies with verified supplement dosing.
The therapeutic potential of phytoecdysteroid-rich extracts extends beyond sports nutrition, with promising applications in treating chronic fatigue, cardiovascular diseases, and neurodegenerative disorders. Rhaponticum is used in preparations such as dietary supplements for its adaptogenic and tonic properties that promote muscle growth and increase the body's resistance to stress, such as trauma and fatigue.
The adaptogenic categorization of R. carthamoides was formalized in the scientific literature when Brekhman and Dardymov (1969) classified R. carthamoides as an adaptogen, a term currently used by herbalists to refer to a natural herb product which increases the body's resistance to stresses such as trauma, anxiety and bodily fatigue. However, rigorous double-blind human clinical trials specifically on phytoecdysteroid-mediated adaptogenic effects remain scarce, and these claims rest predominantly on traditional use and preclinical data.
Diverse bioactivities reported for phytoecdysteroids include antioxidant activity among other properties. Certain isolated phytoecdysteroid compounds display high antioxidant activity, in the same range as ascorbic acid. These findings derive from in vitro assays, and clinical translation to humans has not been established. Despite the copious amount of PE research that has been performed over the past two decades, most of the results cited are based on in vitro studies; data associated with in vivo and clinical studies are very limited.
PEs display anabolic, adaptogenic, anti-diabetic, hypolipidemic, and hepatoprotective activities. Preclinical research has demonstrated that PEs extracted from Ajuga plants are used to treat diabetes-related models. Antidiabetic-guided isolation of the tubers and peels of D. dumetorum afforded three phytoecdysteroids bearing a cis-fused A/B ring junction. These antidiabetic effects are supported by in vitro enzyme inhibition data and animal models, but human clinical trials specifically evaluating glycemic endpoints are lacking in the peer-reviewed literature.
It has been highlighted that ecdysterone is correlated with an increased cell immunity, and that it is also endowed with adaptogenic, anti-diabetic, hepatoprotective, and anti-tumor properties. Preclinical studies have examined hepatoprotective effects, including protection against liver injury in animal models, but these findings have not been confirmed in controlled human trials.
Some of the known PEs, such as paristerone, ecdysterone, and capitasterone isolated from the stems of Diploclisia glaucescens, have shown significant anti-inflammatory activity with IC50 values ranging from 1.5 to 11.6 μmol/L. Anti-inflammatory effects have been demonstrated primarily in cell-based and animal studies, via suppression of NF-κB and modulation of MAPK pathways. No controlled human trials have specifically evaluated phytoecdysteroids for inflammatory endpoints.
An interesting study tested the combinatorial effects of 20-HE with half doses of cisplatin and adriamycin combination on the development of subcutaneously and intraperitoneally transplanted P388 and L1210 leukemia and metastasizing B16 melanoma. 20-HE significantly stimulated the chemotherapeutic effects at low doses via a mechanism involving cytostatic effects, resulting in tumor growth inhibition and an increase in the survival rate and lifespans of mice. Also, 20-HE showed comparably improved antimetastatic activity index at high doses of the antitumor drugs in mice.
These anticancer data are exclusively preclinical (animal and in vitro). Phytoecdysteroids have shown a wide range of biological, pharmacological, and medicinal properties implicated in the prevention and therapy of acute and chronic diseases, and are effective against different types of cancer due to their anti-inflammatory and antioxidant mechanisms. No human clinical trials have evaluated phytoecdysteroids as anticancer agents.
A preclinical study in adult and old mice found that phytoecdysteroids promoted faster recovery of skeletal muscle function following eccentric contraction-induced injury. Phytoecdysteroids, particularly 20E, promote anabolic responses in many tissues, including skeletal muscle. Skeletal muscle protein synthesis signaling, via activation of the mTORC1 pathway, is stimulated in the range of 1–7 days post-damage in response to various eccentric or lengthening contraction protocols in rodents and humans. Human evidence in this area is absent.
20-Hydroxyecdysone (20E) possesses a number of beneficial pharmacological activities in humans including anabolic, antioxidant, hypoglycemic, cardioprotective, hepatoprotective, neuroprotective, and antineoplastic properties. These findings are drawn from preclinical studies; robust human evidence for cardiovascular or neuroprotective endpoints has not been established.
The following dosage ranges appear in the peer-reviewed literature cited above. These are presented purely as reported in sources and do not constitute dosage recommendations.
PEs have several beneficial effects on mammals: they play roles in anabolic, adaptogenic, antidiabetic, anti-inflammatory, antioxidant, antitumor, antimicrobial, and anti-arthritic activity. They also act as hepatoprotectors and immunomodulators.
Performance enhancement in sports was demonstrated recently, and in 2020, ecdysterone was consequently included in the Monitoring Program of the World Anti-Doping Agency to detect potential patterns of misuse in sport.
The 2025 WADA Monitoring Program places ecdysterone under Anabolic Agents, monitored in and out of competition. WADA has not added ecdysteroids to the Prohibited List. However, there has been increasing interest in the potential performance-enhancing effects of ecdysteroids, with WADA adding it to the WADA Monitoring List in 2020.
As ecdysterone-containing plants may be part of common human diet, discrimination between common dietary levels, excessive dietary intake of ecdysterone, and supplementation for misuse is highly desired.
Unlike anabolic steroids, which are controlled substances, ecdysteroids are not classified as such in many countries and are legally available as dietary supplements.
Among a number of plant species containing phytoecdysteroids, R. carthamoides was shown to be very safe even at high doses. In one of the earliest toxicological studies performed by Petkov et al. (1984), a root water–ethanol extract applied intraperitoneally and subcutaneously in doses up to 40,000 mg/kg did not produce mortality in male albino mice even 7 days after its application. This extreme acute-dose tolerance is notable but derives from animal data only.
Safety evaluation was performed on the basis of the serum concentrations of selected biomarkers of kidney and liver function in the Isenmann et al. study, with no significant adverse effects on these markers reported at the doses tested.
Because ecdysterone's principal proposed mechanism in mammals involves ERβ binding, the theoretical potential for estrogenic side effects warrants consideration. However, unlike anabolic steroids, ecdysteroids are believed to promote muscle growth and enhance physical performance without the severe side effects commonly associated with synthetic steroids. The functional significance of ERβ agonism by ecdysterone in humans at supplemental doses has not been fully characterized.
In commercial analyses, it was found that most products do not meet the desired quality and safety standard concerning the correspondence of their actual ecdysterone content with the value reported on the labeling. Post-study analysis of a supplement used in one trial revealed a 20E content of less than 0.1% of the amount claimed by the manufacturer on the label (25 mg 20E). The content differs significantly from that of a prior batch of the same product, illustrating the wide variance in the actual 20E concentration in commercially available ecdysterone products.
Identification and quantitation of ecdysterone and of two metabolites, 14-deoxy-ecdysterone and 14-deoxy-poststerone, was achieved in urine. Ecdysterone was the most abundant analyte present in post-administration urine samples, detected for more than 2 days, with a maximum concentration (Cmax) in the 2.8–8.5 h urine (Cmax = 4.4–30.0 µg/mL).
The main product of ecdysterone biotransformation in urine is deoxyecdysone, detectable up to 21 hours after application.
The literature detailing the urinary excretion profiles of ecdysterone remains noticeably sparse, especially concerning human clinical interventions. Many existing investigations rely on highly restricted sample cohorts. Consequently, current findings must be interpreted with caution. Such preliminary data frequently engenders contradictory assertions across the scientific record. To establish a robust hierarchy of evidence, the execution of meticulously designed, large-scale clinical trials is strictly required.
Up to now, no real therapeutic applications have been materialized. They are actually used for dermatological purposes in cosmetology, and putative anabolic activity is highly promoted via the internet, without too much evidence.
Health conditions that Phytoecdysteroid may help support.
Phytoecdysteroids are plant steroids (notably ecdysterone/20-hydroxyecdysone) found in Rhaponticum, Cyanotis, and spinach that have been studied for anabolic and endurance-enhancing effects. A 2019 double-blind RCT found ecdysterone supplementation significantly increased muscle mass and one-rep maximum in resistance-trained men. They are proposed to act via estrogen receptor beta to stimulate protein synthesis.
Body systems that Phytoecdysteroid may help support.
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