Summary of Ecdysteroids
Primary Information, Benefits, Effects, and Important Facts
Ecdysteroids are a class of compounds (polyhydroxylated ketosteroids, with various tails) that are structurally similar to androgens. They are well studied as plant and insect growth factors, and derived their name (ecdy-) from the process of molting in insects, called ecdysis.
Ecdysteroid is a category, and popular ecdysteroids include 'ecdysone', 'ecdysterone', 'turkesterone' and '20-hydroxyecdysone'. These four are the most commonly studied, but each ecdysteroid shares the same general properties although varies in potency and effects slightly. Turkesterone appears to be the most anabolic.
They have some biological effects in mammals when orally ingested, and have been called by some researchers as "behaving similar to anabolic steroids putatively without the androgenic effect". Due to the lack of androgenicity, their safety profiles are much greater than anabolic androgenic steroids.
Additionally, they seem to have a wide variety of side-effects that are deemed as healthy. Ecdysteroids can lower cholesterol and blood glucose, are seen as healthy for the liver and intestines by increasing protein synthesis rates, and may have protective effects on neural tissue.
A lack of trails are currently available for humans, but promising evidence is available for in vitro studies on human muscle fibers as well as a multitude of animal models showing enhanced growth rates with ecdysteroid ingestion.
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Things To Know & Note
Ecdysterone is non-stimulatory.
How to Take Ecdysteroids
Recommended dosage, active amounts, other details
Hypoglycemic effects of edcdysterone and its plant sources seems to be dose-dependent, although a good dose that is used safely is typically 200mg a day.
An oral dose of 5mg/kg bodyweight in rats seems to possess anabolic properties, and would be a good place to start for increasing muscle mass.
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Human Effect Matrix
The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects ecdysteroids has on your body, and how strong these effects are.
|Grade||Level of Evidence [show legend]|
|Robust research conducted with repeated double-blind clinical trials|
|Multiple studies where at least two are double-blind and placebo controlled|
|Single double-blind study or multiple cohort studies|
|Uncontrolled or observational studies only|
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
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Scientific Research on Ecdysteroids
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Ecdysteroids are present in many plants (about 6% of plants in existence), although at a levels usually seen as insufficient for either extraction or biological activity. Some plants that are higher in certain bioactive ecdysteroids are:
Spinacia oleracea (Spinach, source of 20-hydroxyecdysone)
White button Mushrooms
Ajuga Turkestanica, a source of the C-11 hydroxylated 'Turkesterone'
Silene Praemixta (2-deoxyecdysterone and 2-deoxy-alpha-ecdysone)
Ecdysterones get their name from having a steroid backbone (sterone) and being associated with the process of molting, otherwise known as ecdysis. The reason for their existence in plants (as they are an insect hormone) is that they protect plants from unadapted insects, and thus are a phytoalexin.
'Ecdysteroids' are hormonal compounds involved in the sexual behaviour of insects as well as molting and metamorphisis. Ecdysteroids share structural similarity to testosterone and are seen as the testosterone-like compound most active in insects. They are also present in plants to deter predators. Below is the general backbone of the ecdysterone family, and the molecule depicted is beta-ecdysterone.
Although there are over 200 ecdysteroids known at the time of 2001, and up to 463 registered. most of them are not bioactive when ingested orally. Common ones either in research or taken orally include:
Ecdysterone and Beta-ecdysterone
Sileneoside A and C
In one study, using 0.2mg/kg bodyweight ecdysteroids (as ecdysone and 20-hydroxyecdysone) ecdysone appeared to have an elimination half-life of 4 hours and 20-hydroxyecdysone an elimination half-life of 9 hours in humans. An active half-life is not known in humans.
However, mouse models show a half-life of 8.15 minutes for 20-hydroxyecdysone when injected at a dose of 50mg/kg bodyweight into the caudal vein and similar results have been replicated with 20-hydroxyecdysone elsewhere. A half-life of 48 minutes (for the ecdysteroid ponasterone A) when injected at a dose of 750ug has also been noted.
A cytoplasmic receptor has been cloned in drosophilia, and termed DopEcR, which binds to ecdysterones and dopamine. It has been theorized that some of the mechanisms of action are through this receptor, and are non-genomic in nature (do not influence the nucleus of the cell). Possible non-genomic effects include Calcium ion influx that induces phosphorylation of Akt, which is discussed in the section on protein synthesis.
There are hypothesized nuclear receptors as well (in mammals) in the nuclear receptor superfamily. The Ecdysterone receptor dimerizes with Ultraspiracle (USP) receptors in insects to influence genes, but in humans must dimerize with the RXR receptor. Although in insects USP may dimerize with a wide variety of nuclear receptors, a complex of EcR:RXR must form in mammals for effects to occur. EcR binding with non-RXR receptors result in no genetic effects in vertebrates. It was noted, however, that RXR is a 'reluctant' partner for EcR and a relative surplus of RXR is required for genetic signalling via EcR:RXR; this was mentioned in one study in regards to another investigating an in vitro model on Chinese Hamster Ovary cell line.
Ecdysteroids, specifically 20-hydroxyecdysone and pinnatasterone, have been implicated as inhibitors of P-glycoprotein efflux pumps and may interact with other drugs that are metabolized extensively by P-glycoprotein, such as Berberine or Icariin.
In mice (and humans) excretion is done both fecally and via the urine. Studies suggest that the fecal route is favored as ecdysteroids are picked up by the liver and then ejected in bile acids, however at least one study notes that both routes may be equally important, although the latter study used a 50mg/kg bodyweight injection of ecdysteroids.
When investigating the fecal metabolites, 4-deoxyecdysone was noted as well as compounds with a fully reduced B-ring. It was noted in one review that this metabolism "is reminiscent of the hepatic reduction of the 4-en-3-one on ring-A of vertebrate steroid hormones". When side-chain cleavage occurs between C20 and C22, the metabolites poststerone and 12-deoxypoststerone can result (from 20-hydroxyecdysone). A novel metabolite of 2β,3β,6α,22R,25-pentahydroxy-5β-cholest-8(14)-ene has also been noted in rats. Finally, the metabolite of 14-deoxy-20-ecdysone (noted as the primary metabolite in human urine) may have interactions with gut microflora, as microflora are known to cause dehydroxylation of steroid compounds.
In humans, urinary excretion of ecdysterone tends to be one of three compounds; either the ecdysterone in an unchanged form, 2-deoxyecdysterone or as deoxyecdysone. The primary urinary metabolite, at 99.34%, is deoxyecdysone at 21hours after ingestion of 20mg ecdysterone. A biphasic urinary excretion of the parent compound was noted with urinary analysis at 68 hours as well. These metabolites are also found in rat urine.
There really isn't too much info on this topic that can be seen as 'conclusive'. There appear to be a wide variety of metabolites that have not been studied, and 20-HE either persists for longer in humans than mice (4.1h v. 8.15m) or its a dose-dependent response. Unsure at this time.
Ecdysterone is able to increase enzymatic induction of both acetylcholinesterase and glutamic decarboxylase. These effects are downstream of ecdysteroids being able to increase protein synthesis, as increasing protein synthesis (via increased mRNA efficacy as hypothesized by Uchiyama & Otaka) applies to proteinaceous tissue (skeletal muscle, organ protein) and enzymes. The glutamate decarboxylaze increases were measured at 25-30% in vivo after 2.5-50ug/kg bodyweight, although dose dependence was not clear.
Ecdysterone (interchangeable term with 20-hydroxyecdysterone, or 20-HE) seems to be able to suppress hepatic glucose formation and thus lower blood sugar levels independent of insulin secretion and serum levels. The suppression of glucose metabolism seems to be from phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, as well as to induce Akt phosphorylation in liver cells.
When fed to rats at a dose of 10mg/kg bodyweight, the related compound 20-hydroxyecdysone is able to exert anti-diabetic and anti-obesogenic effects in models of animal obesity suggesting it may exert these same effects in humans. These changes also resulted in more adiponectin secretion from rat adipocytes. It has been shown in other, past models, to exert similar anti-diabetic properties regardless of method of ingestion/injection.
Ecdysterone administration (subcutaneous or intravenous), at around 5mg/kg bodyweight, seems to be able to induce protein synthesis in animal organs such as the liver or skeletal muscle. This is most likely from increased mRNA translation efficiency rather than increased mRNA synthesis (transcription). Additionally, ecdysteroids may be able to increase leucine incorporation into cells at a dose of 5mg/kg bodyweight (study investigated the liver).
In vitro studies on muscle cells (with 20-hydroxyecdysone and turkesterone) have noted statistically significant improvements in protein synthesis in a dose dependent manner starting at 0.08nM, peaking at 0.1nM with 110-120% more protein synthesis than control and plateauing at concentrations ot 1 and 10nM. The mechanism of action seems to be vicariously through PI3K, as an inhibitor of PI3K inhibited gains in muscle mass and grip strength (in mice) The metabolite of 20-hydroxysterone, rubrosterone, appears to be just as potent when looking at the mouse liver.
Relative to control, turkesterone increased rat growth (on a basis of mg/day) by 63.5%, ecdysterone by 51.9%, 2-deoxyecdysterone by 21.2% and alpha-ecdystone by 19.2%. This study used Methylandrostenediol (51.9%) and Nerobol (57.7%) as comparative compounds, although the effects of Nerobol were more localized to skeletal muscle while ecdysteroids had systemic protein synthesis increased (organ and muscle). Ecdysterones in this study did not suppress nor cause development of prostate or seminal vesicles, and did not possess uterotropic effects in female rats; thymus weight also increased by 23-35% whilst it decreased by 20% with Nerobol. Doses used in this study were 5mg/kg bodyweight for all ecdysteroids and 10mg/kg bodyweight for Methylandrostenediol and Nerobol.
As for mechanisms of action, ecydsteroids seem to be able to cause a rapid Ca2+ influx in myocytes which leads to phosphorylation of Akt and thus protein synthesis. This effect occurs after 10s of incubation, and is inhibited by PI3K inhibitors like seen in other studies, but also GPRC and PLC inhibitors; and when the cells are depleted of intra-cellular calcium Akt does not get phosphoraylized, and binding free calcium with EGTA lowered protein synthesis from 16% to 8%. Calcium per se can be an important mediator of Akt and protein synthesis, and ecdysteroids seem to work vicariously through Ca2+ and Akt.
This calcium influx increases Akt phosphorylation more than 3-fold at a 0.1uM concentration, with a diminishing dose-reponse up to 5-fold at 1-10uM. The effect of 1uM 20-hydroxyecdysterone on Akt peaked at 2-4 hours, but was higher than baseline for up to 24 hours.
It has also been noted in one study's discussion that the 'tail' of ecdysteroids (γ-hydroxy-γ-methylpentanoate), when separated from the steroid backbone, resembles the anabolic leucine metabolite HMB (beta-hydroxy methyl-butyrate).
If ecdysteroids get to the cell, they will increase protein synthesis; quickly, potently, and for a fairly long time.
In vivo studies have noted increased anabolism in a wide variety of animals, such as rats and mice, pigs and quail. The effects on improving strength seem to be independent of activity, as assessed by forced swim time in rats improving without consistent training. Some past studies (prior 2000) suggest it may increase protein synthesis in humans as well. Performance enhancements have also been noted with rats.
In sheep, an oral dose of 0.02mcg/kg ecdysteroids per day was able to increase body growth rate and wool production and was more evident with a poorer nutrient intake. A similarily small dose of 0.4mg/kg bodyweight was able to increase nitrogen retention and preserve lean mass (to 112-116% of control) when food intake was decreased by 11-17% in swine.
The increased activity of Alkaline Phosphatase induced by Ecdysterone seems to be through the estrogen receptor. Through this receptor, estrogen reporter gene activity is also increased by ecdysterone.
The increased activity seen in Type I collagen expression, osteocalcin, and Runx2 do not seem to be via the estrogen receptor.
At the moment, only one human study has been conducted with ecdysterone. Dosed at 200mg daily, no results were seen in resistance training males in regards to total and free testosterone or body composition changes when compared to placebo. When tested for binding to the androgen receptor, 20-hydroxyecdysterone does not appear to have any binding affinity and thus cannot activate the androgen receptor.
That being said, despite no influence on testosterone itself ecdysterone may be able to exert testosterone-like effects via signal transduction pathways (although the exact mechanism is not yet known); an action with ultimately the same biological significance as testosterone.
There is not much evidence beyond in vitro to suggest ecdysterone useful for muscle protein synthesis or strength gains.
When tested in vitro in C2C12, 1µM 20-hydroxyecdysone (20-HE) increased myotube diameter in a manner independent of the androgen receptor; both corticosteroids and estrogen receptor blockers prevented 20-HE from promoting muscle growth. When tested further 20-HE appeared to activate both the alpha variants of the estrogen receptor (ERα; EC50 of 25.7nM) and the beta variants (ERβ; EC50 13nM), and 10nM 20-HE was found to promote muscle growth through ERβ.
When tested in vitro, 20-hydroxyecdysone appears to promote muscle cell hypertrophy due to acting on the beta estrogen receptor. This molecule also appears to act on the alpha receptor, and when both receptors are being acted upon simultaneously the muscle cell still experiences hypertrophy
Ecdysterone, at 5mg/kg bodyweight, can restore normal glomerular filtration rate and suppress albuminuria in rats treated with a nephrotoxic mixture and may alleviate symptoms of uremia associated with hepatic damage.
As discussed in the fat metabolism section, ecdysterone is able to increase bile secretion rates as well as improve liver regeneration after toxin (heliotrine) damage.
Ecdysteroids are one of the pair of insect hormones (the other being Juvenile Hormone) that seem to be involved in insect lifespan, with ecdysterone being the agent that increases lifespan. Transfection of Drosophilia with an ecdysone receptor increases lifespan. However, studies in humans are non-existent and other animal models very preliminary.
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