Ec Dy Steroids

(/)

Table of Contents

Summary

Things to Know

How to Take

Editors' Thoughts

Human Effect Matrix

Scientific Research

Citations

EcdysteroidsEcdysteroids are a class of hormones that are the androgens of

insects; they are involved with reproduction and molting, but

human ingestion might be healthy or increase muscle mass.

Human interventions are lacking and problems with ecdysteroid

ingestion exist.

This page features 65 unique references to scientific papers.

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Summary (All Essential Benefits/Effects/Facts & Information)

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.

Follow this Page (/follow/74/) for updates

Things to Know

[1]

Also Known As

Suma extract, pfaffia extract, Brazilian ginseng extract, beta-ecdysterone, turkesterone,

ecdysterone

Things to Note

Ecdysterone is non-stimulatory.

Is a Form of

Testosterone Booster (/supplements/Testosterone+Booster/)

Does Not Go Well With

PI3K, GPCR, and PLC inhibitors (in regards to protein synthesis)

Caution Notice

Examine.com Medical Disclaimer ()

How to Take (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.

Editors' Thoughts on Ecdysteroids

So, humans have an EcR receptor for insect hormones? Weird... Not perfect as we lack the USP

receptor (which logic should dictate, since we aren't insects) but apparently this may be one of the

possible reasons as to why insect hormones actually do work in humans, aside from the cytoplasmic

receptor. There may be an entire ecdysterone signalling system, which is interesting.

I cannot say much about the effects of ecdysteroid supplementation, but it is a very interesting topic. At

least one study says that a certain ecdysteroid (turkesterone) is as potent as an anabolic-androgenic

steroid (Nerobol) and animal models do consistently show increased weight.

But it doesn't increase testosterone at all. This is either a blessing or a curse; it increases protein

synthesis, so isn't that good enough?

Kurtis Frank (/user/KurtisFrank/)

A

B

C

D

Human Effect Matrix

The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what

effect Ecdysteroids has in your body, and how strong these effects are.

GRADE LEVEL OF EVIDENCE

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

() EFFECT

CHANGE

()

MAGNITUDE OF EFFECT SIZE

() SCIENTIFIC CONSENSUS COMMENTS

C Testosterone (/topics/Testosterone/)

100%

See study (/show_rubric_effect.php?

id=74&effect=Testosterone&selection=all)

No alterations

noted in serum

testosterone

associated with

ecdysterone

consumption

LEVEL OF

EVIDENCE ()

EFFECT

CHANGE ()

MAGNITUDE OF

EFFECT SIZE ()

SCIENTIFIC CONSENSUS COMMENTS

C Lean Mass (/topics/Lean+Mass/)

100%


id=74&effect=Lean%

20Mass&selection=all)

No differences

between

ecdysteroids

and placebo in

improving lean

mass accrual

during a weight

lifting program

C Total Cholesterol (/topics/Total+Cholesterol/)

100%


id=74&effect=Total%

20Cholesterol&selection=all)

In resistance

trained males,

no significant

influence of

ecdysterone

supplementation

on cholesterol

C Liver Enzymes (/topics/Liver+Enzymes/)

100%


id=74&effect=Liver%

20Enzymes&selection=all)

No significant

alterations in

any measured

liver enzymes

(ALT, AST,

GGT)

C Power Output (/topics/Power+Output/)

100%


id=74&effect=Power%

20Output&selection=all)

No difference

between

improvements in

power output

between

ecdysteroids

and placebo

C Triglycerides (/topics/Triglycerides/)

100%


id=74&effect=Triglycerides&selection=all)

No significant

influence on

triglycerides

C Cortisol (/topics/Cortisol/) 100%See study (/show_rubric_effect.php?

id=74&effect=Cortisol&selection=all)

No

demonstrated

changes in

cortisol levels

with

ecdysterone

consumption

Disagree? Join the Ecdysteroids Discussion (/discussion/Ecdysteroids/)

Edit (/edit-section/supplements/Ecdysteroids/?section=Sources+and+Structure)

Scientific Research

Table of Contents:

1. Sources and Structure

1.1. Sources

1.2. Structure

2. Pharmacology and Metabolism

2.1. Bioavailability and Pharmacokinetics

2.2. Cellular and Receptor interactions

2.3. Excretion modes and metabolites

3. Neurological implications

4. Ecdysteroids and Longevity

5. Effects on carbohydrate metabolism

6. Effects on lipid (fat) metabolism

7. Effects on protein metabolism and strength

7.1. Protein synthesis

7.2. In vitro studies and overall growth

8. Effects on Bone Metabolism

9. Interactions with Hormones

9.1. Testosterone metabolism

10. Miscellaneous Organ Health

10.1. Liver

10.2. Skin

11. Safety threshold

1. Sources and Structure

1.1. Sources

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:

Asparagus Filicinus

Spinacia oleracea (Spinach, source of 20-hydroxyecdysone)

Quinoa, in the bran mostly, primarily containing 2--hdyroxyecdysone and makisterones and ranging from

450-1300mcg/g ecdysone equivalents.

Yams

[2]

[3]

[4]

[5]

[6]

[7]

White button Mushrooms

Ajuga Turkestanica, a source of the C-11 hydroxylated 'Turkesterone'

Rhaponticum carthamoides

Silene Praemixta (2-deoxyecdysterone and 2-deoxy-alpha-ecdysone)

Vitex Scabra, having 1.8% ecdysteroids by weight as well as other Vitex species such as cymosa

and canescens

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.

1.2. Structure

'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:

Ecdysone

Ecdysterone and Beta-ecdysterone

20-hydroxyecdysone

Turkesterone

Integristerone A

24(28)-dehydramakisterone A

[5]

[8]

[9] [10] [11]

[12]

[13]

[2][4]

[2]

[14] [15]

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Viticosterone E

Sileneoside A and C

Ponasterone A

Cyasterone

2. Pharmacology and

Metabolism

2.1. Bioavailability and Pharmacokinetics

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.

2.2. Cellular and Receptor interactions

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 (/supplements/Berberine/) or Horny Goat

Weed (/supplements/Horny+Goat+Weed/).

2.3. Excretion modes and metabolites

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[15]

[23]

[24]

[15] [25]

[26]

Edit (/edit-section/supplements/Ecdysteroids/?section=Neurological+implications)

Edit (/edit-section/supplements/Ecdysteroids/?section=Ecdysteroids+and+Longevity)

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

2,3,6,22R,25-pentahydroxy-5-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.

3. Neurological implications

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.

It also exerts some protective effects against neurological toxins.

4. Ecdysteroids and

[27]

[28] [16]

[29]

[15]

[17]

[17]

[30]

[31]

[31] [32]

[33]

[34]

[35][36]

[34]

[37][38]

Edit (/edit-section/supplements/Ecdysteroids/?section=Effects+on+carbohydrate+metabolism)

Edit (/edit-section/supplements/Ecdysteroids/?section=Effects+on+lipid+%28fat%29+metabolism)

Edit (/edit-section/supplements/Ecdysteroids/?section=Effects+on+protein+metabolism+and+strength)

Longevity

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.

5. Effects on

carbohydrate metabolism

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.

6. Effects on lipid (fat)

metabolism

Phytoecdysones (the overarching family of which ecdysterone belongs to) shows some promise

as being cholesterol lowering agents , probably through increased conversion of cholesterol

into bile acids. These effects were found at 2.5mg/kg bodyweight.

Ecdysterone also exerts protective effects against lipid peroxidation from free radicals, getting a

status of anti-oxidant. This effect was seen at a very low dose of 0.1mg/kg bodyweight, and

was more potent than Vitamin D (/supplements/Vitamin+D/) on a per molecule basis.

7. Effects on protein

metabolism and strength

[39][40] [41]

[42]

[43]

[43]

[43]

[44][45]

[46]

[47]

7.1. Protein synthesis

Ecdysterone supplementation, at around 5mg/kg bodyweight, seems to be able to induce

protein synthesis in animal organs. 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.

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.

In direct comparative studies, the ecdysteroid called 'Turkesterone' appears to be more potent

relative to other ecdysteroids studied followed by cyasterone and then 20-hydroxysterone.

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.

[48][49]

[38]

[50]

[51]

[48]

[52][8] [53]

[15]

[8]

[8]

[1]

[1] [54]

[55]

[1]

[1]

Edit (/edit-section/supplements/Ecdysteroids/?section=Effects+on+Bone+Metabolism)

Edit (/edit-section/supplements/Ecdysteroids/?section=Interactions+with+Hormones)

It has also been noted in one study's discussion that the 'tail' of ecdysteroids (-hydroxy--

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.

7.2. In vitro studies and overall growth

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%.

8. Effects on Bone

Metabolism

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.

9. Interactions with

Hormones

9.1. Testosterone metabolism

[17]

[49][56][57] [58] [59]

[51]

[60]

[61]

[15]

[58]

[62]

[62]

Edit (/edit-section/supplements/Ecdysteroids/?section=Miscellaneous+Organ+Health)

Edit (/edit-section/supplements/Ecdysteroids/?section=Safety+threshold)

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.

10. Miscellaneous Organ

Health

10.1. Liver

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.

10.2. Skin

In regards to skin, ecdysterone seems to be able to promote keratinocyte differentiation and

accelerate small wounds and burns when externally applied.

11. Safety threshold

Ecdysteroids, in total, are quite safe for ingestion. Benefits seem to show at doses around

10mg/kg bodyweight whereas established toxicity in mammals (rodents) is 6400mg/kg

bodyweight when injected and >9000mg/kg bodyweight when consumed orally.

Scientific Support & Reference Citations

[63]

[51]

[64]

[65]

[38]

[53]

[38]

[38]

[44][43]

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Ecdysteroids are a class of hormones that are the androgens of insects; they are involved with reproduction and molting,

but human ingestion might be healthy or increase muscle mass. Human interventions are lacking and problems with

ecdysteroid ingestion exist.

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