Turkesterone

vetbusd

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I take no credit for this post, Im just compiling research/information I found online and adding some of my info. Im not suggesting anyone to take it and i dont take it myself, just wanted to open the discussion on this substance. NeekBod to GreekGod (u/Mougllii) - Reddit -. He is doing a Log where he is taking this, Follow along for his n=1 expirement. a large part of this post was stolen from his reddit post.

1. What are Ecdysteroids

Turkesterone is a phytoecdysteroid or a polyhydroxylated ketosteroids, plant analogues of insect growth hormone, of which there are hundreds [1] out in nature. The three that get the most hype are, 20-hydroxyecdysone, Spinache extract and Turkesterone which we will be covering in this article specifically after I have gone through the proposed mechanisms.The terms insect growth hormones or plant ketosteroids are enough to make anyone wary, however the reality is a lot less alarming. In insects where these compounds can be found, the insects have specific Ecdysteroid receptor that gets activated when in the presence of it.[2] So, I know it stills sounds a bit mad scientist to go ingesting/injecting these compounds, but it gets better.Ecdysteroids have been found in mammals, though it is poorly understood how these Ecdysteroids came to be in the tissue it is assumed the source is either from dietary intake, gut flora or potentially from a specific infection. [3] How the body then deals with this new compound is still a topic of debate though more recent research has potentially shed some light on the mechanisms involved. There is mounting evidence that Ecdysteroids could act as an agonist for receptors in our bodies [4,5] eliciting the anabolic, adaptogenic and protein synthesis effects that are so often touted.

2. How do they work.

-β2 adrenergic receptor is not likely responsible for the anabolic effects.

-Estrogen receptor beta may have a role to play, but it isnt solely responsible.

-G protein-coupled receptor are also a likely candidate coupled with AKT pathway activation.


I'm sure many of you reading this article are aware of the YouTube channel MorePlatesMoreDates, the host of the channel, who I greatly respect, published a video [6] giving a fairly comprehensive review to Ecdysteroids and Turkesterone. This video was what inspired me to deep dive into this compound in the first place. In this video Derek proposes that the mechanism of action to be the human Estrogen receptor beta (ERβ), he links a study that demonstrates how stimulation of the ERβ can promote skeletal muscle growth [21], this sets the ground work to go onto to suggest that the ERβ could be responsible for the anabolic effect from Ecdysteroids.

The next study that Derek references measures the skeletal muscle hypertrophy from the ERβ by applying a ANTIBETA compound to myotubes. From which they conclude that the effects of Ecdysteroids are mediated by the ERβ. [9] The problem with the studies abstract is that it doesn't state the compound used to block the ERβ, as these receptor blockers can have down stream effects on other systems. I don't have access to this study so I cant elucidate further on the potential down stream or upstream effects, instead I will go over other potential candidates and if they offer a suitable alternative. Regardless though, it offers a potential receptor for these Ecdysteroids.

Next, the β2 adrenergic receptor has been offered as a potential vector for Ecdysteroids effects, [8] as this receptor when agonised is able to produce anabolic effects, see Clenbuterol. [7] A study looked into the homology of the structure in relation to the β2 adrenergic receptor and found a fairly high relation, which suggests the structure of ecdysteroids could "fit" the receptor. [8]

Later research has applied binding studies, with 20-hydroxyecdysone on functional activation assays using cAMP, essentially testing the β2 adrenergic receptor binding affinity for Ecdysteroids. The results showed a complete lack of binding to the receptor which crosses the β2 AR off the list of potential candidates.[10] The study instead suggest that another G protein-coupled receptor (GPCR) could be responsible for the anabolic activity that we see through the literature. It suggests that the pathway AKT is responsible for the increased protein synthesis and therefore the anabolic effect we see from these Ecdysteroids. Indeed, when measured the AKP pathway's activation is drastically increased when 20-hydroxyecdysone is administered and when this pathway is directly inhibited the protein synthesis is also blocked.

Another study conducted just last year came to a similar conclusion, that the ERβ probably isn't solely responsible but rather coupled with a GPCR. Their proposed candidate was the MAS receptor [11] as opposed the AKT activation that is purported by the previously mentioned study. [10] Based on these two studies, links can be drawn between their two conclusions. We know that the AKT pathway can mediate MAS receptor activation. [12] I suspect that the researchers found the downstream effects of AKT pathway activation from the MAS receptors, it is also worth noting that the AKT pathway and ERβ are also intertwined with studies showing their their activation effecting one another. [22] Though this is still only part of the overall story, collaborating this data there is the potential that other unknown GPCR's may still have a strong role to play in the activation of both the ERβ and PLC-IP3 pathway, leading to calcium flux channels that activate the AKT pathway and the resulting anabolic activity. Regardless of the actual mechanism one thing remains certain, Ecdysteroids show no androgenic effects, as it has no affinity for the Androgen receptor. [13,11,10].

3. What do they do

As I briefly mentioned in the introduction, Ecdysteroids as a whole have a whole host of purported benefits, of which where almost unanimously claimed by non speaking eastern researchers. The papers of which have questionable reliability, methods and claims. I will not be doing into detail or really putting to much value in their studies, but here is a list of their studies, their claims and methods that was compiled by another study.

1616145202721.png


Fig.1
These studies should be taken with a big grain of salt, I have only added them in this break down as a nod to what inspired greater research into these compounds. Within this list is the study that demonstrates Ecdysteroids being more potent than D-Bol...With that glossed over I am going to go into the individual effects that are claimed for Turkesterone.

3.a The anabolic effect of Turkesterone and Ecdysteroids

The anabolic effect of Ecdysteroids and Turkesterone in animal studies consistently show significant anabolic effect, increasing lean muscle mass and strength [10,14,15,16,17]. However a key take away from those studies is that non are done on humans. one study conducted on strength trained individuals with ecdysterone from spinach extract at 200mg and another group at 800mg p/day dosage over 10 weeks showed significant muscle hypertrophy and strength gains against control, with the group supplementing with 800mg coming ahead in all metrics. The 800mg group gained an average of 3.2kg (7lb) of muscle mass against the control which had a range of a slight decrease or increase in muscle mass over the 10 weeks. [19] However, another study which ran 20-hydroxyecdysone at 200mg for 8 weeks showed no difference in any strength parameter against control. [18] Why these studies showed such drastic differences in results I'm not sure, the quality of the product may be a factor or perhaps the 20-hydroxyecdysone does not work as well in humans as it does in rodent and other animal models.

3.b Strength and endurance

The two studies that I have linked previously also measured the strength metrics of their athletes, like I afore mentioned the 20-hydroxyecdysone showed no effect at all in any strength metric. The second study however does. over the ten weeks the 800mg group increased their Squat by almost 20% and their bench by 10%. It calls into question again why these two studies have such differentiating results. Unfortunately these are the only two human trails that I can find currently. There are plenty more rodent based models through swimming time and grip strength that demonstrate a dose dependant increase in strength and endurance through supplementation with Ecdysteroids, though like I mentioned prior, I don't want to focus on these as they are generally not great at being applied directly to humans. More clinical data is sorely needed, though it is extremely promising so far.

3.c Adaptogenic effects

Fig.1 showing the list of studies conducted my eastern researchers includes that of adaptogenic benefits of ecdysteroids. Unfortunately this is an area that is lacking a lot of research at the moment, all we can do is hypothesis. I cannot find any studies looking into any detail on the stress resistance benefits of Ecdysteroids.

4.Dosing

From what little data we have from studies and from what is on the market currently, stated doses range from 50mg to 800mg p/day. It does seem to have a dose dependant effect, but there is so little data on the subject it is hard to state a conclusive efficacious dose.

5.Side Effects

Several studies have shown that in animals there seems to be no toxicity at doses as high as 20mg per kg. [20] Luckily one of the human trials I mentioned earlier did blood work on their subjects and found no difference between pre and post supplementation health markers and they dosed as high as 10mg per kg. [19]

6.Bottom line

These compounds had been added to the WADA watch list as a potential agent to be banned in a performance enhancing context, the fact that it hasn't been banned yet is a testament to how lightly researched these Ecdysteroids are. Judging from the animal, and what little human studies we have available to us, I am optimistic that they may well be useful in muscle building context without the androgenic side effects of traditional anabolics. That being said, I want to re iterate that this area of research, although touched on long ago, is still very poorly understood with he mechanisms still in debate.



So i did some more research on this:

A more recent study conducted in 2019 by a team that included the Department for Molecular and Cellular Sports Medicine at the German Sport University Cologne, found that significantly higher increases in muscle mass were observed in participants dosed with ecdysterone, with significantly more pronounced increases in one-repetition bench press performance.[12] The study was funded by the World Anti-Doping Agency (WADA) and demonstrated a significant dose-responsive anabolic effect of 20-Hydroxyecdysone supplementation on athletes during resistance training. Furthermore, recent studies ([13]) have elucidated that the mechanism of action of 20-Hydroxyecdysone on human muscle cells is relatively selective activation of the beta form of the estrogen receptor (ERβ), which is known to result in muscle hypertrophy.

this is the study they are refering to. Their recomendation to WADA is that it should be banned: https://pubmed.ncbi.nlm.nih.gov/31123801/

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".

Sci-Hub | Ecdysteroids as non-conventional anabolic agent: performance enhancement by ecdysterone supplementation in humans. Archives of Toxicology, 93(7), 1807–1816 | 10.1007/s00204-019-02490-x

human studies blood tests:
As source of ecdysterone, the dietary supplement “Peak Ecdysone” (PeakPerformance Products SA, Roodt-surSyre, Luxemburg) was used. The product is labelled to contain 100 mg of ecdysterone from spinach extract plus 100 mg of leucine. The volunteers out of the Ec1 group took two capsules of “Peak Ecdysone” per day as recommended on the label of the product. The Ec2 group took a high dosage of ecdysterone (eight capsules of “Peak Ecdysone” each day) over the entire intervention period. The PL group took two placebo capsules each day over the same period. The CO group took only two capsules of “Peak Ecdysone” without training. Each group took half of their nutritional supplementation dose in the morning after breakfast and the other half on training days immediately after training or on non-training days in the evenin
1616146091095.png

1616146046863.png

This is the same study which noted the major strength increases and suggested for it to be banned
1616146206294.png




Ill link some more anecdotal evidence/videos, ignore the flashy thumbnails since the information is good



Keep in mind the conflict of interest while watching it, since he does sell this product.



Super indepth video and log
 
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Mauritio

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Andman

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Used to be a big fan of Peak waaaayyy back (around 2006/07?)

Tried their Ecdysterone (both old and newer versions)

cant say i noticed much tbh
 

Mauritio

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DenerWerb

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Waiting for someone to post some more technical insight. I’ve actually ordered some to try.
 

DenerWerb

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I’ve been taking like 500mg-1000mg for the last 10 days. Can’t say there’s any difference in muscle growth already, but I’m sleeping like a rock now. Like 10 hours straight if my schedule allows it. It NEVER happened before. I never slept more than 7-8 hours a night, and the vast majority of the nights I would wake up in the middle of the night. I feel like my overall focus and energy is better (probably because of the improved sleep). My mood is definitely better. Anyways, that might be some pretty hardcore placebo effect. I’m from Brazil, and bought from an online manipulation pharmacy so who knows what I’m actually taking.
 

Ben.

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I am confused why there arent more replys here, but i guess Ecdysteroids have been mentioned in this forum before a couple of times.

Derek saying he coudln't find any side effects sounds great at first, but lets not forget he sells his Turkesterone product so it is biased.
I didn't look to much trough the search history but found this from haidut:


The ecdysterones are estrogenic. The same team who did this study has been publishing on ecdysterone for several years and I have been tracking their work. They also have studies that ecdysterone caused liver enlargement even in low doses, which they thought was quite worrying. I guess if a person is after an Olympic gold medal they will probably consider it acceptable risk to dope with this chemical for a few months, but I am not sure this should be a go-to tool for health-conscious people.

https://www.biorxiv.org/content/biorxiv/early/2019/06/27/685230.full.pdf
"...Contrary to the effect of AASs, it appears that the effect of ecdysterone is mediated by an activation of estrogen receptor beta (ERbeta) [1,21-23]. A few studies reported a performance enhancing effect in animals, but only recently a controlled administration trial in humans showed significant performance enhancement in resistance training [24]. Thus, the administration of ecdysterone may be considered as a practice that leads to an unfair advantage in sports competitions and may therefore be considered as doping. Indeed, ecdysterone was already suspected to be used by Olympic athletes since the 1980s and was also called a “Russian secret” [11,19,20,24-26]."

Btw, a progesterone/DHEA combination in a 1:1 up to 3:1 ratio will probably blow out ecdysterone out of the water in terms of both strength and muscle growth. Considering that the "anabolic" effect of steroids is simply blockage of cortisol's catabolic effects, and the fact that both progesterone/DHEA are the most potent anticatabolic endogenous agents, for somebody whose target is health as well as anabolism the progesterone/DHEA is the way to go. Dangerous growth triggered through activation of ER can lead to serious issues (proliferative disorders) down the line.
https://raypeatforum.com/community/threads/structural-requirements-for-an-optimal-anti-catabolic-steroid.20108/

Finally, the ecdysteroids have been shown to be devoid of an innate anabolic effect. They only work in intact (non-castrated) animals, so consequently their effect is dependent on how much endogenous anabolic steroids an organism produces. If the organism is hypothyroid or hypogonadal, there won't be much of an effect. This matches well with their anabolism being through ER. Chemicals that are agonists on ER are known to have hypertrophic effects when combined with legit anabolic steroids but are devoid of such properties when used on their own.
https://core.ac.uk/download/pdf/80769266.pdf
"...Comparing the effect of ecdysteroids and anabolic-androgenic steroids it has been reported [25] that an androgen dependent development is a prerequisite before the action of ecdysteroids in rat. 20-Hydroxyecdysone (6) in 0.5 mg/100 g dose for 7 days resulted in increased weight gain of the whole body, liver, heart, kidneys and musculus tibialis anterior in rats. The accumulation of protein content was also accelerated. These changes were even more pronounced if the animals were still growing (70-80 g). In sexually immature castrated rats the androgenic action of 20- hydroxyecdysone (6) was not demonstrable in contrast to that of methandrostenolone (36). Twenty-four years later an extensive comparative study was presented in English using a number of purified ecdysteroids including turkesterone (18), 20- hydroxyecdysone (6) and methandrostenolone (36) [26]. An early report [27] also implied the difference between the mechanisms of actions of ecdysteroids and anabolic steroids. 20- Hydroxyecdysone (6), turkesterone (18) and 2-deoxyecdysone (13) in the same (0.5 mg/100 g) dose were found to stimulate protein synthesis in the liver of laboratory mice. The protein synthesis increasing ability was associated with polyribosomal activity. The preliminary administration of actinomycin D did not prevent the phytoecdysteroid effect on protein synthesis stimulation. Therefore it has been concluded that the anabolic effect of ecdysteroids is connected with the acceleration of translocation processes instead of the induction of new RNA synthesis. This shows that ecdysteroids are not likely to act as the classical steroids, via cytoplasmic receptor and regulation of gene transcriptional activity."

Either converting to estrogen directly or increased estrogenic signalling for even some non-aromatizable ones. For example, trenbolone is a non-aromatizable steroids but its core is an "estrane" steroid (C18) instead of an androstane (C19) and as such it has inherent estrogenic effects in higher doses. It binds both ERalpha and ERbeta as agonist when used in concentrations above 2 uM/L. So, while it is a weaker "estrogen" than something like estradiol and can even have benefits for breast cancer by displacing estradiol (and suppressing its synthesis through pituitary suppression) it still does have receptor-level estrogenic effects in the doses used by bodybuilders. This probably explains the "mysterious" elevation of liver enzymes on high doses TREN even though non-17-alkylated steroids like TREN base are not supposed to have live toxicity. IMO all 19-nortestosterone (estrane) steroids have this risk so should be used in low doses only. For TREN, the 2 uM / L concentration cutoff seems to correspond to 25mg-30mg daily dose, and this coincides well with the reports on bodybuilding forums with people using 50mg+ TREN getting liver toxicity and even jaundice but lower doses being mostly without liver effects. Animal studies with TREN in HED of 3mg/kg (about 25mg-30mg for a decent size human male) actually showed protective effects on liver and heart while higher doses and testosterone were detrimental.
Trenbolone Improves Cardiometabolic Risk Factors and Myocardial Tolerance to Ischemia-Reperfusion in Male Rats With Testosterone-Deficient Metabolic Syndrome

Same goes for nandrolone, which actually also converts to estrogen quite easily so it is both estrogenic and an estrogen pro-hormone. As I mentioned in another thread, considering the benefits of 19-nortestosterone steroids lies mostly in their opposition of cortisol and the fact that most of them are progestins, then one might as all well use progesterone instead and stack with whatever other steroids the 19-nor steroids are usually stacked with. Progesterone may even protect from many of the side effects of those other stackables including liver damage, blood pressure, kidney damage, etc.
Just my 2c.
 

Brandin

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available to us, I am optimistic that they may well be useful in muscle building context without the androgenic side effects of traditional anabolics. That being said, I want to re iterate that this area of research, although touched on long ago, is still very poorly understood with he mechanisms still in debate.
Just so you know the side effects of traditional anabolics have nothing to do woth them being androgenic, Its the methyl/ester groups that cause the sides. There are plant androgens that give no sides

I have seen a video of Derek talking about muscle anabolism when castrated rats took estrogen. The problem with this study is that eventough it increases muscle growth in itself (especially legs) It would not in mormal rats or humans. Administrating estrogen in humans would lower androgens and increase cortisol tremendously wich wast a factor in a castrated rat. This is why In practice, humans taking estrogen greatly inhibits muscles growth but not in the study Derek touted.

But if we dont consider the downstream effects and just look at the molecules itself then yes estrogen increases anabolism slightly, then testosterone more and last but definitely not least DHT increases anabolism the most.

Considering all of this there could be multiple things at play making turkesterone anabolic:

1: eventough it activates estrogen receptor it does it less than BPA`s and other enviromental estrogens therefore lowering estrogenic load in the body. This would allow cortisol, inflammation, androgens, thyroid and many other muscle building things be increased.

2: might actually directly lower cortisol and activate akt and g protien wich would cause anabolism. Keep in mind this would not be because estrogenic effects since that would lower other strong activators of akt+g protein, Turkesterone would have to be specifically activating them itself.
 

reality

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Been seeing a lot of positive anecdotes on this I’m tempted to try.
Any more experiences?
 
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