Deep dive into Ecdysteroids and Turkesterone.

Deep dive into Ecdysteroids and Turkesterone.

Table of contents:
1.. What are Ecdysteroids
2.. How do they work
3.. What do they do
3.a The Anabolid effect of Turkesterone and ecdysteroids
3.b. Strength and Endurance
3.c. Adaptogenic effects
4.. Dosing
5.. Side effects
6.. Bottom line
7.. parting words
8.. The Experiment
 
 
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.
 
Read this section only if you want to go into the purposed mechanisms of how Ecdysteroids work in the body on a receptor/pathway level.
 
 
The TL;DR of this section is:
-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.
 
 
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 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.
 
 
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.
 
 
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]
 
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.
 
Parting words
 
I hope you all enjoyed this write up, as a follow on to this article I will be doing comprehensive log of Turkesterone supplementation on my self starting from Monday 15th March 2021. I am curious to the benefits of this apparent legal anabolic but like many of you i'm sure, would like further proof of its efficacy.
 
The Experiment
 
My experiment will be structured as follows:
 
500 Calorie deficit (which I have been in for a few months now)
Running Creeping Death 2 by John Meadows
 
9 weeks in length
 
14th March:
fasting blood test
body part measurements
weight
 
15th March,
400mg Turkesterone p/day
 
5th April,
600mg Turkesterone p/day
body part measurements
weight
 
26th April,
fasting blood test
800mg p/day
body part measurements
weight
 
18th May
fasting blood test
body part measurements
weight
End of experiment.
 
 
Along side this I will be posting a daily log including:
 
Full workout log for the day
Any cardio done
Morning fasted weight
Anecdotal log on daily "feel".
 
I honestly have no idea if this will work but there is very little out there in terms of comprehensive real life logs on this supplement and I hope this will ad some benefit.
 
Thats it for me today folks, ill see you Monday for day 1 on this journey!

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