Turkesterone Ecdysterone mechanism

What Are Ecdysteroids: Debunking 5 Myths About Turkesterone and Ecdysterone

The internet is an internationally accessible library of information. The downside is that sometimes there can be more misinformation going around than reliable information. As turkesterone and ecdysterone supplements grow in popularity, we see this same trend with many misconceptions about ecdysteroids circulating around the fitness community. We will evaluate these claims one by one and see what is really supported by the research.

THE MYTHS ABOUT ECDYSTERONE AND TURKESTERONE

  1. Ecdysteroids are the same as steroids.
  2. Ecdysteroids increase testosterone or other hormone levels.
  3. Ecdysterone is the less potent version of turkesterone.
  4. Ecdysteroids are as potent at building muscle as dianabol.
  5. Ecdysteroids have not been studied in humans.

MYTH #1:

Ecdysterone and turkesterone supplements are the same as steroids. 

Ecdysterone and turkesterone belong to a class of molecules known as "phytoecdysteroids" or more simply "ecdysteroids." The prefixes "ecdy-" and "phyto-" refer to insects and plants, respectively.1 Originally, this class of molecules was discovered in insects and called ecdysteroids but later it was discovered that plants produced these molecules as well, hence the name was changed to phytoecdysteroids to include both sources.1 Due to the names of these compounds, there is often a misconception that they are steroids or a subclass of steroids.

As is usually the case with myths, grains of truth can be found with some of them. In general, when someone in the fitness world says "steroids" they mean Androgenic Anabolic Steroids (AAS). Examples of these molecules include testosterone and trenbolone. These compounds are categorized by both their ability to bind to a group of receptors named androgen receptors and their anabolic properties of building muscle and other tissues.2

Scientifically speaking, a steroid simply refers to anything that contains a 17-carbon ring-system in its chemical structure (shown below). The biochemical term steroid actually refers to a large variety of compounds and medications including corticosteroids, hormones, cholesterol esters, and plant-based compounds. Steroids can be further classified under different subgroups as well.

So far, we've introduced steroids and their complex nomenclature, but where do ecdysteroids fall on this spectrum? Ecdysteroids are most closely related in structure to cholesterol and are considered steroids by definition. Because of this, unfortunately, people have the misconception they are the same as anabolic androgenic steroids (AAS). Ecdysteroids are NOT the same as AAS. As previously mentioned, AAS like testosterone bind to the androgen receptors, where they elicit their effects2. This binding is associated with male sex characteristics such as voice deepening, enhanced bone growth, aggression, and acne.3

Ecdysteroids show no binding affinity to the androgen receptor and thus are not associated with the effects mentioned above. This is primarily due to the fact that ecdysteroid molecules are too bulky to fit in the same receptor pockets where AAS work.4

Credit: Vakoc Lab, CSHL

To those of us who are not medicinal chemists, it may seem that testosterone and ecdysterone have very similar chemical structures. But when we consider their stereochemistry (how the molecules look in 3D), we can start to make sense of how they have different  pharmacodynamics (effects on our bodies).

Think of how locks and keys work. In our bodies, an enormous variety of receptor molecules help control almost all biological processes. To maintain the body’s precise balance, these receptor “locks” must be secure and only respond in the right situations, to the right “key”. After a receptor meets the right molecule a whole cascade of downstream effects occur. Ecdysterone and anabolic androgenic steroids work as different "keys" for different "locks". It's also worth mentioning that receptors can range from being either highly or not very selective at all, depending on their biological function.

(https://www.eurekalert.org/news-releases/874635)

MYTH 2:

Ecdysteroids increase testosterone or other hormone levels.

Related to the last myth, is the idea that if ecdysteroids do not work the same way as AAS, then they must be increasing muscle by increasing the levels of other hormones. The claim is that ecdysterone is somehow a precursor to testosterone or other AAS compounds, or that by some unknown mechanism they are able to increase levels of these compounds.

There is no evidence to support that ecdysteroids become AAS, increase AAS, or act in the same manner as AAS in our bodies. On the contrary, there is evidence in humans showing no alterations in hormone bloodwork when subjects were given ecdysterone. Additionally, chemical modifications required to convert ecdysterone into an AAS are numerous and biochemically implausible. 

The exact mechanism of ecdysteroids is debated amongst experts, so stay tuned for a full article discussing this topic. In brief, ecdysteroids increase muscle protein synthesis by binding to the estrogen beta receptor.4 These receptors are found in the nuclei of our cells and are in charge of generating proteins through transcription and translation. 

MYTH 3:

Ecdysterone is a less potent form of Turkesterone.

Unlike the last myth, the origins of this myth are a bit less clear. On a milligram to milligram basis, it is unclear how different ecdysteroids compare to each other in terms of potency. Further research is required to elucidate the comparison between efficacy and potency in ecdysteroids.

There is one study by Syrov et al. that did evaluate the potency of several AAS, SARMs, and ecdysteroids, however this paper has many noteworthy limitations.5 First, the paper is translated from Russian and only a portion of original text remains. Second, because we have no access to the methods of this paper, the results are not reproducible. Lastly, the study used a small sample size of mice and looked at too many compounds to draw anything meaningful for head-to-head statistical comparisons. Ironically, this paper actually found that ecdysterone and turkesterone were relatively comparable in potency (as they had nearly overlapping confidence intervals). However, due to the limitations mentioned, it would be unwise to use this study to support that claim.

While the potency between each ecdysterone and turkesterone are unclear, the dosing and concentration of available products on the market is much clearer. Ecdysterone is the most common and widely available ecdysteroid; plants produce ecdysterone in quantities far greater than any other ecdysteroid.6 Cyanotis plant species can produce ecdysterone accounting for 10% of their dried plant weight. This means they can be more easily purified and isolated from the rest of the plant extract.6

Turkesterone on the other hand is not produced nearly to the same extent by plants as ecdysterone. Turkesterone is primarily sourced from the Ajuga plant species at much lower concentrations. Due to this, turkesterone can be extremely expensive. To cut down on costs, supplement companies sell less refined plant extracts; virtually every turkesterone containing product is standardized to at most 10%, if standardized at all. Ecdysterone products can contain much higher standardizations, thus making it more practical to achieve higher doses.

Because of this limitation, it makes more practical sense to use ecdysterone for most products, especially when there is no strong evidence that turkesterone is more potent or yields greater effectiveness compared to ecdysterone. So while turkesterone may be the trendy one of the two, this is based wholly on marketing and has nothing to do with the science behind each supplement.

In fact the science suggests the opposite, as the overwhelming majority of studies in humans and animals are conducted with ecdysterone (aka 20-hydroxyecdysone) and not turkesterone. More on this point when we talk about myth #5.

MYTH 4:

Ecdysteroids are as potent at building muscle as anabolic androgenic steroids like Dianabol.

While we are on the subject of potency, this myth is directly related to the study that we mentioned earlier. This study showed that turkesterone and ecdysterone were of similar potency at building muscle as some anabolic androgenic (AAS) that the authors investigated.6 This study was then quoted by several fitness influencers and supplement companies trying to market their products. We made mention of the limitations of that study previously in Myth 3.

One quick note though, study mice were injected with either AAS, ecdysteroids, or SARMS, meanwhile injectable ecdysteroids have not yet been investigated in humans. Furthermore, Dianabol has very good bioavailability orally and ecdysteroids have very limited absorption orally.7 Therefore, it would not be appropriate to take the results from a study in mice that used injectable compounds and apply it to humans taking those same compounds orally (even if it was a reliable source). 

(Read more about the problems with oral ecdysteroid supplementation)

Lifters taking ecdysteroids will share their anecdotes and confirm these supplements are not as potent as AAS. Further research is needed to be able to compare these compounds head to head, and it is unlikely that we will get this data as AAS are controlled substances in the US which makes designing studies using these compounds challenging. 

MYTH 5:

Ecdysteroids have no human data to support their use.

Of all the myths on this list, this one has started to spread like wildfire amongst doubters. Even some experts in the fitness industry who are known to be evidence based make this claim. Let's explore why this misconception is inaccurate by comparing supplements to medications and looking at examples of each to identify where ecdysterone falls on that spectrum. 

The problem with this claim is that dietary supplements are different from pharmaceutical drugs. For a medication to reach the market, it first needs to be thoroughly researched. Drug companies will pour billions of dollars and decades of research to make sure they have all the data required for FDA approval. 

With supplements on the other handthe funding for their data comes AFTER the supplement has been widely adopted, because they do not require FDA approval. 

As an example, let's take a look at the most well studied sports supplement in existence: creatine. As a supplement, it actually dates back to the mid-1800s, however after the Olympic Games in 1992, its popularity increased exponentially.8 A quick search on PubMed with the term "creatine supplementation" brings up 2,526 results. Viewing the timeline reveals that the 1992 Olympic Games really got the ball rolling on the research, and a majority of the papers published on creatine are from the last 10 years. 

We can see it took a long time for creatine to catch on, and even still, many misconceptions about creatine still exist. If we "wait for the data" to arrive in a specific sample population that data may never arrive, and even when it does arrive, it will not reach the level of evidence that a medication might have. For example, the anti-nausea medication Zofran was approved in 1992, the same time that creatine began to catch on, yet searching PubMed yields 5,194 results. However, just because supplements are understudied relative to medications does not mean that we have to base our decisions on supplementation using conjecture alone.

Because the fitness community is a relatively small niche, the majority of ecdysterone data in humans actually comes from clinical studies investigating its use as a medication, not a supplement. Currently, ecdysterone is being investigated as a medication for a plethora of different disease states. The effects of ecdysterone have been evaluated in either pre-clinical or clinical trials in healthy volunteers and in patients for the treatment of neuromuscular, cardio-metabolic, and respiratory diseases.9 This means that as far as safety goes, regulatory preclinical and clinical studies in humans have assessed ecdysterone's tolerability, side effect profile, and lack of toxicity to be acceptable for human use.9 

The most relevant disease for this discussion stems from ecdysterone undergoing trials for sarcopenia and cachexia, diseases related to muscle loss and muscle wasting. Currently Biophytis (BIO101) is in stage 3 clinical trials in Europe to treat muscle wasting diseases, and the early findings indicate positive results (https://clinicaltrials.gov/ct2/show/NCT04472728). In other words, if ecdysterone is thought to be a promising compound to put on muscle in the medical world, why are "experts" trying to dismiss it in the fitness world? It is outside the scope of this article to have a discussion of all these findings, the purpose of this article is simply to make aware of the research no one seems to be talking about. In the future, be on the lookout for full research breakdowns. 

As far as the studies done in lifters, they are few and far between. An Isenmann and colleagues paper is often mentioned but contains several important limitations.10 This study has potential author bias, conflicts of interests due to funding from the World Anti-Doping Agency (WADA), and the product studied only contained 6mg of ecdysterone per capsule. It turns out ecdysterone products being mislabeled is not an uncommon finding either. A recent study on ecdysterone supplements found that of the 12 products they analyzed, none were within 90% of what they advertised, and 6 products contained less than 20% of what was stated on the label.11 This is why it is paramount to buy supplements from companies dedicated to quality and who follow good manufacturing practices.

The lack of good data in lifters is not reason to write off these compounds entirely. The fact of the matter is that ecdysterone has more data in humans than in the vast majority of sports supplements on the market. Part of the problem is that the majority of the ecdysterone research is published in basic science journals that are difficult to understand and interpret. The other issue is that the rest of the data on ecdysterone is part of clinical trials which are difficult to access. Knowing this, it starts to make sense why the fitness community has no idea that these studies exist. Furthermore, many lack the proper training to to be able to interpret this data and would be unreliable sources for the mainstream consumer.

Extrapolating the data from various fields of literature paints the picture that ecdysterone is a promising sports supplement and has been shown to be safe in healthy participants and people with various diseases. 

TAKEAWAYS

In summary, ecdysterone is the most common and well studied ecdysteroid, it has been evaluated numerous times in humans and no major safety concerns have been identified. Ecdysteroids have been shown to be anabolic and based on what we know about their mechanisms and animal data they do not act like anabolic androgenic steroids. These compounds are likely not as potent as anabolic androgenic steroids but more research is required. Finally, we lack sufficient data in lifters supplementing with ecdysterone but that does not rule out that they show promise for this indication as well; especially if the studies administer ecdysteroids through non-oral routes of administration, due to their known limited bioavailability.12  

REFERENCES:

  1. Das N, Mishra SK, Bishayee A, Ali ES, Bishayee A. The phytochemical, biological, and medicinal attributes of phytoecdysteroids: An updated review. Acta Pharm Sin B. 2021;11(7):1740-1766. doi:10.1016/j.apsb.2020.10.012
  2. Heinlein CA, Chang C. The roles of androgen receptors and androgen-binding proteins in nongenomic androgen actions. Mol Endocrinol. 2002;16(10):2181-2187. doi:10.1210/me.2002-0070
  3. Nassar GN, Leslie SW. Physiology, Testosterone. [Updated 2022 Jan 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526128/
  4. Báthori M, Tóth N, Hunyadi A, Márki A, Zádor E. Phytoecdysteroids and anabolic-androgenic steroids--structure and effects on humans. Curr Med Chem. 2008;15(1):75-91. doi:10.2174/092986708783330674
  5. Syrov, V.N. Comparative experimental investigation of the anabolic activity of phytoecdysteroids and steranabols. Pharm Chem J. 34, 193–197. https://doi.org/10.1007/BF02524596
  6. Thiem B, Kikowska M, Maliński MP, Kruszka D, Napierała M, Florek E. Ecdysteroids: production in plant in vitro cultures. Phytochem Rev. 2017;16(4):603-622. doi:10.1007/s11101-016-9483-z
  7. van der Vies J. Pharmacokinetics of anabolic steroids. Wien Med Wochenschr. 1993;143(14-15):366-368.
  8. Butts J, Jacobs B, Silvis M. Creatine Use in Sports. Sports Health. 2018;10(1):31-34. doi:10.1177/1941738117737248
  9. Dinan L, Dioh W, Veillet S, Lafont R. 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases. Biomedicines. 2021; 9(5):492. https://doi.org/10.3390/biomedicines9050492
  10. Isenmann E, Ambrosio G, Joseph JF, et al. Ecdysteroids as non-conventional anabolic agent: performance enhancement by ecdysterone supplementation in humans. Arch Toxicol. 2019;93(7):1807-1816. doi:10.1007/s00204-019-02490-x
  11. Ambrosio G, Wirth D, Joseph JF, Mazzarino M, de la Torre X, Botrè F, Parr MK. How reliable is dietary supplement labelling?-Experiences from the analysis of ecdysterone supplements. J Pharm Biomed Anal. 2020 Jan 5;177:112877. doi: 10.1016/j.jpba.2019.112877. Epub 2019 Sep 11. PMID: 31568967.
  12. Dinan L, Balducci C, Guibout L, et al. Ecdysteroid metabolism in mammals: The fate of ingested 20-hydroxyecdysone in mice and rats. J Steroid Biochem Mol Biol. 2021;212:105896. doi:10.1016/j.jsbmb.2021.105896.
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