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Ecdysterone supplementation has been shown to have a significant anabolic effect {1}:

Significantly higher increases in muscle mass were observed in those participants that were dosed with ecdysterone. The same hypertrophic effects were also detected in vitro in C2C12 myotubes. Even more relevant with respect to sports performance, significantly more pronounced increases in one-repetition bench press performance were observed. No increase in biomarkers for liver or kidney toxicity was noticed. 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".

Does ecdysterone supplementation have any deleterious side effects?


What I have found so far:

https://www.webmd.com/vitamins/ai/ingredientmono-1075/ecdysterone states:

There isn't enough reliable information available about ecdysterone to know if it is safe.

https://www.bodybuilding.com/fun/southfacts_ecdy.htm states:

Ecdysterone is safe and it improves nearly every bodily function...without side effects.

https://www.rxlist.com/ecdysterone/supplements.htm:

There isn't enough reliable information available about ecdysterone to know if it is safe.

but those website might be outdated.


References:

  • The rxlist.com link you provided states the information was reviewed 18th June 2019 so that one cannot be outdated. They are also owned and operated by WebMD – Chris Rogers Jul 1 '19 at 8:57
  • @ChrisRogers The rxlist.com link doesn't contain a single scientific reference, which makes me doubtful of the scientific quality of the content. – Franck Dernoncourt Jul 1 '19 at 9:15
3

The sensationalist press release for a small study does not warrant to conclude that

Ecdysterone supplementation has been shown to have a significant anabolic effect

While some previous studies have indicated that there may be an effect in cells, tissues and animals, previous human studies measured the effect for "gaining muscle" at zero!
(Wilborn: "Effects of Methoxyisoflavone, Ecdysterone, and Sulfo-Polysaccharide Supplementation on Training Adaptations in Resistance-Trained Males", 2006.)

The study now circulated is not only very small and didn't account for actual bio-availability of the claimed to fame substance. Further, there are more than 400 substances in this class of ectosteroids identified so far. Which one or which combination of them was used in this particular study or all the others is difficult to ascertain and compare in an SE overview answer.

It also did not explain how the alleged effect should be explained compared to control and placebo results. Unless replicated, the current study is "interesting", and has no real-life value – so far.

The main author of this study gives a lengthy interview (in German) acknowledging quite a few of the limitations of this study and its results in a podcast (at 1:34:00 he can be quoted with "with hard training we saw a small effect" / "don't take supplements"). Coincidentally the manufacturer selling 6mg as 100mg seems to have pulled the product from the market. Whether the heightened awareness due to the study or the many negative testimonials for products claiming this as an ingredient (example) or plain quality issues remains an open speculative question.

One big weakness is then that a very preliminary safety assessment was made looking at a few liver parameters. And "kidney" – via urine samples. That's laudable in itself, for such a study, but not enough.

As among the concerns of "promotes growth" (what "growth", cancer?) the substance is assumed to act on certain receptors

but it is rather exhibited by the activation of the estrogen receptor beta.

And longer term kidney health was not monitored in the new study.

Well, that might mean really bad news, everyone.

Minglei Lu: "Activation of mineralocorticoid receptor by ecdysone, an adaptogenic and anabolic ecdysteroid, promotes glomerular injury and proteinuria involving overactive GSK3β pathway signaling", Scientific Reportsvolume 8, Article number: 12225 (2018)

It seems a rather prudent meaure of supplement vendors to not really rip off consumers by selling them 100mg ecdysterone caps that only contain 6mg (Isenmann). That's actually consumer protection! As now the alleged effects of the supplement should be obtainable with the equivalent of 250 mg of regular spinach. Or some insects, as they contain this steroid hormone, and need it.

Most Internet claims for ‘spectacular’ effects of ecdysteroids on humans and other mammals are unsubstantiated or apocryphal. However, most reports in the scientific literature have demonstrated that the pharmacological effects of ecdysteroids in mammals are positive, and it is clear that ecdysteroids may influence/improve many physiological functions. Unfortunately, no extensive, systematic trials on any mammalian species have been published. Dietary intake of ecdysteroids is possible but limited for most humans, since the crop species which contain phytoecdysteroids are not extensively eaten. Thus, there may be a future for ecdysteroids as dietary supplements to contribute to human well-being (as ‘adaptogenic’ substances). However, more study is required to elucidate the metabolism of exogenous ecdysteroids in mammals and the biochemical modes of action of the parent ecdysteroids and their metabolites. Such studies are also important to underpin the use of ecdysteroid-induced gene switches. These systems possess considerable potential for basic biological studies of gene function and in gene therapy.

A quite recent summary of the sparse overall evidence for human application is found in

We briefly summarise the many attributed positive pharmaceutical effects of ecdysteroids in vertebrates (especially humans) and critically assess the reports associating ecdysteroids with cancer and embryotoxicity and the probable use of ecdysteroids as doping substances for athletes. We stress the need for much more extensive research into the metabolism and mode of action of ecdysteroids particularly in mammals. The presence of natural and, increasingly, man-made ecdysteroid agonists and antagonists may have considerable impact on the environ- ment. On the one hand, non-steroidal (ant)agonists offer considerable promise as environmentally friendlier, more selective pesticides, but, on the other hand, could become endocrine disruptors of non-target species, especially in aquatic ecosystems. We consider in some depth the development of strategies for the identification and environmental monitoring of potential endocrine disruptors affecting ecdysteroid hormonal systems in invertebrates and emphasise the overwhelming need for basic research into the endocrinology of aquatic invertebrates which would be suitable as signal species.

possible harmful effects of ecdysteroids on vertebrates had to be deter- mined, and these molecules have shown very low, if any, toxicity when ingested by mammals: acute toxicity value of 20-hydroxyecdysone for mice after oral adminis- tration could not be determined (so the LD50 is >9 g/kg body weight), whereas that after intraperitoneal injections LD50 was as high as 6.4 g/kg (Ogawa et al., 1974b).

tandard tests with pure molecules are needed to fully establish the lack of toxicity after daily administration over a long period (90-day test) (see also this PDF). Such experiments would allow the removal of ecdysone from the Carcinogenic Potency Database (http://potency.berkeley.edu). Anyway, lack of toxicity does not mean lack of pharmacological effects (see above).

The reported effects of ecdysteroids on tumorous cell induction/proliferation are conflicting (Table 23.2). Experiments are difficult to compare, as they differ in the molecules used (ecdysone, 20-hydroxyecdysone or other ecdysteroids), their concentrations, their purity, the assays used (in vitro/in vivo) and their duration. Thus, Burdette and Richards (1961) observed proliferation-inhibitory effects on sarcoma cells in vitro, but they used a semi-purified extract from silkworm pupae (ecdysone?). Later investigations with crystalline ecdysteroids obtained from plants showed no effects (Burdette, 1974b). Lagova and Valueva (1981) found that 20-hydroxyecdysone (0.1–300mg/kg daily subcutaneous injections for 5 days) was ineffective on the growth of several tumour types, whereas it stimulated that of mammary gland carcinomas. El-Mofty et al. (1987, 1994) reported that ecdysone was able to induce neoplastic lesions in toads and mice; surprisingly, these results were obtained with very low amounts of ecdysone (i.e. only 1μg/mouse (!) given orally twice a week for 22 months) and they are therefore difficult to reconcile with the data of other authors who used amounts several (2–4) orders of magnitude higher (albeit for shorter durations, e.g. 35 days) without observing any adverse effects (e.g. Ogawa et al., 1974b).

These anabolic effects were first described in mice/rats and resulted in increased physical performance/endurance (Syrov, 2000). They have also been observed in humans, according to the few clinical experiments, the details of which are not readily available (Lafont and Dinan, 2003).

The availability of other purified ecdysteroids is, however, seriously limited, and the few which are available are very expensive. The recent availability of large amounts of 20E has been driven by the belief that ecdysteroids possess anabolic properties (which has not been conclusively demonstrated in clinical trials, although a growing body of cir- cumstantial evidence exists) and the wish by many to exploit this. As a consequence, 20E is now a component of a very large number of preparations available over the Web (see Ecdybase), targeted at body-builders, sportsmen, health fanatics and their pets. These formulations incorporate purified 20E, or semi-purified ecdysteroid-containing plant extracts, together with other components; only in one product is 20E the only ‘active’ ingredient. Recommended doses have increased over time from 5 mg/pill in 1995 up to 300 mg/soft gel at the present. It is not clear if this reflects a reassessment of the required dosage, or the greater availability of 20E. One must also question the claimed amount of ecdysteroid present in the preparations, since Jadhav et al. (2007) found much lower levels than those claimed.

–– René Lafont & Laurence Dinan: "Innovative and Future Applications for Ecdysteroids", in: Guy Smagghe (Ed): "Ecdysone: Structures and Functions", Springer, 2009.

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