Ecdysteroids are a group of polyhydroxylated ketosteroids that are similar to androgens (e.g., testosterone). They were initially discovered in insects, where they are used during the molting process (when the exoskeleton is shed to allow for growth). Certain plants also contain ecdysteroids, where they play a role in protection from plant-eating insects. Ecdysteroids found in plants are called phytoecdysteroids, and those derived from animals are called zooecdysteroids.^[5]

Phytoecdysteroids are more frequently used in supplements than zooecdysteroids, and sources include spinach, Cyanotis arachnoidea (a plant found in China), and Ajuga turkestanica (an Asian plant that lends its name to one of the most well-known ecdysteroid products, Turkesterone).^[5][6] While ecdysteroids are a type of steroid hormone, they differ from human androgens in terms of their chemical structure, size, and polarity and therefore do not cause the hormone-related side effects that are associated with androgenic steroids.^[7]

Ecdysteroids are most well known as a supplement for athletic performance and muscle building. Some evidence supports these claims, although few studies have been done on humans. A study in 46 young men showed some benefit as measured by bench press strength and muscle growth compared to a placebo over 10 weeks.^[3][7][8] Other studies to support these claims have been done on rats, showing improved muscle recovery,^[9] increased grip strength,^[10] and endurance (as demonstrated by a swimming test).^[11] Future research in humans will be needed to confirm these findings, but research to date supports the idea that ecdysteroids have potential to improve athletic performance and muscle growth.

An antiobesity effect has been noted in some studies done on rodents. Using 20-hydroxyecdysterone (20HE) in rats and gerbils on a high-calorie diet mitigated weight gain compared to control groups.^[1][12][7] 20HE has also been shown to inhibit glucose production in rats and to lower glucose in a manner that is similar to some of the commonly used diabetic treatments, like metformin.^[13] This could be helpful in people with prediabetes or type 2 diabetes, but it is not yet well studied in human populations.

In menopausal and postmenopausal women, 20HE could help to decrease adipose deposits, particularly visceral fat (fat around the abdominal organs) and fat deposits in the muscles and joints. This has multiple benefits, including a lower incidence of cardiovascular disease, improved mobility, greater muscle mass, and an improved bone density. However, once again, more research is needed in humans to confirm these benefits.^[7][14]

A small in vitro study^[15] showed that ecdysteroids could suppress the growth of and increase cell death in certain types of breast cancer cells. The study also demonstrated a synergistic effect when ecdysterone is combined with doxorubicin (a chemotherapy drug often used in breast cancer treatment).

In acute myeloid leukemia (AML), ecdysteroids have been studied as an alternative to steroids like dexamethasone, which are frequently used in combination with chemotherapy and radiation during treatment. 20HE showed positive results in in vitro studies, decreasing the proliferation of cancer cells, increasing cancer cell death, and improving the efficacy of certain chemotherapy drugs. These results are promising and will pave the way for the clinical trials that are needed to confirm these results in vivo.^[16]

Many other uses for ecdysteroids have been proposed, including respiratory disorders, renal failure, autoimmune disease, and sexual dysfunction.^[7] Research into these areas and others is ongoing, but currently the evidence to support these claims is minimal.

There is minimal research on the use of ecdysteroids in humans, so the dosing remains unclear. While no clear severe side effects have been demonstrated, the safety of these products is also uncertain. A study done in young men without known health conditions found that dosages up to 800 mg daily did not cause any notable damage to the liver or kidneys over a 10-week period.^[3] No adverse effects have been noted in studies done on other mammals, with doses up to 100 mg per kg of body weight producing no noted adverse effects in rabbits.^[7] Studies on other mammals do not always apply to humans, and more evidence is needed to confirm the safe dose for humans.

Another problem is that commercially available ecdysteroid products are not regulated. This means they may not contain what they claim to contain, or they may not contain the amount of the active substance stated on the label.^[17][18]

Ecdysteroids work in insects by binding to a receptor called the ecdysone nuclear receptor (EcR); however, no similar receptor has been found in mammals. In humans, the actions of ecdysteroids must therefore be through a different mechanism.^[3] Given the broad range of effects that ecdysteroids may have in mammals, more than one mechanism of action is possible.

Ecdysteroids may act through a G-protein coupled receptor (GPCR), a receptor found on cell membranes that plays a role in cellular signaling. Specifically, ecdysteroids might bind to GPCRs found in the renin-angiotensin system (RAS) — an important regulator of fluids, blood volume, and vasodilation that acts within the kidney. Ecdysteroids activate the MAS1 proto-oncogene (genes that regulate cell growth and differentiation) within this system, and this could enhance muscle protein synthesis.^[7][19]

Ecdysterone also causes an influx of calcium ions into the cells, which causes an increase in the phosphorylation of Akt. Akt is a protein kinase that mediates protein synthesis, so if ecdysterone increases its activity, then this could be the mechanism through which it enhances muscle growth.^[20]

Finally, a type of estrogen receptor called estrogen receptor beta (ERβ) might be responsible for the actions of ecdysteroids in humans. The activation of ERβ has been related to muscle protein synthesis, and ecdysteroids have been shown to activate this receptor.^[7]

The current data on how ecdysteroids work in mammals, and particularly in humans, is limited, and further research into the mechanisms of action is needed.