Robert Schinetsky

Ecdysterone (20-hydroxyecdysone) is a natural compound found in plants and arthropods, where it serves as a primary steroid hormone. Ecdysterone belongs to a class of compounds called ecdysteroids, which affect a wide range of biological processes, including:

• Bone growth
• Reproduction
• Host defense against predation

While ecdysterone is prized for its potential muscle-building benefits, which we’ve covered several times previously, recently published research continues to unearth some lesser-known, yet equally alluring activities.

Today, we highlight some of the newest findings concerning this potent phytosteroid!

Recent Ecdysterone Research

Ecdysterone + HIIT = Healthier Brain

Ecdysterone is typically heralded in sports nutrition for its potential anabolic and sports-performance benefits. This is due to animal and human data showing ecdysterone supplementation increases protein synthesis, physical endurance, and muscle growth.[1,2,3]

As it turns out, ecdysterone also exhibits antioxidative and neuroprotective effects.[4]

Two recently published studies appearing in the journal Neurochemical Research as well as Physiology & Behavior, found that ecdysterone, in combination with high-intensity interval training (HIIT), led to improvements in amyloid-beta (Aβ)-induced alzheimer’s disease in rats.[4,6]

Amyloid-beta protein is the the key diagnostic criteria of Alzheimer’s disease. Together with tau (τ) protein, they are responsible for much of the neurodegeneration that takes place.

However, these phenomena begin with, and are fueled by, oxidative stress (the imbalance between antioxidants and oxidants). This imbalance develops as a result of increased free radicals or decreased antioxidant defense.

As we just mentioned, ecdysterone demonstrates antioxidative effects, making it a potential option for those looking to improve antioxidant defense.

The new pair of studies examined the beneficial effects of HIIT alone or HIIT + ecdysterone supplementation on rats with Alzheimer’s disease. Previously, moderate intensity cardio as well as high-intensity interval training has emerged recently as a viable option for improving cognitive function and memory[5], with greater improvements in memory function being noted in elderly adults engaging in HIIT.

In this study, adult male rats were treated simultaneously with HIIT exercise and ecdysterone (10 mg/kg/day), beginning 10 days after Aβ-injection, and they continued on this regimen for eight consecutive weeks.[4,6]

Researchers noted that Aβ-injection resulted in impaired learning and memory performances in both novel object recognition and Barnes maze tests as well as greater anxiety-like behavior, increased oxidative stress as evidenced by decreased total antioxidant capacity content, lower glutathione peroxidase enzyme activity, increased total oxidant status, and neuronal loss.[4,6]

Both the HIIT only group as well as the HIIT + ecdysterone group were both effective at improving deficits induced by Aβ-injection. Ecdysterone, by itself, improved spatial/passive avoidance learning and memory impairments, recovered hippocampal activity of superoxide dismutase (SOD), glutathione reductase (GRx), and prevented the hippocampal neuronal loss.

However, the combination of HIIT + ecdysterone proved to be the most effective, resulting in a “more complete and powerful improvement in all the above-mentioned Aβ-related deficits.” The researchers noted that the added benefit of adding ecdysterone to HIIT may due to the phytosteroid’s ability to improve oxidative status in the hippocampus as well as prevent neuronal loss.[4]

Ecdysterone Aids Blood Flow

Anabolic steroids have long been used by athletes to build muscle, accelerate recovery, and improve performance. However, continued use of these pharmaceuticals can suppress luteinizing hormone production as well as decrease the number of cells that produce testosterone.

As a plant steroid that has been found to enhance sports performance and muscle growth, ecdysterone is being utilized more and more by athletes. The question is, being that ecdysterone is a plant steroid, could its use lead to the same deleterious consequences as designer steroids?

Appearing in Future Science OA, groundbreaking research showed for the first time the effects of short-term ecdysterone supplementation (3 days) on progesterone levels in mice and how this might affect the arteries that carry blood to the muscles.[7]

A small, but statistically insignificant, increase in plasma progesterone was noted. Researchers did find that CYP17A1 (the gene which produces the enzyme that breaks progesterone down was considerably decreased.[7]

The reason this is noteworthy is that elevated levels of progesterone were able to dilate both muscle and mesenteric arterioles, as well as enhancing the vasodilatory effect of ecdysterone in these arterioles.[7] Researchers concluded that both of these activities may have the potential to increase muscle blood flow and sports performance.

Ecdysterone Enhances Bone Formation

The final study to recap today comes from Frontiers in Cell and Developmental Biology.[8]

In it, researchers were investigating the potential bone regeneration activities of ecdysterone in vivo and in vitro.

Previous in vivo studies have found that β-ecdysterone can regulate the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by targeting estrogen receptors, thus playing an important role in the process of bone regeneration. Note: BMSCs are cells that possess the ability to differentiate into bone, cartilage, fat, nerves, or myoblasts (muscle cells).

The present study found that β-ecdysterone is a novel bone regeneration regulator that can stimulate MC3T3-E1 cell proliferation and induce bone regeneration through the BMP-2/Smad/Runx2/Osterix pathway. FYI, BMP2 is one of the primary transcription factors involved in bone formation.

Ecdysterone research may have shown osteogenic differentiation of BMSCs by activating estrogen receptors in vivo. Previous research indicates that ecdysterone promotes lean mass gains via estrogen receptor-beta (ERβ) activation.[9]

Concluding their findings, the researchers stated: 

“β-ecdysterone can be used as a safe and effective agent for bone regeneration to resolve insufficient bone regeneration and severe osteoporosis caused by decreased osteogenic capacity.”[8]

What About Turkesterone?

There’s been quite a lot of hype surrounding turkesterone the past couple of years, and we’ve discussed it previously in the AML articles section. Turkesterone is a metabolite of ecdysterone that gained attention due to some research noting that it possessed greater anabolic effect than methandienone.[10]

However, animal and cell studies do not translate on a 1:1 basis (or anywhere remotely close to that) in humans.

Furthermore, whereas ecdysterone continues to have new research published investigating its myriad effects and potential therapeutic applications, there’s a dearth of new science concerning turkesterone. The latest slate of scientific findings only add to the impressive list of beneficial activities of ecdysterone.

Ecdysterone Research: To recap, ecdysterone has been found to:

• Support lean mass gains
• Aid exercise performance
• Help reduce inflammation
• Improve glucose tolerance
• Exert anti-obesity effects
• Enhance blood flow
• Offer neuroprotection
• Bolster antioxidant defense
• Support bone formation

Perhaps most importantly, ecdysterone has been studied in healthy humans and shown to be effective (and SAFE) when taken orally and used in combination with resistance training.

More on Ecdysterone supplements here.

^{©Published by Advanced Research Media, Inc. 2022}

^{©Reprinted with permission from Advanced Research Media, Inc.}

References

1. Cheremnykh NS, Shimanovskii NL, Shutko GV, Syrov VN. The action of methandrostenolone and ecdysterone on the physical endurance of animals and on protein metabolism in the skeletal muscles. Farmakol Toksikol. 1988;51(6):57–60.
2. Parr MK, Botrè F, Naß A, Hengevoss J, Diel P, Wolber G. Ecdysteroids: A novel class of anabolic agents?. Biol Sport. 2015;32(2):169– doi:10.5604/20831862.1144420
3. Isenmann, E., Ambrosio, G., Joseph, J.F. et al. Ecdysteroids as non-conventional anabolic agent: performance enhancement by ecdysterone supplementation in humans. Arch Toxicol 93, 1807–1816 (2019). https://doi.org/10.1007/s00204-019-02490-x
4. Gholipour, P., Komaki, A., Parsa, H. et al. Therapeutic Effects of High-Intensity Interval Training Exercise Alone and Its Combination with Ecdysterone Against Amyloid Beta-Induced Rat Model of Alzheimer’s Disease: A Behavioral, Biochemical, and Histological Study. Neurochem Res 47, 2090–2108 (2022). https://doi.org/10.1007/s11064-022-03603-2
5. Ana Kovacevic, Barbara Fenesi, Emily Paolucci, and Jennifer J. Heisz. The effects of aerobic exercise intensity on memory in older adults. Applied Physiology, Nutrition, and Metabolism. 45(6): 591-600. https://doi.org/10.1139/apnm-2019-0495
6. Gholipour P, Komaki A, Ramezani M, Parsa H. Effects of the combination of high-intensity interval training and Ecdysterone on learning and memory abilities, antioxidant enzyme activities, and neuronal population in an Amyloid-beta-induced rat model of Alzheimer's disease. Physiol Behav. 2022 Jul 1;251:113817. doi: 10.1016/j.physbeh.2022.113817. Epub 2022 Apr 17. PMID: 35443198.
7. Aljaber MY, Orie NN, Raees A, Kraiem S, Al-Jaber M, Samsam W, Hamza MM, Abraham D, Kneteman NM, Beotra A, Mohamed-Ali V, Almaadheed M. Downregulation of CYP17A1 by 20-hydroxyecdysone: plasma progesterone and its vasodilatory properties. Future Sci OA. 2022 Jul 7;8(6):FSO805. doi: 10.2144/fsoa-2022-0006. PMID: 35909994; PMCID: PMC9327640.
8. Yan CP, Wang XK, Jiang K, Yin C, Xiang C, Wang Y, Pu C, Chen L, Li YL. β-Ecdysterone Enhanced Bone Regeneration Through the BMP-2/SMAD/RUNX2/Osterix Signaling Pathway. Front Cell Dev Biol. 2022 May 20;10:883228. doi: 10.3389/fcell.2022.883228. PMID: 35669516; PMCID: PMC9164109.
9. Parr MK, Zhao P, Haupt O, Ngueu ST, Hengevoss J, Fritzemeier KH, Piechotta M, Schlörer N, Muhn P, Zheng WY, Xie MY, Diel P. Estrogen receptor beta is involved in skeletal muscle hypertrophy induced by the phytoecdysteroid ecdysterone. Mol Nutr Food Res. 2014;58:1861–1872
10. Syrov, V. N. (2000). Comparative experimental investigation of the anabolic activity of phytoecdysteroids and steranabols. Pharmaceutical Chemistry Journal, 34(4), 193– doi:10.1007/bf02524596