Ecdysteroids are naturally occurring compounds popular in the supplement market due to claims of promoting muscle growth and enhancing athletic performance. Substances like ecdysterone (20-hydroxyecdysone) are marketed as “natural anabolic agents” that offer the benefits of performance-enhancing steroids without the associated androgenic side effects. Given these potent claims, it is necessary to examine the current scientific evidence to determine the safety profile and potential risks associated with their consumption. This article reviews the available data to provide an objective assessment of ecdysteroid safety.
Understanding Ecdysteroids
Ecdysteroids are polyhydroxylated steroids found naturally in insects, certain fungi, and various plants, where they are classified as phytoecdysteroids. In insects, they function as molting and growth hormones, but their role in mammals is distinct and less understood. The most common ecdysteroid used in supplements is ecdysterone, often extracted from plants like spinach or the Cyanotis arachnoidea root.
These compounds are chemically similar to human steroid hormones but do not bind to the androgen receptor, which causes the harmful side effects associated with synthetic anabolic steroids. The proposed mechanism for their muscle-building effect involves activating the estrogen receptor-beta (ER-beta) in skeletal muscle cells. This interaction is believed to stimulate cellular pathways, such as the PI3K/Akt signaling pathway, leading to increased protein synthesis and muscle hypertrophy.
The levels of ecdysteroids found in a typical Western diet are extremely low, often less than one milligram per day, even when consuming vegetables like spinach. However, the doses used in human studies and by bodybuilders are significantly higher, sometimes reaching 1,000 milligrams per day. This vast difference between dietary intake and supplemental use necessitates a thorough safety investigation of these concentrated compounds.
Documented Adverse Effects
In short-term human clinical trials, ecdysterone has demonstrated a favorable safety profile compared to prohibited anabolic agents. A 10-week study in young men found that daily supplementation did not result in significant increases in biomarkers for liver or kidney toxicity. Participants in these controlled settings also did not report typical hormonal side effects, such as changes in libido or mood, often seen with traditional steroids.
The most frequently reported adverse effect is mild gastrointestinal distress, including nausea or an upset stomach. This reaction is usually transient and dose-dependent, often resolving as the body adjusts to the supplement. However, the long-term safety of ecdysteroid supplementation remains undetermined due to the limited duration of current human studies.
A significant concern arises from mechanistic animal research suggesting potential kidney damage over time. One study in mice indicated that ecdysterone caused kidney enlargement and early signs of chronic kidney injury, such as albuminuria. This harmful effect was attributed to ecdysterone’s ability to activate the mineralocorticoid receptor (MR). MR activation is similar to the hormone aldosterone, which regulates fluid balance and blood pressure. These findings suggest that individuals with pre-existing renal conditions or those using high doses could risk adverse effects mediated by this mineralocorticoid-like activity.
The Regulatory Landscape
Ecdysteroids are currently classified as dietary ingredients by the U.S. Food and Drug Administration (FDA). This means they are not subject to the rigorous pre-market approval process required for pharmaceutical drugs. This regulatory status places the burden of ensuring safety and effectiveness primarily on the supplement manufacturers. Consequently, there is an inherent risk of poor quality control, mislabeling, and contamination within the supplement market.
Independent testing frequently reveals that the actual amount of ecdysterone in commercial products is far lower than the quantity declared on the label, or that the product is contaminated. This lack of purity and standardization means consumers may not be taking the intended substance or dose, introducing unpredictable safety risks. Contamination with undisclosed and prohibited substances, including actual anabolic steroids, is a serious concern for athletes.
The World Anti-Doping Agency (WADA) added ecdysterone to its Monitoring List in 2020 due to its demonstrated anabolic potency. This action signifies that the substance is being closely tracked to determine if it should be moved to the Prohibited List. A human study showing ecdysterone increased muscle mass and performance more effectively than a placebo led researchers to recommend its inclusion in the prohibited class of “other anabolic agents.” For competitive athletes, this WADA monitoring status represents a significant regulatory hazard, as prohibition could occur at any time.
Safety in Specific Populations
For certain demographic groups, the use of ecdysteroids carries a higher degree of uncertainty, and caution is strongly advised. There is a complete absence of reliable scientific data regarding the safety of ecdysteroids for pregnant or breastfeeding individuals. Since the compounds interact with steroid hormone receptors, the recommendation is to avoid use during pregnancy and lactation to prevent potential developmental risks.
Children and adolescents should also refrain from using ecdysteroids. Since their bodies are undergoing complex hormonal changes and growth spurts, introducing an exogenous compound that interacts with ER-beta pathways could interfere with normal development. The long-term effects of such interference on growth plates or endocrine function are entirely unknown.
Individuals with pre-existing medical conditions, particularly those involving the liver, kidneys, or hormonal systems, should exercise extreme prudence. The animal data suggesting a mineralocorticoid-like activity means people with hypertension, heart failure, or kidney disease should avoid the supplement entirely, as it could exacerbate their condition. Consulting a healthcare professional is necessary before beginning any ecdysteroid regimen.