September 28, 2023

Ecdysterone 101:What is Ecdysterone and how does it work?

Ecdysteroids, a fascinating class of compounds with potential for muscle-building benefits, have recently attracted attention in the world of sports and fitness. Beta-ecdysterone, a natural compound related to insect growth hormones, is found in plants and is thought to interact with various receptors in our bodies, with potential benefits including increased muscle growth, adaptability and protein synthesis. But how do these compounds work and what are the potential benefits and side effects. In this comprehensive review we will delve deeper into the world of Ecdysteroids, exploring their mechanisms, potential benefits and important considerations when using them as a supplement. Although Ecdysteroids appear to show promise in improving muscle growth and performance, they remain the subject of ongoing research and intrigue, calling for a deeper understanding of their true potential..

1. What are Ecdysteroids?

Beta-ecdysterone, also known as a phytoecdysteroid, is a natural compound found in plants, similar to insect growth hormones [1]. While the idea of insect hormones or plant ketosteroids may sound strange, it is not as alarming as it seems. In insects containing these compounds, they have specific receptors called Ecdysteroid receptors that respond to them [2]. So, while it may seem a bit unusual to consume or inject these compounds, there is more to the story.

Ecdysteroids have also been discovered in mammals, although we are not entirely sure how they get into our tissues. It is hypothesized that they could come from our diet, gut bacteria or perhaps even specific infections [3]. How our bodies process these new compounds remains a matter of debate, but recent research is beginning to shed some light on the mechanisms involved. There is growing evidence that Ecdysteroids can activate receptors in our body, with desired effects such as increased muscle growth, adaptability and protein synthesis [4,5].

Additionally, there is interesting research suggesting that people who regularly consume spinach or quinoa, or otherwise regularly take Ecdysteroids, may live longer. This idea is supported by an experiment conducted by researchers at Rutgers University with the model organism Caenorhabditis elegans. In this study, nematodes exposed to a quinoa extract lived longer, indicating possible longevity benefits associated with Ecdysteroid use [6].

2. How do Ecdysteroids work??

Let us understand how Ecdysteroids work in simpler terms:

Estrogen Receptor Beta (ERβ): Some researchers suggest that Ecdysteroids may work by interacting with a receptor in our body called ERβ. This receptor is known for promoting skeletal muscle growth when stimulated [7]. So, it is possible that Ecdysteroids cause muscle growth by activating ERβ.

β2-Adrenergic receptor: Another theory is that Ecdysteroids may affect another receptor, the β2-adrenergic receptor. This receptor can also lead to muscle growth when activated, as seen with a compound called Clenbuterol [8]. Some studies found similarities in the structure of Ecdysteroids and this receptor, suggesting that they may "fit" together [9].

Coupled receptors for G proteins (GPCRs): Recent research has raised the possibility that Ecdysteroids may interact with GPCRs, a group of receptors that play various roles in the body. One study tested the ability of Ecdysteroids to bind to the β2-adrenergic receptor and found no significant connection [10]. Instead, it was proposed that another GPCR could be responsible for the anabolic effects seen with Ecdysteroids. This study also indicated that the AKT pathway, which is involved in protein synthesis, could be activated by Ecdysteroids, leading to muscle growth.

MAS receptor: Another study suggested that ERβ may not be the only player in the process and could interact with a GPCR called the MAS receptor [11]. They discovered that the AKT pathway, which is linked to protein synthesis, could be activated via the MAS receptor. Furthermore, there is evidence that the AKT pathway and ERβ can influence each other [1 2].

In summary, although the exact mechanism is not yet fully understood, it appears that Ecdysteroids may act by interacting with receptors such as ERβ, β2-adrenergic receptors and possibly GPCRs such as the MAS receptor. These interactions can activate pathways such as AKT, leading to increased protein synthesis and muscle growth. Importantly, Ecdysteroids do not appear to affect the androgen receptor [9,10,11], which is responsible for some of the unwanted side effects commonly associated with anabolic substances.

3. What are the benefits of Ecdysteroids?

Ecdysteroids are believed to provide several benefits, mainly based on research conducted in Eastern countries. However, the reliability and methods of these studies have raised doubts. Although we will not go into detail about these studies, it is worth acknowledging their existence as they have sparked interest in further research into Ecdysteroids.

Please note that these studies should be treated with caution due to potential limitations.

3.1. Anabolic effects

One of the most talked about effects of Ecdysteroids is their potential to promote muscle growth and improve strength in animals [10,13,14,15,16,17,23]. It is notable that most of these studies have been conducted in animals, not humans. However, there is a study where strength-trained individuals took Ecdysterone from spinach extract at doses of 200 mg and 800 mg per day for 10 weeks, which produced significant muscle growth and strength gains, with the group taking 800 mg having the most impressive results [18]. They gained an average of 3.2 kg of muscle mass compared to the control group. In contrast, another study with 20-hydroxyecdysterone at a dosage of 200 mg for 8 weeks showed no significant differences in strength parameters compared to the control group [19].

The reasons for such divergent results between studies remain unclear. Factors such as product quality and underdosing [20] or differences in how Ecdysteroids affect humans compared to rodents and other animals may play a role.

3.2. Strength and endurance

In the same previously mentioned studies, force measurements were also carried out. The study with 20-hydroxyecdysterone showed no improvement in strength parameters, while the study with spinach extract 800 mg per day for 10 weeks showed remarkable results. The group taking 800 mg increased their squat strength by almost 20% and bench press by 10%. These conflicting results raise questions about the reliability of Ecdysteroids' effects on human strength [18,19].

Although there are several rodent studies indicating dose-dependent increases in strength and endurance with Ecdysteroid supplementation, applying these findings directly to humans can be challenging. More clinical data specific to humans are needed to draw more definitive conclusions.

3.3. Adaptogenic effects

Among the studies conducted by Eastern researchers, adaptogenic benefits of Ecdysteroids are reported, linked to their potential to improve resistance to stress. Unfortunately, this area has not been explored much and detailed research into the benefits of Ecdysteroids for stress resistance is still lacking. Hypotheses exist, but solid scientific evidence is needed to confirm these effects.

4. Dosage of ecdysterone

Regarding Ecdysteroids and their dosages, available data offer a wide range of recommended intakes, ranging from 50 mg to 800 mg per day. It appears that the effects of Ecdysteroids depend on the dose taken, but due to limited research, determining an exact, definitively effective dose remains challenging.

However, it is important to note that there is a major concern in the world of Ecdysterone supplements: almost all of these products are under-dosed. Research [20, 21] has shed light on this, with a recent analysis of 14 Ecdysterone products yielding some worrying findings:

Of these 14 Ecdysterone products analyzed, as many as 13 were found to be under-dosed. This disturbing statistic represents approximately 9 percent of products tested.

What's even more striking is that only 3 out of 14 Ecdysterone supplements contain a sufficient amount of Ecdysterone to potentially exert an anabolic effect. This means that only 21 percent of the products tested can provide the desired benefits of Ecdysterone supplementation.

There is also another study [21] which focuses on the development and optimization of an analytical procedure to quantitatively determine the presence of ecdysterone in commercially available nutritional supplements. Ecdysterone is a naturally occurring compound found in plants and invertebrates that has received attention for its possible anabolic effects.

The research involves extracting ecdysterone from these supplements and using an optimized UHPLC-MS/MS method for analysis. The mass spectrometer operates in positive ionization mode (ESI+), with dynamic multiple reaction monitoring (dMRM) to detect ecdysterone. An internal reference, cortisol, is also used for the analysis.

The study validates this method according to ICH guidelines to ensure accuracy and precision. It is crucial to note that this study concerns the accuracy of dietary supplement labeling regarding their ecdysterone content.

The findings reveal that many dietary supplements claiming to contain ecdysterone do not meet expected quality and safety standards. In most cases, the actual ecdysterone content is significantly lower than what is stated on the product label, raising questions about the integrity and reliability of the product.

This research highlights the importance of accurate labeling and quality control in the dietary supplement industry, especially when it comes to products promoted for their potential performance-enhancing effects.

Financial support for the study is recognized by the World Anti-Doping Agency (WADA), highlighting the importance of this research in the context of doping control and athlete safety.

In summary, although Ecdysteroids appear promising in the areas of muscle growth and strength enhancement, the problem of underdosing in supplements highlights the importance of careful product selection and the need for more extensive research to establish accurate and effective dosage recommendations.

5. Side Effects of Ecdysterone

Research suggests that Ecdysteroids are well tolerated in animals, with no signs of toxicity observed even at high doses, up to 20 mg per kg [22]. Fortunately, one of the human studies we discussed earlier conducted thorough blood tests on participants. They administered doses up to 10 mg per kg and found no notable differences in the subjects' health indicators before and after supplementation [18].

In simpler terms, Ecdysteroids appear to be safe based on animal studies, and human studies have shown no adverse health effects when used within a certain dosage range. However, it is crucial to note that further research is needed to thoroughly understand the safety profile of Ecdysteroids in humans.

6. Can you stack ecdysterone with other (natural) supplements??

Ecdysterone and Creatine:

Combined benefits: Ecdysterone and creatine serve different roles in improving muscle growth and performance. Ecdysterone supports protein synthesis, while creatine increases ATP production, which helps with strength and power during workouts.

Synergy potential: These supplements have potential synergistic effects due to their different mechanisms. Ecdysterone can support muscle building processes, while creatine improves training performance.

Recommended combination: Taking ecdysterone with creatine may be beneficial. Consider ecdysterone as part of your daily routine and use creatine before or after training to maximize the effects during training.

Ecdysterone and Tongkat Ali:

Combined benefits: Ecdysterone and tongkat ali have potentially complementary effects on aspects such as muscle growth and libido. Ecdysterone can support muscle development, while tongkat ali is often used to improve vitality and hormonal balance.

Synergy potential: There could be a synergy between these two products, as Tongkat Ali may have an anti-estrogenic effect and beta-ecdysterone may promote positive estrogen signaling (Estrogen receptor beta).

Recommended combination: Consider taking ecdysterone and tongkat ali at different times of the day as they may interfere with each other's mechanisms of action. For example, you can take tongkat ali in the morning and ecdysterone later in the evening.

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7. What should you pay attention to when buying Ecdysterone?

When purchasing ecdysterone supplements, it is crucial to be vigilant due to possible incorrect labeling and low quality on the market. Here's what to look out for:

Quality and Purity: Be careful with products that claim high percentages of ecdysterone, such as 98%, as these claims may not always be accurate. Ecdysterone is indeed a costly ingredient, and some unreliable suppliers may cut corners. Choose brands that are transparent about their sources and testing methods.

Correct Test Method: The test method is important. UV/Vis testing can sometimes lead to inaccurate results by identifying similar compounds to ecdysterone (other ecdysteroids).

High Performance Liquid Chromatography (HPLC) is a more accurate testing method that specifically identifies ecdysterone and ensures the quality and potency of the supplement.

List of ingredients: Check the supplement's ingredient list to ensure it contains ecdysterone as the primary active ingredient. Avoid supplements with undisclosed, proprietary blends or that are not standardized to a percentage of beta-ecdysterone, as they may not provide transparent information about their contents.

Transparency: Choose brands that provide detailed information about their sources, manufacturing process and testing procedures. Transparent companies are likely to be more focused on quality and safety. Certifications: Some supplements may contain third-party certifications and laboratory testing. Make sure that the laboratory where the sample is taken is ISO certified.

Price: While price should not be the sole determining factor, extremely low prices can indicate a lower quality product. Quality supplements usually cost more due to purity and active ingredient content.

Dosage: Consider the dosage and recommended intake of the supplement. Dosages that are too low may be ineffective, and doses that are too high may incur unnecessary costs.

Reviews and Feedback: Look for reviews and feedback from other users to see if the product has been effective for others. As a general guideline, it is advisable to purchase Ecdysterone supplements from reputable brands that provide transparent information about their products. It is also a good idea to check the product for independent lab testing or certifications to verify purity and potency.

Conclusion

Ecdysteroids, specifically beta-ecdysterone, are an interesting class of compounds that may provide benefits for muscle growth, strength and adaptability. Animal research and limited human studies suggest that Ecdysteroids may have anabolic effects and are well tolerated without serious side effects.

Despite the promising nature of Ecdysteroids, more thorough and extensive research is needed to confirm their effectiveness in humans, determine optimal dosages, and fully understand any potential side effects. The problem of underdosing supplements also highlights the need to carefully select and purchase from reliable sources.

If you are considering using Ecdysteroids as a supplement, it is recommended that you do so under the supervision of a doctor or nutritionist, especially if you have underlying health conditions or are taking other medications. It is also important to choose the right dosages and quality sources.

In summary, research into Ecdysteroids is still in the early stages, and while the potential benefits are promising, more work is needed to understand and utilize their full range. For now, caution and judicious use are advised when considering Ecdysteroids as a supplement for athletic performance or general health.

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References

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