Turkesterone is a type of Ecdysteroid, a steroid hormone found in insects and other animals such as crabs. Certain plants also contain these compounds, and are known as phytoecdysteroids (phyto to denote plant life).

The role of Ecdysteroids in plants is part of their defence mechanism, to deter predators, giving them the title of a phytoalexin. In insects they are androgenic substances needed to regulate key processes in the insect’s development, including moulting, metamorphosis and reproduction. In a way, you could say this is how the insects LVLUP.

The word Ecdysteroid is a combination of the words Ecdy and Steroid. Ecdy comes from the word Ecdysis, the process of molting in insects. Steroid to denote that the compound has a sterone backbone as part of its chemical composition, making it a (you guessed it) steroid. In fact, Ecdysteroids are often referred to as testosterone-like compounds due to the structural similarities with testosterone.

Approximately 6% of plants contain Ecdysteroids, though not at levels sufficient enough to lead to a noticeable effect. Some of the plants with the highest levels include;

• Spinach
• Quinoa
• White button mushrooms
• Yams
• Ajuga Turkestanica

As you may have guessed from the name similarities, Turkesterone is extracted from the Ajuga Turkestanica plant (and others), also known as Bugleweed, Ground Pine or Carpet Bugle. Ajuga, is in the Lamiaceae (mint) family and native to the mountainous areas of Uzbekistan. As you can see from the photo below, it produces light purple flowers. Traditional herbalists would use Ajuga as an overall tonic and liver protecting herb.

Interestingly, Ecdysteroids have also been found in mammals, though it is unclear where they come from.  It is speculated that it may be through diet, intestinal bacteria or potentially pathogenic microorganisms (R).

There is ample evidence to show that Ecdysteroids, including Turkesterone, can agonise (turn on) certain receptors in mammals, including humans.  While they don’t have identical effects in humans and insects (no, you won’t be moulting), there are some similarities.  Ecdysteroids can promote anabolism (muscle growth), increase protein synthesis, improve metabolic function and more.  Some researchers even go so far as to say ‘one of the most interesting properties of Ecdysteroids in mammals is their anabolic effect, behaving similar to anabolic steroids putatively without the androgenic effect’ (link – more on this below. Section 3.1) (">).

There have been many studies performed on Ecdysteroids. Many of these look exclusively at the common Ecdysteroids, including Ecdysterone, 20-Hydroxyecdysone and Turkesterone, while others compare multiple Ecdysteroids.

Whilst Turkesterone has recently seen some popularity as a potential performance and muscle building aid, there are many other studied benefits of Turkesterone and the Ecdysteroids, including immune function, improved metabolism, stress tolerance and more.

Unfortunately, not all the benefits of Ecdysteroids have been studied specifically regarding Turkesterone, and in those instances, this guide will refer to the research on other Ecdysteroids.

Hold on to your hats, we’re about to get a bit technical.

Many herbs, supplements and even anabolic-androgenic-steroids contribute to muscle growth via their effect on androgens and/or androgen receptors. Androgens, such as Testosterone and Dihydrotestosterone (DHT), are the group of hormones that contribute to reproduction in males, muscle growth and repair among other male characteristics. Now, even though we associate Testosterone with men, both men and women have circulating androgens and androgen receptors.

Turkesterone and Ecdysteroids for muscle building and performance

Now, we might think that Turkesterone and the Ecdysteroids act just like testosterone in the human body, attaching to the androgen receptors and exerting their muscle building effects that way. Especially considering that they’re androgenic in insects. But that is not actually true.

Turkesterone and the other Ecdysteroids have many mechanisms by which they can improve our exercise performance, muscle gain and recovery.

These include;

• Stimulating the Estrogen Beta Receptor
• Increasing IGF-1
• AKT pathway activation
• Enhanced protein synthesis
• Decreasing myostatin
• Improving blood flow
• Acting as an adaptogen and modulating our stress response
• Improving bone and joint health

Let’s delve into them now.

Turkesterone stimulates the Estrogen Beta Receptor

Part of how Turkesterone improves muscle building is via agonising (stimulating) the Estrogen Beta Receptor (ERβ). The great news about this is that it DOESN’T interact with any of the androgen receptors. Yes, you read that right, that is the good news.

Estrogen and Androgen receptors

Our cells have receptors for many different compounds. When a compound binds to the correct receptor, the nucleus of our cell tells our cells to perform certain functions.

Androgenic compounds such as Testosterone and DHT exert their effects on the body by agonising (you guessed it) the androgen receptor. Compounds such as Estrone & Estradiol agonise the Estrogen receptors.

Both men and women have androgen and estrogen receptors on cells throughout the body, with men in general having more receptors for androgens and women estrogens.

When it comes to muscle building and performance there are many compounds that act on the androgen receptor, either by increasing the amount of receptors we have available, by binding to them directly or by increasing production of our internal androgens that will bind to them. Eventually there will come a point of diminishing returns, where you simply cannot get much more effect from stimulating androgen receptors further.

This is just one part of what makes Turkesterone such a great supplement to add to your arsenal. By stimulating the ERβ it means we are improving performance through an entirely different vector. We can still use our supplements, herbs and ‘gear’ to enhance muscle gain through their effect on the androgen receptors AND simultaneously use compounds like Turkesterone to upregulate the ERβ and contribute to muscle gain through another pathway. In fact a study on Mice below found that stimulating the ERβ and Androgen receptors simultaneously led to a greater effect than either one alone (Link to that part of the article- find what section it is mentioned in. Heading titled ‘How does stimulating the ERB contribute to muscle growth?’) (R). This is known as an additive effect.

What is the difference between the ERα and ERβ?

While we may think that stimulating any Estrogen receptor will lead to all the effects we typically associate with high Estrogen, such as water retention, gynecomastia, abdominal weight gain and lethargy, we must realise there is some nuance. The Estrogen Alpha and Beta receptors act in quite different ways.

The Alpha receptors are most prominent in mammary glands (breast tissue) and the uterus, while the Beta receptors have a bigger role in the nervous and immune system.  Stimulating the ERα is most commonly associated with hyperproliferation of breast and uterine tissue as we would see in cancerous states while stimulating the ERβ is able to counteract the hyperproliferation.  Both types of receptors play a role in muscle building. (R)

How does stimulating the ERB contribute to muscle growth?

 

Mice studies of both females and males have demonstrated the role of ERβ in muscle growth and regeneration. When mice are engineered to not have ERβ they have substantially less muscle regeneration following muscle injury.  This is seen alongside a decrease in proliferation and increased cell death (apoptosis) of satellite cells.  In the healthy control mice, after muscle injury the satellite cells proliferate and fuse together, making new muscle fibres (R).

The mice without the ERβ had significantly less muscle mass compared to healthy controls. The results of this study show that Estrogens have a key role in female muscle regeneration through the ERβ (R).

Another study looked at the effect of ERβ on male mice. They found that the ERβ also plays a role in muscle building in male mice. The mice had low Testosterone, were given compounds that blocked androgen receptors and then given compounds which stimulated the ERβ.  This was to reduce the effects of androgens on muscle building and better understand how important the ERβ is.  It was found that even WITHOUT the androgen receptors being stimulated, the stimulation of the ERβ was able to contribute to muscle growth (R).

This same study also compared the combined effect of ERβ stimulation and exogenous testosterone (via giving the rats Anabolic Androgenic Steroids) vs exogenous testosterone alone and ERβ stimulation alone. As would be expected the combined effect led to more muscle growth than either Testosterone or ERβ alone. Showing that there can be an additive effect of stimulating both the ERβ and Androgen receptors simultaneously.  This gives credence to the idea that Turkesterone can be stacked with compounds that target androgen receptors (R).

The same study found that ERβ and not ERα plays a role in muscle injury and regeneration via its effect on modulating inflammation, by reducing inflammation after muscle injury to promote regeneration much more rapidly (R). 

ERβ agonism is also shown to increase levels of insulin-like growth factor (IGF-1), leading to increased muscle protein synthesis and satellite cell proliferation and activation (more on this below – link to it. Section 3.2).

Will Turkesterone give me symptoms of Estrogen dominance?

It’s a logical question to ask.  Given Turkesterone interacts with the ERβ would it lead to symptoms of Estrogen dominance such as increased water weight, gynecomastia, abdominal weight gain and more?

As stated above, it is the ERα that is most associated with the aforementioned estrogenic effects. Human and rat studies have found that Ecdysteroids actually lead to decreased blood levels of Estrogen (R, R, R). Additionally, Turkesterone does not aromatise into Estrogen like Testosterone does.

This is a key benefit of Turkesterone over anabolic steroids which can lead to effects of excess estrogen if not managed correctly. 

Will Turkesterone impact my prostate and testicles?

Given that some anabolic substances can increase the size of the prostate and decrease the size of the testicles it is a worthwhile question to ask.  Thankfully, many studies find no negative effect of Turkesterone on either of these organs, which is consistent with its lack of androgenicity. (R)

Insulin Like Growth Factor & IGF-1

In both human and mice studies (R), administration of Ecdysteroids leads to positive effects on IGF-1.  It has been shown that stimulating the ERβ can lead to increased levels of IGF-1, though it is unclear if there are other mechanisms that Turkesterone and the Ecdysteroids increase IGF-1 (R). 

How does IGF-1 help with performance?

IGF-1 is known as an anabolic hormone and it stimulates the growth of skeletal muscle, bone, cartilage, nerves, blood cells and other tissues in the body.  Our Pituitary Gland (in the brain) secretes growth hormone, which stimulates the liver to produce IGF-1 (approximately 75% of it). IGF-1 increases protein synthesis (more on this below – link to it. Section 3.4), to improve muscle growth. 

Low levels of IGF-1 and Growth Hormone are associated with

• Muscle loss
• Loss of neurons
• Thinner skin
• Reduced fertility and libido
• Stunted growth
• Much more

Having optimal levels of IGF-1 can help to increase lean muscle mass, while simultaneously decreasing fat mass. Beyond these effects, it is also able to improve insulin sensitivity, meaning increased performance and recovery whilst also lowering our risk of metabolic diseases (Link to that part of the article. Section 6.2).

AKT pathway activation

A cell study showed that the AKT pathway is likely responsible for part of the muscle building effects. It found that 20-hydroxyecdysone stimulated the AKT pathway, leading to increased muscle protein synthesis and that blocking this pathway delayed muscle protein synthesis.

Ecdysteroids cause Calcium to rapidly enter muscle cells, which leads to phosphorylation (turning on) of the AKT pathway, which then leads to protein synthesis and muscle building (R).  

Turkesterone enhances muscle protein synthesis

We’ve mentioned protein synthesis quite a few times now, so let’s explain what it does.

Via its effect on the ERβ, IGF-1 and AKT pathway, Turkesterone and the Ecdysteroids can stimulate muscle protein synthesis by up to 20%. (R)

What is muscle protein synthesis and why is it important?

Our muscle is made up of protein and muscle protein synthesis is the process whereby protein is produced to repair muscle damage, such as from training. The opposite is muscle protein breakdown, the process by which protein is lost from exercise. Muscle protein synthesis is crucial to building muscle. Higher muscle protein synthesis can increase muscle mass and speed up recovery times.

This process doesn’t just occur in muscle tissue. Protein synthesis occurs in all organs of the body.

When compared to other Ecdysteroids, Turkesterone was the most potent at enhancing muscle protein synthesis (R).

Turkesterone decreases Myostatin

Myostatin is a cytokine in the body that actually works to slow down muscle growth. Yes, slow it down. Curse you myostatin! Thus, lower levels of myostatin make it easier to build muscle and vice versa.

In fact, in rat studies where they decreased levels of myostatin the rats saw increases in overall mass, muscle mass, muscle size and strength (R). 

Thankfully, Turkesterone decreases levels of Myostatin.

In vitro cell studies, found that applying Ajuga turkestanica extract (the plant where Turkesterone is extracted from) to muscle cells led to a significant decrease in Myostatin levels, which would theoretically translate to increased muscle growth and strength (R).

For comparison, in the same study A. turkestanica was compared to the androgenic steroid Methandrostenolone (aka Dianabol or D-Bol).  Ajuga decreased myostatin levels more than twice as much as Dianabol (R)!

The same study found that ERβ and not ERα plays a role in muscle injury and regeneration via its effect on modulating inflammation, by reducing inflammation after muscle injury to promote regeneration much more rapidly (R). 

ERβ agonism is also shown to increase levels of insulin-like growth factor (IGF-1), leading to increased muscle protein synthesis and satellite cell proliferation and activation (more on this below – link to it. Section 3.2).

Will Turkesterone give me symptoms of Estrogen dominance?

It’s a logical question to ask.  Given Turkesterone interacts with the ERβ would it lead to symptoms of Estrogen dominance such as increased water weight, gynecomastia, abdominal weight gain and more?

As stated above, it is the ERα that is most associated with the aforementioned estrogenic effects. Human and rat studies have found that Ecdysteroids actually lead to decreased blood levels of Estrogen (R, R, R). Additionally, Turkesterone does not aromatise into Estrogen like Testosterone does.

This is a key benefit of Turkesterone over anabolic steroids which can lead to effects of excess estrogen if not managed correctly. 

Will Turkesterone impact my prostate and testicles?

Given that some anabolic substances can increase the size of the prostate and decrease the size of the testicles it is a worthwhile question to ask.  Thankfully, many studies find no negative effect of Turkesterone on either of these organs, which is consistent with its lack of androgenicity. (R)

Insulin Like Growth Factor & IGF-1

In both human and mice studies (R), administration of Ecdysteroids leads to positive effects on IGF-1.  It has been shown that stimulating the ERβ can lead to increased levels of IGF-1, though it is unclear if there are other mechanisms that Turkesterone and the Ecdysteroids increase IGF-1 (R). 

How does IGF-1 help with performance?

IGF-1 is known as an anabolic hormone and it stimulates the growth of skeletal muscle, bone, cartilage, nerves, blood cells and other tissues in the body.  Our Pituitary Gland (in the brain) secretes growth hormone, which stimulates the liver to produce IGF-1 (approximately 75% of it). IGF-1 increases protein synthesis (more on this below – link to it. Section 3.4), to improve muscle growth. 

Low levels of IGF-1 and Growth Hormone are associated with

• Muscle loss
• Loss of neurons
• Thinner skin
• Reduced fertility and libido
• Stunted growth
• Much more

Having optimal levels of IGF-1 can help to increase lean muscle mass, while simultaneously decreasing fat mass.  Beyond these effects, it is also able to improve insulin sensitivity, meaning increased performance and recovery whilst also lowering our risk of metabolic diseases (Link to that part of the article. Section 6.2).

AKT pathway activation

A cell study showed that the AKT pathway is likely responsible for part of the muscle building effects. It found that 20-hydroxyecdysone stimulated the AKT pathway, leading to increased muscle protein synthesis and that blocking this pathway delayed muscle protein synthesis.

Ecdysteroids cause Calcium to rapidly enter muscle cells, which leads to phosphorylation (turning on) of the AKT pathway, which then leads to protein synthesis and muscle building (R).  

Turkesterone enhances muscle protein synthesis

We’ve mentioned protein synthesis quite a few times now, so let’s explain what it does.

Via its effect on the ERβ, IGF-1 and AKT pathway, Turkesterone and the Ecdysteroids can stimulate muscle protein synthesis by up to 20%. (R)

What is muscle protein synthesis and why is it important?

Our muscle is made up of protein and muscle protein synthesis is the process whereby protein is produced to repair muscle damage, such as from training.  The opposite is muscle protein breakdown, the process by which protein is lost from exercise.  Muscle protein synthesis is crucial to building muscle. Higher muscle protein synthesis can increase muscle mass and speed up recovery times.

This process doesn’t just occur in muscle tissue. Protein synthesis occurs in all organs of the body.

When compared to other Ecdysteroids, Turkesterone was the most potent at enhancing muscle protein synthesis (R).

Turkesterone decreases Myostatin

Myostatin is a cytokine in the body that actually works to slow down muscle growth. Yes, slow it down. Curse you myostatin! Thus, lower levels of myostatin make it easier to build muscle and vice versa.

In fact, in rat studies where they decreased levels of myostatin the rats saw increases in overall mass, muscle mass, muscle size and strength (R). 

Thankfully, Turkesterone decreases levels of Myostatin.

In vitro cell studies, found that applying Ajuga turkestanica extract (the plant where Turkesterone is extracted from) to muscle cells led to a significant decrease in Myostatin levels, which would theoretically translate to increased muscle growth and strength (R).

For comparison, in the same study A. turkestanica was compared to the androgenic steroid Methandrostenolone (aka Dianabol or D-Bol).  Ajuga decreased myostatin levels more than twice as much as Dianabol (R)!

Turkesterone may improve blood flow

As mentioned above, the ERβ has many roles in the body beyond building and maintaining muscle. It also plays a role in the health and function of our blood vessels in both direct and indirect ways.

On the direct side of things, stimulating the ERβ increases the production of nitric oxide in the cells of our blood vessels (R, R, R).

What is Nitric Oxide and what does it do?

Nitric Oxide is a signalling molecule responsible for a multitude of tasks within the body.  Narrowing in on the performance and muscle building aspects, nitric oxide is responsible for widening blood vessels, allowing blood to flow around the body much easier.  This means better pumps in your workout and better performance. Additionally, you might also expect better recovery as better blood flow allows quicker removal of waste products like lactic acid and enhanced nutrient delivery to the cells damaged from a workout.

How else can the ERβ improve blood flow?

On the indirect side, ERβ plays a role in improving metabolic health.  Poor metabolic health can lead to increased inflammation and oxidative damage which, among other things, can damage blood vessels, making them less elastic and able to widen.  

Are there any studies on Turkesterone and blood flow?

A study on castrated rats looked at the effect of Turkesterone and other Ecdysteroids as a way to stimulate erythropoiesis (red blood cell production).  Turkesterone and the other Ecdysteroids increased the amount of red blood cells and hemoglobin, with Turkesterone being the most effective.  The researchers noted that Turkesterone resembled the activity of Nerobol (AKA Dianabol) for its ability to stimulate red blood cell production (R).

There appear to be no studies directly looking at the effect of Turkesterone or other Ecdysteroids on Nitric Oxide. However, we do know that Turkesterone strongly binds to the ERβ and that in blood vessels, ERβ plays a role in producing nitric oxide. So, at this stage, it appears that Turkesterone may improve nitric oxide levels.

Turkesterone is an Adaptogen

Adapta-what?

Adaptogens have been popularised more and more in the health and fitness industry in recent times. But just what are they and what do they do?

What is an Adaptogen?

The term Adaptogen was coined by Hans Selye in the 1940s. It refers to a class of herbs that makes the user more adaptable (who would have thought?) to physical and emotional stressors as well as their environment.

Adaptogens were said to act as whole body tonics, having widespread, multifaceted effects and bringing the body to a place of balance. For instance, if you were too low in one area, an adaptogen would boost you up and if you were too heightened in another, it would bring you down, closer to what is optimal.

In traditional herbalism, Adaptogens were used in times of exhaustion, stress, recovering from sickness as well as before and after intense exercise.

More recent research on Adaptogenic herbs has found that many of them exert their adaptogenic effect on the Hypothalamic-Pituitary-Adrenal axis (HPA-axis). However, Adaptogens have their nuances, with each affecting the body in a slightly different way. Some are more useful for stimulating while others for calming down. Some are better suited for those with lung issues, while others the kidneys.

So, in short, adaptogens help your body adapt to stress, in whatever form it presents themselves.

The Adaptogenic effects of Turkesterone

A mice study looked at the effects of Turkesterone and Ecdysterone on stress.  The mice were given a sustained stressor and given Turkesterone & Ecdysterone both before and after the stressor.  The authors of the study looked at the effects on the weight of the spleen, thymus gland and adrenal glands, the health of the gut lining/gastric mucosa and more (R).

When Turkesterone and Ecdysterone were given BEFORE the stressor, there was a beneficial effect on the size of the spleen, thymus glands and adrenal glands compared to control mice which had no Ecdysteroids.  There was also a noticeable decrease in the prevalence of bleeding ulcers in the gastric mucosa (R).

When a single dose of Turkesterone and Ecdysterone were given AFTER the stressor, the function of the immune system moved closer to normal much quicker than the control group.  When looking longer term, both the Turkesterone and Ecdysterone mice outperformed the control groups in regards to their normalisation on immune markers (R).

In another study on male rats, Ecdysterone was shown to decrease the stress hormone corticosterone. This is the primary adrenal corticosteroid in rodents, similar to human’s cortisol (R).

Why is it important to lower Cortisol for performance?

We tend to label things as good or bad. The stress hormone, Cortisol is one of those things we tend to label as bad. It is produced in the adrenal gland and is used to maintain blood pressure and blood sugar and to help us get away from or through life threatening situations.

Cortisol helped our ancestors survive acute, life-threatening situations by redirecting our body’s resources to where it was most important. And, in a life threatening situation, actions like digesting food and building muscle are not seen as important. In fact, during these instances, the release of cortisol is likely to break down muscle tissue to fuel our body. This is why Cortisol is known as a catabolic hormone.

In today’s day and age, we’re much less likely to be exposed to actual life threatening stressors, but rather, slow burning chronic stressors like jobs, bills and lockdowns. Our body is not adapted to handling these ongoing stressors. This chronic stress picture can lead to the excessive breakdown of muscle, making it harder to gain muscle even with training.

Perhaps a graphic here on the issues with Cortisol on performance

Excessive cortisol can increase fat gain

Via its interrelationship with insulin, cortisol can increase fat gain and/or make it more difficult to lose fat.  Cortisol decreases our cell’s sensitivity to insulin, known as a state of insulin resistance. This causes our pancreas to secrete more insulin to try and get sugars into the cells where they can be turned into energy. Insulin is a storage hormone and when it is too high it puts a break on fat burning and even promotes fat gain (R).

Lower stress for a happy, healthier and stronger life

We can see just how important it is to include some practices and have some supplements that can improve our stress response.

Anything we can do to lower stress to a healthy level is going to improve our ability to increase muscle and keep body fat low. Of course, it is by no means a be all and end all.

The benefits of improving stress tolerance go well beyond training and can benefit nearly every aspect of life.

Bone strength and Joint health

In a mouse study, supplementation with Beta-Ecdysterone was found to alleviate the symptoms of osteoporosis without side effects commonly seen in osteoporosis drugs.  It is believed to improve bone density via increasing levels of Runx2, osteocalcin and type I collagen expression (R).

A separate mouse study on ovariectomized rats found that Beta-Ecdysterone supplementation led to a significant increase in the thickness of the joint cartilage (R).  

We all know that bone and joint health are important for our quality of life, particularly when we age, but it is also imperative for optimal athletic performance

To give an analogy, you wouldn’t put a Formula 1 engine on a Nissan Pulsar and expect it to be able to handle the power. The same goes with our nervous system. If you have weak bones and poor joint integrity your nervous system won’t allow you to use all the strength you have, in order to reduce the chances of having a serious injury.

Turkesterone and the Ecdysteroids have a multitude of other health benefits beyond just muscle building and performance.

Immune system

In the adaptogen section (link to it- section 3.7), Turkesterone and Ecdysterone were shown to have a positive effect on both stress tolerance and the immune system.  The study showed that giving Turkesterone or Ecdysterone before exposure to a sustained stressor led to a beneficial impact on the size of the spleen and thymus glands, 2 key immune organs (R).  

The mice group that received Turkesterone or Ecdysterone after the stressor also showed beneficial immune effects. Their immune system returned closer to the healthy baseline much quicker than the control mice and over the longer term outperformed the control group (R).

Given that the study also showed decreases in the stress hormones, it is no surprise that Turkesterone and Ecdysterone have a beneficial impact on immune function. Excessive stress hormones lead to a dampening of the immune system, as our body doesn’t give it a high priority in times of acute life-threatening stress (R).

Another rat study comparing Anabolic steroids to Ecdysteroids found differing effects.  Compared to the control group, Anabolic Steroids led to a 20% decreased thymus mass while Ecdysteroids increased thymus mass by 23-35% (R).

Metabolic health

Metabolic health is critical for longevity and overall health.  Beyond that, it’s also quite important for exercise performance and recovery.  The overall health of our metabolism can impact every system of the body via its effect on energy production around the body.  On top of that, as was mentioned previously, it has an effect on the health of the blood vessels which we know can directly impact exercise performance.

Glucose metabolism and fat burning

A cell study found that Ecdysterone was able to reduce the process of gluconeogenesis, the process of the liver making new glucose molecules.  This enables it to lower blood sugar levels, independent of stimulating insulin (R).

When looking at a rat study, 20-hydroxyecdysone was shown to have both anti-obesity and anti-diabetic effects.  Insulin and blood glucose levels were lower in the group treated with 20-hydroxyecdysone showing some potential to improve insulin sensitivity. Additionally, the mice showed an increase in adiponectin production in visceral fat tissue. Adiponectin is commonly known as a fat burning hormone and also plays a role in decreasing inflammation (R).  Those with obesity (R) and diabetes (R) tend to have lower levels of Adiponectin.

Cholesterol homeostasis

Ecdysteroids are able to lower blood levels of cholesterol when it is elevated. It is able to reduce the synthesis of new cholesterol while also stimulating the conversion of cholesterol into bile acids, crucial for fat digestion and metabolism (R).

Antioxidant

Ecdysterone also demonstrates antioxidant status via its ability to protect against lipid peroxidation.  This same study compared Ecdysterone to Vitamin D and found that Ecdysterone was more potent at reducing oxidation.  This may also explain some of the benefits on metabolic health, as a reduction in antioxidant status can impair glucose and fat metabolism (R).

Brain function

Ecdysterone was shown to protect mice against acute cerebral ischemia (stroke) via decreasing excess fatty acid oxidation in brain tissue via increasing the activity of SuperOxide Dismutase (SOD).  Additionally, it was able to improve memory consolidation.  Following cerebral ischemia, treatment with Ecdysterone was able to increase expression of vascular endothelial growth factor (VEGF) and promote angiogenesis and neurological recovery (R).

Skin

Human cell culture studies have demonstrated that 20-Hydroxyecdysterone improves keratinocyte differentiation and therefore may be able to improve wound and burn healing (R).

Kidney and Liver health

The aforementioned human study in Section 4 (may need to update depending on if you change the sections) showed no toxicity on Kidney or Liver health.  Ecdysterone has also been shown to normalise glomerular filtration of the kidney and suppress the development of albuminuria in rats exposed to a compound with nephrotoxic (kidney toxic) effects. Additionally, it also alleviates symptoms of Uremia associated with liver damage. As discussed earlier, Ecdysteroids enhance the conversion of cholesterol to bile acids, which aids in fat metabolism and liver regeneration after exposure to toxins (R).

A 2019 study looked at the effect of 10 weeks of Ecdysteroid supplementation on 46 healthy males.  They had at least 1 year of weight training under their belt, were all non smokers, injury free for at least a year and were not taking any other medication or dietary supplements.  They were also screened for the presence of banned substances (R).

The men were split into 4 groups.

• Placebo Group – A placebo group taking 2 placebo pills + resistance training
• Low Dose Ecdysterone Group – 2 capsules (equivalent to 200mg Ecdysterone + 200mg Leucine) + training.
• High dose Ecdysterone Group – 8 capsules (equivalent to 800mg Ecdysterone + 800mg Leucine) + training.
• Control Group – 2 capsules (equivalent to 200mg Ecdysterone + 200mg Leucine) WITHOUT training

The training consisted of 3 supervised strength training sessions per week.

The Ecdysteroid supplement was listed as containing 100mg Ecdysterone + 100mg Leucine per capsule.

Results

The study looked at many metrics to determine the effect of the Ecdysteroids.

• Body weight
• Muscle mass
• Fat mass
• Total body water
• Strength
• Ecdysteroids in blood
• Estrogen, Testosterone, Luteinising hormone, IGF-1 & T4
• Markers for liver and kidney damage

Body weight & Muscle mass:

Both the low and high dose Ecdysteroid groups outperformed the placebo and control groups with regard to weight gain and muscle mass gain.  Regarding muscle mass, the low dose Ecdysteroid group gained 1.58kg of muscle, though this wasn’t statistically significant compared to placebo (which actually lost muscle mass).  A larger study population may have verified the results.  The high dose group had statistically significant gains in muscle mass (R).

The control group that took Ecdysteroids without training saw no statistically significant change in body weight or muscle mass, suggesting that there needs to be some training stimulus for muscle growth to occur (R).

Fat mass and body water:

There was no statistically significant difference in fat mass or total body water across any of the groups.

Strength

The strength markers were compared for the placebo, low dose and high dose groups.

Vertical Jump:

All training groups saw an improvement;

Placebo – 1.94cm

High dose – 2.39cm

There was no statistically significant difference between the groups though.

1 rep max Back Squat:

All training groups saw an improvement;

Placebo – 15.5%

Low dose – 17.75%

High dose – 19.4%

There was no statistically significant difference between the groups though.

1 rep max Bench Press:

As above, all groups saw an improvement;

Placebo – 3.59%

Low dose – 11.5%

High dose – 9.5%

These results showed a statistically significant benefit for Ecdysteroid supplementation.

Ecdysteroids in blood sample:

As was expected, the higher dose Ecdysterone group had the highest amount of Ecdysterone in the blood at the end of the 10 weeks.

When comparing the low dose Ecdysteroid group with training to the low dose Ecdysteroid group without training, the untrained group had higher amounts of Ecdysterone in the blood.  There are a few potential reasons for this.  Firstly, it may be that the groups were different in regards to how fast they metabolised the compound.  Secondly, it may be the case that exercise enhances the metabolism and excretion of the compound.  Thirdly, it may be that exercise resulted in enhanced usage of the Ecdysteroid, attaching to the cell more readily, meaning there would be less in the blood (R).

Hormone markers

Higher doses of Ecdysteroids led to proportionate drops in Estrogen levels. Given that Ecdysteroids interact with the ERβ, it would be speculated that there would be more Estrogen in the blood, however, this is shown not to be the case with Estrogen levels actually dropping in the Ecdysteroid groups. This may potentially be attributed to the adaptogenic nature of Ecdysteroids.

There were no changes in Testosterone or Luteinising Hormone (a hormone that signals the testicles to produce testosterone).

Both the Ecdysteroid groups had higher levels of IGF-1.

Ecdysteroids appeared to have no effect on levels of the Thyroid hormone, T4.  This dropped in all training groups and Ecdysteroids weren’t able to offset any of this (R).

Liver and Kidney markers:

All the groups that supplemented with Ecdysteroids showed no issues with the Liver and Kidney markers that were measured.  Creatinine, glutamate–oxaloacetate transaminase (GOT), glutamate–pyruvate transaminase (GPT), and gamma-glutamyl transferase (GGT)] did not change significantly over the 10-week intervention period for all groups (R).

The worst and best part – The Supplement was underdosed!

The researchers also performed an analysis on the supplement and found that it only actually contained 6mg of Ecdysteroid per capsule!  As mentioned above, the supplement claimed there was 100 mg per capsule.  Participants were only getting 6% of what they were expecting.

While this is a terrible practice, it also shows that even with this vastly underdosed supplement, Ecdysteroids still had a noticeable effect on performance.

Thankfully, this analysis determined there was no tainting with other performance enhancing drugs (R).

NOTE: This is why we are so strict on our quality standards with all our supplements to ensure they are of the highest quality and standard possible. Including accurate levels of each product.

Could the Leucine be causing the effect?

If the Ecdysteroids were underdosed substantially, is it possible that the 100mg Leucine per capsule was causing all the effects?

It would appear not.

The researchers deduced that the amount of Leucine provided was too small to provide observable physiological effects (R).

Study 1:

A study on male rats looked at the effects of injecting Ecdysterone.  The study corroborated the findings of the earlier mentioned human studies, showing an increase in IGF-1 as well as reductions in 17-Estradiol (Estrogen) and Corticosterone (R).  

A study on male rats looked at the effects of injecting Ecdysterone.  The study corroborated the findings of the earlier mentioned human studies, showing an increase in IGF-1 as well as reductions in 17-Estradiol (Estrogen) and Corticosterone (R).  

What are the differences between type I, IIa and IIb muscle fibres.

Type I are the slow twitch fibres, more important for endurance efforts and more prevalent in distance runners.

Type II are the fast twitch fibres. These fibres produce a larger and quicker amount of force but are quicker to reach fatigue than type I fibres. These are more prevalent in strength athletes.

Type II are further broken down into type IIa and IIb (aka IIX). Type IIb are the most explosive of the two, having the ability to produce the most force but also fatigue the quickest. Type IIa are a mix of type IIb and type I, being in the middle of both regarding their ability to produce force and fatigue.

Study 2:

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Another study on male rats compared the effects of multiple Ecdysteroids and anabolic-androgenic steroids.  The Ecdysteroids studied included Turkesterone, Ecdysterone, Sileneoside A and many more of their derivatives (R) .

There were 3 separate groups that looked at;

• Rats that had reached puberty
• Rats that hadn’t reached puberty and were castrated
• Rats that hadn’t reached puberty and were intact (not castrated)

The study found that Turkesterone performed the best of all the Ecdysteroids in regards to gaining weight in all 3 groups.  Additionally, Turkesterone outperformed the Steroids Nerobol (Dianabol) and Methylandrostenediol (Methandriol) in 2 out of the 3 groups.  Nerobol only outperformed Turkesterone in the group of Castrated rats (which wouldn’t produce adequate amounts of testosterone).  This makes a lot of sense given that Turkesterone and the Ecdysteroids don’t have any androgenic effect on their own and work best in synergy with Testosterone (R).  

Other studies have also found that hypophysectomy, removal of the pituitary gland (that produces growth hormone), reduced the ability of the Ecdysteroids to activate protein synthesis.  From this point and the above point on lack of testosterone, it appears that Ecdysteroids work best in conjunction with a body that has a healthy supply of testosterone and growth hormone (R).

Beyond just looking at body weight, the study compared the effects of Turkesterone, Ecdysterone, Sileneoside A and Nerobol on Muscle mass and organ weight gained (R).

Turkesterone and the Ecdysteroids were found to lead to similar gains in size across the body, meaning the organs and muscles grew via similar proportions.  Comparatively, Nerobol had larger gains in muscle and prostate weight (R).

The Ecdysteroids led to no significant change in the weight of the prostate or seminal vesicles (testicles) while Nerobol led to a significant decrease in the size of the seminal vesicles.  This is consistent with the Ecdysteroids showing no androgenic effect (R).

Another study compared 20-hydroxyecdysone to the Steroid Methandrostenolone. There were 2 groups of mice studied, one that had been preconditioned with a swimming test and another that hadn’t. It was found that Methandrostenolone only improved the physical function of the mice that had been preconditioned, while 20-hydroxyecdysone improved physical function in both groups (R). 

A much older study from 1976, showed that Turkesterone enhanced overall protein synthesis and growth in rats that had reached puberty, rats that were pre-puberty and castrated pre-puberty rats.  It sped up the growth of the sex organs in pre-puberty rats, while leaving the other 2 groups unaffected (R). 

Ajuga Turkestanica, the plant where Turkesterone is extracted from, was studied on both male and female rats.  In the male and female rats A. Turkestanica was able to improve muscle strength regardless of whether the rats were exercising or not (R).   

There was also a group of female and male rats with their ovaries and testicles removed respectively.  In these females, A. Turkestanica led to increased physical activity, while in these males it improved muscle strength and force (R).

Ecdysteroids, similar to steroid hormones and bile acids, form a number of metabolites after being ingested.  Not all of these metabolites have been identified and currently it is unknown if these metabolites contribute to some of the effects of Ecdysteroids or not (ie. whether they’re active or not) (R). 

It appears the main sites of metabolism of Ecdysteroids are the large intestine, its bacterial community and the liver.  Once the Ecdysteroids reach the large intestine metabolism begins.  From there, the metabolites undergo an entero-heptic cycle, again similar to bile acids.  This involves glucuronide conjugation in the liver, packaging the compound into bile, making its way to the small intestine and then to the large intestine where it is deconjugated via bacteria.  This process repeats with each cycle leading to lower levels of Ecdysteroids (R). 

Ecdysteroids have a very short half life in mammals, between 4 and 9 hours in humans depending on the type of Ecdysteroid, so one of the benefits of this enterohepatic cycle is that it can maintain a low amount of Ecdysteroids in the blood for around 24 hours post ingestion (R).  Thankfully, the levels it maintains it at are said to be sufficient enough to evoke the pharmacological effects of Ecdysteroids (R).

A rat study showed that administering Ecdysteroids for 28 days compared to 1 single dose led to enhanced metabolism of the Ecdysteroid.  As stated before, it is unclear whether the metabolites of Ecdysteroids are active or inactive, so whether this amplifies or reduces the effects over time is unclear (R).

As would be expected, injecting Ecdysteroids leads to a more rapid peak in blood levels though also a much quicker metabolism than oral ingestion (R).  

It appears that in mice they excrete the majority of Ecdysteroids and their metabolites via faeces, while in humans urine is another route of significant excretion.  In a trial on one human to assess metabolism, Ecdysteroids could still be detected in the urine 24 hours after the first dose (R).

It appears that higher doses can lead to reduced bioavailability.  Whether this is due to saturation of the gut uptake transporters or poor water solubility is unclear.  Theoretically this may be overcome by improving water-solubility (see section 8 below – link to it) (R). 

Bioavailability

Next comes the topic of bioavailability and possible ways to enhance it.

Studies on 20-hydroxyecdysone in rodents show the bioavailability ranging from 0.43% to 2.04%, averaging 1.2%.  The bioavailability varies for mice and rats and also across the sexes with females having slightly higher bioavailability (R). There don’t appear to be studies looking at Turkesterone’s bioavailability, hence why we’re considering 20-hydroxyecdysone.

It appears the main sites of metabolism of Ecdysteroids are the large intestine, its bacterial community and the liver.  Once the Ecdysteroids reach the large intestine metabolism begins.  From there, the metabolites undergo an entero-heptic cycle, again similar to bile acids.  This involves glucuronide conjugation in the liver, packaging the compound into bile, making its way to the small intestine and then to the large intestine where it is deconjugated via bacteria.  This process repeats with each cycle leading to lower levels of Ecdysteroids (R). 

Ecdysteroids have a very short half life in mammals, between 4 and 9 hours in humans depending on the type of Ecdysteroid, so one of the benefits of this enterohepatic cycle is that it can maintain a low amount of Ecdysteroids in the blood for around 24 hours post ingestion (R).  Thankfully, the levels it maintains it at are said to be sufficient enough to evoke the pharmacological effects of Ecdysteroids (R).

A rat study showed that administering Ecdysteroids for 28 days compared to 1 single dose led to enhanced metabolism of the Ecdysteroid.  As stated before, it is unclear whether the metabolites of Ecdysteroids are active or inactive, so whether this amplifies or reduces the effects over time is unclear (R).

As would be expected, injecting Ecdysteroids leads to a more rapid peak in blood levels though also a much quicker metabolism than oral ingestion (R).  

It appears that in mice they excrete the majority of Ecdysteroids and their metabolites via faeces, while in humans urine is another route of significant excretion.  In a trial on one human to assess metabolism, Ecdysteroids could still be detected in the urine 24 hours after the first dose (R).

It appears that higher doses can lead to reduced bioavailability.  Whether this is due to saturation of the gut uptake transporters or poor water solubility is unclear.  Theoretically this may be overcome by improving water-solubility (see section 8 below – link to it) (R). 

A study looked at how to enhance the bioavailability of 20-hydroxyecdysone and certain substances to complex it with to enhance its bioavailability (R).

It was found that complexing 20-hydroxyecdysone with Hydroxypropyl-B-Cyclodextrin led to a 100-fold increase in water solubility when compared to 20-hydroxyecdysone alone (R)!

This complex was also tested to determine its risk of cytotoxicity (how toxic it is to cells).  No toxicity was seen (R).

LVLUp Health Turkesterone is complexed with Hydroxypropyl B-Cyclodextrin.

Turkesterone acts on different pathways to Anabolic-Androgenic-Steroids. While Steroids target the androgen receptors, Turkesterone targets the ERβ.  Additionally, there is no risk of Turkesterone aromatizing into Estrogen, negatively impacting prostate and testicle weight (R), causing liver and kidney issues or many other issues commonly seen with Steroid use (R,R). Theoretically, this could also mean there is no need to cycle Turkesterone or have a Post Cycle Therapy protocol as would be necessary with Steroid use.  Additionally, while Steroids are shown to have a negative impact on the weight of the Thymus gland, negatively impacting immunity, Turkesterone and the Ecdysteroids show a beneficial effect (R).

When compared to other Ecdysteroids, Turkesterone outperforms them with regards to its ability to stimulate muscle protein synthesis, resulting in the most weight gain and muscle gain. The same study also compared the Ecdysteroids to some anabolic-androgenic steroids such as Methandrostenolone and found that Turkesterone outperformed them in 2 out of the 3 groups.  The only group where Turkesterone didn’t outperform the Steroids was the group without testicles, due to them having no endogenous testosterone production (R).  Cell studies have also shown Turkesterone to decrease myostatin more effectively than Dianabol (R).

Another study looked at Ecdysterone, compared to the Steroids Dianabol, Trenbolox and the Selective Androgen Receptor Modulator (SARM) S1 regarding muscle gain.  Ecdysterone was found to be the most efficacious at building muscle (R). Adding this to the information above that Turkesterone outperforms Ecdysteroids with regards to muscle gain, it appears this is a powerhouse of a compound (R)!

Among all the other benefits mentioned for Turkesterone and the Ecdysteroids, it also has very low toxicity.  20-hydroxyecdysone has an LD50 >9 g/kg when given orally and 6.4g/kg when injected.  For an 80kg person this would translate to over 720g of the product orally (R).

Other studies in humans have shown no toxicity issues from dosing at 10mg per kg (R) and animal studies showing no issues at 20mg per kg (R).

When compared to common steroids, Ecdysteroids lack the androgenic effects and also cannot be aromatised.  This prevents issues with high blood pressure, hair loss, acne, prostate growth, gynecomastia and more.

As mentioned above, the human studies showed no ill effects on kidney and liver health, another common issue with steroid use (R).  On top of that, mice/rat studies actually showed improvements for kidney and liver health markers (R).

In terms of cancer causing potential, it appears that Ecdysteroids may confer a protective role (R).  Additionally, complexing 20-hydroxyecdysone with Hydroxypropyl-B-Cyclodextrin, was also tested for cancer-causing potential and found to be safe (R).

Thankfully, unlike steroids and some other supplements, there doesn’t appear to be a need to cycle Turkesterone. This is due to there being no androgenicity with Turkesterone and studies showing no down-regulation of Testosterone production or aromatisation into Estrogen. Due to this, there also doesn’t appear to be a need for Post Cycle Therapy as would be the case with Androgenic Anabolic Steroids.

We recommend a start dose of around 500 – 1500mg a day.

Stacking Turkesterone:

Due to the nature of how Turkesterone works, via acting on the ERβ, it is possible to stack it with a multitude of other compounds/supplements without concern that they are acting upon the same mechanism as other supplements.

Testosterone boosters, androgen receptor modifiers, growth hormone boosters, estrogen blockers and more can be stacked with Turkesterone. Additionally, due to its ability to enhance carbohydrate and fat metabolism, it may also show some synergy with fat burner supplements. These are all speculative as none of these combinations have been studied.

It is also worth staying away from things that can alter its metabolism. As stated above, it is unclear if the metabolites of Turkesterone and the other Ecdysteroids are responsible for part of their effect or not. As such, it is unclear whether it is beneficial to slow down or speed up the metabolism of these compounds.

As it is metabolised by the Glucuronidation pathway, it may be worth staying away from the following compounds which can alter glucuronidation, while taking Turkesterone:

– Black Pepper
– Green Tea
– Curcumin
– Calcium D-Glucarate