Ostarine (Enobosarm, MK-2866, & GTx-024) No Steroids?

Note: Ostarine and other SARMs alike are considered research chemicals and are not approved for public consumption. Use of ostarine and similar research chemicals should be restricted to a clinical setting.

 

Ostarine (Enobosarm, MK-2866, & GTx-024)

 

Ostarine is one of the most popular research chemicals within the class known as SARMs or Selective Androgen Receptor Modulators. With non-steroidal effects on muscle mass and bone density similar to that afforded by steroids, ostarine has become a significant target for both pharmaceutical companies and the general public.

Research suggests that ostarine could prove useful, in particular, for those experiencing age or disease-related muscle loss, with minimal side effects. However, this reality has made ostarine a target for athletes and bodybuilders to use illicitly (1, 2, 3).

As you'll learn, ostarine is easily one of the most promising research chemicals around, but with a lack of long-term data, use outside of a clinical setting is ill-advised.

Ostarine Essentials

Marketed under many different names, including Enobosarm, MK-2866, and GTx-024, ostarine is an emerging research chemical that is classed as a SARM. Overall, research suggests that ostarine is an option for building lean body mass, in particular for those with muscle wasting disorders (1, 2, 3).

SARMs are a relatively new area of study for their influence on building muscle mass and strength in addition to secondary metabolic benefits like improved insulin sensitivity and favorable adjustments to body fat.

These benefits are similar to those afforded by steroid hormones like estrogen and testosterone. But as a non-steroidal SARM, ostarine can provide many of these benefits without adversely impacting natural hormone production or promoting the typical side effects associated with steroid use (2, 3, 4).

More, SARMs seem to target specific tissues whereas steroids do not. For example, a prostate cancer patient might be able to use ostarine to maintain or build muscle mass without negatively impacting prostate cells. Alternatively, the use of testosterone could initiate additional cancer growth in the prostate, making it a bad choice (5).

Summary: Ostarine is a non-steroidal SARM. Because of its tissue selectivity and ability to promote muscle growth, it’s become a strong candidate for muscle-wasting related disorders, including those related to age, cancer, and disease.Ostarine

Ostarine Alleviates Muscle Wasting

Ostarine is a relatively new substance that has been revealed to improve muscle mass and strength, making it an attractive topic of consideration. But these studies aren't aimed at improving muscle mass for athletic performance or vanity. Instead, clinical experiments have studied ostarine for individuals experiencing the muscle wasting disorder known as cachexia.

Cachexia is a term to describe muscle loss, similar to that of sarcopenia. However, in the case of cachexia, this is muscle loss that occurs in the absence of fat loss. Mostly, this disorder results in pure muscle loss (6).

Cachexia is most often associated with cancer development. In the average population, roughly 1-2% of the population has some form of cachexia, mostly related to aging. In people with cancer, some estimates are closer to around 30%, with even higher percentages for individuals experiencing later stage kidney and non-small cell lung cancer (7).

Unfortunately, cancer-related cachexia is a bit worse than the standard model because it can't be reversed or treated through nutrition and this loss of muscle mass often results in a significant reduction of physical function (7).

Making things worse, treatment for cachexia apart from nutritional interventions do not exist. As you can imagine, this proves useless for a cancer patient unable to eat food. And for obvious reasons already mentioned, use of hormones like testosterone or estrogen could make things even worse (5).

This reality led to the commencement of clinical trials testing the usefulness of ostarine in both healthy and sick individuals to build lean body tissue as an alternative treatment.

Clinical Trials With Ostarine

The inclusion of ostarine in human clinical trials is exciting because it means there is a legitimate chance that it's useful with minimal side effects. Entering into clinical trials takes years and costs manufacturers and scientists millions of dollars, meaning if it makes it through the various stages of clinical trials, it's probably both safe and effective.

Furthermore, the fact that researchers conducted clinical trials in both sick and healthy patients suggests that ostarine's benefits may extend further than only for cancer patients.

Phase 1 Clinical Trial

In phase 1 of clinical trials, 48 post-menopausal women were treated with ostarine to understand its influence on muscle growth. In particular, older, female individuals, who are unlikely to be able to develop significant muscle mass naturally, were the main study population.

Subjects were provided with either 3 mg of ostarine or a placebo daily, for 12 weeks. By the end of the 12 weeks, female subjects consuming 3 mg of ostarine daily displayed significant improvements in lean body mass, suggesting a muscle-building influence. The authors also note there was a trend, albeit, non-significant, for the development of muscular strength (4).

Equally important, these findings were in the absence of an exercise protocol, meaning ostarine promoted the development of muscle mass alone. These results are meaningful for individuals unable to exercise intensely such as the elderly or ill.

Phase 2, Trial 1: Healthy Individuals

Upon the successful completion of phase 1, ostarine was moved on to phase 2 clinical trials, where scientists tested healthy individuals as well as subjects with cancer.

One hundred twenty healthy males and females, aged 60 years or older enrolled in this study to understand how ostarine might influence age-related muscle issues like muscle wasting and reduced physical abilities.

Subjects were split into one of five groups, which varied in dosage. Group dosages included 0.1 mg, 0.3 mg, 1.0 mg, and 3 mg of ostarine or placebo. These subjects consumed their dosage daily for 12 weeks.

Findings of the study indicated that ostarine resulted in the development of total lean body mass in a dose-dependent manner. In the same light, ostarine subjects also experienced a significant decrease in total body fat while also increasing physical performance and power output, which was only statistically significant for those in the 3 mg group (2).

Phase 2 Side Effects

Surprisingly, researchers note a reduction of Sex Hormone Binding Globulin (SHBG), which could mean ostarine does indeed influence the androgen system.

Androgens like testosterone and estrogen come in two forms: bound and free. When SHBG binds to an androgen, it's not able to act on tissues. This is to prevent excess androgen production as well as to avoid the associated adverse side effects. When the androgen is free, it's quite literally able to interact with various tissues at will that stimulate growth like muscle and even the prostate. Further, too much free testosterone, such as what happens with steroid use, can shut down natural production.

When SHBG levels are normal, that means that androgen production is working as intended, within normal ranges. Essentially, normal levels of SHBG indicate that the system is working correctly to maintain the internal environment. When SHBG levels decline as a result of ostarine supplementation, this might suggest that ostarine does have some influence over androgen production. Considering ostarine is often regarded as not influencing natural androgen production, this should be of concern (8).

Otherwise, the authors also mention a dose-dependent decrease in HDL (high-density lipoprotein) cholesterol with no change in low density (LDL). These results could be meaningful. However, a lack of long-duration studies on ostarine means that we don’t know the long-term effects of this adjustment (2).

Fortunately, other side effects were quite mild and not of concern. The authors note that some of the most common effects were a headache, nausea, back pain and some flu-like symptoms, which in the context of preventing muscle wasting may be worthwhile (2).

Phase 2, Trial 2: Cancer Patients

Upon completion of the first trial in healthy individuals, ostarine was then tested with subjects diagnosed with cancer but with a relatively favorable prognosis, (non-terminal and a life expectancy greater than six months).

This study used three groups of randomly assigned subjects based on dosage including 1 mg, 3 mg of ostarine and placebo. These individuals then consumed their dosage or placebo daily for 113 days. During that time, variables like lean body mass and physical function were tested.

The findings of the study revealed that ostarine in both interventions, regardless of dosage, resulted in significant muscle growth and increased power production. Unsurprisingly, these findings were accompanied by mild side effects similar to other trials such as fatigue, nausea, headaches and back pain (3).

It is, however, worth mentioning that some patients in both groups experienced elevations of malignant neoplasm, suggestive of the progression of cancer. Five participants out of 52 receiving 1 mg and 7 participants out of 53 receiving 3 mg displayed these elevations in malignant neoplasm.

However, as the authors mention, it’s unlikely this was a result of ostarine supplementation (3).

Based on the low incidence of progression to occur, it’s likely these individuals would have experienced cancer progression regardless of this intervention. Given that the majority of users did not experience this elevation, it seems promising that ostarine was not to blame.

Phase 3: Late-Stage Cancer Patients

Amazingly, ostarine is one of the few SARMs to have made it all the way to phase 3 of clinical testing. This is significant because it means that the chemical has shown promise for its intended purpose while also being relatively safe.

Phase 3 of clinical trials included two identical studies, encompassing roughly 600 subjects in stage 3 or 4 of non-small cell lung cancer, (~300 in each study). Within each of these studies, participants were provided with 3 mg of ostarine or placebo for 147 days.

The findings of this study, unsurprisingly, were more of the same. In both studies, subjects receiving 3 mg of ostarine displayed improvements in total lean body mass and power production, suggesting a substantial benefit, even for late-stage cancer patients (9).

Unfortunately, however, ostarine failed to meet established criteria, resulting in the abandonment of further trials (10, 11).

Summary: Ostarine is one of the few SARMs to progress as far as stage 3 clinical testing for disease-related muscle wasting. Findings reveal that ostarine is indeed effective at improving lean mass in the absence of resistance training and seems to do so with a lack of any severe adverse side effects. Ostarine, however, was removed from further clinical testing due to the inability to meet established criteria.

Secondary Benefits Of Ostarine

Ostarine's primary benefit is to build lean body mass similarly as steroids, without the adverse side effects. Mostly, this is applicable for individuals experiencing disease-related muscle wasting, like those with cancer or AIDS. But as a secondary effect, ostarine does indeed provide other benefits.

Insulin Sensitivity

Insulin sensitivity is a concept to describe how well insulin is functioning. Insulin is a peptide hormone secreted by cells in the pancreas in response to elevated blood sugar. When you eat carbohydrates (and to some extent protein), blood sugar elevates, and insulin pulls that sugar into different organs and tissues like muscle, the liver, and even fat cells.

In healthy individuals, this works seamlessly as blood sugar rises and insulin shuttles that sugar into various tissues. In unhealthy individuals, however, this process doesn't work as it should. When this happens, it's considered a state of insulin resistance where insulin can no longer effectively remove sugar from the blood. When this happens, it can lead to disorders like metabolic syndrome, excessive weight gain, and even the development of diabetes (12).

Research studies including healthy humans and ostarine have shown a positive influence of this SARM on blood glucose and the action of insulin. Scientists note that ostarine significantly reduced blood insulin levels and spurred a trend of lowering insulin (2).

One hundred twenty senior men and postmenopausal women were recruited for this study and were provided with 1 of 5 ostarine dosages ranging from .01 mg to 3.0 mg. For 12 weeks, subjects ingested their dose daily and then returned for a final assessment.

Researchers mention that in addition to improving lean body mass, subjects also displayed significant reductions of fasting blood glucose and a trend for a reduction in fasting insulin, which is indicative of enhanced insulin sensitivity. And luck would have it; the results showed a dose-dependent decrease in insulin sensitivity with 1 mg subjects receiving an average reduction of insulin resistance by 9.3% while participants receiving 3 mg displayed a drastic reduction of around 27.5% (2).

While these reductions might not mean much at first, the authors note this reduction is on par with other diabetic-specific drugs like metformin at improving insulin resistance. These reductions could be significant for those at risk of developing insulin resistance or even those who already have it.

Summary: Studies have shown that ostarine can improve insulin sensitivity, which could prove to be useful for obese individuals or those with severe insulin resistance.

Body Recomposition

In addition to improving muscle mass and insulin sensitivity, research shows that ostarine can help with reductions of fat mass (2).

Fortunately, in addition to testing lean mass and insulin sensitivity, Dalton et al., in 2011 also measured changes in total body fat throughout the study since body fat levels are also indicative of poor metabolic health.

Unsurprisingly, these scientists again showed a dose-dependent reduction of body fat, with 3 mg users experiencing an average decrease of 0.6 kg. The authors also note this was in the absence of body weight changes, which suggests that while these individuals were building lean body mass, they were also reducing body fat. Quite literally, this is the holy grail of outcomes one can hope for when taking a substance to improve body composition (2).

The amazing thing here is that this was achieved without the addition of exercise and without reducing food intake. This reality means the benefits afforded were a result of ostarine supplementation alone. These findings are undoubtedly the main reason athletes have begun using ostarine illicitly but could also prove useful for treating individuals unable to exercise or diet.

However, as mentioned multiple times, despite the impressive benefits afforded by ostarine, this substance is not approved for human consumption and should not be used.

Summary: Studies on ostarine have revealed improvements in lean mass and reductions of fat mass with no change in body weight, suggesting that muscle growth and fat reduction were happening simultaneously. These findings are easily the prime motivating factors behind the illicit use of ostarine for athletes.

Bone Health

Unfortunately, androgens like testosterone and estrogen play significant roles in the formation and maintenance of bone and bone density. As often observed, old age leads to a reduction in androgen production, which many times results in osteopenia or osteoporosis. These issues often affect women to a greater extent than men for some reasons including lower overall bone mass and lower bone mineral density at baseline (13).

Researchers using a rat model tested 46 female rats eight weeks after having their ovaries removed. This removal of ovaries reduces estrogen production, which ultimately reduces bone density and strength, similar to that of being in a post-menopausal state. Throughout the study, rats were fed varying dosages of ostarine in their foods each day. After 13 weeks, the rats were sacrificed, allowing scientists to measure changes in bone mass and density.

Scientists showed that when consuming higher levels of ostarine, rats with no ovaries showed improvements of both bone mineral density and bone volume, suggesting a growth effect of ostarine. Importantly, the authors note that bone density for rats consuming the intermediate and high doses of ostarine showed bone density levels similar to control rats (14).

These findings are significant, in particular, for post-menopausal women experiencing age-related osteoporosis or osteopenia. Since ostarine is non-estrogenic and can improve bone density with little to no exercise, this is attractive for older individuals or those that already have progressive bone loss and have lost control over physical ability.

Summary: When given to rats with ovaries removed, ostarine significantly elevates bone mineral density and volume. This means ostarine may be an attractive choice for individuals experiencing bone loss, in particular, post-menopausal women.

Other Important Considerations For Ostarine

Ostarine Is Not Approved For Public Consumption

While ostarine has been used in clinical trials and seems to show promise with minimal side effects, this substance is still considered a research chemical and not approved for human consumption.

The impressive benefits and lack of adverse side effects make ostarine an attractive option. But without definitive evidence of long-term safety, use of ostarine should only take place at the request or suggestion of your doctor.

Ostarine Is Orally Bioavailable

Taking androgens like testosterone orally is dangerous and can cause severe liver damage, which is why most hormone therapies are injectable or transdermal (15).

Studies have indicated that ostarine is safe for the liver and can be taken orally. As you can imagine, this makes ingesting ostarine much easier while avoiding the need for injections and it's associated process (2, 16).

Anecdotal Dosages are Extreme

You'll notice that apart from peer-reviewed studies and clinical trials, public knowledge of these chemicals is scarce. Various outlets promoting ostarine even suggest dosages upwards of 25 mg of ostarine daily.

You can notice that clinical trials using subjects with severe muscle wasting provided no more than 3 mg of ostarine daily. As you can imagine, it’s unknown what sort of influence an additional 22 mg each day might have on the body and your health. Considering that even a 3 mg dose resulted in reductions of SHBG, taking significantly higher doses could prove dangerous.

While the use of ostarine should be restricted to a clinical setting, the discrepancy between tested dosages and dosages being used by the general public should raise concern and be considered before use.

Long Term Safety Has Not Been Established

In addition to the former, long-term safety of ostarine use has not been established.

Even the clinical trials testing ostarine could be measured in weeks, so it's difficult to know if the same level of safety will occur with long-term use. Again, the use of ostarine should be restricted to only when your doctor believes it to be necessary.

Final Thoughts on Ostarine

Ostarine is one of the few SARMs to make it phase 3 of clinical trials and based on the findings, could prove useful especially for improving muscle mass and increasing bone density in the elderly and sick.

However, the potent influence of ostarine on muscle growth and reductions of fat mass make it an attractive option for illicit use.

Currently, ostarine is not available for public consumption, and use of this research chemical should be limited to the clinical setting. Keep in mind that even clinical studies involving ostarine were across the duration of a few months. Simply put, data on long-term effectiveness and safety doesn’t exist.

As a result, the personal use of ostarine without the oversight of a doctor is not advised.

Where can I buy Ostarine?

We only recommend purchasing Ostarine from Sarms4you. Sarms4you incorporates third party testing to make sure the product is free of impurities and is safe, we always recommend the best sources as user safety and information is our top priority. The easiest way to purchase Ostarine through Sarms4you is here.

References (Click to Expand)
  1. Srinath, R., & Dobs, A. (2014). Enobosarm (GTx-024, S-22): a potential treatment for cachexia. Future Oncology10(2), 187-194.
  2. Dalton, J. T., Barnette, K. G., Bohl, C. E., Hancock, M. L., Rodriguez, D., Dodson, S. T., … & Steiner, M. S. (2011). The selective androgen receptor modulator GTx‐024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double‐blind, placebo‐controlled phase II trial. Journal of cachexia, sarcopenia and muscle2(3), 153-161.
  3. Dobs, A. S., Boccia, R. V., Croot, C. C., Gabrail, N. Y., Dalton, J. T., Hancock, M. L., … & Steiner, M. S. (2013). Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. The lancet oncology14(4), 335-345.
  4. Jones A, Coss CC, Steiner MS, Dalton JT. An overview on selective androgen receptor modulators: focus on enobosarm. Drugs Future 38(5), 309-316 (2013).
  5. Bhasin, S., & Jasuja, R. (2009). Selective androgen receptor modulators (SARMs) as function promoting therapies. Current opinion in clinical nutrition and metabolic care12(3), 232.
  6. Evans, W. J., Morley, J. E., Argilés, J., Bales, C., Baracos, V., Guttridge, D., … & Marks, D. (2008). Cachexia: a new definition. Clinical nutrition27(6), 793-799.
  7. von Haehling, S., & Anker, S. D. (2014). Prevalence, incidence and clinical impact of cachexia: facts and numbers—update 2014. Journal of cachexia, sarcopenia and muscle5(4), 261-263.
  8. Selby, C. (1990). Sex hormone binding globulin: origin, function and clinical significance. Annals of clinical biochemistry27(6), 532-541.
  9. Crawford, J., Prado, C. M., Johnston, M. A., Gralla, R. J., Taylor, R. P., Hancock, M. L., & Dalton, J. T. (2016). Study design and rationale for the phase 3 clinical development program of enobosarm, a selective androgen receptor modulator, for the prevention and treatment of muscle wasting in cancer patients (POWER trials). Current oncology reports18(6), 37.
  10. Solomon, Z. J., Mirabal, J. R., Mazur, D. J., Kohn, T. P., Lipshultz, L. I., & Pastuszak, A. W. (2018). Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications. Sexual medicine reviews.
  11. GTx Announces Results from Preclinical Studies of SARMs in Duchenne Muscular Dystrophy Models Published in Human Molecular Genetics. (2017, May 03). Retrieved from https://www.businesswire.com/news/home/20170503005176/en/
  12. Kahn, B. B., & Flier, J. S. (2000). Obesity and insulin resistance. The Journal of clinical investigation106(4), 473-481.
  13. Melton Iii, L. J., Khosla, S., Achenbach, S. J., O’Connor, M. K., O’fallon, W. M., & Riggs, B. L. (2000). Effects of body size and skeletal site on the estimated prevalence of osteoporosis in women and men. Osteoporosis international11(11), 977-983.
  14. Hoffmann, D. B., Komrakova, M., Pflug, S., von Oertzen, M., Saul, D., Weiser, L., … & Sehmisch, S. (2018). Evaluation of ostarine as a selective androgen receptor modulator in a rat model of postmenopausal osteoporosis. Journal of bone and mineral metabolism, 1-13.
  15. Kim, J., Wang, R., Veverka, K. A., & Dalton, J. T. (2013). Absorption, distribution, metabolism and excretion of the novel SARM GTx-024 [(S)-N-(4-cyano-3-(trifluoromethyl) phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide] in rats. Xenobiotica43(11), 993-1009.
  1. Osterberg, E. C., Bernie, A. M., & Ramasamy, R. (2014). Risks of testosterone replacement therapy in men. Indian journal of urology: IJU: journal of the Urological Society of India30

Author

Nootropedia is meant to be a resource for individuals researching drugs and supplements that are good for brain health, otherwise known as nootropics, and thus we are the Nootropics Encyclopedia. Because of our in-depth coverage of this topic, our community has requested that we cover other brain health topics and "lifehacks" so that has become the focus of Nootropedia.