SARMs are under contiuous development as promising alternatives to anabolic–androgenic steroids (AAS). SARMs display tissue-selective androgen activation, unlike AAS which bind with androgens throughout the body, adversely affecting untargeted tissues such as prostate, heart, or other organs (source). This tissue-selectivity makes SARMs ideal for improvement of musculoskeletal physical function, as well as bone health, and continues to drive clinical research and testing of these regenerative and restorative drugs.
MK-2866, typically referred to as Ostarine, is an investigational SARM currently developed by pharmaceutical company GTx Incorporated for the treatment of muscle wasting and osteoporosis. Ostarine can be bought online and is currently the most researched SARM in existence.
“Selective androgen receptor modulators (SARMs) differentially bind to androgen receptors depending on each SARM’s chemical structure. As a result, SARMs result in anabolic cellular activity while avoiding many of the side effects of currently available anabolic steroids. SARMs have been studied in the treatment of breast cancer and cachexia and have also been used as performance enhancing agents.” (source: Selective Androgen Receptor Modulators (SARMs) – Current Knowledge and Clinical Applications).
In a 2011 a 12-week double-blind, placebo-controlled phase II clinical trial was conducted to evaluate Ostarine in 120 healthy and women. 120 subjects were randomized to Ostarine 0.1, 0.3, 1.0 or 3.0 mg versus placebo over 3 months. At the end of the trial, a significant increase in total lean body mass and improvement in measures of physical function were measured in the 3-mg group (source: The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women).
Finally, in two separate Phase III trials of Ostarine, 325 patients with stage III or IV NSCLC and muscle wasting were randomized to Ostarine 3 mg versus placebo for 3 months, with primary endpoints including total lean body mass and improvement in physical function. Again, the researchers found a Significant increase in total lean body mass compared with placebo (GTx Announces Late Breaker Presentation on Results from the Two Phase 3 POWER Trials of Enobosarm).
LGD-4033, typically referred to as Ligandrol, is an investigational SARM discovered by Ligand Pharmaceuticals and currently under development by Viking Therapeutics for the treatment of conditions such as muscle wasting and osteoporosis.
Researchers evaluated the safety of Ligandrol in a Phrase I trial that involved 76 healthy men (21–50 years). These men were randomized to placebo or 0.1, 0.3, or 1.0 mg LGD-4033 daily for 21 days. The researchers concluded by saying that Ligandrol was well tolerated (The Safety, Pharmacokinetics, and Effects of LGD-4033, a Novel Nonsteroidal Oral, Selective Androgen Receptor Modulator, in Healthy Young Men).
“LGD-4033 administration was associated with dose-dependent suppression of total testosterone, sex hormone–binding globulin, high-density lipoprotein cholesterol, and triglyceride levels. follicle-stimulating hormone and free testosterone showed significant suppression at 1.0-mg dose only. Lean body mass increased dose-dependently, but fat mass did not change significantly. Hormone levels and lipids returned to baseline after treatment discontinuation,” the researchers noted.
In 2017, Viking Therapeutics completed enrollment in Phase II trial of Ligandrol in patients recovering from hip fracture. Viking Therapeutics plans to administer once-daily doses of 0.5 mg, 1.0 mg, 2.0 mg, or placebo for 12 weeks to 108 patients to study the effects of Ligandrol on lean body mass, functional performance, and quality-of-life, among other things (source).
MK-677, typically referred to as Ibutamoren, a potent non-peptide agonist of the ghrelin receptor and a growth hormone secretagogue. Ibutamoren mimics the growth hormone (GH)-stimulating action of the endogenous hormone ghrelin, which regulates appetite and plays a significant role in regulating the distribution and rate of use of energy.
The effects of MK-677 on the growth hormone (GH)-insulin-like growth factor I axis were studied during a phase I and II trial involving 32 healthy subjects. The subjects received placebo or 2, 10, or 25 mg MK-677, orally, once daily for 2 separate study periods of 14 and 28 days. Once daily treatment of older people with oral MK-677 for up to 4 weeks at a dose of 25 mg/day restored serum IGF-I concentrations to those of young adults (Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects).
During a 1999 trial whose purpose was to determine the effect of chronic administration MK-677 on serum IGF-I and markers of bone turnover in 187 elderly adults, 30 subjects received either placebo for 4 weeks or 25 mg of MK-677 daily for 2 weeks followed by 50 mg daily for 2 weeks. The researchers noted the ability of MK-677 to significantly increase serum IGF-I levels stimulates bone turnover in elderly subjects (Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults).
YK-11 is a myostatin inhibitor, in the form of a synthetic SARM, with significant anabolic activity demonstrated during an in vitro study (Selective androgen receptor modulator, YK11, regulates myogenic differentiation of C2C12 myoblasts by follistatin expression).
Accompanied by follistatin, YK11 causes increased production of myogenin, myogenic factor 5 (Myf5) and myogenic differentiation factor (MyoD). These myogenins cause increases in differentiated muscle cells at a higher rate than DHT or Testosterone alone.
Because in vitro studies are performed with microorganisms, cells, or biological molecules outside their normal biological context, they may not fully or accurately predict the effects on a whole organism.
RAD-140, typically referred to as Testalone, is an a potent, orally highly-bioavailable, nonsteroidal SARM currently under development by Radius Health for the treatment of conditions such as muscle wasting and breast cancer.
Several studies have been conducted showing impressive and muscle-selective anabolic activity. A 2010 study with monkeys produced lean muscle mass weight gain of greater than 10% in just 28 days at a dose of just 0.1 mg/kg, as well as significant reduction in fat tissue. More recently, RAD-140’s inhibiting effect on the growth of the androgen/estrogen receptor has found it to be a very promising drug in the fight against breast cancer. An exciting study in 2014 showed RAD-140 may provide neuroprotective actions and resilience to neurodegenerative diseases, which may indicate an ability to assist in prevention and mitigation of Alzheimer’s and related diseases.
GW-501516, typically referred to as Cardarine, is a PPARδ receptor agonist. It was invented in a collaboration between Ligand Pharmaceuticals and GlaxoSmithKline in the 1990s as a drug candidate for metabolic diseases and cardiovascular diseases.
A 2012 study showed this SARM capable of assisting with repairing liver damage. During animal testing Cardarine was found to cause cancer cells to develop when given to rats at daily ultra-doses of 3 mg per kg of body weight (source). A few clinical trials have also been performed on cardarine and its effects on fat metabolism. Despite pressimistic findings in rodents, “no significant adverse effects were reported in any of the human studies, which may reflect the considerably lower doses administered (up to 10 mg/day) for much shorter periods of time (up to 12 weeks)” (source).
S-4, typically referred to as Andarine, is an investigational SARM developed by GTx Incorporated for treatment of conditions such as muscle wasting, osteoporosis, and benign prostatic hypertrophy. Although Andarine is known to have a similar chemical structure to Ostarine (the chemical structure of Ostarine has never been publicly disclosed), the two drugs are not exactly the same.
In various trials, S-4 treatment was shown to decrease body fat and increase body strength. GTx completed phase I studies on both Andarine and Ostarine and found both drugs equally safe. According to Nonsteroidal Selective Androgen Receptor Modulators (SARMs): Dissociating the Anabolic and Androgenic Activities of the Androgen Receptor for Therapeutic Benefit, “Ostarine was selected for advanced clinical development based on corporate strategy,” while all testing of Andarine was ceased.
SARMs Legal Status
In the US and many other countries, SARMs are currently in the research and testing stages for various physical ailments and medical conditions. As investigational new drugs, SARMs are sold online, but they cannot be legally marketed and labeled as dietary supplements — an important distinction.
In 2017, the FDA’s Center for Drug Evaluation and Research put out a warning regarding the use of SARMs in body-building products: “We are extremely concerned about unscrupulous companies marketing body-building products with potentially dangerous ingredients. Body-building products that contain selective androgen receptor modulators, or SARMs, have not been approved by the FDA and are associated with serious safety concerns, including potential to increase the risk of heart attack or stroke and life-threatening reactions like liver damage.”