RAD-140 and YK-11 Stack: What the Research Actually Shows

Key takeaways

What RAD-140 and YK-11 Are

RAD-140, also known as Testolone, is a nonsteroidal selective androgen receptor modulator (SARM). It was originally developed by Radius Health as an investigational treatment for hormone receptor-positive breast cancer, where the androgen receptor is highly expressed, and it was advanced into a first-in-human phase 1 trial (ClinicalTrials.gov NCT03088527) designed to evaluate safety, tolerability, and maximum tolerated dose in postmenopausal women with metastatic disease. That study reported a provisional maximum tolerated dose of 100 mg once daily and described RAD140 as having 'an acceptable safety profile and preliminary evidence of target engagement and antitumor activity' in that specific patient population, which is not the same population or context in which the compound is used by people seeking muscle gain.

YK-11 is chemically distinct from RAD-140. It is a steroidal compound structurally related to dihydrotestosterone (DHT) that is described in preclinical literature as a partial agonist of the androgen receptor which also upregulates follistatin, a protein that binds and inhibits myostatin, a negative regulator of skeletal muscle growth. Unlike RAD-140, YK-11 has never been advanced into a registered human clinical trial for any indication. A chemical vendor's technical summary of the compound states plainly that 'its safety, pharmacokinetics, and long-term effects remain poorly characterized, with no validated clinical studies to date,' which reflects the actual state of the published evidence.

Neither compound is approved by the FDA or any other regulatory authority for human use, for bodybuilding or for any medical condition.

The Rationale Behind the 'Stack' Is Theoretical, Not Tested

The appeal of combining RAD-140 and YK-11 rests on a mechanistic argument: RAD-140 is an androgen receptor agonist marketed for its muscle-building potential, while YK-11's proposed follistatin-mediated myostatin suppression is described as operating through a different pathway. The idea is that stacking an AR agonist with a purported myostatin inhibitor could produce additive or synergistic muscle growth beyond either compound alone.

This rationale has not been tested in animals or humans as a combination. It is derived entirely from separate, limited data on each compound individually, extrapolated by analogy. No pharmacokinetic, pharmacodynamic, or safety study of RAD-140 combined with YK-11 exists in the peer-reviewed literature, in FDA adverse event data, or in any clinical trial registry.

Human Safety Data on RAD-140: Documented Liver and Cardiac Injury

Unlike YK-11, RAD-140 has an accumulating record of published human case reports describing serious organ injury, despite its short time on the illicit market. Several case reports describe drug-induced liver injury. One report describes a 29-year-old man who developed jaundice and elevated liver enzymes after three months of RAD-140 use, with a liver ultrasound revealing hepatic steatosis and a hyperechoic lesion. A case published in Australian Prescriber described a patient whose liver biochemistry at hospital admission showed a total serum bilirubin concentration of 708 micromol/L with a mixed cholestatic and hepatotoxic picture; the case was formally reported as an adverse drug reaction to Australia's Therapeutic Goods Administration, and liver biochemistry only normalized five months after RAD-140 was stopped. A separate case in the Ochsner Journal described a 24-year-old man with a cholestatic pattern of liver injury and a peak total bilirubin of 38.5 mg/dL, with a liver biopsy showing intracytoplasmic and canalicular cholestasis; his symptoms and liver injury resolved after he stopped the drug. Another case report concluded that clinicians should specifically ask about RAD140 and similar supplements in young men presenting with acute liver injury, warning that if missed and use continues, injury 'can likely lead to fulminant liver failure or decompensated liver cirrhosis.' Across the published cases, discontinuation of RAD-140 has generally led to resolution of liver injury, with no case in the literature review describing permanent liver damage, though this does not establish that irreversible injury is impossible.

RAD-140 has also been linked to cardiac injury. A case published in JACC: Case Reports described a 16-year-old boy who developed chest pain radiating to his left arm within hours of taking a single dose of a RAD-140 product, ultimately diagnosed as myopericarditis; the authors noted this reaction occurred after only one dose and stated that 'even a short course of selective androgen receptor modulators such as RAD-140 can result in life-threatening problems such as myocarditis.' A separate case published in Cureus described a young man who presented with possible acute myocarditis following self-medication with a RAD-140 product for bodybuilding, which the authors identified as the first published case of a SARM implicated in acute myocarditis. The mechanisms behind SARM-associated cardiac injury remain unclear, though researchers have theorized possible interference with steroidogenic enzyme pathways.

Even in the controlled phase 1 oncology trial, where dosing and monitoring were closely supervised, transient elevations of liver transaminases were among the most serious toxicities observed, a finding that has been reported in other SARM trials as well.

Human Safety Data on YK-11: Essentially Nonexistent

A search of the published medical literature did not identify any peer-reviewed human case reports specifically describing liver, cardiac, or other organ injury attributable to YK-11 used alone. This is a notable contrast with RAD-140, which has several such reports.

This absence of documented harm should not be interpreted as evidence of safety. YK-11 has never undergone a registered human clinical trial, so there has been essentially no systematic opportunity to detect adverse events in a monitored setting, and case reports depend on clinicians recognizing and publishing unusual presentations, which is less likely for a compound with lower name recognition than RAD-140. Given that YK-11's proposed mechanism (androgen receptor partial agonism combined with follistatin induction) is itself based on cell-culture and preclinical work rather than confirmed human pharmacology, no reliable statement can be made about its human safety profile, positive or negative.

No Data Exist on Combining the Two Compounds

No study, case series, or regulatory safety communication addresses the combined use of RAD-140 and YK-11. Because SARMs as a class have not been approved for pharmacotherapy, systematic pharmacovigilance for individual compounds is already limited, and it is essentially absent for combinations. A review of suspected SARM-related adverse events noted that the long-term exposure and possible adverse effects of these compounds are not fully known even individually, which is consistent with regulators' position that no SARM has been approved for any indication.

Combining two agents that each carry a plausible mechanism for hepatotoxicity (RAD-140 through documented idiosyncratic drug-induced liver injury, and YK-11 through an unstudied but structurally steroidal profile) is a biologically plausible reason for concern about compounded risk, but plausibility is not evidence. No dose-response, interaction, or additive-risk data exist to confirm or rule out whether combining the two compounds increases the likelihood or severity of liver injury, cardiac injury, or any other adverse event beyond what either compound might cause on its own.

Regulatory and Anti-Doping Status

The FDA has not approved RAD-140, YK-11, or any other SARM as a drug or dietary supplement ingredient for human use. The agency has issued warning letters to companies distributing SARM-containing products and has stated that these products '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.' A 2023 FDA consumer warning aimed at teens and young adults reiterated that SARMs have been associated with increased risk of heart attack or stroke, liver injury or failure, and other serious effects, and emphasized that these substances 'cannot be marketed legally in the U.S. as a dietary supplement or drug.'

Both compounds are prohibited in competitive sport. The World Anti-Doping Agency's Prohibited List names RAD140 and YK-11 explicitly, together with other SARMs such as andarine, enobosarm (ostarine), LGD-4033 (ligandrol), and S-23, under category S1.2, 'Other Anabolic Agents.' Per the U.S. Anti-Doping Agency, SARMs as a class 'are prohibited at all times (both in and out-of-competition) for all athletes, from those competing at the highest level of sport to those competing at the recreational level,' and no SARM is available by prescription because all remain investigational drugs.

Bottom Line

The evidence base for a RAD-140 and YK-11 stack does not exist in any clinically meaningful sense. RAD-140 has enough independent human case-report data to establish that it can cause reversible, and in some reported presentations severe, drug-induced liver injury and myocarditis, even from limited exposure. YK-11 has essentially no human safety data of any kind, positive or negative, because it has never been tested in a registered clinical trial. Layering one compound with a documented injury signal onto another compound with no human data at all does not constitute a studied or evidence-supported practice; it is an untested combination of two unapproved investigational substances, one of which has already produced multiple hospitalizations in the published literature.

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