YK-11 or Ostarine: what is the difference

YK-11 and Ostarine are often mentioned together as “SARMs”, although chemically and pharmacologically they are very different substances. Ostarine has undergone clinical trials in humans, whereas YK-11 exists mainly as a handful of laboratory studies on cells. The editorial team explains what the difference between them is and why this difference matters for assessing risks.

Two substances under one label

The acronym SARM stands for “selective androgen receptor modulator”. The idea of this class is to obtain an anabolic effect in muscle and bone while minimizing the impact on the prostate, skin and other androgen-sensitive tissues. Ostarine (enobosarm, GTx-024, MK-2866) is a classic representative of the nonsteroidal SARMs, created by GTx precisely for this purpose.

YK-11 is formally also called a SARM, but structurally it is a steroid: its molecule is built on the 5α-androstane skeleton, i.e. it is related to dihydrotestosterone. The Japanese researchers who described this compound characterized it as a partial androgen receptor agonist with an unusual feature — the ability to increase follistatin expression in muscle cells.

So combining these substances into one category is largely a marketing move. On sites selling “research chemicals”, both sit side by side in the SARM section, but their history, volume of data and potential risks differ substantially.

For the reader this means one simple thing: comparing YK-11 and Ostarine “by strength” is incorrect without understanding how different the evidence base is. About one substance we know the results of controlled studies in humans; about the other, mainly extrapolations from the test tube.

Structure and mechanism of action

Ostarine is a small nonsteroidal molecule of the arylpropionamide series. It binds to the androgen receptor and changes its conformation so that the set of recruited coactivators differs from the one testosterone engages. This is exactly what accounts for its tissue selectivity: in muscle the effect is pronounced, in the prostate much weaker. Importantly, nonsteroidal SARMs are not substrates of 5α-reductase or aromatase, so they are not converted into DHT or estradiol.

YK-11 acts differently. According to the Kanno group, it binds to the androgen receptor as a partial agonist but does not induce the full interaction between the receptor’s N- and C-terminal domains that is characteristic of “classic” androgens. In a culture of C2C12 myoblasts, YK-11 enhanced their differentiation into muscle fibers, and this effect partly depended on an increase in follistatin — a protein that binds myostatin.

It was precisely this “anti-myostatin” story that made YK-11 popular in online discussions. However, it is important to stress: the link with follistatin has been shown in a cell model, not in the human body. Whether the corresponding concentrations are reached in tissues, how the substance is metabolized and what its metabolites are — these are questions that still have no complete answers.

The steroidal structure of YK-11 also means that notions of the “mildness” of nonsteroidal SARMs cannot be automatically transferred to it. Its potential hepatotoxicity, effect on lipids and effect on the hormonal axis have not been systematically studied.

Evidence base: humans versus the test tube

Ostarine is one of the most studied substances of its class. In a randomized placebo-controlled phase II study (Dalton et al., 2011) in elderly men and postmenopausal women, 12 weeks of enobosarm at a dose of 3 mg per day was accompanied by a gain in lean mass and an improvement on a stair-climbing test. A subsequent study in patients with cancer cachexia (Dobs et al., 2013) also showed an increase in lean mass.

At the same time it is important to grasp the scale of these effects: we are talking about a gain of roughly one to one and a half kilograms of lean mass over several months in elderly or ill people. This is clinically meaningful for preventing sarcopenia, but far from the impressions created by sports advertising. The drug never received regulatory approval for any indication.

For YK-11 the published data are limited to studies on cell lines and isolated experiments in animals. There are no clinical trials in humans, human pharmacokinetics have not been systematically described, and a safe or effective dose is unknown. Any “recommendations” for YK-11 online are based on users’ personal experience, not on science.

This asymmetry is the main difference between the substances. Ostarine has a known, if incomplete, safety profile for short-term use at medical doses. YK-11 has an unknown safety profile altogether.

Risks and side effects

Even in clinical studies Ostarine was not “neutral” for the body. A dose-dependent decrease in HDL (“good” cholesterol) was observed, as well as suppression of total testosterone and sex-hormone-binding globulin. Outside of studies, cases of elevated liver enzymes and drug-induced liver injury have been described in people who used SARMs on their own.

For YK-11 there are no systematic data, but its steroidal nature gives grounds to expect classic androgenic problems: suppression of the hypothalamic–pituitary–gonadal axis, adverse effects on lipids and possible strain on the liver. A few small studies in rodents also raised questions about an effect on nervous tissue, but these data are still fragmentary.

Another risk common to both substances is product quality. An analysis of products sold as SARMs online (Van Wagoner et al., 2017) showed that a significant share of them contained the wrong substance or the wrong amount compared with the label, and some contained no SARM at all. For YK-11, which is hard to synthesize and unstable, this problem may be even more acute.

Finally, for women any androgen receptor agonist carries a risk of virilization. The “selectivity” of SARMs is not absolute, and for YK-11 no one has measured it in humans at all.

• Shared risks:suppression of one’s own testosterone, lowered HDL, product adulteration.
• Ostarine:cases of toxic liver injury with uncontrolled use have been described.
• YK-11:unknown safety profile, steroidal structure, no data on metabolites.

Legal status and anti-doping control

Both substances belong to class S1.2 “Other anabolic agents” of the WADA Prohibited List and are banned in sport at all times — both in and out of competition. Ostarine is one of the most frequently detected SARMs in anti-doping laboratory reports, in particular because of contaminated dietary supplements.

Neither substance is registered as a medicine. In the United States the FDA has repeatedly warned that SARM products sold as dietary supplements are illegal and that their use is associated with risks to the heart and liver. The wording “for research purposes only” on the label does not make such a product safe or legal to consume.

For athletes who undergo testing, the principle of strict liability is also important: the presence of a prohibited substance in a sample is a violation regardless of whether the athlete knew it was in the product. That is why even “ordinary” supplements should be chosen with independent certification for the absence of doping agents.

Legal consequences differ from country to country, but the general trend is toward tighter control over the circulation of such substances, not looser control.

Editorial conclusions

YK-11 and Ostarine differ primarily not in “strength” but in how well they have been studied. Ostarine is a nonsteroidal SARM with clinical study results, a modest effect on lean mass and documented side effects. YK-11 is a steroidal compound with an interesting mechanism in cell models, but without any data on safety in humans.

Neither substance is approved for treatment, both are banned in sport, and products on the market often do not match the label. So if you are concerned with preserving muscle mass or recovering after an injury, the conversation should start with a doctor, not with a choice between two unregistered substances.

The editorial team also recommends reading our materials on the mechanism of action of SARMs in general, on the effect of androgens on the lipid profile and on the tests that help assess the state of the hormonal system.

References

1. Dalton JT, Barnette KG, Bohl CE, et al. 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. J Cachexia Sarcopenia Muscle. 2011;2(3):153–161.
2. Dobs AS, Boccia RV, Croot CC, et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol. 2013;14(4):335–345.
3. Kanno Y, Ota R, Someya K, et al. Selective androgen receptor modulator, YK11, regulates myogenic differentiation of C2C12 myoblasts by follistatin expression. Biol Pharm Bull. 2013;36(9):1460–1465.
4. Narayanan R, Coss CC, Dalton JT. Development of selective androgen receptor modulators (SARMs). Mol Cell Endocrinol. 2018;465:134–142.
5. Van Wagoner RM, Eichner A, Bhasin S, et al. Chemical composition and labeling of substances marketed as selective androgen receptor modulators and sold via the internet. JAMA. 2017;318(20):2004–2010.
6. Solomon ZJ, Mirabal JR, Mazur DJ, et al. Selective androgen receptor modulators: current knowledge and clinical applications. Sex Med Rev. 2019;7(1):84–94.
7. World Anti-Doping Agency. The World Anti-Doping Code International Standard: Prohibited List. Montreal: WADA; чинна редакція.