RAD-140 + MK-677 + YK-11 Stack

RAD-140, MK-677 and YK-11: three substances, one set

RAD-140, MK-677 and YK-11 often appear together in fitness forums. This is referred to as a “stack,” meaning a combination of several substances. At first glance, the three may seem related. In fact, however, they differ greatly in their structure, mode of action and level of research.

This article introduces each of the three substances individually. It then addresses the key question for any combination: What happens when their effects and risks overlap? You’ll also find out what the legal situation is in Germany. Everything is explained so that beginners without medical knowledge can follow along.

One thing up front: This combination has never been studied scientifically. There is not a single study in which humans or animals were given all three substances together. Anything that can be said about how they interact is based on their individual profiles and basic pharmacology.

Overview: Who’s who in the stack?

Before we go into detail, a quick comparison is helpful. The table shows that only two of the three substances act on the same receptor. The third works in a completely different way.

RAD-140 (Testolon, Vosilasarm)

RAD-140 was developed by the US company Radius Health. It is known as Testolon in the fitness community and, in medical research, as Vosilasarm. It belongs to the non-steroidal SARMs. These substances are intended to activate androgen receptors primarily in muscles and bones, while having less effect on other tissues such as the prostate.

What was RAD-140 studied for?

Initially, researchers investigated RAD-140 as a potential treatment for muscle wasting. In animal studies in monkeys and rats, it increased muscle mass and had a weaker effect on the prostate than testosterone. Later, the focus shifted to cancer research. In certain types of breast cancer, activating the androgen receptor can slow tumor growth.

A Phase I study therefore tested RAD-140 in women with advanced, hormone-sensitive breast cancer. Phase I means that the main aim was to assess tolerability and determine the dose in a small group of seriously ill patients. In this study, elevated liver enzyme levels occurred, among other effects. There are no study data for healthy people.

Known risks of RAD-140

• Liver: Several cases of liver damage following the use of RAD-140 products have been described in medical literature, some involving jaundice.
• Hormonal axis: As a potent activator of the androgen receptor, RAD-140 is likely to suppress the body’s own testosterone production.
• Blood lipids: A decrease in protective HDL cholesterol has often been observed with SARMs.
• Unknown long-term effects: There are no long-term data.

MK-677 (Ibutamoren)

MK-677 is often called a SARM, but it is not one. It does not act on the androgen receptor at all. Instead, MK-677 mimics the body’s own hormone ghrelin, often called the “hunger hormone.” Ghrelin not only stimulates appetite, but also prompts the pituitary gland to release growth hormone. This, in turn, increases the production of IGF-1 in the liver, a messenger that mediates many growth processes.

What do studies show about MK-677?

The pharmaceutical company Merck developed MK-677 in the 1990s. Unlike many research substances, it was studied in humans. One well-known study lasted two years and involved older adults. Growth hormone and IGF-1 levels rose significantly, and lean body mass increased. However, fasting blood sugar also rose, and insulin sensitivity decreased.

Another study involving older patients recovering from hip fractures was terminated early. Heart failure occurred more often in the MK-677 group than in the comparison group. Whether there was a causal link remained unclear. However, this finding is important when assessing safety. MK-677 has still not been approved as a medicine.

Known risks of MK-677

• Blood sugar: elevated fasting blood sugar and reduced insulin sensitivity.
• Appetite: significantly increased hunger.
• Water retention: swelling, for example in the hands and feet.
• Joint and muscle pain as well as numbness, for example in the form of carpal tunnel syndrome.
• Heart: signs of a possible risk of heart failure in people with pre-existing conditions.

YK-11

YK-11 is almost always sold as a SARM. Chemically, this is misleading. The molecule is derived from dihydrotestosterone (DHT) and has the typical basic structure of a steroid. Japanese researchers described it in 2011 as a partial activator of the androgen receptor.

What is known about YK-11?

YK-11 became known through a 2013 cell study. In the study, it stimulated follistatin production in mouse muscle precursor cells. Follistatin inhibits myostatin, a substance produced by the body that limits muscle growth. However, this observation comes from cell culture, not a living organism.

Beyond that, there are only a few animal studies. There is almost no data on how it is absorbed, distributed or broken down in the human body. Doping laboratories have shown that YK-11 breaks down into numerous metabolites in the body. Its safety and the amount needed to have any effect are unknown.

Known and potential risks of YK-11

• Hormonal axis: As an androgen, YK-11 is likely to suppress the body’s own testosterone production.
• Liver: Data is lacking. However, its steroidal structure makes a strain on the liver plausible.
• Androgenic effects: Acne, hair loss and effects on the prostate are possible.
• Unknown profile: Without studies in humans, many risks remain unclear.

Why are such stacks offered at all?

Combinations are popular in the fitness world because they sound more effective. The reasoning often goes: if one substance helps, three will help even more. In pharmacology, however, things rarely work that simply. Approved combination products undergo their own studies before reaching the market. Researchers specifically assess whether the substances are compatible and whether the combination offers an advantage over the individual substances.

No such assessment has ever been carried out for this stack. The combination is based on anecdotal reports and marketing, not data. In addition, many forum reports are based on products whose contents have never been verified. These reports should therefore be viewed with caution.

How do the three substances work together?

Combinations are usually based on the assumption that their effects complement each other. The same applies to the risks. Since the combination has never been studied, we can only make reasoned assessments. Three types of interaction are important here.

1. Same target: RAD-140 and YK-11

Two of the three substances activate the same receptor. Their effects on the androgen receptor are therefore likely to be additive. This applies not only to the desired effects, but also to the unwanted ones. In particular, the feedback to the brain is likely to be stronger. This could lead to greater suppression of the body’s own hormone production than with either substance alone.

2. Different systems with shared target organs

MK-677 works through a different pathway. But ultimately, the effects converge in the same organs. The heart, blood vessels, liver and metabolism respond to androgens as well as to growth hormone and IGF-1. If SARMs lower HDL cholesterol while MK-677 simultaneously raises blood sugar, both put strain on the cardiovascular system from two sides.

3. Unknown metabolic interactions

All three substances are likely broken down by the liver. The exact enzymes involved have not been adequately studied for YK-11 and, in part, RAD-140. It is therefore unknown whether the substances affect each other’s breakdown. In theory, their levels could be higher or remain effective for longer than expected.

How the risks add up

The following table shows the areas where the risks of the three substances overlap. The more checkmarks in a row, the more a risk may accumulate.

Heart and circulation: the most critical concern

Particular attention should be paid to the cardiovascular system. Several stressors converge here: falling HDL cholesterol, rising blood sugar, water retention and possibly higher blood pressure. Each of these factors is considered a risk factor on its own. Together, they can amplify one another. The signs of heart failure in the MK-677 study make this concern even more significant.

The liver: several stressors at once

Liver damage from RAD-140 has been documented in case reports. Data on YK-11 are lacking, but its steroidal structure suggests that it could place a strain on the liver. When several substances are metabolized by the liver at the same time, the overall burden increases. Warning signs such as yellowing of the skin or eyes, dark urine, pale stools, itching or pain in the upper right abdomen require emergency medical care.

The hormonal axis: a double brake

RAD-140 and YK-11 both send the brain the signal that there are “enough androgens.” The brain responds by reducing LH and FSH. The testes then produce less testosterone and fewer sperm. After stopping, people often lack their body's own testosterone because the axis is still suppressed. Typical effects include fatigue, loss of libido, erectile problems and low mood. How long recovery takes cannot be predicted.

Which substance causes which side effect?

One problem with any combination that is often overlooked is attribution. If symptoms occur, it is difficult to say which substance is causing them. This also makes medical treatment more difficult. If in doubt, a doctor must consider all three substances as possible causes. That is why it is so important to be honest about what you have taken in an emergency.

Product quality: three substances, three sources of error

Laboratory analyses of SARM products purchased online have repeatedly shown that many labels are inaccurate. The amount of active ingredient was often wrong; sometimes the product contained a different substance or none at all. With a set containing three substances, this uncertainty triples. Each individual component may be mislabeled or contaminated.

For laboratories, this means that each substance should have its own certificate of analysis for the exact batch. It should come from an independent testing laboratory and state the method used, such as HPLC or mass spectrometry. The batch number on the certificate must match the one on the label. For combination capsules, it is also important that the certificate lists all three active ingredients and their amounts separately.

Who would be at particular risk

The risks described would be especially high for some people. These include:

• People with heart disease, high blood pressure or elevated blood lipids,
• People with diabetes, prediabetes or severe obesity,
• People with liver disease or regular alcohol consumption,
• Men who want to have children,
• People with a history of cancer, since growth hormone and IGF-1 promote cell growth,
• Adolescents whose hormonal systems are still developing,
• Women, in whom androgenic substances can cause masculinizing and sometimes permanent changes, as well as pregnant and breastfeeding women.

Legal situation in Germany and the EU

Not approved as a medicinal product

None of the three substances is approved as a medicinal product in Germany, the EU or the US. Under the German Medicines Act (AMG), a substance is considered a medicinal product if it is intended to affect bodily functions in humans. Such a product may not be marketed without approval. The label “for research purposes only” therefore describes the only permitted use.

Not food supplements

SARMs and growth hormone secretagogues may not be sold as food supplements in the EU. Authorities and customs regularly take action against such offers. These products are repeatedly reported through the European rapid alert system.

Anti-Doping Act and WADA

The WADA lists all three substances on its Prohibited List. RAD-140 and YK-11 fall under the anabolic agents in class S1. MK-677 is classified as a growth hormone secretagogue in class S2. All three are prohibited at all times, both in and out of competition, and anti-doping laboratories can detect them. Germany's Anti-Doping Act makes the trafficking and distribution of doping substances a criminal offense, and also criminalizes their use by organized competitive athletes. The Act's annex, in its current version, specifies exactly which individual substances are covered.

Storage and handling

All three substances should be stored in a cool, dry place, protected from light. Containers should remain tightly closed and clearly labeled to prevent mix-ups. Clear labeling is especially important for a set. Keep them out of reach of children and unauthorized persons. In the laboratory, protective gloves and clean work surfaces are standard practice.

Frequently asked questions about the RAD-140 + MK-677 + YK-11 stack

Are all three substances SARMs?

No. Only RAD-140 is a classic non-steroidal SARM. YK-11 is chemically a steroid that acts on the androgen receptor. MK-677 acts through the ghrelin receptor and stimulates the release of growth hormone.

Has this combination ever been studied?

No. There are no studies in which all three substances were tested together. Statements about how they interact are based on their individual profiles.

Is combining them safer than taking high amounts of a single substance?

There is no evidence of this. Because the risks overlap in several areas, the overall burden is more likely to be higher.

Which substance has been studied the most?

MK-677 has been investigated in several clinical studies in humans. There is an early study of RAD-140 in female cancer patients. YK-11 has only been tested in cell cultures and a few animal studies.

Can these substances be detected in doping tests?

Yes. Detection methods exist for all three substances. Positive tests for SARMs and MK-677 have already led to numerous bans.

Are these substances legal in Germany?

None of the three is approved as a medicinal product, and none may be sold for use in humans. The German Anti-Doping Act also applies when they are used for doping purposes.

Conclusion

RAD-140, MK-677 and YK-11 are often mentioned together, but they are fundamentally different. RAD-140 is a SARM from cancer research, MK-677 is a growth hormone secretagogue with known metabolic risks, and YK-11 is a poorly researched steroid. What they have in common is that none of the three substances is approved.

Combining them does not make the situation any simpler; it makes it more confusing. Risks to the hormonal axis, liver, heart and metabolism may overlap and intensify. At the same time, it becomes harder to attribute side effects to a specific substance. Anyone considering this stack should understand these connections and critically assess claims made in forums and advertising.