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What is Cardarine (GW501516)? + Side Effects, Dangers

Written by Helen Quach, BS (Biochemistry) | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Helen Quach, BS (Biochemistry) | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Cardarine is a research chemical that was being investigated for its potential to boost metabolism and fat burning, prevent obesity, and increase muscle growth, but its side effects and risks are often dangerously downplayed. In fact, studies were halted because it was found to cause cancer! Learn all about GW501616, what its proponents use it for, why it’s banned from sanctioned sports, and why it’s so dangerous and should be avoided.

Disclaimer: Cardarine is illegal, its purported “benefits” are unproven, and it was shown to cause cancer as part of standard research before advancing through clinical trials. Do not under any circumstances take this compound. We cannot stress this enough. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the clinical and scientific literature.

What Is Cardarine?

Controversial Drug

Cardarine was developed by GlaxoSmithKline for its potential benefits on the heart, blood vessels, and diabetes. However, studies were halted in Phase II on animals because it caused cancers [1].

Some of cardarine’s proponents argue that cancer risks have not been proven in humans, but this is only because it was never found safe enough to justify long-term safety studies in humans. In fact, most carcinogenic substances usually don’t cause cancer in these types of animal studies because they are not sensitive enough to pick up compounds that only slightly increase the chance of developing cancer. They are designed to pick up on the worst compounds so we don’t risk the lives of human subjects in early clinical work [2].

We cannot stress this enough: cardarine has been shown to cause cancer, period! 

But how did scientists discover cardarine (less elegantly known as GW501516) in the first place?

It’s no secret that the modern inactive lifestyle contributes to many metabolic problems, such as diabetes, inflammation, and heart disease. In the search for substances that could speed up fat burning and increase physical endurance in sedentary adults, scientists turned to the PPAR-delta pathway.

Activation of PPAR-delta is associated with increased energy, fat burning, muscle building, and endurance and decreased lipids in the blood. Cardarine binds to and activates the peroxisome proliferator activator receptor delta (PPAR-delta). A lot of PPAR-delta is in the muscles, and it activates many genes important for energy use [3].

Activating PPAR-delta could play a role in building muscles, improving heart health, boosting metabolism, and reducing inflammation. Targeting this pathway with Cardarine seems promising. But researchers refer to Cardarine as a failed “exercise mimetic,” because it caused cancer in animal studies [3].

According to many researchers, there are natural and safe ways to activate PPAR-delta, such as endurance exercise and sun exposure. Some studies have also suggested that berberine could be a milder and safer PPAR-delta-activating supplement [4, 5, 6].

Scientists discovered cardarine while searching for a chemical that boosted fat burning and exercise performance, but they halted the research due to the fact that it can cause cancer.

Snapshot

Proponents:

  • May shield the brain and blood vessels
  • May boost fat burning and physical performance
  • May improve lipid profile and insulin sensitivity

Skeptics:

  • Banned due to cancer-causing effects in animals
  • It causes cancer!!!!!
  • Not well studied in humans
  • May harm the liver and worsen liver disease
  • May impair fetal development
  • Beyond dangerous
  • May cause brain damage!

Is Cardarine Legal?

Cardarine is not legal, nor is it approved for use in humans.

As its side effects have been downplayed across the internet and various forums, cardarine has gained popularity for bodybuilding and performance enhancement in athletes. With a rise in popularity, cardarine/GW501516/Endurobol is now widely available on the black market and as a research substance.

The World Anti-Doping Agency issued a rare warning about its toxicity to athletes. The agency took an additional step to warn “cheats” that this substance can be quite dangerous, raising awareness about its health risks [3].

Cardarine is popular among bodybuilders despite not being legal or approved for use in humans. Organizations such as the World Anti-Doping Agency have issued warnings about its blatant toxicity.

Is Cardarine a SARM?

Cardarine is not a SARM, which stands for selective androgen receptor modulators. SARMs activate the androgen receptors in specific tissues like bone and muscle, which increases muscle mass. They were first developed in the 40s to mimic testosterone [7].

Cardarine, on the other hand, is a PPAR-delta activator. It doesn’t act directly on androgen receptors.

Investigations of Cardarine

1) Brain

In one of the early animal studies on cardarine, treated mice appeared to have better blood circulation in the brain and reduced oxidative stress [8].

However, cardarine had both pro- and anti-inflammatory effects on inflamed rat brain cells. Some inflammatory substances (like TNF-alpha) were reduced in its presence, but others, such as IL-6, were increased. High IL-6 can cause brain cell damage [9, 10].

According to animal trials, Cardarine may protect brain cells against oxidative stress. However, it also has the potential to damage brain cells due to inflammation.

2) Fat Burning

Cardarine was first researched for this indication. PPAR-delta activates a number of genes involved in burning fat and increasing energy use [11].

Recently, several human studies shed new light on its fat-burning benefits.

In one extremely small study of 13 men with high belly fat and a bad cholesterol profile, those who received 2.5 mg of cardarine a day for 6 weeks had decreased triglycerides, fatty acids, and VLDL proteins (apoB fractions) [12].

Cardarine was associated with increased HDL cholesterol in 2 studies of 305 patients with low HDL. Patients who received cardarine also had reduced LDL, triglycerides, and apoB [13].

In another small study of 12 inactive volunteers, Cardarine increased HDL. Those who received carnitine burned more fats as an energy source and had increased activity of fat-burning and carnitine genes (ABCA1 and CPT1) [14].

Cardarine may boost fat burning and lower blood fats, but the available evidence is considered to be of extremely low quality, especially given the potential dangers.

3) Obesity

In 6 overweight volunteers, cardarine was associated with reduced symptoms of metabolic syndrome. Participants’ liver fat decreased by 20%, insulin decreased by 11%, and blood fats dropped by 23-30% (triglycerides by 30%, VLDL APOB by 26%, LDL by 23%) [14].

Similarly, in obese monkeys, those receiving cardarine had higher HDL cholesterol and lower triglycerides, insulin, and LDL cholesterol [15].

Also, mice given cardarine released less glucose from the liver and became more sensitive to insulin. If this effect could be proven out in humans, it could be helpful for obesity and type II diabetes [16].

Also in mice, cardarine was linked to increased development of muscle fibers [17].

Cardarine was initially under investigation for preventing obesity by enhancing insulin sensitivity, increasing fat-burning, and reducing blood lipids.

4) Heart and Blood Vessels

Aside from lowering cholesterol, Cardarine may have a direct effect on blood vessels.

Cardarine prevented oxidative damage to blood vessels in mice. It may reduce the risk of plaque buildup in the arteries by boosting protective and blood vessel-relaxing nitric oxide [8].

Low doses of Cardarine reduced tissue damage and inflammation in arteries of mice. It could help clear up the blood vessels, this way reducing heart disease risk and complications [18].

Cardarine increased the growth of new blood vessels in human heart cells (increasing VEGF). This could be beneficial for those with heart disease, but could also be problematic if excessive. For example, people prone to cancer should avoid taking substances like Cardarine that increase new blood vessels [19, 20].

According to animal and cell studies, Cardarine may stimulate the growth of blood vessels and protect them against oxidative stress and inflammation.

5) Kidneys

In mice, Cardarine was linked to reduced kidney inflammation, leading the authors to suggest a potential role in protecting against kidney disease. Treated mice also experienced a reduction of the activity of genes linked to kidney disease (MCP-1) [21].

6) Anti-inflammatory and Antioxidant

In general, PPAR-delta activation seems to suppress inflammation [18].

By activating PPAR-delta, cardarine could reduce liver inflammation in animals. Some researchers have concluded that it blocks substances involved in inflammatory responses and reduces the activity of inflammatory genes. In rats, cardarine consumption was associated with reduced inflammatory markers including MCP-1, TNF-alpha, IL-6, and NFκB [22, 23].

Applied on the skin, cardarine was associated with improved healing of diabetic wounds in mice, possibly due to reduced inflammation [24].

Cardarine may also have antioxidant potential:mice given cardarine produced more of the antioxidant enzymes SOD1 and catalase [8].

Cardarine has been associated with lower inflammation, reduced oxidative damage, and improved wound healing in animal trials. Human studies have not yet been conducted and will not be conducted because this compound is way too dangerous to test in humans.

7) Liver Damage

One of the main targets of cardarine is the liver, as the liver is crucial for storing, burning, and releasing fats into the body. PPAR-delta causes the liver to switch its energy source from glucose to fatty acids, thus reducing blood sugar [16].

In mouse and cell studies, cardarine has shown the potential to be beneficial to liver health. Cells expose to cardarine produced less IL-6, which may help prevent insulin resistance. Mice given cardarine suffered less liver damage from a high-fructose diet and were less likely to develop nonalcoholic fatty liver disease [25, 26, 27].

However, cardarine caused cell death in liver cells and liver damage (fibrosis) in some mice with liver disease, further underlining the dangers associated with this compound [28].

Cardarine was thought to prevent liver damage by stimulating fat-burning, improving insulin resistance, and relieving inflammation. However, it may also worsen liver disease and was found to cause liver cell death and liver damage, further demonstrating how dangerous it is.

8) Muscle Growth and Stamina

In one study, the activation of PPAR-delta via cardarine drove the development of muscle fibers in mice. These muscle fibers were associated with increased physical performance: the treated mice had improved endurance and could run for almost twice as long [17].

9) Skin Diseases

Limited research suggests that activation of PPAR-delta could improve the inflammation caused by skin diseases like psoriasis. Cardarine was also linked to reduced inflammation in human skin cells. Remember, however, that there are no approved cardarine products, let alone cardarine creams [29].

10) Blood Flow and Wound Healing

Some researchers have suggested a role for cardarine in improving blood flow and wound healing. In mice, cardarine (and, by association, PPAR-delta activation) is associated with increased levels of blood-vessel relaxing nitric oxide (via BH4). Nitric oxide helps improve blood flow and boosts wound healing [8, 30].

Usage & Potential Dangers

In clinical studies, doses of 2.5 to 10 mg/day were used for up to 12 weeks. Since this drug was never formally approved, and research was halted due to cancer risks, there is no correct dosage. Cardarine is not considered safe in any quantity.

Cardarine increased cell death in liver cells and caused liver damage in some mice with liver disease. Animal studies revealed that cardarine can cause cancer. There are not enough human studies to show the same effect, but sufficient human safety studies will never be undertaken because of the apparent dangers of this compound. Rapid cancer development in several organs in animals was also the main reason why GSK abandoned development of the drug in 2007 [28, 31, 32].

In animals, cardarine was not safe to use during pregnancy as high doses over an extended period of time posed risks to fetal development [33].

Have in mind that internet forums and blogs often downplay the side effects and present only a small fraction of the information. There is a large body of evidence demonstrating that cardarine is very dangerous! 

Cardarine caused rapid cancer development in animal trials, which terminated further drug development. It may also cause liver damage and impair fetal development. Internet forums and bodybuilding blogs often downplay its side effects, but this highly dangerous compound should never be taken by human beings.

Buy

There are vendors who sell cardarine in the United States.

We at SelfHacked advise speaking to a doctor before taking any drug, especially when taking unscheduled drugs with limited safety data. Cardarine is illegal and broadly considered unsafe, as it caused multiple types of cancer in animals. Never take this compound for any reason! We cannot stress this enough. 

Takeaway

Cardarine is a drug developed for its potential to enhance fat-burning and physical performance. However, companies halted the research after animal studies demonstrated that it can cause multiple types of cancer.

Despite the safety warnings, cardarine is popular among bodybuilders and athletes. Users claim that it boosts fat-burning, endurance, and muscle growth.

However, animal studies suggest it may worsen liver disease and impair fetal development. Online retailers and forms often downplay the side effects and health risks of cardarine. Because of the clear dangers associated with this compound, we do not recommend taking cardarine for any purpose.

About the Author

Helen Quach

BS (Biochemistry)

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