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.

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.

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.

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].

 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 triglyceridesinsulin, and LDL cholesterol [15].

Also, mice given cardarine released less glucose from the liver and became more sensitive to insulinIf 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].

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 [1920].

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].

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-alphaIL-6, and NFκB [2223].

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].

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 [252627].

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].

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].

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 [830].