Cardarine (GW501516) is a chemical with many purported health and bodybuilding benefits, most of which have not been backed up. Cardarine may boost metabolism and fat burning, prevent obesity, and increase muscle growth. But its side effects and risks are often dangerously downplayed. Read more below to learn all about this substance and the enigma surrounding its use.
Disclaimer: By writing this post, we are not recommending this drug. 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?
Cardarine is a chemical that 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 [R].
One could argue that cancer risks have not been proven in humans. But the main reason is precisely that it was not shown to be safe even in animals, and because substances usually have to be given over a longer period of time to demonstrate cancerous effects.
But how did scientists discover Cardarine (less elegantly known as GW501516) in the first place?
It’s no secret that our modern inactive lifestyle too often causes many metabolic problems, such as diabetes, inflammation, and heart disease. In the search for substances that could somehow speed up fat burning and increase physical endurance, scientists turned to the PPAR-delta pathway.
Activation of PPAR-delta can increase energy, fat burning, muscle building, endurance, and decrease 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 [R].
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 of its unfortunate cancer-promoting side effects [R+].
Is Cardarine Legal?
Cardarine is not legal, nor is it approved for use in humans.
As the side effects are 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.
However, have in mind that 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 and to raise awareness about the health risks [R].
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 [R].
Cardarine, on the other hand, is a PPAR-delta activator. It doesn’t act directly on androgen receptors.
Potential Uses of Cardarine
However, Cardarine had both pro- and anti-inflammatory effects on inflamed rat brain cells. It reduced some inflammatory substances (like TNF-alpha) but increased other inflammatory ones, such as IL-6. High IL-6 can cause brain cell damage [R, R].
Overall, it’s still unclear if Cardarine protects the brain or if it causes damage.
Cardarine was first researched for this indication. PPAR-delta activates a number of genes involved in burning fat and increasing energy use [R].
Recently, several human studies shed new light on its fat-burning benefits.
In one study of 13 men with belly fat and a bad cholesterol profile (double-blind randomized controlled trial), Cardarine decreased triglycerides, fatty acids, and VLDL proteins (apoB fractions). It worked by forcing the liver to get rid of more VLDL particles. A lower dose of 2.5 mg/day was used for over 6 weeks [R].
Cardarine increased HDL cholesterol in 2 studies (open-label) of 305 patients with low HDL. It also reduced LDL, triglycerides, and APOB. Cardarine was dosed at 5 or 10 mg daily over 12 weeks [R].
In a small study of 12 inactive volunteers, Cardarine increased blood HDL, while the placebo decreased it. It boosted the use of fats as an energy source applied to fat and muscle cells, by activating fat-burning and carnitine genes (ABCA1 and CPT1). The volunteers took 10 mg of Cardarine daily for 2 weeks [R].
In 6 overweight volunteers (double-blind randomized controlled trial), Cardarine reversed the symptoms of metabolic syndrome without causing damage, probably by increasing fat burning and carnitine in muscles. It lowered liver fat by 20%, insulin by 11%, and blood fats (triglycerides by 30%, VLDL APOB by 26%, LDL by 23%). They used 2.5 or 10 mg of Cardarine daily over 2 weeks [R].
Cardarine prevented the activity of inflammatory substances via PPAR delta activation in fat tissue, which could help with chronic inflammation and obesity-induced insulin resistance. This is because the belly fat from obese insulin-resistant patients contains more inflammatory cytokines (TNF-alpha and IL-6) and fewer PPAR-delta compared to healthy people [R].
It increased the development of muscle fibers in mice, as opposed to the energy being turned to fats. It could potentially protect against obesity, even without physical exercise [R].
It may protect against weight gain due to diet, as it helped break down and use fats faster in muscles (tissue study) [R].
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, as it was able to increase levels of protective and blood vessel-relaxing nitric oxide [R].
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 [R].
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 must avoid taking anything that could increase their risk, such as substances like Cardarine that increase new blood vessels [R, R].
6) Anti-inflammatory and Antioxidant
In general, Cardarine seems to suppress inflammation [R].
Applied on the skin, Cardarine improved the healing of diabetic wounds in mice by reducing inflammation [R].
Cardarine could also protect and increase the survival of skin cells, improving the wound healing process by acting on the same pathway [R].
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.
Cardarine causes the liver to switch its energy source from glucose to fatty acids, which can reduce blood sugar (all via PPAR-delta activation) [R].
Short-term use protected the liver from damage due to a high-fructose diet in mice [R].
It also improved nonalcoholic liver disease in mice by helping the liver burn more fats and reducing inflammation [R].
However, Cardarine caused cell death in liver cells and liver damage (fibrosis) in some mice with liver disease [R].
8) Muscle Growth and Stamina
Activation of PPAR-delta via Cardarine drives the development of muscle fibers in mice. These muscle fibers are associated with increased physical performance. The treated mice had improved endurance and could run almost twice as long [R].
9) Skin Diseases
Activation of PPAR-delta could improve the inflammation caused by skin diseases like psoriasis. Cardarine reduced inflammation in human skin cell studies. With more research, new skin products with Cardarine may be developed [R].
10) Blood Flow and Wound Healing
Potential Risks and Side Effects of Cardarine
Cardarine increased cell death in liver cells and caused liver damage in some mice with liver disease [R].
In animals, Cardarine was not safe to use during pregnancy, as high doses over an extended period of time it posed risk to development [R].
In rats, Cardarine can cause cancer. There are not enough studies done on humans to show the same effect [R].
However, this is the main reason GSK abandoned further development of the drug in 2007 – the drug caused cancer to develop rapidly in several organs in animals [R].
Because Cardarine has a vast influence on the whole body, you should be mindful of its side effects before you consider using it [R].
Have in mind that internet forums and blogs often downplay the side effects and present only a small fraction of the information.
Dosage of Cardarine
In clinical studies, doses of 2.5 to 10 mg/day were used for up to 12 weeks.
We at SelfHacked advise speaking to a doctor before taking any drug, especially when taking unscheduled drugs with limited safety data. The safety of Cardarine has not been confirmed in humans and there were cancer risks in animals.