Happy Tuesday!
I just dropped a brand-new episode on Spotify about Cardarine.
Cardarine is one of those compounds that lives in a weird lane.
It’s one of my favorite research compounds. I’ve used it in a cyclical way for years, and at the same time, it’s controversial enough that people throw it out altogether.
So in this episode, I provide my best review of the mechanisms, benefits, literature, dosage, the cancer question, and how to think clearly when the internet screams in absolutes.
Background/History
Cardarine was originally developed in the 1990s through a collaboration between GlaxoSmithKline and Ligand Pharmaceuticals as a potential therapy for metabolic and cardiovascular disease.
Obesity, type 2 diabetes, dyslipidemia, metabolic syndrome, and the downstream cardiovascular consequences are some of the biggest problems in modern medicine.
If you could create something that shifts the body toward burning fat more efficiently, improves lipids, and improves insulin dynamics, you’d have a blockbuster.
And that’s exactly why Cardarine got so much early momentum. It entered Phase 1 and Phase 2 human trials and demonstrated meaningful improvements in lipid markers and metabolic parameters.
But then it got shelved.
Long-term rodent toxicology work that raised major red flags around multi-organ tumor findings.
That’s why you also see WADA issue an explicit warning about it years later, when it started circulating in athletics and on the gray market.
Mechanisms
Contrary to popular belief, Cardarine is not a SARM.
It gets lumped into that world because the SARMS websites sell it, but mechanistically, it’s different.
It’s a potent agonist of PPAR-delta, which is a nuclear receptor involved in gene expression related to fat metabolism and energy expenditure across tissues, especially skeletal muscle and liver.
Once you take it orally, you are essentially flipping a switch that prompts your body to use fatty acids as fuel.
In skeletal muscle, PPAR-delta activation recruits downstream metabolic machinery, including pathways linked to PGC-1 alpha, one of the “master regulators” we associate with endurance adaptation.
As a result, your muscle becomes more oxidative.
Your fibers bias toward fatigue resistance.
You burn more fat.
You spare more glucose.
And when you’re doing cardio, you feel the shift.
It’s part of why in the endurance world this compound got a reputation for making “cardio feel easy.”
Clinical Results
We have limited human data, but the data we have is surprisingly clean in terms of outcomes.
In a 12-week, placebo-controlled trial in people with low HDL, GW501516 showed dose-dependent improvements in lipid markers. At 10 mg daily, HDL increased up to 16.9%, ApoA-I increased, LDL decreased, triglycerides dropped, ApoB dropped, and free fatty acids dropped.
Then there’s the famous 2-week Diabetes paper, where moderately obese men took 10 mg daily.
Even over just two weeks, the study reported reversal of multiple metabolic abnormalities, including reductions in triglycerides, LDL, ApoB, insulin, and even liver fat content, along with increased fat oxidation and a muscle signal shift toward fat utilization (CPT1b upregulation).
You feel an endurance effect, but underneath the hood, there are many more improvements taking place.
Dosage and Cycling
GW501516 is not an approved medication, it is banned in sport, and I’m not telling anyone to use it.
I’m giving you a map of what exists in the literature and what is commonly discussed in real-world use, so you can think like an adult.
In clinical trials, Cardarine was typically dosed orally once daily at 2.5-10 mg. The 12-week lipid trial and the 2-week metabolic trial both used 10 mg as the high end and showed meaningful effects at that level.
In the real world, you’ll see common “performance” use discussed around 10 to 20 mg per day, often for 6 to 8 weeks, followed by 6-8 weeks off.
My personal philosophy, and what I stated in the episode, is that if someone is going to think about this compound at all, cycling on and cycling off is the only rational way to even use it.
I get my Cardarine from two sources:
Final Thoughts
Cardarine is one of the most fascinating “what could have been” molecules in the metabolic world.
Mechanistically, it makes sense. Clinically, the lipid improvements and metabolic effects are real in the limited human trials we have.
Subjectively, it’s one of the most noticeable endurance aids I’ve personally experienced because it changes fuel preference. It just makes the work feel easier when you’re in motion.
But you cannot talk about Cardarine honestly without discussing the reason it died in the pharmaceutical industry.
Rodent cancer findings, WADA warnings, and the reality that we do not have long-term human safety data.
That doesn’t mean it’s guaranteed to cause cancer in humans. It also doesn’t mean you get to pretend the signal isn’t there. It means the only honest conclusion is uncertainty, and uncertainty requires humility.
If you are a high-performance endurance athlete in a tested federation, you already know this is off the table.
However, if you’re someone who is attempting to improve lipids and metabolic health, Cardarine still has a place in some people’s stacks and is worth the research investment.
Best,
Hunter Williams
Further Reading