Cardarine (GW501516) for Endurance & Fat Oxidation — Weight & Metabolism
PPARdelta agonist (NOT a SARM). GSK abandoned after cancer findings in rodent studies. Dramatically increases endurance and fat burning. NOT FDA-approved.
Overview
GW501516 (Cardarine, Endurobol) is a selective peroxisome proliferator-activated receptor delta (PPARδ) agonist developed jointly by GlaxoSmithKline (GSK) and Ligand Pharmaceuticals in the early 2000s for the treatment of metabolic syndrome, dyslipidemia, and cardiovascular disease. Despite being widely marketed as a SARM, Cardarine is NOT a selective androgen receptor modulator — it has no interaction with the androgen receptor and does not affect testosterone, LH, FSH, or the HPG axis. Phase I and Phase II clinical trials demonstrated significant improvements in HDL cholesterol, reductions in LDL cholesterol, triglycerides, and fasting insulin, and increases in fatty acid oxidation markers. However, GSK abandoned all clinical development of GW501516 in 2007 after a 104-week (2-year) carcinogenicity study in Han Wistar rats revealed rapid development of tumors in multiple organs including the colon, liver, stomach, skin, tongue, urinary bladder, and mammary gland at doses of 5mg/kg/day and above. The cancer risk in humans remains debated — proponents argue that the rat doses were far higher than human doses and that the study duration of 2 years represents a disproportionately large portion of a rat lifespan. However, no long-term human safety studies exist to refute the cancer signal, and the precautionary principle strongly argues against human use. GW501516 dramatically increases endurance capacity in animal models — mice treated with GW501516 could run approximately 75% further than controls (Narkar et al., 2008; PMID: 18674809). This earned it the nickname "exercise in a bottle." The compound activates PPARδ in skeletal muscle, shifting fuel substrate utilization from glucose to fatty acids, increasing fat oxidation and endurance simultaneously. GW501516 has been prohibited by WADA since 2009 and was the subject of an unprecedented WADA warning to athletes in 2013. It is NOT FDA-approved and will never receive approval given the carcinogenicity findings.
Indications
- Phase II investigation for metabolic syndrome and dyslipidemia (GSK, abandoned 2007)
- Research into PPARdelta-mediated fatty acid oxidation enhancement
- Preclinical investigation for endurance enhancement (PMID: 18674809)
- Abandoned clinical development due to carcinogenicity findings in rats
- WADA prohibited substance since 2009
- This compound should NOT be used by humans due to cancer risk
Mechanism of Action
GW501516 absorbed orally with high bioavailability. Half-life 16-24 hours. Distributes to skeletal muscle, liver, and adipose tissue where PPARdelta is highly expressed. Does NOT interact with androgen receptors
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| GW501516 (Cardarine) | 10 mg/day | Once daily | Common research dose; cancer risk applies regardless of dose |
| GW501516 (Cardarine) | 20 mg/day | Once daily or split | Higher research dose; no evidence of additional benefit vs increased risk |
| GW501516 (Cardarine) | 10-20 mg/day | 45-60 min pre-exercise | Timed pre-workout for acute endurance enhancement |
Evidence Grade
GRADE D
Safety & Contraindications
- CANCER RISK: Multiple organ tumors in 2-year rat carcinogenicity study (colon, liver, stomach, skin, bladder, tongue, mammary)
- All clinical development abandoned by GSK in 2007 due to cancer findings
- NO long-term human safety data to assess cancer risk in humans
- NOT a SARM — does not interact with androgen receptor
- WADA issued unprecedented warning to athletes in 2013 about health risks
- No HPG axis suppression — no PCT needed (not an androgen)
- Potential promotion of existing precancerous lesions in humans
- Unknown interaction with human tumor suppressor pathways
- Gray-market products of unknown purity and composition
- Half-life 16-24 hours — effects persist after cessation
- Cannot rule out promoter effects on human carcinogenesis at any dose