Cardarine (GW-501516)

Mechanism: PPARdelta agonist. Activates peroxisome proliferator-activated receptor delta (PPARdelta/PPARbeta) in skeletal muscle, fat, and other tissues. This upregulates genes involved in fatty acid oxidation (CPT1, ABCA1, UCP3), shifts fuel preference toward fat at rest and during exercise, increases mitochondrial biogenesis, and improves insulin sensitivity. It has no androgenic activity and does not interact with the HPTA.

NOT a SARM: Cardarine is mechanistically distinct from all SARMs. It does not bind androgen receptors. It is grouped with SARMs in the bodybuilding community by convention, not by pharmacology.

Dosage:

• Bodybuilding: 10-20 mg/day for 8-12 weeks
• Typically once-daily dosing
• No established clinical dose (development halted before Phase II)

Administration:

• Oral. Available as raw powder or liquid suspension (research-chemical grade only; GlaxoSmithKline halted all development; no pharmaceutical form exists).
• Once-daily dosing. Often taken 1-2 hours before training for acute endurance effect.

Key Notes:

• Clinical development was abandoned by GlaxoSmithKline after preclinical carcinogenicity studies demonstrated rapid and multi-tissue tumour formation in rodents (colon, liver, tongue, stomach, skin, testes, ovaries) at doses and durations used in chronic toxicity studies. The carcinogenic mechanism is thought to involve PPARdelta-mediated promotion of cell proliferation.
• The relevance of rodent carcinogenicity data to human risk at lower doses and shorter durations is debated but unresolved. No human carcinogenicity data exists. The risk is theoretical but not dismissible.
• Unlike SARMs, bloodwork effects are typically favourable: HDL increases, triglycerides and LDL decrease, fasting insulin and HOMA-IR may improve. These are the opposite direction to AAS and SARM effects on lipids.
• No HPTA suppression: testosterone, LH, FSH, and SHBG are unaffected. No PCT is required.
• No liver stress at typical doses: ALT, AST, ALP are generally unaffected.
• WADA prohibited under S4 (hormone and metabolic modulators) at all times.
• Detection window is approximately 40 days, notably long for an oral non-hormonal compound. This has led to multiple athlete anti-doping violations from contaminated supplements.
• Monitor: lipid panel (to confirm expected HDL improvement and triglyceride reduction), fasting glucose, and HOMA-IR if combining with GH or peptides.