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DPreclinical / mechanistic only
High riskCarcinogenicity signalNo human data

Cardarine

GW-501516 · GW1516 · Endurobol

Cardarine (GW-501516, GW1516, Endurobol) is a synthetic, highly selective PPARδ (peroxisome proliferator-activated receptor delta) agonist that GlaxoSmithKline originally developed for dyslipidemia and metabolic syndrome. It is not a SARM and not a hormone; it is a research chemical that was never approved for any use in humans. Its reputation as an "endurance/fat-loss" agent comes almost entirely from rodent studies. GSK halted development because long-term rodent carcinogenicity studies produced tumors across multiple organ systems, and independent mouse studies show a PPARδ agonist can accelerate and worsen cancer (mammary and metastatic gastric tumors). There is no adequate human safety data, no human data at the doses and durations people self-administer, and no data on cancer, fertility, or hormonal recovery in humans. Human evidence is limited to two small (roughly 6-9 subjects per arm), 2-week trials measuring blood lipids only. Because the defining hazard is a preclinical cancer signal and long-term human use is completely unstudied, this compound should be treated as high-risk with an unknown but potentially serious carcinogenic liability. Educational information only — not medical advice; 21+.

Clinical readoutPED-adjacent · research-chemical
Hepatic strainNone
CardiovascularNone
HPTA suppressionNone
Half-life
Not well characte…
Route
Oral
Evidence
D
Active
Once-daily dosing was a…
1·t½2·t½3·t½4·t½5·t½
Illustrative single-compartment washout · each mark = one half-life · t½ ≈ Not well characterized in the public human literature. Human trials used once-daily oral dosing, consistent with a half-life on the order of roughly a day, but no rigorously reported terminal half-life is available; treat any single figure as uncertain.
Pharmacology

Mechanism of action

Cardarine is a potent, selective agonist of PPARδ (also called PPARβ/δ), a nuclear hormone receptor / ligand-activated transcription factor. Binding activates PPARδ, which heterodimerizes with the retinoid X receptor and drives transcription of genes governing fatty-acid uptake and beta-oxidation, mitochondrial function, and oxidative muscle-fiber metabolism. In human skeletal muscle cells it upregulates fatty-acid-handling genes (CPT1, CD36) and the cholesterol-efflux transporter ABCA1, increasing fat oxidation; in humans this shifts fuel use toward fat and lowers circulating triglycerides while raising or preserving HDL. PPARδ is also expressed in many other tissues, and the same receptor activation that reprograms muscle metabolism can, in the setting of pre-existing carcinogen exposure, promote tumor cell proliferation, adhesion and invasion in animal models — the mechanistic basis for its cancer signal. Selectivity for PPARδ over PPARα and PPARγ has been characterized in reporter-cell assays.
Kinetics

Pharmacokinetics

Half-life

Not well characterized in the public human literature. Human trials used once-daily oral dosing, consistent with a half-life on the order of roughly a day, but no rigorously reported terminal half-life is available; treat any single figure as uncertain.

Active duration

Once-daily dosing was adequate to produce sustained metabolic effects in human trials, implying a functional duration of at least ~24 hours; exact active duration in humans is not well defined.

Route

Oral (administered orally in all human studies).

Metabolism & clearance

Hepatic metabolism to hydroxy/sulfoxide metabolites, with parent drug and metabolites detectable in urine (the basis for anti-doping detection). Detailed human clearance parameters are not adequately published. PK is noted here only for washout reasoning and clinician discussion — not for evading drug testing.

For monitoring and washout planning, not drug-test evasion.

Reported effects

Physiological & performance effects

  • Increases skeletal-muscle fatty-acid oxidation and shifts fuel utilization toward fat (demonstrated in human muscle cells and in overweight men)
  • Lowers fasting triglycerides and improves post-meal triglyceride clearance in humans
  • Raises or preserves HDL cholesterol and, in overweight men, lowered LDL cholesterol and apolipoprotein B
  • Reduced liver fat content and a marker of oxidative stress (urinary isoprostanes) in a small human trial
  • Enhanced running endurance and increased oxidative muscle-fiber proportion — demonstrated in mice, not in humans
  • Promoted from anecdote as an 'endurance and fat-loss' aid; these performance claims are not established by human data
Safety

Adverse effects by system

Cardiovascular

No adequate human safety data. Short human trials measured favorable lipid changes but were far too small and brief to detect cardiovascular harm; long-term cardiovascular safety in humans is unknown, and with no long-term outcome data available, no cardiovascular safety can be assumed.

Hepatic

No human hepatotoxicity data at self-administered doses. In rodent NASH/steatohepatitis models the compound reduced liver fat and inflammation, and in a small human trial it lowered liver fat — but these are efficacy findings, not proof of hepatic safety. Real-world products are frequently unregulated research chemicals of unknown purity, adding undefined hepatic risk.

Endocrine / HPTA

No known direct action on the hypothalamic-pituitary-gonadal axis and no human endocrine data; PPARδ is not a sex-hormone pathway. Absence of data is not evidence of safety.

Reproductive

No human reproductive or fertility data. Given the multi-organ tumor and developmental concerns of PPARδ agonists in animals, reproductive safety is unknown and it should be considered contraindicated in pregnancy, breastfeeding, and anyone who may become pregnant.

Neuropsychiatric

No human psychiatric data and no established neuropsychiatric effect. Unknown.

Renal

No human renal safety data. No specific renal toxicity established in the available literature; unknown.

Hematologic

No human hematologic safety data and no established hematologic effect. Unknown.

Dermatologic

No human dermatologic data and no established skin effects. Unknown.

Recovery

HPTA suppression & recovery

Suppression: No known HPTA suppression — Cardarine is not a hormone and has no established action on the hypothalamic-pituitary-gonadal axis; however, there is no human endocrine safety data.

Because Cardarine is a PPARδ agonist and not androgenic or estrogenic, classic post-cycle HPTA recovery concerns are not expected to apply, and no SERM-based recovery is indicated for this compound on the basis of its mechanism. This is not a substitute for individual medical assessment. Any concern about hormonal status or recovery — especially if the compound was combined with anabolic agents — should be evaluated with bloodwork and directed by an endocrinologist. Where any recovery pharmacology is considered, only single-SERM approaches are within scope; dual-SERM protocols are out of scope.

Bloodwork & vitals

Monitoring

Recommended labs & checks
Baseline and periodic fasting lipid panelComprehensive metabolic panel including liver enzymes (ALT, AST, ALP, bilirubin)Fasting glucose / HbA1c and insulinComplete blood countAge-appropriate cancer screening per a physician, given the preclinical tumor signal

Cadence: Establish a baseline before any use; because there is no evidence-based safe regimen, the conservative course is not to use it — if a person uses it anyway, bloodwork before starting and at least every 8-12 weeks, with a clinician, plus prompt evaluation of any new symptom.

Warning signs — seek care
  • Any new or growing lump, unexplained weight loss, persistent abdominal or gastric pain, or blood in stool/vomit — stop and seek urgent medical evaluation for possible malignancy
  • Right-upper-quadrant pain, jaundice, dark urine, or nausea (possible liver injury)
  • Unusual fatigue, shortness of breath, chest pain, or leg swelling
  • Any persistent unexplained symptom — discontinue and consult a physician
Do not use if

Contraindications

  • Any personal or strong family history of cancer, or any active/suspected malignancy — the preclinical signal is tumor promotion across multiple organ systems
  • Pregnancy, breastfeeding, or anyone who may become pregnant — no reproductive safety data and animal carcinogenicity/developmental concern
  • Adolescents and anyone under 21
  • Pre-existing liver disease or unexplained transaminase elevation (product quality unknown; no human safety data)
  • Use without medical supervision and baseline/periodic bloodwork
  • Concurrent use of other unregulated research chemicals, SARMs, or anabolic agents, which compounds unknown and known risks
Harm reduction

Reducing harm & when to stop

  • The safest course, given a preclinical multi-organ cancer signal and no adequate human safety data, is not to use this compound.
  • There is no established safe dose or duration in humans; the only human dosing on record is 2.5-10 mg/day for just 2 weeks in tiny lipid studies — this tells you nothing about the safety of the longer, higher-dose use seen in the fitness world.
  • The main danger is cancer promotion shown in animals; anyone with any personal or family cancer history should avoid it entirely, and everyone should keep up age-appropriate cancer screening with a physician.
  • Products sold as 'Cardarine' are unregulated research chemicals of unverified identity, dose, and purity; contamination and mislabeling are common and add unknown risk.
  • If you choose to use it despite the risks, do so only with a physician's knowledge, get baseline bloodwork (lipids, liver enzymes, CBC, metabolic panel) and repeat it periodically.
  • Stop immediately and seek medical care for any new lump, unexplained weight loss, persistent abdominal/gastric pain, GI bleeding, jaundice, dark urine, right-upper-quadrant pain, chest pain, or breathlessness.
  • Do not combine with other research chemicals, SARMs, or anabolic agents; poly-use multiplies unknown and known risks.
  • Do not use if pregnant, breastfeeding, possibly pregnant, or under 21.
  • Any questions about hormonal status or recovery, particularly if combined with anabolic agents, should be evaluated with bloodwork and directed by an endocrinologist.
Evidence

Citations (8)

Every clinical claim above is tied to a primary source. Overall evidence grade D this compound lacks adequate human data; claims rest on preclinical or mechanistic evidence.

  1. 01

    Cardarine (GW-501516) is a potent, selective PPARδ agonist, characterized against PPARα and PPARγ.

    PreclinicalPMID 16038868

  2. 02

    In the first human administration (healthy volunteers, 2.5 mg and 10 mg once daily for 2 weeks), GW501516 raised HDL cholesterol, trended triglycerides downward and improved post-fat-feeding triglyceride clearance; in human skeletal muscle cells it increased fatty-acid oxidation and upregulated CPT1, CD36 and ABCA1.

    RCTPMID 17110604

  3. 03

    In moderately overweight men (10 mg once daily for 2 weeks), GW501516 reduced fasting triglycerides, apolipoprotein B, LDL cholesterol and insulin, reduced liver fat content and urinary isoprostanes (oxidative stress), and increased fat oxidation and skeletal-muscle CPT1b expression.

    RCTPMID 18024853

  4. 04

    A PPARδ agonist (GW501516) accelerated mammary tumor formation and produced more aggressive (adenosquamous/squamous) tumors in a carcinogen/progestin mouse model — a tumor-promotion signal.

    PreclinicalPMID 15867396

  5. 05

    GW501516 induced rapidly progressing, metastatic squamous-cell gastric carcinoma in a carcinogen-primed mouse model, linking PPARδ activation to tumor invasion and progression.

    PreclinicalPMID 21318167

  6. 06

    GW501516 enhanced running endurance and increased oxidative (SDH-positive) muscle-fiber proportion and fatty-acid oxidation in mice — the basis of its 'endurance' reputation, demonstrated only in animals.

    PreclinicalPMID 25943561

  7. 07

    In rodent steatohepatitis (NASH) models GW501516 reduced hepatic triglyceride, inflammation and lipid peroxidation via increased fatty-acid beta-oxidation — an efficacy finding, not proof of human hepatic safety.

    PreclinicalPMID 16574099

  8. 08

    PPARδ activation by GW501516 suppresses IL-6-driven hepatic acute-phase/inflammatory signaling in liver cells (anti-inflammatory mechanism, in vitro).

    PreclinicalPMID 17461989

Last reviewed 2026-07-06 · Verified against PubMed · Educational, not medical advice