Cardarine

updated

Cardarine, or GW501516, is not a SARM. Short human trials changed lipid and fuel-use biomarkers, but no published result establishes weight loss, endurance, cardiovascular benefit, or chronic safety. Two 104-week sponsor toxicology abstracts reported tumors across multiple tissues in rats and mice.

Selective PPAR-beta/delta nuclear-receptor agonist

  • Small molecule, not a peptide or SARM
  • Also called GW501516, GW-1516, and GSK-516
  • No FDA-approved product or prescribing label

Is Cardarine a SARM, peptide, or metabolic drug?

It is an experimental small-molecule agonist of the PPAR-beta/delta nuclear receptor. It is not a peptide and does not act through the androgen receptor, so calling it a SARM is scientifically wrong.

FDA's substance record identifies GW-501516, Cardarine, GSK-516, and GW-1516 as names for the same ingredient substance, with formula C21H18F3NO3S2 and CAS 317318-70-0. The record also says that a UNII is an identity code and does not imply regulatory review or approval.

Online sellers often group it with SARMs. FDA repeated one seller's SARM marketing category in an enforcement letter, but that does not change the molecule's receptor target.

FDA SRS · identity and aliases

Official substance identity record

U.S. Food and Drug Administration.

The record identifies GW-501516 as the preferred substance name and lists Cardarine, GSK-516, GW-1516, GW501516, formula C21H18F3NO3S2, CAS 317318-70-0, and UNII 7I2HA1NU22.

  • Ingredient-substance identity only
  • UNII availability does not imply regulatory review or approval
Participants / model
Not applicable
Treatment
Not applicable
Study design
FDA substance registry
Funding
U.S. Food and Drug Administration

Identity record, not an approval record or clinical study.

Read the original source
First human study · 24 sedentary volunteers

Randomized controlled biomarker trial

Sprecher et al., Arteriosclerosis Thrombosis and Vascular Biology, 2007

Twenty-four healthy hospitalized sedentary volunteers received placebo or one of two GW501516 exposures for two weeks. HDL rose relative to the placebo group's decline, and post-meal triglyceride clearance improved. Exercise capacity, weight loss, and clinical outcomes were not measured.

  • 9 participants in each active group and 6 placebo
  • Two-week exposure
  • Sedentary inpatient setting
Participants / model
24 healthy volunteers
Treatment
Two oral GW501516 groups versus placebo
Follow-up
2 weeks
Study design
Randomized placebo-controlled biomarker study with parallel in-vitro experiments
Funding
GlaxoSmithKline

Small, short, and not a performance or weight-loss trial; the abstract does not provide a complete safety table.

Read the original source
FDA letter · unapproved Cardarine product

FDA enforcement letter

U.S. Food and Drug Administration, May 18, 2021

FDA identified a marketed GW-501516 Cardarine product, said no approved applications were in effect for the named products, and treated their sale as unapproved-new-drug and misbranding violations.

  • No FDA-approved application for the named product
  • Seller's SARM category does not establish receptor pharmacology
Participants / model
A named U.S. online seller and its marketed products
Treatment
Not applicable
Follow-up
Inspection and online review described through 2021
Study design
Regulatory enforcement letter
Funding
U.S. Food and Drug Administration

A warning letter does not establish global approval status or clinical safety.

Read the original source

What did the controlled human studies actually find?

They showed short-term changes in lipids, lipoprotein metabolism, insulin, liver fat, oxidative-stress markers, and meal-fat oxidation. They were biomarker studies lasting two to twelve weeks, not clinical-outcome or athletic-performance trials.

Published controlled human evidence
StudyPopulation and comparatorDurationReported result
First human lipid study24 healthy volunteers: 9 in each active group and 6 placebo; hospitalized and sedentary2 weeksHDL rose relative to a decline in placebo, and post-meal triglyceride clearance improved; this was not an exercise test
Metabolic mechanism study18 moderately overweight healthy men: 6 GW501516, 6 GW590735, 6 placebo2 weeksGW501516 group changes included triglycerides -30%, apoB -26%, LDL -23%, insulin -11%, liver fat -20%, and urinary isoprostanes -30%; HDL was unchanged
Low-HDL study268 adults randomized among three GW501516 groups and placebo; separate exploratory group of 3712 weeksAt the highest active exposure, reported changes from baseline included HDL +16.9%, LDL -7.3%, triglycerides -16.9%, apoB -14.9%, and free fatty acids -19.4%
Lipoprotein-kinetics study13 dyslipidemic men with central obesity in a randomized double-blind crossover against placebo6 weeks per periodChanged VLDL, LDL, apoC-III, and HDL-particle production and clearance measures

Percentages are the publications' reported biomarker changes, not evidence of fewer heart attacks, weight loss, or improved endurance. The abstracts do not provide a complete adverse-event table.

Why does the registry say 424 people while the main paper says 268?

ClinicalTrials.gov lists 424 actual participants for the multi-stage PAD20001 protocol. The 2012 publication reports a 268-person randomized study plus a separate 37-person exploratory study. The registry and paper share the protocol identity, but the public records do not fully reconcile which stages or participants make up the difference. The published effect estimates therefore keep the paper's denominators rather than borrowing 424.

Twelve-week study · 268 randomized adults

Randomized dose-ranging biomarker trial

Olson et al., Arteriosclerosis Thrombosis and Vascular Biology, 2012

The publication reports 268 adults with low HDL randomized to three GW501516 groups or placebo for 12 weeks, plus a separate exploratory study of 37. At the highest active exposure, reported baseline changes included HDL +16.9%, LDL -7.3%, triglycerides -16.9%, apoB -14.9%, and free fatty acids -19.4%.

  • Lipid and apolipoprotein endpoints
  • No cardiovascular events, endurance, or weight-loss endpoint
  • Longest published controlled exposure in the cited human reports was 12 weeks
Participants / model
268 adults with low HDL in the randomized study and 37 in an exploratory study
Treatment
Three oral GW501516 groups versus placebo
Follow-up
12 weeks
Study design
Multicenter randomized dose-ranging biomarker trial
Funding
GlaxoSmithKline

The registry lists 424 participants for the multi-stage protocol; the public records do not fully reconcile that total with the paper's reported groups. The abstract does not provide a complete adverse-event table.

Read the original source
Registry · 424 enrolled, no posted results

Clinical trial registry

ClinicalTrials.gov NCT00158899.

The completed multi-stage low-HDL protocol lists 424 actual enrollment and no posted results. It planned HDL, other lipids, oral clearance, and apparent volume of distribution over a 12-week timeframe. The published paper reports 268 randomized participants plus 37 in a separate exploratory group.

  • Sponsor: GlaxoSmithKline
  • No results posted
  • Registry and publication denominators are not fully reconciled
Participants / model
Adults aged 18 to 75 with low HDL and without diabetes, coronary disease, or atherosclerotic disease
Treatment
Oral GW501516 study tablets versus placebo and protocol comparators
Follow-up
Registered 12-week outcome timeframe
Study design
Randomized double-blind multi-stage Phase 2 registry record
Funding
GlaxoSmithKline

Registry record, not a posted result set; its official title and detailed description also disagree on eight versus twelve weeks.

Read the original source
First human study · 24 sedentary volunteers

Randomized controlled biomarker trial

Sprecher et al., Arteriosclerosis Thrombosis and Vascular Biology, 2007

Twenty-four healthy hospitalized sedentary volunteers received placebo or one of two GW501516 exposures for two weeks. HDL rose relative to the placebo group's decline, and post-meal triglyceride clearance improved. Exercise capacity, weight loss, and clinical outcomes were not measured.

  • 9 participants in each active group and 6 placebo
  • Two-week exposure
  • Sedentary inpatient setting
Participants / model
24 healthy volunteers
Treatment
Two oral GW501516 groups versus placebo
Follow-up
2 weeks
Study design
Randomized placebo-controlled biomarker study with parallel in-vitro experiments
Funding
GlaxoSmithKline

Small, short, and not a performance or weight-loss trial; the abstract does not provide a complete safety table.

Read the original source
Two-week study · six exposed men

Randomized double-blind mechanistic trial

Risérus et al., Diabetes, 2008

Eighteen moderately overweight healthy men were randomized six per group to GW501516, GW590735, or placebo for two weeks. In the GW501516 group, reported changes included triglycerides -30%, apoB -26%, LDL -23%, insulin -11%, liver fat -20%, and urinary isoprostanes -30%; HDL was unchanged. Meal-fat oxidation and skeletal-muscle CPT1b expression increased.

  • Six participants received GW501516
  • Stable-isotope meal test and muscle biopsy
  • No weight-loss or exercise outcome
Participants / model
18 healthy moderately overweight men
Treatment
GW501516 versus a PPAR-alpha agonist versus placebo, six per group
Follow-up
2 weeks
Study design
Double-blind randomized three-group mechanistic trial
Funding
GlaxoSmithKline involvement reported in authorship

The percentages are short-term biomarker changes in a six-person active group, not proof of clinical benefit or chronic safety.

Read the original source
Twelve-week study · 268 randomized adults

Randomized dose-ranging biomarker trial

Olson et al., Arteriosclerosis Thrombosis and Vascular Biology, 2012

The publication reports 268 adults with low HDL randomized to three GW501516 groups or placebo for 12 weeks, plus a separate exploratory study of 37. At the highest active exposure, reported baseline changes included HDL +16.9%, LDL -7.3%, triglycerides -16.9%, apoB -14.9%, and free fatty acids -19.4%.

  • Lipid and apolipoprotein endpoints
  • No cardiovascular events, endurance, or weight-loss endpoint
  • Longest published controlled exposure in the cited human reports was 12 weeks
Participants / model
268 adults with low HDL in the randomized study and 37 in an exploratory study
Treatment
Three oral GW501516 groups versus placebo
Follow-up
12 weeks
Study design
Multicenter randomized dose-ranging biomarker trial
Funding
GlaxoSmithKline

The registry lists 424 participants for the multi-stage protocol; the public records do not fully reconcile that total with the paper's reported groups. The abstract does not provide a complete adverse-event table.

Read the original source
Crossover trial · 13 dyslipidemic men

Randomized double-blind crossover trial

Ooi et al., Journal of Clinical Endocrinology and Metabolism, 2011

Thirteen dyslipidemic men with central obesity completed randomized double-blind crossover periods of GW501516 and placebo. GW501516 changed VLDL, LDL, apoC-III, apoA-II, and HDL-particle production or clearance measures.

  • 13 men
  • Six-week intervention periods with two-week washout
  • Lipoprotein kinetics rather than clinical outcomes
Participants / model
13 dyslipidemic men with central obesity
Treatment
Oral GW501516 versus placebo in crossover periods
Follow-up
6 weeks per period with 2-week washout
Study design
Randomized double-blind crossover mechanistic trial
Funding
National Heart Foundation of Australia collaboration; GW501516 supplied through development program

Small mechanistic study; no performance, weight-loss, or cardiovascular-event outcome.

Read the original source

Did any published controlled human study show weight loss or better endurance?

No published controlled human trial measured durable weight loss, exercise capacity, endurance, body composition, cardiovascular events, or diabetes prevention.

The first human study deliberately kept participants sedentary and measured lipid handling. The two-week metabolic study measured laboratory and imaging markers. The 12-week low-HDL paper measured lipids and apolipoproteins. The 13-man crossover studied lipoprotein kinetics. None was a running, cycling, body-composition, weight-management, or cardiovascular-outcomes trial.

A 71-person registry listed body-fat levels as its primary outcome, but no results are posted. A separate 30-person heart-energetics study is listed as terminated without a reason and also has no posted results. A registered endpoint without results is an unanswered question, not evidence of benefit or failure.

Registry records · unreported body-fat and heart studies

Clinical trial registry record set

ClinicalTrials.gov records

Four relevant records list NCT00158899, NCT00388180, NCT00318617, and NCT00841217. None posts results. NCT00388180 completed with 71 enrolled and registered body fat as the primary outcome. NCT00318617 enrolled 30 and is marked terminated without a reason; it registered cardiac-energetics outcomes.

  • A registered outcome is not a result
  • The terminated record gives no reason
  • The registry misspells the intervention in one record
Participants / model
Four registered human GW501516 studies
Treatment
Oral GW501516 or spelling variants used in the records
Record date
Records last updated between 2009 and 2017
Study design
Four ClinicalTrials.gov records classified by status and posted results

NCT00318617 uses the intervention spelling GW510516X.

Read the original source
First human study · 24 sedentary volunteers

Randomized controlled biomarker trial

Sprecher et al., Arteriosclerosis Thrombosis and Vascular Biology, 2007

Twenty-four healthy hospitalized sedentary volunteers received placebo or one of two GW501516 exposures for two weeks. HDL rose relative to the placebo group's decline, and post-meal triglyceride clearance improved. Exercise capacity, weight loss, and clinical outcomes were not measured.

  • 9 participants in each active group and 6 placebo
  • Two-week exposure
  • Sedentary inpatient setting
Participants / model
24 healthy volunteers
Treatment
Two oral GW501516 groups versus placebo
Follow-up
2 weeks
Study design
Randomized placebo-controlled biomarker study with parallel in-vitro experiments
Funding
GlaxoSmithKline

Small, short, and not a performance or weight-loss trial; the abstract does not provide a complete safety table.

Read the original source
Two-week study · six exposed men

Randomized double-blind mechanistic trial

Risérus et al., Diabetes, 2008

Eighteen moderately overweight healthy men were randomized six per group to GW501516, GW590735, or placebo for two weeks. In the GW501516 group, reported changes included triglycerides -30%, apoB -26%, LDL -23%, insulin -11%, liver fat -20%, and urinary isoprostanes -30%; HDL was unchanged. Meal-fat oxidation and skeletal-muscle CPT1b expression increased.

  • Six participants received GW501516
  • Stable-isotope meal test and muscle biopsy
  • No weight-loss or exercise outcome
Participants / model
18 healthy moderately overweight men
Treatment
GW501516 versus a PPAR-alpha agonist versus placebo, six per group
Follow-up
2 weeks
Study design
Double-blind randomized three-group mechanistic trial
Funding
GlaxoSmithKline involvement reported in authorship

The percentages are short-term biomarker changes in a six-person active group, not proof of clinical benefit or chronic safety.

Read the original source
Twelve-week study · 268 randomized adults

Randomized dose-ranging biomarker trial

Olson et al., Arteriosclerosis Thrombosis and Vascular Biology, 2012

The publication reports 268 adults with low HDL randomized to three GW501516 groups or placebo for 12 weeks, plus a separate exploratory study of 37. At the highest active exposure, reported baseline changes included HDL +16.9%, LDL -7.3%, triglycerides -16.9%, apoB -14.9%, and free fatty acids -19.4%.

  • Lipid and apolipoprotein endpoints
  • No cardiovascular events, endurance, or weight-loss endpoint
  • Longest published controlled exposure in the cited human reports was 12 weeks
Participants / model
268 adults with low HDL in the randomized study and 37 in an exploratory study
Treatment
Three oral GW501516 groups versus placebo
Follow-up
12 weeks
Study design
Multicenter randomized dose-ranging biomarker trial
Funding
GlaxoSmithKline

The registry lists 424 participants for the multi-stage protocol; the public records do not fully reconcile that total with the paper's reported groups. The abstract does not provide a complete adverse-event table.

Read the original source
Crossover trial · 13 dyslipidemic men

Randomized double-blind crossover trial

Ooi et al., Journal of Clinical Endocrinology and Metabolism, 2011

Thirteen dyslipidemic men with central obesity completed randomized double-blind crossover periods of GW501516 and placebo. GW501516 changed VLDL, LDL, apoC-III, apoA-II, and HDL-particle production or clearance measures.

  • 13 men
  • Six-week intervention periods with two-week washout
  • Lipoprotein kinetics rather than clinical outcomes
Participants / model
13 dyslipidemic men with central obesity
Treatment
Oral GW501516 versus placebo in crossover periods
Follow-up
6 weeks per period with 2-week washout
Study design
Randomized double-blind crossover mechanistic trial
Funding
National Heart Foundation of Australia collaboration; GW501516 supplied through development program

Small mechanistic study; no performance, weight-loss, or cardiovascular-event outcome.

Read the original source

What exactly did the 104-week animal toxicology studies report?

Sponsor scientists reported treatment-related neoplasms in multiple tissues at every active dose tested in both Han Wistar rats and CD-1 mice. The evidence is serious, but the public source is two 2009 conference abstracts rather than full peer-reviewed study reports.

What the original Society of Toxicology abstracts report
ModelExposureSurvivalNeoplastic findings
Han Wistar ratsDaily oral gavage for 104 weeks; sex-specific active groups spanning 3 to 40 mg/kg/day, with male levels changed after week 6Female mortality increased at all active levels; uterine endometrial adenocarcinoma contributed to many deathsRelated neoplasms were reported in liver, bladder, thyroid, tongue, stomach, skin, Harderian gland, testes, ovary, and uterus
CD-1 miceDaily oral gavage for 104 weeks at 10, 30, 60, or 80 mg/kg/daySurvival decreased at 30 mg/kg/day and aboveLiver adenoma from the lowest active level, liver carcinoma at 30 and above, and stomach carcinoma plus combined squamous-cell tumors at every active level

The abstracts do not report group sizes, tumor incidence counts, confidence intervals, or a full pathology dataset. Animal exposures are not converted into human doses.

What does the shorter ApcMin/+ mouse experiment add?

In tumor-prone ApcMin/+ mice with intact PPAR-delta, seven weeks of GW501516 produced about a twofold increase in small-intestinal tumor number and a 3.6-fold increase in colon tumor number versus vehicle. The effect did not appear in the PPAR-delta-deleted comparison. This supports a receptor-dependent tumor-promotion mechanism in a genetically susceptible mouse model; it is not a general-population human cancer estimate.

ApcMin/+ mice · receptor-dependent tumor promotion

Mechanistic animal study

Wang et al., Proceedings of the National Academy of Sciences, 2006

After seven weeks, GW501516 increased small-intestinal and colon tumor numbers about twofold and 3.6-fold in male PPAR-delta-intact ApcMin/+ mice versus vehicle. The effect was absent in the PPAR-delta-deleted comparison, and experiments implicated VEGF signaling.

  • Genetically tumor-prone mouse model
  • Receptor-deletion comparison
  • Mechanistic support rather than human risk quantification
Participants / model
PPAR-delta-intact and PPAR-delta-deleted ApcMin/+ mice plus colon-cancer cell experiments
Treatment
Daily oral-gavage GW501516 versus vehicle
Follow-up
7 weeks beginning at 6 weeks of age
Study design
Controlled mechanistic animal and cell study
Funding
U.S. National Institutes of Health grants, as reported

A tumor-prone mouse model cannot estimate cancer incidence in humans or substitute for the chronic sponsor bioassays.

Read the original source
SOT abstracts 895 and 896 · 104-week neoplasia

Sponsor toxicology conference abstracts

Geiger et al. and Newsholme et al., Society of Toxicology Annual Meeting, 2009

Abstract 895 reports treatment-related neoplasms in multiple tissues at all active levels in Han Wistar rats and increased female mortality at all active levels. Abstract 896 reports reduced mouse survival at 30 mg/kg/day and above, liver tumors, and stomach and combined squamous-cell tumors at all active levels in CD-1 mice.

  • Daily oral gavage for 104 weeks
  • Rat neoplasms across ten named tissues
  • Mouse stomach carcinoma and combined squamous tumors at all active levels
Participants / model
Han Wistar rats and CD-1 mice
Treatment
Multiple sex- and species-specific oral GW501516 exposure groups versus vehicle
Follow-up
104 weeks
Study design
Chronic animal carcinogenicity studies reported as conference abstracts
Funding
GlaxoSmithKline and Huntingdon Life Sciences

The public abstracts omit group sizes, incidence counts, statistical analyses, exposure measurements, and full pathology tables. They cannot quantify human cancer risk or a human threshold.

Read the original source

Is there an established safe threshold, human half-life, or interaction guide?

No supported self-use threshold or reliable public human elimination half-life was found. There is also no approved label that defines contraindications, interactions, monitoring, or what to do after stopping.

NCT00158899 planned population estimates for oral clearance and apparent volume of distribution but has no posted results. The cited public records provide no qualifying human concentration-time dataset, Cmax and AUC table, or elimination estimate for GW501516.

The short human abstracts do not supply a complete adverse-event denominator. Their brief exposure cannot exclude cancers or other harms with long latency. The animal abstracts supply no human no-effect exposure.

No public human concentration-time dataset supports vendor claims of a 12-, 16-, or 24-hour half-life. The trials report dosing schedules but no terminal elimination estimate.

Human PK · no public concentration-time estimate

Literature and registry record set

PubMed and ClinicalTrials.gov records

The cited evidence includes four human publications and four registry records under GW501516, GW-501516, GW1516, and Cardarine. One registry planned population pharmacokinetics but posts no results. No qualifying public human concentration-time or elimination estimate appears in the cited records.

  • Vendor half-life claims lack cited human pharmacokinetic data
  • Planned PK endpoints are not results
Participants / model
Public human GW501516 literature and trial records
Treatment
Not applicable
Study design
Public human records under GW501516 aliases
Read the original source
Registry · 424 enrolled, no posted results

Clinical trial registry

ClinicalTrials.gov NCT00158899.

The completed multi-stage low-HDL protocol lists 424 actual enrollment and no posted results. It planned HDL, other lipids, oral clearance, and apparent volume of distribution over a 12-week timeframe. The published paper reports 268 randomized participants plus 37 in a separate exploratory group.

  • Sponsor: GlaxoSmithKline
  • No results posted
  • Registry and publication denominators are not fully reconciled
Participants / model
Adults aged 18 to 75 with low HDL and without diabetes, coronary disease, or atherosclerotic disease
Treatment
Oral GW501516 study tablets versus placebo and protocol comparators
Follow-up
Registered 12-week outcome timeframe
Study design
Randomized double-blind multi-stage Phase 2 registry record
Funding
GlaxoSmithKline

Registry record, not a posted result set; its official title and detailed description also disagree on eight versus twelve weeks.

Read the original source
SOT abstracts 895 and 896 · 104-week neoplasia

Sponsor toxicology conference abstracts

Geiger et al. and Newsholme et al., Society of Toxicology Annual Meeting, 2009

Abstract 895 reports treatment-related neoplasms in multiple tissues at all active levels in Han Wistar rats and increased female mortality at all active levels. Abstract 896 reports reduced mouse survival at 30 mg/kg/day and above, liver tumors, and stomach and combined squamous-cell tumors at all active levels in CD-1 mice.

  • Daily oral gavage for 104 weeks
  • Rat neoplasms across ten named tissues
  • Mouse stomach carcinoma and combined squamous tumors at all active levels
Participants / model
Han Wistar rats and CD-1 mice
Treatment
Multiple sex- and species-specific oral GW501516 exposure groups versus vehicle
Follow-up
104 weeks
Study design
Chronic animal carcinogenicity studies reported as conference abstracts
Funding
GlaxoSmithKline and Huntingdon Life Sciences

The public abstracts omit group sizes, incidence counts, statistical analyses, exposure measurements, and full pathology tables. They cannot quantify human cancer risk or a human threshold.

Read the original source

How can PPAR-beta/delta activation change lipid markers without proving benefit?

PPAR-beta/delta is a nuclear receptor that changes gene transcription involved in fatty-acid handling and oxidation. GW501516 engages that pathway, but target engagement is several steps upstream of body weight, endurance, cardiovascular events, and long-term harm.

  • The receptor-ligand complex alters transcription rather than directly stimulating the androgen receptor.
  • Human studies found changes in lipid particles, meal-fat oxidation, skeletal-muscle CPT1b expression, insulin, and liver fat under short study conditions.
  • Those measurements support metabolic pharmacology, but they do not establish that a person loses fat or performs better.
  • PPAR-delta also participates in cell growth and tumor biology. The direction and relevance vary by model, so the chronic sponsor studies carry more safety weight than any single proposed molecular cancer pathway.
First human study · 24 sedentary volunteers

Randomized controlled biomarker trial

Sprecher et al., Arteriosclerosis Thrombosis and Vascular Biology, 2007

Twenty-four healthy hospitalized sedentary volunteers received placebo or one of two GW501516 exposures for two weeks. HDL rose relative to the placebo group's decline, and post-meal triglyceride clearance improved. Exercise capacity, weight loss, and clinical outcomes were not measured.

  • 9 participants in each active group and 6 placebo
  • Two-week exposure
  • Sedentary inpatient setting
Participants / model
24 healthy volunteers
Treatment
Two oral GW501516 groups versus placebo
Follow-up
2 weeks
Study design
Randomized placebo-controlled biomarker study with parallel in-vitro experiments
Funding
GlaxoSmithKline

Small, short, and not a performance or weight-loss trial; the abstract does not provide a complete safety table.

Read the original source
Two-week study · six exposed men

Randomized double-blind mechanistic trial

Risérus et al., Diabetes, 2008

Eighteen moderately overweight healthy men were randomized six per group to GW501516, GW590735, or placebo for two weeks. In the GW501516 group, reported changes included triglycerides -30%, apoB -26%, LDL -23%, insulin -11%, liver fat -20%, and urinary isoprostanes -30%; HDL was unchanged. Meal-fat oxidation and skeletal-muscle CPT1b expression increased.

  • Six participants received GW501516
  • Stable-isotope meal test and muscle biopsy
  • No weight-loss or exercise outcome
Participants / model
18 healthy moderately overweight men
Treatment
GW501516 versus a PPAR-alpha agonist versus placebo, six per group
Follow-up
2 weeks
Study design
Double-blind randomized three-group mechanistic trial
Funding
GlaxoSmithKline involvement reported in authorship

The percentages are short-term biomarker changes in a six-person active group, not proof of clinical benefit or chronic safety.

Read the original source
Crossover trial · 13 dyslipidemic men

Randomized double-blind crossover trial

Ooi et al., Journal of Clinical Endocrinology and Metabolism, 2011

Thirteen dyslipidemic men with central obesity completed randomized double-blind crossover periods of GW501516 and placebo. GW501516 changed VLDL, LDL, apoC-III, apoA-II, and HDL-particle production or clearance measures.

  • 13 men
  • Six-week intervention periods with two-week washout
  • Lipoprotein kinetics rather than clinical outcomes
Participants / model
13 dyslipidemic men with central obesity
Treatment
Oral GW501516 versus placebo in crossover periods
Follow-up
6 weeks per period with 2-week washout
Study design
Randomized double-blind crossover mechanistic trial
Funding
National Heart Foundation of Australia collaboration; GW501516 supplied through development program

Small mechanistic study; no performance, weight-loss, or cardiovascular-event outcome.

Read the original source
ApcMin/+ mice · receptor-dependent tumor promotion

Mechanistic animal study

Wang et al., Proceedings of the National Academy of Sciences, 2006

After seven weeks, GW501516 increased small-intestinal and colon tumor numbers about twofold and 3.6-fold in male PPAR-delta-intact ApcMin/+ mice versus vehicle. The effect was absent in the PPAR-delta-deleted comparison, and experiments implicated VEGF signaling.

  • Genetically tumor-prone mouse model
  • Receptor-deletion comparison
  • Mechanistic support rather than human risk quantification
Participants / model
PPAR-delta-intact and PPAR-delta-deleted ApcMin/+ mice plus colon-cancer cell experiments
Treatment
Daily oral-gavage GW501516 versus vehicle
Follow-up
7 weeks beginning at 6 weeks of age
Study design
Controlled mechanistic animal and cell study
Funding
U.S. National Institutes of Health grants, as reported

A tumor-prone mouse model cannot estimate cancer incidence in humans or substitute for the chronic sponsor bioassays.

Read the original source
SOT abstracts 895 and 896 · 104-week neoplasia

Sponsor toxicology conference abstracts

Geiger et al. and Newsholme et al., Society of Toxicology Annual Meeting, 2009

Abstract 895 reports treatment-related neoplasms in multiple tissues at all active levels in Han Wistar rats and increased female mortality at all active levels. Abstract 896 reports reduced mouse survival at 30 mg/kg/day and above, liver tumors, and stomach and combined squamous-cell tumors at all active levels in CD-1 mice.

  • Daily oral gavage for 104 weeks
  • Rat neoplasms across ten named tissues
  • Mouse stomach carcinoma and combined squamous tumors at all active levels
Participants / model
Han Wistar rats and CD-1 mice
Treatment
Multiple sex- and species-specific oral GW501516 exposure groups versus vehicle
Follow-up
104 weeks
Study design
Chronic animal carcinogenicity studies reported as conference abstracts
Funding
GlaxoSmithKline and Huntingdon Life Sciences

The public abstracts omit group sizes, incidence counts, statistical analyses, exposure measurements, and full pathology tables. They cannot quantify human cancer risk or a human threshold.

Read the original source

Is Cardarine FDA approved, still in development, or allowed in tested sport?

There is no FDA-approved Cardarine product. WADA says the development program was terminated after serious preclinical toxicities, and the 2026 Prohibited List names GW1516 and GW501516 as PPAR-delta agonist metabolic modulators prohibited at all times.

In a 2021 warning letter, FDA identified a marketed GW-501516 Cardarine product and stated that no approved applications were in effect for the products. FDA treated the sales as unapproved-new-drug and misbranding violations. That action applies to the named U.S. seller and claims; it does not turn Cardarine into a scientifically defined SARM.

WADA's current status is separate from medical approval. The 2026 list places GW1516 and GW501516 under S4.4.1 metabolic modulators and prohibits them in and out of competition. A research-chemical label does not create an exemption.

FDA letter · unapproved Cardarine product

FDA enforcement letter

U.S. Food and Drug Administration, May 18, 2021

FDA identified a marketed GW-501516 Cardarine product, said no approved applications were in effect for the named products, and treated their sale as unapproved-new-drug and misbranding violations.

  • No FDA-approved application for the named product
  • Seller's SARM category does not establish receptor pharmacology
Participants / model
A named U.S. online seller and its marketed products
Treatment
Not applicable
Follow-up
Inspection and online review described through 2021
Study design
Regulatory enforcement letter
Funding
U.S. Food and Drug Administration

A warning letter does not establish global approval status or clinical safety.

Read the original source
WADA alert · terminated development

Official anti-doping safety alert

World Anti-Doping Agency, March 21, 2013

WADA said the developmental drug had been withdrawn from research and terminated after serious toxicities were found in preclinical studies, citing the 2009 rat and mouse abstracts. It warned that the substance was being sold and used on the black market.

  • Program termination statement
  • Links directly to the sponsor toxicology abstracts
  • Alert is not a quantitative human-risk assessment
Participants / model
Athletes and anti-doping organizations
Treatment
Not applicable
Follow-up
Alert issued March 21, 2013
Study design
Official safety alert
Funding
World Anti-Doping Agency

WADA governs sport and is not a medicines regulator; the underlying animal findings are sourced separately.

Read the original source
WADA 2026 · prohibited at all times

Official anti-doping standard

World Anti-Doping Agency, effective January 1, 2026

The 2026 list names GW1516 and GW501516 as PPAR-delta agonists in S4.4.1 metabolic modulators. Section S4 substances are prohibited at all times, in and out of competition.

  • Named explicitly
  • Prohibited in and out of competition
Participants / model
Athletes subject to the World Anti-Doping Code
Treatment
Not applicable
Follow-up
Effective January 1 through December 31, 2026
Study design
Anti-doping prohibited list
Funding
World Anti-Doping Agency

Sport prohibition is separate from medical approval and applies within anti-doping rules.

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Studies and sources

FDA SRS · identity and aliases

Official substance identity record

U.S. Food and Drug Administration.

The record identifies GW-501516 as the preferred substance name and lists Cardarine, GSK-516, GW-1516, GW501516, formula C21H18F3NO3S2, CAS 317318-70-0, and UNII 7I2HA1NU22.

  • Ingredient-substance identity only
  • UNII availability does not imply regulatory review or approval
Participants / model
Not applicable
Treatment
Not applicable
Study design
FDA substance registry
Funding
U.S. Food and Drug Administration

Identity record, not an approval record or clinical study.

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First human study · 24 sedentary volunteers

Randomized controlled biomarker trial

Sprecher et al., Arteriosclerosis Thrombosis and Vascular Biology, 2007

Twenty-four healthy hospitalized sedentary volunteers received placebo or one of two GW501516 exposures for two weeks. HDL rose relative to the placebo group's decline, and post-meal triglyceride clearance improved. Exercise capacity, weight loss, and clinical outcomes were not measured.

  • 9 participants in each active group and 6 placebo
  • Two-week exposure
  • Sedentary inpatient setting
Participants / model
24 healthy volunteers
Treatment
Two oral GW501516 groups versus placebo
Follow-up
2 weeks
Study design
Randomized placebo-controlled biomarker study with parallel in-vitro experiments
Funding
GlaxoSmithKline

Small, short, and not a performance or weight-loss trial; the abstract does not provide a complete safety table.

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Two-week study · six exposed men

Randomized double-blind mechanistic trial

Risérus et al., Diabetes, 2008

Eighteen moderately overweight healthy men were randomized six per group to GW501516, GW590735, or placebo for two weeks. In the GW501516 group, reported changes included triglycerides -30%, apoB -26%, LDL -23%, insulin -11%, liver fat -20%, and urinary isoprostanes -30%; HDL was unchanged. Meal-fat oxidation and skeletal-muscle CPT1b expression increased.

  • Six participants received GW501516
  • Stable-isotope meal test and muscle biopsy
  • No weight-loss or exercise outcome
Participants / model
18 healthy moderately overweight men
Treatment
GW501516 versus a PPAR-alpha agonist versus placebo, six per group
Follow-up
2 weeks
Study design
Double-blind randomized three-group mechanistic trial
Funding
GlaxoSmithKline involvement reported in authorship

The percentages are short-term biomarker changes in a six-person active group, not proof of clinical benefit or chronic safety.

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Twelve-week study · 268 randomized adults

Randomized dose-ranging biomarker trial

Olson et al., Arteriosclerosis Thrombosis and Vascular Biology, 2012

The publication reports 268 adults with low HDL randomized to three GW501516 groups or placebo for 12 weeks, plus a separate exploratory study of 37. At the highest active exposure, reported baseline changes included HDL +16.9%, LDL -7.3%, triglycerides -16.9%, apoB -14.9%, and free fatty acids -19.4%.

  • Lipid and apolipoprotein endpoints
  • No cardiovascular events, endurance, or weight-loss endpoint
  • Longest published controlled exposure in the cited human reports was 12 weeks
Participants / model
268 adults with low HDL in the randomized study and 37 in an exploratory study
Treatment
Three oral GW501516 groups versus placebo
Follow-up
12 weeks
Study design
Multicenter randomized dose-ranging biomarker trial
Funding
GlaxoSmithKline

The registry lists 424 participants for the multi-stage protocol; the public records do not fully reconcile that total with the paper's reported groups. The abstract does not provide a complete adverse-event table.

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Crossover trial · 13 dyslipidemic men

Randomized double-blind crossover trial

Ooi et al., Journal of Clinical Endocrinology and Metabolism, 2011

Thirteen dyslipidemic men with central obesity completed randomized double-blind crossover periods of GW501516 and placebo. GW501516 changed VLDL, LDL, apoC-III, apoA-II, and HDL-particle production or clearance measures.

  • 13 men
  • Six-week intervention periods with two-week washout
  • Lipoprotein kinetics rather than clinical outcomes
Participants / model
13 dyslipidemic men with central obesity
Treatment
Oral GW501516 versus placebo in crossover periods
Follow-up
6 weeks per period with 2-week washout
Study design
Randomized double-blind crossover mechanistic trial
Funding
National Heart Foundation of Australia collaboration; GW501516 supplied through development program

Small mechanistic study; no performance, weight-loss, or cardiovascular-event outcome.

Read the original source
Registry · 424 enrolled, no posted results

Clinical trial registry

ClinicalTrials.gov NCT00158899.

The completed multi-stage low-HDL protocol lists 424 actual enrollment and no posted results. It planned HDL, other lipids, oral clearance, and apparent volume of distribution over a 12-week timeframe. The published paper reports 268 randomized participants plus 37 in a separate exploratory group.

  • Sponsor: GlaxoSmithKline
  • No results posted
  • Registry and publication denominators are not fully reconciled
Participants / model
Adults aged 18 to 75 with low HDL and without diabetes, coronary disease, or atherosclerotic disease
Treatment
Oral GW501516 study tablets versus placebo and protocol comparators
Follow-up
Registered 12-week outcome timeframe
Study design
Randomized double-blind multi-stage Phase 2 registry record
Funding
GlaxoSmithKline

Registry record, not a posted result set; its official title and detailed description also disagree on eight versus twelve weeks.

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SOT abstracts 895 and 896 · 104-week neoplasia

Sponsor toxicology conference abstracts

Geiger et al. and Newsholme et al., Society of Toxicology Annual Meeting, 2009

Abstract 895 reports treatment-related neoplasms in multiple tissues at all active levels in Han Wistar rats and increased female mortality at all active levels. Abstract 896 reports reduced mouse survival at 30 mg/kg/day and above, liver tumors, and stomach and combined squamous-cell tumors at all active levels in CD-1 mice.

  • Daily oral gavage for 104 weeks
  • Rat neoplasms across ten named tissues
  • Mouse stomach carcinoma and combined squamous tumors at all active levels
Participants / model
Han Wistar rats and CD-1 mice
Treatment
Multiple sex- and species-specific oral GW501516 exposure groups versus vehicle
Follow-up
104 weeks
Study design
Chronic animal carcinogenicity studies reported as conference abstracts
Funding
GlaxoSmithKline and Huntingdon Life Sciences

The public abstracts omit group sizes, incidence counts, statistical analyses, exposure measurements, and full pathology tables. They cannot quantify human cancer risk or a human threshold.

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ApcMin/+ mice · receptor-dependent tumor promotion

Mechanistic animal study

Wang et al., Proceedings of the National Academy of Sciences, 2006

After seven weeks, GW501516 increased small-intestinal and colon tumor numbers about twofold and 3.6-fold in male PPAR-delta-intact ApcMin/+ mice versus vehicle. The effect was absent in the PPAR-delta-deleted comparison, and experiments implicated VEGF signaling.

  • Genetically tumor-prone mouse model
  • Receptor-deletion comparison
  • Mechanistic support rather than human risk quantification
Participants / model
PPAR-delta-intact and PPAR-delta-deleted ApcMin/+ mice plus colon-cancer cell experiments
Treatment
Daily oral-gavage GW501516 versus vehicle
Follow-up
7 weeks beginning at 6 weeks of age
Study design
Controlled mechanistic animal and cell study
Funding
U.S. National Institutes of Health grants, as reported

A tumor-prone mouse model cannot estimate cancer incidence in humans or substitute for the chronic sponsor bioassays.

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FDA letter · unapproved Cardarine product

FDA enforcement letter

U.S. Food and Drug Administration, May 18, 2021

FDA identified a marketed GW-501516 Cardarine product, said no approved applications were in effect for the named products, and treated their sale as unapproved-new-drug and misbranding violations.

  • No FDA-approved application for the named product
  • Seller's SARM category does not establish receptor pharmacology
Participants / model
A named U.S. online seller and its marketed products
Treatment
Not applicable
Follow-up
Inspection and online review described through 2021
Study design
Regulatory enforcement letter
Funding
U.S. Food and Drug Administration

A warning letter does not establish global approval status or clinical safety.

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WADA alert · terminated development

Official anti-doping safety alert

World Anti-Doping Agency, March 21, 2013

WADA said the developmental drug had been withdrawn from research and terminated after serious toxicities were found in preclinical studies, citing the 2009 rat and mouse abstracts. It warned that the substance was being sold and used on the black market.

  • Program termination statement
  • Links directly to the sponsor toxicology abstracts
  • Alert is not a quantitative human-risk assessment
Participants / model
Athletes and anti-doping organizations
Treatment
Not applicable
Follow-up
Alert issued March 21, 2013
Study design
Official safety alert
Funding
World Anti-Doping Agency

WADA governs sport and is not a medicines regulator; the underlying animal findings are sourced separately.

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WADA 2026 · prohibited at all times

Official anti-doping standard

World Anti-Doping Agency, effective January 1, 2026

The 2026 list names GW1516 and GW501516 as PPAR-delta agonists in S4.4.1 metabolic modulators. Section S4 substances are prohibited at all times, in and out of competition.

  • Named explicitly
  • Prohibited in and out of competition
Participants / model
Athletes subject to the World Anti-Doping Code
Treatment
Not applicable
Follow-up
Effective January 1 through December 31, 2026
Study design
Anti-doping prohibited list
Funding
World Anti-Doping Agency

Sport prohibition is separate from medical approval and applies within anti-doping rules.

Read the original source

Why is Cardarine in F tier?

F reflects two-to-12-week human biomarker studies, no established clinical benefit, and tumors across multiple tissues in 104-week rat and mouse studies. The cited public evidence contains no human dose threshold or chronic safety dataset.