Cardarine talk

[pickapeck]

I did look up the table but it doesn't appear that the 6.2 is in regards to Cardarine. I'm not sure how 6.2x can be the same for all drugs/compounds across the board.

Another thing to remember is Cardarine is not known to cause cancer in monkeys or humans- only in rats.

Do you know if there were studies in humans and other primates?

 

[pickapeck]

I did look up the table but it doesn't appear that the 6.2 is in regards to Cardarine. I'm not sure how 6.2x can be the same for all drugs/compounds across the board.

Another thing to remember is Cardarine is not known to cause cancer in monkeys or humans- only in rats.

Here are 4 human clinical trials.

Search of: GW501516 - List Results - ClinicalTrials.gov

clinicaltrials.gov

 

[pickapeck]

Randomized Controlled Trial

Arterioscler Thromb Vasc Biol

. 2012 Sep;32(9):2289-94.
doi: 10.1161/ATVBAHA.112.247890. Epub 2012 Jul 19.

Lipid effects of peroxisome proliferator-activated receptor-δ agonist GW501516 in subjects with low high-density lipoprotein cholesterol: characteristics of metabolic syndrome​

Eric J Olson 1 , Gregory L Pearce, Nigel P Jones, Dennis L Sprecher

Affiliations

• PMID: 22814748
• DOI: 10.1161/ATVBAHA.112.247890

Abstract​

Objective: Peroxisome proliferator-activated receptor-δ-induced upregulation in skeletal muscle fatty acid oxidation would predict the modulation of lipid/lipoproteins.

Methods and results: GW501516 (2.5, 5.0, or 10.0 mg) or placebo was given for 12 weeks to patients (n=268) with high-density lipoprotein (HDL) cholesterol <1.16 mmol/L. Fasting lipids/apolipoproteins (apos), insulin, glucose, and free fatty acid were measured; changes from baseline were calculated and assessed. A second smaller exploratory study (n=37) in a similar population was conducted using a sequence of 5 and 10 mg dosing for the assessment of lipoprotein particle concentration. GW501516 demonstrated HDL cholesterol increases up to 16.9% (10 mg) and apoA-I increases up to 6.6%. Reductions were observed in low-density lipoprotein (LDL) cholesterol (-7.3%), triglycerides (-16.9%), apoB (-14.9%), and free fatty acids (-19.4%). The exploratory study showed significant reductions in the concentration of very LDL (-19%), intermediate-density lipoprotein (-52%), and LDL (-14%, predominantly a reduction in small particles), whereas the number of HDL particles increased (+10%; predominantly medium and large HDL).

Conclusions: GW501516 produced significant changes in HDL cholesterol, LDL cholesterol, apoA1, and apoB. Fewer very LDL and larger LDL support a transition toward less atherogenic lipoprotein profiles. These data are consistent with peroxisome proliferator-activated receptor-δ being a potentially important target for providing cardiovascular protection in metabolic syndrome-like patients.

Trial registration: ClinicalTrials.gov NCT00258899 NCT00388180.

 

[pickapeck]

Randomized Controlled Trial

J Clin Endocrinol Metab

. 2011 Oct;96(10):E1568-76.
doi: 10.1210/jc.2011-1131. Epub 2011 Aug 3.

Mechanism of action of a peroxisome proliferator-activated receptor (PPAR)-delta agonist on lipoprotein metabolism in dyslipidemic subjects with central obesity​

Esther M M Ooi 1 , Gerald F Watts, Dennis L Sprecher, Dick C Chan, P Hugh R Barrett

Affiliations

• PMID: 21816786
• DOI: 10.1210/jc.2011-1131

Free article

Abstract​

Context: Dyslipidemia increases the risk of cardiovascular disease in obesity. Peroxisome proliferator-activated receptor (PPAR)-δ agonists decrease plasma triglycerides and increase high-density lipoprotein (HDL)-cholesterol in humans.

Objective: The aim of the study was to examine the effect of GW501516, a PPAR-δ agonist, on lipoprotein metabolism. Design, Setting, and Intervention: We conducted a randomized, double-blind, crossover trial of 6-wk intervention periods with placebo or GW501516 (2.5 mg/d), with 2-wk placebo washout between treatment periods.

Participants: We recruited 13 dyslipidemic men with central obesity from the general community.

Main outcome measures: We measured the kinetics of very low-density lipoprotein (VLDL)-, intermediate-density lipoprotein-, and low-density lipoprotein (LDL)-apolipoprotein (apo) B-100, plasma apoC-III, and high-density lipoprotein (HDL) particles (LpA-I and LpA-I:A-II).

Results: GW501516 decreased plasma triglycerides, fatty acid, apoB-100, and apoB-48 concentrations. GW501516 decreased the concentrations of VLDL-apoB by increasing its fractional catabolism and of apoC-III by decreasing its production rate (P < 0.05). GW501516 reduced VLDL-to-LDL conversion and LDL-apoB production. GW501516 increased HDL-cholesterol, apoA-II, and LpA-I:A-II concentrations by increasing apoA-II and LpA-I:A-II production (P < 0.05). GW501516 decreased cholesteryl ester transfer protein activity, and this was paralleled by falls in the triglyceride content of VLDL, LDL, and HDL and the cholesterol content of VLDL and LDL.

Conclusions: GW501516 increased the hepatic removal of VLDL particles, which might have resulted from decreased apoC-III concentration. GW501516 increased apoA-II production, resulting in an increased concentration of LpA-I:A-II particles. This study elucidates the mechanism of action of this PPAR-δ agonist on lipoprotein metabolism and supports its potential use in treating dyslipidemia in obesity.

Trial registration: ClinicalTrials.gov NCT00841217.

 

[pickapeck]

Handb Exp Pharmacol. 2011;(203):35-51.
doi: 10.1007/978-3-642-17214-4_2.

Dual acting and pan-PPAR activators as potential anti-diabetic therapies​

Monique Heald 1 , Michael A Cawthorne

Affiliations

• PMID: 21484566
• DOI: 10.1007/978-3-642-17214-4_2

Abstract​

The thiazolidinedione PPAR-γ activator drugs rosiglitazone and pioglitazone suppress insulin resistance in type 2 diabetic patients. They lock lipids into adipose tissue triglyceride stores, thereby preventing lipid metabolites from causing insulin resistance in liver and skeletal muscle and β-cell failure. They also reduce the secretion of inflammatory cytokines such as TNFα and increase the plasma level of adiponectin, which increases insulin sensitivity in liver and skeletal muscle. However, they have only a modest effect on dyslipidaemia, and they increase fat mass and plasma volume. Fibrate PPAR-α activator drugs decrease plasma triglycerides and increase HDL-cholesterol levels. PPAR-δ activators increase the capacity for fat oxidation in skeletal muscle.Clinical experience with bezafibrate, which activates PPAR-δ and -α, and studies on the PPAR-α/δ activator tetradecylthioacetic acid, the PPAR-δ activator GW501516, and combinations of the PPAR-α activator fenofibrate with rosiglitazone or pioglitazone have encouraged attempts to develop single molecules that activate two or all three PPARs. Most effort has focussed on dual PPAR-α/γ activators. These reduce both hyperglycaemia and dyslipidaemia, but their development has been terminated by issues such as increased weight gain, oedema, plasma creatinine and myocardial infarction or stroke. In addition, the FDA has stated that many PPAR ligands submitted to it have caused increased numbers of tumours in carcinogenicity studies.Rather than aiming for full potent agonists, it may be best to identify subtype-selective partial agonists or compounds that selectively activate PPAR signalling pathways and use these in combination. Nutrients or modified lipids that are low-affinity agonists may also have potential.

 

[jcc80]

Randomized Controlled Trial

Arterioscler Thromb Vasc Biol

. 2012 Sep;32(9):2289-94.
doi: 10.1161/ATVBAHA.112.247890. Epub 2012 Jul 19.

Lipid effects of peroxisome proliferator-activated receptor-δ agonist GW501516 in subjects with low high-density lipoprotein cholesterol: characteristics of metabolic syndrome​

Eric J Olson 1 , Gregory L Pearce, Nigel P Jones, Dennis L Sprecher

Affiliations

• PMID: 22814748
• DOI: 10.1161/ATVBAHA.112.247890

Abstract​

Objective: Peroxisome proliferator-activated receptor-δ-induced upregulation in skeletal muscle fatty acid oxidation would predict the modulation of lipid/lipoproteins.

Methods and results: GW501516 (2.5, 5.0, or 10.0 mg) or placebo was given for 12 weeks to patients (n=268) with high-density lipoprotein (HDL) cholesterol <1.16 mmol/L. Fasting lipids/apolipoproteins (apos), insulin, glucose, and free fatty acid were measured; changes from baseline were calculated and assessed. A second smaller exploratory study (n=37) in a similar population was conducted using a sequence of 5 and 10 mg dosing for the assessment of lipoprotein particle concentration. GW501516 demonstrated HDL cholesterol increases up to 16.9% (10 mg) and apoA-I increases up to 6.6%. Reductions were observed in low-density lipoprotein (LDL) cholesterol (-7.3%), triglycerides (-16.9%), apoB (-14.9%), and free fatty acids (-19.4%). The exploratory study showed significant reductions in the concentration of very LDL (-19%), intermediate-density lipoprotein (-52%), and LDL (-14%, predominantly a reduction in small particles), whereas the number of HDL particles increased (+10%; predominantly medium and large HDL).

Conclusions: GW501516 produced significant changes in HDL cholesterol, LDL cholesterol, apoA1, and apoB. Fewer very LDL and larger LDL support a transition toward less atherogenic lipoprotein profiles. These data are consistent with peroxisome proliferator-activated receptor-δ being a potentially important target for providing cardiovascular protection in metabolic syndrome-like patients.

Trial registration: ClinicalTrials.gov NCT00258899 NCT00388180.

I'm not great at reading studies admittedly, but a 15% reduction in apoB at a dose of only 10mg... Well, that's pretty enticing.

 

[Type-IIx]

I'm not great at reading studies admittedly, but a 15% reduction in apoB at a dose of only 10mg... Well, that's pretty enticing.

Compared to placebo, this change was not statistically significant, meaning that it cannot be distinguished from random chance; however, due to a small sample size, this could reflect a false negative due to lack of statistical power.

 

[Type-IIx]

My mother took that chance of smoking her entire life and died of LUNG CANCER. So I'm not too keen on taking cancer risks with cardarine

I'm sorry for your loss. I agree that cardarine is a risky drug with little unique benefit.

 

[Cerberus777]

@Type-IIx is there a drug that is in your opinion safer to take in the place of GW1516 that increases endurance, increases insulin sensitivity and improves lipids? In tested athletes Telmisartan at high doses (100-160mg) have been used with some success.

 

[Type-IIx]

@Type-IIx is there a drug that is in your opinion safer to take in the place of GW1516 that increases endurance, increases insulin sensitivity and improves lipids? In tested athletes Telmisartan at high doses (100-160mg) have been used with some success.

The answer depends on whether this is within the context of an athlete who competes for a sporting body that prohibits AAS & haematopoietic agents.

 

[Cerberus777]

The answer depends on whether this is within the context of an athlete who competes for a sporting body that prohibits AAS & haematopoietic agents.

Let's say non tested athletes. What would you suggest the guys here on the board that also want endurance that take GW replace it with?

 

[pickapeck]

I'm not great at reading studies admittedly, but a 15% reduction in apoB at a dose of only 10mg... Well, that's pretty enticing.

it deos seem to work pretty well and i ahve used it and my blood work has been really pristine on it. That asside, none of these studies were long enough or with follow-up to even entertain analysis to detect risk of cancer. So from what I can locate it's still pretty open. there was a thread a while back either here or on AB forum where some guys reported skin tags while on it. That happened to me a few years ago. As far as I know I don't hae any ongogenic stuff boilin out of control but who knows. A lot of guys in the community seem to be using it without any cancer signal that jumps out. That's about all any of us can say as far as human carcinogenesis. Rats don't seem to do so well if you dose them for a long long time.

 

[Type-IIx]

Let's say non tested athletes. What would you suggest the guys here on the board that also want endurance that take GW replace it with?

Not a suggestion, but an answer to this problem as posed, Miotolon (Furazabol; Androfurazanol; 17α-methyl-5α-androstano(2,3-c)(1,2,5) oxadiazol-17β-ol; 17β-hydroxy-17α-methyl-5α-androstano(2,3-c)furazan) fits the bill best if I am limited to a single agent.

It enhances cardiorespiratory endurance by ↑cardiac output, stroke volume, heart rate, & O₂ transport. It is insulin sensitizing via ↓PPARγ & regulation of other key pathways involved in glucose metabolism regulation like leptin, etc.,;↓ fat mass by commitment of preadipocytes to a myogenic rather than adipogenic lineage, and all the other AAS class effects that apply to fat mass regulation, like increased lipolysis (via cAMP and/or by ↑β-adrenoreceptor # in adipocytes), and reduced lipid accumulation. It is used clinically for treating dyslipidaemia in Japan. It is an usual AAS in this effect; don't ask me how or why it is beneficial for lipid derangement, but this effect has been demonstrated repeatedly.

In practice, I would regard the limitation to a single agent to be a false constraint, however. This problem would be better solved by the use of an erythropoietic agent like epocrit, a GLP-1 & GIP agonist like tirzepatide, a statin, and a thiazolidinedione.

 

[gains4000]

Cardarine makes me almost vomit every morning. Everyday I wake up nauseous as hell , I don’t know if anyone else can relate?

 

[IFBBProDomCardone]

I have been using injectable cardarine.. and it brought my LDL down to 15 lol..wish I had this stuff when I was running gear and bodybuilding!

 

[trenned]

If anyone has ever had a cancer scare or a family member with cancer I don't see how something like cardarine that caused cancer in rodents EVERYWHERE doesn't scare the living shit out of you? Fucking cancer... For what? Even a 1% chance this shit is not worth the risk. There's a million other/better drugs for lipids and fat loss.

 

[gains4000]

I have been using injectable cardarine.. and it brought my LDL down to 15 lol..wish I had this stuff when I was running gear and bodybuilding!

I didn’t know that was a thing. What made you choose inject over oral?

 

[Ziath11]

Any opinions on “super cardarine” aka GW-0742? I seem to get better effects with that than GW-501516

 

[IFBBProDomCardone]

I didn’t know that was a thing. What made you choose inject over oral?

Amino asylum has it.. heard it works even better for cardio, and it sure does

 

[riceNkimchi]

Any opinions on “super cardarine” aka GW-0742? I seem to get better effects with that than GW-501516

possible heart enlargement