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Cardarine (GW-501516)

Cardarine (GW-501516)

Cardarine, also known by GW501516, was initially prescribed for the treatment of various disorders related to elevated cholesterol levels such as atherosclerosis, myocardial infarction, stroke, and other blood vessel diseases. Today, this drug has gained popularity among athletes and bodybuilders due to its ability to improve muscle strength and exercise endurance. Researchers believe that cardarine exerts its beneficial effects by activating the peroxisome proliferator-activated receptor delta (PPAR-delta) pathway. Activation of the PPAR-delta pathway is associated with increased energy levels, fat reduction, muscle building, increased endurance, and decreased blood levels of cholesterol.

Overall Health Benefits of Cardarine

  • Improves brain health [1-5]
  • Improves exercise endurance [6-8]
  • Increases muscle mass and strength [9-14]
  • Promotes fat loss [15-23]
  • Lowers cholesterol levels [18] [24-29]
  • Lowers risk for heart disease [1, 30-34]
  • Improves blood sugar levels [7, 35-39]
  • Fights kidney disease [40-43]
  • Improves liver health [39, 44-51]

Proven Health Benefits of Cardarine

Improves Brain Health

Studies show that this PPAR-delta activator can boost cognitive health through different important mechanisms:

  1. In mice, cardarine improved cognitive function by increasing blood flow to the brain. [1]
  2. In rat brain cells, treatment with cardarine reduced brain inflammation. [2]
  3. A cell study found that cardarine can lower the risk for central nervous system disorders by modulating inflammatory signaling network in the cells of the immune system. [3]
  4. In mice, cardarine improved spatial memory by promoting formation of new neurons (neurogenesis). [4]
  5. In a model of brain inflammation, cardarine protected against nerve cell damage by reducing inflammatory processes. [5]

Improves Exercise Endurance

There’s also strong scientific evidence supporting the beneficial effects of cardarine on exercise endurance:

  1. In adult mice, cardarine administration along with exercise training improved running endurance. [6]
  2. In both trained and untrained mice, cardarine treatment enhanced running endurance. [7]
  3. In sedentary mice, cardarine administration improved running endurance by preserving blood sugar. [8]

Increases Muscle Mass and Strength

Evidence also suggests that cardarine regulates muscle metabolism and reprograms muscle fiber types in order to increase muscle mass and strength:

  1. Studies show that cardarine improves muscle health by regulating many different biological activities such as skeletal reprogramming, mitochondrial respiration, lipid and lipoprotein metabolism, body heat production, and muscle regeneration. [9-11]
  2. Studies show that cardarine improves exercise-induced reprogramming of muscle fibers by regulating the formation of genes associated with contractile proteins. [12]
  3. A study found that trained mice treated with cardarine had 113% more muscle fibers than untrained sedentary mice. [7]
  4. In mice with muscle abnormalities, cardarine treatment restored the integrity of skeletal muscle fibers. [13]
  5. A study found that PPAR-delta activator like cardarine regulates muscle fiber contraction and metabolism. [14]

Promotes Fat Loss

Studies show that cardarine does not only increase muscle mass but it can also improve body composition by promoting fat loss:

  1. In men with high belly fat, administration of 2.5 mg of cardarine daily for 6 weeks resulted in weight reduction. [15]
  2. In inactive volunteers, subjects treated with cardarine burned more fats (20%) compared to untreated subjects. [16]
  3. In mice, cardarine protected against diet-induced obesity. [17]
  4. In moderately obese men, cardarine reduced weight by increasing fatty acid oxidation. [18]
  5. In overweight and obese men and women, cardarine reduced body weight by improving cholesterol profile. [19]
  6. A study found that cardarine can significantly reduce weight by correcting the causes of insulin resistance and abnormal cholesterol profile. [20]
  7. A study also found that cardarine helps reduce weight by increasing energy expenditure in muscles. [21]
  8. In overweight and obese healthy volunteers, cardarine treatment at a dose of 10 mg for 12 weeks reduced body fat levels. [22]
  9. A cell study found that cardarine activates pathways involved in fat metabolism. [23]

Lowers Cholesterol Levels

Studies found that cardarine has a positive effect on low density lipoprotein (bad cholesterol) and high-density lipoprotein (good cholesterol):

  1. In moderately obese men, treatment with cardarine reduced low density lipoprotein cholesterol by 23%. [18]
  2. In subjects with abnormally low high-density lipoprotein cholesterol levels, cardarine increased the levels of good cholesterol in just 12 weeks of treatment. [24]
  3. In patients with abnormal cholesterol profile, cardarine treatment reduced low density lipoprotein and increased high density lipoprotein cholesterol levels. [25-26]
  4. In healthy volunteers, cardarine enhanced the levels of high-density lipoprotein. [27]
  5. Administration of cardarine in patients with abnormal cholesterol profile for 12 weeks significantly reduced low-density lipoprotein. [28]
  6. In insulin-resistant middle-aged obese rhesus monkeys, cardarine administration resulted in a dramatic dose-dependent rise in blood levels of high-density lipoprotein cholesterol while lowering the levels of small-dense low-density lipoprotein and fasting triglycerides. [29]

Lowers Risk for Heart Disease

Studies suggest that cardarine can significantly lower one’s risk for heart disease through the following mechanisms:

  1. Cardarine may reduce the risk of plaque build-up in the arteries of the heart (atherosclerosis) by relaxing/widening the blood vessels via nitric oxide production. [1]
  2. Cardarine prevents atherosclerosis by antagonizing multiple proinflammatory pathways. [30]
  3. Cardarine also has the ability to prevent the formation of lesions. [31-32]
  4. Cardarine stimulates the growth of new blood vessels in the heart by boosting the levels of vascular endothelial growth factor (VEGF). [33]
  5. Cardarine improves overall heart health by regulating cardiomyocyte (heart cell) proliferation and cardiac repair. [34]

Improves Blood Sugar Levels

There’s also evidence supporting the anti-diabetic properties of cardarine:

  1. In high fat-fed rats and mice, cardarine improved insulin response which in turn reduced blood sugar levels. [35]
  2. In mice, cardarine enhanced specific consumption of fatty acids and reduced blood sugar utilization. [7]
  3. In a mouse model of metabolic syndrome, cardarine administration ameliorated insulin resistance. [36]
  4. In mice fed with a high-fat diet, cardarine improved blood sugar levels by enhancing insulin signaling. [37]
  5. Cardarine also improved blood sugar in mice with obesity-related disorders by regulating blood sugar metabolism and insulin sensitivity. [38]
  6. In mice, cardarine prevented cytokine-induced insulin resistance in liver cells. [39]

Fights Kidney Disease

Cardarine also has a potential role in protecting against kidney disease according to studies:

  1. Cardarine protects against kidney disease by reducing the activity of MCP-1, a gene related to kidney disorders. [40]
  2. In high-fructose fed mouse model, cardarine improved inflammatory pathways in the kidneys. [41-42]
  3. A study found that cardarine has the potential to reduce kidney inflammation, thus, preventing kidney disease progression. [43]

Improves Liver Health

Aside from the kidneys, cardarine can also protect against various liver diseases:

  1. A study found that cardarine has the potential to treat kidney diseases associated with metabolic syndrome. [44]
  2. In animal models of nonalcoholic fatty liver disease, cardarine treatment reduced liver inflammation. [45]
  3. In mice, cardarine treatment significantly reduced the prevalence of liver damage from a high-fructose diet and the development of nonalcoholic fatty liver disease. [39, 46]
  4. In animal models of non-alcholic steatohepatitis (fat build-up in the liver), cardarine ameliorated symptoms by enhancing fatty acid β-oxidation. [47-50]
  5. A study found that cardarine and other peroxisome proliferator-activated receptors have the ability to stimulate liver regeneration by modulating Akt and E2f Signaling. [51]

References:

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  2. Defaux A, Zurich MG, Braissant O, Honegger P, Monnet-tschudi F. Effects of the PPAR-beta agonist GW501516 in an in vitro model of brain inflammation and antibody-induced demyelination. J Neuroinflammation. 2009;6:15.
  3. John J. Bright, Saravanan Kanakasabai, Wanida Chearwae, and Sharmistha Chakraborty, “PPAR Regulation of Inflammatory Signaling in CNS Diseases,” PPAR Research, vol. 2008, Article ID 658520, 12 pages, 2008. https://doi.org/10.1155/2008/658520.
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  5. Defaux A, Zurich MG, Braissant O, Honegger P, Monnet-Tschudi F. Effects of the PPAR-beta agonist GW501516 in an in vitro model of brain inflammation and antibody-induced demyelination. J Neuroinflammation. 2009;6:15. Published 2009 May 7. doi:10.1186/1742-2094-6-15.
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  27. Sprecher DL, Massien C, Pearce G, Billin AN, Perlstein I, Willson TM, Hassall DG, Ancellin N, Patterson SD, Lobe DC, Johnson TG. Triglyceride:high-density lipoprotein cholesterol effects in healthy subjects administered a peroxisome proliferator activated receptor delta agonist. Arterioscler Thromb Vasc Biol. 2007;27:359–365.
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  47. Nagasawa T, Inada Y, Nakano S, et al. Effects of bezafibrate, PPAR pan-agonist, and GW501516, PPARdelta agonist, on development of steatohepatitis in mice fed a methionine- and choline-deficient diet. Eur J Pharmacol. 2006;536(1-2):182-91.
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  50. Barroso E, Rodríguez-calvo R, Serrano-marco L, et al. The PPARβ/δ activator GW501516 prevents the down-regulation of AMPK caused by a high-fat diet in liver and amplifies the PGC-1α-Lipin 1-PPARα pathway leading to increased fatty acid oxidation. Endocrinology. 2011;152(5):1848-59.
  51. Liu HX, Fang Y, Hu Y, Gonzalez FJ, Fang J, Wan YJ. PPARβ Regulates Liver Regeneration by Modulating Akt and E2f Signaling. PLoS ONE. 2013;8(6):e65644.

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