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LGD-4033

LGD-4033

LGD-4033, also known as Ligandrol, is a non-steroidal selective androgen receptor modulator (SARM) that is designed to cure muscle wasting associated with chronic, progressive, debilitating diseases as well as age-related muscle loss. LGD-4033 is proven to have promising results in gaining lean muscle mass and reducing overall body fat in a short time period. This powerful SARM works by binding itself with specific androgen receptors in the body such as muscle and bone receptors. Unlike steroids, it doesn’t affect the prostate, liver or oil glands, making it a safer alternative for those who want to achieve a well-defined body.

Overall Health Benefits of LGD-4033

  • Improves Muscle Mass and Physical Function [1-11]
  • Strengthens Bones and Lowers Risk for Osteoporosis [12-19]
  • Promotes Fat Loss [20-24]
  • Improves Exercise Performance [25]
  • Increases Libido [27-31]
  • Improves Brain Health [32-38]

Improves Muscle Mass and Physical Function

An overwhelming body of clinical evidence suggests that LGD-4033 is safe and effective in increasing lean body mass in a short time period:

  1. In healthy men (21–50 years), ascending doses (0.1, 0.3, or 1.0 mg) of LGD-4033 administered daily for 21 days increases lean body mass without any adverse side effects. [1-2]
  2. In cancer patients with muscle wasting, LGD-4033 consistently increases lean body mass and improves physical function and quality of life. [3-4]
  3. In healthy men, LGD-4033 increases lean muscle mass and improves functional measures. [5]
  4. Phase I and II clinical studies have shown that LGD-4033 administration in patients with muscle wasting is safe and effective. [6-9]
  5. In aging men and women, LGD-4033 improves lean body mass and physical functioning. [10]
  6. In cancer patients with muscle wasting, LGD-4033 significantly decreases morbidity and mortality by improving muscle mass and strength, thereby allowing them to undergo more intensive treatments such as radiation and chemotherapy. [11]

Strengthens Bones and Lowers Risk for Osteoporosis

Preventing bone loss and increasing bone formation are two important mechanisms involved in maintaining optimum bone health. Studies show that LGD-4033 does have potent bone-building capacity and may help prevent osteoporosis and fractures:

  1. LGD-4033 appears to decrease bone breakdown, thereby preventing fractures and decreased bone mineral density (BMD). [12]
  2. In patients with osteoporosis, SARMs such as LGD-4033 increases BMD. [13]
  3. In preclinical models, LGD-4033 increases BMD and bone strength at various skeletal sites. [14]
  4. In rats, LGD-4033 promotes bone growth, prevents bone breakdown, and increases skeletal muscle mass/strength. [15-18]
  5. In animal models, LGD-4033 accelerates healing of bone injuries. [19]

Promotes Fat Loss

Because LGD-4033 exclusively binds with muscle receptors, it may significantly reduce overall body fat percentage. Numerous high quality studies support the fat-burning effect of LGD-4033:

  1. In healthy, young men, LDG-4033 use is associated with significant reduction in fat mass and increase in lean body mass. [20]
  2. In men, oral administration of LGD-4033 promotes fat loss by reducing triglyceride levels. [21-23]
  3. In rats, LGD-4033 reduces body fat significantly. [24]

Improves Exercise Performance

LGD-4033 supplementation may help athletes and physically active individuals stay fit by improving their exercise performance. Studies show that with LGD-4033’s beneficial effects on muscle mass and strength as well as bone health, this powerful SARM may enhance exercise endurance, strength, and recovery. [25]

Increases Libido

SARMs such as LGD-4033 may help boost one’s self-confidence by ramping up sexual power. Numerous studies assessing the beneficial effects of SARMs in sexual health have shown positive results:

  1. In women, LGD-4033 enhances or stimulates libido and other parameters of sexuality. [26]
  2. In rats, LGD-4033 enhances sexual preference of females for males. [27]
  3. In female rats that had undergone surgical removal of the ovaries, LGD-4033 increases sexual motivation, with potency and efficacy comparable with testosterone propionate. [28]
  4. LGD-4033 penetrates the brains of female rats and stimulates sexual behaviour. [29]
  5. In male rats, LGD-4033 and other SARMs improve mounts, intromissions, ejaculations, and copulation efficiency. [30]
  6. In castrated rodent models, LGD-4033 maintains male reproductive behaviour. [31]

Improves Brain Health

There is robust evidence that LGD-4033 and other SARMs possess the ability to protect nerve cells (neurons) of the brain from injury or damage:

  1. In an ongoing clinical trial, LGD-4033 appears to protect the brains of men with minor cognitive impairment from further deterioration. [32]
  2. In rat models of Alzheimer’s disease (AD), LGD-4033 decreases the levels of abnormal protein plaques known as amyloid beta, which is the causative agent of AD. [33]
  3. LGD-4033 and other SARMs stimulate growth and development of brain tissues, enhance communication of neurons, and promote cell survival. [34-37]
  4. In rats, LGD-4033 protects new neurons in the brain. [38]

References:

  1. Basaria S, Collins L, Dillon EL, et al. The Safety, Pharmacokinetics, and Effects of LGD-4033, a Novel Nonsteroidal Oral, Selective Androgen Receptor Modulator, in Healthy Young Men. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2013;68(1):87-95. doi:10.1093/gerona/gls078.
  2. Dalton JT, Barnette KG, Bohl CE, et al. The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial. J Cachexia Sarcopenia Muscle. 2011;2:153–161.
  3. Dalton JT, Taylor RP, Mohler ML, Steiner MS. Selective androgen receptor modulators for the prevention and treatment of muscle wasting associated with cancer. Current opinion in supportive and palliative care. 2013; 7(4):345-51.
  4. Steiner M. S.; Barnette K. G.; Hancock M. L.; Dodson S. T.; Rodriguez D.; Morton R. A. Effect of GTx-024, a selective androgen receptor modulator (SARM), on stair climb performance and quality of life (QOL) in patients with cancer cachexia. ASCO Meeting Abstracts 2010, 28, 9147.
  5. Retrieved from http://www.biotechduediligence.com/uploads/6/3/6/7/6367956/lgnd_sarm_poster.pdf.
  6. Chekler E. L.. Tissue selective androgen receptor modulators (SARMs): A path to a clinical candidate. Abstracts of Papers, 250th ACS National Meeting & Exposition, Boston, MA, United States, August 16–20, 2015; MEDI-345.
  7. Study To Evaluate Safety And Tolerability of Single and Multiple Ascending Doses of PF-06260414 in Healthy Western and Japanese Male Subjects. www.clinicaltrials.gov/ct2/show/NCT02070939 (accessed April 16, 2015).
  8. Product Pipeline. www.pfizer.com/pipeline (accessed March 6, 2018).
  9. Basaria S.; Collins L.; Dillon E. L.; Orwoll K.; Storer T. W.; Miciek R.; Ulloor J.; Zhang A.; Eder R.; Zientek H.; Gordon G.; Kazmi S.; Sheffield-Moore M.; Bhasin S. The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men. J. Gerontol., Ser. A 2013, 68, 87–9510.1093/gerona/gls078.
  10. Dalton J. T.; Barnette K. G.; Bohl C. E.; Hancock M. L.; Rodriguez D.; Dodson S. T.; Morton R. A.; Steiner M. S. The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial. J. Cachexia Sarcopenia Muscle 2011, 2, 153–16110.1007/s13539-011-0034-6.
  11. Narayanan R, Mohler ML, Bohl CE, Miller DD, Dalton JT. Selective androgen receptor modulators in preclinical and clinical development . Nuclear Receptor Signaling. 2008;6:e010. doi:10.1621/nrs.06010.
  12. “Examining the SARM LGD-4033 | IronMag™ Bodybuilding & Fitness Portal.” IronMagâ?¢ Bodybuilding & Fitness Portal. N.p., n.d. Web. 6 March. 2018.
  13. Cilotti A, Falchetti A. Male osteoporosis and androgenic therapy: from testosterone to SARMs. Clinical Cases in Mineral and Bone Metabolism. 2009;6(3):229-233.
  14. Miner JN, Chang W, Chapman MS, et al. An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. Endocrinology.
  15. Kearbey JD, Gao W, Fisher SJ, Wu D, Miller DD, Dalton JT. Effects of selective androgen receptor modulator (SARM) treatment in osteopenic female rats. Pharmaceutical research. 2009; 26(11):2471-7.
  16. Gao W, Reiser PJ, Coss CC, Phelps MA, Kearbey JD, Miller DD, Dalton JT. Selective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats. Endocrinology. 2005;146:4887–4897.
  17. Gao W, Reiser PJ, Kearbey JD, Phelps MA, Coss CC, Miller DD, Dalton JT. Effects of Novel Selective Androgen Receptor Modulator (SARM) on Skeletal Muscle Mass and Strength in Castrated Male Rats. The Endocrine Society; New Orleans: 2004.
  18. Kearbey JD, Gao W, Narayanan R, Fisher SJ, Wu D, Miller DD, Dalton JT. Selective Androgen Receptor Modulator (SARM) treatment prevents bone loss and reduces body fat in ovariectomized rats. Pharmaceutical research. 2007;24:328–335.
  19. Seeman E. Periosteal bone formation–a neglected determinant of bone strength. The New England journal of medicine. 2003; 349(4):320-3.
  20. Basaria S, Collins L, Dillon EL, et al. The Safety, Pharmacokinetics, and Effects of LGD-4033, a Novel Nonsteroidal Oral, Selective Androgen Receptor Modulator, in Healthy Young Men. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2013;68(1):87-95. doi:10.1093/gerona/gls078.
  21. Wu FC, von Eckardstein A. Androgens and coronary artery disease. Endocr Rev. 2003;24:183–217.
  22. Schroeder ET, Singh A, Bhasin S, et al. Effects of an oral androgen on muscle and metabolism in older, community-dwelling men. Am J Physiol Endocrinol Metab. 2003;284:E120–E128.
  23. Thompson PD, Cullinane EM, Sady SP, Chenevery C, Saritelli AL, Sady MA. Contrasting effects of testosterone and stanozolol on serum lipoprotein levels. JAMA. 1989;261:1165–1168.
  24. Kearbey JD, Gao W, Narayanan R, Fisher SJ, Wu D, Miller DD, Dalton JT. Selective Androgen Receptor Modulator (SARM) treatment prevents bone loss and reduces body fat in ovariectomized rats. Pharmaceutical research. 2007;24:328–335.
  25. Thevis M, Thomas A, Möller I, Geyer H, Dalton JT, Schänzer W. Mass spectrometric characterization of urinary metabolites of the selective androgen receptor modulator S-22 to identify potential targets for routine doping controls. Rapid communications in mass spectrometry : RCM. 2011; 25(15):2187-95.
  26. Negro-Vilar A. Selective androgen receptor modulators (SARMs): a novel approach to androgen therapy for the new millennium. The Journal of clinical endocrinology and metabolism. 1999; 84(10):3459-62.
  27. Kudwa AE, López FJ, McGivern RF, Handa RJ. A selective androgen receptor modulator enhances male-directed sexual preference, proceptive behavior, and lordosis behavior in sexually experienced, but not sexually naive, female rats. Endocrinology. 2010; 151(6):2659-68. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20392832.
  28. Jones A, Hwang DJ, Duke CB. Nonsteroidal selective androgen receptor modulators enhance female sexual motivation. The Journal of pharmacology and experimental therapeutics. 2010; 334(2):439-48.
  29. Retrieved from https://academic.oup.com/endo/article/151/6/2659/2456825.
  30. Miner JN, Chang W, Chapman MS. An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. Endocrinology. 2007; 148(1):363-73. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/17023534.
  31. Miner JN, Chang W, Chapman MS, Finn PD, Hong MH, Lopez FJ, Marschke KB, Rosen J, Schrader W, Turner R, van Oeveren A, Viveros H, Zhi L, Negro-Vilar A. An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. Endocrinology. 2007;148:363–373.
  32. Retrieved from https://www.nature.com/scibx/journal/v3/n24/full/scibx.2010.724.html#B7.
  33. Jayaraman A, Christensen A, Moser VA, et al. Selective Androgen Receptor Modulator RAD140 Is Neuroprotective in Cultured Neurons and Kainate-Lesioned Male Rats. Endocrinology. 2014;155(4):1398-1406. doi:10.1210/en.2013-1725. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959610/.
  34. Bajetto A, Barbero S, Bonavia R, et al. Stromal cell-derived factor-1α induces astrocyte proliferation through the activation of extracellular signal-regulated kinases 1/2 pathway. J Neurochem. 2001;77:1226–1236. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11389173.
  35. Qui MS, Green SH. PC12 cell neuronal differentiation is associated with prolonged p21ras activity and consequent prolonged ERK activity. Neuron. 1992;9:705–717. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/1382473.
  36. Krapivinsky G, Krapivinsky L, Manasian Y, et al. The NMDA receptor is coupled to the ERK pathway by a direct interaction between NR2B and RasGRF1. Neuron. 2003;40:775–784. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/14622581.
  37. Alonso M, Viola H, Izquierdo I, Medina JH. Aversive experiences are associated with a rapid and transient activation of ERKs in the rat hippocampus. Neurobiol Learn Mem. 2002;77:119–124. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11749089.
  38. Hamson DK, Wainwright SR, Taylor JR, Jones BA, Watson NV, Galea LA. Androgens increase survival of adult-born neurons in the dentate gyrus by an androgen receptor-dependent mechanism in male rats. Endocrinology. 2013; 154(9):3294-304. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23782943.
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