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Note: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor. Ligandrol is specifically a drug that we at SelfHacked would recommend against.

What is LGD-4033?

LGD-4033, a novel nonsteroidal, oral selective androgen receptor modulator (SARMs), binds to the androgen receptor with high affinity and selectivity. It demonstrates anabolic activity in muscles, anti-resorptive and anabolic activity in bones and a robust selectivity for muscle and bone versus prostate and sebaceous glands.(R)

LGD-4033 has undergone several recent studies and trials to find the best and safest way to use it. From these trials, the results have shown increases in lean body mass and decreases in body fat. There is also a significant increase in strength, well being, as well as healing possibilities.(R)

Scientific Uses/Potential Benefits of LGD

LGD-4033 Prevents Muscle Wasting

Muscle wasting, including a loss of skeletal muscle, is a cancer-related symptom that begins early in the progression of cancer and affects a patient’s quality of life, ability to tolerate chemotherapy, and survival. SARMs increase muscle mass and improve physical function in healthy and diseased individuals, and potentially may provide a new therapy for muscle wasting and cancer cachexia. SARMs modulate the same anabolic pathways targeted with classical steroidal androgens, but within the dose range in which expected effects on muscle mass and function are seen androgenic side-effects on prostate, skin, and hair have not been observed. Unlike testosterone, SARMs are orally active, non aromatizable, non virilizing, and tissue-selective anabolic agents. (R)

LGD-4033 May Prevent Cancer Cachexia

Cachexia often occurs in patients with AIDS, cancer, kidney disease, sepsis, and burns and is characterized by weight loss, muscle wasting, and decrease in appetite. Elevated levels of cytokines, namely IL-6, TNFα, INF 1β, INFγ, and proteolysis inducing factor are thought to be the main contributors. At least 30% of cancer-related deaths result from cachexia due to wasting of the respiratory muscles, which eventually causes pneumonia.(R)

Studies with anabolic agents such as nandrolone for cachexia have shown improvements in lean body mass and bone density, however, side effects such as liver toxicity and masculinization in women occur. Increases in lean mass and muscle performance in HIV-infected men with wasting disorders upon testosterone treatment have also been shown. The proliferative effects on the prostate and elevation of hematocrit remain drawbacks, however. An ideal SARM, like LGD-4033, that selectively increases muscle mass and lacks the growth effect on prostate and increase in hematocrit, would make androgen treatment a more beneficial option. Improvement of muscle strength will conceivably result in decreased morbidity and mortality in cachectic individuals and may allow patients to undergo more intensive treatments (e.g., radiation and chemotherapy regimens).(R)

LGD-4033 May Help Against Osteoporosis

Preventing bone loss and increasing bone formation are two mechanisms of protecting against osteoporosis. In addition to calcium and vitamin D supplementation, bisphosphonates are agents available to both men and women. These drugs increase bone mineral density (BMD) by inhibiting osteoclast activity.

Hormone replacement therapy (HRT) is commonly utilized to treat menopausal symptoms, but is no longer recommended for long-term treatment, due to increases in the risk of breast and endometrial cancer, gallbladder disease, and thromboembolism.(R)

Androgens are known to have a positive effect on BMD through increase in periosteal bone formation . Their importance in maintaining bone mass is further exemplified by the occurrence of osteopenia in male AR knockout mice and evidence that men undergoing androgen deprivation therapy (ADT) for a prolonged period suffer from decreases in BMD. (R)

The use of SARMs for osteoporosis is likely to provide benefit in both men and women, as they lack the side effects of virilization seen with steroidal androgens. A 120-day study comparing SARM S-4 and dihydrotestosterone (DHT) treatment in ovariectomized rats demonstrated that S-4 was able to maintain bone mass and bone strength to the levels of intact controls and exhibited greater efficacy than DHT.(R)

LGD-4033 Has No Known Adverse Effects

In this placebo-controlled study, 76 healthy men (21–50 years) were randomized to placebo or 0.1, 0.3, or 1.0 mg LGD-4033 daily for 21 days.

LGD-4033 was well tolerated. There were no drug-related serious adverse events. Frequency of adverse events was similar between active and placebo groups. Hemoglobin, prostate-specific antigen, aspartate aminotransferase, alanine aminotransferase, or QT intervals did not change significantly at any dose.

LGD-4033 had a long elimination half-life and dose-proportional accumulation upon multiple dosing. (R)
LGD-4033 administration was associated with dose-dependent suppression of total testosterone, sex hormone–binding globulin, high density lipoprotein cholesterol, and triglyceride levels. Follicle-stimulating hormone and free testosterone showed significant suppression at 1.0-mg dose only. Lean body mass increased dose dependently, but fat mass did not change significantly. Hormone levels and lipids returned to baseline after treatment discontinuation.(R)

LGD-4033 was safe, had favorable pharmacokinetic profile, and increased lean body mass even during this short period without change in prostate-specific antigen. Longer randomized trials should evaluate its efficacy in improving physical function and health outcomes in select populations.(R)

Technical Section

The tissue selectivity of SARMs could be related to differences in their tissue distribution, potential interactions with 5α-reductase or CYP19 aromatase, or tissue-specific expression of coregulators. However, autoradiography studies with bicalutamide and hydantoin derivatives showed that they do not preferentially accumulate in anabolic tissues.
Testosterone actions in some androgenic tissues are amplified by its conversion to 5α-DHT; nonsteroidal SARMs do not serve as substrates for 5α-reductase. Tissue selectivity of SARMs might be related to tissue-specific expression of co regulatory proteins.(R)

Testosterone and DHT promote the association of liganded AR with its co-activator, β-catenin; this interaction stabilizes β-catenin, promotes its translocation into the nucleus and association with TCF-4, and transcriptional activation of a number of Wnt-target genes. β-catenin plays an essential role in mediating the effects of testosterone on myogenic differentiation.(R)

Ligand-induced protein-protein interactions contribute to interactions between the amino and carboxyl terminal ends of the AR (i.e., N/C interaction) and co-activator recruitment. Both interactions are mediated by the interaction between the AF2 (second activation function) region of AR and the FXXLF or LXXLL binding motifs. The hydrophobic groove present in the AF2 region of AR LBD appears to be more favorable for phenylalanine binding, which suggests that the N/C interaction is preferred. (R)

Buy LGD-4033 (Ligandrol)

LGD-4033 (Ligandrol) is a research chemical and only sold for research purposes. sells LGD-4033 to researchers, but they don’t require you to verify that you’re a researcher.

Health Tools I Wish I Had When I Was Sick

At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.

That’s why I decided to create tools that will help others cut down the guesswork:

  • Lab Test Analyzer – a software tool that will analyze your labs and tell you what the optimal values are for each marker — as well as provide you with actionable tips and personalized health and lifestyle recommendations to help you get there.
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  • SelfHacked Secrets – an ebook where we examine and explain the biggest overlooked environmental factors that cause disease. This ebook is a great place to start your journey if you want to learn the essential steps to optimizing your health.
  • SelfHacked Elimination Diet course – a video course that will help you figure out which diet works best for you
  • Selfhacked Inflammation course – a video course on inflammation and how to bring it down
  • Biohacking insomnia – an ebook on how to get great sleep
  • Lectin Avoidance Cookbook – an e-cookbook for people with food sensitivities
  • BrainGauge – a device that detects subtle brain changes and allows you to test what’s working for you
  • SelfHacked VIP – an area where you can ask me (Joe) questions about health topics

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  • Danko Mirvic

    Hi TYLER KNIGHT Did you figure this out? sounds worrying if one is taking Finasteride or the stronger Dutasteride. Do you have the appropriate research articles discussing the neuroplasticity and neurogenesis effects of all the above?

  • Tyler Knight

    Hi Joe,

    I took LGD a year ago and have since developed similar symptoms to post finasteride syndrome as well as have been tested for lower levels of DHT. I was curious what you think about LGD affecting 5a-r permanently similar to finasteride. This can effect neuroplasticity and neurogenesis in a negative way and I have noticed significant changes in memory and cognition. Do you have an opinion of what I should do to possibly fix this?

  • Lou

    Most informative article I’ve EVER read concerning this particular Sarm

  • Cristian

    Do you recommend only solution and not oral peptides?? I mean, im totally newbie about research compounds so I wanna know if powders can be taken oral with the same safety and effects.

  • devyn

    Extremely informative article! Well done! LGD 4033

  • Don

    Have you tried this Joe?

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