Abstract
LGD-4033, also known as Ligandrol or VK5211, is a nonsteroidal selective androgen receptor modulator (SARM) under investigation for muscle wasting disorders, age-related sarcopenia, and osteoporosis. It binds selectively to androgen receptors in muscle and bone, promoting anabolic activity with reduced androgenic effects compared to testosterone. Phase I clinical trials have demonstrated increases in lean body mass with short-term use, making LGD-4033 one of the most clinically studied SARMs to date. This review summarizes its mechanism of action, research findings, experimental dosing, safety considerations, and includes a frequently asked questions (FAQ) section.
1. Introduction
SARMs represent a novel class of compounds designed to provide the anabolic effects of androgens in muscle and bone, while minimizing side effects in reproductive and other tissues. LGD-4033, developed by Ligand Pharmaceuticals, is one of the most promising SARMs due to its high selectivity, oral bioavailability, and clinical trial data. Unlike anabolic steroids, it does not convert to estrogen or dihydrotestosterone (DHT), reducing risk of off-target effects.
2. Mechanism of Action
- Androgen receptor binding: Strong affinity for androgen receptors in skeletal muscle and bone.
- Tissue selectivity: Promotes muscle growth and bone density without significant stimulation of prostate tissue.
- Nonsteroidal structure: Lacks steroid conversion pathways, contributing to a cleaner endocrine profile compared to testosterone.
3. Research Findings
3.1 Clinical trials
- In a 21-day phase I human trial, LGD-4033 produced dose-dependent increases in lean body mass (up to ~1.2 kg at 1 mg/day) without significant adverse effects.
- Demonstrated good tolerability and favorable pharmacokinetics.
3.2 Muscle wasting and sarcopenia
- Investigated for potential in treating muscle loss due to aging, immobilization, or chronic illness.
3.3 Bone health
- Preclinical evidence suggests positive effects on bone strength and density, supporting exploration for osteoporosis treatment.
3.4 Comparison to anabolic steroids
- LGD-4033 produces anabolic effects similar to low-dose testosterone but with greater receptor selectivity and fewer androgenic effects.
4. Typical Experimental Dosing
⚠️ Disclaimer: These values reflect research-only contexts and limited clinical trials. Not approved for medical use.
- Phase I clinical trial doses: 0.1–1 mg/day orally for 21 days.
- Non-clinical research reports: 5–10 mg/day orally for 6–12 weeks.
- Stacking protocols: Sometimes studied with other SARMs or GH secretagogues in research contexts.
5. Safety & Limitations
- Suppression: Clinical trial data show suppression of endogenous testosterone and sex hormone–binding globulin (SHBG) even at low doses.
- Reported side effects: fatigue, headaches, mild nausea, and hormone suppression.
- Liver impact: No strong evidence of hepatotoxicity in trials, but long-term safety unknown.
- Regulatory status: Not FDA-approved. WADA has banned LGD-4033 for athletic use.
6. Conclusion
LGD-4033 is one of the most clinically advanced SARMs, with human trial data supporting its anabolic activity and tolerability in the short term. It shows promise for conditions like sarcopenia and osteoporosis, but concerns about hormonal suppression and lack of long-term safety data limit its use to research settings.
7. References (sample)
- Basaria S, et al. (2013). Safety, pharmacokinetics, and effects on lean body mass of LGD-4033 in healthy men. J Gerontol A Biol Sci Med Sci.
- Dalton JT, et al. (2013). Selective androgen receptor modulators in preclinical and clinical development. Endocr Rev.
- Jayaraman A, et al. (2014). SARMs: emerging therapies for muscle wasting and bone disorders. Curr Opin Clin Nutr Metab Care.
8. Frequently Asked Questions (FAQ)
Q1: What is LGD-4033?
A: LGD-4033 (Ligandrol) is a nonsteroidal selective androgen receptor modulator (SARM) being researched for muscle wasting, osteoporosis, and age-related sarcopenia.
Q2: How does LGD-4033 work?
A: It binds selectively to androgen receptors in muscle and bone, promoting anabolic effects while minimizing androgenic stimulation of tissues like the prostate.
Q3: What makes LGD-4033 different from RAD-140?
A: Both are potent SARMs, but LGD-4033 has more human clinical data and may be slightly less anabolic than RAD-140, with a stronger record of tolerability in trials.
Q4: What are the typical research doses?
A: Clinical studies used 0.1–1 mg/day. Non-clinical reports often reference 5–10 mg/day over 6–12 weeks.
Q5: Does LGD-4033 suppress testosterone?
A: Yes. Even low doses (1 mg/day) suppressed testosterone and SHBG in clinical studies, requiring consideration of recovery strategies post-use in research.
Q6: Is LGD-4033 toxic to the liver?
A: Clinical data show no strong hepatotoxicity signals in short-term use, but long-term effects remain unknown.
Q7: Is LGD-4033 legal?
A: It is not FDA-approved and is banned by WADA for competitive athletes. It is available only as a research chemical.
Q8: Has LGD-4033 been tested in humans?
A: Yes. Phase I trials demonstrated dose-dependent increases in lean body mass with short-term use, making it one of the most clinically studied SARMs.
⚠️ Note: This review is for educational and research purposes only. LGD-4033 is an experimental compound not approved for human use.
