C tier · mixed
A single well-conducted 21-day phase 1 safety and PK study in 76 healthy men is the entire published human evidence base, and it was a safety study never designed to demonstrate clinical benefit.
lgd-4033
LGD-4033 has one published randomised phase 1 human trial establishing short-term tolerability, dose-proportional pharmacokinetics and dose-dependent lean mass increase over three weeks. Beyond that single 21-day study there is no published human efficacy data, no long-term safety data, and no regulatory approval in any jurisdiction.
// we supply this one
available as a research reagent
≥ 98% HPLC · research solution · batch certificate published. Grade C above is our own and is not adjusted because we stock it.
the explanation
One proper human study exists, and it ran for just three weeks in healthy young men to check whether the compound was tolerated. It did add about a kilogram of lean mass at the top dose, but a three-week safety study cannot tell you what happens over months or years.
regulatory status
Not approved by FDA or any regulator; WADA-prohibited; not a lawful dietary supplement ingredient
LGD-4033 has never been approved for any indication; it was originated by Ligand Pharmaceuticals and licensed to Viking Therapeutics in 2014, and has been reported in phase 2 development for muscle atrophy and hip fracture without completing clinical development. FDA treats SARMs in bodybuilding products as unapproved drugs and has issued public safety notifications naming liver injury and acute liver failure, heart attack and stroke among the risks. LGD-4033 is prohibited at all times under WADA class S1.2, with high-profile adverse analytical findings including Joakim Noah (2017), Shayna Jack (2019) and Tristan Thompson (2024). The SARMs Control Act (S.2742 in 2018, S.2895 in 2019) proposed Schedule III placement for SARMs but was never enacted; per USADA no further action had been taken as of 2022.
how it works · proposed mechanism
LGD-4033 is a high-affinity non-steroidal androgen receptor agonist with tissue-selective activity favouring muscle and bone.
High-affinity AR agonism
LGD-4033 binds the androgen receptor with high affinity as a non-steroidal ligand, driving nuclear translocation and androgen-response-element-mediated transcription. Its non-steroidal scaffold is not a substrate for aromatase or 5-alpha reductase.
Selective anabolic transcription
The compound is reported to produce anabolic transcriptional programmes in skeletal muscle and bone with reduced activity at prostate tissue relative to testosterone. This selectivity is derived from preclinical models and has not been characterised in long-term human tissue endpoints.
HPG axis and lipid effects
Phase 1 data show dose-dependent suppression of total testosterone, SHBG and HDL cholesterol within 21 days, with FSH and free testosterone suppressed at the highest dose tested. Suppression was reported to be reversible within the five-week post-intervention follow-up window of that study.
what’s reported
evidence shape
9 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
The Basaria phase 1 trial found no significant aminotransferase change at any dose, and that single reassuring line is widely quoted as evidence that LGD-4033 is not hepatotoxic. The published case literature since then describes exactly the opposite in real-world use, which is the clearest illustration in this index of why a 21-day, 76-person, sub-milligram safety study cannot underwrite months of unsupervised exposure at far higher amounts.
key published findings
- Human trial (phase 1, Basaria et al., Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2013): 76 healthy men aged 21–50 randomised to placebo or 0.1, 0.3 or 1.0 mg LGD-4033 daily for 21 days with 5 weeks follow-up; the compound was reported well tolerated over this window.
- Human trial (phase 1): lean body mass increased dose-dependently, with a 1.2 kg gain reported at 1 mg/day over 21 days.
- Human trial (phase 1): dose-dependent suppression of total testosterone, sex hormone-binding globulin and HDL cholesterol was observed; FSH and free testosterone were significantly suppressed only at the 1.0 mg dose, and LH and PSA were unaffected.
- Human trial (phase 1, PK): LGD-4033 showed a long elimination half-life (24–36 hours) with dose-proportional accumulation on multiple dosing.
- Human case reports: LiverTox documents ligandrol among the SARMs implicated in clinically apparent cholestatic liver injury, despite the absence of aminotransferase signal in the phase 1 trial — a discrepancy attributable to the trial's very low doses and short duration.
limitations of the evidence
- The entire published human evidence base is a single 21-day phase 1 study at doses of 1 mg/day or below, far below amounts described in non-medical use, so both efficacy and safety extrapolation are unsupported.
- No published human trial has evaluated any clinical outcome endpoint; lean body mass by DXA is a surrogate measure.
- Reversibility of HPG axis suppression was assessed only over a five-week follow-up after three weeks of exposure and says nothing about recovery after prolonged use.
documented safety signals
- Drug-induced liver injury: LGD-4033 (ligandrol) is specifically named in the NIH LiverTox SARMs chapter, which assigns the class a likelihood score of B — a likely cause of clinically apparent liver injury.
- The injury pattern is cholestatic jaundice with marked hyperbilirubinaemia (initially 4.0–8.0 mg/dL, often peaking above 30 mg/dL) but only modest ALT elevation (2–5 × ULN) and near-normal alkaline phosphatase; latency is typically 2–3 months. Severe hyperbilirubinaemia has occasionally produced reversible renal dysfunction requiring temporary dialysis.
- Dose-dependent HDL cholesterol suppression documented in phase 1, an established adverse cardiovascular risk marker.
- Dose-dependent suppression of endogenous testosterone, free testosterone, FSH and SHBG documented in phase 1; long-term recovery kinetics are unknown.
- FDA public safety notification on SARM-containing bodybuilding products names heart attack, stroke, psychosis and hallucinations, sleep disturbance, sexual dysfunction, liver injury and acute liver failure, infertility, miscarriage and testicular shrinkage, and notes hospitalisation-requiring liver injuries.
- Consumer products sold as LGD-4033 are unregulated and frequently misrepresent identity and content, so trial-derived safety data do not describe them.
- Repeated adverse analytical findings in elite sport, including athletes attributing positives to contaminated supplements, indicate widespread presence of the compound in products that do not declare it.
identity
| full name | LGD-4033 (ligandrol, VK5211) |
| category | Anabolic & Receptor |
| modality | small molecule |
| formula | C14H12F6N2O |
| molar mass | 338.25 g/mol |
| cas | 1165910-22-4 |
| half-life | 24–36 hours (elimination half-life) |
laboratory handling
| storage | Reference material: store as a solid, desiccated and protected from light, at -20 °C for long-term stability; stock solutions typically stored at -80 °C with freeze-thaw cycles minimised. |
| solubility | Lipophilic small molecule; soluble in DMSO and ethanol, poorly soluble in water. Lot-specific solubility should be taken from the certificate of analysis. |
| co-studied with | Evidence caveat only: the hepatotoxicity case literature for ligandrol commonly involves concurrent exposure to other unapproved compounds and unlabelled product contents, which limits attribution of causality to LGD-4033 specifically. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
5 citedLiverTox: Clinical and Research Information on Drug-Induced Liver Injury, NIDDK/NIH · 2024 · official
U.S. Food and Drug Administration · 2025 · official
United States Anti-Doping Agency · 2022 · official
The Journals of Gerontology: Series A, Biological Sciences and Medical Sciences · 2013 · randomized
Cureus · 2023 · observational
others in Anabolic & Receptor