Ligandrol LGD-4033 between a 21-day healthy-men RCT and a grey-market DILI case layer

01 Names and chemistry

Ligandrol is a nonsteroidal oral selective androgen receptor modulator coded LGD-4033. Development synonyms include VK5211 in Viking Therapeutics hip-fracture work. It is not enobosarm, not RAD140, not andarine, and not Cardarine. PubChem and CAS agreement are required before a paper is admitted; bottle labels are not identity.

Open PubMed counts for LGD-4033 OR ligandrol OR VK5211 were on the order of fifty indexed records at harvest — enough for a compound monograph, not enough for a mature approved anabolic drug.

02 Mechanism claims

LGD-4033 binds the androgen receptor with high affinity and was designed for tissue-selective activation of androgenic signalling with reduced prostate liability relative to classical androgens (Basaria et al., 2013, background). Human selectivity is inferred from short-trial endpoints (lean mass, PSA, lipids, aminotransferases), not proven as an absolute firewall at every exposure.

03 Basaria et al., 2013 — the controlled record

Basaria and colleagues randomised 76 healthy men (21–50 years) to placebo or 0.1, 0.3, or 1.0 mg LGD-4033 daily for 21 days in a placebo-controlled study evaluating safety, tolerability, pharmacokinetics, lean body mass, muscle strength, stair-climbing power, and sex hormones (PMID 22459616). Lean body mass rose dose-dependently. Total testosterone, SHBG, HDL cholesterol and triglycerides fell. Prostate-specific antigen and aminotransferases did not change significantly in that short window. Hormones and lipids moved back toward baseline after stopping in that study. That is the peer-reviewed human backbone for ligandrol.

Twenty-one days is enough to see composition direction and axis/lipid shifts; it is not enough to settle long-term hepatic risk, cardiovascular outcomes, or functional benefit in sarcopenia or fracture recovery. Holding that limit in view is mandatory when grey-market lore cites “Basaria” as if it were a lifestyle endorsement.

04 VK5211 hip-fracture thread

Viking Therapeutics advanced LGD-4033 as VK5211 for muscle and bone endpoints after hip fracture. Phase 2 topline press claims lean-mass gains in recovery populations. Those communications remain secondary until a peer-reviewed full text is admitted. SEC filings and press wires surfaced in the Tavily harvest are discovery leads, not primary efficacy tables for this monograph.

05 Metabolism and anti-doping

Human excretion and metabolite profiling of LGD-4033 supports WADA-oriented detection (PMID 30255601 and related elimination-profile work). That stream confirms exposure interest and detection chemistry; it does not validate therapeutic claims. Equine and micro-dosing metabolite papers enlarge the analytical map without enlarging the clinical evidence.

06 Drug-induced liver injury

Peer-reviewed case reports document cholestatic hepatitis temporally associated with consumer Ligandrol / LGD-4033 products. Flores et al. (2020) described a 32-year-old man with severe DILI after Ligandrol use, biopsy showing cholestatic hepatitis with mild fibrosis (PMID 32637435). German-language and Cureus-indexed cases continue the series. LiverTox’s class chapter places such injuries beside anabolic-steroid-pattern jaundice. Product identity is often unverified; multi-compound stacks are common.

A 2022 case report of co-administered LGD-4033 and MK-677 described increases in body mass and lean mass with adverse shifts in lipids, liver enzymes, and testosterone (PMID 36303408) — a stack exposure, not a clean LGD-4033 monotherapy RCT, and not a protocol recommendation.

07 Regulatory status

Ligandrol is not FDA-approved for bodybuilding or aging. SARMs are WADA S1 prohibited substances. FDA consumer warnings on SARM-containing body-building products apply to the market context in which “LGD” is sold.

08 Absences

Independent long-term RCTs of grey-market ligandrol do not exist. Peer-reviewed VK5211 Phase 2 full text was not admitted at harvest. Head-to-head trials versus enobosarm or testosterone on hard clinical outcomes are sparse.

10 Harvest literature map

The 5 August 2026 deep harvest (Tavily/Exa/PubMed) clustered ligandrol evidence into four strata: (1) the Basaria 2013 RCT island; (2) human and equine metabolite / anti-doping methods; (3) Viking VK5211 secondary communications for hip-fracture recovery; (4) consumer DILI and stack case reports. PubMed open count for LGD-4033 OR ligandrol OR VK5211 was approximately fifty. Firecrawl returned empty markdown for the Basaria PubMed URL; NCBI efetch abstracts were used instead. Class reviews (PMID 38059982; 35340496; 30503797) supply the shared hepatotoxicity frame without converting ligandrol into enobosarm.

Rat osteoporosis-model work with ligandrol (PMID 37407738) is preclinical bone pharmacology and is not transcribed as a human fracture-outcome claim. Analytical papers on sequential metabolite levels in anti-doping urine samples document detection windows; they are not pharmacokinetic advice for consumers.

09 Reading order

The class monograph maps shared SARM pharmacology and DILI themes. This document carries the Basaria island, the VK5211 secondary thread, and the ligandrol-named case layer. Cardarine adjacency is labelled non-SARM wherever it appears.

How this document was assembled

Commissioned 5 August 2026 in the Adjacent Compounds / SARMs group and rewritten the same day after a deep research-API harvest (Tavily, Exa, PubMed E-utilities, ClinicalTrials.gov API v2, Camoufox for selected primary pages). Artefacts live under projects/adjacent_compounds_research_2026/deep_harvest/. HOUSE_STYLE governs presentation. PubMed-indexed references are NCBI-resolved.

Evidence handling

Study type is named in the reporting sentence. Animal and in-vitro results are not phrased as human outcomes. Sponsor press is secondary until peer-reviewed full text is admitted. Consumer case reports are grey-market exposure literature unless product analytics accompany the report. Cardarine is never called a SARM.

References

1. Barbara M, Dhingra S, Mindikoglu AL. Ligandrol (LGD-4033)-Induced Liver Injury. ACG Case Rep J. 2020;7(6):e00370.
   PMID 32637435 · doi:10.14309/crj.0000000000000370 · PMC7304490
2. Basaria S, Collins L, Dillon EL, Orwoll K, Storer TW, Miciek R, et al.. The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men. J Gerontol A Biol Sci Med Sci. 2013;68(1):87-95.
   PMID 22459616 · doi:10.1093/gerona/gls078 · PMC4111291
3. Cardaci TD, Machek SB, Wilburn DT, Heileson JL, Harris DR, Cintineo HP, et al.. LGD-4033 and MK-677 use impacts body composition, circulating biomarkers, and skeletal muscle androgenic hormone and receptor content: A case report. Exp Physiol. 2022;107(12):1467-1476.
   PMID 36303408 · doi:10.1113/EP090741
4. Fragkaki AG, Sakellariou P, Kiousi P, Kioukia-Fougia N, Tsivou M, Petrou M, et al.. Human in vivo metabolism study of LGD-4033. Drug Test Anal. 2018;10(11-12):1635-1645.
   PMID 30255601 · doi:10.1002/dta.2512
5. Hoffmann DB, Derout C, Müller-Reiter M, Böker KO, Schilling AF, Roch PJ, et al.. Effects of ligandrol as a selective androgen receptor modulator in a rat model for osteoporosis. J Bone Miner Metab. 2023;41(6):741-751.
   PMID 37407738 · doi:10.1007/s00774-023-01453-8
6. Khan S, Fackler J, Gilani A, Murphy S, Polintan L. Selective Androgen Receptor Modulator Induced Hepatotoxicity. Cureus. 2022;14(2):e22239.
   PMID 35340496 · doi:10.7759/cureus.22239 · PMC8929477
7. Leciejewska N, Jędrejko K, Gómez-Renaud VM, Manríquez-Núñez J, Muszyńska B, Pokrywka A. Selective androgen receptor modulator use and related adverse events including drug-induced liver injury: Analysis of suspected cases. Eur J Clin Pharmacol. 2024;80(2):185-202.
   PMID 38059982 · doi:10.1007/s00228-023-03592-3 · PMC10847181
8. Solomon ZJ, Mirabal JR, Mazur DJ, Kohn TP, Lipshultz LI, Pastuszak AW. Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications. Sex Med Rev. 2019;7(1):84-94.
   PMID 30503797 · doi:10.1016/j.sxmr.2018.09.006 · PMC6326857
9. U.S. Food and Drug Administration. Consumer updates and warning letters on body-building products containing SARMs. Regulatory context.
   https://www.fda.gov/
10. World Anti-Doping Agency. Prohibited List — S1 Anabolic Agents (selective androgen receptor modulators).
    https://www.wada-ama.org/
11. NIDDK LiverTox. Selective Androgen Receptor Modulators (SARMs). NCBI Bookshelf NBK619971.
    https://www.ncbi.nlm.nih.gov/books/NBK619971/
12. ClinicalTrials.gov. Protocol inventory via API v2; not peer-reviewed results.
    https://clinicaltrials.gov/
13. PubChem compound summary pages used for identity cross-checks.
    https://pubchem.ncbi.nlm.nih.gov/