ligandrol (VK5211) / Ligand, Viking Therap - LARVOL DELTA

Not Safer Than Steroids: Biopsy-Proven Designer Androgen Cholestasis Following Multi-Agent âSARMâ Supplement Use (ACG 2026) - "Case Description/ A 31-year-old man without prior liver disease presented with one month of progressive pruritus, jaundice, and acholic stools following use of a bodybuilding supplement âIron Solderâ containing four SARMs (LGD-4033, MK-2866, RAD-150, YK-11), a growth hormone secretagogue (MK-677/ibutamoren), and an aromatase inhibitor (arimistane)...The supplement was discontinued and the patient received cholestyramine and ursodiol symptomatically...Databases such as LiverTox provide freely accessible hepatotoxicity profiles for SARMs and may aid evaluation. Figure: Figure 1: H&E, low power - Liver biopsy core demonstrating preserved lobular architecture with bland cholestasis and minimal inflammation Figure: Figure 2: H&E, high power â canalicular bile plugging with intrahepatic cholestasis and focal hepatocyte dropout"

Biopsy • Cholestasis • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Pruritus

Severe Cholestatic Drug-Induced Liver Injury Associated With SARM Stacking and Herbal Supplements (ACG 2026) - "He reported three years of Ashwagandha, Fadogia root, and Tongkat Ali herbal use, with recent stacking of RAD-140, LGD-4033, and MK-677...N-acetylcysteine and ursodiol were initiated...He was discharged on an oral prednisone taper...Lastly, transaminase fluctuations during recovery should be interpreted with adjunctive markers such as creatine phosphokinase, aldolase, and 5'-nucleotidase to avoid unnecessary steroid use. Figure: Figure 1: Visualization of the liver enzyme and total bilirubin trend during the treatment and recovery course with significant events noted."

Cholestasis • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Myositis • Pruritus

Quantification of the Carboxylated LGD-4033 Long-Term Metabolite in Human Micro-Dose Excretion Study Urine Samples. (PubMed, Drug Test Anal) - "Accumulation effects during multiple-dose intake resulted in sustained urinary concentrations and prolonged detectability. The quantitative data generated in this study provide an important basis for improved interpretation of adverse analytical findings involving LGD-4033 and support a more evidence-based distinction between different intake scenarios."

Journal

Selective Androgen Receptor Modulation Restores Detrusor Contractility and Protects Smooth Muscle Cells from Hypoxic Injury (AUA 2026) - "Groups received vehicle, LGD-4033 (10 mg/kg/day), enzalutamide (10 mg/kg/day), or combination for 4 weeks. SARM dramatically restores bladder contractility in ischemia-induced DU via AR-dependent mechanisms. Direct cytoprotective effects on hypoxic smooth muscle cells provide mechanistic insight. The dual action of functional restoration and cell protection supports SARMs as a promising therapeutic for DU."

Cardiovascular • Urology

Further Insights Into the Metabolism of LGD-4033 in Human Urine. Part 1. Structure Elucidation of Additional Important Metabolites. (PubMed, Drug Test Anal) - "These findings expand current knowledge of LGD-4033 metabolism. From a doping control perspective, the proposed synthetic pathways may facilitate the production of reference materials for the detection and identification of a more comprehensive metabolite profile that will increase metabolic certainty in future LGD-4033 adverse analytical findings."

Journal

Further Insights Into the Metabolism of LGD-4033 in Human Urine. Part 2. A New Minor Metabolite With Antagonistic Activity on the Androgen Receptor Can Indicate Recent Substance Intake. (PubMed, Drug Test Anal) - "Additionally, the detection of M8, which is an early-stage excreted metabolite, is valuable for estimating sample collection time relative to LGD-4033 intake. When combined with the evaluation of other long-term metabolites like M5b, M5a, M2c, and M2d, M8 detection can aid in distinguishing adverse analytical findings, associated abuse through regular dosing, from unintentional doping caused by certain contamination scenarios or abuse through microdosing."

Journal • AR

In Vitro Metabolism of Doping Agents (Stanozolol, LGD-4033, Anastrozole, GW1516, Trimetazidine) by Human Seminal Vesicle and Liver Fractions. (PubMed, Metabolites) - "Gene expression and enzymatic activity in CYP3A4 and CYP1A2-major hepatic enzymes-were absent in SV-S9. Overall, these pilot study results suggest that the seminal vesicle has only a low capacity for xenobiotic metabolism, which translates into a limited role in the biotransformation of drugs and, hence, the metabolic pattern."

Journal • Preclinical • CYP1A2 • CYP2C9 • CYP2E1 • CYP3A4

Exploring transdermal SARMs exposure: Analysis of the elimination profiles and metabolism for doping control purposes. (PubMed, J Anal Toxicol) - "The objective of this project was to simulate a transdermal contamination scenario and investigate the skin penetration and subsequent metabolism of microdoses of three commonly used SARMs: LGD-4033, RAD140, and S-23. It was demonstrated for all three SARMs that they penetrate the skin and may-even in trace amounts-produce AAFs when administered transdermally. Information on urinary concentrations and metabolism following transdermal administration of SARMs may assist in the interpretation of AAFs, particularly when dermal contamination or intentional doping via the skin is discussed."

Journal

Rapid detection of illegal selective androgen receptor modulators in unregistered supplements using a combination of selected solid-state analytical methods. (PubMed, ADMET DMPK) - "Unregistered dietary supplements containing anabolic substances, specifically selective androgen receptor modulators (SARMs) such as andarine, ligandrol, ostarine, and testolone became the subject of investigation. Overall, almost half of the analyzed samples of unregistered/illegal sports dietary supplements purchased anonymously online in the Slovak Republic with declared content of at least one SARM did not contain what is declared on the label. Thus the combination of several solid-state analytical techniques without complex sample preparation has proven valuable for rapid identification of APIs in supplements."

Journal

SARMs, Metabolic Modulators and Growth Hormone Secretagogues in Suspected Illegal Medicines, Bought as Sport Performance Enhancers: A Retro- and Prospective Study Within the GEON. (PubMed, Drug Test Anal) - "Eighteen different molecules, within the scope of the study, were reported with as top 5: ibutamoren, ligandrol, ostarine, cardarine and andarine. From the limited quantitative data reported, it can be assumed that the majority of the samples contain active doses and some are even overdosed, so health risks for the consumers cannot be neglected."

Journal

Protective Role of Harmol Against β-Cell Toxicity And Glucose Dysregulation In Type 2 Diabetes Mellitus. (PubMed, Eur J Pharmacol) - "Harmol and ligandrol improved glucose tolerance in diabetic male rats induced by a high-fat diet and streptozotocin. Our results suggest that harmol could serve as a novel anti-diabetic agent for T2DM with a unique mechanism that targets AR for β-cell revival and enhances glucose tolerance."

Journal • Diabetes • Endocrine Disorders • Metabolic Disorders • Solid Tumor • Type 2 Diabetes Mellitus • NEUROG3

Drug transfer during intimate moments can produce an adverse analytical finding during a doping control. Case report with ligandrol. (PubMed, J Anal Toxicol) - "The Court of Arbitration for Sports accepted the athlete's explanation that she had been exposed to ligandrol through the exchange of bodily fluids with her husband and lifted her provisional ban. This case demonstrates that drug transfer between two subjects is possible during intimate moments."

Journal

Ligandrol lowers endurance and negatively affects lipid and hormonal profile of male rats. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Endurance training alone had favorable effects, and its combination with ligandrol did not seem to have an advantage. In the training group, ligandrol decreased Vegf-a gene expression and the size of muscle fibers type I and IIa."

Journal • Preclinical • Hematological Disorders • IGF1

Detection of LGD-4033 Metabolites in Camel Urine, Plasma, and Hair Following Oral Administration for Doping Control. (PubMed, Rapid Commun Mass Spectrom) - "The findings from this study will improve the rapid identification of LGD-4033 and related compounds, supporting effective doping control in camel racing. These results enhance understanding of LGD-4033 metabolism in camels and advance the development of reliable methods for detecting SARMs in this field."

Journal

Ligandrol Ameliorates High-Fat Diet- and Streptozotocin-Induced Type 2 Diabetes Mellitus and Prevents Pancreatic Islets Degeneration. (PubMed, Assay Drug Dev Technol) - "Histopathological staining studies showed that ligandrol prevents pancreatic islet degeneration compared with the HFD and STZ group. Our findings suggest that ligandrol's protective effect on pancreatic islets leading to its antidiabetic effect occurs through the activation of AR."

Journal • Diabetes • Genito-urinary Cancer • Metabolic Disorders • Oncology • Prostate Cancer • Solid Tumor • Type 2 Diabetes Mellitus

LGD-4033 and a Case of Drug-Induced Liver Injury: Exploring the Clinical Implications of Off-Label Selective Androgen Receptor Modulator Use in Healthy Adults. (PubMed, Cureus) - "A diagnostic workup ruled out other potential causes of liver injury, implicating SARM use as the likely etiology. This case underscores the necessity for heightened clinical vigilance, early diagnosis, and prompt intervention to mitigate serious health outcomes associated with SARM misuse."

Journal • Cardiovascular • Hepatology • Liver Failure • Osteoporosis • Psychiatry • Rheumatology

Selective Androgen Receptor Modulators (SARMs) Effects on Physical Performance: A Systematic Review of Randomized Control Trials. (PubMed, Clin Endocrinol (Oxf)) - "SARMs have a positive effect on physical performance and body composition and are associated with moderate rates of mild to moderate adverse effects (AEs) and a low rate of severe AEs."

Journal • Review • Cachexia • Oncology • Sarcopenia

The disordering effect of SARMs on a biomembrane model. (PubMed, Phys Chem Chem Phys) - "Here, we report significant information related to the changes that ostarine, ligandrol, andarine, and cardarine produce in the thermodynamic properties of a lipid biomembrane model. By employing theoretical calculations, we gained insights into the possible electrostatic interactions between SARMs and phospholipid molecules, enhancing our understanding of the driving forces behind the interactions of SARMs with lipid membranes. Overall, this investigation provides relevant knowledge related to the biophysical-chemical effects that SARMs produce in biomembrane models and could be of practical reference for promising applications of SARMs in medicine and sport."

Journal

A screening method for the quantitative determination of selective androgen receptor modulators (SARMs) in capsules by high resolution 19F- and 1H-NMR spectroscopy. (PubMed, Anal Methods) - "A new method for rapid determination of the content of selective androgenic receptor modulators (SARMs) andarine, cardarine, ligandrol, ostarine and S-23 in capsules by 1H- and 19F-high resolution nuclear magnetic resonance spectroscopy was described and validated. The statistical analysis of the results from 19F- and 1H-quantitative NMR showed that both approaches were equally effective, thus expanding the potential use of the methodology to non-fluorinated SARMs. At present, no SARM has been approved for human consumption; however, SARMs are actually used by bodybuilders and recreational athletes, who purchase them even though the risk-benefit ratio of these molecules has not been definitively established."

Journal

Targeted Metabolic Investigation of Ligandrol and Analytical Methods Validation for Its Main Long-term Metabolite. (PubMed, Chempluschem) - "Further clarifying ligandrol's metabolic profile, the availability of synthetic reference material permitted the structural elucidation of a previously reported pyrrolidinone-type metabolite and revealed its potential analytical utility as an additional long-term marker. Moreover, synthetic reference material enabled the comparison and validation of liquid chromatography coupled with mass spectrometry (LC-MS)-based and gas chromatography coupled with mass spectrometry (GC-MS)-based detection and identification methods focusing on the LGD-LTM1 marker."

Journal

Detection of anabolic agents including selective androgen receptor modulators in samples outside of sport. (PubMed, Drug Test Anal) - "The top three SARMs found were LGD-4033 followed by RAD140 and ostarine. Our results indicate that SARM use might be a concern outside of sport. Subsequently, in addition to AAS, the healthcare system should also be informed about SARM abuse and the associated adverse side effects."

Journal

Investigation of in vitro generated metabolites of LGD-4033, a selective androgen receptor modulator, in homogenized camel liver for anti-doping applications. (PubMed, Rapid Commun Mass Spectrom) - "These findings provide valuable insights into the metabolism of LGD-4033 in camels and aid in the development of effective doping control methods for the detection of SARMs in camel racing."

Journal • Preclinical

Selective Androgen Receptor Modulators Combined with Treadmill Exercise Have No Bone Benefit in Healthy Adult Rats. (PubMed, Pharmaceuticals (Basel)) - "The effects of combination treatments using the selective androgen receptor modulators (SARMs) ostarine (OST) or ligandrol (LIG) with treadmill exercise (TE) were studied in healthy adult rats. TE represents a safe treatment. Because SARMs are increasingly applied in gyms along with physical activities, attention should be paid to possible side effects."

Journal • Preclinical

Variation of Sequential Ligandrol (LGD-4033) Metabolite Levels in Routine Anti-Doping Urine Samples Detected with or without Other Xenobiotics. (PubMed, Molecules) - "It is also worth noting that dietary supplements may contain ligandrol as an official ingredient or as a contaminant. The described method may be usefully applied by other anti-doping or toxicological laboratories."

Journal

Effects of ligandrol as a selective androgen receptor modulator in a rat model for osteoporosis. (PubMed, J Bone Miner Metab) - "Ligandrol at high dose showed a subtle anabolic effect on structural properties without any improvement in biomechanical properties of osteoporotic bones. Considering side effects of ligandrol at this dose, its further investigation for the therapy of postmenopausal osteoporosis should be reevaluated."

Journal • Preclinical • Osteoporosis • Rheumatology