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

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."

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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."

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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."

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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."

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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."

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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."

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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."

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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."

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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."

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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."

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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

Investigations into the concentration and metabolite profiles of stanozolol and LGD-4033 in blood plasma and seminal fluid using liquid chromatography high-resolution mass spectrometry. (PubMed, Anal Bioanal Chem) - "The developed assays proved appropriate for the detection of the target substances in both matrices with detection limits between 10 and 40 pg/mL for the unmetabolized drugs in sf and bp, allowing to estimate the concentration of stanozolol in bp (0.02-0.40 ng/mL) and in sf (0.01-0.25 ng/mL) as well as of LGD-4033 in bp (0.21-2.00 ng/mL) and in sf (0.03-0.68 ng/mL) post-administration. In addition, metabolites resulting from different metabolic pathways were identified in sf and bp, with sf resembling a composite of the metabolic profile of bp and urine."

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Structure revision and chemical synthesis of ligandrol's main bishydroxylated long-term metabolic marker. (PubMed, Org Biomol Chem) - "A chemically more robust structure was postulated as an alternative to the one previously established. The NMR spectra of the synthesized material and its LC-HRMS comparison with a relevant metabolic sample support the proposed structural revision."

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Ligandrol-induced liver injury - Case Report (PubMed, Z Gastroenterol) - "Ligandrol is misused as a selective androgen receptor modulator to promote muscle building. This case represents a typical case of abuse of anabolic substances in amateur sports."

Journal • Cholestasis • Dermatology • Fibrosis • Hepatology • Immunology • Liver Failure • Pain • Pruritus

Severe cholestatic injury following use of RAD-140, a novel, easily accessible body-building supplement (AGW 2022) - "Introduction: Selective androgen receptor modulators (SARMS), such as RAD-140, ligandrol, and enobosarm, promote anabolic actions without significant androgenic side effects...Both patients commenced treatment with ursodeoxycholic acid 500 mg twice daily and cholestyramine 4 g four times daily... SARMs have the potential to cause severe cholestatic injury that is not extensively documented. Given the ease of access of these supplements, clinicians should be aware of severe cholestatic liver injury associated with their use and the prolonged recovery."

Cholestasis • Fatigue • Hepatology • Liver Failure

Detection of selective androgen receptor modulators (SARMs) in serum using a molecularly imprinted nanoparticle surface plasmon resonance sensor. (PubMed, J Mater Chem B) - "Here we present a surface plasmon resonance sensor for three commonly-used SARMS, Andarine, Ligandrol and RAD-140, using high-affinity molecularly imprinted nanoparticles (nanoMIPs) as the recognition element. Crucially these levels are below the minimum required performance limit (MRPL) set for these compounds by WADA. This study highlights the power of modern molecular imprinting to rapidly address required molecular recognition for new compounds of interest."

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Development and validation of SARMs and metabolic modulators screening in hair using UHPLC-MS/MS: Application to a doping case and first identification of S23 in authentic human hair. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "A method has been developed and validated for the analysis in hair of 9 SARMs (AC262536, ACP-105, andarine, LGD-4033, MK-0773, MK 677, ostarine, RAD 410 and S23) and 2 other metabolic modulators (GW501516, SR9009), using liquid chromatography coupled to tandem mass spectrometry. After addition of bicalutamide-D used as internal standard and incubation in phosphate buffer pH = 9.5, 20 mg of hair samples were extracted with liquid/liquid extraction...The application and the interest of SARMs screening was demonstrated in a doping case. Three SARMs were detected namely andarine (120-1644 pg/mg), ostarine (1-9 pg/mg) and S23 (0.6-16 pg/mg) in 6x1 cm segments of the subject."

Clinical • Journal

Investigations into the elimination profiles and metabolite ratios of micro-dosed selective androgen receptor modulator LGD-4033 for doping control purposes. (PubMed, Anal Bioanal Chem) - "The metabolite M1, representing the epimer of LGD-4033, was synthesized and the structure elucidated by NMR spectroscopy. As the M1/LGD-4033 ratio changes over time, the ratio and the approximate LGD-4033 concentration can contribute to estimating the time point of drug intake and dose of LGD-4033 in doping control urine samples, which is particularly relevant in anti-doping result management."

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