madman
Super Moderator
Abstract
Purpose
Selective androgen receptor modulators (SARMs) have demonstrated agonist activity on the androgen receptor in various tissues, stimulating muscle mass growth and improving bone reconstruction. Despite being in clinical trials, none has been approved by the Food and Drug Administration (FDA) or the European Medicines Agency for pharmacotherapy. Still, SARMs are very popular as performance-enhancing drugs. The FDA has issued warnings about the health risks associated with SARMs, but the long-term exposure and possible adverse events still need to be fully understood. This review aims to evaluate the adverse events associated with using SARMs by humans.
Methods
PubMed database was searched from September 16, 2022, to October 2, 2023. In total, 20 records were included in the final review. Data from preclinical and clinical studies supported the review.
Results
Since 2020, 20 reports of adverse events, most described as drug-induced liver injury associated with the use of SARM agonists, have been published. The main symptoms mentioned were cholestatic or hepatocellular liver injury and jaundice. Limited data are related to the dosages and purity of SARM supplements.
Conclusion
Promoting SARMs as an anabolic agent in combination with other performance-enhancing drugs poses a risk to users not only due to doping controls but also to health safety. The lack of quality control of consumed supplements makes it very difficult to assess the direct impact of SARMs on the liver and their potential hepatotoxic effects. Therefore, more detailed analyses are needed to determine the safety of using SARMs.
Introduction
Selective androgen receptor modulators (SARMs) are a group of compounds with therapeutic potential. SARMs act as ligands by diffusing into the cell and binding to the androgen receptor in the cytoplasm. This creates a receptor–ligand complex that translocates to the nucleus where it binds to DNA and acts as a transcriptional regulator of androgen genes response. Unlike natural ligands of this receptor, SARMs have a tissue-selective effect, which gives them a significant advantage over other steroidal anabolic substances [1]. Currently, only SARMs antagonists, such as flutamide, nilutamide, bicalutamide, andenzalutamide, have been introduced to pharmacotherapy as nonsteroidal antiandrogen drugs for the treatment of prostate cancer. However, SARM agonists, which have shown the potential to stimulate muscle growth (anabolic effect) and improve bone reconstruction, are undergoing clinical trials and have not yet been approved by the Food and Drug Administration (FDA) or European Medicine Agency (EMA) for pharmacotherapy [2].
Recently, there have been many reports of liver damage caused by SARMs, as well as a comprehensive review of the probable causative mechanisms [28, 29]. Our review also takes into account changes in carbohydrate and lipid metabolism, including studies on animal models. Moreover, we summarized the toxicophores in more common SARM on the black market. Emerging work indicates a problem with the potential risk posed by the use of SARMs and a comprehensive analysis is necessary to better understand the causes of toxic effects.
The aim of this review is to evaluate liver injury cases associated with the use of SARM agonists by humans and to assess their safety according to the most current available knowledge.
Conclusions
Our review provides a comprehensive overview of the harmful effects of SARMs on the liver. However, current knowledge of the toxicity mechanisms of SARMs is insufficient. Uncontrolled dosing and/or combining several SARM compounds in one product may lead to AEs related to liver damage and affect lipid metabolism disorders. Withdrawal of the substance often results in liver recovery, but the actual number of SARM users remains unclear. Analytical tests have confirmed many discrepancies in both quantity and quality analysis, indicating a very low quality of SARM products available on the market. Labels often do not provide accurate information for consumers, and cases of counterfeit and fake manipulation among ingredients and declared doses have been confirmed.
Assessing liver damage, severity, and potential hepatotoxicity of SARM compounds, as well as their causality, can be helpful in the diagnosis and implementation of effective treatment in clinical practice. Promoting SARMs as a safe alternative to other anabolic compounds is significantly dangerous and poses a risk to public health. Increasing consumer awareness of the risks of SARM supplementation is crucial in preventing harmful effects.
Purpose
Selective androgen receptor modulators (SARMs) have demonstrated agonist activity on the androgen receptor in various tissues, stimulating muscle mass growth and improving bone reconstruction. Despite being in clinical trials, none has been approved by the Food and Drug Administration (FDA) or the European Medicines Agency for pharmacotherapy. Still, SARMs are very popular as performance-enhancing drugs. The FDA has issued warnings about the health risks associated with SARMs, but the long-term exposure and possible adverse events still need to be fully understood. This review aims to evaluate the adverse events associated with using SARMs by humans.
Methods
PubMed database was searched from September 16, 2022, to October 2, 2023. In total, 20 records were included in the final review. Data from preclinical and clinical studies supported the review.
Results
Since 2020, 20 reports of adverse events, most described as drug-induced liver injury associated with the use of SARM agonists, have been published. The main symptoms mentioned were cholestatic or hepatocellular liver injury and jaundice. Limited data are related to the dosages and purity of SARM supplements.
Conclusion
Promoting SARMs as an anabolic agent in combination with other performance-enhancing drugs poses a risk to users not only due to doping controls but also to health safety. The lack of quality control of consumed supplements makes it very difficult to assess the direct impact of SARMs on the liver and their potential hepatotoxic effects. Therefore, more detailed analyses are needed to determine the safety of using SARMs.
Introduction
Selective androgen receptor modulators (SARMs) are a group of compounds with therapeutic potential. SARMs act as ligands by diffusing into the cell and binding to the androgen receptor in the cytoplasm. This creates a receptor–ligand complex that translocates to the nucleus where it binds to DNA and acts as a transcriptional regulator of androgen genes response. Unlike natural ligands of this receptor, SARMs have a tissue-selective effect, which gives them a significant advantage over other steroidal anabolic substances [1]. Currently, only SARMs antagonists, such as flutamide, nilutamide, bicalutamide, andenzalutamide, have been introduced to pharmacotherapy as nonsteroidal antiandrogen drugs for the treatment of prostate cancer. However, SARM agonists, which have shown the potential to stimulate muscle growth (anabolic effect) and improve bone reconstruction, are undergoing clinical trials and have not yet been approved by the Food and Drug Administration (FDA) or European Medicine Agency (EMA) for pharmacotherapy [2].
Recently, there have been many reports of liver damage caused by SARMs, as well as a comprehensive review of the probable causative mechanisms [28, 29]. Our review also takes into account changes in carbohydrate and lipid metabolism, including studies on animal models. Moreover, we summarized the toxicophores in more common SARM on the black market. Emerging work indicates a problem with the potential risk posed by the use of SARMs and a comprehensive analysis is necessary to better understand the causes of toxic effects.
The aim of this review is to evaluate liver injury cases associated with the use of SARM agonists by humans and to assess their safety according to the most current available knowledge.
Conclusions
Our review provides a comprehensive overview of the harmful effects of SARMs on the liver. However, current knowledge of the toxicity mechanisms of SARMs is insufficient. Uncontrolled dosing and/or combining several SARM compounds in one product may lead to AEs related to liver damage and affect lipid metabolism disorders. Withdrawal of the substance often results in liver recovery, but the actual number of SARM users remains unclear. Analytical tests have confirmed many discrepancies in both quantity and quality analysis, indicating a very low quality of SARM products available on the market. Labels often do not provide accurate information for consumers, and cases of counterfeit and fake manipulation among ingredients and declared doses have been confirmed.
Assessing liver damage, severity, and potential hepatotoxicity of SARM compounds, as well as their causality, can be helpful in the diagnosis and implementation of effective treatment in clinical practice. Promoting SARMs as a safe alternative to other anabolic compounds is significantly dangerous and poses a risk to public health. Increasing consumer awareness of the risks of SARM supplementation is crucial in preventing harmful effects.
