The study, published in the journal EBioMedicine, highlights the power of genomic and metabolomic profiling to better understand drug mechanisms of action and metabolism even in common drugs such as acetaminophen.
The researchers first looked at 455 active adults over age 18 who were divided into two groups—a 208-person machine learning training set and a 247-person test set. As a validation set, the team included 1,880 European ancestry twins from the TwinsUK cohort and 1,235 individuals of African American and Hispanic ancestry from the Insulin Resistance Atherosclerosis Study. Metabolomic analysis of more than 700 metabolites was conducted by the company Metabolon.
The team identified depletion of sulfated sex hormones associated with acetaminophen use in all the study populations. The results showed that use of acetaminophen is roughly equivalent to 35 years of aging on sulfated hormone levels, which could affect placental health and general reproductive health. While there are many factors that go into reproductive health, this new study identified an area of acetaminophen’s effects that weren’t previously known, offering some insight into previous studies suggesting that acetaminophen exposure during gestation may impact development of masculine and behavioral characteristics.
These sulfated sex hormones, also referred to as neurosteroids, have many effects in the brain. There are no currently approved drugs that are specifically designed to target neurosteroid metabolism. Drugs that target this pathway could potentially treat many diseases of the nervous system, for example chronic pain and depression.
“These findings are significant for they showcase how the body is impacted by seemingly innocuous everyday medications like Tylenol,” said Amalio Telenti. “There are hundreds of other drugs that no one has done this research for. We delineate a general strategy that should be applied broadly in the study of medications in common use.”
First author Isaac Cohen, PharmD candidate at UC San Diego, added, “This study reveals significant new opportunities for pharmaceutical research to better understand common medications and their effects on human health and patient safety. Our research also emphasizes how the integration of genomics and metabolomics should enable better outcomes for clinical trials.”
Other authors on the paper were from the following organizations: J. Craig Venter Institute, the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California San Diego, Metabolon Inc. and the Department of Twin Research and Genetic Epidemiology at King’s College London, UK