Repeated Acetaminophen Use May Not Be as Safe as Previously Thought

Tylenol tablets, which contain acetaminophen, are shown in Chicago on April 14, 2015. Scott Olson/Getty Images

A study in the United Kingdom found that “repeated doses” of acetaminophen for people aged 65 and older may lead to health complications.

University of Nottingham researchers found that people who often take acetaminophen, the active ingredient in Tylenol and which is called paracetamol in several other countries, should take extra care when dosing for chronically painful conditions such as osteoarthritis, according to a news release issued on Dec. 12.

“Due to its perceived safety, paracetamol has long been recommended as the first line drug treatment for osteoarthritis by many treatment guidelines, especially in older people who are at higher risk of drug-related complications,” said University of Nottingham professor Weiya Zhang in a statement published in the Arthritis Care and Research journal.

The study’s authors said they analyzed data from the Clinical Practice Research Datalink-Gold, a UK medical database, and analyzed participants aged 65 and older who had an average age of 75. The subjects used acetaminophen between 1998 and 2018.

The researchers also evaluated health records for 180,483 people who were prescribed acetaminophen on a regular basis, which the authors defined as two prescriptions or more within a six-month period. Their health outcomes were then compared with 402,478 individuals who were not repeatedly prescribed the painkiller, the authors said.

Prolonged usage of acetaminophen was associated with a higher risk of developing heart failure, chronic kidney disease, hypertension, and peptic ulcers, or a type of ulcer that affects the lining of the upper part of the small intestine and stomach.

What Other Recent Studies Say

Earlier this year, researchers at the University of California, Davis, also called into question whether regular use of acetaminophen is safe after finding that the painkiller was found to alter proteins in heart tissue. Published in April, the study was conducted on mice, researchers said.

“We found that regular use of acetaminophen at concentrations that are considered safe—equivalent to 500 mg/day—causes numerous signaling pathways inside the heart to be altered,” Gabriela Rivera, the study’s first author, said in a statement.

“These results prompt me to consider using acetaminophen at the lowest effective dose and for the shortest duration possible.”

In the study, mice given acetaminophen showed changes in the protein levels that are associated with “biochemical pathways involved in a range of functions, such as energy production, antioxidant usage and the breakdown of damaged proteins,” according to a news release.

They stressed that long-term medium or high-dose usage of the medication could cause “heart issues” due to an increase in oxidative stress or a higher amount of toxins that get produced when the drug breaks down.

A study released in 2022, published in the journal Circulation, found that acetaminophen may raise blood pressure when it’s taken on a regular basis.

Researchers evaluated 110 people with high blood pressure who were randomly assigned to take 1,000 milligrams of the painkiller, or about three Tylenol regular strength tablets, or a placebo four times a day for two weeks. That amounts to about 4,000 milligrams, reaching the upper maximum daily dose for a healthy adult.

After the period ended, people who took acetaminophen were switched to taking the placebo, while those taking the placebo were given the acetaminophen for another two weeks. It was found that those taking acetaminophen saw their blood pressure rise by 5 points on average.

University of Nottingham researchers said that more work is needed to gain a better understanding of acetaminophen’s impacts.

“Despite its perceived safety, acetaminophen is associated with several serious complications,” their study’s abstract said.

“Given its minimal analgesic effectiveness, the use of acetaminophen as the first-line oral analgesic for long-term conditions in older people requires careful reconsideration.”