Magnesium supplements might be able to blunt a well-known side effect of the painkiller acetaminophen, new research suggests. The study found evidence in lab animals that oral magnesium can prevent acetaminophen-related liver damage by affecting the gut microbiome. More research will be needed to confirm this potential protective benefit, however.
Acetaminophen, either taken alone or in combination with other drugs, is one of the most widely used medications in the world. Sold generically and under the popular brand name Tylenol, it can alleviate fever and mild to moderate pain. But too much acetaminophen over a short period of time can cause acute and even life-threatening liver injury. It’s thought to be the leading cause of acute liver failure in the U.S, with an estimated 56,000 emergency room visits, 26,000 hospitalizations, and 500 deaths attributed annually to the drug, according to a 2005 study.
The drug’s harmful liver effects come from how the drug is metabolized by the body. The primary culprit appears to be an enzyme called CYP2E1, which breaks acetaminophen down into byproducts that can be toxic to the liver in high enough levels. So finding a way to safely inhibit CYP2E1 activity while taking acetaminophen might allow us to prevent overdoses and even allow the drug to be more useful than it already is.
In a study published Monday in Cell Host and Microbe, scientists in China and California describe how magnesium might do the trick.
Magnesium plays an important role in keeping many parts of the body healthy, including our heart—often by influencing hundreds of different enzymes. The researchers theorized that magnesium might also interact in important ways with the gut microbiome, the community of usually harmless or helpful bacteria and other microbes that live along our digestive tract. The researchers conducted experiments with mice, pigs, and humans to test out their hypothesis. In one experiment, for instance, the team seeded the guts of mice with the microbiomes of people who took magnesium supplements, then gave the mice high doses of acetaminophen.
Across these tests, the team found evidence that magnesium can prevent acetaminophen-related liver damage by inducing metabolic changes in the gut microbiome. Specifically, oral magnesium seemed to stimulate the metabolism of gut bacteria called Bifidobacterium, leading to increased levels of a compound called indole-3-carboxylic acid (I3C), which then bound to and inactivated CYP2E1.
“We provide a valuable approach, oral magnesium intake, as a potentially safe and effective strategy to prevent CYP2E1-mediated [acute liver failure],” the authors wrote.
The findings are largely limited to animals, so they’re not proof that people can just take magnesium supplements to keep themselves safe from a potential acetaminophen overdose. And it’s too early to know if its protective effect could be easily applied to everyone, since different people and their microbiomes might respond in different ways to magnesium.
But the results do offer some intriguing new avenues for research, the team says. Finding a way to boost levels of Bifidobacterium or I3C even without magnesium could help prevent acute liver injury from acetaminophen, for instance. And since CYP2E1 is also thought to be involved in other kinds of liver failure, such treatments could have more applications beyond making acetaminophen safer.
In any case, the authors say that “more experiments with an expanded spectrum of human subjects are required in the future.”