Bring On the Exercise, Hold the Painkillers

By GRETCHEN REYNOLDS JULY 5, 2017

Taking ibuprofen and related over-the-counter painkillers could have unintended and worrisome consequences for people who vigorously exercise. These popular medicines, known as nonsteroidal anti-inflammatory drugs, or NSAIDs, work by suppressing inflammation. But according to two new studies, in the process they potentially may also overtax the kidneys during prolonged exercise and reduce muscles’ ability to recover afterward.

Anyone who spends time around people who exercise knows that painkiller use is common among them. Some athletes joke about taking “vitamin I,” or ibuprofen, to blunt the pain of strenuous training and competitions. Others rely on naproxen or other NSAIDs to make hard exercise more tolerable.

NSAID use is especially widespread among athletes in strenuous endurance sports like marathon and ultramarathon running. By some estimates, as many as 75 percent of long-distance runners take ibuprofen or other NSAIDs before, during or after training and races.

But in recent years, there have been hints that NSAIDs might not have the effects in athletes that they anticipate. Some studies have found that those who take the painkillers experience just as much muscle soreness as those who do not.

A few case studies also have suggested that NSAIDs might contribute to kidney problems in endurance athletes, and it was this possibility that caught the attention of Dr. Grant S. Lipman, a clinical associate professor of medicine at Stanford University and the medical director for several ultramarathons.

NSAIDs work, in part, by blunting the body’s production of a particular group of biochemicals, called prostaglandins, that otherwise flood the site of injuries in the body. There, they jump-start processes contributing to pain and inflammation. Prostaglandins also prompt blood vessels to dilate, or widen, increasing blood flow to the affected area.

Taking NSAIDs results in fewer prostaglandins and consequently less inflammation and less dilation of blood vessels.

Whether these effects are advisable in people exercising for hours has been uncertain, however.

So for one of the new studies, published Wednesday in the Emergency Medical Journal, Dr. Lipman asked 89 participants in several multiday ultramarathons around the world to swallow either an ibuprofen pill or a placebo every four hours during a 50-mile stage of their race.

Afterward, he and his colleagues drew blood from the racers and checked their levels of creatinine, a byproduct of the kidneys’ blood filtering process. High levels of creatinine in an otherwise healthy person are considered to be a sign of acute kidney injury.

The researchers found that many of the ultra runners, about 44 percent, had creatinine levels high enough to indicate acute kidney injury after running 50 miles.

But the incidence was particularly high among the runners who had taken ibuprofen. They were about 18 percent more likely to have developed an acute kidney injury than the racers swallowing a placebo. Furthermore, their injuries, based on creatinine levels, tended to be more severe.

The study did not follow the racers in subsequent days or weeks, but Dr. Lipman believes that they all recovered normal kidney function soon after the event ended.

The experiment also was not designed to determine why ibuprofen might have increased the risk for kidney problems in the racers. But Dr. Lipman and his colleagues suspect that, by inhibiting prostaglandins, the drug prevented blood vessels from widening as they otherwise might have. Slightly strangling blood flow to the kidneys, he says, might make it harder for those organs to filter the blood.

The second study, published in May in the Proceedings of the National Academy of Sciences, raised similar concerns. It found that by reducing the production of prostaglandins, NSAIDs change how a body responds to exertion, this time deep within the muscles.

For that study, researchers in the department of microbiology at Stanford University looked first at muscle cells and tissue from mice that had experienced slight muscular injuries, comparable to those we might develop during strenuous exercise. The tissue soon filled with a particular type of prostaglandin that turned out to have an important role: It stimulated stem cells within the muscles to start multiplying, creating new muscle cells that then repaired the tissue damage. Afterward, tests showed that the healed muscle tissue was stronger than it had been before.

This microscopic process mimics what should happen when we exercise strenuously, straining and then rebuilding our muscles.

But when the researchers used NSAIDs to block the production of prostaglandins within the muscles, they noted that fewer stem cells became active, fewer new cells were produced, and the muscle tissue, even after healing, was not as strong and springy as in tissues that had not been exposed to the drug. They saw the same reaction both in isolated muscle cells in Petri dishes and in living mice treated with NSAIDs.

We are not mice, of course. But the findings imply that in people, too, anti-inflammatory painkillers might slightly impair muscles’ ability to regenerate and strengthen after hard workouts, says Helen Blau, the director of the Baxter Laboratory for Stem Cell Biology at Stanford, who oversaw the experiment.

“There’s a reason for the inflammation” in the body after exercise, she says. “It’s part of the regenerative process and not a bad thing.” In fact, at the cellular level, she says, “it does look as if no pain means no gain.”

She suggests that those of us who exercise might want to consider options others than NSAIDs to relieve the aches associated with working out and competing.

Dr. Lipman, who is a clinician as well as a distance runner, agrees. “Maybe consider acetaminophen,” he says, a painkiller found in Tylenol that does not affect inflammation. Or skip the drugs altogether. “I often tell people, think ice baths,” he says.

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