High levels of antihistamine drugs can reduce fitness gains, study finds

For some, the word “histamine” might evoke thoughts of seasonal allergies: runny noses, scratchy throats and itchy eyes. But the molecule also influences exercise performance.

A new study from the University of Oregon underscores its beneficial role in aerobic activity and exercise recovery, showing that blocking histamine at high levels interferes with fitness gains. It remains to be seen if lower-dose, over-the-counter antihistamine drugs have the same effect.

The study was published in the Journal of Applied Physiology.

Histamine is a small signaling molecule that evolved long ago. It is found in many plants and animals, including single-celled organisms, which use it to signal and adapt to stress.

“In exercise, it actually seems to be playing a very similar role of facilitating our adaptation to stress,” said John Halliwill, a professor of human physiology at the University of Oregon and an author on the study.

In humans, histamine is part of the immune system; it passes along the message that inflammation is needed somewhere. During allergy season, for example, pollen triggers the release of histamine from mast cells, an immune system component.

Then, an inflammatory response floods the area to try and get rid of the pollen, causing typical seasonal allergy symptoms. That’s why drugs known as antihistamines, such as Claritin and Zyrtec, are used to treat seasonal allergies.

Inflammation is also linked to fitness improvements because muscles are microscopically damaged during exercise and need to be repaired, which also builds new muscle tissue. Halliwill and colleagues found that when histamine is blocked, aerobic fitness improvements were slashed in half.

The team compared the improvements in a group of 16 men and women participating in a six-week cycling regimen. Participants pedaled on stationary bikes three to four times a week over the course of the study. One group received a dose of antihistamine medication before each training session while the other group took a placebo. Then, researchers compared how the groups’ bodies adapted.

When it came to their actual performance—how hard they could bike—the placebo group saw about twice the improvement of the histamine-blocker group. Improvements in blood flow were also significantly higher in the placebo group, the team reported.

Interestingly, there wasn’t a strong difference between the groups’ improvements in maximum oxygen consumption. Often called VO₂ max in the fitness world, it’s the maximum amount of oxygen the body can absorb and use, with a higher VO₂ max signaling better fitness.

It could be the study size was too small to see a difference, or six weeks might not have been long enough to uncover a change between the groups, Halliwill said.

Scientists first suspected that histamine might be a part of the body’s response to exercise in the 1970s. The idea didn’t gain traction until the last decade or so, with researchers now trying to tease apart the relationship.

Just like an allergic reaction, it starts with mast cells, which are found throughout skeletal muscle tissue. When those muscles are working, they trigger the mast cells to spill their histamine, although researchers aren’t yet sure what spurs that reaction.

The histamine causes blood vessels to dilate, allowing more blood flow to the muscles. When the muscle goes back to resting, the histamine continues to have an effect by prompting a cascade of immune responses, which brings beneficial inflammation to the area.

“We’ve got a whole village of cell types that are turning on programs to remodel and restructure and improve the function of the skeletal muscle-organ system,” Halliwill said. “Mast cells and the histamine that they release are a major coordinator of all those cell types.”

Histamine also seems to boost the response of certain genes during exercise. When histamine is blocked, about a quarter of those 3,000 or so genes aren’t amplified. That means fewer new proteins get produced by muscles as they recover from exercise, and those proteins likely play key roles in fitness gains, like the ones measured in the UO study.

Before Halliwill’s paper came out, a different group published a similar study looking at the effect of antihistamines during high-intensity interval training. Halliwill said both studies’ results are in agreement that blocking histamine reduced a person’s fitness gains. The results could apply to any form of aerobic activity, be it cycling, running, swimming or something else.

Halliwill emphasized that the new studies and other related research use very high doses of antihistamines, much higher than what a person would consume to combat allergies. More evidence is needed to know whether a low-dose daily allergy medication could interfere with fitness.