Running regularly has long been linked to a host of health benefits, including weight control, stress reduction, better blood pressure and cholesterol.

However, recent research suggests there may a point of diminishing returns with running.

A number of studies have suggested that a "moderate" running regimen -- a total of two to three hours per week, according to one expert -- appears best for longevity, refuting the typical "more is better" mantra for physical activity.

The researchers behind the newest study on the issue say people who get either no exercise or high-mileage runners both tend to have shorter lifespans than moderate runners. But the reasons why remain unclear, they added.

The new study seems to rule out cardiac risk or the use of certain medications as factors.

"Our study didn't find any differences that could explain these longevity differences," said Dr. Martin Matsumura, co-director of the Cardiovascular Research Institute at the Lehigh Valley Health Network in Allentown, Pa.

Matsumura presented the findings Sunday at the American College of Cardiology's annual meeting in Washington, D.C. Studies presented at medical meetings are typically viewed as preliminary until published in a peer-reviewed journal.

Matsumura and his colleagues evaluated data from more than 3,800 men and women runners, average age 46. They were involved in the Masters Running Study, a web-based study of training and health information on runners aged 35 and above. Nearly 70 percent reported running more than 20 miles a week.

The runners supplied information on their use of common painkillers called NSAIDs (nonsteroidal anti-inflammatory medications such as ibuprofen and naproxen/Aleve), which have been linked with heart problems, as well as aspirin, known to be heart-protective. The runners also reported on known heart risk factors such as high blood pressure, high cholesterol, diabetes, family history of heart disease and smoking history.

None of these factors explained the shorter lives of high-mileage runners, the researchers said. Use of NSAIDs was actually more common in runners who ran less than 20 miles weekly, Matsumura's team noted. "The study negates the theory that excessive use of NSAIDs may be causing this loss of longevity among high-mileage runners," Matsumura said.

So what's the advice to fitness-oriented Americans?

"I certainly don't tell patients 'Don't run,' " Matsumura said. But, he does tell high-mileage runners to stay informed about new research into the mileage-lifespan link as more becomes known.

"What we still don't understand is defining the optimal dose of running for health and longevity," he said.

Even though the heart disease risk factors couldn't explain the shorter longevity of high-mileage runners, there do seem to be potentially life-shortening ill effects from that amount of running, said Dr. James O'Keefe, director of preventive cardiology at the Mid-American Heart Institute in Kansas City.

O'Keefe, who reviewed the findings, believes there may simply be "too much wear and tear" on the bodies of high-mileage runners. He has researched the issue and is an advocate of moderate running for the best health benefits. Chronic extreme exercise, O'Keefe said, may induce a "remodeling" of the heart, and that could undermine some of the benefits that moderate activity provides.

In O'Keefe's view, the "sweet spot" for jogging for health benefits is a slow to moderate pace, about two or three times per week, for a total of one to 2.5 hours.

"If you want to run a marathon," he said, "run one and cross it off your bucket list." But as a general rule, O'Keefe advises runners to avoid strenuous exercise for more than an hour at a time.