EXERCISE & HEART DISEASE: Understanding Exercise/Cholesterol Paradox Underscores Importance of Workout Consistency

If you're going to do it, stick to it...

That message is among those gleaned from research at the Emory University School of Medicine that is beginning to show, at the molecular level, the relation of exercise to coronary artery disease.

Theoretically, exercise should trigger coronary heart disease, says lead researcher Sampath Parthasarathy, Ph.D. Exercise puts oxidative stress on the body, spurring the production of dangerous free radicals that oxidize low-density lipoprotein (LDL or the "bad" cholesterol) and contribute to vessel-clogging atherosclerosis. Yet research, and even anecdotal evidence, suggests regular exercise lowers the risk for heart disease.

"We hypothesized that either the overall benefits of exercise far outweigh the harmful effects of this oxidative stress or the oxidative stress itself is a part of the beneficial package," Dr. Parthasarathy says.

He and his Emory team began to explain this paradox in a paper published this summer in the American Heart Association journal Arteriosclerosis, Thrombosis and

Vascular Biology. Blood tests of Emory students just beginning exercise classes showed higher oxidizability of LDL cholesterol than tests of a control group of sedentary students. In addition, blood tests of new, short-term exercisers did not show the presence of an antioxidant defense that researchers discovered in a group of regular long-term exercisers who were members of Atlanta running clubs.

The researchers theorize that with regular exercise, LDL oxidation begins to occur less in blood vessel walls and more in the bloodstream where oxidized LDL cholesterol can be excreted from the body through the liver rather than imbedded in vessel walls to incite plaque formation.

They believe regular exercise increases blood levels of the body's own antioxidants, thus offering protection against free radicals in much the same way immune system antibodies defend against microbes.

"As a person begins to exercise, oxidative stress might increase oxidation of LDL in the bloodstream and clear oxidized LDL rapidly by the liver," Dr. Parthasarathy says. "This could be seen as a beneficial effect and might even explain the mechanism by which exercise could lower cholesterol levels. But the important goal is to protect against oxidation in the artery. Our studies suggest this could be achieved by long-term, sustained exercise during which oxidative stress appears to induce antioxidant defense mechanisms in the artery," says Dr. Parthasarathy, who was a leading member of the California research team that convinced the world in the early 90s of the antioxidant theory of atherosclerosis. He is a professor of Gynecology and Obstetrics, and he built and directs that department's active research program. Dr. Parthasarathy also is a professor of Cardiology.

"A number of intriguing questions remain to be answered," he says. "First, would beginning exercisers lose the long-term benefits if they also consume antioxidants?

More importantly, the question remains, how long, how intense and how often should one exercise to convert oxidative stress into an antioxidant defense?"

The Southeast Affiliate of the American Heart Association has sponsored studies related to some of these questions, and Dr. Parthasarathy and his associates are intensively looking for further answers. Drs. Robin Shern Brewer, Nalini Santanam, Jill Welkeley and Carla Wetstein were co-authors of this paper.