Newswise — Moderate exercise in conjunction with common dietary supplements significantly reduce the risk of atherosclerosis because, combined, they boost the body's production of nitric oxide, which protects against a variety of cardio-vascular disorders, a new UCLA study led by 1998 Nobel Laureate in medicine Louis J. Ignarro shows.

The study, "Long Term Beneficial Effects of Physical Training and Metabolic Treatment on Atherosclerosis in Hypercholesterolemic Mice," will be published the week of May 24 in the online edition of the Proceedings of the National Academy of Sciences (http://www.pnas.org). It found that moderate exercise reduced the development of atherosclerosis, or hardening of the arteries, in mice that are genetically prone to heart disease, because exercise alone has been shown to increase nitric oxide in the body. Adding the amino acid L-arginine and the anti-oxidants Vitamins C and E to the mix, however, significantly magnified the effect, said Ignarro, professor of molecular and medical pharmacology in the David Geffen School of Medicine at UCLA.

And what's good for mice is good for humans, said Ignarro, who shared the Nobel Prize for his discoveries in the role that nitric oxide (NO) plays in the cardiovascular system.

"It wasn't just exercise, it was exercise combined with two common dietary supplements," he said. "This is the first study that shows that if you exercise in addition to taking dietary supplements you have a markedly enhanced production of nitric oxide—in science, we like to call it a synergistic effect."

The researchers studied six groups of eight-week-old LDL receptor-deficient male mice with high cholesterol over 18 weeks. The mice were randomly divided into three dietary groups: one fed a high cholesterol diet alone, another fed a high cholesterol diet along with the antioxidant vitamins C and E, and a third fed a high cholesterol diet and given both the antioxidants and L-arginine. Some of the mice were also put on a swimming regimen while others did not exercise.

Researchers found that the mice from all three dietary groups lost weight and had lower cholesterol when they exercised. They also found that atherosclerotic legions were significantly reduced in the mice whose diets included the antioxidants and amino acid.

Here's how exercise, L-arginine and vitamins C and E work together. Exercise increases the amount endothelial NO synthase, an enzyme that converts L-arginine to nitric oxide, which in turn lowers abnormally elevated blood pressure, prevents unwanted blood clotting and early inflammation associated with coronary artery disease, and protects against stroke and myocardial infarction. The antioxidant vitamins C and E work together to remove destructive oxidants from the blood stream, thereby stabilizing the nitric oxide, which can thus rise to higher levels in the blood stream and produce a more beneficial effect.

Sedentary mice fed with the supplements showed a 40 percent reduction in atherosclerosis lesions compared with the mice that were on a regular, high cholesterol diet but neither given the supplements nor put on an exercise regimen. The mice that exercised, but were not fed the supplements, showed a 35 percent reduction in the legions.

"This is interesting, because it shows that the supplements work well even in the absence of exercise," Ignarro said.

Ignarro recommends making simple lifestyle changes that include moderate exercise, eating a low-fat diet, and taking dietary supplements that are commercially available anywhere, which together can make a difference in one's vascular health. "I would say just do it," he said. "It works in mice, it'll work in humans."

Grants from the National Institutes of Health, the Mayo Foundation, and National Research Funds from the University of Naples supported the research.

Other researchers included Sharon Williams-Ignarro of the division of anesthesiology at the UCLA medical school; Claudio Napoli, Filomena de Nigris, Loredana Rossi, Carmen Guarino, Gelsomina Mansueto, Francesco Di Tuoro, Orlando Pignalosa, Gaetano De Rosa and Vicenzo Sica of the University of Naples in Italy; and Lilach O. Lerman of the Mayo Clinic Foundation in Rochester, N.Y.

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CITATIONS

Proceedings of the National Academy of Sciences (May-2004)