Low vitamin C levels linked to inflammation in people with severe leg artery disease

April 09, 2001

DALLAS, April 10 - Low levels of vitamin C in the blood are linked to a more severe form of peripheral artery disease, an often painful condition in which the leg blood vessels become blocked, according to a report in today's Circulation: Journal of the American Heart Association.

Peripheral artery disease (PAD) is a form of atherosclerosis in which fatty deposits build up along artery walls impairing blood circulation primarily in the arteries leading to the legs and feet. A common symptom is intermittent claudication - leg cramping or fatigue that subsides when standing still. It is associated with an increased risk of death from heart attack and stroke.

New research has found that the disease may spur the inflammatory process and the release of oxygen-free radicals, which deplete the body's supply of vitamin C. Researchers compared blood levels of vitamin C in three groups: 85 individuals with PAD, l06 individuals with hypertension, but without PAD, and 113 healthy subjects. Researchers asked about dietary habits to assess their level of vitamin C intake, as well as intensity and duration of exercise. Blood samples were taken and participants took graded treadmill tests.

"We found that concentrations of vitamin C were almost twice as low in those with PAD compared to the two groups without it," says Michel Langlois, M.D., Ph.D., a specialist in clinical pathology at the University Hospital of Ghent, Belgium. "Lower vitamin C levels were associated with poor performance on treadmill tests and those with PAD also had elevated plasma levels of C-reactive protein, which is a marker for the ongoing inflammation in the blood vessels associated with severe atherosclerosis."

Elevated C-reactive protein levels are probably not the direct cause of arterial damage but a by-product of an inflammatory response in atherosclerosis, he says.

Atherosclerosis can lead to the accumulation of fat and white blood cells and other inflammatory cells on the inner walls of the arteries. These cells can release oxygen-free radicals, unstable molecules that further damage the blood vessels. The increase in free radicals may result in a depletion of the body's supply of antioxidants, like vitamin C, that rid the body of the oxidants, says Langlois.

Vitamin C, a water-soluble antioxidant found in many fruits and vegetables, which is also taken as a supplement by millions of Americans, is the "first-line defense" in controlling oxidative stress, says Langlois. It scavenges destructive free radicals, sparing other antioxidants from consumption but is itself destroyed.

"From our data, we cannot conclude that peripheral artery disease or atherosclerosis could be prevented by taking more vitamin C, since this wasn't studied," he says. "Other studies and clinical trials, however, provide controversial data that antioxidant supplements - including vitamin C, vitamin E and beta-carotene may prevent atherosclerotic disease in healthy subjects. "We're currently setting up another clinical study in which vitamin C supplements will be given to patients with peripheral vascular disease in order to try to determine just what effect these supplements may have," he says.

While vitamin C's antioxidant properties have been widely reported, the vitamin may also have pro-oxidant effects in some instances, meaning that it could actually promote the production of free radicals in certain biological conditions and diseases. "This has led to some paradoxical observations," Langlois adds. "Many clinical trials, for example, have failed to demonstrate a beneficial effect of vitamin C supplements on cardiovascular disease and death, and part of the reason may be the pro-oxidant effect of vitamin C."

People who took regular supplements of vitamin C or other antioxidants were excluded from their study because the supplements "could interfere with the biological mechanisms" which cause vitamin C depletion in severe atherosclerosis, says Langlois. Despite hypertension being among the key risk factors for PAD, hypertensive patients without PAD had blood concentrations of vitamin C that were almost as high as those of healthy subjects.

"We found no relationship between blood pressure and blood vitamin C levels," he says, "so we can't provide any evidence that high concentrations of vitamin C may somehow offset the ill-effects of hypertension."

The American Heart Association recommends that healthy individuals obtain their vitamin C from foods, such as citrus fruits, broccoli, red bell peppers and many other fruits and vegetables. The association states that vitamin supplements are not a substitute for a balanced and nutritious diet.

American Heart Association

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