Two oranges a day may do more than keep colds at bay. They just might prevent what is thought to be the first step in hardening of the arteries, according to new research in the Center for Human Nutrition. Researchers have proven in a laboratory setting that vitamin C, and vitamin E to a lesser degree, can prevent atherosclerosis. While the study's principal investigator, Dr. Ishwarlal Jialal, assistant professor of clinical nutrition and internal medicine, isn't ready to make a wholesale recommendation for vitamin mega dosing, human trials are under way in the Center, and results should be ready in about a year.

In his study, published in the June issue of Atherosclerosis, he examined the effects of vitamins C and E found at normal levels in the human body on the oxidation of low-density lipoprotein (LDL), the "bad" form of blood cholesterol. "We know that a high blood cholesterol is a major risk factor for heart disease," Dr. Jialal said. "What we don't know is how cholesterol builds up in the artery wall and causes atherosclerosis." LDL transports 60 to 70 percent of the cholesterol in the blood, he explained. The higher the level of LDL, the greater the risk of coronary heart disease. Once LDL is inside the artery, it can be oxidized by cells that produce reactive oxygen.

Oxidation can alter or destroy substances found in food and important in the body. It is the same process that causes some oils to turn rancid when exposed to air. Vitamins C and E, because they can be oxidized themselves, act as bodyguards of oxidizable substances, sacrificing themselves to save another life. Chemists call such bodyguards antioxidants. "Oxidative modification of LDL is the most plausible explanation of how cholesterol promotes atherosclerosis," Dr. Jialal said. "What we wanted to do with this research was look at the effect of antioxidant vitamins on the process. Nobody had looked at the effect of vitamin C on LDL oxidation."

Dr. Jialal's research partners were Dr. Scott M. Grundy, director of the Center for Human Nutrition, and Dr. Gloria Lena Vega, associate professor of clinical nutrition.
"The earliest sign of atherosclerosis is the accumulation of cholesterol-filled white blood cells (monocytes or macrophages) in the lining of the artery wall," Dr. Jialal said.
Macrophages cannot take up normal LDL, but oxidized LDL binds itself to special receptors on the cells. These receptors take up oxidized LDL and its cholesterol in an unregulated fashion and become engorged with LDL cholesterol. Oxidized LDL also can function as a cell toxin, poisoning the cells, impairing their function and allowing more monocytes to enter the lining of the artery wall.

"If oxidized LDL is crucial to the development of coronary plaque, the potential role of antioxidants in the prevention of oxidation of LDL assumes great importance," Jialal stated in the report. "Although the effect of vitamin E on LDL oxidation had been noted previously, the effect of vitamin C at normal levels on the oxidation of LDL has received little attention. The present study was undertaken to compare the effects of these two antioxidants, vitamins C and E, specifically on the oxidation of LDL."
In a test tube environment, human monocytes were isolated from the blood of subjects who had normal blood lipids, or fats, When LDL was oxidized for five hours, both vitamins C and E "significantly" inhibited the oxidation of LDL. After 24 hours, however, only vitamin C continued to demonstrate this effect, suggesting that vitamin C is more potent than vitamin E in inhibiting LDL oxidation.

For now, Dr. Jialal suggests that people at risk for heart attack--especially cigarette smokers, who have low vitamin C levels--may need to increase their daily intake of vitamin C to 120 milligrams, or twice the U.S. Recommended Daily Allowance. This can be accomplished by eating a variety of citrus fruits and vegetables, such as oranges or broccoli. He cautions that boiling can destroy vitamin C, which is heat-sensitive and water-soluble. Dr. Jialal suggests that vitamin E would be safe at five to 10 times the RDA, or 50 to 100 milligrams. "We're researching these vitamins," Dr. Jialal said, "because we want to find nutritional antioxidants that are not harmful to people--that are not drugs with other side effects."