The effect of dietary fat, antioxidants, and pro-oxidants on blood lipids, lipoproteins, and atherosclerosis.

A number of primary and secondary prevention trials, including angiographic studies, have indicated that a decrease in dietary saturated fat and cholesterol produces a decrease in the blood levels of cholesterol and low-density lipoprotein (LDL) cholesterol, leading to a decrease in coronary artery disease (CAD). Increasing evidence indicates that the oxidation of LDL in human beings is atherogenic. Of the three major antioxidants, vitamin E, beta carotene, and vitamin C, the evidence is strongest that vitamin E (at a minimum dose of 100 IU/day) has a strong and independent inverse association with CAD. Selenium and flavonoids also have antioxidant properties, but their association with CAD in human beings is equivocal. Two prooxidants, homocysteine and iron, have been found to be associated with CAD. Blood homocysteine levels can be lowered significantly by an increase in dietary folic acid. Clinical trials are needed to assess expeditiously the effect of antioxidants, particularly vitamin E, and of folic acid on CAD and atherosclerosis. The substitution of monounsaturated fat for saturated fat lowers LDL and makes it less susceptible to oxidation without decreasing high-density lipoprotein (HDL) cholesterol. Studies in transgenic mice indicate that apolipoprotein A-I, the major protein of HDL, may inhibit the oxidation of LDL. Dietary trans fatty acids at the level consumed by many Americans can increase LDL cholesterol and may decrease HDL cholesterol. Individuals who have CAD or have family members who have premature CAD have delayed clearance of dietary fat, as judged by studies of postprandial triglyceride metabolism. The importance of decreasing dietary saturated fat and cholesterol is well established, but a number of other factors appear to influence the risk of CAD significantly and provide important areas for future investigation to improve prevention and treatment through better nutrition.