Recent results of studies completed by the Center for Human Nutrition in conjunction with other departments at the University of Texas Health Science Center at Dallas offer new hope for patients with dangerously high levels of blood cholesterol--and the promise of dietary control of cholesterol levels in the millions of Americans with moderately high cholesterol.
Human trials with the experimental drug, mevinolin, were conducted by Dr. Scott Grundy; Dr. David Bilheimer, head of the Lipid Metabolism Unit and associate dean for clinical affairs at Parkland Memorial Hospital; Dr. Joseph Goldstein, chairman of the Department of Molecular Genetics; and Dr. Michael Brown, director of the Center for Genetic Disease.
The researchers found that in the six patients studied, mevinolin lowered their levels of cholesterol an average 27 percent. The patients were all victims of hypercholesterolemia (FH), a genetic disorder which causes premature atherosclerosis, which leads to heart attack and stroke. According to Dr. Goldstein, their patients may be studied as models of how the general population develops atherosclerosis. "The theory is that what happens to them in their 30s and 40s may happen to other people in their 60s and 70s."
FH, affecting about one in 500 Americans, causes a retention of abnormally large amounts of cholesterol in the blood. When blood cholesterol becomes excessive, cells in artery walls are force-fed the fatty substance. Bloated cells, described as "foam cells," gradually replace normal tissue. Scar tissue eventually forms, hardening and narrowing the vessels with connective tissue and calcium. Reduced blood flow to the heart and brain produces devastating results.
The defect in FH, first identified by Goldstein and Brown, is a lack of cell receptors for LDL, which carries cholesterol in the blood. Without receptors, LDL cannot enter cells to release cholesterol. Instead, cholesterol-laden LDL molecules accumulate in the bloodstream and form deposits on artery walls.
Mevinolin blocks the cell's capability to produce cholesterol and stimulates the production of more LDL receptors. More receptors then take cholesterol from the blood into tissue, and the patient's cholesterol count falls to a safer level. Dr. Grundy calls mevinolin "a significant step forward," comparing the drug treatment for high cholesterol to insulin treatment for diabetes. But more importantly, according to Dr. Grundy, the recent results -- and results from research accumulated over the past five years -- more clearly define the cause of high blood cholesterol, leading researchers closer to an effective treatment.
Studies at the Center for Human Nutrition have shown that many people with moderately high cholesterol, like FH victims, have poor removal of cholesterol from the bloodstream apparently as a result of a low number of LDL receptors. But unlike FH patients, whose problems are due to genetics, most individuals with moderately high cholesterol are victims only of a typical American diet."Most people who have heart attacks fall into the category of mildly high blood cholesterol," says Grundy. "We believe the problem, and the solution, is diet."
The Center for Human Nutrition currently advises this large group of people, which comprises 20 to 30 percent of the adult population, to change their diets. A lower intake of total fat and saturated fat should increase LDL receptors and help to lower blood cholesterol. More research is planned to accurately determine the effect of modified diets on patients with moderately high cholesterol. For those patients who so not respond to such treatment, drugs such as mevinolin may be effective. By using both treatments, Grundy believes, "we have the potential to eliminate the problem of high blood cholesterol."
