A growing body of evidence suggests that diets and drugs that lower blood cholesterol levels may indirectly raise the risk of certain types of violent death by producing personality changes--inducing anger, irritability, aggressiveness and increased risk-taking.
The studies have set off competing waves of concern and skepticism in the medical community. Although some are calling for a serious re-examination of across-the-board cholesterol-lowering tactics, many others say the results have been overblown and that much more evidence is needed to justify the reversal of such an established medical policy.
Several large studies in the United States and Europe have shown that lowering cholesterol reduces the risk of fatal heart attacks, as it was intended to do.
But, through mechanisms that scientists do not understand, the decrease in deaths from heart attacks has been offset by an increased risk of death from suicides, violence and accidents.
Some researchers now believe that lowering cholesterol levels can, in at least some individuals, affect the levels of brain neurotransmitters, the chemicals by which individual brain cells communicate with each other.
Experiments in monkeys show that lowering cholesterol reduces levels of the neurotransmitter serotonin. Low levels of serotonin in humans have previously been linked to an increased risk of suicide and aggressive behavior.
"These studies throw into a cocked hat the whole proposition that every American should lower his cholesterol levels," said Dr. Hyman Engleberg, an internist at Cedars-Sinai Medical Center. "People who have had a heart attack, stroke or a very bad early history have far more to gain than to lose by lowering their cholesterol, but for a healthy population, they have as much to lose as to gain."
"Right now is a good time for people to pause and look at the recommendations (for lowering cholesterol) more critically," said Dr. Matthew Muldoon, a clinical pharmacologist at the University of Pittsburgh who conducted one of the major studies. "But not enough is known yet to say that the recommendations ought to be changed or that there are definite dangers."
Many researchers think the concern is overblown. "I don't dismiss it, but I don't think the data for harm is particularly impressive," said Dr. Basil M. Rifkind, chief of the lipid metabolism and atherogenesis branch at the National Heart, Lung and Blood Institute in Bethesda, Md. "To draw any conclusive results from (the data available) is hazardous and, perhaps, stretching the data beyond the point where it should be stretched."
The questions about cholesterol are of more than academic interest. Coronary artery disease is the nation's No. 1 killer. Each year, 1.5 million Americans suffer heart attacks and 550,000 die. The primary causes of heart disease include smoking, high blood pressure, obesity, family gene inheritance--and high cholesterol.
Cholesterol is a waxy, odorless substance that is synthesized by the body, but that is also present in a number of foods, especially meat and dairy products. It plays a variety of positive roles in the body, serving as a precursor for sex hormones, as a building block for the membranes that surround all cells in the body and as an aid to digestion.
The problems begin when the body has too much cholesterol, either because there is an overabundance in the diet or because the individual is genetically inefficient at removing it from the blood stream. In either case, the excess cholesterol is slowly deposited on the walls of blood vessels, building up over decades until an artery suddenly becomes too constricted to sustain blood flow.
If the artery is in the heart, the constriction usually leads to a heart attack, killing that part of the heart muscle fed by the artery. If the artery is in the brain, the individual has a stroke and brain tissue dies. If the artery is in the leg, the blockage may lead to its amputation.
Public health authorities have long urged Americans to lower the amount of fats in their diet to reduce cholesterol, but the campaign took on new urgency in 1985 with the launching of the National Cholesterol Education Program, sponsored by 26 organizations and funded by the National Heart, Lung and Blood Institute. Its goal is for Americans to know their cholesterol level and take action if it reaches dangerous levels: 200 milligrams of cholesterol per deciliter of blood if two other risk factors are also present or 240 mg/dl with no other risk factors.
More than 25% of the American population have levels higher than 240 mg/dl, as do fully half of those ages 45 to 65.
No one is questioning the value of reducing cholesterol in those individuals at high risk of heart disease. "The evidence is overwhelming that mortality . . . is diminished by lowering serum cholesterol after a heart attack," said Dr. Thomas Chalmers, a clinical epidemiologist at the Harvard School of Public Health.