After the third workshop, Levy and his NHLBI colleagues concluded that the evidence still didn’t imply cause and effect. They believed that high cholesterol caused heart disease and that low cholesterol was only a sign of people who might be cancer-prone, perhaps because of a genetic predisposition. This seemed like an arbitrary distinction, and it was certainly based on assumptions more than facts. The NHLBI administrators acknowledged that further research would be necessary to clarify “the perplexing inconsistencies.” Still, the evidence did “not preclude, countermand, or contradict the current public health message which recommends that those with elevated cholesterol levels seek to lower them through diets.”

In the early 1970s, the National Heart, Lung, and Blood Institute had bet its heart-disease prevention budget on two enormous trials that held out hope of resolving the controversy.

The first was the Multiple Risk Factor Intervention Trial, known as MRFIT and led by Jeremiah Stamler. The goal of MRFIT was to “throw the kitchen sink” at heart disease: to convince the subjects to quit smoking, lower their cholesterol, and lower their blood pressure—the multiple-risk-factor interventions. The MRFIT investigators tested the cholesterol of 362,000 middle-aged American men and found twelve thousand (the top 3 percent) whose cholesterol was so high, more than 290 mg/ml, that they could be considered at imminent risk of having a heart attack. The MRFIT investigators believed that these men were so likely to succumb to heart disease that preventive measures would be even more likely to demonstrate a benefit. (If men with lower cholesterol were included, or if women were included, the study would require a considerably greater number of subjects or a longer follow-up to demonstrate any significant benefit.) These twelve thousand men were randomly divided between a control group—told to live, eat, and address their health problems however they desired—and a treatment group—advised to quit smoking, take medication to lower their blood pressure if necessary, and eat a low-fat, low-cholesterol diet, which meant drinking skim milk, using margarine instead of butter, eating only one or two eggs a week, and avoiding red meat, cakes, puddings, and pastries. All twelve thousand were then followed for seven years, at a cost of $115 million.

The results were announced in October 1982, and a Wall Street Journal headline captured the situation succinctly: “Heart Attacks: A Test Collapses.” There had been slightly more deaths among those men who had been counseled to quit smoking, eat a cholesterol-lowering diet, and treat their high blood pressure than among those who had been left to their own devices.*17