unpublished for sixteen years, by which time the controversy had been publicly settled. The principal investigator on the trial was Ivan Frantz, Jr., who worked in Keys’s department at the University of Minnesota. Frantz retired in 1988 and published the results a year later in a journal cal ed Arteriosclerosis, which is unlikely to be read by anyone outside the field of cardiology.*10
The Minnesota trial began in November 1968 and included more than nine thousand men and women in six state mental hospitals and one nursing home. Half of the patients were served a typical American diet, and half a cholesterol-lowering diet that included egg substitutes, soft margarine, low-fat beef, and extra vegetables; it was low in saturated fat and dietary cholesterol and high in polyunsaturated fat. Because the patients were not confined to the various mental hospitals for the entire four and a half years of the study, the average subject ate the diet for only a little more than a year. Average cholesterol levels dropped by 15 percent. Men on the diet had a slightly lower rate of heart attacks, but the women had more. Overal , the cholesterol-lowering diet was associated with an increased rate of heart disease. Of the patients eating the diet, 269 died during the trial, compared with only 206 of those eating the normal hospital fare. When I asked Frantz in late 2003 why the study went unpublished for sixteen years, he said, “We were just disappointed in the way it came out.” Proponents of Keys’s hypothesis who considered the Helsinki Mental Hospital Study reason enough to propose a cholesterol-lowering diet for the entire nation, never cited the Minnesota Coronary Survey as a reason to do otherwise.
As I implied earlier, we can only know if a recommended intervention is a success in preventive medicine if it causes more good than harm, and that can be established only with randomized, control ed clinical trials. Moreover, it’s not sufficient to establish that the proposed intervention reduces the rate of only one disease—say, heart disease. We also have to establish that it doesn’t increase the incidence of other diseases, and that those prescribed the intervention stay healthier and live longer than those who go without it. And because the diseases in question can take years to develop, enormous numbers of people have to be included in the trials and then fol owed for years, or perhaps decades, before reliable conclusions can be drawn.
This point cannot be unduly emphasized. An unfortunate lesson came in the summer of 2002, when physicians learned that the hormone-replacement therapy they had been prescribing to some six mil ion postmenopausal women—either estrogen or a combination of estrogen and progestin—seemed to be doing more harm than good. The paral els to the dietary-fat controversy are worth pondering. Since 1942, when the FDA first approved hormone replacement therapy (HRT) for the treatment of hot flashes and night sweats, reams of observational studies comparing women who took hormone replacements with women who did not (just as dietary-fat studies compared populations that ate high-fat diets with populations that did not) reported that the therapy dramatical y reduced the incidence of heart attacks. It was only in the 1990s that the National Institutes of Health launched a Women’s Health Initiative that included the first large-scale, double-blind, placebo-control ed trial of hormone-replacement therapy. Sixteen thousand healthy women were randomly assigned to take either hormone replacement or a placebo, and then fol owed for at least five years. Heart disease, breast cancer, stroke, and dementia were al more common in the women prescribed hormone replacement than in those on placebos.*11
The episode was an unfortunate lesson in what the epidemiologist David Sackett memorably cal ed the “disastrous inadequacy of lesser evidence.” In an editorial published in August 2002, Sackett argued that the
The Minnesota trial began in November 1968 and included more than nine thousand men and women in six state mental hospitals and one nursing home. Half of the patients were served a typical American diet, and half a cholesterol-lowering diet that included egg substitutes, soft margarine, low-fat beef, and extra vegetables; it was low in saturated fat and dietary cholesterol and high in polyunsaturated fat. Because the patients were not confined to the various mental hospitals for the entire four and a half years of the study, the average subject ate the diet for only a little more than a year. Average cholesterol levels dropped by 15 percent. Men on the diet had a slightly lower rate of heart attacks, but the women had more. Overal , the cholesterol-lowering diet was associated with an increased rate of heart disease. Of the patients eating the diet, 269 died during the trial, compared with only 206 of those eating the normal hospital fare. When I asked Frantz in late 2003 why the study went unpublished for sixteen years, he said, “We were just disappointed in the way it came out.” Proponents of Keys’s hypothesis who considered the Helsinki Mental Hospital Study reason enough to propose a cholesterol-lowering diet for the entire nation, never cited the Minnesota Coronary Survey as a reason to do otherwise.
As I implied earlier, we can only know if a recommended intervention is a success in preventive medicine if it causes more good than harm, and that can be established only with randomized, control ed clinical trials. Moreover, it’s not sufficient to establish that the proposed intervention reduces the rate of only one disease—say, heart disease. We also have to establish that it doesn’t increase the incidence of other diseases, and that those prescribed the intervention stay healthier and live longer than those who go without it. And because the diseases in question can take years to develop, enormous numbers of people have to be included in the trials and then fol owed for years, or perhaps decades, before reliable conclusions can be drawn.
This point cannot be unduly emphasized. An unfortunate lesson came in the summer of 2002, when physicians learned that the hormone-replacement therapy they had been prescribing to some six mil ion postmenopausal women—either estrogen or a combination of estrogen and progestin—seemed to be doing more harm than good. The paral els to the dietary-fat controversy are worth pondering. Since 1942, when the FDA first approved hormone replacement therapy (HRT) for the treatment of hot flashes and night sweats, reams of observational studies comparing women who took hormone replacements with women who did not (just as dietary-fat studies compared populations that ate high-fat diets with populations that did not) reported that the therapy dramatical y reduced the incidence of heart attacks. It was only in the 1990s that the National Institutes of Health launched a Women’s Health Initiative that included the first large-scale, double-blind, placebo-control ed trial of hormone-replacement therapy. Sixteen thousand healthy women were randomly assigned to take either hormone replacement or a placebo, and then fol owed for at least five years. Heart disease, breast cancer, stroke, and dementia were al more common in the women prescribed hormone replacement than in those on placebos.*11
The episode was an unfortunate lesson in what the epidemiologist David Sackett memorably cal ed the “disastrous inadequacy of lesser evidence.” In an editorial published in August 2002, Sackett argued that the
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