Good Calories, Bad Calories (10 page)

Not even randomization, though, is sufficient to assure that the only meaningful difference between the experimental group and the control group is the treatment being studied. This is why, in drug trials, placebos are used, to avoid any distortion that might occur when comparing individuals who are taking a pil in the belief that their condition might improve with individuals who are not. Drug trials are also done double-blind, which means neither subjects nor physicians know which pil s are placebos and which are not. Double-blind, placebo-controlled clinical trials are commonly referred to in medicine as the gold standard for research. It’s not that they are better than other methods of establishing truth, but that truth, in most instances, cannot be reliably established without them.

Diet trials are particularly troublesome, because it’s impossible to conduct them with placebos or a double-blind. Diets including copious meat, butter, and cream do not look or taste like diets without them. It is also impossible to make a single change in a diet. Saturated fats cannot be eliminated from the diet without decreasing calories as wel . To ensure that calories remain constant, another food has to replace the saturated fats. Should polyunsaturated fats be added, or carbohydrates? A single carbohydrate or mixed carbohydrates? Green leafy vegetables or starches? Whatever the choice, the experimental diet is changed in at least two significant ways. If saturated-fat calories are reduced and carbohydrate calories are increased to compensate, the investigators have no way to know which of the two was responsible for any effect observed. (To state that “saturated fats raise cholesterol,” as is the common usage, is meaningful only if we say that saturated fat raises cholesterol compared with the effect of some other nutrient in the diet—polyunsaturated fats, for instance.)

Nonetheless, dietary trials of diet and heart disease began appearing in the literature in the mid-1950s. Perhaps a dozen such trials appeared over the next twenty years. The methods used were often primitive. Many had no controls; many neglected to randomize subjects into experimental and control groups.

Only two of these trials actual y studied the effect of a low-fat diet on heart-disease rates—not to be confused with a cholesterol-lowering diet, which replaces saturated with polyunsaturated fats and keeps the total fat content of the diet the same. Only these two trials ever tested the benefits and risks of the kind of low-fat diet that the American Heart Association has recommended we eat since 1961, and that the USDA food pyramid recommends when it says to “use fats and oils sparingly.” One, published in a Hungarian medical journal in 1963, concluded that cutting fat consumption to only 1.5 ounces a day reduced heart-disease rates. The other, a British study, concluded that it did not. In the British trial, the investigators also restricted daily fat consumption to 1.5 ounces, a third of the fat in the typical British diet. Each day, the men assigned to this experimental diet, al of whom had previously had heart attacks, could eat only half an ounce of butter, three ounces of meat, one egg, and two ounces of cottage cheese, and drink two ounces of skim milk. After three years, average cholesterol levels dropped from 260 to 235, but the recurrence of heart disease in the control and experimental groups was effectively identical. “A low-fat diet has no place in the treatment of myocardial infarction,” the authors concluded in 1965 in The Lancet.

In al the other trials, cholesterol levels were lowered by changing the fat content of the diet, rather than the total amount of fat consumed.

Polyunsaturated fats replaced saturated fats, without altering the calorie content. These diet trials had a profound influence on how the diet/heart-disease controversy played out.

The first and most highly publicized was the Anti-Coronary Club Trial, launched in the late 1950s by New York City Health Department Director Norman Jol iffe. The eleven hundred middle-aged members of Jol iffe’s Anti-Coronary Club were prescribed what he cal ed the “prudent diet,” which included at least one ounce of polyunsaturated vegetable oil every day. The participants could eat poultry or fish anytime, but were limited to four meals a week containing beef, lamb, or pork. This made Jol iffe’s prudent diet a model for future health-conscious Americans. Corn-oil margarines, with a high ratio of polyunsaturated to saturated fat, replaced butter and hydrogenated margarines, which were high in saturated fats. In total, the prudent diet was barely 30

percent fat calories, and the proportion of polyunsaturated to saturated fat was four times greater than that of typical American diets. Overweight Anti-Coronary Club members were prescribed a sixteen-hundred-calorie diet that consisted of less than 20 percent fat. Jol iffe then recruited a control group to use as a comparison.

Jol iffe died in 1961, before the results were in. His col eagues, led by George Christakis, began reporting interim results a year later. “Diet Linked to Cut in Heart Attacks,” reported the New York Times in May 1962. “Special Diet Cuts Heart Cases Here,” the Times reported two years later. Christakis was so confident of the prudent-diet benefits, reported Newsweek, that he “urged the government to heed the club results and launch an educational and food-labeling campaign to change U.S. diet habits.”

The actual data, however, were considerably less encouraging. Christakis and his col eagues reported in February 1966 that the diet protected against heart disease. Anti-Coronary Club members who remained on the prudent diet had only one-third the heart disease of the controls. The longer you stayed on the diet, the more you benefited, it was said. But in November 1966, just nine months later, the Anti-Coronary Club investigators published a second article, revealing that twenty-six members of the club had died during the trial, compared with only six of the men whose diet had not been prudent. Eight members of the club died from heart attacks, but none of the controls. This appeared “somewhat unusual,” Christakis and his col eagues acknowledged.

They discussed the improvements in heart-disease risk factors (cholesterol, weight, and blood pressure decreased) and the significant reduction in debilitating il ness “from new coronary heart disease,” but omitted further discussion of mortality.

This mortality problem was the bane of Keys’s dietary-fat hypothesis, bedeviling every trial that tried to assess the effects of a low-fat diet on death as wel as disease. In July 1969, Seymour Dayton, a professor of medicine at the University of California, Los Angeles, reported the results of the largest diet-heart trial to that date. Dayton gave half of nearly 850 veterans residing at a local Veterans Administration hospital a diet in which corn, soybean, safflower, and cottonseed oils replaced the saturated fats in butter, milk, ice cream, and cheeses. The other half, the controls, were served a placebo diet in which the fat quantity and type hadn’t been changed. The first group saw their cholesterol drop 13 percent lower than the controls; only sixty-six died from heart disease during the study, compared with ninety-six of the vets on the placebo diet.*8

Thirty-one of the men eating Dayton’s experimental cholesterol-lowering diet, however, died of cancer, compared with only seventeen of the controls.

The risk of death was effectively equal on the two diets. “Was it not possible,” Dayton asked, “that a diet high in unsaturated fat…might have noxious effects when consumed over a period of many years? Such diets are, after al , rarities among the self-selected diets of human population groups.”

Because the cholesterol-lowering diet failed to increase longevity, he added, it could not provide a “final answer concerning dietary prevention of heart disease.”

If these trials had demonstrated that people actual y lived longer on cholesterol-lowering diets, there would have been little controversy. But almost four decades later, only one trial, the Helsinki Mental Hospital Study, seemed to demonstrate such a benefit—albeit not from a low-fat diet but from a high-polyunsaturated, low-saturated-fat diet.

The Helsinki Study was a strange and imaginative experiment. The Finnish investigators used two mental hospitals for their trial, dubbed Hospital K

(Kel okoski Hospital) and Hospital N (Nikkilä Hospital). Between 1959 and 1965, the inmates at Hospital N were fed a special cholesterol-lowering diet,†

9 and the inmates of K ate their usual fare; from 1965 to 1971, those in Hospital K ate the special diet and the Hospital N inmates ate the usual fare. The effect of this diet was measured on whoever happened to be in the hospitals during those periods; “in mental hospitals turnover is usual y rather slow,” the Finnish investigators noted.

The diet seemed to reduce heart-disease deaths by half. More important to the acceptance of Keys’s hypothesis, the men in the hospitals lived a little longer on the cholesterol-lowering diet. (The women did not.)

Proponents of Keys’s hypothesis wil stil cite the Helsinki Study as among the definitive evidence that manipulating dietary fats prevents heart disease and saves lives. But if the lower death rates in the Helsinki trial were considered compel ing evidence that the diet worked, why weren’t the higher death rates in the Anti-Coronary Club Trial considered evidence that it did not?

The Minnesota Coronary Survey was, by far, the largest diet-heart trial carried out in the United States, yet it played no role in the evolution of the dietary-fat hypothesis. Indeed, the results of the study went 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 blame lay solely with those medical authorities who, for numerous reasons, including “a misguided attempt to do good, advocate ‘preventive’ maneuvers that have never been validated in rigorous randomized trials. Not only do they abuse their positions by advocating unproven ‘preventives,’ they also stifle dissent.”

From 1960 onward, those involved in the diet-heart controversy had intended to conduct precisely the kind of study that three decades later would reverse the common wisdom about the long-term benefits of hormone-replacement therapy. This was the enormous National Diet-Heart Study that Jeremiah Stamler in 1961 had predicted would take five or ten years of hard work to complete. In August 1962, the National Heart Institute awarded research grants to six investigators—including Stamler, Keys, and Ivan Frantz, Jr.—to explore the feasibility of inducing a hundred thousand Americans to change the fat content of their diet.*12 In 1968, the National Institutes of Health assembled a committee led by Pete Ahrens of Rockefel er University to review the evidence for and against the diet-heart hypothesis and recommend how to proceed. The committee published its conclusions in June 1969. Even though the American Heart Association had been recommending low-fat diets for almost a decade already, Ahrens and his col eagues reported, the salient points remained at issue. “The essential reason for conducting a study,” they noted, “is because it is not known whether dietary manipulation has any effect whatsoever on coronary heart disease.” And so they recommended that the government proceed with the trial, even though, Ahrens recal ed, the committee members came to believe that any trial large enough and sufficiently wel control ed to provide a reliable conclusion “would be so expensive and so impractical that it would never get done.”