Good Calories, Bad Calories

later, NCI researchers themselves published the results of a study similar to the Nurses Health Study but smaller, also suggesting that eating more fat and more saturated fat correlated with less breast cancer. The NCI study went virtually unnoticed, as Science later noted, “perhaps because no one wanted to hear the message that a promising avenue of research was turning into a blind alley, and perhaps because it swam against the ‘medically politically correct’ idea that fat is bad.”

In 1992, Willett published the results from eight years of observation of the Nurses cohort. Fifteen hundred nurses had developed breast cancer, and, once again, those who ate less fat seemed to have more breast cancer. In 1999, the Harvard researchers published fourteen years of observations. By then almost three thousand nurses had contracted breast cancer, and the data still suggested that eating fatty foods (even those with copious saturated fat) might protect against cancer. For every 5 percent of saturated-fat calories that replaced carbohydrates in the diet, the risk of breast cancer decreased by 9 percent. This certainly argued against the hypothesis that excessive fat consumption caused breast cancer.

Despite this accumulation of contradictory evidence, Peter Greenwald and the administrators at NCI refused to let their hypothesis die. This was Rose’s philosophy at work. After Willett’s publication of the first Nurses Health Study results, Greenwald and his NCI colleagues had responded with an article in JAMA entitled “The Dietary Fat–Breast Cancer Hypothesis Is Alive.” The NCI administrators argued that any study that generated evidence refuting the hypothesis could be flawed. The existence of any positive evidence, they argued, even if it came from admittedly rudimentary studies—in other words, studies that almost assuredly were flawed—was sufficient to keep such a critical hypothesis alive.

The only evidence that Greenwald and his collaborators considered “indisputable” was that laboratory rats fed “a high-fat, high-calorie diet have a substantially higher incidence of mammary tumors than animals fed a low-fat, calorie-restricted diet.” In this they were right, but they did not rule out the possibility that it was the calories or whatever caused weight gain (what they implied by the adjective “high-calorie”) and not the dietary fat itself that was to blame, which was very likely the case. Even in 1982, when the authors of Diet, Nutrition, and Cancer had reviewed the animal evidence for fat-induced tumor growth, it had been less than indisputable. Adding fat to the diets of lab rats certainly induced tumors or enhanced their growth, but the most effective fats by far at this carcinogenesis process were polyunsaturated fats—saturated fats had little effect unless “supplemented with” polyunsaturated fats. This raised questions about the applicability of these observations to Western diets, which were traditionally low in polyunsaturated fats, at least until the 1960s, when the AHA started advocating polyunsaturated fats as a tool to lower cholesterol. Adding fat to rat chow also caused the rodents to gain weight, which was among the foremost reasons why obesity researchers came to believe that dietary fat caused human obesity. But it was hard to determine in these experiments whether it was the fat or the weight gain itself that led to increased tumor growth.

This laboratory evidence that dietary fat caused breast cancer began to evaporate as soon as Diet, Nutrition, and Cancer was published, and researchers could get funding to study it. By 1984, David Kritchevsky, one of the authors of Diet, Nutrition, and Cancer, had published an article in Cancer Research reporting on experiments that had been explicitly designed to separate out the effects of fat and calories on cancer, at least in rats. As Kritchevsky reported, low-fat, high-calorie diets led to more tumors than high-fat, low-calorie diets, and tumor production was shut down entirely in underfed rats, regardless of how fatty their diet was. Kritchevsky later reported that if rats were given only 75 percent of their typical daily calorie requirements, they could eat five times as much fat as usual and still develop fewer tumors. Mike Pariza of the University of Wisconsin had published similar results in 1986 in the Journal of the National Cancer Institute. “If you restrict calories just a little bit,” Pariza later said, “you completely wipe out this so-called fat enhancement of cancer.” This observation has been confirmed repeatedly. Demetrius Albanes of the National Cancer Institute later described the data as “overwhelmingly striking.” And he added: “Those data have very largely been ignored and strongly downplayed.”

By 1997 when the World Cancer Research Fund and American Institute for Cancer Research released a seven- hundred-page report titled Food, Nutrition and the Prevention of Cancer, the assembled experts could find neither “convincing” nor even “probable” reason to believe that fat-rich diets increased the risk of cancer. A decade later still, Arthur Schatzkin, chief of the nutritional epidemiology branch at the National Cancer Institute, described the accumulated results from those trials designed to test the hypothesis as “largely null.”

Nonetheless, the pervasive belief that eating fat causes breast cancer has persisted, partly because it once seemed undeniable. Purveyors of health advice just can’t seem to let go of the notion. When the American Cancer Society released its nutrition guidelines for cancer prevention in 2002, the document still recommended that we “limit consumption of red meats, especially those high in fat,” because of the same epidemiologic associations that had generated the fat-cancer hypothesis thirty years earlier. By 2006, with the next release of cancer-prevention guidelines by the American Cancer Society, the ACS was acknowledging that “there is little evidence that the total amount of fat consumed increases cancer risk.” But we were still advised to eat less fat and particularly meats (“major contributors of total fat, saturated fat and cholesterol in the American diet”), because “diets high in fat tend to be high in calories and may contribute to obesity, which in turn is associated with increased risks of cancers.” (Saturated fats, in particular, the ACS added, “may have an effect on increasing cancer risk,” a statement that seemed to be based solely on the belief that if saturated fat causes heart disease it probably causes cancer as well.)

Belief in the hypothesis persists also because of the time lag involved in research of this nature. In 1991, the National Institutes of Health launched the $700 million Women’s Health Initiative to test the hypothesis (and also the hypothesis that hormone-replacement therapy protects against heart disease and cancer). The WHI investigators enrolled forty-nine thousand women, aged fifty to seventy-nine. They randomly assigned twenty-nine thousand to eat their usual diets, and twenty thousand were prescribed a low-fat diet. The goal was to induce these women to consume only 20 percent of their calories from fat; to do this, they were told to eat more vegetables and fresh fruits, as well as whole grains, in case fiber was beneficial as well. If the diet succeeded in preventing breast cancer, or any chronic disease, the WHI investigators wouldn’t know if it was because these women ate less fat or because they ate more fruits, vegetables, and grains. It’s conceivable that a diet of fruits, vegetables, grains, and more fat, or of vegetables and fruits but less grains, could be even more protective. The women on the diet also consumed fewer calories—averaging 120 calories a day less than the controls over the eight years of the study.^*23 So, similarly, if this diet appeared to prevent cancer, the WHI investigators wouldn’t know whether it did so because it contained less fat (or more fruits and vegetables) or fewer calories. To induce those on the diet to stick to it for the better part of a decade, the WHI investigators provided them with an intensive nutritional and behavioral-education program. The women assigned to eat their usual diets received no such attention, which means they would be considerably less likely to change their lives in other ways that might also have an effect on breast cancer—to exercise or maintain their weight, stay away from sweets, refined flour, fast-food joints, and smoky bars. This disparity in counseling is known as an intervention effect, and it is precisely to avoid such an effect that drug trials must be done with placebos and double-blind.

All of these effects would be expected to bias the trial in favor of observing a beneficial effect where none exists, but the WHI trial still came up negative. In the winter of 2006, the WHI investigators reported that those women who were eating what we today consider the essence of a healthy diet—little fat, lots of fiber, considerable fruits, vegetables, and whole grains, fewer calories—had no less breast cancer than those who ate their typical American fare. (The women on the diet had no less heart disease, colon cancer, or stroke, either.) The results confirmed those of every study that had been done on diet and breast cancer since 1982. This, however, was still not generally perceived as a definitive refutation of the hypothesis. Rose’s logic of preventive medicine held fast (it