Good Calories, Bad Calories

still does). In a press release on the findings, NHLBI Director Elizabeth Nabel stated, “The results of this study do not change established recommendations on disease prevention.” In editorials that accompanied the WHI articles in JAMA, in virtually every press report, and even in the World Health Organization’s official statement on the trial, it was said that this particular study may have failed to show a beneficial effect of a low-fat, high-fiber diet on breast cancer (and heart disease, stroke, colon cancer, and weight), but that was not a reason to disbelieve the hypotheses. (The WHO press release was entitled “The World Health Organization Notes the Women’s Health Initiative Diet Modification Trial, but Reaffirms That the Fat Content of Your Diet Does Matter.”) Rather than enumerate the ways the WHI trial was biased to find a positive relationship, which was one facet of the controversy in the early 1990s over whether the trial should be funded to begin with, the WHI investigators and those like-minded now enumerated all the reasons why the study might have failed to find an effect.

At the core of all such ongoing scientific controversies is the inability to measure accurately the phenomenon at issue—the effect of dietary fat, for instance, on heart disease or cancer—either because it is negligible or nonexistent, or because the epidemiological tools available lack sufficient resolution for the task. Even clinical trials, unless done with meticulous attention to detail, double-blind, and placebo-controlled, cannot do the job. And if fat consumption has no effect whatsoever on heart disease or breast cancer, the available clinical and epidemiological tools will always be incapable of demonstrating such a fact, because it is impossible in science to prove the nonexistence of a phenomenon. So the effect of saturated fat on heart disease—or the benefit of replacing saturated fat in the diet with carbohydrates or unsaturated fats—will remain beyond the realm of science to demonstrate unambiguously. Investigators and public-health authorities will continue to base their conclusions on their personal assessment of the totality of the data or the consensus of opinion among their colleagues.

One challenge in this kind of controversy is to determine whether those skeptical of the established wisdom are incapable of accepting reality, closed-minded, or self-serving, or whether their skepticism is well founded. In other words, is the evidence invoked to support the established wisdom the product of sound scientific thinking and reasonably unambiguous, in which case the skeptics are wrong, or is it what Francis Bacon would have called “wishful science,” based on fancies, opinions, and the exclusion of contrary evidence, in which case the skeptics are right to be so skeptical? Bacon offered one viable suggestion for differentiating. Good science, he observed, is rooted in reality, and so it grows and develops, and the evidence grows increasingly more compelling, whereas wishful sciences remain “stuck fast in their tracks,” or “rather the reverse, flourishing most under their first authors before going downhill ever since.”

Wishful science eventually devolves to the point where it is kept alive simply by the natural reluctance of its advocates to recognize or acknowledge error, rather than compelling evidence that it is right. “These are cases where there is no dishonesty involved,” explained the Nobel Prize–winning chemist Irving Langmuir in a celebrated 1953 lecture, “but where people are tricked into false results by a lack of understanding about what human beings can do to themselves in the way of being led astray by subjective effects, wishful thinking or threshold interactions.” Whereas good science would blossom over time, Langmuir noted, this “pathological science” would not. The most concise statement of this philosophy may be an unwritten rule of experimental physics credited originally to Wolfgang Panofsky, a former Manhattan Project physicist and presidential science adviser. “If you throw money at an effect and it doesn’t get larger,” Panofsky said, “that means it is not real.”

That has certainly been the case with the dietary-fat/breast-cancer hypothesis. The relationship between dietary fat, cholesterol, and heart disease is more complicated, because the hypothesis constitutes three independent propositions: first, that lowering cholesterol prevents heart disease; second, that eating less fat or less saturated fat not only lowers cholesterol and prevents heart disease but, third, that it prolongs life.

Since 1984, the evidence that cholesterol-lowering drugs, particularly those known as statins, are beneficial—proposition number one—has certainly blossomed, particularly regarding people at high risk of heart attack. These drugs reduce serum-cholesterol levels dramatically, and they seem to prevent heart attacks, although whether they actually do so by lowering cholesterol levels or by other means as well is still an open question. (“Most drugs have multiple actions,” notes the University of Washington biostatistician Richard Kronmal. Saying that statins reduce heart-disease risk by lowering cholesterol, he adds, is like “saying that aspirin reduces heart-disease risk by reducing headaches.”) There is also a legitimate question as to whether they will prolong the life of anyone who is not in imminent danger of having a heart attack, but new trials consistently seem to confirm their benefits. All this may be irrelevant to the question of a healthy diet, however, because there is no compelling reason we should believe that a drug and a diet will have equivalent effects on our health, even if they both happen to lower cholesterol.

The evidence supporting the second and third propositions—that eating less fat, or less saturated fat, makes for a healthier and longer life—has remained stubbornly ambiguous. The message of the 1984 consensus conference and the ensuing expert reports was that the benefits of low-fat diets were effectively indisputable, and so pursuing further research on these questions was unnecessary. This in turn led to the ubiquitous belief in the validity of Keys’s hypothesis and the unwholesome nature of saturated fat, but the reality is that since the early 1980s the evidence has become progressively less compelling.

Keys’s own experience stands as an example. In the early 1950s, Keys had based his dietary-fat hypothesis of heart disease to a great extent on the congruence between the changing-American-diet story and the appearance of a heart-disease epidemic. By the early 1970s, however, he had publicly acknowledged that the heart-disease epidemic may indeed have been a mirage. There was “no basis” to make the claim, he admitted, that trends in heart-disease mortality in the United States reflect changes in the consumption of any item in the diet.

In the late 1950s, Keys supported his fat hypothesis with the disparity in fat consumption, cholesterol levels, and heart-disease mortality he found among Japanese men living in Japan, Hawaii, and Los Angeles. This association was then confirmed, more or less, in his Seven Countries Study, in which the Japanese villagers still had remarkably little fat in their diets, low cholesterol levels, and fewer heart-disease deaths over ten years than any other population with the exceptions of those of the islands of Crete and Corfu and the village of Velika Krsna in what is now Serbia. By the mid-1990s, however, the Japanese contingent of the Seven Countries Study, led by Yoshinori Koga, reported that fat intake in Japan had increased from the 6 percent of calories they had measured in the farming village of Tanushimaru thirty-five years earlier, to 22 percent of calories. “There have been progressive increases in consumption of meats, fish and shellfish and milk,” they reported. Mean cholesterol levels rose in the community from 150 mg/dl to nearly 190 mg/dl, which is only 6 percent lower than the average American values (202 mg/dl as of 2004). Yet this change went along with a “remarkable reduction” in the incidence of strokes and no change in the incidence of heart disease. In fact, the chance that a Japanese man of any particular age would die of heart disease had steadily diminished since 1970. “It is suggested that dietary changes in Tanushimaru in the last thirty years have contributed to the prevention of cardiovascular disease,” Koga and his colleagues concluded.

In the late 1950s, Keys had dismissed the possibility that misdiagnosis might have contributed to the extremely low heart-disease death rates in Japan they had observed initially. In 1984, Keys reversed himself, saying that the Japanese cardiologists who had worked with his Seven Countries Study “might have been misled by the local physicians who signed the death certificates and provided details.”

Three years later, Keys acknowledged to the New York Times that he had re- evaluated his hypothesis. “I’ve come to think that cholesterol is not as important as we used to think it was,” he said, “Let’s reduce cholesterol by reasonable means, but let’s not get too excited about it.”