Good Calories, Bad Calories

in the United States for whom [coronary heart disease] is the outstanding cause of premature death.” Now, however, with “the large number of deaths accumulated over the years,” they realized that coronary heart disease accounted for less than one-third of all deaths, and so this “forced attention to total mortality.”

Now the story changed: High cholesterol did not predict increased mortality, despite its association with a greater rate of heart disease. Saturated fat in the diet ceased to be a factor as well. The U.S. railroad workers, for instance, had a death rate from all causes lower—and so a life expectancy longer—than the Finns, the Italians, the Yugoslavs, the Dutch, and particularly the Japanese, who ate copious carbohydrates, fruits, vegetables, and fish. Only the villagers of Crete and Corfu could still expect to live significantly longer than the U.S. railroad workers. Though this could be explained by other factors, it still implied that telling Americans to eat like the Japanese might not be the best advice. This was why Keys had begun advocating Mediterranean diets, though evidence that the Mediterranean diet was beneficial was derived only from the villagers of Crete and Corfu in Keys’s study, and not from those who lived on the Mediterranean coast of Yugoslavia or in the cities of Italy.

In discussions of dietary fat and heart disease, it is often forgotten that the epidemiologic tools used to link heart disease to diet were relatively new and had never been successfully put to use previously in this kind of challenge. The science of epidemiology evolved to make sense of infectious diseases, not common chronic diseases like heart disease. Though the tools of epidemiology—comparisons of populations with and without the disease— had proved effective in establishing that a disease such as cholera is caused by the presence of micro-organisms in contaminated water, as the British physician John Snow demonstrated in 1854, it is a much more complicated endeavor to employ those same tools to elucidate the subtler causes of chronic disease. They can certainly contribute to the case against the most conspicuous determinants of noninfectious diseases—that cigarettes cause lung cancer, for example. But lung cancer was an extremely rare disease before cigarettes became widespread, and smokers are thirty times as likely to get it as nonsmokers. When it comes to establishing that someone who eats copious fat might be twice as likely to be afflicted with heart disease—a very common disorder—as someone who eats little dietary fat, the tools were of untested value.

The investigators attempting these studies were constructing the relevant scientific methodology as they went along. Most were physicians untrained to pursue scientific research. Nonetheless, they decided they could reliably establish the cause of chronic disease by accumulating diet and disease data in entire populations, and then using statistical analyses to determine cause and effect. Such an approach “seems to furnish information about causes,” wrote the Johns Hopkins University biologist Raymond Pearl in his introductory statistics textbook in 1940, but it fails, he said, to do so.

“A common feature of epidemiological data is that they are almost certain to be biased, of doubtful quality, or incomplete (and sometimes all three),” explained the epidemiologist John Bailar in The New England Journal of Medicine in 1980. “Problems do not disappear even if one has flawless data, since the statistical associations in almost any nontrivial set of observations are subject to many interpretations. This ambiguity exists because of the difficulty of sorting out causes, effects, concomitant variables, and random fluctuations when the causes are multiple or diffuse, the exposure levels low, irregular, or hard to measure, and the relevant biologic mechanisms poorly understood. Even when the data are generally accepted as accurate, there is much room for individual judgment, and the considered conclusions of the investigators on these matters determine what they will label ‘cause’…”

The only way to establish cause and effect with any reliability is to do “controlled” experiments, or controlled trials, as they’re called in medicine. Such trials attempt to avoid all the chaotic complexities of comparing populations, towns, and ethnic groups. Instead, they try to create two identical situations—two groups of subjects, in this case—and then change only one variable to see what happens. They “control” for all the other possible variables that might affect the outcome being studied. Ideally, such trials will randomly assign subjects into an experimental group, which receives the treatment being tested—a drug, for instance, or a special diet—and a group, which receives a placebo or eats their usual meals or some standard fare.

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 pill 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 pills 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 well. 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 actually 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, all 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 all 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 Jolliffe. The eleven hundred middle-aged members of Jolliffe’s Anti- Coronary Club were prescribed what he called the “prudent diet,” which included at least one ounce of