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Keys encountered similar skepticism in 1953, when he argued the same proposition, using comparisons of diet and heart-disease mortality in the United States, Canada, Australia, England and Wales, Italy, and Japan. The higher the fat intake, Keys said, the higher the heart-disease rates. Americans ate the most fat and had the highest heart-disease mortality. This was a “remarkable relationship,” Keys wrote: “No other variable in the mode of life besides the fat calories in the diet is known which shows anything like such a consistent relationship to the mortality rate from coronary or degenerative heart disease.”

Many researchers wouldn’t buy it. Jacob Yerushalmy, who ran the biostatistics department at the University of California, Berkeley, and Herman Hilleboe, the New York State commissioner of health, co-authored a critique of Keys’s hypothesis, noting that Keys had chosen only six countries for his comparison though data were available for twenty-two countries. When all twenty-two were included in the analysis, the apparent link between fat and heart disease vanished. Keys had noted associations between heart-disease death rates and fat intake, Yerushalmy and Hilleboe pointed out, but they were just that. Associations do not imply cause and effect or represent (as Stephen Jay Gould later put it) any “magic method for the unambiguous identification of cause.”

This is an irrefutable fact of logical deduction, but confusion over the point was (and still is) a recurring theme in nutrition research. George Mann, a former director of the famous Framingham Heart Study, called this drawing of associations between disease and lifestyles “a popular but not very profitable game.” When the science of epidemiology was founded in 1662 by John Graunt, a London merchant who had undertaken to interpret the city’s mortality records, Mann noted, even Graunt realized the danger of confusing such associations with cause and effect. “This causality being so uncertain,” Graunt wrote, “I shall not force myself to make any inference from the numbers.”

The problem is simply stated: we don’t know what other factors might be at work. Associations can be used to fuel speculation and establish hypotheses, but nothing more. Yet, as Yerushalmy and Hilleboe noted, researchers often treat such associations “uncritically or even superficially,” as Keys had: “Investigators must remember that evidence which is not inherently sound cannot serve even for partial support.” It “is worse than useless.”

Ironically, some of the most reliable facts about the diet-heart hypothesis have been consistently ignored by public-health authorities because they complicated the message, and the least reliable findings were adopted because they didn’t. Dietary cholesterol, for instance, has an insignificant effect on blood cholesterol. It might elevate cholesterol levels in a small percentage of highly sensitive individuals, but for most of us, it’s clinically meaningless.*5 Nonetheless, the advice to eat less cholesterol—avoiding egg yolks, for instance—remains gospel. Telling people they should worry about cholesterol in their blood but not in their diet has been deemed too confusing.

The much more contentious issues were how the quantity and type of fat influenced cholesterol levels, and, ultimately more important, whether cholesterol is even the relevant factor in causing heart disease. Keys and his wife had measured only total cholesterol in the blood, and he was comparing this with the total amount of fat in the diet. Through the mid-1950s, Keys insisted that all fat—both vegetable and animal—elevated cholesterol. And if all fat raised cholesterol, then one way to lower it was to eat less fat. This was the basis of our belief that a healthy diet is by definition a low-fat diet. Keys, however, had oversimplified. Since the mid-1950s, researchers have known that the total amount of dietary fat has little effect on cholesterol levels.

In 1952, however, Laurance Kinsell, director of the Institute for Metabolic Research at the Highland–Alameda County Hospital in Oakland, California, demonstrated that vegetable oil will decrease the amount of cholesterol circulating in our blood, and animal fats will raise it. That same year, J. J. Groen of the Netherlands reported that cholesterol levels were independent of the total amount of fat consumed: cholesterol levels in his experimental subjects were lowest on a vegetarian diet with a high fat content, he noted, and highest on an animal-fat diet that had less total fat. Keys eventually accepted that animal fats tend to raise cholesterol and vegetable fats to lower it, only after he managed to replicate Groen’s finding with his schizophrenic patients in Minnesota.

Kinsell and Edward “Pete” Ahrens of Rockefeller University then demonstrated that the crucial factor in controlling cholesterol was not whether the fat was from an animal or a vegetable, but its degree of “saturation,” as well as what’s known as the chain length of the fats. This saturation factor is a measure of whether or not the molecules of fat—known as triglycerides—contain what can be considered a full quotient of hydrogen atoms, as they do in saturated fats, which tend to raise cholesterol, or whether one or more are absent, as is the case with unsaturated fats, which tend, in comparison, to lower it. This kind of nutritional wisdom is now taught in high school, along with the erroneous idea that all animal fats are “bad” saturated fats, and all “good” unsaturated fats are found in vegetables and maybe fish. As Ahrens suggested in 1957, this accepted wisdom was probably the greatest “handicap to clear thinking” in the understanding of the relationship between diet and heart disease. The reality is that both animal and vegetable fats and oils are composed of many different kinds of fats, each with its own chain length and degree of saturation, and each with a different effect on cholesterol. Half of the fat in beef, for instance, is unsaturated, and most of that fat is the same monounsaturated fat as in olive oil. Lard is 60 percent unsaturated; most of the fat in chicken fat is unsaturated as well.

In 1957, the American Heart Association opposed Ancel Keys on the diet-heart issue. The AHA’s fifteen-page report castigated researchers—including Keys, presumably—for taking “uncompromising stands based on evidence that does not stand up under critical examination.” Its conclusion was unambiguous: “There is not enough evidence available to permit a rigid stand on what the relationship is between nutrition, particularly the fat content of the diet, and atherosclerosis and coronary heart disease.”

Less than four years later, the evidence hadn’t changed, but now a sixman ad-hoc committee, including Keys and Jeremiah Stamler, issued a new AHA report that reflected a change of heart. Released to the press in December 1960, the report was slightly over two pages long and had no references.*6 Whereas the 1957 report had concluded that the evidence was insufficient to authorize telling an entire nation to eat less fat, the new report argued the opposite—“the best scientific evidence of the time” strongly suggested that Americans would reduce their risk of heart disease by reducing the fat in their diets, and replacing saturated fats with polyunsaturated fats. This was the AHA’s first official support of Keys’s hypothesis, and it elevated high cholesterol to the leading heart-disease risk. Keys considered the report merely an “acceptable compromise,” one with “some undue pussy-footing” because it didn’t insist all Americans should eat less fat, only those at high risk of contracting heart disease (overweight middle-aged men, for instance, who smoke and have high cholesterol).