Good Calories, Bad Calories

The condition of having very high cholesterol—say, above 300 mg/dl—is known as hypercholesterolemia. If the cholesterol hypothesis is right, then most hypercholesterolemics should get atherosclerosis and die of heart attacks. But that doesn’t seem to be the case. In the genetic disorder familial hypercholesterolemia, cholesterol is over 300 mg/dl for those who inherit one copy of the defective gene, and as high as 1,500 mg/dl for those who inherit two. One out of every two men and one out of every three women with this condition are likely to have a heart attack by age sixty, an observation that is often evoked as a cornerstone of the cholesterol hypothesis. But certain thyroid and kidney disorders will also cause hypercholesterolemia; autopsy examinations of individuals with these maladies have often revealed severe atherosclerosis, but these individuals rarely die of heart attacks.

Autopsy examinations had also failed to demonstrate that people with high cholesterol had arteries that were any more clogged than those with low cholesterol. In 1936, Warren Sperry, co-inventor of the measurement technique for cholesterol, and Kurt Landé, a pathologist with the New York City Medical Examiner, noted that the severity of atherosclerosis could be accurately evaluated only after death, and so they autopsied more than a hundred very recently deceased New Yorkers, all of whom had died violently, measuring the cholesterol in their blood. There was no reason to believe, Sperry and Landé noted, that the cholesterol levels in these individuals would have been affected by their cause of death (as might have been the case had they died of a chronic illness). And their conclusion was unambiguous: “The incidence and severity of atherosclerosis are not directly affected by the level of cholesterol in the blood serum per se.”

This was a common finding by heart surgeons, too, and explains in part why heart surgeons and cardiologists were comparatively skeptical of the cholesterol hypothesis. In 1964, for instance, the famous Houston heart surgeon Michael DeBakey reported similarly negative findings from the records on seventeen hundred of his own patients. And even if high cholesterol was associated with an increased incidence of heart disease, this begged the question of why so many people, as Gofman had noted in Science, suffer coronary heart disease despite having low cholesterol, and why a tremendous number of people with high cholesterol never get heart disease or die of it.

Ancel Keys deserves the lion’s share of credit for convincing us that cholesterol levels predict heart disease and that dietary fat is a killer. Keys ran the Laboratory of Physiological Hygiene at the University of Minnesota and considered it his franchise, as he would tell Time magazine, “to find out why people get sick before they got sick.” He became famous during World War II by developing the K ration for combat troops—the “K,” it is said, stood for “Keys.” He spent the later war years doing the seminal study of human starvation, using conscientious objectors as his subjects. He then documented the experience, along with the world’s accumulated knowledge on starvation, in The Biology of Human Starvation, a fourteen-hundred-page tome that cemented Keys’s reputation. (I’ll talk more about Keys’s remarkable starvation study in chapter 15.)

Keys’s abilities as a scientist are arguable—he was more often wrong than right—but his force of will was indomitable. Henry Blackburn, his longtime collaborator at Minnesota, described him as “frank to the point of bluntness, and critical to the point of sharpness.” David Kritchevsky, who studied cholesterol metabolism at the Wistar Institute in Philadelphia and was a competitor, described Keys as “pretty ruthless” and not a likely winner of any “Mr. Congeniality” awards. Certainly, Keys was a relentless defender of his own hypotheses; he minced few words when he disagreed with a competitor’s interpretation of the evidence, which was inevitably when the evidence disagreed with his hypothesis.