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 Lande 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
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
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.
When Keys launched his crusade against heart disease in the late 1940s, most physicians who believed that heart disease was caused by diet implicated dietary cholesterol as the culprit. We ate too much cholesterol-laden food—meat and eggs, mostly—and that, it was said, elevated our blood cholesterol. Keys was the first to discredit this belief publicly, which had required, in any case, ignoring a certain amount of the evidence. In 1937, two Columbia University biochemists, David Rittenberg and Rudolph Schoenheimer, demonstrated that the cholesterol we eat has very little effect on the amount of cholesterol in our blood. When Keys fed men for months at a time on diets either high or low in cholesterol, it made no difference to their cholesterol levels. As a result, Keys insisted that dietary cholesterol had little relevance to heart disease. In this case, most researchers agreed.
In 1951, Keys had an epiphany while attending a conference in Rome on nutrition and disease, which focused exclusively, as Keys later recalled, on malnutrition. There he was told by a physiologist from Naples that heart disease was not a problem in his city. Keys found this comment remarkable, so he and his wife, Margaret, a medical technician whose specialty was fast becoming cholesterol measurements, visited Naples to see for themselves. They concluded that the general population was indeed heart-disease-free—but the rich were not. Margaret took blood-cholesterol readings on several hundred workers and found that they had relatively low cholesterol. They asked “a few questions about their diet,” Keys recalled, and concluded that these workers ate little meat and that this explained the low cholesterol. As for the rich, “I was taken to dine with members of the Rotary Club,” Keys wrote. “The pasta was loaded with meat sauce and everyone added heaps of parmesan cheese. Roast beef was the main course. Dessert was a choice of ice cream or pastry. I persuaded a few of the diners to come for examination, and Margaret found their cholesterol levels were much higher than in the workmen.” Keys found “a similar picture” when he visited Madrid. Rich people had more heart disease than poor people, and rich people ate more fat.
This convinced Keys that the crucial difference between those with heart disease and those without it was the fat in the diet. A few months later, he aired his hypothesis at a nutrition conference in Amsterdam—“fatty diet, raised serum cholesterol, atherosclerosis, myocardial infarction.” Almost no one in the audience, he said, took him seriously. By 1952, Keys was arguing that Americans should reduce their fat consumption by a third, though simultaneously acknowledging that his hypothesis was based more on speculation than on data: “Direct evidence on the effect of the diet on human arteriosclerosis is very little,” he wrote, “and likely to remain so for some time.”
Over the next half-dozen years, Keys assembled a chain of observations that became the bedrock of his belief that fat caused heart disease. He fed high-fat and medium-fat diets to schizophrenic patients at a local mental hospital and reported that the fat content dramatically raised cholesterol. He traveled to South Africa, Sardinia, and Bologna, where Margaret measured cholesterol and they assessed the fat content of the local diet. In Japan, they measured the cholesterol levels of rural fisherman and farmers; they did the same for Japanese immigrants living in Honolulu and Los Angeles. He concluded that the cholesterol/heart-disease association was not peculiar to race or nationality, not a genetic problem, but a dietary one. They visited a remote logging camp in Finland and learned that these hardworking men were plagued by heart disease. A local clinic had six patients, including three young men, who “suffered from myocardial infarction.” They shared a snack with the loggers: “slabs of cheese the size of a slice of bread on which they smeared butter,” Keys wrote; “they washed it down with beer. It was an object lesson for the coronary problem.”
Keys bolstered his hypothesis with a 1950 report from Sweden that heart disease deaths had virtually disappeared there during the German occupation of World War II. Similar phenomena were reported in nations that had undergone severe food-rationing during the war—Finland, Norway, Great Britain, Holland, the Soviet Union. Keys concluded that the dramatic reduction in coronary deaths was caused by decreased consumption of fat from meat, eggs, and dairy products. Skeptics observed, however, that these are among many deprivations and changes that accompany food rationing and occupation. Fewer calories are consumed, for instance, and weight is lost. Unavailability of gasoline leads to increased physical activity. Sugar and refined-flour consumption decreases. Any of these might explain the reduction in heart-disease mortality, these investigators noted.
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
