Good Calories, Bad Calories

By then, however, the science had already become secondary to more practical issues. Despite JAMA’s optimism that a new era was dawning, it was no longer a question of whether it was cholesterol or triglycerides that caused atherosclerosis and heart disease, whether saturated fat or carbohydrates were to blame, but which of the two hypotheses dominated the research. Here Keys’s hypothesis had precedence. A generation of clinical investigators—the “cholesterol bandwagon”—had gathered an enormous amount of data, however ambiguous, on cholesterol levels and heart disease; only Albrink, Kuo, and a handful of other researchers had studied triglycerides. Only Gofman had studied the VLDL particles that transport triglycerides through the circulation.

Moreover, measuring triglycerides was still much more difficult than measuring cholesterol, and so only the rare laboratory had the facilities to do it. The National Institutes of Health, which was effectively the only source of funding for this research in the United States, had already committed its resources to three enormous studies—the Framingham Heart Study, Keys’s Seven Countries Study, and the pilot programs of the National Diet-Heart Study. These studies would measure only cholesterol and so test only Keys’s hypothesis. No consideration was given to any alternative hypothesis. By 1961, Keys and his collaborators in the Seven Countries Study had measured cholesterol in over ten thousand men. By 1963, they had completed the exams on another eighteen hundred men. Even had it been technically possible to include triglycerides in the measurements, or to return to the original locales and retest for triglycerides, the cost would have been astronomical. The result, as we’ve seen, was considered a resounding victory for Keys’s fat-cholesterol hypothesis.

The research that would finally lead to a large-scale test of the carbohydrate/ triglyceride/heart-disease hypothesis emerged from the National Institutes of Health in early 1967. This was a collaboration between Donald Fredrickson and Robert Levy, who would become directors of the National Institutes of Health and the National Heart, Lung, and Blood Institute respectively, and Robert Lees, then of Rockefeller University. It was published in a fifty-page, five-part series in The New England Journal of Medicine. First Fredrickson, Levy, and Lees proposed a simplified classification of lipoproteins (perhaps an oversimplification, they acknowledged), which divided the lipoproteins in the bloodstream into four categories: LDL, which typically carried most of the cholesterol; VLDL, which carried most of the triglycerides; the high-density lipoproteins, HDL; and chylomicrons, which carry dietary fat from the intestine to the fat tissue. Then they proposed a classification scheme for disorders of lipoprotein metabolism, each delineated by a roman numeral, that included both those of abnormally high amounts of LDL cholesterol, which they suggested might be ameliorated by low-fat diets, as well as those characterized by abnormally high triglycerides carried in VLDL, which would be ameliorated by low-carbohydrate diets.

Four of the five lipoprotein disorders described in this series were characterized by abnormally elevated levels of triglycerides in the very low-density lipoproteins. For this reason, Fredrickson, Levy, and Lees also warned against the dangers of advocating low-fat diets for all patients, because these diets increased carbohydrate consumption and so would elevate triglycerides and VLDL even further. By far the most common of the five lipoprotein disorders was the one designated Type IV, characterized by elevated VLDL triglycerides—“sometimes considered synonymous with ‘carbohydrate-induced hyperlipemia,’” they wrote—and it had to be treated with a low-carbohydrate diet. “Patients with this syndrome,” Lees later wrote, “form a sizable fraction of the population suffering from coronary heart disease.”^*43

Because Fredrickson, Levy, and Lees had also described an innovative and inexpensive technique for measuring the triglycerides and cholesterol carried in these different lipoproteins, the NIH provided the necessary funding for five studies—in Framingham, Puerto Rico, Honolulu, Albany, and San Francisco—to measure LDL cholesterol and VLDL triglycerides in these populations and determine their significance as risk factors for heart disease. This research would take almost a decade to complete, and would constitute the first time that NIH-funded research projects would measure anything other than total cholesterol in large populations.