were published in 1984, they were presented to the world as proof that lowering cholesterol by eating less fat and more carbohydrates was the dietary answer to heart disease. There was simply no room now in the dogma for a hypothesis that suggested that raising HDL (and lowering triglycerides) by eating more fat and less carbohydrates might be the correct approach. No clinical trials of the HDL hypothesis would begin in the U.S. until 1991, when the Veterans Administration funded a twenty-center drug trial. The results, published in 1999, supported the hypothesis that heart disease could be prevented by raising HDL. The drug used in the study, gemfibrozil, also lowered triglyceride levels and VLDL, suggesting that a diet that did the same by restricting carbohydrates might have a similarly beneficial effect. As of 2006, no such dietary trials had been funded.
Through the 1980s and 1990s, as our belief in the low-fat heart-healthy diet solidified, the official reports on nutrition and health would inevitably discuss the apparent benefits of raising HDL—the “good cholesterol”—and would then observe correctly that no studies existed to demonstrate this would prevent heart disease and lengthen life. By 2000, well over $1 billion had been spent on trials of cholesterol-lowering, and a tiny fraction of that amount on testing the benefits of raising HDL. Thus, any discussions about the relative significance of raising HDL versus lowering total cholesterol would always be filtered through this enormous imbalance in the research efforts. Lowering LDL cholesterol would always have the
It was the revelations that emerged from the two HDL publications in 1977 that led to the conventional wisdom about LDL, triglycerides, and HDL that we live with today. The National Heart, Lung, and Blood Institute and the American Heart Association responded to the new research by focusing on two pragmatic concerns: first, to keep the science sufficiently simple that it could be translated into equally simple guidelines for patient care, and, second, to reconcile these new observations with Keys’s hypothesis and the $250 million worth of studies that were putting it to the test. If total cholesterol was not a risk factor for heart disease above the age of fifty, as Gordon’s Framingham analysis noted, then that seemed to refute Keys’s hypothesis. One immediate goal, therefore, was to make sure that those aspects of the hypothesis that had seemed reasonably certain were not discarded prematurely on the basis of findings that might also someday turn out to be erroneous.
Since both of the new analyses had concluded that LDL cholesterol was associated with a slightly increased risk of heart disease, and since up to 70 percent of the total cholesterol in the circulation may be found in LDL, the American Heart Association and the proponents of Keys’s hypothesis now shifted the focus of scientific discussions from the benefits of lowering total cholesterol to the benefits of lowering LDL cholesterol. “Whatever the underlying disorder,” noted the Framingham investigators in 1979, “much of what has been learned in the past about the ill effects of a high serum total cholesterol can be attributed to the associated elevated levels of LD lipoprotein….”
Making LDL the “bad cholesterol” oversimplified the science considerably, but it managed to salvage two decades’ worth of research, and to justify why physicians had bothered to measure total cholesterol in their patients. One consequence of this effort was an upgrading of the adjectives used to describe the predictive ability of LDL. In 1977, Gordon and his collaborators had described LDL cholesterol as a “marginal risk factor” for heart disease. Within two years, the same authors were using the identical data to describe LDL as a “
Another shift in emphasis was to incorporate HDL and some combination of triglycerides, LDL, and total cholesterol into the calculation of a “lipid profile” of heart-disease risk, a process that was initiated with the very first articles by Gordon and his collaborators. These lipid profiles allowed for the continued use of LDL or total cholesterol in the calculation of heart-disease risk, even though they added little or no predictive power to the use of HDL alone.
Ironically, these lipid profiles also provided the rationale for physicians to keep measuring total cholesterol in their patients, even though it had now been confirmed, as Gofman had noted a quarter-century earlier, that it was a dangerously unreliable predictor of risk. The reason is that LDL cholesterol itself happened to be particularly difficult to measure.†46 It was not the kind of measurement that physicians could easily order up for their patients. And since it didn’t seem to matter in these lipid profiles whether it was total or LDL cholesterol that was included along with HDL—either way, HDL was the dominant predictor of risk—then, “from a practical point of view,” as Gordon and his colleagues noted, “total cholesterol can substitute for LDL cholesterol” in calculating risk. Total cholesterol could be measured easily in the clinic, so physicians would continue to measure it. The evidence had dictated a complete turnabout in the science, and then pragmatic considerations had turned it about again, until the clinical management of patients and the public perception were back exactly where they had started.
The revelations about HDL had equally little influence on the institution of a national low-fat, high-carbohydrate diet. Whether or not triglycerides were an independent risk factor, once the protective nature of HDL was confirmed, then Gofman’s argument of 1950 was also reaffirmed: there were at least two potential diet-related ways of preventing heart disease, and any treatment that improved the situation with one risk factor had to avoid exacerbating the situation with the other. In the 1960s, Gofman, Ahrens, Albrink, and Fredrickson, Levy, and Lees had all discussed the dangers of replacing the fat in the diet with carbohydrates because this would elevate triglycerides. Now the dangers of lowering HDL became the issue. “In the search for an optimal therapy for avoiding or correcting atherosclerosis,” as the Framingham investigators noted in 1979, “the ideal lipid response would appear to be the one that raises HD lipoprotein as it lowers LD lipoprotein. Therapeutic maneuvers that affect only one of these lipoprotein particle systems in a favorable way, while adversely affecting the other, may be less promising….”
Diets that lowered cholesterol by replacing saturated fat with polyunsaturated fats would have accomplished such a balancing act, but there was legitimate concern that polyunsaturated fats were carcinogenic, and so the AHA had simply recommended fat reduction in general. This meant replacing the fat calories with carbohydrates. But the “good cholesterol” in HDL would be diminished by eating more carbohydrates. By the 1980s, discussions of heart-disease prevention typically avoided this dilemma by neglecting to mention the effect of carbohydrates on HDL.*47 Instead, people were told to raise their HDL through exercise and weight loss, and then prescribed, as the American Heart Association did, low-fat, high-carbohydrate diets as the means to lose that weight.
In 1985, Scott Grundy and his colleague Fred Mattson provided what appeared to be the ideal compromise—a dietary means both to lower LDL cholesterol and to raise HDL cholesterol without consuming more carbohydrates or saturated fats. This was monounsaturated fats, such as the oleic acid found in olive oil, and it served to keep the focus on the fat in the diet, rather than the carbohydrates. In the 1950s, Keys had assumed that monounsaturated fats were neutral, because they had no effect on total cholesterol. But this apparent neutrality, as Grundy reported, was due to the ability of these fats simultaneously to raise HDL cholesterol
The observation that monounsaturated fats both lower LDL cholesterol and raise HDL also came with an ironic
