Good Calories, Bad Calories (32 page)

This is where the story now takes some peculiar turns. One immediate effect of the revelation about HDL, paradoxical y, was to direct attention away from triglycerides, and with them the conspicuous link, until then, to the carbohydrate hypothesis. Gordon and his col eagues had demonstrated that when both HDL and triglycerides were incorporated into the risk equations of heart disease, or when obesity and the prediabetic condition of glucose intolerance were included in the equations along with triglycerides, the apparent effect of triglycerides diminished considerably. This result wasn’t surprising, considering that low HDL, high triglycerides, obesity, and glucose intolerance al seemed to be related, but that wasn’t the point. The relevant question for physicians was whether high triglycerides by themselves caused heart disease. If so, then patients should be advised to lower their triglycerides, however that might be accomplished, just as they were being told already to lower cholesterol. These risk-factor equations (known as multivariate equations) suggested that triglycerides were not particularly important when these other factors were taken into account, and this was how they would be perceived for another decade. Not until the late 1980s would the intimate association of low HDL, high triglycerides, obesity, and diabetes be considered significant—in the context of Gerald Reaven’s Syndrome X hypothesis—but by then the heart-disease researchers would be committed to the recommendations of a national low-fat, high-carbohydrate diet.

Heart-disease researchers would also avoid the most obvious implication of the two analyses—that raising HDL offers considerably more promise to prevent heart disease than lowering either LDL or total cholesterol—on the basis that this hadn’t been tested in clinical trials. Here the immediate obstacle, once again, was the institutional investment in Keys’s hypothesis. The National Institutes of Health had committed its heart-disease research budget to two ongoing studies, MRFIT and the Lipid Research Clinics Trial, which together would cost over $250 mil ion. These studies were dedicated solely to the proposition that lowering total cholesterol would prevent heart disease. There was little money or interest in testing an alternative approach.

Gordon later recal ed that, when he presented the HDL evidence to the team of investigators overseeing MRFIT, “it was greeted with a silence that was very, how should I say it, expressive. One of them spoke up indicating he suspected this was a bunch of shit. They didn’t know how to deal with it.”

Indeed, the timing of the HDL revelations could not have been less convenient. The results were first revealed to the public in an American Heart Association seminar in New York on January 17, 1977. This was just three days after George McGovern had announced the publication of the Dietary Goals for the United States, advocating low-fat, high-carbohydrate diets for al Americans, based exclusively on Keys’s hypothesis that coronary heart disease was caused by the effect of saturated fat on total cholesterol. If the New York Times account of the proceedings is accurate, the AHA and the assembled investigators went out of their way to ensure that the new evidence would not cast doubt on Keys’s hypothesis or the new dietary goals. Rather than chal enge the theory that excess cholesterol can cause heart disease, the Times reported, “the findings re-emphasize the importance of a fatty diet in precipitating life-threatening hardening of the arteries in most Americans,” which is precisely what they did not do. According to the Times, saturated fat was now indicted not just for increasing LDL cholesterol, which it does, but for elevating VLDL triglycerides and lowering HDL, which it does not, and certainly not compared with the carbohydrates that McGovern’s Dietary Goals were recommending al Americans eat instead.

In a more rational world, which means a research establishment not already committed to Keys’s hypothesis and not whol y reliant on funding from the institutions that had embraced the theory, the results would have immediately prompted smal clinical trials of the hypothesis that raising HDL prevented heart disease, just like those smal trials that had begun in the 1950s to test Keys’s hypothesis. If those confirmed the hypothesis, then longer, larger trials would be needed to establish whether the short-term benefits translated to a longer, healthier life. But the NIH administrators decided that HDL studies would have to wait. Once the Lipid Research Clinics Trial results 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, wel over $1 bil ion 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 appearance of being more important.

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 equal y simple guidelines for patient care, and, second, to reconcile these new observations with Keys’s hypothesis and the $250 mil ion 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 il 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 col aborators 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 “powerful predictor of risk in subjects younger than the age of 50”

and as showing “a significant contribution…to coronary heart disease in persons older than the age of 50 and practical y up into the eighties.” This practice has continued unabated.*45

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 col aborators. These lipid profiles al owed 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.

Ironical y, 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 col eagues 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 equal y 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 al 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 typical y 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 col eague 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 and lower LDL cholesterol. Saturated fats raise both HDL and LDL cholesterol. Carbohydrates lower LDL cholesterol but also lower HDL. Grundy and Mattson’s discovery of the double-barreled effect of monounsaturated fats, and particularly oleic acid, reignited the popular interest in the Mediterranean diet as the ideal heart-healthy diet, though it seemed to be heart-healthy only in some Mediterranean regions and not in others, and such diets, as even Grundy conceded, had never been tested. When they final y were tested in two clinical trials in the 1990s—the Lyon Diet Heart Trial and an Italian study known as GISSI-Prevenzione—both supported the contention that the diet prevented heart attacks, but neither provided evidence that it did so by either raising HDL or lowering LDL, which was how it was now al eged to work.

The observation that monounsaturated fats both lower LDL cholesterol and raise HDL also came with an ironic twist: the principal fat in red meat, eggs, and bacon is not saturated fat, but the very same monounsaturated fat as in olive oil. The implications are almost impossible to believe after three decades of public-health recommendations suggesting that any red meat consumed should at least be lean, with any excess fat removed.

Consider a porterhouse steak with a quarter-inch layer of fat. After broiling, this steak wil reduce to almost equal parts fat and protein.*48 Fifty-one percent of the fat is monounsaturated, of which 90 percent is oleic acid. Saturated fat constitutes 45 percent of the total fat, but a third of that is stearic acid, which wil increase HDL cholesterol while having no effect on LDL. (Stearic acid is metabolized in the body to oleic acid, according to Grundy’s research.) The remaining 4 percent of the fat is polyunsaturated, which lowers LDL cholesterol but has no meaningful effect on HDL. In sum, perhaps as much as 70 percent of the fat content of a porterhouse steak wil improve the relative levels of LDL and HDL cholesterol, compared with what they would be if carbohydrates such as bread, potatoes, or pasta were consumed. The remaining 30 percent wil raise LDL cholesterol but wil also raise HDL