Good Calories, Bad Calories

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.

The new research would also mark the first time that HDL was measured in large populations, and this would further confuse the diet/heart-disease relationship. The hypothesis that HDL particles or the cholesterol in HDL protects against heart disease had first been proposed in 1951 by David Barr and Howard Eder of New York Hospital–Cornell Medical Center. It had been confirmed in a handful of small studies through the 1950s, and by Gofman in the last paper he published on lipoproteins and heart disease, as had the observation that when HDL was low triglycerides tended to be high, and vice versa, which suggested some underlying mechanism linking the two. Nonetheless, heart-disease researchers had paid little attention to HDL, as the NIH biostatistician Tavia Gordon later explained, because the idea of a “negative relation” between cholesterol and heart disease—high HDL cholesterol implies a low risk of heart disease—“simply ran against the grain.” “It was easy to believe that too much cholesterol in the blood could ‘overload’ the system and hence increase the risk of disease,” Gordon wrote, “but how could ‘too much’ of one part of the total cholesterol reduce the risk of disease? To admit that fact challenged the whole way of thinking about the problem.” Now HDL, too, would be measured in these populations.^*44

The results from the five studies were released in 1977 and divided into two publications, although Gordon had done the analyses for both. One reported on a comparison of nine hundred heart-disease cases with healthy controls from all five of the populations. The other addressed the prospective evidence from Framingham alone—measuring triglyceride, lipoprotein, and cholesterol levels in twenty-eight hundred subjects and then waiting four years to see how well these levels predicted the appearance of heart disease. The findings were consistent. Both analyses confirmed Gofman’s argument that total cholesterol said little about the risk of heart disease, and that the measurement of the triglycerides and cholesterol in the different lipoproteins was considerably more revealing. In men and women fifty and older, Gordon and his collaborators wrote in the Framingham paper, “total cholesterol per se is not a risk factor for coronary heart disease at all.” LDL cholesterol was a “marginal” risk factor, they reported. Triglycerides predicted heart disease in men and women in the analysis of cases from all five studies, but only in women in the Framingham analysis.

HDL was the “striking” revelation. Both analyses confirmed that the higher the HDL cholesterol the lower the triglycerides and the risk of heart disease. The inverse relationship between HDL and heart disease held true for every age group from forty-year-olds to octogenarians, in both men and women, and in every ethnic group from Framingham, Massachusetts, to Honolulu. “Of all the lipoproteins and lipids measured HDL had the largest impact on risk,” Gordon and his colleagues wrote. For those fifty and over, which is the age at which heart disease ceases to be a rare condition, HDL was the only reliable predictor of risk.

The finding that high HDL cholesterol was associated with a low risk of heart disease did not mean that raising HDL would lower risk, as Gordon and his colleagues noted, but it certainly suggested the possibility. Only a few studies had ever looked at the relationship of diet and lifestyle to HDL, and the results had suggested, not surprisingly, that anything that raised triglycerides would lower HDL, and vice versa. The “fragmentary information on what maneuvers will lead to an increase in HDL cholesterol levels,” Gordon and his collaborators wrote, “suggests that physical activity, weight loss and a low carbohydrate intake may be beneficial” (my italics).

This is where the story now takes some peculiar turns. One immediate effect of the revelation about HDL, paradoxically, was to direct attention away from triglycerides, and with them the conspicuous link, until then, to the carbohydrate hypothesis. Gordon and his colleagues 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 all 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 million. 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 recalled 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 all 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 challenge 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 all Americans eat instead.

In a more rational world, which means a research establishment not already committed to Keys’s hypothesis and not wholly reliant on funding from the institutions that had embraced the theory, the results would have immediately prompted small clinical trials of the hypothesis that raising HDL prevented heart disease, just like those small 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