“Everything should be made as simple as possible,” Albert Einstein once supposedly said, “but no simpler.” Our understanding of the nutritional causes of heart disease started with Keys’s original oversimplification that heart disease is caused by the effect of all dietary fat on total serum cholesterol. Total cholesterol gave way to HDL and LDL cholesterol and even triglycerides. All fat gave way to animal and vegetable fat, which gave way to saturated, monounsaturated, and polyunsaturated fat, and then polyunsaturated fats branched into omega-three and omega-six polyunsaturated fats. By the mid-1980s, these new levels of complexity had still not deterred the AHA and NIH from promoting carbohydrates as effectively the antidote to heart disease, and either all fats or just saturated fats as the dietary cause.

What would now become apparent was that LDL cholesterol is little more than an arbitrary concept that oversimplifies its own complex diversity. The fact that LDL and LDL cholesterol are not synonymous complicates the science. Just as Gofman had reported in 1950 that cholesterol itself was divided up among different lipoproteins, and those lipoproteins had different atherogenic properties and responded differently to diet, a lipid metabolism specialist named Ronald Krauss, using Gofman’s ultracentrifuge, began reporting in 1980 that low-density lipoproteins were in turn composed of different, distinct subclasses, each containing differing amounts of cholesterol, and each, once again, with different atherogenic properties and different behavior in response to the carbohydrates and fats in our diet. Although Krauss has long been considered one of the most thoughtful researchers in nutrition and heart disease—the American Heart Association has treated him as such—it’s worth noting in advance that his dietary research has been almost universally ignored, precisely because of its ultimate implications for what constitutes a healthy diet and what does not.

LDL cholesterol is only a “marginal risk factor,” Tavia Gordon and his colleagues had observed in 1977. In other words, little difference can be observed between the average LDL cholesterol of those with and without heart disease. Only by comparing the LDL-cholesterol and heart-disease rates between nations (with all the attendant complications of such comparisons) can conspicuous differences be seen. In the analysis from Framingham, San Francisco, Albany, Honolulu, and Puerto Rico published by Gordon and his collaborators, the average LDL cholesterol of heart-disease sufferers was only a few percentage points higher than the average of those who remained healthy. “If you look in the literature and just look at the average coronary patients,” Krauss says, “their LDL-cholesterol levels are often barely discernibly elevated compared to patients who do not have coronary disease.”

In the late 1940s, Gofman and his collaborators began asking why the same level of LDL cholesterol will cause heart disease in some people but not in others. Krauss and his collaborators began asking this question again, thirty years later.