Krauss himself is an idiosyncratic figure in this world. He has produced a dozen years of research suggesting that high-carbohydrate diets, for the great proportion of the population, are the nutritional cause of heart disease, and yet he has also chaired the nutrition committee of the American Heart Association and was the primary author of the 1996 and 2000 AHA nutrition guidelines. In the process, he eased the AHA away from its thirty-year-old position that the maximum fat content of a heart-healthy diet should be 30 percent of calories. Or, as Krauss remarked, he managed to put the “30-percent-fat recommendation in small print.” Krauss trained as a physician in the late 1960s and then worked with Fredrickson and Levy at the NIH, where he discovered a protein known as hepatic lipase that regulates how the liver metabolizes lipoproteins. He then moved to Berkeley to practice internal medicine, and it was there, in 1976, that he began working with Gofman’s ultracentrifuge and with Alex Nichols and Frank Lindgren, both of whom had collaborated with Gofman in the 1950s.

When Krauss began his research at Berkeley, he had what he calls “this conventional notion, which many people still have, that LDL is just one thing, a single entity.” But that turned out not to be the case. Using data from the ultracentrifuge dating back to the early 1960s, Krauss discovered that LDL actually comes in distinct subspecies, all characterized by still finer gradations in density and size. “It was blazingly obvious. Unignorable,” says Krauss.*49 Eventually, Krauss identified seven discrete subclasses of LDL. He also noted that the smallest and densest of the low-density lipoproteins had two significant properties: it had a strong negative correlation with HDL, and it was the subspecies that was elevated in patients with heart disease.

In the early 1980s, Krauss published three papers on what he calls the “remarkable heterogeneity of LDL,” all of which, he says, were met with indifference mixed with occasional hostility. Acceptance of Krauss’s research was also constrained by the fact that Gofman’s ultracentrifuge had been necessary to differentiate these LDL subclasses, which meant that this, too, was not the kind of measurement that could be ordered up easily by physicians. In his later publications, Krauss described a simpler, inexpensive measurement technique, but the research was still perceived as an esoteric endeavor.

To understand the implications of this association between small, dense LDL and heart disease, it helps to picture the configuration of the low-density lipoprotein itself. Imagine it as a balloon. It has a single protein—known as apo B, for short—that serves as the structural foundation of the balloon and holds it together. It has an outer membrane that is composed of cholesterol and fats of yet another type, called phospholipids. And then, inside the balloon, inflating it, are triglycerides and more cholesterol. The size of the LDL balloon itself can vary, depending on the amount of triglycerides and cholesterol it contains. Thus, as Krauss reported, some people have mostly large, fluffy LDL, with a lot of cholesterol and triglycerides inflating the balloon, and some people have mostly smaller, denser LDL particles, with less cholesterol and triglycerides.