Good Calories, Bad Calories

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.

In the 1970s, investigators had developed yet another way to quantify the concentration of these circulating lipoproteins, in this case by counting only the number of apo B proteins that provide the structural foundation to the LDL balloon. Because there’s only one protein per LDL particle, and because VLDL is also composed of identical apo B proteins, this technique measured the number of LDL and VLDL particles in a blood sample, rather than the cholesterol or triglycerides they contained. As it turned out, the number of apo B proteins, and so the total number of LDL and VLDL particles combined, is also abnormally elevated in heart-disease patients. This was first reported in 1980 by Peter Kwiterovich, a lipid-metabolism specialist from Johns Hopkins, together with Allan Sniderman, a cardiologist from McGill University. Kwiterovich and Sniderman then collaborated with Krauss on the last of his three papers on the heterogeneity of LDL. In 1983, they reported that the disproportionate elevation in the apo B protein in heart-disease patients was due to a disproportionate elevation in the amount of the smallest and densest of the low-density lipoproteins.