THE DANGER OF SIMPLIFYING A MEDICAL ISSUE for public consumption is that we may come to believe that our simplification is an appropriate representation of the biological reality. We may forget that the science is not adequately described, or ambiguous, even if the public-health policy seems to be set in stone. In the case of diet and heart disease, Ancel Keys’s hypothesis that cholesterol is the agent of atherosclerosis was considered the simplest possible hypothesis, because cholesterol is found in atherosclerotic plaques and because cholesterol was relatively easy to measure. But as the measurement technology became increasingly more sophisticated, every one of the complications that arose has implicated carbohydrates rather than fat as the dietary agent of heart disease.

In 1950, the University of California medical physicist John Gofman wrote an article in Science that would be credited, albeit belatedly, with launching the modern era of cholesterol research. Gofman pointed out that cholesterol is only one of several fatlike substances that circulate through the blood and are known collectively as lipids or blood lipids. These include free fatty acids and triglycerides,*41 the molecular forms in which fat is found circulating in the bloodstream. These could also be players in the heart-disease process, Gofman noted, and the fact that there was no easy way to measure their concentrations in the circulation didn’t change that. Both cholesterol and triglycerides are shuttled through the circulation in particles called lipoproteins, and these could also be players. The amount of cholesterol and triglycerides varies in each type of lipoprotein. So, when physicians measure total cholesterol levels, they have no way of knowing how the cholesterol itself is apportioned in individual lipoproteins. It is possible, Gofman noted, that in heart disease the problem may be caused not by cholesterol but by a defect in one of these lipoproteins, or an abnormal concentration of the lipoproteins themselves.

Eventually, researchers came to identify these different classes of lipoproteins by their density. Of those that appeared to play obvious roles in heart disease, three in particular stood out even in the early 1950s. Two of these are familiar today: the low-density lipoproteins, known as LDL, the bad cholesterol, and the high-density variety, known as HDL, the good cholesterol. (This is an oversimplification, as I will explain shortly.) The third class is known as VLDL, which stands for “very low-density lipoproteins,” and these play a critical role in heart disease. Most of the triglycerides in the blood are carried in VLDL; much of the cholesterol is found in LDL. That LDL and HDL are the two species of lipoproteins that physicians now measure when we get a checkup is a result of the oversimplification of the science, not the physiological importance of the particles themselves.