Good Calories, Bad Calories

consumption of excess calories of all types), any possible link to carbohydrate consumption or “carbohydrate overfeeding” is overlooked. Even Landsberg has concentrated almost exclusively on the obesity-insulin-hypertension connection and ignored the idea that the increase in insulin levels due to excessive carbohydrate consumption, or due to the consumption of refined and easily digestible carbohydrates, might have a similar effect.

One question that will be addressed in the coming chapters is why medical investigators and public-health authorities, like Landsberg, will accept the effects of insulin on chronic diseases as real and potentially of great significance, and yet inevitably interpret their evidence in ways that say nothing about the unique ability of refined and easily digestible carbohydrates to chronically elevate insulin levels. This is the dilemma that haunts the past fifty years of nutrition research, and it is critical to the evolution of the science of metabolic syndrome. As we will discuss, the observation of diseases of civilization was hardly the only evidence implicating sugar and refined carbohydrates in these diseases. The laboratory research inevitably did, too. Yet the straightforward interpretation of the evidence—from carbohydrates to the chronic elevation of insulin to disease—was consistently downplayed or ignored in light of the overwhelming belief that Keys’s dietary-fat hypothesis had been proved correct, which was not the case.

The coming chapters will discuss the history of the science of metabolic syndrome both in the context of how the research was interpreted at the time, in a universe dominated by Keys’s hypothesis, and then how it arguably should have been interpreted if the research community had approached this science without bias and preconceptions. The next five chapters describe the science that was pushed aside as investigators and public- health authorities tried to convince first themselves and then the rest of us that dietary fat was the root of all nutritional evils. These chapters divide the science of metabolic syndrome and the carbohydrate hypothesis into five threads, to simplify the telling (although by doing so, they admittedly oversimplify).

The first (Chapter 9) covers the research that directly challenged the fundamental premise of Keys’s hypothesis that cholesterol itself is the critical component in heart disease, and instead implicated triglycerides and the kinds of molecules known as lipoproteins that carry cholesterol through the blood, both of which are effectively regulated by the carbohydrate content of the diet rather than saturated fat. The chapter then explains how this research, despite its refutation of the fat-cholesterol hypothesis, has been assimilated into it nonetheless.

The second thread (Chapter 10) follows the evolution of the science of insulin resistance and hyperinsulinemia, the condition of having chronically elevated insulin levels, and how that emerged out of attempts to understand the intimate relationship of obesity, heart disease, and diabetes and led to the understanding of metabolic syndrome and the entire cluster of metabolic and hormonal abnormalities that it entails.

The third (Chapter 11) discusses the implications of metabolic syndrome in relation to diabetes and the entire spectrum of diabetic complications.

The fourth (Chapter 12) discusses table sugar and high-fructose corn syrup, in particular, and the research suggesting that they have negative health effects that are unique among refined carbohydrate foods.

The last section of this history (Chapter 13) discusses how metabolic syndrome, and particularly high blood sugar, hyperinsulinemia, and insulin resistance, have physiological repercussions that can conceivably explain the appearance of even Alzheimer’s disease and cancer.

Throughout these five chapters, the science will be more technical than has typically been the case in popular discussions of what we should eat and what we shouldn’t. I believe it is impossible, though, to make the argument that nutritionists for a half century oversimplified the science to the point of generating false ideas and erroneous deductions, without discussing the science at the level of complexity that it deserves.

Chapter Nine

TRIGLYCERIDES AND THE COMPLICATIONS OF CHOLESTEROL

Oversimplification has been the characteristic weakness of scientists of every generation.

ELMER MCCOLLUM, A History of Nutrition, 1957

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.

In 1950, the only instrument capable of measuring the density of lipoproteins was an ultracentrifuge, and the only ultracentrifuge available for this work in America was being used by Gofman at the University of California, Berkeley. Gofman was both a physician and a physical chemist by training. During World War II, he worked for the Manhattan Project, and developed a process to separate plutonium that would later be used to produce H-bombs. After the war, Gofman set out to use the Berkeley ultracentrifuge to study how cholesterol and fat are transported through the blood and how this might be affected by diet and perhaps cause atherosclerosis and heart disease.