Good Calories, Bad Calories (30 page)

One question that wil be addressed in the coming chapters is why medical investigators and public-health authorities, like Landsberg, wil accept the effects of insulin on chronic diseases as real and potential y 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 chronical y 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 wil 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 wil 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 al nutritional evils. These chapters divide the science of metabolic syndrome and the carbohydrate hypothesis into five threads, to simplify the tel ing (although by doing so, they admittedly oversimplify).

The first (Chapter 9) covers the research that directly chal enged 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) fol ows the evolution of the science of insulin resistance and hyperinsulinemia, the condition of having chronical y 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 wil be more technical than has typical y 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.

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 col ectively 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 cal ed 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.

Eventual y, 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 wil 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 I , 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.

This was the research Gofman first reported in Science in 1950. He described how his ultracentrifuge “fractionated” lipoproteins into different classes depending on their density, and he noted that one particular class of lipoproteins, which would later be identified as LDL,*42 is more numerous in patients with atherosclerosis than in healthy subjects, in men than in women, in older individuals than in younger, and particularly conspicuous in diabetics, al of which suggested a possible role in heart disease. What these low-density lipoproteins did not do, Gofman reported, was to reflect consistently the amount of cholesterol in the blood, even though they carry cholesterol within them. Sometimes total cholesterol levels would be low in his subjects, he noted, and yet the concentration of these low-density lipoproteins would be abnormal y high. Sometimes total cholesterol would be high while the cholesterol contained in the low-density lipoproteins was low. “At a particular cholesterol level one person may show 25 percent of the total serum cholesterol in the form of [low-density lipoproteins], whereas another person may show essential y none in this form,” Gofman wrote.

After Science published Gofman’s article, and after aggressive lobbying on Gofman’s part, the National Advisory Heart Council agreed to fund a test of his hypothesis that lipoproteins are the important factor in heart disease and that cholesterol itself is not. The test would be carried out by four research groups—led by Gofman at Berkeley, Irving Page at the Cleveland Clinic, Fred Stare and Paul Dudley White at Harvard, and Max Lauffer of the University of Pittsburgh—that col ectively identified five thousand men who were free of heart disease. When heart disease eventual y appeared, they would determine whether total cholesterol or Gofman’s lipoproteins was the more accurate predictor.

While the three Eastern laboratories took three years to learn how to use an ultracentifruge for fractionating lipoproteins, Gofman proceeded with his own research, refined his understanding of how these lipoproteins predicted heart disease, and he then insisted that the analysis techniques be updated accordingly. The other investigators, however, were having considerable trouble duplicating Gofman’s original analysis, and so they refused to accept any further modifications.

In 1956, the four groups published a report in the American Heart Association journal Circulation, with a minority opinion written by Gofman and his Berkeley col eagues and a majority opinion authored by everyone else. As the majority saw it, based on the state of Gofman’s research in 1952, cholesterol was indeed a questionable predictor of heart disease risk, but the measurements of lipoproteins added little predictive power. “The lipoprotein measurements are so complex,” the majority report declared, “that it cannot be reasonably expected that they could be done reliably in hospital laboratories.” Gofman’s minority opinion, based on the state of his research in 1955, was that LDL and VLDL, the very low-density lipoproteins, were good predictors of heart disease, but that the single best predictor of risk was an atherogenic index, which took into account these two lipoprotein classes measured individual y and added them together. The greater the atherogenic index, the greater the risk of atherosclerosis and heart disease.

Gofman would later be vindicated, but the majority opinion prevailed at the time: studying lipoproteins held no value in the clinical management of heart disease. Gofman and his Berkeley col aborators continued the research alone through 1963, when Gofman left to establish a biomedical-research division at the Lawrence Livermore National Laboratory and spent the rest of his career working on the health effects of radiation.

Lost entirely in the contretemps were the dietary implications of Gofman’s research. “While it is true that, for certain individuals, the amount of dietary fat is an important factor,” Gofman explained, “it turns out that there are other more significant factors that need to be considered. Human metabolism is so regulated that factors other than the actual dietary intake of one of these constituents may determine the amount of that constituent that wil circulate in the bloodstream. Indeed, important observations have been made which indicate that certain substances in the diet that are not fatty at al may stil have the effect of increasing the concentration of the fat-bearing lipoprotein substances in the blood.”

Though Gofman’s studies had demonstrated that the amount of LDL in the blood can indeed be elevated by the consumption of saturated fats, it was carbohydrates, he reported, that elevated VLDL—containing some cholesterol and most of the triglycerides in the blood—and only by restricting carbohydrates could VLDL be lowered.

This fact was absolutely critical to the dietary prevention of heart disease, Gofman said. If a physician put a patient with high cholesterol on a low-fat diet, that might lower the patient’s LDL, but it would raise VLDL. If LDL was abnormal y elevated, then this low-fat diet might help, but what Gofman cal ed the “carbohydrate factor” in these low-fat diets might raise VLDL so much that the diet would do more harm than good. Indeed, in Gofman’s experience, when LDL decreased, VLDL tended to rise disproportionately. And if VLDL was abnormal y elevated to begin with, then prescribing a low-fat, high-carbohydrate diet would certainly increase the patient’s risk of heart disease.

This was why Gofman described the measurement of total cholesterol as a “false and highly dangerous guide” to the effect of diet on heart disease.

Total-cholesterol measurements tel us nothing about the status of VLDL and LDL. Prescribing low-fat diets indiscriminately to anyone whose cholesterol appears to be elevated, or bombarding us with “generalizations such as ‘we al eat too much fat,’ or ‘we al eat too much animal fat,’” would increase heart-disease risk for a large proportion of the population. “Neglect of [the carbohydrate] factor can lead to rather serious consequences,” wrote Gofman in 1958, “first, in the failure to correct the diet in some individuals who are very sensitive to the carbohydrate action; and second, by al owing certain individuals sensitive to the carbohydrate action to take too much carbohydrate as a replacement for some of their animal fats.”

By 1955, Pete Ahrens at Rockefel er University had come to this same conclusion, although Ahrens was specifical y studying triglycerides, rather than the VLDL particles that carry the triglycerides. Ahrens was considered by many investigators to be the single best scientist in the field of lipid metabolism. He had observed how the triglycerides of some patients shoot up on low-fat diets and fal on high-fat diets. This led Ahrens to describe a phenomenon that he called carbohydrate-induced lipemia (an excessive concentration of fat in the blood). When he gave lectures, Ahrens would show photos of two test tubes of blood serum obtained from the same patient—one when the patient was eating a high-carbohydrate diet and one on a high-fat diet. One test tube would be milky white, indicating the lipemia. The other would be absolutely clear. The surprising thing, Ahrens would explain, was “that the lipemic plasma was obtained during the high-carbohydrate period, and the clear plasma during the high-fat regimen.” (Joslin had reported the same phenomenon in diabetics thirty years earlier. “The percent of fat” in the blood, he wrote, “rises with the severity of the disease…and is especial y related to the quantity of carbohydrate, which is being oxidized, rather than with the fat administered.”)