Diet-Heart Hypothesis

MD Conf, May 1961: Margaret Albrink, Yale: Elevated Triglycerides (TG) - not cholesterol - were asso w/ increased risk of heart disease. Low-fat, high-carb diets raised TG. Albrink: Ancel Keys' supporters attacked me, "They were so angry," & the science bullies prevailed.

The occasional occurrence of lactescent or milky serum in patients with certain diseases caused interest and speculation at least as long ago as 1799 when Mariet described turbid sera in some patients with diabetic acidosis (1). The lightscattering fat particles or chylomicrons causing lactescence are present in modest numbers after a fat meal but become scarce in normal postabsorptive sera. In certain pathological states, however, chylomicrons occur in excessive numbers, giving rise to a characteristic milky appearance of the sera. In a previous study, lactescence was reported to be directly proportional to the total triglyceride concentration in serum (2). Turbidity was invariably present when total triglyceride fatty acid concentration exceeded 20 mEq per L. As triglyceride concentration increased further, a progressively greater proportion of cholesterol and phospholipids also occurred in the particulate lipid fraction which could be readily removed by flotation of unaltered serum at moderate speeds in the ultracentrifuge. Serum lipids are now known to exist in a spectrum of lipoproteins of varying density, from very low density particulate chylomicrons composed chiefly of triglycerides, through various classes of low density lipoproteins relatively rich in cholesterol, to high density lipoproteins in which phospholipids are prominent (3). Interest in various classes of low density lipoproteins has been stimulated because of their possible role in the etiology of coronary arterial disease (4). Studies from this laboratory (5-7) have shown serum triglyceride concentration to be intimately associated with this disease. Antonis and Bersohn have also found elevation of serum triglycerides in ischemic heart disease (8). From the known composition of very low density lipoproteins, it might be inferred that their presence in abnormally high concentrations would be associated with increased concentration of total serum triglycerides. The present study was undertaken to learn whether total triglyceride concentration might determine not only the fraction of lipids present in chylomicrons but also the partition of lipids among the various low density lipoproteins. At the same time the lipoprotein composition of the relatively clear subnatant fluid after removal of the chylomicron "cream" layer of lactescent sera could be determined. This clear fraction was previously analyzed in toto (2), but no analysis of lipoproteins was made.

* Supported (in part) by Grant H-3498(C2) from the National Heart Institute, Bethesda, Md., and by a grant from The James Hudson Brown Memorial Fund. This work was done during tenure of an established investigatorship of the American Heart Association.

An early and celebrated trial was called the Anti-Coronary Club, launched by Norman Jolliffe, director of the New York City Health Department, in 1957. Jolliffe was a well-regarded authority in his day, the author of a popular diet book called Reduce and Stay Reduced on the Prudent Diet, which even President Eisenhower had used. Jolliffe had also read Keys’s work, and decided to test these ideas over a sustained period. He signed up eleven hundred men to his Anti-Coronary Club and instructed them to reduce their consumption of red meat, such as beef, lamb, or pork, to no more than four times a week (which would be considered a lot by today’s standards!) while consuming as much fish and poultry as they liked. Eggs and dairy were limited. The men also drank at least two tablespoons of polyunsaturated vegetable oil a day. Overall, the diet was about 30 percent fat, but the ratio of polyunsaturated fats (vegetable oils, mostly) to saturated fats was four times greater than what Americans regularly ate. Jolliffe also recruited a control group to eat normal American fare, with an estimated 40 percent fat, although he failed to record the diet of the controls.

“Diet Linked to Cut in Heart Attacks,” reported the New York Times in 1962, when the coronary trial results started to come out: they showed that men who stayed on the diet saw a drop in both cholesterol and blood pressure and lost weight. Their risk for heart disease appeared to be slamming into reverse, an outcome that looked like a reassuring condemnation of saturated fats. But then, a decade into the trial, investigators began to find “somewhat unusual” results: twenty-six members of the diet club had died during the trial, compared to only six men from the controls. Eight members of the club had died of heart attacks, but not one of the controls. In the discussion section of the final report, the authors (who no longer included Jolliffe, because he had died of a heart attack in 1961) emphasized the improved risk factors among the men in the diet club but ignored what those risk factors had blatantly failed to predict: their higher death rate. That result was buried in the study report. The authors avoided the very question that mattered most: Would someone live longer on a “prudent” diet? The answer from the Anti-Coronary Club was clearly no.

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The Anti-Coronary Club trial, despite its scientific weaknesses, became one of the foundational studies for the idea that a diet low in saturated fat will protect against heart disease.

The biggest attempt to create a truly blind trial, in which subjects would switch to a vegetable-oil-based diet without knowing it, was conducted by the National Heart, Lung, and Blood Institute with Jerry Stamler as one of the principal investigators. NHLBI was aware of the ongoing problems with the diet trials. It was clear that only an enormous, well-controlled clinical trial could definitively establish the link between saturated fat and heart disease. Such a trial would need to enroll a hundred thousand Americans in order to get statistically significant results and would need a follow-up period of forty-five years. To see if such a giant undertaking was even possible, NHLBI first conducted a feasibility study in 1962. This in itself was a giant effort involving multistep studies on nearly twelve hundred subjects in five different cities, including Baltimore, Boston, Chicago, the Minnesota Twin Cities, and Oakland, as well as a mental hospital in Minnesota.

Coincidentally, the oversight for these studies fell to those most invested in their outcome: Keys and Stamler. Stamler remembers walking the streets in New York City “all night long” with Keys, debating how they might set up the study so people could be “blinded” to the food they ate. Eventually, they came up with a solution that satisfied them:

the food company Swift & Co. would make custom margarines with varying levels of fatty acids that both groups would eat; butter would therefore be a non-issue. Even so, the undertaking remained daunting, because other special foods also had to be made for all diet groups, in order to assure that the taste, texture, and cooking experience for all participants would be the same. Hamburger patties and hot dogs were therefore made in two versions: one high in vegetable oil and one made with tallow or lard. Milk and cheese for the intervention group came “filled” with soybean oil. (No one could figure out how to make a simulacrum of an egg, however, so everyone just got two normal eggs a week.) “A housewife would order once a week from a special store that had been set up for the study and was sent the proper foods assigned to her group,” says Stamler. Neither the participants nor the study administrators knew who was getting which diet, in an attempt to “double-blind” the study, which was a milestone in diet-heart research. No one had ever managed to do this before, and according to various confirmation tests performed by the investigators, their methods were largely successful: “No one noticed who was getting which types of food! It was all done so well,” Stamler asserted.

In retrospect, it is perplexing why scientists did not question the assumption that entirely newfangled foodstuffs could restore a population to good health. How could it be that a healthy diet would depend upon these just-invented foods, such as milk “filled” with soybean oil?

It’s true that vegetable oils had been shown to lower total cholesterol successfully, and this effect held great appeal to a research community obsessed with cholesterol. Yet cholesterol-lowering was just one of the many effects of these oils on biological processes, not all of which seemed to be so beneficial. In fact, no human population had been documented surviving long-term on oils as a major source of fat until 1976, when researchers studied the Israelis, who at the time consumed “the highest reported” quantity of vegetable oils in the world. Their rates of heart disease turned out to be relatively high, however, contradicting the belief that vegetable oils were protective.

When I asked Stamler about the novelty of vegetable oils he said that he and Keys had been concerned about the absence of any historical record for human consumption of these oils, but that ultimately it wasn’t considered an impediment to promoting a “prudent” diet.

While Keys and others firmly believed that polyunsaturated oils would help prevent heart disease due to their cholesterol-lowering properties, it’s also true that the AHA received millions of dollars in support from the food companies that manufactured those oils. Remember that the AHA’s very launch as a nationally influential group in 1948 depended upon Procter & Gamble’s “Truth or Consequences” radio show. Campbell Moses, AHA medical director in the late 1960s, even posed with a bottle of Crisco Oil in an AHA educational film. And remarkably, when Jerry Stamler reissued his 1963 book, Your Heart Has Nine Lives, it was published as a “professional” red leather edition by the Corn Products Company and distributed free of charge to thousands of doctors. Inside, Stamler thanks both that company and the Wesson Fund for Medical Research for “significant” research support. “Scientists in public health must make alliances with industry,” he told me, unabashedly, when I asked him about the connection. “It’s tough.”

Stamler is correct; nutrition studies are expensive and funding sources limited (although less so in his day), and researchers have long solicited food companies to fill the financing gap. Yet one could reasonably argue that the connections forged by Stamler, Keys, and others in those early days had an exceptionally outsized influence on the course of the American diet. Replacing saturated fat with vegetable oils, after all, became the backbone of the “prudent diet,” which endures to the present day.

The Evidence against Saturated Fat: Epidemiological Studies

Of the vast quantities of imperfect data that were interpreted to support the diet-heart hypothesis, much came not from clinical trials but from large epidemiological undertakings, of the kind that Keys had pioneered with his Seven Countries study. These are studies where the diets of populations are not changed in any way: they are simply observed over time, and at the end, investigators try to link health outcomes such as disease and death back to their subjects’ dietary patterns. Researchers had done these kinds of studies earlier—on the Italians in Roseto, the Irish, the Indians, and others—but those efforts had all been much smaller. The new studies followed thousands of people over many years, and their results made a highly influential contribution to the growing body of scientific papers that were used by experts to support the diet-heart hypothesis.

Stamler inherited one of the earliest of these studies, involving two thousand men who worked at the Western Electric Company near Chicago. The men were medically evaluated and their diets measured from 1957 onward. In the paper’s abstract, which is often the only part of scientific papers that busy doctors and scientists ever read, Stamler wrote that his results supported cholesterol-lowering through diet. But the results, after twenty years of study, actually showed that diet affected blood cholesterol only a tiny bit and that the “amount of saturated fatty acids in the diet was not significantly associated with risk of death from CHD [coronary heart disease],” as the authors wrote. It seems clear that Stamler could not countenance such results. In the discussion section of the paper, he and his colleagues dismiss their own data outright and immediately move on to talk about other studies that did have the “correct” outcome.

When I asked Stamler about that, he said, “What we showed was that saturated fat had no independent effect on end points.”

“So, in the end, saturated fat in the diet didn’t matter, right?” I asked.

“It had no INDEPENDENT effect,” Stamler yelled, meaning that on its own, it didn’t matter. The Western Electric Study has nevertheless been regularly cited in support of the diet-heart hypothesis.

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Abstract

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"Since the Fall of 1957, a long-term study of coronary heart disease has been in progress at the Hawthornie Works of the Western Electric Company in Chicago under the auspices of the University of Illinois College of Medicine and Presbyterian-St. Luke 's Hospital. The study was unidertaken in the belief that coronary heart disease was a disease resulting from the interplay of multiple factors and that there was indeed to delineate these factors further. The data presented herein represent the initial compilation of data centering on this problem; a discriminiate functional analysis is to be undertaken next. The report which follows has been made possible through the efforts of a large group of physicians and other scientists who have volunteered their time in the project to permit the accumulation of a large body of data, a portion of which is presented below. Acknowledgment must also be made to the Western Electric Company, which has been most cooperative and helpful throughout, to its employees who have participated in the study, and to the agencies and donors partially recognized below* who have financed the survey since its inception."