Good Calories, Bad Calories (18 page)

This was compounded by what may have been the single most striking result in the history of the cholesterol controversy, although it passed without comment by the authorities: those Framingham residents whose cholesterol declined over the first fourteen years of observation were more likely to die prematurely than those whose cholesterol remained the same or increased. They died of cardiovascular disease more frequently as wel . The Framingham investigators rejected the possibility that the drop in cholesterol itself was diet-related—the result of individuals’ fol owing AHA recommendations and eating low-fat diets. Instead, they described it as a “spontaneous fal ,” and insisted that it must be caused by other diseases that eventual y led to death, but they offered no evidence to support that claim.

The association between low cholesterol and higher mortality prompted administrators at the National Heart, Lung, and Blood Institute once again to host a workshop and discuss it. Researchers from nineteen studies around the world met in Bethesda, Maryland, in 1990 to report their results. The data were completely consistent (see charts on fol owing page): when investigators tracked al deaths, not just heart-disease deaths, it was clear that men with cholesterol levels above 240 mg/dl tended to die prematurely because of their increased risk of heart disease. Those whose cholesterol was below 160

mg/dl tended to die prematurely with an increased risk of cancer, respiratory and digestive diseases, and trauma. As for women, if anything, the higher their cholesterol, the longer they lived.*25

The proponents of Keys’s hypothesis said the results could not be meaningful. The excess deaths at low cholesterol levels had to be due to pre-existing conditions; chronic il ness leads to low cholesterol, they concluded, not vice versa, and then the individuals die from the il nesses, which confuses the mortality issue. This was the assumption the Framingham researchers had made. At the one end of the population distribution of cholesterol, low cholesterol is the effect and disease is the cause. At the other end of the distribution, high cholesterol is the cause and disease is the effect. This, of course, is a distinction based purely on assumptions rather than actual evidence, and one consistent with the universal recommendations to lower cholesterol by diet. When NIH Administrator Basil Rifkind offered this interpretation during my interview with him in 1999, he pointed to the report of the 1990 conference as the definitive document in support of it. But the report, which Rifkind co-authored, states unequivocal y that this interpretation was not supported by the available evidence.

The relationship between blood cholesterol (horizontal axes) and all deaths (total mortality) or just heart disease deaths, as reported in a 1990

NIH conference.

In an alternate interpretation, both ends of the cholesterol distribution are treated identical y. Whether high or low, either our cholesterol levels directly increase mortality or they’re a symptom of an underlying disorder that itself increases our risk of disease and death. In both cases, diet leads to disease, although whether it does so directly, via its effect on cholesterol, or through other mechanisms would stil be an open question. In this interpretation, what a cholesterol-lowering diet does to cholesterol levels, and what that in turn does to arteries, may be only one component of the diet’s effect on health. So lowering cholesterol by diet might help prevent heart disease for some individuals, but it might also raise susceptibility to other conditions—such as stroke and cancer—or even cause them. This is what had always worried those investigators who were skeptical of Keys’s hypothesis. “Questions should be pursued about biological mechanisms that might help explain low [total cholesterol]: disease associations,” noted the report from the 1990 NHLBI workshop. Nonetheless, public-health recommendations to eat low-fat diets and lower cholesterol would remain inviolate and unconditional.

In 1964, when the physicist Richard Feynman presented what would become a renowned series of lectures at Cornel University, he observed that it was a natural condition of scientists to be biased or prejudiced toward their beliefs. That bias, Feynman said, would ultimately make no difference, “because if your bias is wrong a perpetual accumulation of experiments wil perpetual y annoy you until they cannot be disregarded any longer.” They could be disregarded, he said, only if “you are absolutely sure ahead of time” what the answer must be.

In the case of Keys’s hypothesis, the annoying evidence was consistently disregarded from the beginning. Because the totality of evidence was defined as only those data that confirmed the hypothesis, Keys’s hypothesis would always appear monolithic. Annoying observations could not force a reanalysis of the underlying assumptions, because each of those observations would be discarded immediately as being inconsistent with the totality of the evidence. This was a self-fulfil ing phenomenon. It was unlikely, however, to lead to reliable knowledge about either the cause of heart disease or the routes to prevention. It did not mean the hypothesis was false, but its truth could never be established, either.

One other method can be employed to judge the validity of the hypotheses that dietary fat or saturated fat causes heart disease, and that cholesterol-lowering diets prevent it. This is a technique known as meta-analysis, viewed as a kind of last epidemiological resort in these kinds of medical and public-health controversies: if the existing studies give ambiguous results, the true size of a benefit or harm may be assessed by pooling the data from al the studies in such a way as to gain what’s known as statistical power. Meta-analysis is controversial in its own right. Investigators can choose, for instance, which studies to include in their meta-analysis, either consciously or subconsciously, based on which ones are most likely to give them the desired result.

For this reason, a col aboration of seventy-seven scientists from eleven countries founded the Cochrane Col aboration in 1993. The founders, led by Iain Chalmers of Oxford University, believed that meta-analyses could be so easily biased by researchers’ prejudices that they needed a standardized methodology to minimize the influence of such prejudice, and they needed a venue that would al ow for the publication of impartial reviews. The Cochrane Col aboration methodology makes it effectively impossible for researchers to influence a meta-analysis by the criteria they use to include or exclude studies. Cochrane Col aboration reviews must include al studies that fit a prespecified set of criteria, and they must exclude al that don’t.

In 2001, the Cochrane Col aboration published a review of “reduced or modified dietary fat for preventing cardiovascular disease.” The authors combed the literature for al possibly relevant studies and identified twenty-seven that were performed with sufficient controls and rigor to be considered meaningful.*26 These trials encompassed some ten thousand subjects fol owed for an average of three years each. The review concluded that the diets, whether low-fat or cholesterol-lowering, had no effect on longevity and not even a “significant effect on cardiovascular events.” There was only a

“suggestion” of benefit from the trials lasting more than two years. In 2006, the Cochrane Col aboration published a review of multiple-risk-factor interventions—including lowering blood pressure and cholesterol—for the prevention of coronary heart disease. In this case, thirty-nine trials were identified of which ten (comprising over nine-hundred thousand patient years of observation) included sufficient data and were carried out with sufficient rigor to draw meaningful inferences. “The pooled effects suggest multiple risk factor intervention has no effect on mortality,” the authors concluded.

Although, once again, a “smal ” benefit of treatment, perhaps “a 10 percent reduction in CHD mortality,” may have been missed, they added.

If we believe in Rose’s philosophy of preventive medicine, this suggestion of benefit or the possibility that even a “smal ” benefit was missed stil constitutes sufficient motivation to advocate cholesterol-lowering diets to the entire population, as indeed the authors of the first Cochrane review suggested. We could also assume that if a suggestion of a benefit can be induced after two years on such a diet, we might do considerably better after ten or twenty years, although we would stil need trials to test that assumption.

We might also compare this conclusion to the original predictions of Keys’s hypothesis in the mid-1950s. When Keys first suggested that eating fat caused heart disease, as we discussed, he did so partly on the basis of the experience in wartime Europe, where food shortages of a few years’ duration coincided with dramatic decreases in the incidence of heart disease. Keys had attributed those decreases to the reduced availability of meat, eggs, and dairy products. Other investigators pointed out that the war changed many other aspects of diet and lifestyle. Mortality from infectious diseases, diabetes, tuberculosis, and cancer al dropped during the war. Stil , to Keys it was the fat, particularly saturated fat, that was crucial. “A major lesson gained from World War I ,” he wrote in 1975, “is the proof that in a very few years the incidence of CHD [coronary heart disease] could drop to a level of the order of one-fourth the preceding rate.” If this were indeed possible, or even vaguely possible based on the col ective European experience during World War I , as the evidence indeed suggested, then something considerably more profound had been happening than was reflected in only the “suggestion” of a reduction in mortality seen in the clinical trials of cholesterol-lowering diets. Other factors of diet or lifestyle that had changed during wartime must have played far more significant roles in improving the health of the populations.

THE CARBOHYDRATE HYPOTHESIS

The world is gradual y going carbohydrate. That is because there are more people than there have ever been before (one would like to add “or ever wil be again”) so there must be more food. You can get about eight times as many calories from an acre of corn as you can from the flesh of pigs fed on this same corn. Because of population pressure, certain sections of the world are progressively using more of the vegetable and less of animal materials. This means that the carbohydrates, from sugar and cereals particularly, are increasing steadily in quantity. One does not need to view this with alarm, but it is not amiss to point out that this tendency is not the best road to health. Not that starches and sugars are harmful, but they are low in the essentials we must have for good health. If the proportion of carbohydrates is high then the amount of something else of greater importance is low. Nutrition is a six-way teeter-totter. Have you ever tried to balance such a device?

C. C. FURNAS AND S. M. FURNAS, Man, Bread & Destiny: The Story of Man and his Food, 1937

DISEASES OF CIVILIZATION

The potato took 200–250 years, in spite of organized encouragement, to become accepted in England. It took only fifty years in Ireland. Maize and cassava have come to be accepted in parts of Africa in considerably less time…. Tea, white bread, rice and soft drinks have entered many African dietaries in even shorter time and the extent to which they have spread and their consequences to nutrition have been rather severe.

F. T. SAI, Food and Agricultural Organization regional nutrition officer for Africa, 1967

ON APRIL 16, 1913, ALBERT SCHWEITZER arrived at Lambaréné, a smal vilage in the interior lowlands of West Africa, to establish a missionary hospital on the banks of the Ogowe River. Attended by his wife, Hélène, who had trained as a nurse, he began treating patients the very next morning. Schweitzer estimated that he saw almost two thousand patients in the first nine months, and then averaged thirty to forty a day and three operations a week for the better part of four decades. The chief complaints, at least in the beginning, were endemic diseases and infections: malaria, sleeping sickness, leprosy, elephantiasis, tropical dysentery, and scabies.

Forty-one years after Schweitzer’s arrival, and a year and a half after he received the Nobel Peace Prize for his missionary work, Schweitzer encountered his first case of appendicitis among the African natives. Appendicitis was not the only Western disease to which the natives seemed to be resistant. “On my arrival in Gabon,” he wrote, “I was astonished to encounter no cases of cancer…. I can not, of course, say positively that there was no cancer at al , but, like other frontier doctors, I can only say that if any cases existed they must have been quite rare.” In the decades that fol owed, he witnessed a steady increase in cancer victims. “My observations inclined me to attribute this to the fact that the natives were living more and more after the manner of the whites.”

As Schweitzer had suggested, his experience was not uncommon for the era. In 1902, Samuel Hutton, a University of Manchester–trained physician, began treating patients at a Moravian mission in the town of Nain, on the northern coast of Labrador, or about as far from the jungles of West Africa as can be imagined, in both climate and the nature of the indigenous population. As Hutton told it, his Eskimo patients fel into two categories: There were those who lived isolated from European settlements and ate a traditional Eskimo diet. “The Eskimo is a meat eater,” he wrote, “the vegetable part of his diet is a meager one.” Then there were those Eskimos living in Nain or near other European settlers who had taken to consuming a “settler’s dietary,”

consisting primarily of “tea, bread, ship’s biscuits, molasses, and salt fish or pork.” Among the former, European diseases were uncommon or remarkably rare. “The most striking is cancer,” noted Hutton on the basis of his eleven years in Labrador. “I have not seen or heard of a case of malignant growth in an Eskimo.” He also observed no asthma and, like Schweitzer, no appendicitis, with the sole exception of a young Eskimo who had been “living on a ‘settler’

dietary.” Hutton observed that the Eskimos who had adopted the settlers’ diet tended to suffer more from scurvy, were “less robust,” and endured “fatigue less easily, and their children are puny and feeble.”