New research muddies cholesterol debate
a wholesome diet for Americans last summer and said, among other things, that there was "no basis for recommending that healthy adults The question of whether lowering decrease dietary cholesterol" (C&EN, cholesterol or saturated fat levels in June 9,1980, page 22). the diet really will improve health sits If opinion was divided then, it may at the middle of a controversy that is be even more so now. Since Hegsted's growing more intense. talk, results of two large-scale studies As recently as the beginning of this of the effects of cholesterol on human month, D. Mark Hegsted, adminis- health have been published, and they trator of the U.S. Department of Ag- come out on opposite sides of the riculture's Office of Human Nutrition cholesterol question, albeit in relation and a proponent of lowering the levels to different diseases. One study links of cholesterol in the diet, told scien- high consumption of cholesterol with tists at the annual meeting of the increased risk of early heart attack in American Association for the Ad- men, and the other finds, again in vancement of Science in Toronto that men, that high levels of serum choof all the recommendations on diet lesterol seem to reduce the risk of that USDA and other federal agencies certain forms of cancer. have made in the past year or so, the The first study, conducted by a recommendation to eat less saturated team of researchers under the direcfat and cholesterol has the strongest tion of Richard B. Shekelle of the scientific base. department of preventive medicine, Even as Hegsted made his remarks, Rush-Presbyterian-St. Luke's Medthere were prominent voices in the ical Center, Chicago, examined the nutrition community that would have diet and serum cholesterol levels of disagreed. Notable among these is. the 1900 middle-aged men in 1957 and National Research Council's Food & again in 1958 who worked in Western Nutrition Board. This group pub- Electric Co.'s Hawthorne Works near lished its own recommendations for Chicago [New Engl. J. Med., 304,65
Higher serum cholesterol lowers cancer risk for men Serum cholesterol level (mg/100 ml) 126-189
18-year Incidence of colon cancer
18-year Incidence of cancer other than colon
4.6%
13.4%
190-219 1.7 10.5 220-249 1.3 9.8 250-279 1.5 9.2 280-545 0.4 7.2 Note: Data are age-adjusted for men aged 35 to 69 years. The populations at risk vary from 242 for the lowest serum cholesterol level to 570 for the median serum cholesterol level.
(1981)]. The researchers now have gone back to see what happened to these men in the following 20 years. Theyfindthat the risk of death from coronary heart disease is greatest in those men with the highest levels of serum cholesterol and least in those with the lowest levels. Further, the amount of cholesterol in these men's diets was also positively related to their risk of coronary heart disease. The amount of polyunsaturated fatty acids in the diet was inversely related to heart attack risk in the study. These associations, though con-
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sidered statistically significant, are not very large, the researchers point out—a fact that has been true in earlier epidemiological studies of the effect of diet on heart disease. Indeed, this is one of the reasons that the Food & Nutrition Board and others have not put great weight on such studies. However, the authors of the present study say that the correlation persists even when the effects of other factors that may affect the risk of heart disease, such as age, body size, blood pressure, cigarette smoking, and alcohol consumption, are taken into account. "If viewed in isolation, the conclusions that can be drawn from a single epidemiologic study are limited," the study's authors say. "However, the present observations support the conclusions that the lipid composition of the diet affects the level of serum cholesterol and the long-term risk of death from coronary heart disease in middle-aged American men." The second study, conducted by researchers at the National Institutes of Health, Bethesda, Md., and at Boston University Medical Center, examines the fate of 5209 people first
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studied in Framingham, Mass., in 1948 who have been examined regularly at two-year intervals since then [J. Am. Med. Assoc, 245,247 (1981)]. The study was undertaken to examine factors that might be related to heart disease, such as serum cholesterol levels. It is, in fact, one of the studies that Hegsted and others cite when they call for lowering cholesterol and saturated fat consumption. Now the Framingham data have been re-examined to see what they show about cancer rates. The researchers find colon cancer in men with the lowest levels of serum cholesterol (less than 190 mg per 100 ml) is about three times as likely as for men with higher levels. The incidence of cancers other than that of the colon in men also decreases with increasing cholesterol level. There are no clearcut effects in women. The researchers also checked a list of factors such as cigarette smoking, alcohol consumption, education, and age that have been shown in previous studies to be linked with cancer risk. The results in this study generally agree with those of earlier studies for these factors except that the Framingham study found the incidence of colon cancer in men who smoked more than one pack of cigarettes a day to be four times less than for nonsmokers. What these new findings mean about serum cholesterol's relationship to cancers of the colon and other organs in men is difficult to guess. One possibility, which researchers themselves suggest, is that competing lethal diseases, such as heart disease, decrease the incidence of cancer in men with high serum cholesterol. In other words, these men may die too early from some other diseases to develop cancer. Similarly, increased risk of lung cancer and other lethal diseases among cigarette smokers may be the reason they develop less colon cancer than nonsmokers. There have been a few studies before the Framingham one that found low cholesterol levels in cancer patients or more cancer in special groups on controlled diets that were low in cholesterol. These findings, however, are directly opposite to most of the studies based on incidence of disease in different countries. These studies generally find that countries that have a high incidence of heart disease also have high levels of many forms of cancer, particularly colon and breast cancer. The suggestion has been made that a diet in which a high portion of total calories comes from
fats may be responsible for both of these trends. However, as the Framingham researchers point out, the highly developed countries, which are the ones with high levels of both heart disease and cancer, have many factors in common other than a large amount of fat in their diets. Diets in these countries also contain relatively high levels of salt, sugar, and alcohol; a much larger percentage of the population is employed in manufacturing; stress factors are different; and cancer diagnosis is better. The National Cancer Institute points out that the current study is only one and that there seems to be more research showing an increase in coronary heart disease in people with high serum cholesterol levels than there is for decreased cancer risk in these people. This study alone is hardly reason for people who have been put on low-cholesterol diets to abandon them, NCI says, but it is a finding that bears following up. Hegsted has not been available for comment since the Framingham study was released. At the AAAS meeting, however, he summarized the research findings to that time on both heart disease and cancer and used them to support USDA's call to avoid eating too much fat, saturated fat, and cholesterol. "The most solid evidence relating dietary practice to the chronic diseases is available for coronary heart disease," Hegsted says, which currently is responsible for about 40% of deaths in the U.S. More than one third of these deaths occur in people younger than 65 and thus may be considered premature. "All of the evidence from animal experimentation, epidemiologic data, and clinical findings is consistent in showing that elevated serum cholesterol levels, specifically elevated levels of lowdensity lipoprotein, are associated with and almost certainly cause atherosclerosis; that heart attacks are extremely rare in individuals who have low levels of low-density lipoproteins and little atherosclerosis; that the risk of heart attacks is linearly related to serum cholesterol levels or nearly so; and that serum cholesterol and low-density lipoprotein levels are responsive to diet, especially to dietary fat and cholesterol intake," he says. Thus, "the average American has cholesterol levels which place him at some risk [of heart disease] and, therefore, he should be advised to develop more moderate dietary habits." Rebecca Rawls, Washington
