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January 1, 1956

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Yerushalmy and Hilleboe refute use of epidemiology for Keys Diet-Heart Hypothesis





Fat in the diet and mortality from heart disease; a methodologic note


Important Text:

The next year an article by Yerushalmy and Hilleboe appeared in what was a direct, and for Keys, painful sequel to the Geneva meeting. We learn from their footnote that: “The authors became interested in this question (diet vs. national mortality data) during a meeting of a WHO study group on atherosclerosis and ischemic heart disease in Geneva, Switzerland, November 1955. At that meeting statements were made about the association between heart disease and mortality and fat in the diet. As it later developed, these were based on a few selected countries and were of questionable validity. On their return to the United States, the authors reviewed the available data carefully, and the results indicated that the subject required further study.”

I recall well the reaction in Minnesota and in epidemiological circles to this article and the challenge it represented for proponents of the diet-heart idea. The article seemed to magnetize the pre-existing polar elements of the scientific community: the lines of force were drawn. Meanwhile, proponents were already reviewing data from several North American cohort studies showing the short-term predictive relationship of serum cholesterol level in health to risk of subsequent coronary events. Moreover, several investigators were involved in feeding experiments of the effects of fatty acid composition of diet on serum cholesterol level. Keys, meanwhile, had made new comparisons of diet and blood lipids among casual samples of men in South Africa and Japan, to test the relation in contrasting populations.

The tone of the Yerushalmy-Hilleboe “methodologic note” was authoritative, pedantic, and patronizing, beginning with: “The evidence which has been presented for the existence of a relationship between diet and heart disease, however, is, for the most part, derived from indirect methods of study. In these indirect methods the primary unit of observation is the group; in the direct method the primary unit of observation is the individual. . . .It is well known that the indirect method merely suggests that there is an association between the characteristics studied and mortality rates and, further, that no matter how plausible such an association may appear, it is not in itself proof of a cause-effect relationship.”

The authors go on to editorialize and scold the naïve: “The quotation and repetition of the suggestive association soon creates the impression that the relationship is truly valid, and ultimately it acquires status as a supporting link in a chain of presumed proof.” After admitting, however, that such an indirect method of study may be valuable, they again wax pedantic: “unfortunately, however, if you superficially accept and do not properly augment it, the indirect method has many weaknesses. The most serious is the fact that the apparent association often proves to be the result of non-pertinent extraneous factors. Therefore, it is always necessary to probe further, to go beyond the simple, apparent association and to investigate related variables.”

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Diet-Heart Hypothesis
The diet-heart hypothesis, also known as the lipid hypothesis, proposes that there is a direct relationship between dietary fat intake, particularly saturated fat and cholesterol, and the development of heart disease. It suggests that consuming high amounts of these fats leads to an increase in blood cholesterol levels, specifically low-density lipoprotein (LDL) cholesterol, which in turn contributes to the formation of atherosclerotic plaques in the arteries. Some consider this hypothesis nothing more than wishful thinking.
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