The other disconcerting aspect of these studies is that they suggested (with the notable exception of three Chicago studies reported by Jeremiah Stamler and colleagues) low cholesterol levels were associated with a higher risk of cancer. This link had originally been seen in Seymour Dayton’s VA Hospital trial in Los Angeles, and Dayton and others had suggested that polyunsaturated fats used to lower cholesterol might be the culprits. This was confirmed in 1972 by Swiss Red Cross researchers. In 1974, the principal investigators of six ongoing population studies—including Keys, Stamler, William Kannel of Framingham, and the British epidemiologist Geoffrey Rose—reported in The Lancet that the men who had developed colon cancer in their populations had “surprisingly” low levels of cholesterol, rather than the higher levels that they had initially expected. In 1978, a team of British, Hungarian, and Czech researchers reported similar findings from a sixteen-thousand-man clinical trial of a cholesterol-lowering drug. By 1980, this link between cancer and low cholesterol was appearing in study after study. The most consistent association was between colon cancer and low cholesterol in men. In the Framingham Study those men whose total cholesterol levels were below 190 mg/dl were more than three times as likely to get colon cancer as those men with cholesterol greater than 220; they were almost twice as likely to contract any kind of cancer than those with cholesterol over 280 mg/dl. This finding was met with “surprise and chagrin,” Manning Feinleib, a National Heart, Lung, and Blood Institute (NHLBI) epidemiologist, told Science.

This association was considered sufficiently troublesome that the NHLBI hosted three workshops between 1980 and 1982 to discuss it. In this case, however, the relevant administrators and investigators did not consider it sufficient to pay attention only to the positive evidence (that low cholesterol was associated with an increased risk of cancer even in clinical trials) and reject the negative evidence as irrelevant or erroneous, as they had when implicating high cholesteral as a cause of heart disease. Instead, they searched the literature and found a few studies—including a Norwegian study published a decade earlier in a Scandinavian journal supplement—that reported no link between low cholesterol and cancer. As a result, the NHLBI concluded that the evidence was inconsistent, only “suggestive” that “low cholesterol may be in some way associated with cancer risk,” said Robert Levy after the first workshop. After the second workshop, by which time the Framingham, Honolulu, and Puerto Rico studies had reported the same association, the NHLBI administrators still considered the results inconclusive: “The findings do not represent a public health challenge; however, they do present a scientific challenge,” they wrote. Levy did tell the journal Science that this low-cholesterol/cancer link might make those investigators who were arguing that everyone’s cholesterol should be as low as possible “a little more cautious.”