Three large dietary trials in the late 60s and early 70s were used to substantiate the central claims of the diet-heart hypothesis, specifically that dietary saturated fat and cholesterol increase blood cholesterol and heart disease risk. These trials, however, each had flaws in their design, outcomes, or interpretation that undermine their use in support of this conclusion.
A 1965 trial randomized 80 patients with heart disease to one of three groups: a control group that maintained a usual diet or one of two groups that took a dietary supplement of corn or olive oil for 24 months. Dropout rates were high in the treatment group, largely because many patients complained of distaste, nausea, and diarrhea. The control group and the olive oil group showed no change in dietary cholesterol, while the corn oil group showed a significant decrease; however, both the corn and olive oil groups showed no significant increase in heart disease incidence (Table V). The authors concluded, “Under the circumstances of this trial corn oil cannot be recommended as a treatment of ischaemic heart disease. It is most unlikely to be beneficial, and it is possibly harmful.”
The Dayton Trial (also known as the L.A. Veterans Trial) of 1969 looked at the impact of a cholesterol-lowering intervention among male veterans. The trial randomized 846 volunteers to a control or dietary treatment group. All subjects resided in the Los Angeles domicile and were closely monitored throughout the study. Subjects received either the standard institutional diet, which contained ~40% of calories as fat (mostly animal fat), or a control diet in which all saturated fat was replaced with soybean oil and other unsaturated fats (such as “filled milk,” which is skim milk with soybean oil added to give it equivalent fat content to whole milk). Dietary cholesterol was also reduced in the treatment group. The experimental diet led to a significant reduction in blood cholesterol levels (12.7%) but had no impact on the primary endpoint of total myocardial infarction and sudden death, nor on total mortality.
The Finnish Mental Hospital Trial was carried out in two institutions near Helsinki between 1959 and 1971. In one hospital, all dietary saturated fats were replaced by vegetable oils (primarily soybean oil), like in the Dayton Trial. At the 6-year mark, the interventions were swapped, with each hospital switching from control to treatment diet or vice versa. Averaging across the two periods, the dietary intervention led to an average 41.4 mg/dL decrease in serum cholesterol levels. The treatment diet was associated with a reduced number of major and intermediate coronary events (not coronary deaths, but these results are complicated by low event rates, with only 34 and 38 coronary events observed, respectively, at each hospital across both trial periods combined), different psychotropic drug-use patterns between the normal and treatment groups, and high dropout rates, with only 53% of subjects present in both the treatment and control study periods.
Taken together, alongside the results of MRFIT, these trials suggest dietary substitution of unsaturated fats for saturated fat has at most a limited impact on mortality.