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Countries Study also demonstrated strong associations between mean intakes of SFA and mean levels of serum total cholesterol [Keys, 1980]. The study prompted the ‘diet heart’ hypothesis that high intakes of SFA and cholesterol and low intakes of polyunsaturated fats (PUFA) increase the level of total cholesterol and ultimately result in the development of CHD. Indeed, the early results of the Seven Countries Study prompted an explosion of epidemiological, clinical, and basic research into the role of dietary fat in CHD. The results of dietary feeding trials (or ‘metabolic ward’ studies) which measured blood lipids in healthy volunteers after administration of controlled diets with varying intakes of fats were concordant with the findings of the associations observed between intakes of different fatty acids and changes in blood cholesterol levels observed in the ecological studies. In particular, Keys et al. [1965] and Hegsted et al. [1965] demonstrated that average change in serum cholesterol concentrations could be predicted as equations for the changes in intake of SFA and PUFA and dietary cholesterol. The concordance of the results of the ecological and the metabolic ward studies probably relate to the limited amount of measurement error in both study designs. In view of these findings, some investigators have concluded that use of cholesterol as an intermediary factor is the most rational way of studying the associations between dietary fat and CHD, Introduction

Dietary Fat and Coronary Heart Disease: Summary of Evidence from Prospective Cohort and Randomised Controlled Trials