为了应对冠心病的流行，安塞尔·凯斯 (Ancel Keys) 于 1953 年提出了脂质心脏假说，该假说声称，摄入大量总脂肪、饱和脂肪和胆固醇会导致动脉粥样硬化，因此应减少摄入脂肪和胆固醇，并用饱和脂肪替代含有多不饱和脂肪，会降低血清胆固醇，从而降低患心脏病的风险。 Keys 提出了一个方程，可以根据饱和脂肪 (ΔS)、多不饱和脂肪 (ΔP) 和胆固醇 (ΔZ) 的消耗来预测血清胆固醇 (ΔChol.) 浓度：ΔChol。 = 1.2(2ΔS - ΔP) 1.5ΔZ。然而，Keys 方程将天然饱和脂肪和工业反式脂肪合并为一个参数，并仅将亚油酸视为多不饱和脂肪。这忽视了反式脂肪的广泛消费及其对血清胆固醇的影响，并促进了饮食中 omega-6 与 omega-3 脂肪酸的不平衡。许多观察性、流行病学、介入性和尸检研究均未能验证凯斯方程和脂质-心脏假说。然而，这些一直是国家和国际饮食指南的基石，这些指南过分关注心脏病，更不用说癌症和代谢紊乱了，自从采用这一假设以来，癌症和代谢紊乱的发病率一直在稳步增加。

In response to a perceived epidemic of coronary heart disease, Ancel Keys introduced the lipid-heart hypothesis in 1953 which asserted that high intakes of total fat, saturated fat, and cholesterol lead to atherosclerosis and that consuming less fat and cholesterol, and replacing saturated fat with polyunsaturated fat, would reduce serum cholesterol and consequently the risk of heart disease. Keys proposed an equation that would predict the concentration of serum cholesterol (ΔChol.) from the consumption of saturated fat (ΔS), polyunsaturated fat (ΔP), and cholesterol (ΔZ): ΔChol. = 1.2(2ΔS - ΔP) + 1.5ΔZ. However, the Keys equation conflated natural saturated fat and industrial trans-fat into a single parameter and considered only linoleic acid as the polyunsaturated fat. This ignored the widespread consumption of trans-fat and its effects on serum cholesterol and promoted an imbalance of omega-6 to omega-3 fatty acids in the diet. Numerous observational, epidemiological, interventional, and autopsy studies have failed to validate the Keys equation and the lipid-heart hypothesis. Nevertheless, these have been the cornerstone of national and international dietary guidelines which have focused disproportionately on heart disease and much less so on cancer and metabolic disorders, which have steadily increased since the adoption of this hypothesis.