#493: The Keys Equation – How Dietary Fats Impact Blood Cholesterol

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One of the most important and influential papers in nutrition science is one by Ancel Keys and his colleagues that was published in The Lancet in 1957. This seminal paper examined the relationship between dietary fat intake and serum cholesterol levels. The researchers investigated how different types of fats in the diet affected cholesterol levels in a series of their previous tightly-controlled dietary experiments..

Those studies involved feeding the participants various diets with different compositions of fats. The researchers analyzed the participants’ blood samples to measure changes in serum cholesterol levels in response to dietary changes.

The most important aspect of this paper is the presentation of the ‘Keys Equation’; a predictive equation for the impacts of saturated, monounsaturated, and polyunsaturated fats, and dietary cholesterol, on blood cholesterol levels.

Crucially, the Keys Equation identifies the importance of the ratio of polyunsaturated to saturated fats in the diet; known as the ‘P:S ratio’. It showed that the P:S ratio is the most important dietary factor impacting blood cholesterol levels. And specifically that saturated fats increase total and LDL cholesterol twice as much as polyunsaturated fats lower them.

The findings of this study were significant in highlighting the potential impact of dietary fat subtypes on serum cholesterol levels and heart disease risk. It contributed to the growing body of evidence supporting the hypothesis that high serum cholesterol levels, particularly due to a diet rich in saturated fats, were associated with an increased risk of cardiovascular diseases.

In this episode, as part of our new series taking an in-depth look at seminal nutrition studies, we go through this influential paper from Keys, Anderson and Grande.

Co-hosts for this Episode

Dr. Alan Flanagan has a PhD in nutrition from the University of Surrey, where his doctoral research focused on circadian rhythms, feeding, and chrononutrition.

This work was based on human intervention trials. He also has a Masters in Nutritional Medicine from the same institution.

Dr. Flanagan is a regular co-host of Sigma Nutrition Radio. He also produces written content for Sigma Nutrition, as part of his role as Research Communication Officer.

Danny Lennon has a master’s degree (MSc.) in Nutritional Sciences from University College Cork, and he is the founder of Sigma Nutrition.

Danny is currently a member of the Advisory Board of the Sports Nutrition Association, the global regulatory body responsible for the standardisation of best practice in the sports nutrition profession.


  • Early Work Leading to Lipid Hypothesis
  • Metabolic Ward Controlled Feeding Studies
  • Prediction of Serum Cholesterol Response to Fats in the Diet
  • Impact on Subsequent Research
  • P:S Ratio
  • Considering Dietary Cholesterol: Keys-Hegsted Equation
  • Impact of Monounsaturated Fat

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