Dietary protein, cholesterol and atherosclerosis: a review of the early history

The first purely nutritional investigation into experimental atherosclerosis was carried out by Ignatowski in 1908. Believing that a toxic metabolite of animal protein led to atherosclerosis, he fed meat to adult rabbits and milk and egg yolk to weanling rabbits and caused atherosclerosis. For the next two decades experimental efforts from many laboratories were directed at determining which, if any, animal protein was the most atherogenic. The discovery in 1912 that dietary cholesterol per se was atherogenic turned attention to fat and cholesterol, eclipsing work on dietary protein. In 1926 Clarkson and Newburgh showed that the amount of cholesterol present in the animal protein they fed was insufficient to be atherogenic, demonstrating that some factor other than lipid determined atherogenicity. In 1940 Meeker and Kesten showed that animal protein (casein) was more atherogenic that plant protein (soy). Carroll and his co-workers showed that most proteins of animal origin were more cholesterolemic for rabbits than were proteins of vegetable origin, although there was some overlap. Cholesterol turnover is slower and fecal excretion of cholesterol is reduced in rabbits fed casein as opposed to those fed soy protein. The mechanisms underlying this effect are moot.