Is high cholesterol a cause of coronary heart disease?

Part 1: The diet-heart hypothesis

Cholesterol is the compound most blamed for coronary heart disease. However, the rationale behind this hypothesis is very shaky indeed.

The underlying condition in heart disease is the narrowing or hardening of the arteries which transport blood away from the heart to various organs in the body. This transportation ensures that oxygen and nutrients are delivered to all areas of the body. The process by which arteries become narrow or hardened due to a build-up of material in their walls is referred to as atherosclerosis. This greatly inhibits circulation, and as the heart muscle is supplied in this way, a heart attack occurs when there is insufficient oxygen reaching the heart muscle.

Coronary heart disease was so rare before 1920 that most doctors had never seen a case, even if they had heard of it. During the next three decades all that changed as the death toll from coronary heart disease, originally called angina pectoris, which means 'pain in the chest', rose dramatically. By the 1940s it had become a major cause of premature death.

As there are no symptoms associated with the partial blockage of the coronary arteries, how could they tell, without a direct examination of those arteries, who was in danger? They had to find what was different in those with the disease and those free of it.

Rabbit studies

In 1913 a Russian physiologist named Anitschkow conducted a cholesterol experiment on rabbits that was to change the history of atherosclerosis for most of the following century.[1] The experiment consisted of feeding huge doses of cholesterol to rabbits, a vegetarian animal which would never normally eat food that contains cholesterol and whose liver is not equipped to excrete the excess cholesterol. Not surprisingly, the rabbits' cholesterol shot up to very high levels and the concentrations proved toxic; some atherosclerosis of the blood vessels was discovered at autopsy.

Anitschkow was no fool; he realised that this experiment had no practical significance for humans. Similar experiments on dogs, rats and humans showed that the rises of blood cholesterol and atherosclerosis didn't happen in them. This is because cholesterol is a natural part of their diets and their livers are equipped to cope with any excess.

In 1950, team led by Dr John Gofman, again hypothesised that blood cholesterol was to blame.[2] Quickly, trials were conducted on rabbits based on Anitschkow's 1913 study and rabbits fed a high-cholesterol diet again developed blockages in their arteries. Several scientists pointed out that the results were more likely to be an allergic reaction to the unnatural diet. One such, Ancel Keys, pointed out the error of the approach when he wrote in 1956:

'For many years there was argument as to whether cholesterol in the diet promotes atherosclerosis in man. One cause of the disagreement resided in the persistent error in attributing to man the same responses seen in rabbits and chicks fed large amounts of cholesterol. . . . It is now clear that dietary cholesterol per se, which is contained in almost all foods of animal origin, has little or no effect on the serum cholesterol concentration in man'.[3] (emphasis added)


1. Anitschkow N. On variations in the rabbit aorta in experimental cholesterol feeding. Beitr Path Anat u allgem Path 1913; 56: 379.
2. Gofman JW, Lindgren F, Elliot H, et al. The role of lipids and lipoproteins in atherosclerosis. Science 1950; 111: 166-171, 186.
3. Keys A. The Diet and The Development of Coronary Heart Disease. J Chron Dis 1956; 4: 364-380.

Part 1: Diet-heart hypothesis | Part 2: Cholesterol? No! | Part 3: Early work confirmed | Part 4: Dietary cholesterol

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Last updated: December 9, 2011