Brown and Goldstein, Nobel Laureates

Nobel Hype

You will note in the above description of the the work of Brown and Goldstein it is claimed that their “discovery of the mechanism by which cholesterol accumulates in the bloodstream, leading to a condition known as atherosclerosis, which is responsible for more than half the deaths in the United States by heart attack or stroke.”

In reality, the vast majority of patients with atherosclerosis in the general population do not have a deficiency of LDL receptors, their blood cholesterol is not markedly elevated and they do not have the clinical characteristics of those very rare patients with congenital LDL receptor abnormalities such as xanthomas. This is not to say that their discoveries do not have major scientific interest in terms of biochemical regulation, but their relation to common diseases is tenuous.

In contrast to the hype surrounding the Nobel Prize, here is what Brown and Goldstein said themselves in a review in Science.

“How does elevated plasma LDL produce the complex lesions of atherosclerosis, with their hallmark features of inflammation, necrosis, cellular proliferation, and lipid deposition? The answer may lie in the unsaturated fatty acids of the cholesteryl esters and phospholipids of which LDL is composed. One of these, arachidonic acid, is the precursor of inflammatory prostaglandins. Within the artery wall other unsaturated fatty acids of LDL can undergo oxidation to generate toxic aldehydes and epoxides that induce the production of inflammatory cytokines. Thus, although the principal job of LDL is to transport cholesterol, and although its metabolism is regulated in response to cellular demands for cholesterol, the pathological consequence of its accumulation may be traced to the localized deposition of its fatty acids at sites of damage in artery walls.”

In other words, according to Nobel Prize winners in cholesterol metabolism, atherosclerosis is not a disease of cholesterol metabolism and has nothing to do with cholesterol, per se, but a disease of fatty acid modification of the cholesterol package, LDL. Statins have no known effect on LDL modification, a crucial step in the development of plaque and, therefore, should not be expected to have a major effect on plaque development and indeed they don’t.

A xanthoma on the thumb of a patient with congenital LDL receptor deficiency.

Flat and tuberous xanthomas on buttocks of an 18 year old women with LDL receptor deficiency. Typically xanthomas appear at sites of pressure on the skin.

99.999% of patients with coronary atherosclerosis in the general population do not have the LDL receptor deficiency and do not have xanthomas. The discoveries of Brown and Goldstein are irrelevant to their disease.