How do polyunsaturated fatty acids lower plasma cholesterol levels?

Abstract

For 30 years it has been known that linoleic acid can lower elevated cholesterol levels. Large increases in linoleic acid have been widely recommended as a way of reducing the risk of cardiovascular disease. Such recommendations have resulted in major dietary shifts in some countries, including the USA. Yet the precise characteristics of the linoleic acid molecule which confer on it cholesterol-lowering properties are unknown. gamma-Linolenic acid, the first essential fatty acid metabolite of linoleic acid, has been found to have cholesterol-lowering actions ca. 170 times greater than the parent molecule, suggesting that linoleic acid must be converted to gamma-linolenic acid to exert its desirable effects on cholesterol metabolism. Aging, sex, diabetes mellitus, alcohol, catecholamines and trans fatty acids and saturated fats can all modulate the delta-6-desaturase enzyme which converts linoleic acid to gamma-linolenic acid. This provides a possible unifying explanation for the actions of these known risk factors for cardiovascular disease.