Down-regulation of the low-density lipoprotein receptor by dietary cholesterol

To determine the effect of dietary cholesterol on the low-density lipoprotein (LDL) receptor of circulating mononuclear cells, nine adults (six men, three women) consumed a natural diet consisting of 45% of the calories as carbohydrate, 40% as fat, and 15% as protein, polyunsaturated/saturated fatty acid ratio 0.80 to 0.84, and either 137 +/- 25 mg cholesterol per day (low cholesterol phase) or 1034 +/- 25 mg cholesterol per day (high cholesterol phase). The study lasted 2 months with 1 month in each phase and used a cross-over design. The levels of plasma triglyceride, plasma cholesterol, very low-density and high-density lipoprotein cholesterol, and apolipoproteins B, A-I, and A-II were similar in the two diet phases. The high cholesterol diet was associated with an 11 +/- 9% increase (p less than 0.02) in LDL cholesterol level and a 41 +/- 14% decrease in LDL receptor activity (p less than 0.05, n = 6). The percentage decrease in LDL receptor activity correlated with the percentage increase in LDL cholesterol (r = -0.796, p = 0.06, n = 6). Thus, high levels of dietary cholesterol can down-regulate the LDL receptor in humans.