A RATIONALE FOR PLASMA-CHOLESTEROL MODULATION BY DIETARY FATTY-ACIDS - MODELING THE HUMAN RESPONSE IN ANIMALS

At low levels of dietary cholesterol intake (<200 mg/day human equivalent), the plasma cholesterol response in different species (man and animals) is governed by two key dietary fatty acids: myristic acid (14:0) and linoleic acid (18:2). Thus, in human subjects and animals with presumably normal lipoprotein metabolism, 14:0-rich fats routinely raise the plasma cholesterol in a linear relationship, whereas 18:2-rich fats lower it in a curvilinear fashion, i.e., there is a ''threshold'' intake of 18:2 above which a further decline in plasma cholesterol is less pronounced. Palmitic (16:0) and oleic (18:1) acids appear to be neutral under these circumstances. In situations involving impaired lipoprotein metabolism (e.g., diminished low density lipoprotein [LDL] receptor activity), or in the presence of high levels of dietary cholesterol (probably >500 mg/day), the plasma cholesterol response is no longer described accurately by dietary 14:0 and 18:2 alone. In such situations 16:0 appears to contribute to plasma cholesterol elevation. The hypercholesterolemic potential of 16:0, possibly reflecting a synergism between dietary cholesterol and 16:0, is thought to reside, in part, in the ability of 16:0 to increase the transport of very low density lipoprotein (VLDL) apoB. Increased production of VLDL, coupled with impaired LDL receptor activity, results in an expansion of the LDL pool when the ability to clear VLDL remnants is impaired, Evidence is also available to suggest that the position of saturated fatty acids on the TG molecule affects its hypercholesterolemic ability. An argument is made for selecting animal models for investigation of the fat saturation effect based initially on the total plasma cholesterol (TC) response, with subsequent emphasis being placed on lipoproteins and the actual control mechanism(s) once the generic similarity in the TC response with that in humans has been established.