Influence of dietary fat, apolipoprotein E phenotype, and sex on plasma lipoprotein levels.

BACKGROUND The "Western" diet, sex, and apolipoprotein (Apo) E polymorphism have been implicated as codeterminants of lipid levels. METHODS AND RESULTS In a retrospective analysis, we evaluated the combined impact of dietary fat, sex, and Apo E phenotype on lipoprotein levels in 67 subjects fed two contrasting, metabolically controlled diets: one a "Western" diet, with a low polyunsaturated to saturated (P:S) fatty acid ratio and the other a "therapeutic" diet, with a high P:S ratio. The high P:S diet compared with P:S diet exerted a far stronger predictive influence on lipoprotein concentrations than Apo E phenotype, sex, or the latter two factors combined. Apo E phenotype alone was associated with a stepwise increase in low density lipoprotein cholesterol (LDL-C), such that 3/2 less than 3/3 less than 4/3 on either the low or the high P:S diets. On the low P:S diet only, sex was shown to be a significant predictor of high density lipoprotein cholesterol (HDL-C) levels, with women greater than men, and the associated LDL/HDL ratio with men greater than women. On the high P:S diet, women displayed a dramatic fall in HDL-C, effectively raising the LDL/HDL ratio to equivalency with men and obliterating the sex influence seen with the low P:S diet. Controlled for dietary fat, Apo E and sex exerted independent, additive effects on lipoprotein levels on the low P:S diet only. Only the Apo E phenotype remained predictive on the high P:S diet. CONCLUSIONS Women of the Apo E 3/2 phenotype stand to benefit the least from a high P:S diet because of reduction in the more "protective" HDL-C, whereas men of the 4/3 phenotype showed the greatest improvement in the LDL/HDL ratio.