Heterogeneity of low density lipoprotein responses to fish-oil supplementation in hypertriglyceridemic subjects.

Previous studies have demonstrated a variable effect of fish oil on low density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B levels, particularly in hypertriglyceridemic subjects. Since heterogeneity of LDL composition and metabolism in hypertriglyceridemic subjects is well described, the present study was undertaken to determine if the response of LDL to dietary fish-oil supplementation is dependent upon pretreatment differences in LDL composition. A single-blind, cross-over design was used with 18 hypertriglyceridemic subjects, who were given supplements of a safflower-oil placebo or a fish-oil concentrate (4.0 g omega-3 fatty acids; [F4 dose]) for 1 month. Sixteen subjects then received an additional month of fish-oil supplementation at a higher dose (7.5 g omega-3 fatty acids [F7.5 dose]). The initial LDL cholesterol/apo B ratio, an index of LDL composition, was correlated positively with changes in LDL apo B levels (F4.0 dose: r = 0.41, p = 0.06; F7.5 dose: r = 0.51, p = 0.03) and negatively with changes in LDL cholesterol concentrations (F4.0 dose: r = -0.51, p = 0.01; F7.5 dose: r = -0.50, p = 0.02). Twelve subjects with LDL cholesterol/apo B ratios above 1.4 had large increases in LDL apo B (51% at both doses, p less than 0.05) but much smaller changes in LDL cholesterol levels during fish-oil treatment. Six subjects with LDL cholesterol/apo B ratios below 1.4 showed a trend toward increased LDL cholesterol (12% increase from baseline at F4 dose, 10% increase from baseline at F7.5 dose, p greater than 0.05) but not in LDL apo B levels during fish-oil therapy. These data suggest that LDL responses to fish oil may be linked to underlying differences in LDL composition and, presumably, to differences in LDL metabolic behavior.