Unlike the well-established hypotriglyceridemic effect of omega-3 fatty acid supplementation, the influence of more clinically tolerable doses on lipoproteins and apolipoproteins is less well characterized. Therefore, we compared the relative effects of modest doses of omega-3 fatty acid supplementation with a corn oil control on lipids, lipoproteins, and apolipoproteins in a randomized, double-blind controlled crossover study. Eight hypertriglyceridemic subjects ingested 4.6 g/d of omega-3 fatty acids or 5.4 g/d of linoleic acid (supplied as corn oil) for 8 weeks, then crossed over to the alternative encapsulated oil for another 8 weeks, following an interposed 4-week wash-out period. Compared with the corn oil control, fish oil supplementation caused a significant reduction in triglyceride levels by a mean of 2.21 mmol/L and increased the high-density lipoprotein cholesterol by a mean of 0.13 mmol/L, associated with a significant rise in the high-density lipoprotein 3 subfraction. Furthermore, there was a significant increase in low-density lipoprotein (LDL) apolipoprotein B levels by a mean of 0.246 g/L. Compared with corn oil, no statistically significant change for LDL cholesterol or other apolipoprotein levels occurred, although LDL cholesterol showed a mild elevation. These data suggest that unlike large doses of omega-3 fatty acids, the hypotriglyceridemic effect of modest amounts of encapsulated fish oil supplementation is unaccompanied by favorable changes in LDL cholesterol or LDL apolipoprotein B levels; the potential therapeutic usefulness of modest doses of dietary fish oil for the treatment of hypertriglyceridemia, therefore, may be limited.

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