Short-term effects of fish oil on human plasma lipid levels

Fish oils rich in eicosopentaenoic acid (EPA) are potent hypotriglyceridemic agents in both normal subjects and in hypertriglyceridemic patients. However, the rapidity with which fish oil exerts this effect has not been studied systematically, nor has the temporal relationship between decreasing triglyceride levels and increasing EPA and low density lipoprotein cholesterol (LDL-C) levels been defined. To examine these interactions, we recruited 9 normal subjects who were given a single dose of fish oil (0.25 g/kg) and 5 other subjects who were given a single dose of a safflower oil placebo. Fasting plasma triglyceride levels were measured at baseline and at 24, 48, and 72 hr post-dosing. In a second study, a group of 5 hypertriglyceridemic patients were given 12 capsules of fish oil/day for 14 days. Plasma triglyceride and LDL-C levels were measured at baseline and every 2-3 days thereafter, including a 10-day washout period. In the single dose study, triglyceride levels decreased by 15% at 24 hr and 16% at 48hr (P < 0.001 both), and began to normalize at 72 hr. Triglyceride levels in the placebo group did not change significantly. Plasma EPA levels increased 4-fold at 24 hr, and then began to return towards baseline. In the multiple dose study, fish oil began lowering triglyceride levels by day 1, and continued doing so through day 14 (7.97 ± 3.06 to 4.57 ± 1.58, P < 0.01). LDL-C levels began rising immediately from 2.51 ± 0.87 mM/L at baseline to a plateau of 3.65 ± 0.59 (P < 0.01) after only 4 days. Both triglyceride and LDL-C levels returned toward normal in the washout period. We conclude that fish oil treatment altered plasma EPA levels very quickly, and produced measurable decreases in triglyceride levels which were preceded by increases in LDL-C levels.