Effects of two types of fish oil supplements on serum lipids and plasma phospholipid fatty acids in coronary artery disease. Fish oil has consistently been shown to lower triglyceride levels, but its effects on low-density lipoprotein (LDL) cholesterol remain controversial. The current study compares the long-term effects of 2 different fish oil preparations (ethyl ester and triglyceride) versus olive oil in patients with coronary artery disease. Eighty-nine subjects were randomly assigned to receive capsules containing 6 g/day (triglyceride group) or 7 g/day (ethyl ester group) of n-3 fatty acids, or capsules containing 12 g/day of olive oil for 6 months. Mean triglyceride levels decreased by 28% in the ester and 32% in the triglyceride fish oil groups (p less than 0.05 for both). LDL cholesterol levels increased by 3% (difference not significant) in the ester and 12% (p less than 0.05) in the triglyceride fish oil groups; in hypertriglyceridemic subjects the increase was 23% (p less than 0.01) and 14% (difference not significant), respectively. Plasma phospholipid fatty acid analysis showed a fivefold increase in eicosapentaenoic acid levels in both fish oil groups (p less than 0.001), and a long-term decrease in arachidonic acid levels (p less than 0.001). Achieved eicosapentaenoic acid level correlated with the degree of increase in LDL cholesterol (r = 0.38, p less than 0.05). These data suggest that fish oil administration is associated with an increase in LDL cholesterol levels in a diverse group of patients with coronary artery disease; this change appears to be correlated with n-3 fatty acid absorption. The impact of this increase in LDL is unknown, but should be considered as potentially adverse. 