Fish Oil–Induced Changes in Apolipoproteins in IDDM Subjects

The aim of this study was to examine the effect of Max EPA (a commercially available fish oil preparation) on serum cholesterol lipoproteins and apolipoproteins in insulin-dependent diabetic (IDDM) men with dosages that were likely to be acceptable to patients. Twenty-two male IDDM patients aged 20–41 yr, 6 of whom had retinopathy, were recruited from the Royal Perth Hospital diabetic clinic. After screening, subjects were divided into three groups. Six of the subjects without retinopathy were randomly selected and allocated to a control group. The remaining 16 patients (10 without and 6 with retinopathy) received a fish oil supplement. All subjects were advised to maintain their usual dietary patterns. Sixteen patients, including the 6 with retinopathy, were instructed to take 15 Max EPA fish oil capsules/day with meals. Patients in the control group did not take Max EPA. Three weeks of Max EPA supplementation without other dietary modification led to a significant rise in total cholesterol (P < 0.01), which could be accounted for by increases in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. The increase in HDL cholesterol was explained by a 33% rise (P < 0.001) in its HDL₂ subclass. Changes in apolipoproteins were examined and showed that the level of apolipoprotein A-l increased after ingestion of fish oil and correlated significantly (P < 0.05) with the rise in HDL cholesterol. Apolipoprotein A-ll showed a significant fall at the end of Max EPA intake in a subgroup of patients with retinopathy, and this correlated significantly (P < 0.05) with the fall in HDL₃ cholesterol observed at this time. A significant rise in apolipoprotein B (P < 0.05) was correlated with the rise in LDL cholesterol. Possible adverse effects of the increase in both total and LDL cholesterol after 15 g/day Max EPA may be compensated for by a rise in the protective HDL₂ subclass. However, in view of this hypercholesterolemic effect and evidence that suggests that LDL apolipoprotein B may be a risk factor for coronary heart disease, these findings raise questions regarding the safety of fish oils in patients with IDDM.