Abstract

Introduction: Current guidelines recommend a diet rich in fish or n-3 polyunsaturated fatty acid (PUFA) supplementation in patients with cardiovascular disease including PAD. The omega-3 index represents the red blood cell (RBC) content of the two major long-chain n-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with less within-patient variation compared to plasma levels of n-3 PUFA. We aimed to quantify the change in the omega-3 index with high-dose n-3 PUFA supplementation in a PAD cohort. Methods: This study was a secondary analysis of the OMEGA-PAD I Trial (NCT01310270), a randomized, double-blinded, placebo-controlled trial addressing the hypothesis that short-duration, high-dose n-3 PUFA oral supplementation improves endothelial function and inflammation in subjects with PAD. Eighty patients with stable claudication received 4.4g of fish oil (2.6g of EPA + 1.8g of DHA) daily (n=40) or placebo capsules (n=40) for 1 month. The RBC fatty acids (FA) content was measured by gas chromatography (OmegaQuant Analytics, Sioux Falls, SD) and expressed as a percent of total FA. Results: There was no difference in baseline PUFA content between the two groups. There was a shift in the n-6:n-3 ratio in RBC from 5 ± 1 to 3 ± 1 (p<0.0001) and the omega-3 index increased from 5 ± 1 to 9 ± 2 (p<0.0001) in the fish but not in the placebo group (Table). There was a significant increase in EPA, DHA, and n-3 docosapentaenoic acid and a significant decrease in all n-6 PUFA content of RBC in the fish oil but not in the placebo group. Following treatment, there was also a significant reduction in plasma triglycerides (-34 ± 46, p<0.001) in the fish oil group. The change in triglycerides was significantly correlated with the change in omega-3 index (p=0.03). Conclusions: High-dose fish oil supplementation increases the omega-3 index and reduces n-6 PUFA levels. The implications of these changes for patients with PAD will continue to be investigated in a follow-up trial (OMEGA-PAD II).

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