Influence of long-term intervention with dietary counseling, long-chain n-3 fatty acid supplements, or both on circulating markers of endothelial activation in men with long-standing hyperlipidemia

Abstract

Background: Dietary factors and very-long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) may influence the atherothrombotic process. Elevated concentrations of circulating cell adhesion molecules, thrombomodulin (TM), von Willebrand factor (vWF), and tissue-type plasminogen activator antigen (tPAag) are related to atherothrombotic cardiovascular disease. Objective: The randomized Diet and Omega-3 Intervention Trial (DOIT) targeted a comparison of the effect of 3-y dietary counseling, n-3 PUFA supplementation (2.4 g/d), or both on circulating markers of endothelial activation. Design: The study included 563 elderly men with long-standing hyperlipidemia. The men were randomly assigned by factorial design into 4 groups: control (no dietary counseling and placebo capsules), dietary counseling (and placebo capsules), n-3 PUFA supplementation (no dietary counseling), and dietary counseling and n-3 PUFA supplementation. Results: Serum concentrations of fatty acids reflected good compliance. Dietary counseling was followed by significantly reduced concentrations of soluble intercellular adhesion molecule 1 (sICAM-1; P < 0.001), sTM (P = 0.004), and tPAag (P < 0.001) than in subjects without dietary counseling. After n-3 PUFA supplementation, significantly reduced concentrations of sICAM-1 (P < 0.001) and sTM (P = 0.006) were observed when compared with subjects receiving placebo capsules. An increase in tPAag was not significantly different from that observed in subjects receiving placebo capsules. For sICAM-1, a significant effect was observed for both interventions combined. Conclusions: Each intervention (dietary counseling or n-3 PUFA supplements) reduced sTM and sICAM-1 concentrations, indicating decreased endothelial activation. The tPAag increase in the groups not receiving dietary counseling (pooled), which indicates progression of atherosclerosis, was significantly counteracted by dietary counseling. © 2005 American Society for Clinical Nutrition.