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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^1,2,3

¹ From the Center for Clinical Research (EMH, IS, LS, and HA) and the Department of Preventive Cardiology (IE and IH), Ullevaal University Hospital, Oslo, and the Institute for Nutrition Research (PB), University of Oslo

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.

Key Words: Dietary intervention • n–3 PUFA supplementation • adhesion molecules • endothelial activation • tissue-type plasminogen activator antigen • tPAag • hyperlipidemia

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