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.
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.


METHODS
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.
Hjerkinn
Elsa M
EM
Center for Clinical Research, Ullevaal University Hospital, Oslo, Norway. elsa.hjerkinn@ulleval.no
Seljeflot
Ingebjørg
I
Ellingsen
Ingrid
I
Berstad
Paula
P
Hjermann
Ingvar
I
Sandvik
Leiv
L
Arnesen
Harald
H
D000368:Aged; D001161:Arteriosclerosis / Q000097:blood* / Q000517:prevention & control; D015415:Biomarkers / Q000097:blood; D003376:Counseling; D004032:Diet; D019587:Dietary Supplements; D018450:Disease Progression; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D006949:Hyperlipidemias / Q000178:diet therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood* / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018180:Thrombomodulin / Q000097:blood* / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000097:blood* / Q000187:drug effects; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D018180:Thrombomodulin; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D010959:Tissue Plasminogen Activator