BACKGROUND: Leukocyte adhesion and transendothelial migration, the critical pathogenic components in the development of atherosclerotic lesions, are largely mediated by cellular adhesion molecules (CAMs). We examined whether dietary supplementation with alpha-linolenic acid (ALA, 18:3n-3) affects the levels of soluble forms of CAMs in dyslipidaemic patients. METHODS: We recruited 90 male dyslipidaemic patients (mean age=51+/-8 years) following a typical Greek diet. They were randomly assigned either to 15 ml of linseed oil (rich in ALA) per day (n=60) or to 15 ml of safflower oil (rich in linoleic acid [LA, 18:2n-6]) per day (n=30). The ratio of n-6:n-3 in linseed oil supplemented group was 1.3:1 and in safflower oil supplemented group 13.2:1. Dietary intervention lasted for 12 weeks. Blood lipids, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) were measured. RESULTS: Dietary supplementation with ALA significantly decreased sVCAM-1 levels (median decrease 18.7% [577.5 ng/ml versus 487 ng/ml, P=0.0001]). In the LA supplemented group, sVCAM-1 was also significantly decreased but to a lesser extent (median decrease 10.6% [550.5 ng/ml versus 496 ng/ml, P=0.0001]). After controlling for smoking habits, no significant difference was observed in the reduction of sVCAM-1 levels between the two treatment arms (P=0.205). The decrease of sVCAM-1 was independent of lipid changes in both groups. CONCLUSIONS: Dietary supplementation with ALA for 12 weeks significantly decreases sVCAM-1 levels in dyslipidaemic patients. This effect presents a potential mechanism for the beneficial effect of plant n-3 polyunsaturated fatty acids in the prevention of coronary artery disease. In addition, dietary supplementation with LA significantly decreases sVCAM-1 levels, an effect which requires further investigation.