Copper supplementation in humans does not affect the susceptibility of low density lipoprotein to in vitro induced oxidation (FOODCUE project).

The oxidative modification of low-density lipoprotein cholesterol (LDL) has been implicated in the pathogenesis of atherosclerosis. Copper (Cu) is essential for antioxidant enzymes in vivo and animal studies show that Cu deficiency is accompanied by increased atherogenesis and LDL susceptibility to oxidation. Nevertheless, Cu has been proposed as a pro-oxidant in vivo and is routinely used to induce lipid peroxidation in vitro. Given the dual role of Cu as an in vivo antioxidant and an in vitro pro-oxidant, a multicenter European study (FOODCUE) was instigated to provide data on the biological effects of increased dietary Cu. Four centers, Northern Ireland (coordinator), England, Denmark, and France, using different experimental protocols, examined the effect of Cu supplementation (3 or 6 mg/d) on top of normal Cu dietary intakes or Cu-controlled diets (0.7/1.6/6.0 mg/d), on Cu-mediated and peroxynitrite-initiated LDL oxidation in apparently healthy volunteers. Each center coordinated its own supplementation regimen and all samples were subsequently transported to Northern Ireland where lipid peroxidation analysis was completed. The results from all centers showed that dietary Cu supplementation had no effect on Cu- or peroxynitrite-induced LDL susceptibility to oxidation. These data show that high intakes (up to 6 mg Cu) for extended periods do not promote LDL susceptibility to in vitro-induced oxidation.

Effects of dietary fish oil supplementation on the phospholipid composition and fluidity of cell membranes from human volunteers.

BACKGROUND: Membrane fluidity is an important aspect of cellular physiology which may be manipulated by diet. METHODS: We studied the effect of dietary fish oil on the membrane composition of erythrocytes and cheek cells, and on membrane fluidity of erythrocytes as assessed by fluorescence recovery after photobleaching (FRAP). Healthy volunteers received a daily supplement of fish oil (930 mg EPA, 630 mg DHA) for 42 days. RESULTS: The intervention reduced the ratio of n-6 to total fatty acid in the phospholipid fraction of erythrocyte membranes but the n-3 fraction remained stable and the ratio of cholesterol to phospholipid increased. The level of EPA and DHA in cheek cells increased significantly during the intervention period. The mean diffusion coefficient of the fluorescent probe in erythrocyte membranes increased from 7.2 +/- 0.7 x 10-9 cm2/s at the start to 9.8 +/- 0.5 x 10-9 cm2/s after 21 days. Membrane fluidity remained higher than the initial value 42 days after withdrawal of the supplement. Fish oil also reduced platelet aggregation in response to ADP but there was no effect on plasma lipid profiles. CONCLUSION: We conclude that n-3 fatty acids influence erythrocyte membrane composition at relatively low levels of supplementation by a mechanism which does not necessarily involve an increase in the level of EPA or DHA present in the membrane.