Fish-oil supplementation can reduce circulating triacylglycerol (TG) levels and cardiovascular risk. This study aimed to assess independent associations between changes in platelet eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and fasting and postprandial (PP) lipoprotein concentrations and LDL oxidation status, following fish-oil intervention. Fiftyfive mildly hypertriacylglycerolaemic (TG 1·5-4·0 mmol/l) men completed a double-blind placebo controlled cross over study, where individuals consumed 6 g fish oil (3 g EPA þ DHA) or 6 g olive oil (placebo)/d for two 6-week intervention periods, with a 12-week wash-out period in between. Fish-oil intervention resulted in a significant increase in the platelet phospholipid EPA (+491 %, P,0·001) and DHA (+44 %, P,0·001) content and a significant decrease in the arachidonic acid (210 %, P,0·001) and g-linolenic acid (224 %, P,0·001) levels. A 30 % increase in ex vivo LDL oxidation (P,0·001) was observed. In addition, fish oil resulted in a significant decrease in fasting and PP TG levels (P,0·001), PP non-esterified fatty acid (NEFA) levels, and in the percentage LDL as LDL-3 (P¼0·040), and an increase in LDLcholesterol (P¼0·027). In multivariate analysis, changes in platelet phospholipid DHA emerged as being independently associated with the rise in LDL-cholesterol, accounting for 16 % of the variability in this outcome measure (P¼0·030). In contrast, increases in platelet EPA were independently associated with the reductions in fasting (P¼0·046) and PP TG (P¼0·023), and PP NEFA (P¼0·015), explaining 15 -20 % and 25 % of the variability in response respectively. Increases in platelet EPA þ DHA were independently and positively associated with the increase in LDL oxidation (P¼0·011). EPA and DHA may have differential effects on plasma lipids in mildly hypertriacylglycerolaemic men.

No abstract

No abstract

No abstract

No abstract

No abstract

The LDL oxidation hypothesis proposes that LDL is oxidised in arterial interstitial fluid and macrophages take it up rapidly, becoming foam cells. LDL oxidation is inhibited by interstitial fluid and large clinical trials have shown no protection by antioxidants, including probucol. We therefore proposed that LDL might be nonoxidatively modified and aggregated by enzymes in interstitial fluid, rapidly phagocytosed by macrophages and oxidised by iron inside lysosomes, which have a pH of about 4.5. We investigated the mechanisms of LDL oxidation by iron at lysosomal pH. LDL (50 µg LDL protein/ml) was oxidised by FeSO4 or FeCl3 (5 µM) at 37°C in 150 mM NaCl/10 mM sodium acetate buffer, pH 4.5. Lipid oxidation was measured in terms of conjugated dienes at 234 nm and tryptophan oxidation by the loss of fluorescence (Ex/Em 282/331 nm). Interestingly, probucol did not inhibit lipid oxidation for about 100 min for Fe2+ and Cu2+ at pH 4.5 and did not decrease the loss of tryptophan fluorescence. As probucol was unable to prevent loss of tryptophan fluorescence, but would be expected to scavenge lipid radicals, the initial oxidation of LDL at pH 4.5 might be due to the formation of tryptophan radicals which attack the lipids. We propose the following mechanism of LDL oxidation by Fe2+ at lysosomal pH. Fe2+ + O2 → Fe3+ + O2●- O2●- + H+ ↔ HO2● (pKa 4.8) HO2● + TrpH → Trp● + H2O2 Trp● + O2 → TrpOO● LH + TrpOO● → L● + TrpOOH.