Increased F3-isoprostanes in the canadian inuit population could be cardioprotective by limiting F2-isoprostane production

Abstract

Context: F3-isoprostanes (F3-IsoPs), derived from peroxidation of eicosapentaenoic acid (C20:5n-3), could be cardioprotective by limiting production of F2-isoprostanes (F2-IsoPs), a cardiovascular disease risk factor. Objective: The objective of the study was to determine whether the n-3-polyunsaturated (PUFA)- rich Inuit diet is associated with a lower plasma ratio of F2-IsoPs to F3-IsoPs. Design: This was a cross-sectional observational study. Setting: The study was conducted in 36 Canadian Arctic Inuit communities. Participants: Participants included a random subset (n = 233) of Inuit adults taken from a population- based survey. Main Outcome Measures: Plasma F2-IsoPs and F3-IsoPs, cardiometabolic risk factors (blood lipids, C-reactive protein, blood pressure, fasting glucose) and markers of dietary exposure (erythrocyte n-3 and n-6 PUFA, blood levels of Se, mercury, polychlorinated biphenyls) were measured. Results: Inuit aged 40 years old and older vs younger Inuit showed higher concentrations of plasma F3-IsoPs and erythrocyte n-3 PUFA and lower plasma F2-IsoPs concentrations despite having higher blood lipids, fasting glucose, systolic blood pressure, and percentage body fat. Plasma F3-IsoPs were not associated with any cardiometabolic measures. When subjects were categorized into tertiles according to total n-3 PUFA erythrocyte concentrations, F3-IsoPs increased with increasing tertiles, whereas the F2-IsoP to F3-IsoP ratio was lowest at the highest n-3 tertile. The F2-IsoP to F3-IsoP ratio was significantly predicted by C20:5n-3 (β=-365, P=002); C20:4n-6:C20:5n-3 (β=.056, P=.006), blood mercury (β =-812, P =.015), blood Se (β= -1.95, P β .015), and smoking (β =- .745, P = .025). Conclusions: Plasma F3-IsoPs were not associated with cardiometabolic risk factors previously seen with F2-IsoPs. Higher n-3 fatty acid status was associated with lower plasma F2-IsoPs and higher plasma F3-IsoPs, which provides partial explanation to the cardioprotective effects of the n-3 PUFA-rich Inuit diet.