Oxidative stress as a cardiovascular risk factor in Canadian Inuit

A decline in the traditional food consumption among the Inuit poses a nutritional problem, as it provides nutrients associated with protection from cardiovascular diseases (CVD). Controversy exists, however, regarding oxidative stress status among Inuit due to possible higher tissue oxidizability of n-3 polyunsaturated fatty acids (PUFA) from the traditional Inuit n-3 PUFA rich diet and their dietary exposure to pro-oxidative contaminants such as methylmercury and polychlorinated biphenyls (PCBs). We proposed that determining whole body oxidative stress status via the gold standard isoprostane biomarker that reflects an overall response to the various metabolic and xenobiotic burdens could be an indicator of the adaptations and predispositions of the Inuit to CVD. The objectives of this thesis were: (i) to quantify plasma levels of F2-isoprostanes, F3-isoprostanes, and isofurans and to assess their relationship to cardiometablic risk factors; (ii) to evaluate the relationship between the selenium (Se) status and plasma isoprostanes and to assess the interrelationship between dietary methylmercury exposure and tissue selenium on oxidative stress status; (iii) to examine the impact of decreased consumption of traditional foods on oxidative stress parameters; and (iv) to evaluate the pro-oxidant contribution of PCBs on oxidative stress status. A series of cross-sectional studies were conducted using data from the International Polar Year Inuit Health Survey (2007-2008). Cross-sectional analyses were conducted to examine the relationship between diet (Se, n-3 and n-6 PUFAs, trans and saturated fat), contaminants (MeHg and PCBs), obesity, and cardiovascular risk factors including hypertension, dyslipidemia, smoking and C-reactive protein in relation to oxidative stress using the gold standard F2-isoprostanes and the novel isoprostane biomarkers F3-isoprostanes and isofurans. Plasma levels of isoprostanes were determined by gas chromatography/negative ion chemical ionization/mass spectrometry methodology. Multivariate analyses were employed to determine final correlates of isoprostanes. Results showed that the Inuit are protected from mercury-induced oxidative stress because of their high Se status and that highest consumers of traditional foods were most protected. The isoprostane isoforms, F2-isoprostanes and isofurans, were both associated with increased obesity. F2-isoprostanes and isofurans were additionally associated to C-reactive protein and blood pressure. The F3-isoprostane isoform was shown to be quantifiable for the first time in human plasma, which was likely due to the C20:5n-3 rich Inuit diet. F3-isoprostanes and isofurans were more related to contaminants than F2-isoprostanes. Generally, this thesis demonstrates that the contaminants in the Arctic do not appear to pose a significant oxidative stress risk among the Inuit; however, shifting away from the traditional food is associated with obesity and inflammatory-induced oxidative stress. An important finding is that each isoprostane isoform has a unique attribute to explain the potential CVD risk and that simultaneous measurement of isoprostane species provides an advantageous mechanistic insight into oxidative stress status not captured by F2-isoprostanes alone.

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