An Investigation of the Influence of Fish Oil Supplementation on IL-8: A Possible Protection Against Preeclampsia
Edwards, Sara Mitchell
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Session presented on Monday, July 28, 2014: Purpose: Ten million women develop preeclampsia each year around the world. Of those, about 76,000 pregnant women will die from preeclampsia and related hypertensive disorders. Further, the annual infant mortality rate from these disorders is estimated to be approximately 500,000. Land-locked or mountainous regions of the globe, and thus with less oily ocean fish available in the diet, tend to have higher rates of preeclampsia. Poor women are also more vulnerable to the disease. A woman is seven times more likely to develop preeclampsia in a developing country than a woman in an industrialized country. Preeclampsia is an insidious disease with a long pre-clinical phase followed by a phase when maternal systemic effects of proteinuria and elevated blood pressure appear, mainly due to endothelial dysfunction. The current hypothesis of the etiology of preeclampsia is an exaggerated maternal inflammatory response to fetal antigens which causes a cascade of events culminating in the release of pro-inflammatory cytokines into the maternal circulation. Specifically, Interleukin-8 (IL-8) levels have been found to be higher in women who develop preeclampsia in pregnancy. Interleukin-8 (IL-8) is a chemokine that regulates pathologic angiogenesis and tumor growth. It also plays a role in endothelial cell proliferation. Abnormal endothelial cells cause the majority of internal organ dysfunction in preeclampsia. IL-8 attracts and activates neutrophils and is elevated in multiple systemic inflammatory diseases. It is plausible that IL-8 either contributes to or could be used as a marker of inflammation and endothelial dysfunction in early preeclampsia due to the abnormal cytokine response involved in the progression of this systemic disease. There are two main types of bioactive polyunsaturated fatty acids (PUFAs), the omega-6 (n-6) series, and the omega-3 (n-3) series (linolenic acid [ALA], eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA]). They are important constituents of all cell membranes and essential for the survival of all mammals. PUFAs cannot be synthesized in the body and can only be obtained from our diet, thus they are called essential fatty acids. The cardio-protective action of anti-inflammatory eicosanoid levels (derived from omega 3 fatty acids in fish oil) is believed to occur via enhanced endothelial production of a vascular-relaxing factor. This results in vasodilatation which leads to a reduction in blood pressure. Reduced platelet aggregation is another potential benefit of fish oil supplementation in pregnancy and both actions could counteract or limit the preeclampsia-related hypertension and hypercoagulability. The aim of this analysis was to investigate the reported use of fish oil supplementation during pregnancy, the factors that predict its use, and any association with serum levels of IL-8. Methods: A total of 189 pregnant women in Colorado and Ohio who met inclusion criteria (e.g. general good health, no chronic medications, non-smokers) were enrolled in a longitudinal study during their 3rd trimester and followed through 6 months postpartum. This analysis only examined the single prenatal time point. Fish oil supplementation was determined by self-report with a yes/no. Demographic information (age, status of government support from the Special Supplemental Nutrition Program for Women, Infants, and Children [WIC], marital status, race/ethnicity) was collected through self-report survey. Plasma levels of pro- and anti-inflammatory cytokines were collected to measure inflammatory response. Results: Logistic regression was performed to assess for possible factors (age, BMI, Caucasian race or other, WIC status) on the likelihood a woman would supplement with fish oil in pregnancy. The full model containing all 4 predictors was statistically significant, Chi-square (6, N=188) =23.43, p<.000, indicating the model was able to distinguish between respondents who reported they did or did not take fish oil. Women who used fish oil supplements were more likely to be older (p<.01), thinner (p=.03), Caucasian (p=.02) and not on WIC (p<.001). While the model as a whole only explained between 11.7 and 17.8 % of the variance in fish oil intake, it correctly classified 76.6% of cases. Only one of the variables, WIC status, made a unique, statistically significant contribution to the model. The odds ratio of .20 for WIC status indicated that subjects on WIC were .20 times less likely to take fish oil than those without WIC. There were only 7 women who were underweight, with a BMI less than 18.5, so they were removed from the analysis to improve the strength of the findings related to the other BMI categories. After controlling for Caucasian or other race, WIC status and normal/overweight/obese status (all but underweight), linear regression analysis revealed IL-8 levels were significantly lower among women taking fish oil supplementation (p=.03) compared to those not taking this supplement. Conclusion: Analysis was limited by how fish oil intake was reported. The subjects were merely asked if they were taking a fish oil supplement, and it was recorded as yes/no. No amount or frequency of dose is known. Despite this limitation, there were significant associations with fish oil use: higher age, higher income, lower weight, and Caucasian race. Fish oil supplements are expensive and elective so they are unlikely to be consumed unless it is considered affordable and necessary. There is no current recommendation for fish oil supplementation as there are minimal and conflicting findings of beneficial use in pregnancy. Given the growing global incidence of preeclampsia, closer study of fish oil supplementation in pregnancy may prove to reduce risk or severity of the disease. Prenatal surveillance of IL-8 levels may serve as an early marker or risk factor of the disease. Intervention before maternal and fetal effects have progressed is needed to improve the devastating outcomes of preeclampsia in pregnancy.