A Mediterranean diet increases intakes of n-3 and n-9 fatty acids and lowers intake of n-6 fatty acids. This can impact colon cancer risk since n-6 fatty acids are metabolized to pro-inflammatory eicosanoids. The purpose of this study was to evaluate interactions of polymorphisms in the fatty acid desaturase genes, FADS1 and FADS2, and changes in diet on fatty acid concentrations in serum and colon. A total of 108 individuals at increased risk of colon cancer were randomized to either a Mediterranean or a Healthy Eating diet. Fatty acids were measured in both serum and colonic mucosa at baseline and after 6 months. Each individual was genotyped for four single nucleotide polymorphisms in the FADS gene cluster. Linear regression was used to evaluate the effects of diet, genotype and the diet by genotype interaction on fatty acid concentrations in serum and colon. Genetic variation in the FADS genes was strongly associated with baseline serum arachidonic acid (n-6, AA) but serum eicosapentaenoic acid (n-3) and colonic fatty acid concentrations were not significantly associated with genotype. After intervention, there was a significant diet by genotype interaction for AA concentrations in colon. Subjects who had all major alleles for FADS1/2 and were following a Mediterranean diet had 16% lower AA concentrations in the colon after 6 months of intervention than subjects following the Healthy Eating diet. These results indicate that FADS genotype could modify the effects of changes in dietary fat intakes on AA concentrations in the colon.
Implementation of the Medicare ESRD prospective payment system (PPS) and changes to dosing guidelines for erythropoiesis-stimulating agents (ESAs) in 2011 appear to have influenced use of injectable medications among dialysis patients. Given historically higher ESA and vitamin D use among black patients, we assessed the effect of these policy changes on racial disparities in the management of anemia and mineral metabolism. Analyses used cross-sectional monthly cohorts for a period-prevalent sample of 7384 maintenance hemodialysis patients at 132 facilities from the Dialysis Outcomes and Practice Patterns Study (DOPPS) Practice Monitor. Linear splines with knots at each policy change were used in surveyweighted regressions to estimate time trends in hemoglobin (Hgb), erythropoietin (EPO) dose, intravenous (IV) iron dose, ferritin, transferrin saturation (TSAT) concentration, parathyroid hormone (PTH), IV vitamin D dose, cinacalcet use, and phosphate binder use. From August 2010 to December 2011, mean Hgb declined from 11.5 to 11.0 g/dl (P,0.001), mean EPO dose declined from 20,506 to 14,777 U/wk (P,0.001), and mean serum PTH increased from 340 to 435 pg/ml (P,0.001). No meaningful differences by race were observed regarding the rates of change of management practices or laboratory measures (all P.0.21). Mean EPO and vitamin D dose and serum PTH levels remained higher in blacks. Despite evidence that anemia and mineral metabolism management practices have changed significantly over time, there was no immediate indication of racial disparities resulting from implementation of the PPS or ESA label change. Further studies are needed to examine effects among patient and facility subgroups.
A Mediterranean diet increases intake of n‐3 and n‐9 fatty acids and lowers intake of n‐6 fatty acids. Limiting n‐6 fatty acid levels is expected to decrease levels of pro‐inflammatory eicosanoids such as prostaglandin E2 (PGE2) that increase colon cancer risk. This study evaluated whether polymorphisms in fatty acid desaturases (FADS1 and FADS2) genes may identify subgroups that have a greater response to dietary changes. A total of 107 individuals with a personal history of adenomas or colon cancer were randomized to either a Mediterranean diet or a Healthy diet. Fatty acids were measured in both serum and colonic mucosa at baseline and at 6 months. Each individual was genotyped for 4 SNPs in the FADS1/FADS2 cluster. Genetic variation in the FADS cluster was strongly associated with baseline serum arachidonic acid (p<0.0001) but less evidence was present for serum and colonic mucosa n3 fatty acids. Minor allele carriers had lower 20:4, n6 levels at baseline than major allele carriers. Both diets led to slightly but not significantly lower 20:4, n6 levels at 6 months. The Mediterranean diet intervention increased long chain n3 fatty acids in the colonic mucosa. There was a significant interaction of diet and FADS genotype on changes in fatty acid levels after intervention indicating that a Mediterranean intervention may have a relatively larger impact in specific subgroups.
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