BACKGROUND: Metabolism of arachidonic acid by cytochrome P450 ω-hydroxylase leads to the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) that regulates vascular function, sodium homeostasis and blood pressure (BP). Supplementation with n-3 fatty acids is known to alter arachidonic acid metabolism and reduce the formation of the lipid peroxidation products F2-isoprostanes, but the effect of n-3 fatty acids on 20-HETE has not been studied. METHOD: We previously reported a significant effect of n-3 fatty acids but not coenzyme Q10 (CoQ) to reduce BP in a double-blind, placebo-controlled intervention, wherein patients with chronic kidney disease (CKD) were randomized to n-3 fatty acids (4 g), CoQ (200 mg), both supplements or control (4 g olive oil), daily for 8 weeks. This study examined the effect of n-3 fatty acids on plasma and urinary 20-HETE in the same study, as well as plasma and urinary F2-isoprostanes, and relate these to changes in BP. RESULTS: Seventy-four patients completed the 8-week intervention. n-3fatty acids but not CoQ significantly reduced plasma 20-HETE (P = 0.001) and F2-isoprostanes (P < 0.001). In regression models adjusted for BP at baseline, postintervention plasma 20-HETE was a significant predictor of the fall in SBP (P < 0.0001) and DBP (P < 0.0001) after n-3 fatty acids. CONCLUSION: This is the first report that n-3 fatty acid supplementation reduces plasma 20-HETE in humans and that this associates with reduced BP. These results provide a plausible mechanism for the reduction in BP observed in patients with CKD following n-3 fatty acid supplementation.
RCT Entities:
BACKGROUND: Metabolism of arachidonic acid by cytochrome P450 ω-hydroxylase leads to the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) that regulates vascular function, sodium homeostasis and blood pressure (BP). Supplementation with n-3 fatty acids is known to alter arachidonic acid metabolism and reduce the formation of the lipid peroxidation products F2-isoprostanes, but the effect of n-3 fatty acids on 20-HETE has not been studied. METHOD: We previously reported a significant effect of n-3 fatty acids but not coenzyme Q10 (CoQ) to reduce BP in a double-blind, placebo-controlled intervention, wherein patients with chronic kidney disease (CKD) were randomized to n-3 fatty acids (4 g), CoQ (200 mg), both supplements or control (4 g olive oil), daily for 8 weeks. This study examined the effect of n-3 fatty acids on plasma and urinary 20-HETE in the same study, as well as plasma and urinary F2-isoprostanes, and relate these to changes in BP. RESULTS: Seventy-four patients completed the 8-week intervention. n-3 fatty acids but not CoQ significantly reduced plasma 20-HETE (P = 0.001) and F2-isoprostanes (P < 0.001). In regression models adjusted for BP at baseline, postintervention plasma 20-HETE was a significant predictor of the fall in SBP (P < 0.0001) and DBP (P < 0.0001) after n-3 fatty acids. CONCLUSION: This is the first report that n-3 fatty acid supplementation reduces plasma 20-HETE in humans and that this associates with reduced BP. These results provide a plausible mechanism for the reduction in BP observed in patients with CKD following n-3 fatty acid supplementation.
Authors: Victor Garcia; Ankit Gilani; Brian Shkolnik; Varunkumar Pandey; Frank Fan Zhang; Rambabu Dakarapu; Shyam K Gandham; N Rami Reddy; Joan P Graves; Artiom Gruzdev; Darryl C Zeldin; Jorge H Capdevila; John R Falck; Michal Laniado Schwartzman Journal: Circ Res Date: 2017-03-21 Impact factor: 17.367
Authors: Silvia M Titan; Gabriela Venturini; Kallyandra Padilha; Alessandra C Goulart; Paulo A Lotufo; Isabela J Bensenor; Jose E Krieger; Ravi I Thadhani; Eugene P Rhee; Alexandre C Pereira Journal: PLoS One Date: 2019-03-18 Impact factor: 3.240
Authors: Anne Barden; Nathan O'Callaghan; Valerie Burke; Emile Mas; Lawrence J Beilin; Michael Fenech; Ashley B Irish; Gerald F Watts; Ian B Puddey; Rae-Chi Huang; Trevor A Mori Journal: Nutrients Date: 2016-03-19 Impact factor: 5.717
Authors: Kanyarat Boonprasert; David A Vesey; Glenda C Gobe; Ronnatrai Ruenweerayut; David W Johnson; Kesara Na-Bangchang; Soisungwan Satarug Journal: Clin Kidney J Date: 2018-02-02