A randomized controlled trial of the effects of n-3 fatty acids on resolvins in chronic kidney disease

Published:April 13, 2015DOI:https://doi.org/10.1016/j.clnu.2015.04.004


      Background and objective

      The high incidence of cardiovascular disease (CVD) in chronic kidney disease (CKD) is related partially to chronic inflammation. n-3 Fatty acids have been shown to have anti-inflammatory effects and to reduce the risk of CVD. Specialized Proresolving Lipid Mediators (SPMs) derived from the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) actively promote the resolution of inflammation. This study evaluates the effects of n-3 fatty acid supplementation on plasma SPMs in patients with CKD.


      In a double-blind, placebo-controlled intervention of factorial design, 85 patients were randomized to either n-3 fatty acids (4 g), Coenzyme Q10 (CoQ) (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. The SPMs 18-HEPE, 17-HDHA, RvD1, 17R-RvD1, and RvD2, were measured in plasma by liquid chromatography–tandem mass spectrometry before and after intervention.


      Seventy four patients completed the 8 weeks intervention. n-3 Fatty acids but not CoQ significantly increased (P < 0.0001) plasma levels of 18-HEPE and 17-HDHA, the upstream precursors to the E- and D-series resolvins, respectively. RvD1 was significantly increased (P = 0.036) after n-3 fatty acids, but no change was seen in other SPMs. In regression analysis the increase in 18-HEPE and 17-HDHA after n-3 fatty acids was significantly predicted by the change in platelet EPA and DHA, respectively.


      SPMs are increased after 8 weeks n-3 fatty acid supplementation in patients with CKD. This may have important implications for limiting ongoing low grade inflammation in CKD.



      EPA (eicosapentaenoic acid), DHA (docosahexaenoic acid), LC–MS/MS (liquid chromatography–tandem mass spectrometry), 18-HEPE (18R/S-hydroxy-5Z, 8Z, 11Z, 14Z, 16E-eicosapentaenoic acid), 17-HDHA (17S-hydroxy-4Z, 7Z, 10Z, 13Z,15E, 19Z-docosahexaenoic acid), RvD1 (7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid), 17R-RvD1 (7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E19Z-docosahexaenoic acid), RvD2 (7S,16R,17S-trihydroxy-4Z,8E,10Z,12E,14E,19Z-docosahexaenoic acid), 10S,17S-diHDHA (10S,17S-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoic acid), protectin D1, PD1 (10R,17S-dihydroxy-4Z,7Z,11E,13E,15Z,19Z-docosahexaenoic acid), LTB4-d4 (leukotriene B4-d4), EDTA (ethylenediaminetetraacetic acid), CVD (cardiovascular disease), CKD (chronic kidney disease), SPM (specialized proresolving lipid mediator), CoQ (coenzyme Q10), ESRD (end stage renal disease), COX-2 (cyclooxygenase-2), BHT (butylated hydroxytoluene), GSH (reduced glutathione), LTB4-d4 (leukotriene B4-deuterated), TNF-α (tumor necrosis factor-alpha), IL-10 (interleukin-10), RvE1 (resolvin E1), BMI (body mass index), eGFR (estimated glomerular filtration rate)
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