title: Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia.
abstract: BACKGROUND
  Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to reduce cardiovascular mortality at a dose of ≈1 g/d. Studies using higher doses have shown evidence of reduced inflammation and improved endothelial function. Few studies have compared these doses.
  
  
  OBJECTIVE
  The objective of this study was to compare the effects of a nutritional dose of EPA+DHA (0.85 g/d) with those of a pharmaceutical dose (3.4 g/d) on serum triglycerides, inflammatory markers, and endothelial function in healthy subjects with moderately elevated triglycerides.
  
  
  METHODS
  This was a placebo-controlled, double-blind, randomized, 3-period crossover trial (8 wk of treatment, 6 wk of washout) that compared the effects of 0.85 and 3.4 g EPA+DHA/d in 23 men and 3 postmenopausal women with moderate hypertriglyceridemia (150-500 mg/dL).
  
  
  RESULTS
  The higher dose of EPA+DHA lowered triglycerides by 27% compared with placebo (mean ± SEM: 173 ± 17.5 compared with 237 ± 17.5 mg/dL; P = 0.002), whereas no effect of the lower dose was observed on lipids. No effects on cholesterol (total, LDL, and HDL), endothelial function [as assessed by flow-mediated dilation, peripheral arterial tonometry/EndoPAT (Itamar Medical Ltd, Caesarea, Israel), or Doppler measures of hyperemia], inflammatory markers (interleukin-1β, interleukin-6, tumor necrosis factor-α, and high-sensitivity C-reactive protein), or the expression of inflammatory cytokine genes in isolated lymphocytes were observed.
  
  
  CONCLUSIONS
  The higher dose (3.4 g/d) of EPA+DHA significantly lowered triglycerides, but neither dose improved endothelial function or inflammatory status over 8 wk in healthy adults with moderate hypertriglyceridemia. The trial was registered at clinicaltrials.gov as NCT00504309.
authors.affiliation: Department of Nutritional Sciences, Pennsylvania State University, University Park, PA, USA. aus164@psu.edu
authors.forename: Ann C
authors.initials: AC
authors.lastname: Skulas-Ray
authors.forename: Penny M
authors.initials: PM
authors.lastname: Kris-Etherton
authors.forename: William S
authors.initials: WS
authors.lastname: Harris
authors.forename: John P
authors.initials: JP
authors.lastname: Vanden Heuvel
authors.forename: Paul R
authors.initials: PR
authors.lastname: Wagner
authors.forename: Sheila G
authors.initials: SG
authors.lastname: West
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy*; D007249:Inflammation / Q000097:blood*; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017698:Postmenopause; D012016:Reference Values; D014280:Triglycerides / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D018836:Inflammation Mediators; D014280:Triglycerides