Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia

Am J Clin Nutr. 2011 Feb;93(2):243-52. doi: 10.3945/ajcn.110.003871. Epub 2010 Dec 15.

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.

Design: 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.

Conclusion: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Cross-Over Studies
  • Dietary Fats / administration & dosage*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology
  • Fatty Acids, Omega-3 / administration & dosage*
  • Fatty Acids, Omega-3 / therapeutic use
  • Female
  • Humans
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / drug therapy*
  • Inflammation / blood*
  • Inflammation Mediators / metabolism*
  • Male
  • Middle Aged
  • Postmenopause
  • Reference Values
  • Triglycerides / blood*
  • Young Adult

Substances

  • Biomarkers
  • Dietary Fats
  • Fatty Acids, Omega-3
  • Inflammation Mediators
  • Triglycerides

Associated data

  • ClinicalTrials.gov/NCT00504309