Differential effects of eicosapentaenoic acid and docosahexaenoic acid on vascular reactivity of the forearm microcirculation in hyperlipidemic, overweight men

Circulation. 2000 Sep 12;102(11):1264-9. doi: 10.1161/01.cir.102.11.1264.


Background: Recent evidence supports differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the 2 major omega3 fatty acids of marine origin, on blood pressure in humans and vascular reactivity in adult spontaneously hypertensive rats. We investigated possible differences in the effects of purified EPA or DHA on forearm vascular reactivity in overweight hyperlipidemic men that might contribute to the blood pressure-lowering effects of fish oils.

Methods and results: With a double-blind, placebo-controlled trial of parallel design, 59 overweight, mildly hyperlipidemic men were randomized to receive 4 g/d purified EPA, DHA, or olive oil (placebo) capsules while continuing their usual diets for 6 weeks. Forearm blood flow (FBF) was measured with venous occlusion, strain-gauge plethysmography during the sequential intra-arterial administration of acetylcholine (7.5, 15, and 30 microg/min), sodium nitroprusside (1.5, 3, and 10 microg/min), norepinephrine (10, 20, and 40 ng/min), a single-dose infusion of N:(G)-monomethyl-L-arginine (L-NMMA) (1 mg/min), and coinfusion of acetylcholine (7.5, 15, and 30 microg/min) and L-NMMA. Forty of the 56 subjects who completed the study underwent FBF measurements. Plasma phospholipid EPA levels increased significantly (P:<0.0001) after supplementation with EPA, and DHA composition increased with DHA supplementation (P:<0.0001). Relative to placebo, DHA, but not EPA, supplementation significantly improved FBF in response to acetylcholine infusion (P:=0.040) and coinfusion of acetylcholine with L-NMMA (P:=0.040). Infusion of L-NMMA alone showed no group differences. DHA significantly enhanced dilatory responses to sodium nitroprusside (P:<0.0001) and attenuated constrictor responses to norepinephrine (P:=0.017).

Conclusions: Relative to placebo, DHA, but not EPA, enhances vasodilator mechanisms and attenuates constrictor responses in the forearm microcirculation. Improvements in endothelium-independent mechanisms appear to be predominant and may contribute to the selective blood pressure-lowering effect observed with DHA compared with EPA in humans.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Adrenergic alpha-Agonists / pharmacology
  • Adult
  • Aged
  • Blood Glucose / analysis
  • Docosahexaenoic Acids / pharmacology*
  • Double-Blind Method
  • Eicosapentaenoic Acid / pharmacology*
  • Forearm / blood supply*
  • Humans
  • Hyperlipidemias / complications
  • Hyperlipidemias / physiopathology*
  • Insulin / blood
  • Lipids / blood
  • Lipoproteins, LDL / blood
  • Male
  • Microcirculation
  • Middle Aged
  • Muscle, Smooth, Vascular / drug effects
  • Nitric Oxide Donors / pharmacology
  • Nitroprusside / pharmacology
  • Norepinephrine / pharmacology
  • Obesity / complications
  • Obesity / physiopathology*
  • Particle Size
  • Plethysmography
  • Vasoconstriction / drug effects*
  • Vasoconstrictor Agents / pharmacology
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology
  • omega-N-Methylarginine / pharmacology


  • Adrenergic alpha-Agonists
  • Blood Glucose
  • Insulin
  • Lipids
  • Lipoproteins, LDL
  • Nitric Oxide Donors
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Nitroprusside
  • Docosahexaenoic Acids
  • omega-N-Methylarginine
  • Eicosapentaenoic Acid
  • Acetylcholine
  • Norepinephrine