Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study

Circulation. 2005 Jan 25;111(3):343-8. doi: 10.1161/01.CIR.0000153272.48711.B9. Epub 2005 Jan 17.


Background: The metabolic syndrome is associated with increased angiotensin II activity, induction of a proinflammatory and oxidative state, and endothelial dysfunction. We evaluated the ability of irbesartan, an angiotensin receptor blocker, and lipoic acid, an antioxidant, to affect endothelial function and inflammation in patients with the metabolic syndrome.

Methods and results: We randomized 58 subjects with the metabolic syndrome in a double-blinded manner to irbesartan 150 mg/d (n=14), lipoic acid 300 mg/d (n=15), both irbesartan and lipoic acid (n=15), or matching placebo (n=14) for 4 weeks. Endothelium-dependent and -independent flow-mediated vasodilation was determined under standard conditions. Plasma levels of interleukin-6, plasminogen activator-1, and 8-isoprostane were measured. After 4 weeks of therapy, endothelium-dependent flow-mediated vasodilation of the brachial artery was increased by 67%, 44%, and 75% in the irbesartan, lipoic acid, and irbesartan plus lipoic acid groups, respectively, compared with the placebo group. Treatment with irbesartan and/or lipoic acid was associated with statistically significant reductions in plasma levels of interleukin-6 and plasminogen activator-1. In addition, treatment with irbesartan or irbesartan plus lipoic acid decreased 8-isoprostane levels. No significant changes in blood pressure were noted in any of the study groups.

Conclusions: Administration of irbesartan and/or lipoic acid to patients with the metabolic syndrome improves endothelial function and reduces proinflammatory markers, factors that are implicated in the pathogenesis of atherosclerosis.

Publication types

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

MeSH terms

  • Adult
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Antioxidants / therapeutic use*
  • Biomarkers / blood
  • Biphenyl Compounds / therapeutic use*
  • Brachial Artery / drug effects
  • Brachial Artery / physiopathology
  • Dietary Supplements
  • Dinoprost / analogs & derivatives*
  • Dinoprost / blood
  • Double-Blind Method
  • Drug Therapy, Combination
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Interleukin-6 / blood
  • Irbesartan
  • Male
  • Metabolic Syndrome / physiopathology*
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / blood
  • Tetrazoles / therapeutic use*
  • Thioctic Acid / therapeutic use*
  • Vasodilation / drug effects


  • Angiotensin II Type 1 Receptor Blockers
  • Antioxidants
  • Biomarkers
  • Biphenyl Compounds
  • Interleukin-6
  • Plasminogen Activator Inhibitor 1
  • Tetrazoles
  • 8-epi-prostaglandin F2alpha
  • Thioctic Acid
  • Dinoprost
  • Irbesartan