Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study

Eur Heart J. 2012 Jul;33(13):1589-97. doi: 10.1093/eurheartj/ehr482. Epub 2012 Jan 11.

Abstract

Aims: Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive.

Methods and results: Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P < 0.0001), while no change was observed with placebo (5.4 ± 2.4 to 4.7 ± 2.0; P = 0.051). This difference between study groups was significant [estimated treatment effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F(2t)-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo.

Conclusion: This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress.

Trial registration: ClinicalTrials.gov NCT00641758.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents / administration & dosage
  • Antihypertensive Agents / administration & dosage
  • Antioxidants / administration & dosage*
  • Arginine / analogs & derivatives
  • Arginine / metabolism
  • Biomarkers / metabolism
  • Blood Platelets / drug effects
  • Blood Pressure / drug effects
  • C-Reactive Protein / metabolism
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / physiopathology
  • Cross-Over Studies
  • Double-Blind Method
  • Endothelin-1 / drug effects
  • Endothelium, Vascular / drug effects*
  • Female
  • Flavonoids / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects
  • Plant Extracts
  • Prospective Studies
  • Shear Strength
  • Treatment Outcome
  • Vasodilation / drug effects*
  • Vasodilator Agents / administration & dosage

Substances

  • Anti-Inflammatory Agents
  • Antihypertensive Agents
  • Antioxidants
  • Biomarkers
  • Endothelin-1
  • Flavonoids
  • Plant Extracts
  • Vasodilator Agents
  • dimethylarginine
  • pycnogenols
  • C-Reactive Protein
  • Arginine

Associated data

  • ClinicalTrials.gov/NCT00641758