Purified anthocyanin supplementation improves endothelial function via NO-cGMP activation in hypercholesterolemic individuals

Clin Chem. 2011 Nov;57(11):1524-33. doi: 10.1373/clinchem.2011.167361. Epub 2011 Sep 16.


Background: Anthocyanins have been shown to improve endothelial function in animal models. However, whether these compounds have similar beneficial effects in humans is largely unknown.

Methods: In a short-term crossover study, 12 hypercholesterolemic individuals were given oral anthocyanins (320 mg) isolated from berries or placebo. Brachial artery flow-mediated dilation (FMD) was assessed before and after the intervention. In a long-term intervention trial (12 weeks), 150 hypercholesterolemic individuals were given anthocyanins (320 mg/day, n = 75) or placebo (n = 75), after which we measured FMD, plasma cGMP, and other serum biomarkers. Another short-term intervention was conducted in the presence of NO-cGMP inhibitors in 6 people and in a rat aortic ring model (n = 8).

Results: Significant increases of FMD from 8.3% (0.6%) at baseline to 11.0% (0.8%) at 1 h and 10.1% (0.9%) at 2 h were observed after short-term anthocyanin consumption, concomitantly with increases of plasma anthocyanin concentrations (P < 0.05). In the study participants who received long-term anthocyanin intervention, compared with the control group, we observed significant increases in the FMD (28.4% vs 2.2%), cGMP (12.6% vs -1.2%), and HDL-cholesterol concentrations, but decreases in the serum soluble vascular adhesion molecule-1 and LDL cholesterol concentrations (P < 0.05). The changes in the cGMP and HDL cholesterol concentrations positively correlated with FMD in the anthocyanin group (P < 0.05). In the presence of NO-cGMP inhibitors, the effects of anthocyanin on endothelial function were abolished in human participants and in a rat aortic ring model.

Conclusions: Anthocyanin supplementation improves endothelium-dependent vasodilation in hypercholesterolemic individuals. This effect involves activation of the NO-cGMP signaling pathway, improvements in the serum lipid profile, and decreased inflammation.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Animals
  • Anthocyanins / therapeutic use*
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiopathology
  • Body Weights and Measures
  • Brachial Artery / drug effects
  • Brachial Artery / physiopathology
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Cross-Over Studies
  • Cyclic GMP / blood
  • Dietary Supplements
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Humans
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / physiopathology
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Rats
  • Ribes
  • Time Factors
  • Vaccinium myrtillus
  • Vascular Cell Adhesion Molecule-1 / blood
  • Vasodilation / drug effects


  • Anthocyanins
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Vascular Cell Adhesion Molecule-1
  • Cyclic GMP