Association of hydroxytyrosol enriched olive oil with vascular function in chronic coronary disease

Eur J Clin Invest. 2023 Jul;53(7):e13983. doi: 10.1111/eci.13983. Epub 2023 Mar 24.


Background: Hydroxytyrosol reduces low-density lipoprotein oxidation, contributing to prevention of atherosclerosis progression.

Methods: In a prospective, crossover, double-blind, placebo-controlled trial, 30 chronic coronary artery syndrome (CCAS) patients were randomized to 4 capsules/day, containing 412.5 mg olive oil with 2.5 mg hydroxytyrosol (OOHT) each one or placebo for 1 month and then were crossed over to the alternate treatment (placebo or OOHT). We measured (a) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced glycocalyx thickness), (b) flow-mediated dilation (FMD), (c) Coronary Flow Reserve (CFR) and markers of LV diastolic function by Doppler echocardiography, (d) pulse wave velocity (PWV), and (e) oxidative stress, inflammatory biomarkers and blood lipids at baseline and after treatment.

Results: Treatment with OOHT improved PBR, FMD, CFR and PWV compared to baseline (1.8 ± .3 vs. 1.7 ± .4 μm, p = .040, 3.7 ± 2.1 vs. 6.5% ± 2.3%, p < .001, 2.3 ± .4 vs. 2.5 ± .4, p = .030 and 11.1 ± 1.8 vs. 11.8 ± 2.3 m/s, p = .002) while there was no effect after placebo (p = NS). No effect of OOHT treatment was observed on blood pressure. There was a parallel improvement of E' of the mitral annulus and deceleration time of the E wave of mitral inflow after OOHT (p < .05) but not after placebo. Compared to baseline, treatment with OOHT reduced malondialdehyde, a marker of lipid peroxidation, oxidized LDL, triglycerides, PCSK9 and CRP blood levels (p < .05) in contrast to placebo.

Conclusions: Hydroxytyrosol-enriched olive oil may have beneficial effects on endothelial, arterial and LV diastolic function likely by reducing oxidative and inflammatory burden in CCAS, though further studies are needed to confirm this mechanism.

Keywords: Hydroxytyrosol; coronary flow reserve; endothelial function; flow-mediated dilation; oxidative stress; pulse wave velocity.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Coronary Disease*
  • Heart Diseases*
  • Humans
  • Olive Oil
  • Proprotein Convertase 9
  • Prospective Studies
  • Pulse Wave Analysis


  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Olive Oil
  • 3,4-dihydroxyphenylethanol