Effects of oral lycopene supplementation on vascular function in patients with cardiovascular disease and healthy volunteers: a randomised controlled trial.

AIMS: The mechanisms by which a 'Mediterranean diet' reduces cardiovascular disease (CVD) burden remain poorly understood. Lycopene is a potent antioxidant found in such diets with evidence suggesting beneficial effects. We wished to investigate the effects of lycopene on the vasculature in CVD patients and separately, in healthy volunteers (HV). METHODS AND RESULTS: We randomised 36 statin treated CVD patients and 36 healthy volunteers in a 2∶1 treatment allocation ratio to either 7 mg lycopene or placebo daily for 2 months in a double-blind trial. Forearm responses to intra-arterial infusions of acetylcholine (endothelium-dependent vasodilatation; EDV), sodium nitroprusside (endothelium-independent vasodilatation; EIDV), and NG-monomethyl-L-arginine (basal nitric oxide (NO) synthase activity) were measured using venous plethysmography. A range of vascular and biochemical secondary endpoints were also explored. EDV in CVD patients post-lycopene improved by 53% (95% CI: +9% to +93%, P = 0.03 vs. placebo) without changes to EIDV, or basal NO responses. HVs did not show changes in EDV after lycopene treatment. Blood pressure, arterial stiffness, lipids and hsCRP levels were unchanged for lycopene vs. placebo treatment groups in the CVD arm as well as the HV arm. At baseline, CVD patients had impaired EDV compared with HV (30% lower; 95% CI: -45% to -10%, P = 0.008), despite lower LDL cholesterol (1.2 mmol/L lower, 95% CI: -1.6 to -0.9 mmol/L, P<0.001). Post-therapy EDV responses for lycopene-treated CVD patients were similar to HVs at baseline (2% lower, 95% CI: -30% to +30%, P = 0.85), also suggesting lycopene improved endothelial function. CONCLUSIONS: Lycopene supplementation improves endothelial function in CVD patients on optimal secondary prevention, but not in HVs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01100385

Post-hoc correlation between serum lycopene concentrations and EDV.

<p>Relationship between absolute change in serum lycopene concentrations and absolute change in endothelial dependent vasodilatation (EDV; forearm blood flow response to 15 µg/min acetylcholine measured as %change from preceding saline baseline) for all trial subjects. Absolute change in serum lycopene calculated as final visit serum lycopene minus baseline serum lycopene. Absolute change in EDV calculated as final visit EDV minus baseline EDV. r: correlation coefficient calculated using Pearson correlation analysis.</p

Baseline Demographics of CVD Patients and HV arms.

<p>Data are presented as mean (standard deviation - SD) or numbers (%). ACE-I: Angiotensin Converting Enzyme Inhibitor; ARB: Angiotensin Receptor Blocker; CVD: cardiovascular disease; EtOH: Alcohol; HV: healthy volunteer.</p

Flow diagram of subjects through the study.

<p>The safety population consisted of anyone who received at least 1*Reasons for failure to enrol included not meeting inclusion criteria, an inability to attend laboratory for assessments within the appropriate timeframe, patient withdrawal, inability to lie flat for a period of time for the studies, or an inability to cannulate the brachial artery. **Quality control evaluation done by two independent parties. Reasons for non-evaluable data and consequent exclusion from final forearm blood flow (FBF) analysis (before unblinding and statistical analysis) included incomplete data sets, non-evaluable sets, and FBF procedure variation.</p

Post-hoc comparisons of baseline values between CVD Patients and HV arms.

<p>Data are presented as mean values (standard deviation - SD). *<i>P</i>-value is for comparison between cardiovascular disease (CVD) patients arm and healthy volunteer (HV) arm at baseline using unpaired, 2-tailed Student <i>t</i>-tests. AIx – augmentation index; DBP – diastolic blood pressure; HDL – high-density lipoprotein; hsCRP – high sensitivity C-reactive protein; LDL – low-density lipoprotein; ox-LDL – oxidised low-density lipoprotein, PWV – pulse wave velocity; SBP – systolic blood pressure.</p