Effects of Dark vs. White Chocolate on the Postprandial Increase in Portal Pressure in Cirrhosis

This study was aimed at testing the hypothesis that supplementing a meal with dark chocolate, which holds potent antioxidant properties, might attenuate the postprandial increase in the hepatic venous pressure gradient (HVPG, clinical equivalent of portal pressure) in patients with cirrhosis

Study Overview

• Status: Completed
• Conditions: Cirrhosis; Portal Hypertension
• Intervention / Treatment: Dietary supplement: DarkChocolate; Dietary supplement: WhiteChocolate

Detailed Description

Previous studies showed that the intrahepatic circulation in cirrhosis is not able to adapt to sudden increases in blood flow, such as that occurring after a meal, due to endothelial dysfunction. This leads to a brisk increase in portal pressure (estimated by the HVPG). This method is therefore useful to assess the efficacy of compounds potentially ameliorating intrahepatic endothelial dysfunction. Dark chocolate, which contains a high proportion of cocoa flavonoids such as cathechin and epicatechin- powerful antioxidants, increases NO availability in the systemic circulation and improves systemic endothelial function. We hypothesised that the antioxidant properties of dark chocolate could be beneficial in patients with cirrhosis, since they might improve intrahepatic endothelial dysfunction. Consequently, the aim of this study was to evaluate whether a dark chocolate-containing test meal may attenuate the post-prandial increase in HVPG in patients with cirrhosis and portal hypertension.

HVPG was measured at baseline and 30 minutes after the administration of a test meal supplemented by either dark or white chocolate. Portal vein blood flow and hepatic artery blood flow were measured by Doppler ultrasound. Catechins and NOx were determined for both timepoints.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hepatic Hemodynamic Laboratory. Liver Unit. Hospital Clinic.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. age over 18 years
2. diagnosis of cirrhosis (proven by biopsy or clinical, laboratory and imaging procedures)
3. presence of esophageal varices of any grade
4. HVPG ≥ 10 mmHg during the hemodynamic study

Exclusion Criteria:

1. food allergy to chocolate
2. ongoing treatment with ascorbic acid and/or other antioxidants
3. diffuse or multinodular hepatocellular carcinoma
4. pregnancy
5. advanced hepatic failure (defined as prothrombin ratio < 40% and bilirubin > 5 mg/dL)
6. renal failure (defined by a serum creatinine level > 1.5 mg/dL)
7. portal vein thrombosis
8. cardiac or respiratory failure
9. previous surgical or transjugular intrahepatic portosystemic shunt

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DarkChocolate; 11 patients were randomized to receiving dark chocolate 0.55 g/kg of body weight (Lindt Excellence 85% Cocoa, Lindt & Sprüngli España) together with the test meal	Dietary supplement: DarkChocolate; Dark chocolatee 0.55 g/kg of body weight was given together with the test meal in sitting position after the baseline measurement of HVPG. The meal + chocolate was ingested in 8 minutes.; Other Names: Lindt Excellence 85% Cocoa, Lindt & Sprüngli España
Placebo Comparator: White chocolate supplementation; 11 patients received 0.63 g/kg white chocolate (Lindt Excellence Natural Vanilla, Lindt & Sprüngli España) in an iso-caloric and iso-volumetric proportion adjusted to body weight.	Dietary supplement: WhiteChocolate; White chocolate 0.63 g/kg white chocolate (Lindt Excellence Natural Vanilla, Lindt & Sprüngli España) in an iso-caloric and iso-volumetric proportion adjusted to body weight was used as a control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Postprandial change in HVPG (% change and absolute change in mmHg)	30 minutes

Secondary Outcome Measures

Outcome Measure	Time Frame
Post-prandial change in portal vein blood flow by US-Doppler	30 minutes
Post-prandial change in nitric oxide metabolites	30 minutes
Post-prandial changes in catechin and epicatechin	30 minutes
Post-prandial changes in mean arterial pressure	30 minutes

Collaborators and Investigators

• Sponsor: Hospital Clinic of Barcelona
• Collaborators: Instituto de Salud Carlos III; Consorcio Centro de Investigación Biomédica en Red, M.P.

Publications and helpful links

General Publications

• De Gottardi A, Berzigotti A, Seijo S, D'Amico M, Thormann W, Abraldes JG, Garcia-Pagan JC, Bosch J. Postprandial effects of dark chocolate on portal hypertension in patients with cirrhosis: results of a phase 2, double-blind, randomized controlled trial. Am J Clin Nutr. 2012 Sep;96(3):584-90. doi: 10.3945/ajcn.112.040469. Epub 2012 Jul 18.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: August 2, 2011
• First Submitted That Met QC Criteria: August 2, 2011
• First Posted (Estimate): August 3, 2011

Study Record Updates

• Last Update Posted (Estimate): August 3, 2011
• Last Update Submitted That Met QC Criteria: August 2, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Cirrhosis; Portal Hypertension; Catechins; Dark chocolate; Intrahepatic endothelial dysfunction
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Liver Diseases; Fibrosis; Hypertension; Liver Cirrhosis; Hypertension, Portal
• Other Study ID Numbers: DarkChocolateinHTP2008