Postprandial effects of dark chocolate on portal hypertension in patients with cirrhosis: results of a phase 2, double-blind, randomized controlled trial.
BACKGROUND
In cirrhosis, hepatic endothelial dysfunction as a result of oxidative stress contributes to the postprandial increase in hepatic venous pressure gradient (HVPG).


OBJECTIVE
We aimed at testing the hypothesis that dark chocolate, which holds potent antioxidant properties, might attenuate the postprandial increase in HVPG in patients with cirrhosis.


METHODS
In this phase 2, double-blind, controlled study, 22 cirrhotic patients referred for HVPG measurement were included and randomly assigned to receive a liquid meal containing either dark chocolate (active treatment; 85% cocoa, 0.55 g/kg body wt; n = 11) or isocaloric amounts of white chocolate (devoid of cocoa flavonoids; control subjects; n = 11). HVPG, arterial pressure, portal blood flow, serum flavonoids (catechin and epicatechin), and nitric oxide were measured at baseline and 30 min after meal administration. The main outcome measure was the change in HVPG 30 min after the test meal.


RESULTS
Postprandial hyperemia was accompanied by a marked increase in HVPG in the white-chocolate group (16.0 ± 4.7-19.7 ± 4.1 mm Hg or +26.4 ± 12.7%; P < 0.0001), whereas the postprandial increase in HVPG was markedly attenuated in the dark-chocolate group (16.9 ± 2.9-18.7 ± 3.5 mm Hg or +11.5 ± 15.9%; P = 0.02 compared with white chocolate). Portal blood flow increased similarly after meals containing dark or white chocolate (median increase: 32% compared with 39%). Plasma flavonoids increased 15-50-fold after dark chocolate consumption. Dark but not white chocolate induced a mild increase in arterial pressure (+8.8 ± 8.8% compared with -0.3 ± 4.9%; P = 0.002).


CONCLUSIONS
In patients with cirrhosis, dark chocolate blunted the postprandial increase in HVPG by improving flow-mediated hepatic vasorelaxation and ameliorated systemic hypotension. This trial was registered at clinicaltrials.gov as NCT01408966.
Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
Andrea
A
De Gottardi
Annalisa
A
Berzigotti
Susana
S
Seijo
Mario
M
D'Amico
Wolfgang
W
Thormann
Juan G
JG
Abraldes
Juan Carlos
JC
García-Pagán
Jaime
J
Bosch
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D002099:Cacao / Q000737:chemistry; D002392:Catechin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D005526:Food, Formulated / Q000032:analysis*; D006801:Humans; D006940:Hyperemia / Q000209:etiology / Q000517:prevention & control; D006975:Hypertension, Portal / Q000209:etiology / Q000517:prevention & control*; D008102:Liver Circulation; D008103:Liver Cirrhosis / Q000097:blood / Q000178:diet therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress; D010858:Pigmentation; D019518:Postprandial Period
D000975:Antioxidants; D005419:Flavonoids; D009569:Nitric Oxide; D002392:Catechin