Pilot translational study of dietary vitamin C supplementation in Barrett's esophagus

Abstract

The transcription factor Nuclear factor kappa B (NF-κB) is central to the regulation of genes encoding for mediators of inflammation and carcinogenesis. In the esophagus, NF-κB is progressively activated from inflammation to Barrett's metaplasia and adenocarcinoma. Vitamin C, an antioxidant, can inhibit NF-κB in in vitro models, and the aim of this study was to prospectively assess the effect of supplemental vitamin C on NF-κB and associated cytokines in patients with Barrett's esophagus. Twenty-five patients with long-segment Barrett's and specialized intestinal metaplasia received dietary vitamin C (1000 mg/day) orally for four weeks, and had pre- and post-vitamin C endoscopic biopsies. NF-κB activity (activated p50 and p65 subunits) of nuclear extracts was assessed using the Active Motif NF-κB assay, and cytokines and growth factors were measured using the Evidence Investigator biochip array. NF-κB and related pro-inflammatory cytokines and growth factors (IL-8, VEGF, IL-10) were activated in all Barrett's tissue pre-treatment. Down-regulation in activated NF-κB and cytokines was observed in 8/25 (35%) patients. Dietary vitamin C supplementation may down-regulate pro-inflammatory markers in a subset of Barrett's patients. Further studies with larger numbers of endpoints will be needed to further evaluate this effect. © 2009 Copyright the Authors, Journal compilation © 2010, Wiley Periodicals, Inc. and the International Society for Diseases of the Esopha.