Plasma and Esophageal Mucosal Levels of Vitamin C: Role in the Pathogenesis and Neoplastic Progression of Barrett's Esophagus

Abstract

Antioxidants may protect against the development of esophageal adenocarcinoma. Blood samples and endoscopic biopsies (squamous, Barrett's, and gastric mucosa) were obtained from 48 Barrett's esophagus (BE) patients, while 48 age- and sex-matched controls provided blood samples only. Plasma concentrations of vitamins A, C, and E were measured in all subjects, while vitamin C was measured in relation to the type of mucosa. Plasma total vitamin C level, but not vitamin A or E, was lower in BE patients compared to controls (P = 0.014). Tissue levels of total vitamin C were significantly lower in Barrett's compared with squamous mucosa (P = 0.047). A positive association was observed between plasma vitamin C and dietary intake of vitamin C, while there was an inverse association with alcohol consumption. The lower levels of vitamin C in plasma of BE patients and in Barrett's mucosa compared with squamous mucosa are consistent with oxidative stress being of importance in the pathogenesis and neoplastic progression of BE.

Molecular alterations during development of esophageal adenocarcinoma

“…Plasma and tissue vitamin C levels, but not vitamin E levels, were decreased in Barrett's esophagus compared with normal squamous epithelium [19]. Although not all enzymes involved in detoxification of radicals are decreased in Barrett's esophagus and adenocarcinoma, overall scavenging capacity seems diminished during esophageal carcinogenesis.…”

Risk factors for Barrett’s oesophagus and oesophageal adenocarcinoma: Results from the FINBAR study

“…Fruit and vegetables are high in anti-oxidants, especially in vitamin C, dietary intake of which is reduced in oesophageal adenocarcinoma patients [38,[67][68][69][70] . Tissue levels of vitamin C are also lower in areas of specialised intestinal metaplasia than in squamous mucosa suggesting that oxidative stress may be implicated in the neoplastic progression of Barrett's oesophagus [71] . Reflux of gastric contents into the oesophagus can enhance the production of free radicals which may cause damage to lipids, proteins and DNA through oxidative stress and may be implicated in the development of Barrett's oesophagus and/or oesophageal adenocarcinoma.…”

Dietary Supplement Use and Risk of Neoplastic Progression in Esophageal Adenocarcinoma: A Prospective Study

“…The anti-inflammatory effect of antioxidants may also reduce hydroperoxides in esophageal epithelium, which can otherwise activate lipoxygenase and cyclooxygenase, leading to the production of inflammatory prostaglandins and leukotrienes, an important step in the inflammatory process (54,55). The potential importance of antioxidant defenses against excessive freeradical production in the esophageal epithelium can be gathered from studies that have found lower levels of plasma and mucosal vitamin C in the metaplastic epithelium of Barrett's esophagus samples (56) and complete loss of glutathione peroxidase-3 expression, an antioxidative selenoenzyme, in EA tumors (57). Smoking, another source of oxidative damage, has been associated with a twofold increased risk of EA (58).…”