Effect of acute copper exposure on gastrointestinal permeability in healthy volunteers

In vitro studies indicate that treating cells with copper results in altera tion of tight junction permeability. In humans, ingestion of a single bolus of up to 10 mg Cu/L (as copper sulfate) causes nausea and vomiting in appr oximately 20 and 5% of the volunteers, respectively. To understand better t he gastric and intestinal effects of copper, in this study we evaluated in asymptomatic volunteers (1) the effects of acute copper ingestion on gastri c and intestinal permeability and (2) whether the appearance of gastrointes tinal symptoms is associated with changes in mucosal permeability. Thirty-o ne asymptomatic subjects were assessed in a randomized, double-blind, cross over study that included two permeability tests, one after ingesting 200 ml distilled water and the other after ingesting 200 ml water containing 10 m g Cu/L (as copper sulfate). Fifteen minutes after ingestion subjects drank a second solution containing 40 g sucrose, 7.5 g lactulose, and 2 g mannito l, and urine was collected for 5 hr. Sugar concentrations were determined b y gas chromatography. Symptoms during the trials were recorded in self-admi nistered questionnaires. Ingestion of the 10 mg/L copper solution significa ntly increased gastric permeability to sucrose [20.8 (11.8-73.4) vs 28.4 (1 6.6-113.9) mg, respectively; P = 0.0064] but did not change intestinal perm eability to lactulose/mannitol [0.87 (0.53-2.06) vs 1.17 (0.58-2.39)%, resp ectively; P = 0.18]. Gastrointestinal symptoms were reported during both th e basal and the experimental conditions, but after copper ingestion they in creased to 22.6% of the subjects and were significantly more intense than u nder basal conditions (P = 0.047). However, changes in permeability were no t related to the appearance of symptoms. These results indicate that acute oral exposure to 10 mg Cu/L exerts an effect on gastric but not intestinal mucosa, reducing the gastric mucosal barrier capacity, independently of the appearance of gastrointestinal symptoms.