Effect of acute copper exposure on gastrointestinal permeability in healthy volunteers

In vitro studies indicate that treating cells with copper results in alteration 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 approximately 20 and 5% of the volunteers, respectively. To understand better the gastric and intestinal effects of copper, in this study we evaluated in asymptomatic volunteers (1) the effects of acute copper ingestion on gastric and intestinal permeability and (2) whether the appearance of gastrointestinal symptoms is associated with changes in mucosal permeability. Thirty-one asymptomatic subjects were assessed in a randomized, double-blind, crossover study that included two permeability tests, one after ingesting 200 ml distilled water and the other after ingesting 200 ml water containing 10 mg 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 mannitol, and urine was collected for 5 hr. Sugar concentrations were determined by gas chromatography. Symptoms during the trials were recorded in self-administered questionnaires. Ingestion of the 10 mg/L copper solution significantly increased gastric permeability to sucrose [20.8 (11.8-73.4) vs 28.4 (16.6-113.9) mg, respectively; P = 0.0064] but did not change intestinal permeability to lactulose/mannitol [0.87 (0.53-2.06) vs 1.17 (0.58-2.39)%, respectively; P = 0.18]. Gastrointestinal symptoms were reported during both the basal and the experimental conditions, but after copper ingestion they increased to 22.6% of the subjects and were significantly more intense than under basal conditions (P = 0.047). However, changes in permeability were not 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.