Gastrointestinal symptoms and blood indicators of copper load in apparently healthy adults undergoing controlled copper exposure

Background: Mild and moderate effects of marginally low and marginally high copper exposure are poorly understood in humans. Objective: The objective was to assess acute gastrointestinal effects and blood markers of copper status in apparently healthy adults who underwent controlled copper exposure for 2 mo. Design: This was a 2-mo, randomized, controlled, double-blind study of 1365 apparently healthy adults in whom acute gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain) were assessed as responses to copper exposure (< 0.01, 2, 4, or 6 mg/L water). Blood markers were measured in 240 participants at the end of the survey. Subjects with anemia, inflammation, or infection were excluded. Serum and erythrocyte copper, peripheral mononuclear cell copper, serum ceruloplasmin, the nonceruloplasmin bound copper fraction, superoxide dismutase activity, hemoglobin, mean corpuscular volume, serum ferritin, and liver enzyme activities were measured. Results: The percentage of subjects reporting gastrointestinal symptoms was higher in the 6-mg Cu group than in the < 0.01-mg Cu group (P < 0.02). One hundred ninety-five subjects fulfilled the inclusion criteria for the blood studies. Although a significant relation between copper intake and total gastrointestinal symptoms was observed, no relation was found between copper intake or reported symptoms and copper-load variables. Conclusions: Gastrointestinal symptoms increased significantly in response to 6 mg Cu/L water. No detectable changes were observed in indicators of copper status, which suggests competent homeostatic regulation. The results of liver function tests remained normal in all subjects. The lack of change in superoxide dismutase activity supports the Food and Nutrition Board's latest recommendation of 0.9 mg Cu/d for adults.