Novel edible toys as iron carrier to prevent iron deficiency of postweaned pigs.

The current preventive treatment for iron deficiency in pigs is inefficient, resulting in a high prevalence of iron-deficient or anemic postweaned pigs. The aim of this study was to develop and characterize edible toys (ETs) to be used as oral iron supplements, and to assess their effect on feeding behavior and iron status of postweaned pigs. Three types of ETs, varying in sweetness, were produced by ionic gelation, using whey, sodium alginate, ferrous sulfate and atomized bovine erythrocytes. ET control (ETC) was developed without sweetener, ET1 contained 15% w/v sucrose and ET2 contained 0.03% w/v of Sucram (98% sodium saccharin, 1% neosperidine dihydrocalcone and 1% maltol). ETs were mainly composed of carbohydrates and protein, with a similar concentration of iron (2.2-2.7 mg/g). The ETs were offered to 24 postweaned pigs to measure acceptability and preference. The animals preferred ETC and ET2 over ET1. To assess the nutritional benefit of the ETs, 24 postweaned pigs were distributed into three groups: ETC (without iron), ETC-Fe (ETC with iron) and ET2-Fe (with iron and Sucram). Iron-loaded ET (ETC-Fe and ET2-Fe) significantly increased the concentration of red blood cells (from 6.1 to 7.5·106 x mm3 for ETC-Fe and from 6.2 to 7.8 for ET2-Fe), hematocrit (from 32.8 to 37.9% for ETC-Fe and from 32.3 to 35.1 for ET2-Fe), serum iron (from 28.6 to 120.6 µmol/L for ETC-Fe and from 34.9 to 145.4 for ET2-Fe) and serum ferritin (from 7.8 to 18.5 µg/L for ETC-Fe and from 8.1 to 20.2 for ET2-Fe). In conclusion, the ETs developed in this study were accepted by the pigs and provided adequate iron to improve the iron status of postweaned pigs.

[Revista Chilena de Pediatría/Andes Pediatrica in the new millennium. Bibliometric analysis]. / Revista Chilena de Pediatría/Andes Pediatrica en el nuevo milenio. Análisis bibliométrico.

INTRODUCTION: Andes Pediatrica/Revista Chilena de Pediatría (AP/RChP), maintains a document profile that covers all scientific publication formats, from Original Articles (OAs) to Letters to the Editor. Adequate editorial planning requires a long-term bibliometric analysis. OBJECTIVE: To describe the profile of OAs published in AP/RChP in the last two decades. METHODOLOGY: From a controlled vocabulary list, the thematic and methodological descriptors of the documents from 2000 to 2020 were standardi zed. Nationality, sex, and profession of the authors, document typology, and design of the OAs were analyzed, as well as the descriptors cited in Google Scholar and the most visited descriptors on the journal's website in recent years. RESULTS: 1738 manuscripts were published, 580 (33.4%) were OAs, with an increase from 59 to 129 OAs between the first and last three years. The average number of authors was higher for OAs (4.7) than for non-originals (3.0). In 2020, there were nine multicenter collaborations from different countries. The number of OAs by foreign authors increased from 3.3% to 28.7%, the first authorship by non-medical professionals increased from 15% to 31%, and there was a predominance of female first authors (ratio 1.4/1). Of the OAs, 9.1% were experimental, 3.3% were qualitative and the rest were quantitative observational. The most published descriptors were Nutrition, Infectious Diseases, Neonatology, and Pneumonology, while the most cited descriptors were Nutrition, Neonatology, and Oral Health, with no trend among the most visited. 44% of the most cited articles and 35% of the most visited articles were OAs. CONCLUSIONS: A significant increase in published OAs stands out, with a low frequency of experimental designs. Authors of different na tionalities and professions participated. OAs represent one-third of the visits and almost half of the citations, with no correlation between the most published and most cited descriptors.

Recomendación Clínica: "Recomendaciones para el manejo de pacientes con COVID-19 con indicación terapéutica de ventilación mecánica que eventualmente son conectados a máquinas de anestesia" / Recommendations for patient management with COVID-19 with therapeutic indication mechanical ventilation that eventually are connected to anesthesia machines

La pandemia de COVID-19 producida por SARS-CoV-2 actualmente en curso anticipa una gran demanda por ventiladores mecánicos (VM), ya que un porcentaje relevante de los contagiados cae rápidamente en insuficiencia respiratoria y requiere de cuidados intensivos. Anticipándose a ese exceso de demanda y considerando que es muy probable que el número actual de ventiladores mecánicos en las unidades de cuidados intensivos (UCI) sean insuficientes, se ha solicitado a la SACH un informe técnico en relación al uso de las máquinas de anestesia como VM.

Expression of genes associated with inflammation and iron metabolism in 3T3-L1 cells induced with macrophages-conditioned medium, glucose and iron.

Obesity is characterized by a chronic inflammatory process, with an increased volume of total adipose tissue, especially visceral, which secretes pro-inflammatory cytokines such as TNF-α and IL-6. Hepcidin (Hpc), a main iron metabolism regulator, is synthetized by an IL-6 stimuli, among others, in liver and adipose tissue, favoring an association between the inflammatory process and iron metabolism. Still there are questions remain regarding the interaction of these factors. Our aim was to study the effect of a macrophage-conditioned medium (MCM) on adipocyte cells challenged with glucose and/or iron. We studied the mRNA relative abundance of genes related to inflammation in differentiated 3T3-L1 cells challenged with Fe (40 µM), glucose (20 mM) or Fe/glucose (40 µM/20 mM) with or without MCM for 24 h. We also measured the intracellular iron levels under these conditions. Our results showed that when adipocytes were challenged with MCM, glucose and/or Fe, the intracellular iron and mRNA levels of pro-inflammatory cytokines increased. These responses were higher when all the stimuli were combined with MCM from macrophages. Thus, we showed that combined high glucose/high Fe alone or with MCM may contribute to an increase on intracellular iron and inflammatory response in 3T3-L1 differentiated cells, by increased mRNA levels of IL-6, TNF-α, MCP-1, Hpc and reducing adiponectin levels, enhancing the inflammatory processes.

Effect of calcium, tannic acid, phytic acid and pectin over iron uptake in an in vitro Caco-2 cell model.

Calcium, phytic acid, polyphenols and fiber are major inhibitors of iron absorption and they could be found in excess in some diets, thereby altering or modifying the iron nutrition status. The purpose of this study is to evaluate the effect of calcium, tannic acid, phytic acid, and pectin over iron uptake, using an in vitro model of epithelial cells (Caco-2 cell line). Caco-2 cells were incubated with iron (10-30 µM) with or without CaCl2 (500 and 1,000 µM) for 24 h. Then, cells were challenged with phytic acid (50-150 µM); pectin (50-150 nM) or tannic acid (100-500 µM) for another 24 h. Finally, (55)Fe (10 µM) uptake was determined. Iron dialyzability was studied using an in vitro digestion method. Iron uptake in cells pre-incubated with 20 and 30 µM Fe was inhibited by CaCl2 (500 µM). Iron uptake decreased in cells cultured with tannic acid (300 µM) and CaCl2 (500-1,000 µM) (two-way ANOVA, p = 0.002). Phytic acid also decreased iron uptake mainly when cells were treated with CaCl2 (1,000 µM) (two-way ANOVA; p < 0.05). Pectin slightly decreased iron uptake (p = NS). Iron dialyzability decreased when iron was mixed with CaCl2 and phytic or tannic acid (T test p < 0.0001, for both) but not when mixed with pectin. Phytic acid combined with calcium is a strong iron uptake inhibitor. Pectin slightly decreased iron uptake with or without calcium. Tannic acid showed an unexpected behavior, inducing an increase on iron uptake, despite its low Fe dialyzability.

Pediatric liver transplantation experience and outcome in Chile.

INTRODUCTION: In 1994 our group began its experience with pediatric liver transplantation. The experience gained during this period is the largest in the country, positioning the Hospital Luis Calvo Mackenna and Clinica Las Condes as major referral centers in the public and private sectors. The aim of this study was to report our experience of our pediatric liver transplantation program during this period. METHODS: The liver transplantation database of Hospital Luis Calvo Mackenna and Clinica Las Condes between January 1994 and July 2011 was reviewed recording age, gender, indications for transplantation, surgical technique, complications, and survival. Survival rates were calculated using Kaplan-Meier analysis. RESULTS: During the period described 230 transplantations were performed in 189 pediatric patients. Fifty-five percent were male patients. The average age was 5 years. The main causes of transplantation were biliary atresia (50%), fulminant hepatic failure (25%), and other cholestatic diseases by 10%. Vascular and biliary complications were the leading cause of graft loss and retransplantation. The overall rate of retransplantation at 5 years was 20%. The technique of living donor was used in 28% of the cases. The 1-year patient actuarial survival rate was 80%, 73% at 5 years, and 68% at 10 years. In the last 3 years the survival rate at 1 year exceeds 90%. DISCUSSION: Our program includes more than 90% of the national liver experience. The incorporation of living donor is a milestone that has enabled us to save many patients who previously died while waiting for an organ. Its use in cases of full acute liver failure has allowed us to dramatically reduce mortality on the waiting list. Our results in the last 3 years reflect the experience that results in a significant decrease in mortality, comparing favorably to other series published in the international literature.

Evolución de la ingesta y del estado nutricional de zinc, hierro y cobre en mujeres sometidas a cirugía bariátrica hasta el segundo año postoperatorio / Evolution of the intake and nutritional status of zinc, iron and copper in women undergoing bariatric surgery until the second year after surgery

Introducción: La cirugía bariátrica permite una reducción significativa de peso y mejoría de comorbilidades asociadas a la obesidad a largo plazo, pero también puede afectar negativamente el estado nutricional de algunos micronutrientes. Objetivos: Evaluar cambios en ingesta e indicadores del estado nutricional de zinc, hierro y cobre en mujeres sometidas a bypass gástrico en Y de Roux (BPG) o gastrectomía tubular (GT), hasta el segundo año postoperatorio. Métodos: Se estudió prospectivamente 45 mujeres sometidas a BPG o GT (edad promedio 35,2 ± 8,4 años, IMC promedio 39,8 ± 4,0 kg/m2), cada 6 meses se realizaron determinaciones de ingesta e indicadores del estado nutricional de zinc, hierro y cobre, y en forma anual se evaluó la composición corporal. El aporte de minerales a través de los suplementos representaba dos veces la ingesta recomendada para una mujer sana en las pacientes sometidas a GT y tres veces para BPG. Resultados: 20 mujeres se sometieron a GT y 25 a BPG. En ambos grupos se produjo una reducción significativa de peso y del porcentaje de masa grasa, que se mantuvo hasta el segundo año postoperatorio. Las mujeres sometidas a BPG presentaron un mayor compromiso del estado nutricional de zinc, hierro y cobre, que las pacientes sometidas a GT. Conclusiones: El bypass gástrico en Y de Roux produce un compromiso mayor del estado nutricional de zinc, hierro y cobre que la gastrectomía tubular. Se debería evaluar si la administración fraccionada de la suplementación mejoraría la absorción de estos nutrientes (AU)

Introduction: Bariatric surgery allows a significant reduction in weight and improvement of comorbidities associated with obesity in the long term, but it can also adversely affect the nutritional status of some micronutrients. Objectives: To evaluate changes in intake and parameters of nutritional status of zinc, iron and copper in patients undergoing Roux-en-Y gastric bypass (GBP) or sleeve gastrectomy (SG), until the second postoperative year. Methods: We prospectively studied 45 women undergoing GBP or SG (mean age 35.2 ± 8.4 years, mean BMI 39.8 ± 4.0 kg/m2), every 6 months We measured intake and status indications nutritional zinc, iron and copper, and annually evaluated body composition. The contribution of minerals through supplements represented twice the recommended intake for a healthy woman in patients undergoing GT and three times for GBP. Results: 20 women underwent GBP and 25 SG. In both groups there was a significant reduction in weight and body fat percentage, which was maintained until the second postoperative year. Women who have had a greater commitment GBP nutritional status of zinc, iron and copper, that patients undergoing SG. Conclusions: Gastric bypass Roux-Y produces a greater commitment of nutritional status of zinc, iron and copper sleeve gastrectomy. It should evaluate whether administration of supplementation fractional improve the absorption of these nutrients (AU)

[Evolution of the intake and nutritional status of zinc, iron and copper in women undergoing bariatric surgery until the second year after surgery]. / Evolución de la ingesta y del estado nutricional de zinc, hierro y cobre en mujeres sometidas a cirugía bariátrica hasta el segundo año postoperatorio.

INTRODUCTION: Bariatric surgery allows a significant reduction in weight and improvement of comorbidities associated with obesity in the long term, but it can also adversely affect the nutritional status of some micronutrients. OBJECTIVES: To evaluate changes in intake and parameters of nutritional status of zinc, iron and copper in patients undergoing Roux-en-Y gastric bypass (GBP) or sleeve gastrectomy (SG), until the second postoperative year. METHODS: We prospectively studied 45 women undergoing GBP or SG (mean age 35.2 ± 8.4 years, mean BMI 39.8 ± 4.0 kg/m²), every 6 months We measured intake and status indications nutritional zinc, iron and copper, and annually evaluated body composition. The contribution of minerals through supplements represented twice the recommended intake for a healthy woman in patients undergoing GT and three times for GBP. RESULTS: 20 women underwent GBP and 25 SG. In both groups there was a significant reduction in weight and body fat percentage, which was maintained until the second postoperative year. Women who have had a greater commitment GBP nutritional status of zinc, iron and copper, that patients undergoing SG. CONCLUSIONS: Gastric bypass Roux-Y produces a greater commitment of nutritional status of zinc, iron and copper sleeve gastrectomy. It should evaluate whether administration of supplementation fractional improve the absorption of these nutrients.

Transepithelial heme-iron transport: effect of heme oxygenase overexpression.

BACKGROUND: Heme iron is found in the diet mainly in the form of hemoglobin and myoglobin. It is known that heme iron (heme-Fe) and inorganic iron are absorbed differently. Intracellularly, heme oxygenase-1 (HO1) participates in the cleavage of the heme ring producing biliverdin, CO and ferrous iron. Iron released from heme becomes part of labile iron pool, and it can be stored in ferritin or released through the basolateral membrane. The mechanism by which heme-Fe is metabolized within cells is not completely understood. OBJECTIVE: This study focused on the uptake and transport of heme iron and on the role of heme oxygenase-1 on heme iron metabolism. DESIGN: Caco-2 cells were incubated with different concentrations of heme-Fe. A full-length heme oxygenase-1 cDNA was expressed in Caco-2 cells and intracellular iron and heme-Fe content, heme uptake, heme and iron transport and heme oxygenase-1 immunolocalization were assessed in these cells. RESULTS: Heme-Fe was bioavailable and induced an intracellular increase in iron, ferritin and HO1 levels and a decrease in DMT1 expression. In cells overexpressing HO1, heme-Fe uptake and transepithelial Fe transport was higher than in controls. Most heme-Fe was metabolized to free iron, most of which was found mainly in the basolateral chamber. However, there is a fraction of heme that is delivered intact to the basolateral side. In a high heme-Fe condition, HO1 is found near the plasma membrane. CONCLUSIONS: These results suggest that heme oxygenase-1 catabolizes most of the heme-Fe and favors iron influx and efflux in intestinal cells.

Blood biochemical indicators in young and adult Cebus apella of both sexes.

BACKGROUND: A frequent drawback in physiology of non-human primates is that normal values for a variety of indicators (haematological, biochemical and others) are scant. METHODS: We report here the blood values in a series of 92 healthy Cebus apella (divided by sex, age and pregnancy status). Health check-ups indicated that animals were healthy for the month prior to and after the sampling. Dietary intake was estimated on the basis of two semi-balance studies. RESULTS: Values of haematological indicators, serum LDH activity, micronutrient indicators (serum copper, iron and serum ceruloplasmin concentrations, Zn-Cu-superoxide dismutase activity in erythrocytes) agreed with previous results and provide some values that were not available. Activities of liver enzymes were lower than some previously reported. CONCLUSIONS: These results provide valuable information that help understanding the physiology of C. apella.

Zinc inhibits nonheme iron bioavailability in humans.

There is increasing concern about potential negative interactions in combined iron and zinc supplementation. The aim of the present study was to determine the dose-response effect of zinc, given as a solution, on iron bioavailability. Twenty-two healthy adult women were selected to participate in the study. Iron, with or without zinc was given as an aqueous solution on d 1,2,14, and 15 of the study. Iron bioavailability was measured on the basis of erythrocyte incorporation of 55Fe or 59Fe 14 d after administration. Subjects received 0.5 mg of iron together with graded zinc concentrations (0-11.71 mg). No significant effect of zinc on iron absorption was found at Zn:Fe molar ratios up to 2:1. At 5:1,10:1, and 20:1 molar ratios, a dose-dependent inhibitory effect on iron absorption was observed (28-40% of iron absorption inhibition; one-way repeated-measures ANOVA, F=4.48, p=0.02). In conclusion, zinc administration combined with iron in an aqueous solution leads to the inhibition of iron bioavailability, which occurs in a dose-dependent way. This negative interaction should be considered for supplementation programs with both microminerals.

Erythrocyte CuZn superoxide dismutase activity is decreased in iron-deficiency anemia.

Iron and copper are essential microminerals that are intimately related. The present study was performed to determine the effect of iron-deficiency anemia (IDA) and treatment with iron on laboratory indicators of copper status. Hemoglobin, mean corpuscular volume erythrocyte Zn protoporphyrin, serum ferritin, serum copper, serum ceruloplasmin, and erythrocyte CuZn-superoxide dismutase (SOD) activity were studied in 12 adult women with IDA before and after iron treatment for 60-90 d (100 mg/d Fe, as ferric polymaltose) and in 27 women with normal iron status. Prior to treatment with iron, serum copper and ceruloplasmin were not different between the groups and treatment with iron did not affect these measures. IDA women, before and after treatment with iron, presented a 2.9- and 2-fold decrease in erythrocyte CuZn-SOD activity compared to women with normal iron status (p < 0.001). Treatment with iron increased erythrocyte CuZn-SOD activity of the IDA group; however, this change was not statistically significant. In conclusion, CuZn-SOD activity is decreased in IDA. Measurement of this enzyme activity is not useful for evaluating copper nutrition in iron-deficient subjects.

Nutritional status, food consumption and physical activity among Chilean school children: a descriptive study.

OBJECTIVE: To assess the nutritional status, food consumption and physical activity (PA) habits of Chilean school children, as a baseline for developing an educational intervention. DESIGN: Cross-sectional study. SUBJECTS: A total of 1701 children from 3rd to 7th grade in nine schools located in three geographical regions. METHODS: We determined body mass index, food consumption (quantified FFQ which we categorised into five groups), PA in terms of TV viewing and frequency of after school PA. The data were analysed according to age, nutritional status and gender. A logistic regression analysis was performed using obesity as outcome. RESULTS: Obesity was higher among boys; younger children presented higher prevalence in both genders. Daily intake of dairy products varied between 240 and 308 g, fruits/vegetables, between 197 and 271 g, energy-dense foods between 343 and 460 g. In all, 22.3 and 47% of the children watched over 3 h of TV during the week and weekend, respectively. Older children watched significantly more TV during the week, while on weekends all children increased this time significantly. Boys were more active than girls after school. The logistic regression analysis showed a significant association between obesity and low intake of dairy products. CONCLUSIONS: Prevalence of obesity among Chilean children is high. Although TV time, intake of energy dense foods and fruits/vegetables appeared as risk factors for obesity, only dairy consumption was significantly associated with obesity. SPONSORSHIP: FAO

Bioavailability of elemental iron powder in white wheat bread.

OBJECTIVE: Iron fortification of wheat flour is widely used. In most cases, elemental iron powders are utilized as fortificants due to their lower cost and few, if any, sensory problems. However, their bioavailability is unknown. We aimed to measure the bioavailability of H(2)-reduced elemental iron powder in white wheat bread made from 72% extraction flour. DESIGN: A stable isotope of H(2)-reduced iron powder (mean particle size 15 microm) was used as fortificant in bread prepared from unfortified wheat flour. In all, 12 5- to 7-y-old children were fed bread with 4 mg of H(2)-reduced (58)Fe /100 g of flour. The next day (57)Fe ascorbate was given as reference dose. After 14 days, erythrocytes were analyzed for isotopic enrichment using mass spectrometry. RESULTS: When normalized to 40% absorption of the reference dose, the geometric mean (+/-range of 1 s.d.) bioavailability of reduced (58)Fe in wheat bread rolls was 6.5% (3.7-11.8). CONCLUSIONS: When compared to previous radioiron studies of ferrous sulfate showing 10% absorption from an identical meal in adult women, the relative bioavailability can be estimated at about 65%. However, the bioavailability of this smaller particle size (58)Fe (15 microm) is likely to be higher than that of commercial iron powder (45 microm) although the precise difference cannot be ascertained with current methods. Thus, the bioavailability of commercial elemental iron powders currently used in fortification programs is likely to be substantially lower than that of ferrous sulfate. SPONSORSHIP: This work was funded in part by Grant No 910313 by Micronutrient Initiative, IDRC, Ottawa, Canada.

Health and aesthetic impacts of copper corrosion on drinking water.

Traditional research has focused on the visible effects of corrosion--failures, leaks, and financial debits--and often overlooked the more hidden health and aesthetic aspects. Clearly, corrosion of copper pipe can lead to levels of copper in the drinking water that exceed health guidelines and cause bitter or metallic tasting water. Because water will continue to be conveyed to consumers worldwide through metal pipes, the water industry has to consider both the effects of water quality on corrosion and the effects of corrosion on water quality. Integrating four key factors--chemical/biological causes, economics, health and aesthetics--is critical for managing the distribution system to produce safe water that consumers will use with confidence. As technological developments improve copper pipes to minimize scaling and corrosion, it is essential to consider the health and aesthetic effects on an equal plane with chemical/biological causes and economics to produce water that is acceptable for public consumption.

Bioavailability of iron bis-glycinate chelate in water.

Iron amino acid chelate is being increasingly considered in programs for iron fortification of foods. The bioavailability of iron bis-glycinate chelate given in water was studied using a double-isotopic method in a group of 14 women. Iron absorption from aqueous solutions of 15 mg/L of elemental iron as either iron bis-glycine chelate or ferrous ascorbate was not significantly different (34.6% and 29.9% respectively). Standardized iron absorption of the iron bis-glycinate was 46.3% (standardized to 40% absorption of the reference dose). There was a significant correlations between (ln) iron absorption of iron bis-glycinate chelate with (ln) serum ferritin (r = -0.60, p < 0.03) and with (ln) iron absorption from ferrous ascorbate (r = 0.71, p < 0.006), suggesting that iron bis-glycinate chelate absorption is indeed regulated by the iron stores of the body.

Gastrointestinal effects associated with soluble and insoluble copper in drinking water.

The aim of this study was to determine whether total copper or soluble copper concentration is associated with gastrointestinal signs and symptoms. Forty-five healthy adult women (18-55 years of age), living in Santiago, Chile, ingested tap water with 5 mg/L of copper containing different ratios of soluble copper (copper sulfate) and insoluble copper (copper oxide) over a 9-week period. Three randomized sequences of the different copper ratios (0:5, 1:4, 2:3, 3:2, and 5:0 mg/L) were followed. Subjects recorded their water consumption and gastrointestinal symptoms daily on a special form. Mean water consumption was similar among groups. Serum copper levels, ceruloplasmin, and activities of liver enzymes were within normal limits. No differences were detected between the means of biochemical parameters at the beginning and at the end of the study. Twenty subjects presented gastrointestinal disturbances at least once during the study, 9 suffered diarrhea (with or without abdominal pain and vomiting), and the other 11 subjects reported abdominal pain, nausea, or vomiting. No differences were found in incidence of abdominal pain, nausea, vomiting, and diarrhea regardless of the ratio of copper sulfate to copper oxide. In conclusion, both copper sulfate (a soluble compound) and copper oxide (an insoluble compound) have comparable effects on the induction of gastrointestinal manifestations, implying that similar levels of ionic copper were present in the stomach.

Determination of an acute no-observed-adverse-effect level (NOAEL) for copper in water.

A prospective, double-blind controlled study was designed to determine the acute no-observed-adverse-effect level (NOAEL) of nausea in an apparently healthy population of 179 individuals who drank copper-containing water as the sulfate salt. Subjects were recruited at three different international sites and given a blind, randomly selected dose (0, 2, 4, 6, or 8 mg Cu/L) in a bolus of 200 ml (final total copper dose was equivalent to 0, 0.4, 0.8, 1.2, and 1.6 mg) once weekly over a consecutive 5-week period. Gastrointestinal (GI) symptoms of nausea, abdominal pain, vomiting, or diarrhea were screened for a period of up to 24 h. Nausea was the most frequently reported effect and was reported within the first 15 min of ingestion. For the combined trisite population (n=179), 8, 9, 14, 25, and 44 subjects responded positively to one or more GI symptoms at 0, 2, 4, 6, and 8 mg Cu/L, respectively. Analysis of the data demonstrated a clear dose response to the combined positive GI effects and to nausea alone. Statistically significant greater reporting of effects occurred at 6 and 8 mg Cu/L. Therefore, an acute NOAEL and lowest-observed-adverse-effect level of 4 and 6 mg Cu/L (0.8 and 1.2 mg Cu), respectively, were determined in drinking water for a combined international human population.

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.