Abnormalities in Zinc Homeostasis in Young Infants with Cystic Fibrosis

Abstract

Low plasma zinc concentrations have been reported in approximately 30% of young infants with cystic fibrosis identified by newborn screening. The objective of this study was to examine zinc homeostasis in this population by application of stable isotope methodology. Fifteen infants with cystic fibrosis (9 male, 6 female; 7 breast-fed, 8 formula-fed) were studied at a mean (ϮSD) age of 1.8 Ϯ 0.7 mo. On d 1, 70 Zn was administered intravenously, and 67 Zn was quantitatively administered with all human milk/formula feeds during the day. Three days later, a 3-d metabolic period was initiated, during which time intake was measured and complete urine and fecal collections were obtained. Fractional zinc absorption, total absorbed zinc, endogenous fecal zinc, and net absorbed zinc were measured; fecal fat excretion was also determined. Fractional absorption was significantly higher for the breast-fed infants (0.40 Ϯ 0.21) compared with the formula-fed group (0.13 Ϯ 0.06) (p ϭ 0.01), but with the significantly higher dietary zinc intake of the formula-fed group, total absorbed zinc was higher for those receiving formula (p ϭ 0.01). In 11 infants with complete zinc metabolic data, excretion of endogenous zinc was twofold greater for the formula-fed infants (p Ͻ 0.05); net absorption (mg zinc/d) was negative for both feeding groups: Ϫ0.04 Ϯ 0.52 for breast-fed; Ϫ0.28 Ϯ 0.57 for formula-fed. Endogenous fecal zinc losses correlated with fecal fat excretion (r ϭ 0.89, n ϭ 9, p ϭ 0.001), suggesting interference with normal conservation of endogenously secreted zinc. These findings indicate impaired zinc homeostasis in this population and suggest an explanation for the observations of suboptimal zinc status in many young infants with cystic fibrosis prior to diagnosis and treatment. The prevalence of zinc deficiency in individuals with cystic fibrosis has been an area of some uncertainty. Young infants, because of their rapid rates of growth, have relatively high physiologic zinc requirements. There have been several reports of young infants with cystic fibrosis presenting with signs and symptoms of severe zinc deficiency (1-3). Previous observations from the Colorado Newborn Screening Program suggested that zinc status was frequently suboptimal by 6 wk of age in infants found to have cystic fibrosis. Nearly 30% of subjects were found to have plasma zinc concentrations below the normal range, consistent with moderate zinc deficiency. In the same infants, treatment with pancreatic enzymes was associated with significant increases in plasma zinc concentrations (4). To investigate the potential underlying perturbations, we undertook detailed studies of zinc metabolism in these infants by the application of zinc stable isotope methodology.The objectives were to examine fractional absorption and fecal excretion of endogenous zinc according to type of feeding and degree of fat malabsorption. METHODS Study design.This was a cross-sectional study of zinc homeostasis in young infants with cystic fibrosis who were identified by newborn ...

Serum Zinc Concentrations in Cystic Fibrosis Patients Aged Above 4 Years: A Cross-sectional Evaluation

“…Since in our healthy controls (1) 12.6 % has a serum Zn concentration below the lower cut-off of the NHANES II study (3), they could be considered as a population at risk for Zn deficiency. Therefore it is interesting to have a closer look at populations with diseases known to cause increased Zn losses such as CF (2,32). Especially since the data on prevalence of Zn deficiency in the CF population are inconsistent (32)(33)(34)(35)(36).…”

Antioxidants in cystic fibrosis☆Conclusions from the CF Antioxidant Workshop, Bethesda, Maryland, November 11-12, 2003

“…Twenty to 30% of infants with CF identified by newborn screening have insufficient plasma levels of Zn by 2 months of age [160], and some infants with CF can have severe Zn deficiency by that time [161,162], resulting in rash, diarrhea, and a potentially fatal decrease in resistance to infection. Because Zn pools in the body depend on fat absorption [160], pancreatic enzyme administration greatly increases Zn levels [163], but supplementation is still needed for normalizing plasma levels in many individuals with CF.…”

Extracellular Zinc and ATP Restore Chloride Secretion across Cystic Fibrosis Airway Epithelia by Triggering Calcium Entry

“…It is derived from human diets and is required for healthy function of the body, and no chronic disorders are known to be associated with its accumulation (49,50). Zinc oxide creams alleviate dermatitis, including acrodermatitis enteropathica in at least 30% of CF patients caused by zinc malabsorption and deficiency (51). Defective activity of a zinc transporter, hZip4, in the intestinal mucosa is also linked to this form of dermatitis (52).…”