The reproducibility of the plasma response to a physiological dose of zinc in healthy subjects. Implications for study design (original) (raw)
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International Journal for Vitamin and Nutrition Research, 2005
The focus of this paper is on the application of measurements of zinc absorption in human research, especially studies designed to assess the efficacy of intervention strategies to prevent and manage zinc deficiency in populations. Emphasis is given to the measurement of quantities of zinc absorbed rather than restricting investigations to measurements of fractional absorption of zinc. This is especially important when determining absorption of zinc from the diet, whether it be the habitual diet or an intervention diet under evaluation. Moreover, measurements should encompass all meals for a minimum of one day with the exception of some pilot studies. Zinc absorption is primarily via an active saturable transport process into the enterocytes of the proximal small intestine. The relationship between quantity of zinc absorbed and the quantity ingested is best characterized by saturable binding models. When applied to human studies that have sufficient data to examine dose-response rel...
Effects of oral zinc loading on zinc metabolism in humans—I: Experimental studies
Metabolism, 1982
The effects of oral zinc on distribution, retention and excretion of orally administered '%I were studied in 56 patients with taste and smell dysfunction. The study was conducted in three phases. In the first phase all patients were studied for 21 days after receiving 3-18 &i of %n as ZnCI, orally after an overnight fast. In the second phase, started after 21 days and continued for 290 to 446 (mean 338) days, all 56 patients received placebo for Zn80,. In the third phase 14 patients continued on placebo while 38 received ZnSO, (1 Wmg/day Znf + 1 for 112 to 440 (mean 307) days. Phases two and three were a controlled clinical trial of the effects of zinc on retention of "Zn tracer. Total body retention and activity in plasma and red blood cells were measured for all patients throughout the study. Ten of the 38 patients treated with ZnSO., had additional measurements of 66Zn activity in liver and thigh made using external detectors. Total body retention during the second phase placebo period was not significantly different (p > 0.25) for the 36 subjects subsequently treated with ZnSO, (biological half-time (T,) 378 + 12 days) (mean + SEMI and the 14 who were continued on placebo through the third phase of the study (T, = 384 + 8 days). During the third phase patients receiving ZnSO, showed an accelerated loss of total body "Zn (T, = 235 f 8 days) which was significantly different (p < 0.001) from half-time values during placebo treatment. Accelerated loss of "Zn from the thigh was apparent immediately, while that from the liver began after a mean delay of 107 days. There was no apparent effect of zinc on loss of mean =Zn activity from red blood cells.
Effect of acute zinc depletion on zinc homeostasis and plasma zinc kinetics in men
The American Journal of Clinical Nutrition, 2001
Background: Zinc homeostasis and normal plasma zinc concentrations are maintained over a wide range of intakes. Objective: The objective was to identify the homeostatic response to severe zinc depletion by using compartmental analysis. Design: Stable zinc isotope tracers were administered intravenously to 5 men at baseline (12.2 mg dietary Zn/d) and after 5 wk of acute zinc depletion (0.23 mg/d). Compartmental modeling of zinc metabolism was performed by using tracer and mass data in plasma, urine, and feces collected over 6-14 d. Results: The plasma zinc concentration fell 65% on average after 5 wk of zinc depletion. The model predicted that fractional zinc absorption increased from 26% to essentially 100%. The rate constants for zinc excretion in the urine and gastrointestinal tract decreased 96% and 74%, respectively. The rate constants describing the distribution kinetics of plasma zinc did not change significantly. When zinc depletion was simulated by using an average mass model of zinc metabolism at baseline, the only change that accounted for the observed fall in plasma zinc concentration was a 60% reduction in the rate constant for zinc release from the most slowly turning over zinc pool. The large changes in zinc intake, excretion, and absorption-even when considered together-only explained modest reductions in plasma zinc mass. Conclusion: The kinetic analysis with a compartmental model suggests that the profound decrease in plasma zinc concentrations after 5 wk of severe zinc depletion was mainly due to a decrease in the rate of zinc release from the most slowly turning over body zinc pool.
The American journal of clinical nutrition, 2008
No studies have examined the independent effects of current and longer-term dietary zinc intakes on zinc absorption. We determined the effects of current compared with longer-term zinc intake on fractional zinc absorption (FZA). We studied 9 men whose usual zinc intakes were >11 mg/d. FZA was measured at baseline, depletion (0.6 mg Zn/d for 1 wk and 4 mg Zn/d for 5 wk), and repletion (11 mg Zn/d for 4 wk with 20 mg supplemental Zn/d for first 7 d). During 2 successive days after each dietary period, subjects consumed either adequate-zinc meals (11 mg Zn/d) with a zinc stable isotope tracer for 1 d, followed by low-zinc meals (4 mg Zn/d) with zinc tracer, or vice versa. Five days after oral dosing, a zinc tracer was infused intravenously. FZA was measured with the use of a modified double isotope tracer ratio method with urine samples collected on days 5-7 and 10-12 of absorption studies. Plasma and urinary zinc did not vary by dietary period. Mean FZA was greater from low-zinc me...
Zinc bioavailability and homeostasis
The American Journal of Clinical Nutrition, 2010
Zinc has earned recognition recently as a micronutrient of outstanding and diverse biological, clinical, and global public health importance. Regulation of absorption by zinc transporters in the enterocyte, together with saturation kinetics of the absorption process into and across the enterocyte, are the principal means by which whole-body zinc homeostasis is maintained. Several physiologic factors, most notably the quantity of zinc ingested, determine the quantity of zinc absorbed and the efficiency of absorption. Other factors are age and the time over which zinc is ingested. Zinc from supplements has not been shown to be absorbed differently from that taken with meals that lack inhibitors of zinc absorption. The principal dietary factor known to impair zinc bioavailability is inositol hexa-(and penta-) phosphate or phytate. Modeling of zinc absorption as a function of dietary zinc and phytate accounts for .80% of the variability in the quantity of zinc absorbed. Fitting the model to new data has resulted in continual improvement in parameter estimates, which currently indicate a maximal absorption in adults of '6 mg Zn/d and that the average estimated dietary requirement doubles with 1000 mg dietary phytate/d. Intestinal excretion of endogenous zinc is regulated in response to recent absorption and to zinc status. The quantitative relation of intestinal excretion of endogenous zinc to zinc absorption is currently considered to be of major importance in the determination of zinc requirements. The effects of phytate on intestinal losses of endogenous zinc merit further investigation but are probably not of the same magnitude as its inhibitory effects on absorption of exogenous zinc.
Zinc pharmacokinetic parameters in the determination of body zinc status in children
European Journal of Clinical Nutrition, 2014
BACKGROUND/OBJECTIVES: Serum or tissue zinc concentrations are often used to assess body zinc status. However, all of these methods are relatively inaccurate. Thus, we investigated three different kinetic methods for the determination of zinc clearance to establish which of these could detect small changes in the body zinc status of children. SUBJECTS/METHODS: Forty apparently healthy children were studied. Renal handling of zinc was investigated during intravenous zinc administration (0.06537 mg Zn/kg of body weight), both before and after oral zinc supplementation (5 mg Zn/day for 3 months). Three kinetic methods were used to determine zinc clearance: CZn-Formula A and CZn-Formula B were both used to calculate systemic clearance; the first is a general formula and the second is used for the specific analysis of a single-compartment model; CZn-Formula C is widely used in medical practices to analyze kinetic routine. RESULTS: Basal serum zinc values, which were within the reference range for healthy children, increased significantly after oral zinc supplementation. The three formulas used gave different results for zinc clearance both before and after oral zinc supplementation. CZn-Formula B showed a positive correlation with basal serum zinc concentration after oral supplementation (R 2 ¼ 0.1172, P ¼ 0.0306). In addition, CZn-Formula B (P ¼ 0.0002) was more effective than CZn-Formula A (P ¼ 0.6028) and CZn-Formula C (P ¼ 0.0732) in detecting small variations in body zinc status. CONCLUSIONS: All three of the formulas used are suitable for studying zinc kinetics; however, CZn-Formula B is particularly effective at detecting small changes in body zinc status in healthy children.
Zinc and Its Paradoxes Involving some Human Health Issues on Supplementation
This paper aims at echoing the health implications of zinc in humans to the scientific world in order to designing a proper means to streamlining its research. The paper looks at some important functions of zinc, some health risks of zinc deficiency and, the boons and ambiguities associated with zinc supplementation trials. Zinc supplementations have, among others, such important health benefits as; improving immune system functions, reducing the duration and severity of diarrhea in children, and of common cold, reducing the incidence of pneumonia and of HIV/AIDS infections, may reducing the incidence of clinical attacks of malaria in children. However, the optimum zinc doses and dosages for these health conditions have not been ascertained for supplementation due to lack of its sensitive nutritional status biomarker and or improper zinc study design. Zinc bioavailability is relatively high in meat, eggs and seafood because of the relative absence of compounds that inhibit its absorption and the presence of sulfur-containing amino acids like cysteine and methionine that improve its absorption. The future of zinc research is promising as it would help addressing such health challenges as malaria, tuberculosis, diabetes, blindness, sexual dysfunction, diarrhea, cancer and others when at the cutting edge. It is therefore suggested, inter alia, that a sensitive and specific biomarker should be holistically designed for zinc to help detecting marginal zinc deficiency in humans as this will streamline its associated health studies; Review Article Sheriff; BJMMR, 17(11): 1-13, 2016; Article no.BJMMR.19886 2 more and well-designed randomized controlled trials of zinc supplementation should be conducted to determining optimum dosage, formulation and duration of treatment for a specific health condition.
The Journal of nutrition, 2004
The search for a reliable, convenient indicator of Zn status was the focus of research for several decades. Plasma Zn concentration is still the most widely used clinical measurement, despite the known problems of interpretation. More recently, researchers suggested that isotopically determined kinetic parameters, such as the exchangeable Zn pool (EZP), may more accurately and reliably reflect body Zn status. The objective of this study was to examine the relationship between net body Zn loss and gain during acute changes in dietary Zn intake with biochemical and kinetic indices of Zn status. Five men participated in an 85-d Zn depletion/repletion study. Net body Zn loss and gain were determined from the difference between dietary plus intravenously administered Zn and Zn excretion. Biochemical indicators of Zn status included plasma Zn, plasma alkaline phosphatase activity, and plasma retinol binding protein concentration. Following intravenous administration of (70)Zn or (67)Zn, a...
Plasma and serum zinc concentrations: Effect of time between collection and separation
Clinica Chimica Acta, 1988
The effect of time between collection and separation of blood samples obtained from 9 subjects was examined with respect to plasma and serum zinc concentrations. There was a linear increase of 6% in zinc concentrations for the first 2 h that was similar for plasma and serum. Plasma zinc continued to increase linearly over the next 2 h, but increase in serum zinc concentrations was less for the second 2 h. It is concluded that differences between heparinized plasma and serum zinc concentration observed previously in this laboratory and elsewhere are attributable primarily to differences in time between collection and separation.