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Zinc protoporphyrin, zinc ion, and protoporphyrin reduce focal cerebral ischemia.

BACKGROUND AND PURPOSE: Zinc protoporphyrin pretreatment protects against temporary focal ischemic brain injury in rats. However, it is not known whether the zinc or the protoporphyrin portion of zinc protoporphyrin has effects on focal cerebral ischemia. Hence, all three agents were compared with regard to infarct size and edema in a rat model of middle cerebral artery occlusion. METHODS: Four groups of adult male Sprague-Dawley rats were subjected to 2 hours of temporary middle cerebral artery occlusion followed by 22 hours of reperfusion. Each group was pretreated 30 minutes before middle cerebral artery occlusion with 0.9% NaCl, and then three groups were given equimolar doses of zinc protoporphyrin, zinc chloride, or protoporphyrin, respectively. Regional cerebral blood flow in the ischemic cortex was monitored with a laser Doppler flowmeter. Cerebral infarct size, brain water content, and ion content were measured 24 hours after the onset of occlusion. RESULTS: Regional cerebral blood flow during middle cerebral artery occlusion was approximately 9.2% to 13% of baseline in all four groups. Brain water content in the infarcted zone after temporary focal ischemia in control, zinc protoporphyrin, zinc chloride, and protoporphyrin groups was 85.7%, 80.6%, 85.6%, and 81.4%, respectively. Brain sodium content in the same areas in all four groups paralleled the water content. Infarct size in the controls and groups treated with zinc protoporphyrin, zinc, and protoporphyrin was 25.6%, 7.2%, 7.6%, and 7.2%, respectively. Compared with the control group, the infarct volume in all three treated groups was significantly reduced (P < .05). CONCLUSIONS: The present results indicate that zinc protoporphyrin, but also zinc and protoporphyrin, contribute to brain-protective effects when administered early in a temporary focal ischemia model. Zinc chloride reduced infarct size but not edema formation when compared with zinc protoporphyrin and protoporphyrin. Zinc ion in vivo has brain-protective effects, confirming in vitro studies previously reported by some but contrary to reports of others. Blood versus brain neuropil and cell body concentrations of zinc ion need to be studied in the future to define the precise role of zinc in the complex mechanisms involved in brain ischemia.

Animals↗

Phytate:zinc and phytate X calcium:zinc millimolar ratios in self-selected diets of Americans, Asian Indians, and Nepalese.

The literature indicates that phytate:zinc and phytate X calcium:zinc millimolar ratios of a diet may provide useful indexes of the bioavailability of dietary zinc. However, there is little information on the phytate:zinc and phytate X calcium:zinc millimolar ratios for total human diets. We have therefore determined the phytate:zinc and phytate X calcium:zinc millimolar ratios of self-selected diets of 29 American omnivores, 23 American vegetarians, 30 Asian Indian immigrant vegetarians, and 26 Nepalese lactating vegetarians. Criteria for selection of subjects were: good health, no extreme dietary habits, and no intake of nutrient supplements. According to the limited literature, the suggested critical values for phytate:zinc and phytate X calcium:zinc millimolar ratios in animal diets and retrospective calculations from human diets are greater than 10 and greater than 200, respectively. The mean phytate:zinc and phytate X calcium:zinc millimolar ratios of American omnivorous diets in the present study were less than 10 and 200, respectively. Confirmation of the critical molar ratios as indexes of the bioavailability of zinc in human diets has not been established by experimentation. However, if the data from animal studies are applicable to human diets, the present study suggests that phytate has little influence on zinc bioavailability of most American diets. In contrast, the mean phytate:zinc and phytate X calcium:zinc millimolar ratios of all vegetarian diets were above the proposed critical levels. Those data, therefore, suggest that phytate might increase the risk of impaired zinc bioavailability for vegetarians consuming a relatively high level of calcium.

Biological Availability↗

The influence of chemical form of zinc on the effects of toxic intraruminal doses of zinc to sheep.

The EDTA, sulphate and oxide compounds of zinc were administered to sheep as a single intraruminal dose (480, 240 or 120 mg Zn per kg body weight) or as thrice-weekly doses (240 mg Zn per kg body weight per dose) for 4 weeks. In the single-dose experiment, serum zinc concentrations rose most rapidly, were highest and fell most rapidly in those animals receiving zinc EDTA. In the sheep receiving the sulphate, serum zinc concentrations were high and stayed high for 2 or 3 days. Zinc oxide caused slight, but prolonged, elevation of serum zinc. High concentrations of zinc were present in urine after administration of zinc EDTA. In the multiple-dose experiments, the sheep dosed with zinc sulphate showed progressively higher elevations of serum zinc (first dose, 5-10 micrograms Zn ml-1; day 13, 30-60 micrograms Zn ml-1) and six of the seven sheep so dosed died before the final dose. At post mortem examination, many of these had lesions of the upper gastrointestinal tract and showed evidence of haemolytic crises. Sheep dosed with zinc oxide also had progressively higher peak serum zinc concentrations. In contrast, the peak serum concentrations for the zinc EDTA-dosed sheep declined as the experiment progressed. No deaths occurred in the sheep dosed with zinc oxide or EDTA. Major pancreatic injury occurred in sheep dosed with the sulphate or oxide, but was only mild in the sheep dosed with the zinc EDTA. Diarrhoea was mild and transitory in the EDTA-dosed sheep, but more severe and persistent in those dosed with the sulphate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cofortification of iron-fortified flour with zinc sulfate, but not zinc oxide, decreases iron absorption in Indonesian children.

BACKGROUND: Iron deficiency is a major nutritional concern in developing countries, and food fortification is a common strategy to treat it. In Indonesia wheat flour is fortified with 60 mg Fe/kg, but because of increasing concerns about marginal zinc status in at-risk populations, consideration is being given to cofortifying flour with zinc. However, little is known about the effect of zinc fortification of flour on iron bioavailability or about the optimum form of zinc supplementation. OBJECTIVE: We measured iron and zinc bioavailability from wheat-flour dumplings containing 25 g flour fortified with 60 mg Fe/kg, either alone or with 60 mg Zn/kg as zinc oxide or as zinc sulfate. DESIGN: Ninety children aged 4-8 y were recruited and assigned randomly to the 3 groups; 86 completed the study. Iron and zinc absorption were measured with established stable-isotope methods. RESULTS: Iron absorption from the flour fortified with iron only was good (15.9 +/- 6.8%), but when corrections were made for hemoglobin concentrations, it was significantly lower from the flour cofortified with zinc sulfate (11.5 +/- 4.9%; P < 0.05) but not from the flour cofortified with zinc oxide (14.0 +/- 8.9%). Zinc absorption was not significantly different between the zinc oxide and zinc sulfate cofortified flours (24.1 +/- 8.2% compared with 23.7 +/- 11.2%; P = 0.87). CONCLUSIONS: Iron and zinc appear to be highly bioavailable from foods made from fortified flour, but zinc sulfate cofortification may have a detrimental effect on iron absorption.

Biological Availability↗

Daily zinc supplementation effect on zinc deficiency in rats during prolonged restriction of motor activity.

The objective of this investigation was to evaluate the effect of 47 mg zinc supplementation on deficiency of zinc in rats during 98 d of restriction of motor activity (hypokinesia), which appeared by higher plasma zinc concentration. One Hundred 13-week-old Sprague-Dawley male rats weighing 360-390 g were used to perform the studies: They were equally divided into four groups: 1. Unsupplemented control animals (UCA); 2. Unsupplemented hypokinetic animals (UHA); 3. Supplemented control animals (SCA); and 4. Supplemented hypokinetic animals (SHA). For the simulation of the effect of hypokinesia (HK), the UHA and SHA were kept in small individual cages made of wood, which restricted their movements in all directions without hindering food and water intake. The SCA and SHA received daily with their food an additional amount of zinc. Before and during the experimental period of 98 d, plasma, urinary and fecal zinc, balance of zinc, food intake, and body weight were determined at different intervals. In the SHA and UHA, the concentration of zinc in plasma, and the elimination of zinc in urine and feces increased significantly when compared with the SCA and UCA, whereas the balance of zinc was negative. The body weight and food intake decreased significantly in the SHA and UHA when compared with the SCA and UCA. The increased plasma concentration of zinc in both the SHA and UHA groups was in contrast to the observed hypozincnemia during prolonged immobilization as during prolonged hospitalization. This reaction suggests that there may be some other mechanisms that are affecting the process of control and regulation of zinc metabolism during prolonged HK. It was concluded that exposure to prolonged restriction of motor activity of rats induces significant increases in plasma concentration, fecal and urinary elimination of zinc in the presence of negative zinc balance and regardless the daily intake of large amounts of zinc with their food, leading to zinc deficiency.

Animals↗

Esophageal cancer prevention in zinc-deficient rats: rapid induction of apoptosis by replenishing zinc.

BACKGROUND: Nutritional zinc deficiency in rats increases esophageal cell proliferation and the incidence of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumors. Replenishing zinc with a zinc-sufficient diet reduces these effects in zinc-deficient (ZD) rats. We investigated whether apoptosis was involved in the reduction of NMBA-induced esophageal tumors when ZD rats consumed a zinc-sufficient diet. METHODS: Weanling rats were fed a ZD diet (zinc at 3-4 ppm) for 5 weeks to establish esophageal cell proliferation, then treated once with NMBA (2 mg/kg body weight), and divided into the following five groups (47-100 per group). One ZD group was fed the ZD diet, and four zinc-replenished (ZR) groups, ZR(1), ZR(24), ZR(72), and ZR(432), were fed a zinc-sufficient diet (zinc at 74-75 ppm) beginning 1, 24, 72, and 432 hours, respectively, after NMBA treatment. From 24 hours to 2 weeks after beginning a zinc-sufficient diet, esophagi from all ZR groups were analyzed for apoptosis and cell proliferation; ZD esophagi were the controls. Tumor incidence was determined 15 weeks after zinc replenishment. All statistical tests were two-sided. RESULTS: Zinc replenishment initiated shortly after NMBA treatment effectively reduced esophageal tumorigenesis; 8% (three of 37) of ZR(1), 14% (five of 37) of ZR(24), 19% (five of 26) of ZR(72), and 48% (19 of 40) of ZR(432) rats developed esophageal tumors compared with 93% (14 of 15) of ZD animals (all P<.001). Importantly, 24 and 30 hours after zinc replenishment, esophagi had numerous apoptotic cells (% apoptotic cells: 0 hour = 2.9%, 95% confidence interval [CI] = 2.5% to 3.3%; 24 hours = 9.4%, 95% CI = 8.2% to 10.6%), and the expression of the proapoptotic Bax protein doubled. Within 48 hours, the ZR(1) epithelium was three to five cell layers thick compared with 10-20 layers before zinc replenishment. CONCLUSIONS: Zinc replenishment of NMBA-treated ZD rats rapidly induces apoptosis in esophageal epithelial cells and thereby substantially reduces the development of esophageal cancer.

Animals↗

Serum zinc levels in diabetic patients and effect of zinc supplementation on glycemic control of type 2 diabetics.

OBJECTIVE: The present study is an attempt to assess serum zinc level in a sample of diabetic patients (both type 1 and type 2 diabetics) in comparison with those of apparently healthy controls, and to ascertain the relationship between the levels of serum zinc with some epidemiological variables. Furthermore, a trial of zinc supplementation for 3 months conducted to assess the effect of zinc supplementation on glycemic control of the studied type 2 diabetic patients, and the factors that affect the response to this supplementation. METHODS: Collection of data was carried out during the period between November 2002 to February 2003 at the Diabetic Center of Merjan Teaching Hospital in Babil Governorate, Iraq. In the first part of the study (a case-control study), the diabetic group included 133 diabetic patients (type 1 and 2) who were chosen from patients attending the Diabetic Center during the period of the study. The control group included 133 apparently healthy subjects who were selected from the workers of the same hospital. Selection of cases and controls was carried out by using systematic random sampling procedure. In the second part of the study (single blind were intervention study), type 2 diabetic patients (101 patients) divided into 2 groups; the first group included 50 patients supplemented with oral zinc sulfate (30 mg of elemental zinc/cap/day) for 3 months and second group included 51 patients given placebo and designed as control group. RESULTS: The first part of the study shows that the mean value for serum zinc level was significantly lower in diabetic patients than healthy controls (64.2 +/- 12.6 microg/dl for type 1 diabetics, and 68.9 +/- 11.9 microg/dl for type 2 diabetics versus 83.4 +/- 12.5 microg/dl for healthy controls). Using simple linear regression, significant positive correlation was found between serum zinc level and years of education and significant negative correlation was found between serum zinc level and baseline HbA1c% value, in the diabetic group. While significant positive correlation found between serum zinc level and estimated zinc intake in the control group. Using multiple regression analysis, serum zinc level showed significant positive correlation with gender (being a male compared with female), and estimated zinc intake and significant negative correlation with diabetes state (diabetic compared with non-diabetic), residence (urban compared with rural residents), and plant protein intake. The second part of the study shows that the mean value for HbA1c% concentration of the supplemented group decreased significantly at the end of the 3 months of follow up, while no significant changes were found in the mean value for HbA1c% of the control group. The present study showed that the change in HbA1c% after supplementation had significant negative correlation with baseline HbA1c% value. CONCLUSION: Diabetic patients have significantly lower mean serum zinc levels compared with healthy controls. Zinc supplementation for type-2 diabetics has beneficial effects in elevating their serum zinc level, and in improving their glycemic control that is shown by decreasing their HbA1c% concentration.

Adult↗

Differential regulation of zinc efflux transporters ZnT-1, ZnT-5 and ZnT-7 gene expression by zinc levels: a real-time RT-PCR study.

Intracellular zinc levels are strictly regulated by zinc channels and zinc-binding proteins to maintain cellular zinc-dependent functions. We demonstrated a correlation between extracellular zinc concentration and intracellular exchangeable zinc levels using the fluorescent zinc-specific probes zinquin and zinpyr-1. The effect of extracellular zinc status on the regulation of the two trans-Golgi network directed zinc transporters ZnT-5 and ZnT-7 was next studied by real-time RT-PCR in zinc supplemented or depleted HeLa cells. While sub-toxic extracellular zinc addition strongly induced the efflux transporter ZnT-1 gene expression, consistent with its activation by the transcription factor MTF-1, treated HeLa cells did not display any change in ZnT-5 and ZnT-7 mRNA levels compared to control cells. In contrast, zinc depletion induced by non-toxic doses of the zinc chelator TPEN (N,N,N',N' tetrakis-(2 pyridylmethyl) ethylene diamine) resulted in a up to eight-fold induction of transporters ZnT-5 and ZnT-7 mRNA levels, providing the first evidence of a transcriptional control of these two zinc efflux transporters by zinc deficiency in cultured cells.

Cation Transport Proteins↗

Zinc homeostasis in the hippocampus of zinc-deficient young adult rats.

On the basis of the evidence of the transient learning impairment of young adult rats fed a zinc-deficient diet for 4 weeks, zinc concentration in the hippocampus was examined in the zinc-deficient rats to understand the mechanism of brain dysfunction in zinc deficiency. Zinc concentration in the hippocampus, as well as that in other brain regions, was not decreased by 4-week zinc deprivation. When Timm's stain, with which histochemically reactive zinc in the presynaptic vesicles is detected, was compared between the control and zinc-deficient rats, the intensity of Timm's stain in the hippocampus was almost the same between them. In the hippocampus, zinc concentration in the synaptosomal fraction was not also decreased by 4-week zinc deprivation, whereas that in the crude nuclear fraction was significantly increased. These results suggest that zinc concentration in the presynaptic vesicles is not decreased in young adults rats by 4-week zinc deprivation. It is likely that zinc-requiring systems in the nucleus are more responsive to zinc deficiency than vesicular zinc. This responsiveness appears to be involved in the transient learning impairment.

Animals↗

Assessment of zinc and copper status in weaned piglets in relation to dietary zinc and copper supply.

The aim of the study was to determine the effect of weaning and the effect of increasing dietary zinc concentrations on the zinc and copper status of weaned piglets (study 1) and to study the effect of high concentrations of dietary zinc and/or copper on zinc and copper status of weaned piglets (study 2). Study 1 included 54 piglets (six litters of nine piglets). One piglet from every litter was killed 1 day before weaning. The remaining 48 piglets were allocated at weaning (28 days) to four dietary zinc treatments (100, 250, 1000 or 2500 ppm) and subsequently killed 1-2, 5-6 or 14-15 days after weaning. Study 2 included 48 piglets (six litters of eight piglets) allocated to four dietary treatments, consisting of low or high dietary zinc (100 or 2500 ppm) in combination with low or high dietary copper (20 or 175 ppm). All piglets in study 2 were killed 5-7 days after weaning. In both studies, the trace mineral status was assessed by zinc and copper concentrations and alkaline phosphatase (AP) activity in plasma and mucosal tissue. In study 2, lymphocyte metallothionein (MT) mRNA and intestinal mucosa MT mRNA concentrations were included as zinc status markers. The results showed that the zinc status, measured as zinc in plasma and mucosa, was not affected by weaning of the piglets. Plasma copper concentrations decreased during the first 2 weeks after weaning. High dietary copper concentrations did not affect the concentration of copper in plasma, but increased the concentration of copper in mucosa and the concentration of zinc in plasma. The dietary zinc treatments increased the zinc concentration in plasma as well as the zinc and MT mRNA concentration in mucosa. Lymphocyte MT mRNA concentrations did not reflect the differences in dietary zinc supplementation.

Administration, Oral↗

Clinical experience of zinc supplementation during intravenous nutrition in Crohn's disease: value of serum and urine zinc measurements.

Serum zinc concentrations and urine zinc excretion have been studied in 10 patients with severe Crohn's disease before and during 59 patient-weeks of intravenous nutrition. Before serum zinc concentrations (9.9 +/- 1.0 mumol/l: mean +/- SEM) and urine zinc excretion (3-3 +/- 0.6 mumol/24h) were less than controls (p less than 0.01). No patients had clinical signs of zinc deficiency before intravenous nutrition and none developed signs during it. There was no overall change in serum zinc concentrations, despite improvements in body weight, skinfold thickness, and mid-arm circumference in all patients, and increased serum albumin and serum transferrin concentrations during all but two periods of intravenous nutrition. Nor was there any relationship between serum zinc concentrations and zinc uptake (up to 220 mumol/day), serum zinc concentrations remaining significantly lower than control levels. Urine zinc excretion during the first week of intravenous nutrition showed a 1.2 to 53-fold increase (mean 11-fold) over pre-intravenous nutrition levels, and a positive relationship was demonstrated between zinc intake and urine zinc excretion. It is suggested that zinc supplied by the intravenous route is inefficiently transported to the tissues, and that some is excreted in the form of small molecular weight chelates into urine. Recommendations are made for the supply of intravenous zinc, based on monitoring urine zinc excretion in individual patients.

Adolescent↗

Effects of oyster extract on the reproductive function of zinc-deficient mice: bioavailability of zinc contained in oyster extract.

Zinc is a vital nutrient in the normal reproductive function and embryonic development of mammals, and it is well known that oyster extract contains significant amounts of zinc. The effects of oyster extract on reproductive function, such as embryonic development, serum levels of zinc and sperm maturation were examined in zinc-deficient mice. Zinc deficiency in dams during pregnancy induced a decrease in the successful pregnancy rate, maternal weight gain, the number of live fetuses and fetal body weight. Zinc deficiency for 12 weeks in male mice induced a decrease in body weight, testis weight and sperm count in the epididymis. However, reproductive failure, embryonic defects and decreased sperm motility in zinc-deficient mice were improved by supplementation with oyster extract. Some nutrients contained in oyster extract, such as taurine and glycogen, may be related to the recovery of reproductive function. There were significantly lower serum concentrations of zinc in dams fed a zinc-deficient diet. However, the serum zinc concentration was normal in the oyster extract-supplemented group. No difference in the concentration of serum zinc was observed between the oyster extract- and zinc carbonate-supplemented groups. From these findings, it is suggested that oyster extract is a useful supplement that can prevent reproductive defects from zinc deficiency, and the bioavailability of zinc may be identical to zinc carbonate.

Animals↗

Zinc metabolism in Ehrlich cells: properties of a metallothionein-like zinc-binding protein.

Host zinc deficiency halts the proliferation of the mouse Ehrlich ascites tumor. The major site of measurable cellular zinc depletion is a cytosolic zinc binding protein. This protein is characterized as a metallothionein on the basis of its presence as two isoproteins which behave on DEAE-Sephadex and in polyacrylamide gel electrophoresis like metallothioneins, the lack of protein absorbance at 280 nm, its sulfhydryl/zinc ratio of 3.5, and its reactivity in zinc transfer to apocarbonic anhydrase. Finally, the protein exhibits cross-reactivity with a known rat metallothionein in a radioimmunoassay. Coupled with the similarity in structure and antigenicity of rat and mouse metallothioneins, this adds strong support to the identification of the zinc-binding protein as a metallothionein. In zinc-deficient cells this metallothionein-like protein appears to exist as an apoprotein. When small amounts of dietary zinc stimulate the deficient cells to divide, zinc is not observed in metallothionein. Larger concentrations of dietary zinc support both proliferation and the steady state presence of zinc in this protein. It is demonstrated that metallothionein is the principal donor of zinc to apocarbonic anhydrase added to Ehrlich cytosol. These results are used to construct a model of zinc metabolism in which zinc metallothionein is a labile depot of zinc in the Ehrlich cell which can be mobilized under zinc-deficient conditions.

Animals↗

Local absorption of zinc from wounds treated with different concentrations of zinc sulphate.

In the present study it was shown in rats that zinc is absorbed from excisional wounds treated with zinc sulphate. Systemic toxic effects were observed in the group treated with 20% zinc sulphate. Local toxic effects were seen in wounds treated with 0.2%, 2% and 20% zinc sulphate. An inhibitory effect of zinc on the migration of granulocytes was suggested on the basis of microscopic observation. In the operated groups which were not treated with zinc and the group treated with 0.02% zinc sulphate a decline was observed in the concentration of zinc in serum. The zinc concentration in serum increased in proportion to the zinc sulphate concentration (0.2%, 2% and 20%) applied to the wounds, while the copper concentration decreased in the groups treated with 2% and 20% zinc sulphate. In all operated groups an increase in zinc and copper concentrations was observed in liver. This was most pronounced in groups treated with higher concentrations of zinc sulphate (0.2%, 2% and 20%). The groups treated with higher concentrations of zinc sulphate also had higher pancreas zinc concentrations than the remaining groups.

Absorption↗

Increase in synaptic hippocampal zinc concentration following chronic but not acute zinc treatment in rats.

Electroconvulsive seizures (ECS), one of the most effective treatments of depression, induce mossy fiber sprouting (when assayed by means of synaptic zinc method), and this indicates an increase in the synaptic zinc level in the hippocampus following such therapy. The aim of the present study was to investigate the influence of acute and chronic zinc hydroaspartate administration on the synaptic and total zinc level in the rat hippocampus. We used two methods of zinc determination: (1) zinc-selenium method, which images the pool of synaptic zinc, and (2) flame atomic absorption spectrometry, which assays the total concentration of zinc. Our results indicate that chronic (14 x 65 mg/kg), but not acute, zinc hydroaspartate administration intraperitoneally (i.p.) increases the pool of synaptic zinc in the majority of rat hippocampal layers (by 72-190%), except for the stratum moleculare and stratum radiatum CA, and perforant path DG. On the other hand, no changes were found in total hippocampal zinc level, measured by flame atomic absorption spectrometry. These data suggest that chronic zinc treatment increases the pool of synaptic zinc in the hippocampus, and this effect is similar to that observed following chronic ECS treatment. The measurement of zinc concentration in the whole hippocampus by the flame atomic absorption spectrometry method is not sensitive enough to detect such subtle alteration.

Animals↗

The effects of zinc supplementation on serum zinc concentration and protein catabolic rate in hemodialysis patients.

OBJECTIVE: To examine the effect of zinc sulfate supplementation on serum zinc concentrations and protein catabolic rate (PCR) in hemodialysis (HD) patients. DESIGN: Randomized, double-blind, before-after trial. SETTING: Outpatient dialysis center in a large metropolitan city. PATIENTS: Twenty-eight maintenance HD patients were selected. Twenty (15 women, 5 men) subjects completed the study. Subjects were identified for inclusion in the study by the following criteria: a history of low PCR (<0.09 g/kg body weight), HD treatment for a minimum of 6 months, no signs of gastrointestinal disorders, and no record of hospitalizations for reasons other than access complication within the last 3 months. INTERVENTIONS: Patients consumed 7.7 pmol zinc sulfate (2,200 microg) or a cornstarch placebo capsule daily for 90 days. In addition, patients completed a 2-day food record representative of 1 dialysis day and 1 nondialysis day. MAIN OUTCOME MEASURE: Fasting, predialysis serum samples were collected on days 0, 40, and 90 to determine serum zinc concentration and PCR. Dietary parameters including intake of zinc, protein, and energy were analyzed on Days 0 and 90. RESULTS: Initial analysis at Day 0 of serum zinc concentration indicated subjects were below the normal range for serum zinc standards (12.2 micromol/L [80 microg/dL]). After supplementation, subjects in the zinc-supplemented group showed significant increases in serum zinc concentrations from 12.2 micromol/L (80 microg/dL) at Day 0 to 15.3 pmol/L (100 microg/dL) at Day 90. A significant positive correlation (r = +0.61) was shown between PCR and serum zinc concentrations at the end of the study. Reported dietary protein intake did not change with zinc supplementation. CONCLUSION: Low serum zinc concentrations are reversible with zinc supplementation. Improvement in serum zinc concentration increases the PCR of HD patients.

Adult↗

Influence of usual zinc intake and zinc in a meal on 65Zn retention and turnover in the rat.

The influences of zinc in a meal and usual zinc intake on zinc retention and turnover were investigated in 7-wk-old male rats fed diets containing 12-151 mg Zn/kg for 3 wk before and after consuming a 65Zn-labeled meal containing ZnCl2. Retention corrected to zero time and turnover rate were determined by whole-body counting. Percent zinc retention was inversely proportional to the natural logarithm of the meal zinc, between 0.09 and 26 mumol. In comparison to lower doses, higher doses resulted in lower percent retention but greater amounts of zinc retained. Although the latter relationship was slightly curvilinear, there was no indication of a limited capacity for zinc retention with high doses. However, doses above 4 mumol resulted in higher turnover rates in rats accustomed to lower zinc intakes. Percent retention and the reciprocal of the turnover rate were proportional to the reciprocal of the dietary zinc concentration. The greatest differences in retention and turnover occurred between 12 and 26 mg Zn/kg diet. The zinc dose in a meal and the usual dietary zinc separately influenced percent zinc retention. These factors also interacted, such that greater dose effects were observed at lower zinc intakes and greater dietary zinc effects were observed at lower doses.

Animals↗

The effect of five-year zinc supplementation on serum zinc, serum cholesterol and hematocrit in persons randomly assigned to treatment group in the age-related eye disease study: AREDS Report No. 7.

The effects of long-term supplementation with pharmacologic doses of zinc oxide on serum levels of zinc, lipids and hematocrit have not been studied systematically to date. Eleven Clinical Centers enrolled 4757 participants from 1992 to 1998 as part of the Age-Related Eye Disease Study (AREDS). Of these, 3640 participants, aged 55-80 y, who had early-to-late age-related macular degeneration (AMD) were randomly assigned to daily supplementation with or without 80 mg of zinc as zinc oxide plus 2 mg of copper as cupric oxide to study the effects of zinc supplementation on the progression to late AMD. This paper reports on the effect of a 5-y supplementation with zinc oxide and cupric oxide on serum zinc, copper, lipids, and hematocrit for 717 participants from three clinical centers. At the 5-y exam, the median increase in serum zinc levels for participants assigned to zinc formulations was 17% compared with a 2% increase for participants not assigned to zinc (P < 0.001). The differential effect on serum zinc was observed at 1 y and remained fairly constant over the 5-y period. After 5 y, no significant differences in changes in serum hematocrit, copper or lipids were found between participants assigned to formulations containing zinc and copper, and those assigned to formulations without zinc and copper. Estimates from a modified Block Food-Frequency Questionnaire suggest the AREDS population at baseline had a zinc intake from diet similar to that of the general population.

Administration, Oral↗