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Metabolic balance studies for zinc and copper in housebound elderly people and the relationship between zinc balance and leukocyte zinc concentrations.

Five-day metabolic balance studies for zinc and copper were carried out in 20 housebound elderly people with stable chronic diseases. Subjects were age 70.0-85.1 y, lived in their own homes, and ate self-selected diets. Mean daily intakes for Zn and Cu were 90 mumol and 13.4 mumol with mean negative balances of -16 and -1.1 mumol, respectively. Both balance values significantly differed from equilibrium (p less than 0.05). For Zn and Cu, respectively, mean concentrations were 11.3 and 22.1 mumol/L plasma, 103 and 19.4 mumol/L whole blood, and 98 and 8.7 pmol/10(6) leukocytes. The results for Zn and Cu balance and leukocyte concentrations were different from those obtained by us for healthy elderly people (Am J Clin Nutr 1984;40: 1096-120). A highly significant (r = 0.75, p less than 0.001) correlation was observed between zinc balance and leukocyte zinc concentrations.

Aged↗

Nitric oxide destroys zinc-sulfur clusters inducing zinc release from metallothionein and inhibition of the zinc finger-type yeast transcription activator LAC9.

Nitric oxide, generated from S-nitrosocysteine or applied as gas mediates metal ion release from the Zn2+/Cd(2+)-complexing protein metallothionein via oxidation of SH-groups. Time-dependent S-nitrosylation and subsequent disulfide formation of metallothionein are demonstrated. Furthermore, nitric oxide inhibits DNA binding activity of the yeast transcription factor LAC9 containing a zinc finger like DNA binding domain. These results show that nitric oxide interacts with and destroys zinc-sulfur clusters in proteins.

Animals↗

Reactivity of the B-H Bond in tris(pyrazolyl)hydroborato zinc complexes: unexpected example of zinc hydride formation in a protic solvent and its relevance towards hydrogen transfer to NAD(+) mimics by tris(pyrazolyl)hydroborato zinc complexes in alcoholic media.

Solutions of the zinc hydroxide complex [Tp(Bu(t),Me)]ZnOH in alcohols (ROH; R = Me, Et, Pr(i)) achieve hydride transfer to the NAD(+) model, 10-methylacridinium perchlorate. Deuterium labeling studies, however, demonstrate that the source of the hydride is not the alcohol but, rather, the B [bond] H group of the [Tp(Bu(t),Me)] ligand. A further example in which a [Tp(Bu(t),Me)] ligand acts as a hydride donor is provided by the reaction of the aqua complex [[Tp(Bu(t),Me)]Zn(OH(2))][HOB(C(6)F(5))(3)] with MeOH to generate the zinc hydride complex [Tp(Bu(t),Me)]ZnH. The present study therefore provides a caveat for the often assumed inertness of the B [bond] H group in tris(pyrazolyl)hydroborato ligands, especially in the presence of reactive cationic species.

Acridines↗

Effects of zinc complexes on the distribution of zinc in calcareous soil and zinc uptake by maize.

The movement and availability of Zn from six organic Zn sources in a Typic Xerorthent (calcareous) soil were compared by incubation, column assay, and in a greenhouse study with maize (Zea mays L.). Zinc soil behavior was studied by sequential, diethylenetriaminepentaacetate, and Mehlich-3 extractions. In the incubation experiment, the differences in Zn concentration observed in the water soluble plus exchangeable fraction strongly correlated with Zn uptake by plants in the greenhouse experiment. Zinc applied to the surface of soil columns scarcely moved into deeper layers except for Zn-ethylenediaminetetraacetate (EDTA) that showed the greatest distribution of labile Zn throughout the soil and the highest proportion of leaching of the applied Zn. In the upper part of the column, changes in the chemical forms of all treatments occurred and an increase in organically complexed and amorphous Fe oxide-bound fractions was detected. However, the water soluble plus exchangeable fraction was not detected. The same results were obtained at the end of the greenhouse experiment. Significant increases were found in plant dry matter yield and Zn concentration as compared with the control treatment without Zn addition. Increasing Zn rate in the soil increased dry matter yield in all cases but Zn concentration in the plant increased only with Zn-EDTA and Zn-ethylenediaminedi-o-hydroxyphenyl-acetate (EDDHA) fertilizers. Higher Zn concentration in plants (50.9 mg kg(-)(1)) occurred when 20 mg Zn kg(-)(1) was added to the soil as Zn-EDTA. The relative effectiveness of the different Zn carriers in increasing Zn uptake was in the order: Zn-EDTA > Zn-EDDHA > Zn-heptagluconate >/= Zn-phenolate approximately Zn-polyflavonoid approximately Zn-lignosulfonate.

Chemical Fractionation↗

Effect of infant formula zinc and iron level on zinc absorption, zinc status, and immune function in infant rhesus monkeys.

To evaluate the effects of marginal zinc (Zn) deficiency on Zn absorption and metabolism, three groups of infant rhesus monkeys (n = 4/group) were fed from birth to 5 months of age either a regular infant formula (5 mg Zn/L) or a low-Zn formula (1 mg Zn/L). Since iron (Fe) intake may affect Zn absorption, the low-Zn formula was given without (1 mg Fe/L) or with Fe fortification (12 mg/L). At monthly intervals, Zn absorption and retention were assessed by gavage feeding with 65Zn and whole-body counting immediately after and on days 4, 7, and 11 after intubation. Blood samples were drawn before dosing for analyses of various potential markers of Zn status. Infants fed low-Zn formula had lower weight gain than controls; however, length growth was similar in all groups. 65Zn retention was considerably higher in both groups fed low-Zn formula (40%) than in the control group (20%), whereas plasma Zn levels were normal in all infants. Plasma metallothionein levels were generally very low and detectable in only 5 samples of 48; however, 4 of these were found in control infants. Neutrophil chemotaxis assessed at the end of the study was impaired in low-Zn infants compared to controls. In addition, low-Zn infants had increased levels of interleukin-2 at the end of the study. No differences were seen between the groups in hemoglobin levels, total white blood cells/absolute neutrophil counts, or plasma activities of 5'-nucleotidase or angiotensin converting enzyme. In conclusion, marginal Zn intake in infant rhesus monkeys resulted in increased Zn retention, which was not enough to completely compensate for the lower Zn intake. The higher level of iron fortification studied did not affect Zn retention significantly.

5'-Nucleotidase↗

Genetic analysis of the zinc finger in the Moloney murine leukemia virus nucleocapsid domain: replacement of zinc-coordinating residues with other zinc-coordinating residues yields noninfectious particles containing genomic RNA.

The effect of changing zinc (Zn2+)-coordinating residues in the nucleocapsid protein of Moloney murine leukemia virus was investigated by introducing a His-34-to-Cys or Cys-39-to-His mutation into the putative Zn2+ finger. Mutant virions contained normal levels of properly processed Gag and Env proteins and wild-type levels of full-length viral RNA. However, the specific infectivity of the mutants was approximately 4 x 10(-4) that of wild-type particles. They were probably noninfectious because of the inability of the particles to synthesize cDNA transcripts, since full-length viral DNA could not be detected in Hirt supernatants of NIH 3T3 cells infected with the CCCC or CCHH virus. These mutants will provide an extremely valuable tool for analysis of the role of retroviral Zn2+ fingers in infection processes, independent of viral RNA recognition and packaging.

3T3 Cells↗

Effect of zinc source (zinc oxide vs zinc proteinate) and level on performance, carcass characteristics, and immune response of growing and finishing steers.

Sixty Angus and Angus x Hereford steers (246 kg initial BW) were used to determine the effects of Zn level and source on performance, immune response, and carcass characteristics of growing and finishing steers. Treatments consisted of 1) control (no supplemental Zn), 2) ZnO, 3) Zn proteinate-A (ZnProt-A, 10% Zn), and 4) ZnProt-B (15% Zn). Treatments 2, 3, and 4 supplied 25 mg of supplemental Zn/kg diet. Steers were individually fed a corn silage-based diet during the 84-d growing phase and a high corn diet during the finishing phase. Cell-mediated and humoral immune response measurements were obtained between d 67 and 74 of the growing phase. Equal number of steers per treatment were slaughtered after receiving the finishing diets for 84 or 112 d. Performance and carcass measurements were similar in steers fed the two ZnProt sources. Zinc supplementation, regardless of source, increased (P < 0.05) ADG during the growing phase. In the finishing phase, ADG (P = 0.10) and gain/feed (P = 0.07) tended to be higher for steers fed ZnProt compared with those supplemented with ZnO. Gain and feed efficiency were similar for control and ZnO-supplemented steers during the finishing phase. Steers fed ZnProt had heavier (P < 0.05) hot carcass weights and slightly higher (P < 0.05) dressing percentages than those in the control or ZnO treatments. Quality grade, yield grade, marbling, and backfat were increased by Zn supplementation, but were not affected by Zn source. In vitro response of lymphocytes to mitogen stimulation and in vivo swelling response following intradermal injection of phytohemagglutinin were not affected by Zn level or source. Humoral immune response following vaccination with infectious bovine rhinotracheitis also was not affected by treatment. Soluble concentrations of Zn in ruminal fluid were higher (P < 0.05) in steers fed ZnProt compared to ZnO steers. Results indicate that ZnProt may improve performance of finishing steers above that observed with inorganic Zn supplementation.

Animal Feed↗

Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females.

Response of iron, copper, and zinc status to supplementation with Zn or a combination of Zn and Fe was assessed in adult females in a 10-wk study. Group Z received 50 mg Zn/d as Zn gluconate; group F-Z received 50 mg Fe as ferrous sulfate monohydrate in addition to the Zn. For Group Z, serum ferritin, hematocrit, and erythrocyte Cu,Zn-superoxide dismutase (ESOD) were significantly lower (p less than 0.05) after 10 wk supplementation compared with pretreatment levels. Serum Zn increased (p less than 0.01) but no change occurred in serum ceruloplasmin, hemoglobin, or salivary sediment Zn with treatment. For Group F-Z ESOD decreased with treatment as did salivary sediment Zn (p less than 0.05). Serum ferritin and serum Zn increased significantly, but hemoglobin, hematocrit, and ceruloplasmin were not affected by this treatment. Supplementation with Zn poses a risk to Fe and Cu status. Inclusion of Fe with Zn ameliorates the effect on Fe but not on Cu status.

Adult↗

Kinetics of copper absorption in zinc-overload states and following the withdrawal of zinc supplement: the role of endogenous zinc status.

Zinc (Zn), in therapeutic dosages, has been used to inhibit copper (Cu) absorption in patients with Wilson's disease. A series of experiments were conducted to substantiate the effects of high dosages of Zn on Cu absorption using the experimental animal model. In the first experiment, five groups of mice were fed five different levels of Zn: 6 ppm (basal diet), 30 ppm (control), 750 ppm, 1,000 ppm, and 2,400 ppm, for a period of 35 days. 64Cu-loading test was conducted to measure whole body retention (WBR) of 64Cu at the 10th, 14th, 21st, and 35th day. Results showed that the inhibition of 64Cu absorption by Zn is dose- and time-dependent. However, maximum inhibition occurred in mice fed 1,000 ppm of Zn, and no additional effect was observed in mice fed 2,400 ppm of Zn. In the second experiment, the distribution between the gastrointestinal tract (GIT) and gut-free carcass, of the retained dose of 64Cu, was measured in controls and in the group fed 750 ppm of Zn. While WBR of 64Cu was significantly lower (p less than 0.01) in mice fed 750 ppm of Zn, the distribution of the retained dose was not affected. In the third experiment, a group of mice was fed 30 ppm of Zn for a period of 70 days (control), and a second group was fed 1,000 ppm of Zn for the first 35 days (repletion), after which they were switched to the basal diet (6 ppm) for the following 35 days (depletion). WBR of 64Cu was conducted in intervals throughout the experimental period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Trichomes of tobacco excrete zinc as zinc-substituted calcium carbonate and other zinc-containing compounds.

Tobacco (Nicotiana tabacum L. cv Xanthi) plants were exposed to toxic levels of zinc (Zn). Zn exposure resulted in toxicity signs in plants, and these damages were partly reduced by a calcium (Ca) supplement. Confocal imaging of intracellular Zn using Zinquin showed that Zn was preferentially accumulated in trichomes. Exposure to Zn and Zn + Ca increased the trichome density and induced the production of Ca/Zn mineral grains on the head cells of trichomes. These grains were aggregates of submicrometer-sized crystals and poorly crystalline material and contained Ca as major element, along with subordinate amounts of Zn, manganese, potassium, chlorine, phosphorus, silicon, and magnesium. Micro x-ray diffraction revealed that the large majority of the grains were composed essentially of metal-substituted calcite (CaCO3). CaCO3 polymorphs (aragonite and vaterite) and CaC2O4 (Ca oxalate) mono- and dihydrate also were identified, either as an admixture to calcite or in separate grains. Some grains did not diffract, although they contained Ca, suggesting the presence of amorphous form of Ca. The presence of Zn-substituted calcite was confirmed by Zn K-edge micro-extended x-ray absorption fine structure spectroscopy. Zn bound to organic compounds and Zn-containing silica and phosphate were also identified by this technique. The proportion of Zn-substituted calcite relative to the other species increased with Ca exposure. The production of Zn-containing biogenic calcite and other Zn compounds through the trichomes is a novel mechanism involved in Zn detoxification. This study illustrates the potential of laterally resolved x-ray synchrotron radiation techniques to study biomineralization and metal homeostasis processes in plants.

Calcium Carbonate↗

Zinc repletion with organic or inorganic forms of zinc and protein turnover in marginally zinc-deficient calves.

We conducted two experiments using marginally Zn-deficient (-Zn) calves to determine which supplemental chemical form of Zn would most rapidly reverse certain Zn deficiency signs and to determine whether a change in protein turnover had occurred in Zn deficiency. In Exp. 1, 40 crossbred beef heifers were allocated by BW to four groups. The control group received 23 mg Zn/kg diet DM from ZnSO4 supplemented to the -Zn diet (17 mg Zn/kg diet DM). The three other groups received the -Zn diet. After 21 d, based on a decreased (P < .05) feed efficiency, they were deemed -Zn. Cell-mediated immune (CMI) response to phytohemagglutinin (PHA) was reduced (P < .05) but plasma and liver Zn were unaffected in the -Zn calves. Zinc was repleted by feeding iso-Zn amounts (23 mg Zn/kg diet DM) from Zn lysine, Zn methionine, or ZnSO4. At 8 h after injection of PHA, control CMI response values were similar to Zn Methionine, and Zn lysine was lower (P < .05). In Exp. 2, 10 Holstein steers were allocated by BW to two groups. One group received the -Zn diet, and the other received the +Zn diet. Urine collections were obtained from both groups of calves when the -Zn calves showed a decrease (P < .05) in feed efficiency relative to the controls and when they were repleted with 23 mg Zn/kg diet DM from ZnSO4 and their feed efficiency had returned to that of the controls. Urinary 3-methylhistidine indicated that -Zn calves had less (P < .05) daily protein degradation than the controls. Refeeding Zn to the -Zn group did not change BW or daily protein degradation. Results indicated that a marginal Zn deficiency decreased fractional accretion rate, increased (P < .05) urine excretion, and tended to increase (P < .19) Na and decrease (P < .12) K concentrations in the urine.

Animals↗

Maternal, placental and cord zinc components in healthy women with different levels of serum zinc.

Serum zinc is known to decrease during pregnancy, but the range of individual values at the end of normal gestation may be considerably large, with uncertain physiological significance in terms of maternal zinc status and maternal-fetal transfer of zinc. In this study we compared several maternal and cord blood indices of zinc status, placental zinc, placental metallothionein and the relationship between maternal, cord and placental components, in 40 healthy pregnant women at delivery with different levels of serum zinc. Subjects were divided into three groups according to serum zinc using as cutoff points the lower and upper quartile values [LZn, < 7.6 mumol/l (n = 10); MZn, 7.6-10.7 mumol/l (n = 20), and HZn, > 10.7 mumol/l (n = 10)]. Habitual zinc intakes were similar in all groups (average 11.5 mg/day). Considering all women, maternal serum and erythrocyte zinc correlated significantly (r = 0.40; p = 0.021). Maternal erythrocyte zinc was higher (p < 0.01) in HZn compared to the other groups. Maternal and cord values of serum zinc correlated significantly (r = 0.43; p = 0.006). Cord serum zinc values were very similar in LZn and MZn but were higher (p < 0.01) in HZn. Cord erythrocyte zinc levels were similar in all groups and about 20-25% of the maternal values. Cord erythrocyte metallothionein levels were also similar in all groups and similar to maternal values. Comparing the percentage distribution of zinc in maternal and cord serum fractions, major differences were observed in HZn, with zinc in albumin fraction being 70% in cord compared to 56% in maternal serum. There was a higher (p < 0.01) percentage of zinc bound to alpha 2-macroglobulin fraction in maternal serum of HZn compared to maternal serum of the other groups. Maternal and cord zinc in the albumin fractions correlated significantly (r = 0.48; p = 0.002) particularly in HZn (r = 0.71; p < 0.021). Placental zinc correlated negatively (r = -0.34; p = 0.035) with zinc in the maternal alpha 2-macroglobulin fraction, but did not relate to placental metallothionein, which had similar levels in all groups (average 0.28 nmol/g wet tissue). Placental zinc levels were lower (p < 0.01) in HZn. Our results indicate that high levels of maternal serum zinc in healthy women at delivery may be related to maternal tissue zinc redistribution that could favor diffusional components of maternal-fetal transfer of zinc.

Body Mass Index↗

Effect of zinc status on salivary zinc concentrations in the rat.

Three experiments were done to determine whether salivary zinc concentration is a more sensitive indicator of zinc status than plasma zinc. Weanling male rats fed a low zinc (less than 1 ppm) diet for 5 weeks with or without zinc (100 ppm) in the drinking water had salivary zinc concentration of 0.19, 0.16, and 0.20 microgram/ml for the zinc-deficient, zinc-supplemented restricted-intake, and zinc-supplemented ad libitum-fed groups, respectively. Combined values for male and female rats after 4 weeks of the same treatments in experiment 2 were 0.60, 1.2 and 0.44 microgram/ml. Saliva collected on day 22 of pregnancy contained 0.30 and 0.24 microgram/ml from zinc-supplemented and zinc-deficient rats, respectively. Salivary zinc concentrations in the deficient rats did not differ from those of the zinc-supplemented ad libitum-fed controls in any of the experiments. Salivary zinc concentration in the zinc-supplemented restricted-intake group in experiment 2 was significantly higher than that in the other two groups. Decreases in serum, bone, and fetal zinc concentrations indicated that the rats were definitely zinc-deficient. Since zinc concentration of mixed saliva in the rat was not decreased by even a severe zinc deficiency, salivary zinc does not appear to be as good an indicator of zinc status as plasma zinc.

Animals↗

Effect of hypothyroidism on intestinal zinc absorption and renal zinc disposal in five-sixths nephrectomized rats.

Both hypothyroid (Hypo) and hypozincemia are commonly observed in patients and animals with chronic renal failure (CRF). In CRF whether the hypothyroid plays a role in the pathogenesis of hypozincemia is unclear. This study is designed to investigate the effects of hypothyroid on intestinal zinc absorption and urinary zinc excretion in 5/6 nephrectomized (Nx) rats, because plasma zinc balance is attained through a controlled rate of intestinal uptake as well as renal reabsorption. Intestinal zinc absorption was carried out in jejunum and ileum segments by an in vivo perfusion technique and the renal zinc disposal was evaluated by a conventional method using a standard formula to calculate the zinc tubular reabsorption and the excretion of urinary zinc in 5/6 Nx rats with hypothyroidism. The Hypo-NxT rats showed a significant decrease in the rate of intestinal zinc absorption and in the response of plasma zinc levels during intestinal zinc perfusion compared with Eu-NxT rats. They also had significantly lower levels of mucosal zinc and MT as well as lower content of liver zinc than Eu-NxT rats after intestinal zinc perfusion for 80 min. Hypo-NxT rats showed low plasma zinc levels, but had a similar output of pancreaticobiliary zinc and excretion of 24-h urine zinc compared with the Eu-NxT rats. When 2% alcohol intestinal perfusion was used to produce water diuresis, the Hypo-NxT rats presented a higher excretion of urinary zinc than the Eu-NxT rats did, especially during 2% alcohol intestinal zinc perfusion. In the Hypo-NxT rats, the lower plasma zinc levels may thus result from the hypothyroid because it reduces intestinal zinc absorption. Increasing the urine flow rate may aggravate the reduction of plasma zinc level in Hypo-NxT rats because of the increased excretion of urinary zinc.

Animals↗

The effects of zinc supplementation on serum zinc and cholesterol concentrations in hemodialysis patients.

OBJECTIVE: To examine the effect of zinc sulfate supplementation on the concentrations of serum zinc and serum cholesterol in hemodialysis (HD) patients. SETTING: Outpatient dialysis center in a large metropolitan city. DESIGN: Randomized, double-blind, before-after trial. PATIENTS: Twenty-eight maintenance HD patients were selected. Twenty (15 women and 5 men) completed the study. Subjects were identified for inclusion in the study by the following criteria: HD treatment for a minimum of 6 months, no signs of gastrointestinal disorders, and no record of hospitalizations for reasons other than vascular access complications within the last 3 months. INTERVENTIONS: Patients were given a daily supplement of 7.7 micromol zinc sulfate (50 mg elemental zinc) or a cornstarch placebo capsule for 90 days. Patients completed 2-day food records, at day 0 and day 90 of the study, which included 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 and total cholesterol (TCHOL) concentrations. Dietary parameters, including zinc, protein, and energy intake, were also analyzed on days 0 and 90. RESULTS: Initial concentrations of serum zinc indicated subjects were below the normal range for serum zinc standards (12 micromol/L [80 microg/dL]). After supplementation, subjects in the zinc-supplemented group showed significant increases in serum zinc concentrations from 0.79 microg/mL at day 0 to 0.96 microg/mL at day 90. Serum TCHOL concentrations were initially low among subjects in the control (2.914 +/- 0.158 mmol/L [112.7 +/- 6.1 mg/dL]) and zinc-supplemented (3.155 +/- 0.354 mmol/L [122.0 +/- 13.7 mg/dL]) groups. Serum TCHOL concentrations in the control group increased slightly throughout the study period but did not reach statistical significance. A progressive increase in serum TCHOL concentration was observed in the zinc-supplemented group from the beginning (3.155 +/- 0.354 mmol/L [122.0 +/- 13.7 mg/dL]) to the end (4.445 +/- 0.478 mmol/L [171.9 +/- 18.5 mg/dL]) of the study (r =.63, P <.05). Mean serum high-density lipoprotein (HDL) cholesterol concentrations for the zinc-supplemented group were 0.959 mmol/L +/- 0.11 (37.1 mg/dL +/- 4.3), 0.825 mmol/L +/- 0.08 (31.9 mg/dL +/- 3.2), and 0.908 mmol/L +/- 0.10 (35.1 mg/dL +/- 3.9) from the beginning to the end of the experimental period. The mean serum HDL cholesterol concentrations for the control group were 0.760 mmol/L +/- 0.075 (29.4 mg/dL +/- 2.9), 0.760 +/- 0.08 (29.4 mg/dL +/- 3.0), and 0.799 mmol/L +/- 0.13 (30.9 mg/dL +/- 4.9) from the beginning to the end of the experimental period. A progressive increase in low-density lipoprotein (LDL) cholesterol concentration was observed for the zinc-supplemented group throughout the study. Mean LDL cholesterol concentrations for the zinc-supplemented group were 2.19 mmol/L +/- 0.39 (85 mg/dL +/- 15.0), 3.30 mmol/L +/- 0.36 (127.8 mg/dL +/- 14.1), and 3.53 mmol/L +/- 0.53 (136.7 mg/dL +/- 20.6) from the beginning to the end of the study period. When serum zinc concentration was correlated with serum LDL cholesterol concentration, a significant correlation was found (r =.62, P <.03) for the zinc-supplemented group and no significant difference was found for the control group. No significant differences in LDL cholesterol concentrations were found within the control group from the beginning to the end of the study. Dietary intake of zinc, cholesterol, total fat, and saturated fat remained constant and did not statistically influence serum values. Reported energy intake increased significantly in the zinc-supplemented group from 5,799 kJ/24 h (1,385 kcal/d) at day 0 to 7,042 kJ/24 h (1,682 kcal/d) at day 90. CONCLUSION: Zinc supplementation is an effective means of improving serum levels of zinc and cholesterol in the HD patient.

Astringents↗

Zinc requirements and the risks and benefits of zinc supplementation.

The adult human contains 2-3g of zinc, about 0.1% of which are replenished daily. On this basis and based on estimates of bioavailability of zinc, dietary recommendations are made for apparently healthy individuals. Absent chemical, functional, and/or physical signs of zinc deficiency are assumed indicative of adequacy. More specific data are seldom available. Changing food preferences and availability, and new food preparation, preservation, and processing technologies may require re-evaluation of past data. Conservative estimates suggest that 25% of the world's population is at risk of zinc deficiency. Most of the affected are poor, and rarely consume foods rich in highly bioavailable zinc, while subsisting on foods that are rich in inhibitors of zinc absorption and/or contain relatively small amounts of bioavailable zinc. In contrast, among the relatively affluent, food choice is a major factor affecting risk of zinc deficiency. An additional problem, especially among the relatively affluent, is risk of chronic zinc toxicity caused by excessive consumption of zinc supplements. High intakes of zinc relative to copper can cause copper deficiency. A major challenge that has not been resolved for maximum health benefit is the proximity of the recommended dietary allowance (RDA) and the reference dose (RfD) for safe intake of zinc. Present recommendations do not consider the numerous dietary factors that influence the bioavailability of zinc and copper, and the likelihood of toxicity from zinc supplements. Thus the current assumed range between safe and unsafe intakes of zinc is relatively narrow. At present, assessment of zinc nutriture is complex, involving a number of chemical and functional measurements that have limitations in sensitivity and specificity. This approach needs to be enhanced so that zinc deficiency or excess can be detected early. An increasing number of associations between diseases and zinc status and apparently normal states of health, where additional zinc might be efficacious to prevent certain conditions, point at the pharmacology of zinc compounds as a promising area. For example, relationships between zinc and diabetes mellitus are an area where research might prove fruitful. In our opinion, a multidisciplinary approach will most likely result in success in this fertile area for translational research.

Animals↗

Adding zinc to prenatal iron and folate supplements improves maternal and neonatal zinc status in a Peruvian population.

BACKGROUND: Maternal zinc deficiency during pregnancy may be widespread among women in developing countries, but few data are available on whether prenatal zinc supplementation improves maternal and neonatal zinc status. OBJECTIVE: We studied whether maternal zinc supplementation improved the zinc status of mothers and neonates participating in a supplementation trial in a shantytown in Lima, Peru. DESIGN: Beginning at gestation week 10-24, 1295 mothers were randomly assigned to receive prenatal supplements containing 60 mg Fe and 250 microg folate, with or without 15 mg Zn. Venous blood and urine samples were collected at enrollment, at gestation week 28-30, and at gestation week 37-38. At birth, a sample of cord vein blood was collected. We measured serum zinc concentrations in 538 women, urinary zinc concentrations in 521 women, and cord zinc concentrations in 252 neonates. RESULTS: At 28-30 and 37-38 wk, mothers receiving zinc supplements had higher serum zinc concentrations than mothers who did not receive zinc (8.8 +/- 1.9 compared with 8.4 +/- 1.5 micromol/L and 8.6 +/- 1.5 compared with 8.3 +/- 1.4 micromol/L, respectively). Urinary zinc concentrations were also higher in mothers who received supplemental zinc (P < 0.05). After adjustment for covariates and confounding factors, neonates of mothers receiving zinc supplements had higher cord zinc concentrations than neonates of mothers who did not receive zinc (12.7 +/- 2.3 compared with 12.1 +/- 2.1 micromol/L). Despite supplementation, maternal and neonatal zinc concentrations remained lower than values reported for well-nourished populations. CONCLUSION: Adding zinc to prenatal iron and folate tablets improved maternal and neonatal zinc status, but higher doses of zinc are likely needed to further improve maternal and neonatal zinc status in this population.

Adult↗