Does the oral zinc tolerance test measure zinc absorption?

Increases in plasma zinc concentration were compared with radiozinc absorption after oral test doses. Ten healthy, fasting subjects were each given 385 mumol zinc chloride (25 mg Zn) labelled with 0.5 muCi 65ZnCl2 and a non-absorbed marker, 51CrCl3, dissolved in 100 ml of water; another 10 persons were given 354 mumol zinc chloride and 125 g of minced turkey containing 31 mumol zinc also labelled with 65Zn and 51Cr. Measurements were made of plasma zinc concentration at hourly intervals for 5 hours, radiozinc absorption by stool counting of unabsorbed radioactivity 12-36 hours later, and radiozinc retention by whole body counting at 7 days. The mean percentage of radiozinc absorbed and retained in the body from the two test meals was found to be identical (42%). In contrast the increased area under the plasma zinc curve up to 5 hours after the turkey meal, 28 +/- 9 mumol/L (mean +/- SD) was significantly less than that for zinc chloride alone, 47 +/- 15 mumol/L, p less than 0.005. Despite this difference, a good correlation was found between the area under the plasma zinc curve and 65Zn absorption in individual subjects after each meal. The discrepancy between the results of zinc absorption derived from the plasma zinc curve and 65Zn absorption for the liquid and solid test meals was most likely explained by binding of zinc to food and delayed gastric emptying of the solid meal. With a test meal of turkey meat at least this dampened the plasma appearance of zinc but did not affect its overall absorption.     

Iron, zinc and copper interactions: chronic versus acute responses of rats

Several methodologies were evaluated to study iron, zinc and copper interactions. In three studies, rats were fed diets containing adequate levels of iron (33-35 micrograms Fe/g diet) and zinc (15-25 micrograms Zn/g diet) and diets with excessive levels of zinc (2441-2470 micrograms Zn/g diet) or iron (1408-3042 micrograms Fe/g diet). Consumption of excess iron for several weeks or in one test meal did not alter tissue levels of zinc or apparent absorption of 65Zn. In contrast rats fed excess zinc throughout the three studies had depressed hematocrits and serum copper levels, apparently absorbed 59Fe less efficiently and retained less 59Fe in livers and tibias than control animals. Nutritional status with regard to iron or zinc, not just the intakes of iron and zinc, also influenced the interactions between zinc and iron. Rats fed excess iron for several weeks retained less 65Zn from a test meal in their tibias than rats fed excessive iron in only the test meal. Although chronic ingestion of excess zinc depressed apparent absorption of 59Fe from a test meal, the ingestion of one test meal with excess zinc did not. Investigators studying nutrient interactions should not rely solely on studies in which unadjusted humans or animals are given a single dose of test substances because acute responses do not reflect all the changes induced by chronic feeding.     

Zinc absorption and achlorhydria

Zinc absorption from 40 mumol of zinc in a water solution and from a test meal containing 22 mumol of zinc was studied in 8 patients with achlorhydria (no basal acid secretion and no secretion after pentagastrin stimulation). The test dose and the meal was labelled with 0.1 MBq of 65Zn and absorption was determined from measurement of the whole-body retention of the isotope. Zinc absorption was 68 +/- 16 per cent (mean +/- s.d.) from the water solution and 33 +/- 10 per cent from the test meal. The results did not differ from absorption in control subjects and indicate that achlorhydria per se does not affect zinc absorption.     

Studies of iron:zinc interactions in adult rats and the effect of iron fortification of two commercial infant weaning products on iron and zinc status of weanling rats

The effect of iron on zinc absorption in the rat, and vice versa, was investigated from single starch:sucrose test meals (containing 65Zn or 59Fe) by whole body counting. Zinc had no effect on iron absorption, but iron reduced zinc absorption when the total ionic species in the meal (iron plus zinc) reached 1.36 mg. Below this level, high iron:zinc molar ratios (10:1) had no effect on zinc absorption, presumably because the transport mechanism for zinc had not reached full capacity. Previous iron intake had no effect on zinc absorption. The relevance of these findings to infant foods was explored by feeding rats exclusively a vegetable or cereal weaning product, with or without additional iron, for 12 d and measuring zinc and iron status. The added iron raised body iron stores and caused a small reduction in zinc status in animals fed the oat, but not the vegetable, diet as measured by plasma and femur zinc concentrations. Since the threshold level of 1.36 mg ionic species would be exceeded when the animal ate 3-4 g of the iron-fortified weaning food at any one time, it appears that the iron:zinc interactive effect was absent in the vegetable and less potent in the oat formulation than in a carbohydrate test meal. Alternatively, it may be the case that the animals had responded over time to reduced zinc availability by increasing whole body zinc retention.(ABSTRACT TRUNCATED AT 250 WORDS)     

Absorption of zinc from wheat products fortified with iron and either zinc sulfate or zinc oxide

BACKGROUND: Several chemical forms of zinc have been proposed for food fortification, but information is needed on their absorption from common cereals having varied phytate content. OBJECTIVE: The goal was to measure zinc absorption from wheat products fortified with iron sulfate and either zinc sulfate or zinc oxide. DESIGN: Adult volunteers received either low-phytate bread (n = 11) or higher-phytate porridge (n = 11) once weekly on 2 or 3 occasions. The foods were fortified with 1 of the 2 zinc salts (60 mg elemental Zn/kg wheat flour) during week 1 and with the other during week 2, in random order. (65)Zn in the same chemical form as the fortificant was incorporated in each food to assess zinc absorption with the use of whole-body counting. The porridge group received an additional test meal fortified with zinc oxide during week 3, but the (65)Zn tracer was given as an oral solution of (65)ZnCl(2). RESULTS: Zinc absorption from bread (13.8%; 95% CI: 11.8%, 16.2%) was significantly (P < 0.001) greater than from porridge (6.4%; 5.5%, 7.6%), presumably because of the greater phytate content of the porridge. With control for food type, there were no significant differences in zinc absorption from meals fortified with zinc sulfate or zinc oxide (P = 0.24). When the porridge was fortified with zinc oxide and labeled with (65)ZnCl(2), absorption of the tracer (8.9%; 7.1%, 11.0%) was significantly (P = 0.007) greater than when (65)ZnO was incorporated in the porridge (5.6%; 4.5%, 6.9%). CONCLUSIONS: Either zinc oxide or zinc sulfate can be used to fortify wheat products consumed by presumably healthy persons. Isotopic tracers used to assess the absorption of mineral fortificants should have the same chemical form as the fortificant.     

Oral iron, dietary ligands and zinc absorption

The effect of iron on zinc absorption in humans was investigated by using 65Zn and whole-body counting after 2 wk. Increasing the molar ratio of ferrous iron (with ascorbic acid) to zinc from 1:1 to 2.5:1 did not affect absorption of zinc from water when given in a fasting state; 59 and 58% was absorbed, respectively. However, at an Fe:Zn ratio of 25:1, zinc absorption from water decreased significantly to 34%. When oral iron in the same ratio to zinc was given with a meal, no inhibitory effect was observed (25, 23 and 22%, respectively). Addition of the zinc ligand, histidine, to the water solution decreased the inhibitory effect of the higher dose of iron, resulting in a zinc absorption of 47%. Two weeks of iron preloading did not affect zinc absorption from water. The results demonstrate that when a multimineral supplement is taken on an empty stomach, excessive iron levels can negatively affect zinc absorption. Intake of the supplement with a meal or with a zinc ligand (such as histidine) may overcome this inhibitory effect.     

Zinc absorption in humans from meals based on rye, barley, oatmeal, triticale and whole wheat

The absorption of zinc from meals based on 60 g of rye, barley, oatmeal, triticale or whole wheat was studied by use of extrinsic labelling with 65Zn and measurement of the whole-body retention of the radionuclide. The cereals were prepared in the form of bread or porridge and were served with 200 mL of milk. The oatmeal flakes were also served without further preparation. The absorption of zinc was negatively correlated to the phytic acid content of the meal with the highest absorption, 26.8 +/- 7.4%, from the rye bread meal containing 100 mumol of phytic acid and the lowest, 8.4 +/- 1.0%, from oatmeal porridge with a phytic acid content of 600 mumol. It is concluded that food preparation that decreases the phytic acid content improves zinc absorption.     

Effect of protein level and protein source on zinc absorption in humans

The effect of increasing levels of various protein sources on zinc absorption from a legume-based meal was studied in humans with the use of a radionuclide technique. The meals were extrinsically labelled with 65Zn and absorption was determined from measurements of the whole-body retention of the isotope. The mean fractional zinc absorption for the 13 meals was 24.7 +/- 6.9% and was only influenced by the protein content of the meal to a limited extent (r = 0.45). However, the amount of zinc absorbed from the meals was strongly correlated with both the protein (r = 0.85) and zinc content (r = 0.86): 5.9 +/- 1.7 mumol of zinc was absorbed from the basal bean meal which had the lowest protein content; the addition of low zinc chicken doubled the protein content and increased zinc absorption to 10.3 +/- 2.0 mumol; the addition of zinc-rich beef also doubled the protein content, however, zinc absorption was increased to 15.9 +/- 4.7 mumol. It is concluded that the zinc content of the main protein source of the diet determines the amount of zinc absorbed to a large extent. However, relatively small amounts of animal protein can significantly improve the value of a legume-based meal as a source of zinc.     

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.     

Effect of ascorbic acid on the absorption of zinc and calcium in man

The effect of ascorbic acid on the absorption of zinc and calcium, was studied in healthy subjects by a radionuclide technique with 65Zn and 47Ca and whole body retention measurements. Addition of 100 mg of ascorbic acid to a water solution of 40 or 200 mumol zinc and 1 g of ascorbic acid to a high phytate meal with wholemeal bread had no effect on zinc absorption. Neither did 1 g of ascorbic acid added to 6.4 mmol of calcium influence the retention and calculated absorption of calcium. The results suggest that ascorbic acid does not affect the absorption of normal dietary levels of zinc and calcium.     

Zinc metabolism in celiac disease

The turnover of a radiolabeled (65Zn) pool of endogenous zinc was monitored by using a whole-body counter in eight patients with celiac disease (CD) and analyzed by using a two-compartment model. The biological half-life of the first compartment (1-3 wk postadministration) was similar in healthy volunteers (122 +/- 34 d, means +/- SD) and untreated patients (97 +/- 21 d). The second compartment in the patients (3-12 wk postadministration) was shorter (159 +/- 22.5 d. p less than 0.001) than were reference values (218 +/- 27 d) but increased (291 +/- 71 d) after the patients started gluten-free diets. The percentage absorption of 65Zn (9.25 kBq) from a test meal containing 31 mumol (2 mg) zinc was similar in untreated patients (30.0 +/- 13%) and healthy volunteers (32.5 +/- 12.4%). These data show that in mild untreated CD increased turnover and loss of endogenous zinc occurs whereas the absorption of zinc from a customary zinc intake may be normal. The pathophysiological basis of this loss was not investigated.     

Supplemental zinc lowers measures of iron status in young women with low iron reserves

Zinc and iron compete during intestinal absorption, but postabsorptive interactions between these nutrients are less clear. Understanding these interactions is important to determine when supplementation with iron or zinc is proposed. The effect of zinc supplementation (22 mg Zn/d as zinc gluconate) or of iron supplementation (100 mg Fe/d as ferrous sulfate) for 6 wk on iron and zinc metabolism and absorption was evaluated in young women with low iron reserves. Young adult women (ages 20-28 y), nonanemic but with low iron stores (plasma ferritin< 20 microg/L), participated in the 70-d study. The women were divided in two groups (zinc-supplemented, n = 11; iron-supplemented, n = 12). The supplements were taken at bedtime. Iron and zinc biochemical indices and intestinal absorption were measured on d 1 and 56. Radioiron and stable isotopes of zinc were used to measure iron and zinc absorption from a test meal. In the iron-supplemented group, blood hemoglobin, plasma ferritin and the percentage of transferrin saturation increased (P < 0.01). Zinc indices did not change. In the zinc-supplemented group, plasma ferritin and the percentage of transferrin saturation decreased (P < 0.05), whereas the plasma transferrin receptor and erythrocyte zinc protoprophyrin levels increased (P < 0.05). Plasma and urinary zinc also increased (P < 0.01). Iron absorption (%) from the test meal increased (P < 0.01), whereas zinc absorption (%) decreased (P < 0.01) compared with baseline in the Zn-supplemented women. Our results indicate that the use of iron supplements in women with marginal iron status improves iron indices with no effect on zinc status. However, use of a modest zinc supplement improves zinc indices, but also appears to induce a cellular iron deficiency and, possibly, further reduce iron status.     

Milk consumption and zinc retention in postmenopausal women

We measured intestinal 65Zn absorption and whole-body retention in postmenopausal women following a meal extrinsically labeled with 65Zn. The meal was consumed with 200 mL of milk or with a calcium phosphate supplement. Fifteen elderly (mean age 69) subjects were studied during three 12-d experimental periods in which they were fed either a basal diet containing 16 mg Zn or the basal diet supplemented either with 400 mL of milk or with dibasic calcium phosphate supplements containing an equivalent amount of calcium (468 mg) and phosphorus (360 mg). Measurements of fractional zinc absorption were made in 9 of the 15 subjects by a dual-isotope technique using 65Zn and 51Cr (as nonabsorbable fecal markers). Fractional zinc absorption was 0.22 +/- 0.06 (mean +/- SEM) after the standard meal, 0.23 +/- 0.06 with added milk and 0.22 +/- 0.03% with the added calcium phosphate supplement. The corresponding values for 65Zn retention in 15 subjects 12 d after dosing were 0.10 +/- 0.01% for all treatments. No significant effect of milk or calcium phosphate supplementation was observed on either 65Zn absorption or retention. We conclude that increased milk consumption with meals has no detrimental consequences on zinc nutriture in elderly women.     

Predicting bioavailable zinc from lower phytate forms, folic Acid and their interactions with zinc in vegetarian meals

OBJECTIVE: To develop a statistical model for predicting zinc bioavailability from cereal-based vegetarian meals using relative proportion of nutrients, non-nutrients and their interactive effects. METHODS: A database on in vitro zinc dialysability (by isotopic tracer, 65Zn) of vegetarian meals (266 out of 326) from Asia, Africa, Europe /US and Latin America was used to develop a model for estimating zinc bioavailability. A multiple regression analysis adjusted for energy content was carried out for net bioavailable zinc from a meal with the predictor variables as meal contents of iron, zinc, copper, ascorbic acid, beta-carotene, riboflavin, thiamine, folic acid, tannic acid, fiber, phytate degradation products (IP6 to IP1), along with their interaction terms. Reproducibility of the model was tested with remaining 60 meals. Validation of the model was done with zinc absorption data of i) 12 young adults on 24 meals and ii) 5 adults with ileostomy on 7 meals. RESULTS: Folic acid, IP3 and IP5 were significant influencing factors for bioavailable zinc. Weighted multiple regression equation was: ln (bioavailable zinc in mg) = -1.701 + 1.285 x ln [(IP5 in mg] x (Zn in mg)] -1.222 x ln(IP5 in mg) -0.0078 x folic acid in microg -0.137 x ln [(IP3 in mg) x (Zn in mg)] with adjusted R--[2] = 0.64, p = 0.0001. The correlation between predicted and observed dialysability of meals was found to be 0.96 (p < 0.01). A significant correlation between observed and predicted amount of absorbed zinc (r = 0.85, p < 0.01) was obtained for the human data of zinc absorption in 12 healthy and 5 subjects with ileostomy. CONCLUSIONS: Bioavailable amount of zinc from vegetarian meals was influenced by IP3, IP5 and folic acid content and their interactive effect with zinc content.     

Folic acid: effect on zinc absorption in humans and in the rat

The effect of folic acid on zinc absorption and utilization was studied in humans and in rats. Serum Zn response curves after a 25-mg oral dose of Zn was measured for 4 h with and without 10 mg folic acid. The increase in serum Zn expressed as AUC (area under the curve) was 57 mumol/L for Zn alone and 65 mumol/L with folate. Zn intragastric intubation experiments with rats showed that adding 4.4 or 176 micrograms of folate to test meals containing 13 micrograms Zn did not affect the bioavailability of Zn as measured by the retention of 65Zn by the liver and kidney. A 3-wk feeding test carried out with diets containing either 6 or 12 mg Zn/kg diet showed that adding either 2 or 160 mg of folic acid had no effect on growth or Zn uptake by the femur. These results do not indicate any inhibition of Zn utilization by folic acid.     

Iron supplements inhibit zinc but not copper absorption in vivo in ileostomy subjects

BACKGROUND: Iron supplements may inhibit intestinal zinc and copper uptake because these elements may compete for binding to a transporter molecule (divalent metal transporter 1) that is located on the apical side of the small intestinal epithelium. OBJECTIVE: We quantified the interaction between different amounts of administered iron and the absorption of zinc and copper in humans. DESIGN: Eleven subjects with an ileostomy [mean (+/- SD) age: 55 +/- 9 y] ingested a stable-isotope-labeled zinc and copper solution containing 12 mg Zn ((66)Zn and (67)Zn) and 3 mg Cu ((65)Cu) in the presence of 0, 100, or 400 mg Fe as ferrous gluconate on 3 respective test days. Subsequently, 1 mg (70)Zn was injected intravenously. Subjects collected ileostomy effluent and urine for 24 h and 7 d, respectively. Zinc status and true zinc absorption were calculated from the urinary excretion of the zinc isotopes. Apparent copper absorption was calculated from ileostomy effluent excretion of the orally administered copper isotopes. RESULTS: Zinc status did not differ significantly between the 3 iron doses. Mean (+/- SEM) zinc absorption was significantly higher in the absence of iron than with the concomitant ingestion of 100 or 400 mg Fe (44 +/- 22% compared with 26 +/- 14% and 23 +/- 6%, respectively; P < 0.05), whereas zinc absorption did not differ significantly between the 100- and 400-mg Fe doses. Apparent copper absorption was 48 +/- 14%, 54 +/- 26%, and 53 +/- 7% in the presence of 0, 100, and 400 mg Fe, respectively, and did not differ significantly between the 3 iron doses. CONCLUSION: Oral iron therapy may impair zinc absorption and thus zinc status in a dose-independent fashion but does not affect copper absorption.     

Competitive inhibition of iron absorption by manganese and zinc in humans

Zinc and manganese may interfere with iron absorption because of similar physicochemical properties and shared absorptive pathways. The effects of zinc and manganese on iron absorption were studied in human subjects by using paired observations and a dual-radioisotope method (55Fe and 49Fe). Manganese inhibited iron absorption both in solutions and in a hamburger meal. Fractional iron absorption is strongly dose dependent. Adding 2.99 mg Mn to 0.01 mg Fe reduced iron absorption to the same extent as increasing the iron dose 300-fold to 3 mg, strongly indicating a direct competitive inhibition of manganese on iron absorption. In the same experiment with zinc, no inhibitory effect was observed, suggesting different pathways for the absorption of zinc and iron. An intraluminal interaction may occur, because a fivefold excess of zinc to iron (15 mgZn/3 mg Fe) reduced iron absorption by 56% when given in a water solution but not when given with a hamburger meal.     

Zinc absorption from zinc oxide, zinc sulfate, zinc oxide + EDTA, or sodium-zinc EDTA does not differ when added as fortificants to maize tortillas

The fortification of staple foods with zinc may play an important role in achieving adequate zinc intakes in countries at risk of zinc deficiency. However, little is known about the relative bioavailability of different zinc compounds that may be used in food fortification. The objective of this study was to measure and compare fractional zinc absorption from a test meal that included a maize tortilla fortified with zinc oxide, zinc sulfate, zinc oxide + EDTA, or sodium-zinc EDTA. A double isotopic tracer ratio method ((67)Zn as oral tracer and (70)Zn as intravenous tracer) was used to estimate zinc absorption in 42 Mexican women living in a periurban community of Puebla State, Mexico. The test meal consisted of maize tortillas, yellow beans, chili sauce, and milk with instant coffee; it contained 3.3 mg zinc and had a phytate:zinc molar ratio of 17. Fractional zinc absorption did not differ significantly between the test groups (ANOVA; P > 0.05). Percent absorptions were (mean +/- SD) zinc oxide, 10.8 +/- 0.9; zinc sulfate, 10.0 +/- 0.02; zinc oxide + EDTA, 12.7 +/- 1.5; and sodium-zinc EDTA, 11.1 +/- 0.7. We conclude that there was no difference in zinc absorption from ZnO and ZnSO(4) when added as fortificants to maize tortillas and consumed with beans and milk. The addition of EDTA with zinc oxide or the use of prechelated sodium-zinc EDTA as fortificants did not result in higher zinc absorption from the test meal.     

Bioavailability of zinc to rats as affected by protein source and previous dietary intake

The bioavailability of zinc from defatted soy flour, dried chicken meat or mixed (50:50 dry weight basis) soy flour and chicken meat included in egg white-based diets was investigated in rats. Following a 6-d experimental diet (9 ppm Zn) feeding period, marginally zinc-depleted weanling rats were fed a test meal, identical in composition to the experimental diet except that the protein source was labeled either intrinsically or extrinsically with 65Zn. Retention of 65Zn from the chicken test meal was significantly higher than that from the soy test meal. Retention of 65Zn from the mixed soy/chicken test meal was midway between the retention values for either protein alone regardless of which protein source was labeled. Intrinsic and extrinsic labeling techniques resulted in similar assessment of zinc bioavailability. Additionally, the influence of previous dietary protein source on zinc retention from a soy test meal was investigated. Retention of 65Zn from an intrinsically labeled soy test meal was higher in rats adapted to chicken protein than in rats adapted to soy protein. The levels of tibia zinc and tibia 65Zn were associated with whole-body retention of 65Zn.     

Short-term ingestion of chlorogenic or caffeic acids decreases zinc but not copper absorption in rats, utilization of stable isotopes and inductively-coupled plasma mass spectrometry technique

The amount of dietary trace elements absorbed from a meal depends, among other factors, on the quantities of certain minor plant constituents present in the meal. These substances can act as ligands and bind trace elements in the digestive tract in available or unavailable forms for absorption. The present study was designed to investigate the extent to which different polyphenols (PP) may influence Zn and Cu absorption in rats. Different PP of nutritional interest (chlorogenic acid, caffeic acid, catechin and rutin) were studied using meals extrinsically-labelled with stable isotopes 67Zn and 65Cu. Male Wistar rats were fed on a non-labelled semi-synthetic diet containing (mg/kg) 38 Fe, 35 Zn and 7.5 Cu for 8 d. PP were dissolved in dimethyl sulfoxide as the solvent and added to the meal at 1 g/kg during 3 d before isotope administration and until the end of the experiment (a further 3 d). The control group received the dimethyl sulfoxide only. After overnight food deprivation, rats were fed on the labelled test meals (4 g diet +0.1 mg 67Zn and 0.1 mg 65Cu) with 0.5 mg Dy as a faecal marker. Faeces and urine pools were collected for 3 d and analysed for 67Zn and 65Cu isotopic enrichment using the inductively-coupled plasma mass spectrometry technique. Zn absorption was significantly less in rats fed on chlorogenic acid or caffeic acid than in the control group. Catechin ingestion non-significantly inhibited 67Zn absorption. However, the PP studied were without effect on Cu absorption. The study illustrates the effect of metal-binding phenolic compounds on mineral nutrition in the rat, and the possible importance of the effects of different foods rich in these compounds on mineral absorption in man.