Hepatic-Specific Decrease in the Expression of Selenoenzymes and Factors Essential for Selenium Processing After Endotoxemia.

Background: Selenium (Se) levels decrease in the circulation during acute inflammatory states and sepsis, and are inversely associated with morbidity and mortality. A more specific understanding of where selenoproteins and Se processing are compromised during insult is needed. We investigated the acute signaling response in selenoenzymes and Se processing machinery in multiple organs after innate immune activation in response to systemic lipopolysaccharide (LPS). Methods: Wild type (WT) adult male C57/B6 mice were exposed to LPS (5 mg/kg, intraperitoneal). Blood, liver, lung, kidney and spleen were collected from control mice as well as 2, 4, 8, and 24 h after LPS. Plasma Se concentration was determined by ICP-MS. Liver, lung, kidney and spleen were evaluated for mRNA and protein content of selenoenzymes and proteins required to process Se. Results: After 8 h of endotoxemia, plasma levels of Se and the Se transporter protein, SELENOP were significantly decreased. Consistent with this timing, the transcription and protein content of several hepatic selenoenzymes, including SELENOP, glutathione peroxidase 1 and 4 were significantly decreased. Furthermore, hepatic transcription and protein content of factors required for the Se processing, including selenophosphate synthetase 2 (Sps2), phosphoseryl tRNA kinase (Pstk), selenocysteine synthase (SepsecS), and selenocysteine lyase (Scly) were significantly decreased. Significant LPS-induced downregulation of these key selenium processing enzymes was observed in isolated hepatocytes. In contrast to the acute and dynamic changes observed in the liver, selenoenzymes did not decrease in the lung, kidney or spleen. Conclusion: Hepatic selenoenzyme production and Se processing factors decreased after endotoxemia. This was temporally associated with decreased circulating Se. In contrast to these active changes in the regulation of Se processing in the liver, selenoenzymes did not decrease in the lung, kidney or spleen. These findings highlight the need to further study the impact of innate immune challenges on Se processing in the liver and the impact of targeted therapeutic Se replacement strategies during innate immune challenge.

Comparison of complementary feeding strategies to meet zinc requirements of older breastfed infants.

BACKGROUND: The low zinc intake from human milk at ∼6 mo of age predicts the dependence on complementary foods (CF) to meet the zinc requirements of older breastfed-only infants. OBJECTIVE: The objective of this study was to compare major variables of zinc homeostasis and zinc status in 9-mo-old breastfed infants who were randomly assigned to different complementary food regimens. DESIGN: Forty-five exclusively breastfed 5-mo-old infants were randomly assigned to receive commercially available pureed meats, iron-and-zinc-fortified infant cereal (IZFC), or whole-grain, iron-only-fortified infant cereal (IFC) as the first and primary CF until completion of zinc metabolic studies between 9 and 10 mo of age. A zinc stable-isotope methodology was used to measure the fractional absorption of zinc (FAZ) in human milk and CF by dual-isotope ratios in urine. Calculated variables included the dietary intake from duplicate diets and 4-d test weighing, the total absorbed zinc (TAZ) from FAZ × diet zinc, and the exchangeable zinc pool size (EZP) from isotope enrichment in urine. RESULTS: Mean daily zinc intakes were significantly greater for the meat and IZFC groups than for the IFC group (P < 0.001); only intakes in meat and IZFC groups met estimated average requirements. Mean (±SEM) TAZ amounts were 0.80 ± 0.08, 0.71 ± 0.09, and 0.52 ± 0.05 mg/d for the meat, IZFC, and IFC groups, respectively (P = 0.027). Zinc from human milk contributed <25% of TAZ for all groups. The EZP correlated with both zinc intake (r = 0.43, P < 0.01) and TAZ (r = 0.54, P < 0.001). CONCLUSION: Zinc requirements for older breastfed-only infants are unlikely to be met without the regular consumption of either meats or zinc-fortified foods.

Zinc absorption and zinc status are reduced after Roux-en-Y gastric bypass: a randomized study using 2 supplements.

BACKGROUND: Micronutrient deficiencies are common in patients undergoing gastric bypass. The effect of this type of surgery on zinc absorption and zinc status is not well known. OBJECTIVE: The objective was to evaluate the effects of Roux-en-Y gastric bypass (RYGBP) on zinc status and zinc absorption at different stages after surgery. We hypothesized that zinc status would be significantly impaired after surgery and that this impairment would be less severe in subjects receiving increased supplemental zinc. We also hypothesized that zinc absorption would be lower after surgery. DESIGN: Anthropometric and body-composition variables and dietary and biochemical indexes of zinc status and zinc absorption were determined in 67 severe and morbidly obese women [mean (±SD) age: 36.9 ± 9.8 y; BMI (in kg/m(2)): 45.2 ± 4.7] who underwent RYGBP. The subjects were randomly assigned to 1 of 2 vitamin-mineral supplementation groups. Measurements were made before and 6, 12, and 18 mo after surgery. Fifty-six subjects completed the 18-mo follow-up. RESULTS: Mean plasma zinc, erythrocyte membrane alkaline phosphatase activity, and the size of the rapidly exchangeable zinc pool decreased after RYGBP. Percentage zinc absorption decreased significantly from 32.3% to 13.6% at 6 mo after RYGBP and to 21% at 18 mo after surgery. No effect of supplement type was observed. CONCLUSIONS: Zinc status is impaired after RYGBP, despite the finding that dietary plus supplemental zinc doubled recommended zinc intakes in healthy persons. Zinc absorption capacity is significantly reduced soon after RYGBP, with no major changes until 18 mo after surgery.

The use of dysprosium to measure endogenous zinc excretion in feces eliminates the necessity of complete fecal collections.

The secretion of endogenous zinc (Zn) into the gut and subsequent excretion in the feces is understood to play a major role in maintaining Zn homeostasis in humans. Therefore, the measurement of endogenous Zn losses in the feces (EFZ) can be an important aspect of the study of Zn metabolism and homeostasis. The methods currently used to measure EFZ have the disadvantage of requiring complete fecal collections over multiple days. We have investigated the use of dysprosium (Dy), a nonabsorbable rare earth metal, in a method of determining EFZ that does not require complete fecal collections and permits the measurement of EFZ from several fecal samples. The method was evaluated using data from a study of free-living adult females in which Dy was administered 3-4 times/d over a period of 5 or 6 d to monitor completeness of fecal collections. The results did not differ from those obtained using an established isotope dilution method. We found that the measurement of the sample Dy:Zn ratio was useful for selecting samples for measurement. We conclude that the Dy method of determining EFZ is a valid and less burdensome alternative to current techniques.

Iron absorption and iron status are reduced after Roux-en-Y gastric bypass.

BACKGROUND: Iron deficiency and iron deficiency anemia are common in patients who undergo gastric bypass. The magnitude of change in iron absorption is not well known. OBJECTIVE: The objective was to evaluate the effects of Roux-en-Y gastric bypass (RYGBP) on iron status and iron absorption at different stages after surgery. We hypothesized that iron absorption would be markedly impaired immediately after surgery and would not improve after such a procedure. DESIGN: Anthropometric, body-composition, dietary, hematologic, and iron-absorption measures were determined in 67 severe and morbidly obese women [mean age: 36.9 +/- 9.8 y; weight: 115.1 +/- 15.6 kg, body mass index (BMI: in kg/m(2)); 45.2 +/- 4.7] who underwent RYGBP. The Roux-en-Y loop length was 125-150 cm. Determinations were carried out before and 6, 12, and 18 mo after surgery. Fifty-one individuals completed all 4 evaluations. RESULTS: The hemoglobin concentration decreased significantly throughout the study (repeated-measures analysis of variance). The percentage of anemic subjects changed from 1.5% at the beginning of the study to 38.8% at 18 mo. The proportion of patients with low serum ferritin increased from 7.5% to 37.3%. The prevalence of iron deficiency anemia was 23.9% at the end of the experimental period. Iron absorption from both a standard diet and from a standard dose of ferrous ascorbate decreased significantly after 6 mo of RYGBP to 32.7% and 40.3% of their initial values, respectively. No further significant modifications were noted. CONCLUSION: Iron absorption is markedly reduced after RYGBP with no further modifications, at least until 18 mo after surgery.

Absorption of calcium from tortilla meals prepared from low-phytate maize.

BACKGROUND: Calcium fortification of maize has been achieved for millennia in Central America by the process of nixtamalization. Bioavailability of calcium is, however, compromised by phytate, which is present in large quantities in maize kernels and is only modestly reduced by nixtamalization. OBJECTIVE: The objective was to compare the absorption of calcium from tortilla meals prepared from low-phytate maize with that from meals prepared from maize with typical phytate content. DESIGN: At 1-mo intervals, 5 healthy adult women were fed 2 test meals of approximately 140 g tortillas in lieu of breakfast. On one occasion, the tortillas were prepared from maize with approximately 60% phytate reduction, and, on the other occasion, they were prepared from the matching isohybrid wild-type maize. Beginning midway through the test meal, (44)Ca (0.3 mg/kg body wt) was administered in water as an extrinsic label; (42)Ca (0.06 mg/kg body wt) was administered intravenously immediately after the test meal. Isotope ratios of (42)Ca to (43)Ca and of (44)Ca to (43)Ca were measured by inductively coupled plasma mass spectrometry in urine collected as an 8-h pool from the period 16-24 h after intravenous tracer administration and prepared by the oxalate precipitation method. Fractional absorption of calcium was determined by using a dual-isotope ratio technique. RESULTS: Mean fractional absorption of calcium from tortillas prepared from the low-phytate maize (0.50 +/- 0.03) was significantly (P = 0.003) greater than that from tortillas prepared from the control maize (0.35 +/- 0.07). CONCLUSION: The increase in the quantity of calcium absorbed could be of practical importance for calcium nutriture when the intake of dairy products is limited.

Zinc absorption from low-phytate hybrids of maize and their wild-type isohybrids.

BACKGROUND: Identification of allelic variants in a single gene that determine the phytate content of maize kernels and the subsequent breeding of low-phytate maize have facilitated studies designed to determine quantitatively the effects of maize phytate on the bioavailability of minerals in maize. OBJECTIVE: The objective was to determine the relation between the fractional absorption of zinc (FAZ) and the phytate content and phytate:zinc molar ratios of maize tortillas prepared from hybrids with different phytate contents. DESIGN: Six healthy adults were fed, as the only food for 2 d, maize tortillas prepared from 1 of 2 low-phytate mutants: lpa1-1 (lpa1-1-LP) or Nutridense Low Phytate (ND-LP), which have phytate reductions of approximately 60% and approximately 80%, respectively, compared with their respective wild-type isohybrids. Four additional subjects were fed tortillas prepared from the corresponding wild-type isohybrids (lpa1-1-WT and ND-WT) according to the same study design. Meals were extrinsically labeled with zinc stable isotopes, and FAZ was determined with a dual-isotope-tracer ratio technique. Overall FAZ values were examined in relation to dietary phytate and phytate:zinc molar ratios by using a mixed nonlinear regression model. RESULTS: The mean (+/-SD) FAZ values from tortillas prepared from ND-LP, lpa1-1-LP, lpa1-1-WT, and ND-WT were 0.38 +/- 0.07, 0.28 +/- 0.04, 0.15 +/- 0.07, and 0.13 +/- 0.05, respectively. A negative relation (P < 0.001) was found between FAZ and both dietary phytate and the phytate:zinc molar ratio. The effect of dietary zinc (8-14 mg Zn/d) under these experimental conditions was not significant. CONCLUSIONS: FAZ from maize tortillas is positively related to the extent of phytate reduction achieved with low-phytate hybrids.

Exchangeable zinc pool size in infants is related to key variables of zinc homeostasis.

The exchangeable zinc pool (EZP) is the sum of the combined pools that exchange with zinc in the plasma within 48-72 h and is thought to be critical for zinc-dependent biological processes. The size of the EZP in adults has been found to be positively related to dietary zinc intake, daily absorbed zinc and fecal excretion of endogenous zinc. In this study, we examine data on EZP size in relation to variables of zinc homeostasis in normal infants on different feeding regimens. Data from 45 male infants who participated in one of four different studies contribute to the analysis. The feeding regimens include exclusive breastfeeding (n = 9; age, 2-5 mo); breastfeeding plus modest supplementation with cow's milk-based formula (n = 16; age, 3-4 mo); exclusive formula feeding (n = 4; age, 3-4 mo) and exclusive breastfeeding plus complementary foods (n =16; age, 7 mo). Fractional absorption was determined by fecal monitoring after oral administration of zinc-stable isotopes. Urine enrichment 4-8 d posttracer was used to determine endogenous fecal zinc (7-mo-old infants excepted) and EZP size. Univariate correlations and multivariate regression analyses were performed between EZP and age, weight, dietary zinc intake, fractional absorption, total absorbed zinc and endogenous fecal zinc. Results include no significant relationship between EZP size and age, body weight or fractional absorption but a positive relationship with daily absorbed zinc and endogenous fecal zinc excretion. We conclude that the amount of absorbed zinc is not tightly regulated, and that endogenous fecal zinc is dependent on and responsive to the zinc status of the organism.

The use of zinc stable isotopes in the study of iron-zinc interactions in Chilean women.

The objective of this study was to compare the fractional zinc absorption (FAZ) and the size of the rapidly exchangeable zinc pool (EZP) after three months of iron supplementation in women consuming ferrous sulfate between meals. Twenty-one non-anemic apparently healthy women received on average 55.1 +/- 18.5 mg elemental iron per day as ferrous sulfate, and five received no supplemental iron. Fractional absorption of zinc was determined before and three days after finishing the third month of iron supplementation by using an extrinsic labeling with zinc stable isotopes and a dual isotope enrichment method in urine. EZP was determined from urine enrichment following intravenous administration of 70Zn. Results of selected zinc-related variables in the iron supplemented women were (before vs. after iron supplementation): FAZ with meal 0.22 vs. 0.24, p = .23; FAZ in fasting state 0.58 vs. 0.69, p = .005; EZP 177 mg vs. 160 mg, p = .058; plasma zinc 90.6 vs. 86.1 micrograms/dl, p = .065. The control group remained unchanged. The capacity to absorb zinc was increased three days after terminating a period of iron supplementation as compared with the pre-iron period. This may be attributable to impairment of zinc status by the iron supplements as evidenced by a trend for lower plasma zinc and EZP.

Zinc absorption from a low-phytic acid maize.

BACKGROUND: Phytic acid reduction in cereal grains has been accomplished with plant genetic techniques. These low-phytic acid grains provide a strategy for improving the mineral (eg, zinc) status in populations that are dependent on grains, including maize (Zea mays L.), as major dietary staples. OBJECTIVE: The objective was to compare the fractional absorption of zinc from polenta prepared from maize low in phytic acid with that prepared from a wild-type isohybrid maize (control) after short-term consumption by adults whose habitual diet is low in phytic acid. DESIGN: Healthy adults served as their own control subjects in a crossover design. All meals on 1 d consisted of polenta prepared from a low-phytic acid maize homozygous for the recessive low phytic acid 1-1 (lpa1-1). On the preceding or following day, all meals consisted of polenta prepared from a sibling isohybrid homozygous wild-type maize with a "normal" phytic acid content. The low-phytic acid maize contained approximately 60% less phytic acid than did the wild-type maize. All test meals were extrinsically labeled with zinc stable-isotope tracers. The fractional absorption of zinc was determined on the basis of fecal enrichment. RESULTS: The molar ratios of phytic acid to zinc in the polenta prepared from lpa1-1 maize and the wild-type maize were 17:1 and 36:1, respectively. The corresponding fractional absorptions of zinc were 0.30 +/- 0.13 and 0.17 +/- 0.11, respectively (P < 0.005). CONCLUSION: Substitution of a low-phytic acid grain in a maize-based diet is associated with a substantial increase in zinc absorption.

Zinc homeostasis during lactation in a population with a low zinc intake.

BACKGROUND: There is a major increase in endogenous zinc excretion, specifically via the mammary gland, in early human lactation. Whereas fractional absorption of dietary zinc has been reported to increase in early human lactation, it is not known to what extent adaptive mechanisms may maintain zinc homeostasis, especially when dietary zinc intake is relatively low. OBJECTIVE: The objective of this study was to quantitate major variables of zinc homeostasis during early lactation in subjects from a population whose habitual dietary zinc intake is low. DESIGN: We studied 18 free-living lactating women from a rural community of northeast China whose infants were exclusively breast-fed. The subjects were studied at approximately 2 mo of lactation with use of stable isotopes of zinc and metabolic collection techniques. Milk volume was measured with use of a deuterium enrichment method. RESULTS: The mean (+/-SD) secretion of zinc in milk was 2.01 +/- 0.97 mg/d, the intake of zinc was 7.64 +/- 1.61 mg/d, and the fractional absorption of zinc was 0.53 +/- 0.09, for a total daily zinc absorption of 4.00 +/- 0.71 mg/d. Endogenous zinc excretion in urine and feces was 0.30 +/- 0.10 and 1.66 +/- 0.97 mg/d, respectively. CONCLUSIONS: Zinc balance, including zinc secreted in breast milk, was maintained at approximately 2 mo of lactation in women whose habitual diet was low in zinc. Homeostasis was achieved by high fractional absorption of zinc and intestinal conservation of endogenous fecal zinc.

PHYTIC ACID INTAKE AND ITS EFFECT ON THE BIOAVAILABILITY OF ZINC IN PRESCHOOL CHILDREN / 营养学报

Phytic acid intake of preschool children was measured with modified ion exchange method. Zinc bioavailability was assessed by metabolic balance experiment and phytic acid/zinc molar ratio was calculated.The average intake of phytic acid in the diet was 499mg/day. The average of phytic acid/zinc molar ratio was 6.66. Even the subjects ingested foods rich in phytic acid, the phytic acid/zinc molar ratio (10.6) still remained at the lower limit of the critical value (10-20), that will inhibit zinc bioavailability. Metabolic balance study indicated that zinc bioavailability was not inhibited.Therefore, the phytic acid in present Chinese diet is unlikely a factor of zinc deficiency among children.