Zinc Absorption from Micronutrient Powders Is Low in Bangladeshi Toddlers at Risk of Environmental Enteric Dysfunction and May Increase Dietary Zinc Requirements.

Background: Environmental enteric dysfunction (EED), a chronic inflammatory disorder of the small bowel, is suspected to impair absorption of micronutrients, including zinc. Objective: The objective of this study was to compare zinc absorption from micronutrient powder (MNP) over a range of zinc doses in young children screened for EED with use of the lactulose:mannitol ratio (L:M). Methods: Bangladeshi children aged 18-24 mo, grouped according to high and low L:M (≥0.09 and <0.09, respectively), were randomly assigned to MNP with 0, 5, 10, or 15 mg Zn/sachet (10 subjects per dose per L:M group). Over a day, fractional absorption of zinc was measured from an MNP-fortified meal and from unfortified meals with stable isotope tracers; total daily absorbed zinc (TAZ, milligrams per day) was determined as the primary outcome. Secondary outcomes included investigation of relations of TAZ to intake, to physiologic requirement, and to other variables, including biomarkers of systemic and intestinal inflammation, using nonlinear models. TAZ was also compared with published data on child zinc absorption. Results: In 74 subjects who completed the study, zinc absorption did not differ by L:M grouping. Most biomarkers of intestinal inflammation were elevated in both L:M groups. For combined L:M groups, mean ± SD TAZ for each MNP dose (0, 5, 10, and 15 mg/sachet) was 0.57 ± 0.30, 0.68 ± 0.31, 0.90 ± 0.43, and 1.0 ± 0.39 mg/d, respectively (P = 0.002), and exceeded the estimated physiologic requirement only for the 10- and 15-mg MNP doses. Zinc absorption was notably lower at all intake levels compared with published data (P < 0.0001) and was inversely related to serum α-1 acid glycoprotein and to fecal Entamoeba histolytica (P = 0.02). Conclusion: Results indicate impaired absorption of zinc, which may predispose to zinc deficiency in young children with evidence of enteropathy. These findings suggest that current doses of zinc in MNP may be insufficient to yield zinc-related preventative benefits in similar settings. This study is registered at clinicaltrials.gov as NCT02758444.

Zinc Absorption and Endogenous Fecal Zinc Losses in Bangladeshi Toddlers at Risk for Environmental Enteric Dysfunction.

OBJECTIVES: Environmental enteric dysfunction (EED) impairs zinc absorption from food, and zinc deficiency may contribute to the poor growth associated with EED. We examined zinc absorption from a standardized aqueous zinc dose, and habitual daily endogenous fecal zinc excretion (EFZ) and compared these outcomes between children grouped by the lactulose to mannitol ratio (L:M). METHODS: Bangladeshi toddlers (18-24 months) with low (<0.09) and high (≥0.09) L:M were administered isotope-labeled 3 mg aqueous zinc in the fasted state. Fractional absorption of zinc (FAZ) and EFZ were measured by dual stable isotope tracer method and an isotope dilution method, respectively. Secondary aims included examining relationships of biomarkers of systemic and intestinal inflammation and gut function with FAZ and EFZ. RESULTS: Forty children completed the study; nearly all had evidence of EED. No differences in zinc homeostasis measurements (mean ±â€ŠSD) were observed between high and low L:M groups: FAZ was 0.38 ±â€Š0.19 and 0.31 ±â€Š0.19, respectively; both figures were within estimated reference range. Means of EFZ were 0.73 ±â€Š0.27 and 0.76 ±â€Š0.20 mg/day for high and low L:M, respectively, and were 10% to 15% above estimated reference range. Regression analyses indicated that biomarkers of systemic inflammation were directly associated with increasing FAZ, consistent with increased gut permeability. Biomarkers of intestinal inflammation were negatively associated with EFZ, consistent with low-zinc intake and chronic deficiency. CONCLUSIONS: In these children at risk of EED, endogenous zinc losses were not markedly increased. Results suggest that efforts to improve zinc status in EED should focus on substantially improving zinc intakes.

Exchangeable Zinc Pool Size at Birth in Pakistani Small for Gestational Age and Appropriate for Gestational Age Infants Do Not Differ But Are Lower Than in US Infants.

OBJECTIVES: Small for gestational age (SGA) infants are more susceptible to infectious morbidity and growth faltering compared to their appropriate for gestational age (AGA) counterparts. Zinc supplementation of SGA infants may be beneficial but the underlying susceptibility to zinc deficiency of SGA infants has not been examined. METHODS: In a community-based, observational, longitudinal study in a peri-urban settlement of Karachi, Pakistan, we compared the size of the exchangeable zinc pools (EZPs) in term SGA and AGA infants at birth and at 6 months of age, hypothesizing that the EZP would be lower in the SGA group. To measure EZP size, a zinc stable isotope was intravenously administered within 48 hours of birth (n = 17 and 22) at 6 months (n = 11 and 14) in SGA and AGA infants, respectively. Isotopic enrichment in urine was used to determine EZP. RESULTS: No significant difference was detected in the mean (±standard deviation) EZP between SGA and AGA infants at birth, with values of 9.8 ±â€Š3.5 and 10.1 ±â€Š4.1 mg/kg, respectively (P = 0.86), or at 6 months. Longitudinal EZP measurements demonstrated a significant decline in EZP relative to body weight in both groups at 6 months (P < 0.001). Mean EZP (adjusted for body weight) size at birth for the combined Pakistani groups was significantly lower than AGA infants at birth in the United States (P = 0.017). CONCLUSIONS: These results did not support a difference in zinc endowment between SGA and AGA Pakistani infants. They, however, do suggest lower in utero zinc transfer to the fetus in a setting where poor maternal nutritional status may confer a high susceptibility to postnatal zinc deficiency.

Predictors of the Size of the Exchangeable Zinc Pool Differ between Children and Adults.

BACKGROUND: The size of the rapidly exchanging pool of body zinc has been suggested as having potential utility as a biomarker of zinc status. Knowledge of the relations of exchangeable zinc pool (EZP) size to relevant variables is necessary to adequately evaluate its use as a biomarker. OBJECTIVE: We used regression analysis to investigate associations of EZP with age, sex, body size, and zinc nutrition variables. METHODS: Data were compiled from 18 isotope tracer studies of zinc absorption in 247 children and adults (248 observations) in which EZP and relevant variables (e.g., weight, age, absorbed zinc) were measured. Linear regression analyses were performed separately on data from adults and children. RESULTS: In children, EZP was most strongly associated with weight (r = 0.78). The best-fitting regression models of EZP (R2 ≥ 0.68) had weight or age and weight-for-age z score as predictors. Other variables had little effect on EZP when controlling for weight. Absorbed zinc was observed to be a predictor of EZP only in zinc intervention trials of infants. The mean EZP/wt was 4 mg/kg between 8 and 120 mo of age. In adults, EZP was observed to vary in a complex manner with (in order of importance) age, absorbed zinc, weight, sex, and plasma zinc concentration. EZP data from zinc-deprived subjects were lower than the 95% prediction interval of a model of normative data. CONCLUSIONS: EZP was observed to maintain a constant size relative to weight and was influenced only slightly by other factors in children. In contrast, EZP in adults varied with several factors, including absorbed zinc, and was statistically smaller in zinc-deprived individuals. The findings suggest that EZP may have utility as an indicator of zinc status in adults, but there is less evidence for this in children. Additional data are needed to reach a definitive conclusion.

Upregulation of Zinc Absorption Matches Increases in Physiologic Requirements for Zinc in Women Consuming High- or Moderate-Phytate Diets during Late Pregnancy and Early Lactation.

Background: Estimated physiologic requirements (PRs) for zinc increase in late pregnancy and early lactation, but the effect on dietary zinc requirements is uncertain.Objective: The aim of this study was to determine changes in daily fractional absorbed zinc and total absorbed zinc (TAZ) from ad libitum diets of differing phytate contents in relation to physiologic zinc requirements during pregnancy and lactation.Methods: This was a prospective observational study of zinc absorption at 8 (phase 1) and 34 (phase 2) wk of gestation and 2 (phase 3) and 6 (phase 4) mo of lactation. Participants were indigenous Guatemalan women of childbearing age whose major food staple was maize and who had been randomly assigned in a larger study to either of 2 ad libitum feeding groups: low-phytate maize (LP; 1.6 mg/g; n = 14) or control maize (C; 7.1 mg/g; n = 8). Total dietary zinc (milligrams per day, TDZ) and phytate (milligrams per day) were determined from duplicate diets and fractional absorption (FAZ) by dual isotope ratio technique (TAZ = TDZ × FAZ). All variables were examined longitudinally and by group and compared with PRs. TAZ values at later phases were compared with phase 1. Measured TAZ was compared with predicted TAZ for nonpregnant, nonlactating (NPNL) women.Results: TAZ was greater in the LP group than in the C group at all phases. All variables increased from phase 1 to phases 2 and 3 and declined at phase 4. TAZ increased by 1.25 mg/d (P = 0.045) in the C group and by 0.81 mg/d (P = 0.058) in the LP group at phase 2. At phase 3, the increases were 2.66 mg/d (P = 0.002) in the C group and 2.28 mg/d (P = 0.0004) in the LP group, compared with a 1.37-mg/d increase in PR. Measured TAZ was greater than predicted values in phases 2-4.Conclusions: Upregulation of zinc absorption in late pregnancy and early lactation matches increases in PRs of pregnant and lactating women, regardless of dietary phytate, which has implications for dietary zinc requirements of pregnant and lactating women.

Zinc Absorption Is Not Related to Dietary Phytate Intake in Infants and Young Children Based on Modeling Combined Data from Multiple Studies.

BACKGROUND: It is widely understood that the 2 primary factors affecting dietary zinc absorption in adults are the quantities of zinc and phytate in the diet. Although a similar association of absorption to dietary zinc and phytate is presumed to exist in children, to our knowledge, no large-scale examination of the relation of zinc absorption to dietary and growth factors has been conducted. OBJECTIVE: The goal was to apply an adult absorption model and related models to data from zinc absorption studies of infants and children in order to determine the nature of the relation of zinc absorption to dietary zinc and phytate, age, body size, and zinc homeostatic variables. METHODS: Data from 236 children between 8 and 50 mo of age were obtained from stable-isotope studies of zinc absorption. Statistical and mechanistic models were fit to the data using linear and nonlinear regression analysis. RESULTS: The effect of dietary phytate on zinc absorption when controlling for dietary zinc was very small and not statistically discernable (P = 0.29). A 500-mg/d increase in dietary phytate reduced absorbed zinc by <0.04 mg/d. Absorption was observed to vary with age, weight, and height (P < 0.0001) when controlling for dietary zinc. For example, absorption from 6 mg/d of dietary zinc increased by as much as 0.2 mg/d with a 12-mo increase in age. Absorption varied with weight and exchangeable zinc pool size (0.01 < P < 0.05) when controlling for dietary zinc and age. CONCLUSIONS: The absence of a detectable phytate effect on zinc absorption raises caution about use of dietary phytate:zinc molar ratios to predict zinc bioavailability and does not support phytate reduction as a strategy to improve zinc status of young children. The effect of age on zinc absorption and the absence of a phytate effect should facilitate estimations of dietary zinc needs in young children.

Mathematical model of zinc absorption: effects of dietary calcium, protein and iron on zinc absorption.

A previously described mathematical model of Zn absorption as a function of total daily dietary Zn and phytate was fitted to data from studies in which dietary Ca, Fe and protein were also measured. An analysis of regression residuals indicated statistically significant positive relationships between the residuals and Ca, Fe and protein, suggesting that the presence of any of these dietary components enhances Zn absorption. Based on the hypotheses that (1) Ca and Fe both promote Zn absorption by binding with phytate and thereby making it unavailable for binding Zn and (2) protein enhances the availability of Zn for transporter binding, the model was modified to incorporate these effects. The new model of Zn absorption as a function of dietary Zn, phytate, Ca, Fe and protein was then fitted to the data. The proportion of variation in absorbed Zn explained by the new model was 0·88, an increase from 0·82 with the original model. A reduced version of the model without Fe produced an equally good fit to the data and an improved value for the model selection criterion, demonstrating that when dietary Ca and protein are controlled for, there is no evidence that dietary Fe influences Zn absorption. Regression residuals and testing with additional data supported the validity of the new model. It was concluded that dietary Ca and protein modestly enhanced Zn absorption and Fe had no statistically discernable effect. Furthermore, the model provides a meaningful foundation for efforts to model nutrient interactions in mineral absorption.

Fecal calprotectin levels are higher in rural than in urban Chinese infants and negatively associated with growth.

BACKGROUND: Fecal calprotectin (FC) is an established simple biomarker of gut inflammation. To examine a possible relationship between linear growth and gut inflammation, we compared fecal calprotectin levels in 6 month old infants from poor rural vs affluent urban families. METHODS: The project was a cross-sectional comparison of FC from rural and urban populations in China. The relationship between length-for-age Z-score (LAZ) and FC concentrations were also compared. Single fecal samples were assayed for FC using EK-CAL ELISA kits. RESULTS: The age of subjects for both locations was 6.1 ± 0.2 mo; all were apparently healthy. The mean ± SD of the LAZ for the rural and urban infants were -0.6 ± 0.9 and 0.4 ± 0.9, respectively. FC had a non-normal distribution. The median FC of 420.9 and 140.1 µg/g for rural and urban infants, respectively, were significantly different (P < 0.0001). For the rural group, linear regression analysis showed that an increase in FC of 100 µg/g was associated with a decrease of 0.06 in LAZ. CONCLUSION: FC levels were significantly elevated in the rural infants and high concentrations accounted for approximately one-third of the low LAZ scores of these infants.

Physiological requirements for zinc.

The estimates of zinc physiological requirements by the International Zinc Nutrition Consultative Group (IZiNCG) in 2004 were conspicuously low in comparison with those estimated by the Institute of Medicine (IOM) in 2001. The objective of this review is to explore the reasons for this gap and to reflect on lessons learned. All estimates of inevitable losses of endogenous zinc, especially intestinal excretion of endogenous zinc, were reviewed. An error in zinc menstrual losses, as well as a minor error in the linear regression of endogenous fecal zinc (EFZ) vs. total daily zinc absorption (TAZ) by IOM, were corrected. The review revealed an error by IZiNCG in selecting two data points for the linear regression of EFZ on TAZ. A second major reason for the "gap" is attributable to weighting of the data in the regression analysis by number of subjects per study by IZiNCG. Adjusting for these factors, together with use of the same reference data for body weights, resulted in satisfactory agreement between the two estimates of physiological requirements. The lessons to be learned from this review are discussed together with suggestions for future action by IOM as well as a constructive role for IZiNCG.

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.

The quantity of zinc absorbed from wheat in adult women is enhanced by biofortification.

Biofortification of crops that provide major food staples to large, poor rural populations offers an appealing strategy for diminishing public health problems attributable to micronutrient deficiencies. The objective of this first-stage human study was to determine the increase in quantity of zinc (Zn) absorbed achieved by biofortifying wheat with Zn. Secondary objectives included evaluating the magnitude of the measured increases in Zn absorption as a function of dietary Zn and phytate. The biofortified and control wheats were extracted at high (95%) and moderate (80%) levels and Zn and phytate concentrations measured. Adult women with habitual diets high in phytate consumed 300 g of 95 or 80% extracted wheat as tortillas for 2 consecutive days using either biofortified (41 mg Zn/g) or control (24 mg Zn/g) wheat. All meals for the 2-d experiment were extrinsically labeled with Zn stable isotopes and fractional absorption of Zn determined by a dual isotope tracer ratio technique. Zn intake from the biofortified wheat diet was 5.7 mg/d (72%) higher at 95% extraction (P < 0.001) and 2.7 mg/d (68%) higher at 80% extraction compared with the corresponding control wheat (P = 0.007). Zn absorption from biofortified wheat meals was (mean +/- SD) 2.1 +/- 0.7 and 2.0 +/- 0.4 mg/d for 95 and 80% extraction, respectively, both of which were 0.5 mg/d higher than for the corresponding control wheat (P < 0.05). Results were consistent with those predicted by a trivariate model of Zn absorption as a function of dietary Zn and phytate. Potentially valuable increases in Zn absorption can be achieved from biofortification of wheat with Zn.

Measurement of zinc absorption from meals: comparison of extrinsic zinc labeling and independent measurements of dietary zinc absorption.

BACKGROUND: Extrinsic labeling techniques are typically used to measure fractional absorption of zinc (FAZ(extrinsic)) but none have been adequately evaluated. OBJECTIVE: To compare determination of the quantity of zinc absorbed (TAZ(extrinsic)) using measurements of FAZ(extrinsic) with results of simultaneous determinations of dietary zinc absorbed (TAZ(metabolic)) that are not dependent on labeling ingested food with an extrinsic tracer (modified metabolic balance technique). DESIGN: (70)Zn was administered orally with all meals for 6 consecutive days to 21 healthy, free-living adult women consuming a constant diet. (68)Zn and (67)Zn were administered intravenously. FAZ(extrinsic) was measured using a dual isotope tracer ratio technique and multiplied by dietary zinc to give TAZ(extrinsic). TAZ(metabolic) was determined by addition of net absorption of zinc and endogenous fecal zinc, the latter determined by an isotope dilution technique. RESULTS: TAZ(extrinsic) and TAZ(metabolic) were 3.0 +/- 1.1 mg/day and 3.1 +/- 1.1 mg/day respectively, paired t-test p = 0.492. The correlation coefficient for TAZ(extrinsic) and TAZ(metabolic) was 0.91, and for FAZ(extrinsic) and FAZ(metabolic) was 0.95. A Bland Altman analysis indicated a bias of 0.07, and the limits of agreement of -0.86 to 1.01 for TAZ(extrinsic) and TAZ(metabolic). CONCLUSION: These results from two independent methods provide reasonable validation of our extrinsic labeling technique for a wide range of composite diets.

Dietary reference intakes for zinc may require adjustment for phytate intake based upon model predictions.

The quantity of total dietary zinc (Zn) and phytate are the principal determinants of the quantity of absorbed Zn. Recent estimates of Dietary Reference Intakes (DRI) for Zn by the Institute of Medicine (IOM) were based on data from low-phytate or phytate-free diets. The objective of this project was to estimate the effects of increasing quantities of dietary phytate on these DRI. We used a trivariate model of the quantity of Zn absorbed as a function of dietary Zn and phytate with updated parameters to estimate the phytate effect on the Estimated Average Requirement (EAR) and Recommended Daily Allowance for Zn for both men and women. The EAR predicted from the model at 0 phytate was very close to the EAR of the IOM. The addition of 1000 mg phytate doubled the EAR and adding 2000 mg phytate tripled the EAR. The model also predicted that the EAR for men and women could not be attained with phytate:Zn molar ratios > 11:1 and 15:1, respectively. The phytate effect on upper limits (UL) was predicted by first estimating the quantity of absorbed Zn corresponding to the UL of 40 mg for phytate-free diets, which is 6.4 mg Zn/d. Extrapolation of the model suggested, for example, that with 900 mg/d phytate, 100 mg dietary Zn is required to attain 6.4 mg absorbed Zn/d. Experimental studies with higher Zn intakes are required to test these predictions.

Calcium absorption may be affected after either sleeve gastrectomy or Roux-en-Y gastric bypass in premenopausal women: a 2-y prospective study.

Background: Although Roux-en-Y gastric bypass (RYGBP) is known to reduce calcium absorption (CA), the effects of vertical sleeve gastrectomy (SG) and its long-term implications on CA have not yet been studied. Objective: The aim of this study was to evaluate changes in CA and its relation with modifications of bone mineral density (BMD), intakes of calcium and vitamin D, vitamin D status, and parathyroid hormone (PTH) concentrations ≤24 mo after SG and RYGBP, respectively. Design: Twenty-six premenopausal women undergoing SG [mean ± SD body mass index (BMI; kg/m2): 37.3 ± 3.2; age: 34.2 ± 10.2 y] and 32 undergoing RYGBP (BMI: 42.0 ± 4.2; age: 37.3 ± 8.1 y) were studied at baseline (presurgery) and followed up at 12 and 24 mo after surgery. BMD, bone alkaline phosphatase activity, and serum PTH, 25-hydroxyvitamin D [25(OH)D], calcium, magnesium, and phosphorus concentrations were determined. Food and supplement intakes were recorded. CA was measured by using a dual stable isotope method. Results: In premenopausal women, CA was significantly reduced from 36.5% ± 2.0% preoperatively to 21.0% ± 2.3% and 18.8% ± 3.4% at 12 and 24 mo post-SG surgery, respectively. CA also decreased significantly from 41.5% ± 2.8% preoperatively to 27.9% ± 3.8% and 18.5% ± 2.2% 12 and 24 mo after RYGBP, respectively. No difference was found between type of surgery (time × group interaction, P = 0.60). Considering both groups combined, 56.6% of the variance in CA at the 12-mo but not at the 24-mo follow-up was explained by serum PTH and 25(OH)D concentrations, together with vitamin D and calcium intakes. Conclusions: CA was similarly reduced in both SG and RYGBP compared with baseline, and it was not associated with changes in BMD or body weight loss. This reduction in CA could be explained only partially by calcium intake increase. This trial is registered at http://www.isrctn.com as ISRCTN31937503.

Preconception Micronutrient Supplementation Reduced Circulating Branched Chain Amino Acids at 12 Weeks Gestation in an Open Trial of Guatemalan Women Who Are Overweight or Obese.

Elevated branched chain amino acids (BCAAs: valine, leucine, and isoleucine) are well-established biomarkers of obesity-associated insulin resistance (IR). Mounting evidence suggests that low- and middle-income countries are suffering from a "double burden" of both undernutrition (growth stunting) and overnutrition (obesity) as these countries undergo a "nutrition transition". The purpose of this study was to examine if pre-pregnancy body mass index (BMI, kg/m²) and a daily lipid-based micronutrient supplement (LNS, Nutriset) would lead to cross-sectional differences in circulating levels of branched chain amino acids (BCAAs) in Guatemalan women experiencing short stature during early pregnancy. Using data from an ongoing randomized controlled trial, Women First, we studied women who were normal weight (NW, BMI range for this cohort = 20.1⁻24.1 kg/m²) or overweight/obese (OW/OB, BMI range for this cohort = 25.6⁻31.9 kg/m²), and divided into two groups: those who received daily LNS ≥ 3 months prior to conception through 12 weeks gestation (+LNS), or no LNS (-LNS) (n = 9⁻10/group). BCAAs levels were obtained from dried blood spot card samples (DBS) assessed at 12 weeks gestation. DBS cards provide a stable, efficient, and reliable means of collecting, transporting, and storing blood samples in low resource or field settings. Circulating maternal leptin, adiponectin, and insulin were determined by immunoassays from serum samples collected at 12 weeks gestation. We found maternal pre-pregnancy body mass index (ppBMI) was associated with higher circulating BCAAs (r² = 0.433, p = 0.002) and higher leptin/adiponectin ratio (r = 0.466, p = 0.044) in -LNS mothers at 12 weeks gestation. +LNS mothers demonstrated no correlations between BCAAs or leptin/adiponectin ratio across ppBMI suggesting LNS may be effective at improving metabolic status in OW/OB mothers during early pregnancy.

Drug-development concepts as guides for optimizing clinical trials of supplemental zinc for populations at risk of deficiency or diarrhea.

Studies on the efficacy of zinc supplementation for treatment or prevention of diarrhea have shown an inconsistent effect in populations at risk for zinc deficiency. Unlike drugs, which have no preexisting presence in the body, endogenous zinc must be assessed pharmacokinetically by isotope tracer studies. Although such methods have produced much data, very few studies have estimated the dose and the timing of dosing of zinc supplementation. This review examines drug kinetics used to establish the best dose, the timing of such doses, and the mechanism of action through pharmacodynamic markers and applies them, where possible, to zinc supplements. The findings reveal that little is known, especially in children at highest risk of zinc deficiency. Key data missing to inform proper dosing, whether for treatment of disease or for preventive nutrient supplementation, are noted. Addressing these uncertainties could improve study design, leading to future studies of zinc supplements that might be of greater benefit.

Exchangeable zinc pool size at birth is smaller in small-for-gestational-age than in appropriate-for-gestational-age preterm infants.

BACKGROUND: Small-for-gestational-age (SGA) infants are susceptible to postnatal zinc deficiency, but whether this susceptibility is due to intrauterine factors or to high postnatal growth requirements is unknown. OBJECTIVE: We hypothesized that the size of the exchangeable zinc pool (EZP), which reflects metabolically available zinc, would be smaller in SGA than in appropriate-for-gestational-age (AGA) infants born prematurely. DESIGN: Intravenous 70Zn (45 microg/kg) was administered to 10 SGA infants (8 boys) with a mean (+/-SD) gestational age of 33.3 +/- 1.8 wk and to 11 AGA infants (8 boys) with a mean (+/-SD) gestational age of 32.4 +/- 1.2 wk within 24 h of birth. The EZP was determined from isotope enrichment in spot urine collections on days 3-7. RESULTS: The mean birth weight of the SGA infants was 1.30 +/- 0.2 kg and of the AGA infants was 1.84 +/- 0.3 kg (P = 0.0001). The EZP size was significantly smaller in the SGA than in the AGA infants on an absolute basis (13.3 +/- 2.8 and 25.2 +/- 8.1 mg; P = 0.0002) and relative to body weight (10.3 +/- 2.5 and 13.9 +/- 4.5 mg/kg; P = 0.02). The difference remained significant after adjustment for gestational age and birth weight. CONCLUSION: These data provide evidence for differential zinc status at birth between SGA and AGA infants born prematurely at similar stages of gestation and offer at least a partial explanation for the reported benefits of postnatal zinc supplementation.

Zinc absorption during late pregnancy in rural southern Ethiopia.

BACKGROUND: Little is yet known about zinc absorption in late pregnancy, and no information on absorption from the total diet is available. OBJECTIVE: The objective was to measure the fractional absorption of zinc (FAZ) and to estimate the total quantity of absorbed zinc (TAZ) each day during the third trimester of pregnancy in poor rural southern Ethiopian women. DESIGN: The participants (n = 17) were a convenience sample from a larger study population. The third stage of pregnancy was estimated from fundal height by the Bushulo Health Center prenatal outreach program. FAZ was determined with a dual-isotope tracer ratio technique that uses measurements of urine enrichment with zinc stable isotopes administered intravenously and orally, as an extrinsic label, with all meals in 1 d. Total dietary zinc (TDZ) was calculated from weighed diet records and Ethiopian food-composition tables supported by zinc and phytate analyses of major food items for individual meals. Plasma zinc and exchangeable zinc pool size were also estimated. RESULTS: Mean (+/-SD) FAZ was 0.35 +/- 0.11, TDZ was 6.0 +/- 3.2 mg/d, TAZ was 2.1 +/- 1.0 mg/d, phytate intake was 1033 +/- 843 mg/d, plasma zinc was 44.1 +/- 6.0 microg/dL, and the exchangeable zinc pool size was 142 +/- 39 mg. The molar ratio of phytate to zinc was 17:1. CONCLUSIONS: Women from a poor rural population who were dependent on a moderately high-phytate diet had low TDZ and low plasma zinc concentrations in the third trimester of pregnancy. TAZ was modestly higher than that predicted but did not meet physiologic requirements.

Dysprosium as a nonabsorbable fecal marker in studies of zinc homeostasis.

BACKGROUND: Dysprosium is a nonabsorbable rare earth element that has had successful application as a marker for fecal excretion of unabsorbed zinc. OBJECTIVE: Our goals were 1) to evaluate the efficacy of administering dysprosium with all meals over several days as a method of determining the completeness of fecal collections, 2) to determine the similarity of gastrointestinal transit kinetics and excretion patterns of dysprosium and zinc tracer administered simultaneously over several days, and 3) to evaluate alternative methods of using the data for fecal excretion of orally administered zinc tracer and dysprosium to measure the fractional absorption of zinc. DESIGN: 70Zn and dysprosium were administered orally with all meals for 5 consecutive days to 7 healthy, free-living adults consuming a constant diet based on habitual intake. Additional tracers, 67Zn and 68Zn, were administered intravenously. Urine and fecal samples were collected during tracer administration and for 8 d after the last dose. Isotope ratios were measured in urine and feces, and total zinc and dysprosium were measured in fecal samples. RESULTS: The mean recovery of dysprosium was 101.3 +/- 2.4%. The zinc oral tracer and dysprosium had similar fecal excretory patterns; the correlation coefficient for 70Zn and dysprosium in fecal samples exceeded 0.99 (P < 0.0001) for each subject. Fractional zinc absorption measurements using various dysprosium methods correlated well (r > 0.95) with those from the fecal monitoring and dual-isotope-tracer ratio methods. CONCLUSION: Administration of dysprosium is a useful means of determining the completeness of fecal collections and of measuring zinc absorption.

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.