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Background: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited., Objectives: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry., Methods: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point., Results: At 12-wk gestation and 3-mo postpartum, no statistical differences in mean SZC were observed among arms. At 34-wk, mean SZC for arms 1 and 2 were significantly higher than for arm 3 (50.3, 50.8, 47.8 μg/dL, respectively; P = 0.005). Results were not impacted by correction for inflammation or albumin concentrations. Prevalence of hypozincemia at 12-wk (<56 μg/dL) was 23% in Guatemala, 26% in India, and 65% in Pakistan; at 34 wk (<50 μg/dL), 36% in Guatemala, 48% in India, and 74% in Pakistan; and at 3-mo postpartum (<66 μg/dL) 79% in Guatemala, 91% in India, and 92% in Pakistan. Maternal hypozincemia at 34-wk was associated with lower birth length-for-age Z-scores (all sites P = 0.013, Pakistan P = 0.008) and weight-for-age Z-scores (all sites P = 0.017, Pakistan P = 0.022)., Conclusions: Despite daily zinc supplementation for ≥7 mo, high rates of maternal hypozincemia were observed. The association of hypozincemia with impaired fetal growth suggests widespread zinc deficiency in these settings. This trial is registered at clinicaltrials.gov as #NCT01883193., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The multicountry Women First trial demonstrated that nutritional supplementation initiated prior to conception (arm 1) or early pregnancy (arm 2) and continued until delivery resulted in significantly greater length at birth and 6 mo compared with infants in the control arm (arm 3)., Objectives: We evaluated intervention effects on infants' longitudinal growth trajectory from birth through 24 mo and identified predictors of length status and stunting at 24 mo., Methods: Infants' anthropometry was obtained at 6, 12, 18, and 24 mo after the Women First trial (registered at clinicaltrials.gov as NCT01883193), which was conducted in low-resource settings: Democratic Republic of Congo, Guatemala, India, and Pakistan. Longitudinal models evaluated intervention effects on infants' growth trajectory from birth to 24 mo, with additional modeling used to identify adjusted predictors for growth trajectories and outcomes at 24 mo., Results: Data for 2337 (95% of original live births) infants were evaluated. At 24 mo, stunting rates were 62.8%, 64.8%, and 66.3% for arms 1, 2, and 3, respectively (NS). For the length-for-age z-score (LAZ) trajectory, treatment arm was a significant predictor, with adjusted mean differences of 0.19 SD (95% CI: 0.08, 0.30; P < 0.001) and 0.17 SD (95% CI: 0.07, 0.27; P < 0.001) for arms 1 and 2, respectively. The strongest predictors of LAZ at 24 mo were birth LAZ <-2 and <-1 to ≥-2, with adjusted mean differences of -0.76 SD (95% CI: -0.93, -0.58; P < 0.001) and -0.47 SD (95% CI: -0.56, -0.38; P < 0.001), respectively. For infants with ultrasound-determined gestational age (n = 1329), the strongest predictors of stunting were birth LAZ <-2 and <-1 to ≥- 2: adjusted relative risk of 1.62 (95% CI: 1.39, 1.88; P < 0.001) and 1.46 (95% CI: 1.31, 1.62; P < 0.001), respectively., Conclusions: Substantial improvements in postnatal growth are likely to depend on improved intrauterine growth, especially during early pregnancy., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Adequate gestational weight gain (GWG) is essential for healthy fetal growth. However, in low- and middle-income countries, where malnutrition is prevalent, little information is available about GWG and how it might be modified by nutritional status and interventions., Objective: We describe GWG and its associations with fetal growth and birth outcomes. We also examined the extent to which prepregnancy BMI, and preconception and early weight gain modify GWG, and its effects on fetal growth., Methods: This was a secondary analysis of the Women First Trial, including 2331 women within the Democratic Republic of Congo (DRC), Guatemala, India, and Pakistan, evaluating weight gain from enrollment to ∼12 weeks of gestation and GWG velocity (kg/wk) between ∼12 and 32 weeks of gestation. Adequacy of GWG velocity was compared with 2009 Institute of Medicine recommendations, according to maternal BMI. Early weight gain (EWG), GWG velocity, and adequacy of GWG were related to birth outcomes using linear and Poisson models., Results: GWG velocity (mean ± SD) varied by site: 0.22 ± 0.15 kg/wk in DRC, 0.30 ± 0.23 in Pakistan, 0.31 ± 0.14 in Guatemala, and 0.39 ± 0.13 in India, (P <0.0001). An increase of 0.1 kg/wk in maternal GWG was associated with a 0.13 cm (95% CI: 0.07, 0.18, P <0.001) increase in birth length and a 0.032 kg (0.022, 0.042, P <0.001) increase in birth weight. Compared to women with inadequate GWG, women who had adequate GWG delivered newborns with a higher mean length and weight: 47.98 ± 2.04 cm compared with 47.40 ± 2.17 cm (P <0.001) and 2.864 ± 0.425 kg compared with 2.764 ± 0.418 kg (P <0.001). Baseline BMI, EWG, and GWG were all associated with birth length and weight., Conclusions: These results underscore the importance of adequate maternal nutrition both before and during pregnancy as a potentially modifiable factor to improve fetal growth., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Roux-en-Y gastric bypass (RYGBP) is known to reduce zinc absorption; the effects of vertical sleeve gastrectomy (SG) and its long-term implications on zinc absorption have not yet been studied., Objective: The aim was to evaluate the effects of SG and RYGBP on zinc absorption and zinc status in premenopausal women with severe obesity up to 24 mo after surgery., Methods: Twenty-six premenopausal women undergoing SG [BMI (in kg/m2): 37.3 ± 3.2] and 32 undergoing RYGBP (BMI: 42.0 ± 4.2) were studied. A series of anthropometric, dietary, and zinc status parameters (plasma and hair zinc), and the size of the exchangeable zinc pool (EZP), as well as percentage zinc absorption from a standardized dose using a stable isotope methodology were evaluated in the patients before the surgical procedure and at 12 and 24 mo after SG or RYGBP. SG patients received 15 mg and RYGBP received 25 mg of supplemental Zn/d., Results: In premenopausal women, zinc absorption was decreased by 71.9% and 52.0% in SG and RYGBP, respectively, 24 mo postsurgery, compared with initial values. According to 2-factor repeated-measures ANOVA, time effect was significant (P = <0.0001), but not time × group interaction (P = 0.470). Plasma zinc below the cutoff point of 70 µg/dL increased from 0 to 15.4% and 38.1% in SG and RYGBP, respectively. Mean EZP was significantly reduced 24 mo after surgery, although no time × group interactions were observed. Hair zinc did not change across time or between groups., Conclusions: Both SG and RYGBP have profound effects on zinc absorption capacity, which are not compensated for after 24 mo. Although zinc absorption reduction was similar in both types of surgeries, plasma zinc was more affected in RYGBP than SG, despite greater zinc supplementation in RYGBP.This trial was registered at http://www.isrctn.com as ISRCTN31937503., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Preconceptional maternal small-quantity lipid-based nutrient supplementation (SQLNS) improved intrauterine linear growth in low-resource countries as demonstrated by the Women First Preconception Maternal Nutrition Trial (WF). Fetal growth is dependent on nutrient availability and regulated by insulin-like growth factor 1 (IGF-1) through changes in placental transfer capacity, mediated by the mechanistic target of rapamycin (mTOR) pathway., Objectives: Our objective was to evaluate the role of placental mTOR and IGF-1 signaling on fetal growth in women from 2 low-resource countries with high rates of stunting after they received preconceptional SQLNS., Methods: We studied 48 women from preconception through delivery who were from Guatemala and Pakistan and received SQLNS or not, as part of the WF study. Placental samples were obtained at delivery (control, n = 24; SQLNS, n = 24). Placental protein or mRNA expression of eukaryotic translation initiation factor binding protein-1 (4E-BP1), ribosomal protein S6 (rpS6), AMP-activated protein kinase α (AMPKA), IGF-1, insulin-like growth factor receptor (IGF-1R), and pregnancy associated plasma protein (PAPP)-A, and DNA methylation of the IGF1 promoter were determined. Maternal serum IGF-1, insulin-like growth factor binding protein (IGFBP)-3, IGFBP-4, IGFBP-5, PAPP-A, PAPP-A2, and zinc were measured., Results: Mean ± SEM maternal prepregnancy BMI differed between participants in Guatemala (26.5 ± 1.3) and Pakistan (19.8 ± 0.7) (P < 0.001). In Pakistani participants, SQLNS increased the placental rpS6(T37/46):rpS6 ratio (1.5-fold) and decreased the AMPKA(T172):AMPKA ratio. Placental IGF1 mRNA expression was positively correlated with birth length and birth weight z-scores. Placental PAPP-A (30-fold) and maternal serum zinc (1.2-fold) increased with SQLNS. In Guatemalan participants SQLNS did not influence placental mTOR signaling. Placental IGF-1R protein expression was positively associated with birth length and birth weight z-scores. SQLNS increased placental PAPP-A (40-fold) and maternal serum IGFBP-4 (1.6-fold)., Conclusions: In Pakistani pregnant women with poor nutritional status, preconceptional SQLNS activated placental mTOR and IGF-1 signaling and was associated with improved fetal growth. In contrast, in Guatemalan women SQLNS did not activate placental nutrient-sensing pathways. In populations experiencing childhood stunting, preconceptional SQLNS improves placental function and fetal growth only in the context of poor maternal nutrition. This trial was registered at clinicaltrials.gov as NCT01883193., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Reported benefits of maternal nutrition supplements commenced during pregnancy in low-resource populations have typically been quite limited., Objectives: This study tested the effects on newborn size, especially length, of commencing nutrition supplements for women in low-resource populations ≥3 mo before conception (Arm 1), compared with the same supplement commenced late in the first trimester of pregnancy (Arm 2) or not at all (control Arm 3)., Methods: Women First was a 3-arm individualized randomized controlled trial (RCT). The intervention was a lipid-based micronutrient supplement; a protein-energy supplement was also provided if maternal body mass index (kg/m2) was <20 or gestational weight gain was less than recommendations. Study sites were in rural locations of the Democratic Republic of the Congo (DRC), Guatemala, India, and Pakistan. The primary outcome was length-for-age z score (LAZ), with all anthropometry obtained <48 h post delivery. Because gestational ages were unavailable in DRC, outcomes were determined for all 4 sites from WHO newborn standards (non-gestational-age-adjusted, NGAA) as well as INTERGROWTH-21st fetal standards (3 sites, gestational age-adjusted, GAA)., Results: A total of 7387 nonpregnant women were randomly assigned, yielding 2451 births with NGAA primary outcomes and 1465 with GAA outcomes. Mean LAZ and other outcomes did not differ between Arm 1 and Arm 2 using either NGAA or GAA. Mean LAZ (NGAA) for Arm 1 was greater than for Arm 3 (effect size: +0.19; 95% CI: 0.08, 0.30, P = 0.0008). For GAA outcomes, rates of stunting and small-for-gestational-age were lower in Arm 1 than in Arm 3 (RR: 0.69; 95% CI: 0.49, 0.98, P = 0.0361 and RR: 0.78; 95% CI: 0.70, 0.88, P < 0.001, respectively). Rates of preterm birth did not differ among arms., Conclusions: In low-resource populations, benefits on fetal growth-related birth outcomes were derived from nutrition supplements commenced before conception or late in the first trimester. This trial was registered at clinicaltrials.gov as NCT01883193.

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., Competing Interests: 2: Author disclosures: KM Hambidge, LV Miller, M Mazariegos, J Westcott, NW Solomons, V Raboy, JF Kemp, A Das, N Goco, T Hartwell, L Wright, and NF Krebs, no conflicts of interest., (© 2017 American Society for Nutrition.)

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 (R 2 ≥ 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., (© 2017 American Society for Nutrition.)

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., (© 2015 American Society for Nutrition.)

Background: The zinc content of maize, a major global food staple, is generally insufficient alone to meet the requirements of young children., Objectives: The primary objective of this study was to determine whether substitution of biofortified maize (34 μg zinc/g grain) for control maize (21 μg zinc/g) was adequate to meet zinc physiologic requirements in young children for whom maize was the major food staple. A secondary objective was to compare total daily zinc absorption when maize flour was fortified with zinc oxide to a total concentration of 60 μg zinc/g., Methods: Participants included 60 rural Zambian children with a mean age of 29 mo who were randomly assigned to receive 1 of 3 maize types (control, biofortified, or fortified) all of which were readily consumed (>100 g on 1 d). Total daily zinc intake (from maize and low-zinc relish) was determined from duplicate diet collections. Multiplication by fractional absorption of zinc, measured by a dual isotope ratio technique, determined the total daily zinc absorption on the day the test meals were given., Results: The mean ± SD total daily zinc intake (milligrams per day) from the biofortified maize (5.0 ± 2.2) was higher (P < 0.0001) than for the control maize (2.3 ± 0.9). Intake of zinc from the fortified maize (6.3 ± 2.6) did not differ from the biofortified maize. Fractional absorption of zinc from control maize (0.28 ± 0.10) did not differ from the biofortified maize (0.22 ± 0.06). Total daily absorption of zinc (milligrams per day) from the biofortified maize (1.1 ± 0.5) was higher (P = 0.0001) than for the control maize (0.6 ± 0.2), but did not differ from the fortified maize (1.2 ± 0.4)., Conclusions: These results indicate that feeding biofortified maize can meet zinc requirements and provide an effective dietary alternative to regular maize for this vulnerable population. This trial was registered at clinicaltrials.gov as NCT02208635., (© 2015 American Society for Nutrition.)

Background: Antenatal corticosteroids for pregnant women at risk of preterm birth are among the most effective hospital-based interventions to reduce neonatal mortality. We aimed to assess the feasibility, effectiveness, and safety of a multifaceted intervention designed to increase the use of antenatal corticosteroids at all levels of health care in low-income and middle-income countries., Methods: In this 18-month, cluster-randomised trial, we randomly assigned (1:1) rural and semi-urban clusters within six countries (Argentina, Guatemala, India, Kenya, Pakistan, and Zambia) to standard care or a multifaceted intervention including components to improve identification of women at risk of preterm birth and to facilitate appropriate use of antenatal corticosteroids. The primary outcome was 28-day neonatal mortality among infants less than the 5th percentile for birthweight (a proxy for preterm birth) across the clusters. Use of antenatal corticosteroids and suspected maternal infection were additional main outcomes. This trial is registered with ClinicalTrials.gov, number NCT01084096., Findings: The ACT trial took place between October, 2011, and March, 2014 (start dates varied by site). 51 intervention clusters with 47,394 livebirths (2520 [5%] less than 5th percentile for birthweight) and 50 control clusters with 50,743 livebirths (2258 [4%] less than 5th percentile) completed follow-up. 1052 (45%) of 2327 women in intervention clusters who delivered less-than-5th-percentile infants received antenatal corticosteroids, compared with 215 (10%) of 2062 in control clusters (p<0·0001). Among the less-than-5th-percentile infants, 28-day neonatal mortality was 225 per 1000 livebirths for the intervention group and 232 per 1000 livebirths for the control group (relative risk [RR] 0·96, 95% CI 0·87-1·06, p=0·65) and suspected maternal infection was reported in 236 (10%) of 2361 women in the intervention group and 133 (6%) of 2094 in the control group (odds ratio [OR] 1·67, 1·33-2·09, p<0·0001). Among the whole population, 28-day neonatal mortality was 27·4 per 1000 livebirths for the intervention group and 23·9 per 1000 livebirths for the control group (RR 1·12, 1·02-1·22, p=0·0127) and suspected maternal infection was reported in 1207 (3%) of 48,219 women in the intervention group and 867 (2%) of 51,523 in the control group (OR 1·45, 1·33-1·58, p<0·0001)., Interpretation: Despite increased use of antenatal corticosteroids in low-birthweight infants in the intervention groups, neonatal mortality did not decrease in this group, and increased in the population overall. For every 1000 women exposed to this strategy, an excess of 3·5 neonatal deaths occurred, and the risk of maternal infection seems to have been increased., Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Stunting is prevalent by the age of 6 months in the indigenous population of the Western Highlands of Guatemala., Aim: The objective of this study was to determine the time course and predictors of linear growth failure and weight-for-age in early infancy., Study Design and Subjects: One hundred and forty eight term newborns had measurements of length and weight in their homes, repeated at 3 and 6 months. Maternal measurements were also obtained., Results: Mean ± SD length-for-age Z-score (LAZ) declined from newborn -1.0 ± 1.01 to -2.20 ± 1.05 and -2.26 ± 1.01 at 3 and 6 months respectively. Stunting rates for newborn, 3 and 6 months were 47%, 53% and 56% respectively. A multiple regression model (R(2) = 0.64) demonstrated that the major predictor of LAZ at 3 months was newborn LAZ with the other predictors being newborn weight-for-age Z-score (WAZ), gender and maternal education∗maternal age interaction. Because WAZ remained essentially constant and LAZ declined during the same period, weight-for-length Z-score (WLZ) increased from -0.44 to +1.28 from birth to 3 months. The more severe the linear growth failure, the greater WAZ was in proportion to the LAZ., Conclusion: The primary conclusion is that impaired fetal linear growth is the major predictor of early infant linear growth failure indicating that prevention needs to start with maternal interventions., (© 2013.)

Millet is unusually drought resistant and consequently there is a progressive increase in the use of these grains as a human food staple, especially in large areas of India and sub-Saharan Africa. The purpose of this study was to determine the absorption of iron and zinc from pearl millet biofortified with 2 micronutrients that are typically deficient in nonfortified, plant-based diets globally. The study was undertaken in 40 children aged 2 y in Karnataka, India (n = 21 test/19 controls). Three test meals providing ∼84 ± 17 g dry pearl millet flour were fed on a single day for zinc and 2 d for iron between 0900 and 1600 h. The quantities of zinc and iron absorbed were measured with established stable isotope extrinsic labeling techniques and analyses of duplicate diets. The mean (± SD) quantities of iron absorbed from test and control groups were 0.67 ± 0.48 and 0.23 ± 0.15 mg/d, respectively (P < 0.001). The quantities of zinc absorbed were 0.95 ± 0.47 and 0.67 ± 0.24 mg/d, respectively (P = 0.03). These data did not include absorption of the modest quantities of iron and zinc contained in snacks eaten before and after the 3 test meals. In conclusion, quantities of both iron and zinc absorbed when iron and zinc biofortified pearl millet is fed to children aged 2 y as the major food staple is more than adequate to meet the physiological requirements for these micronutrients.

Background: The effect of bariatric surgery on iron absorption is only partially known., Objective: The objective was to study the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) on heme- and nonheme-iron absorption and iron status., Design: Fifty-eight menstruating women were enrolled in this prospective study [mean (±SD) age: 35.9 ± 9.1 y; weight: 101.7 ± 13.5 kg; BMI (in kg/m²): 39.9 ± 4.4]. Anthropometric, body-composition, dietary, and hematologic indexes and heme- and nonheme-iron absorption-using a standardized meal containing 3 mg Fe-were determined before and 12 mo after surgery. Forty-three subjects completed the 12-mo follow-up. Iron supplements were strictly controlled., Results: Heme-iron absorption was 23.9% before and 6.2% 12 mo after surgery (P < 0.0001). Nonheme-iron absorption decreased from 11.1% to 4.7% (P < 0.0001). No differences were observed by type of surgery. Iron intakes from all sources of supplements were 27.9 ± 6.2 mg/d in the SG group and 63.2 ± 21.1 mg/d in the RYGBP group (P < 0.001). Serum ferritin and total-body iron decreased more after RYGBP than after SG., Conclusions: Iron (heme and nonheme) absorption is markedly reduced after SG and RYGBP. The magnitude of the decrease in heme-iron absorption is greater than that of nonheme iron. The amounts suggested as iron supplements may need to be increased to effectively prevent iron-status impairment.

Background: Improved complementary feeding is cited as a critical factor for reducing stunting. Consumption of meats has been advocated, but its efficacy in low-resource settings has not been tested., Objective: The objective was to test the hypothesis that daily intake of 30 to 45 g meat from 6 to 18 mo of age would result in greater linear growth velocity and improved micronutrient status in comparison with an equicaloric multimicronutrient-fortified cereal., Design: This was a cluster randomized efficacy trial conducted in the Democratic Republic of Congo, Zambia, Guatemala, and Pakistan. Individual daily portions of study foods and education messages to enhance complementary feeding were delivered to participants. Blood tests were obtained at trial completion., Results: A total of 532 (86.1%) and 530 (85.8%) participants from the meat and cereal arms, respectively, completed the study. Linear growth velocity did not differ between treatment groups: 1.00 (95% CI: 0.99, 1.02) and 1.02 (95% CI: 1.00, 1.04) cm/mo for the meat and cereal groups, respectively (P = 0.39). From baseline to 18 mo, stunting [length-for-age z score (LAZ) <-2.0] rates increased from ~33% to nearly 50%. Years of maternal education and maternal height were positively associated with linear growth velocity (P = 0.0006 and 0.003, respectively); LAZ at 6 mo was negatively associated (P < 0.0001). Anemia rates did not differ by group; iron deficiency was significantly lower in the cereal group., Conclusion: The high rate of stunting at baseline and the lack of effect of either the meat or multiple micronutrient-fortified cereal intervention to reverse its progression argue for multifaceted interventions beginning in the pre- and early postnatal periods.

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.

Background: Celiac disease (CD) is an immunologic enteropathy triggered by the intake of gluten. It is thought that the enteropathy impairs gut function and absorption., Objective: We assessed the zinc-absorption capacity and small-bowel integrity in children with CD., Design: Children in whom a diagnosis of CD was considered clinically and either confirmed (n = 16; Marsh score ≥3) or not (n = 22; Marsh score of 0) with a small-bowel biopsy (SBB) were recruited. The fractional absorption of zinc (FAZ) was determined by the administration of an oral (67)Zn dose (2.5 mg) and an intravenous (70)Zn dose (0.2 mg) 2 h before and during the SBB, respectively. Spot urine samples were collected, and zinc isotopic ratios were determined by ion-coupled plasma mass spectrometry. Gut health was assessed by the ingestion of (13)C-sucrose (20 g) after an overnight fast, and breath samples were collected and analyzed by isotope ratio mass spectrometry., Results: There was no difference in FAZ between children with a Marsh score ≥3 (mean ± SEM: 0.68 ± 0.05) and children with a Marsh score of 0 (0.74 ± 0.05). The exchangeable zinc pool (EZP) was significantly (P < 0.05) lower in children with a Marsh score ≥3 (2.6 ± 0.8 mg/kg) than in children with a Marsh score of 0 (3.8 ± 1.4 mg/kg). Gut function in children with a Marsh score ≥3 (4.5 ± 0.7% cumulative dose recovered at 90 min) was lower than the lower cutoff of a normal gut-function breath test (5.06% cumulative dose recovered at 90 min) but not significantly different from that in children with a Marsh score of 0 (4.9 ± 0.4%). There was a significant (P < 0.01) correlation between zinc absorption and gut function in children with CD., Conclusions: Zinc absorption did not appear below usual amounts in subjects with CD. Children with CD have impaired gut function that may affect their zinc nutritional status as shown by a smaller EZP. However, the EZP decrease in children with CD was not compared with that in healthy control subjects, and its biological meaning is uncertain.

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 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.

This article provides a review of how the challenge of bioavailability was approached in establishing the Dietary Reference Intakes, with a special focus on folic acid, vitamin B-12, beta-carotene, iron, selenium, and zinc, the targeted micronutrients for this workshop. In a future perspective, the necessity of having a clear working definition of bioavailability is emphasized. The bioavailability of micronutrients should be considered, with advantage, under subheadings determined by the broad factors that affect bioavailability. Special emphasis is given to giving greater and specific attention to factors involved in the maintenance of homeostasis. These factors, it is argued, are best considered separately from even a broad definition of bioavailability and have the potential to provide new insights into some micronutrient requirements.

After age 6 mo, the combination of breast-feeding and unfortified plant-based complementary feeding provides inadequate zinc (Zn). Additionally, high phytate intakes compromise the bioavailability of zinc. Our principal objective in this randomized controlled, doubly masked trial was to determine the effect of substituting low-phytate maize, a daily 5-mg zinc supplement, or both, in infants between ages 6-12 mo on impaired linear growth velocity, a common feature of zinc deficiency. In the Western Highlands of Guatemala, 412 infants were randomized to receive low-phytate or control maize. Within each maize group, infants were further randomized to receive a zinc supplement or placebo. Length, weight, and head circumference were measured at 6, 9, and 12 mo of age. There were no significant differences between the 2 maize groups or between the Zn supplement and placebo groups and no treatment interaction was observed for length-for-age (LAZ), weight-for-length (WLZ) or head circumference Z-scores. Overall mean (+/- SD) Z-scores at 6 mo for combined treatment groups were: LAZ, -2.1 +/- 1.1; WLZ, 0.7 +/- 1.0; and head circumference Z-score, -0.7.0 +/- 1.0. At 12 mo, these had declined further to: LAZ, -2.5 +/- 1.1; WLZ, -0.0 +/- 0.9; and head circumference Z-score, -0.9 +/- 1.1; 83.3% were stunted and 2% were wasted. Low linear growth in older Guatemalan infants was not improved with either low-phytate maize or a daily 5-mg zinc supplement. Low contribution of maize to the complementary food of the infants negated any potential advantage of feeding low-phytate maize.

Zinc has earned recognition recently as a micronutrient of outstanding and diverse biological, clinical, and global public health importance. Regulation of absorption by zinc transporters in the enterocyte, together with saturation kinetics of the absorption process into and across the enterocyte, are the principal means by which whole-body zinc homeostasis is maintained. Several physiologic factors, most notably the quantity of zinc ingested, determine the quantity of zinc absorbed and the efficiency of absorption. Other factors are age and the time over which zinc is ingested. Zinc from supplements has not been shown to be absorbed differently from that taken with meals that lack inhibitors of zinc absorption. The principal dietary factor known to impair zinc bioavailability is inositol hexa- (and penta-) phosphate or phytate. Modeling of zinc absorption as a function of dietary zinc and phytate accounts for >80% of the variability in the quantity of zinc absorbed. Fitting the model to new data has resulted in continual improvement in parameter estimates, which currently indicate a maximal absorption in adults of approximately 6 mg Zn/d and that the average estimated dietary requirement doubles with 1000 mg dietary phytate/d. Intestinal excretion of endogenous zinc is regulated in response to recent absorption and to zinc status. The quantitative relation of intestinal excretion of endogenous zinc to zinc absorption is currently considered to be of major importance in the determination of zinc requirements. The effects of phytate on intestinal losses of endogenous zinc merit further investigation but are probably not of the same magnitude as its inhibitory effects on absorption of exogenous zinc.

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.

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.

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.

The etiology of anemia during pregnancy in rural Southern Ethiopia is uncertain. Intakes of animal-source foods are low and infections and bacterial overgrowth probably coexist. We therefore measured the dietary intakes of a convenience sample of Sidama women in late pregnancy who consumed either maize (n = 68) or fermented enset (Enset ventricosum) (n = 31) as their major energy source. Blood samples were analyzed for a complete blood count, vitamin B-12 and folate status, plasma ferritin, retinol, zinc, albumin, and C-reactive protein (CRP). The role of infection and gravida was also examined. Dietary intakes were calculated from 1-d weighed records. No cellular animal products were consumed. Of the women, 29% had anemia, 13% had iron deficiency anemia, 33% had depleted iron stores, and 74 and 27% had low plasma zinc and retinol, respectively. Only 2% had low plasma folate (< 6.8 nmol/L) and 23% had low plasma vitamin B-12 (< 150 pmol/L), even though 62% had elevated plasma methylmalonic acid (MMA) (> 271 nmol/L). None had elevated plasma cystathionine or total homocysteine (tHcys). Women with enset-based diets had higher (P = 0.052) plasma vitamin B-12 concentration and lower (P < 0.05) cell volume, plasma cystathionine, and retinol than women consuming maize-based diets, but mean hemoglobin, plasma ferritin, MMA, tHcys, and folate did not differ. Plasma zinc, followed by CRP (< or = 5 mg/L), gravida (< or = 4), and plasma ferritin (> or = 12 microg/L) status were major positive predictors of hemoglobin. Despite some early functional vitamin B-12 deficiency, there was no macrocytic anemia. Consumption of fermented enset may have increased vitamin B-12 levels in diet and plasma.

The intestine is the major route of excretion of endogenous zinc (Zn) and has a key role in maintaining Zn homeostasis. The principal objective of this paper is to provide an interpretative report of quantities of endogenous fecal Zn (EFZ) excreted by rural Guatemalan school children fed either normal or low phytate maize as their principal food staple. EFZ was measured by a Zn stable isotope technique. EFZ did not differ between control and low phytate maize groups. The overall EFZ (n = 53) was (mean +/- SD) 1.56 +/- 0.69 mg Zn/d or 0.07 +/- 0.03 mg Zn x kg body wt(-1) x d(-1). EFZ was not correlated with the quantity of Zn absorbed. The estimated EFZ at the level of absorption that matched the physiologic requirement (EFZ(PR)) did not differ from the above mean value. The EFZ(PR) of 0.07 +/- 0.03 mg Zn/kg body wt is twice the value currently used in the estimation of Dietary Reference Intakes. Supported by other recent childhood data, these results suggest that the current estimates of EFZ(PR) used in the calculation of Zn requirements for children are misleadingly low.

In the development and testing of programs designed to improve complementary feeding globally, local nonfortified food-based solutions comprise an important strategy for the foreseeable future. These solutions are especially vital for the rural poor of less-developed countries. Zinc is notable among individual nutrients that have been designated as "problem" nutrients, adequate intake of which is difficult from complementary foods without fortification. This article considers the potential role of meat +/- liver in addressing this apparent problem. In a recent Colorado study, beef and cereal have been determined to be equally acceptable between age 5-7 mo as first and regular complementary foods. Average intake and absorption of Zn from beef by 7 mo of age, together with the modest intake/absorption of Zn from breast milk at that age, were adequate to meet average dietary and physiologic zinc requirements, respectively. Barriers to acceptability and availability of affordable meat are considered, but these are neither universal nor irresolvable in all populations.

Exclusive breastfeeding for the first 6 mo of life followed by optimal complementary feeding are critical public health measures for reducing and preventing morbidity and mortality in young children. Clinical factors, such as birth weight, prematurity, and illness, that affect the iron and zinc requirements of younger infants are discussed. Maternal diet and nutritional status do not have a strong effect on the mineral content of human milk, but physiologic changes in milk and the infants' status determine the dependence of the infant on complementary foods in addition to human milk to meet iron and zinc requirements after 6 mo. The nature of zinc absorption, which is suitably characterized by saturation response modeling, dictates that plant-based diets, which are low in zinc, are associated with low absolute daily absorbed zinc, which is inadequate to meet requirements. Foods with a higher zinc content, such as meats, are much more likely to be sufficient to meet dietary requirements. Current plant-based complementary feeding patterns for older fully breastfed infants in both developed and developing countries pose a risk of zinc deficiency. The strong rationale for the potential benefits of providing meat as an early complementary food, and the examples of successful intervention programs, provide potent incentives to pursue broader implementation programs, with concurrent rigorous evaluation of both efficacy and effectiveness.

The quantities of zinc and phytate in the diet are the primary factors determining zinc absorption. A mathematical model of zinc absorption as a function of dietary zinc and phytate can be used to predict dietary zinc requirements and, potentially, enhance our understanding of zinc absorption. Our goal was to develop a model of practical and informative value based on fundamental knowledge of the zinc absorption process and then fit the model to selected published data to assess its validity and estimate parameter values. A model of moderate mathematical complexity relating total zinc absorption to total dietary zinc and total dietary phytate was derived and fit to 21 mean data from whole day absorption studies using nonlinear regression analysis. Model validity, goodness of fit, satisfaction of regression assumptions, and quality of the parameter estimates were evaluated using standard statistical criteria. The fit had an R(2) of 0.82. The residuals were found to exhibit a normal distribution, constant variance, and independence. The parameters of the model, A(MAX), K(R), and K(P), were estimated to have values of 0.13, 0.10, and 1.2 mmol/d, respectively. Several of these estimates had wide CI attributable in part to the small number and the scatter of the data. The model was judged to be valid and of immediate value for studying and predicting absorption. A version of the model incorporating a passive absorption mechanism was not supported by the available data.

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.

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.

Background: Measurement of the major variables of zinc homeostasis is an essential prerequisite for estimating human zinc requirements, which currently require a factorial approach. The data required for this approach have not been available for toddlers, whose requirements have been estimated by extrapolation from other age groups., Objective: The objective of the study was to measure key variables of zinc homeostasis in rural and small-town Chinese toddlers., Design: Zinc stable-isotope tracers were administered intravenously and orally with all meals for 1 d to 43 toddlers. Subsequent metabolic collections in the homes included duplicate diets, quantitative fecal collections, and spot urine sampling. Fractional absorption of zinc (FAZ) was measured by a dual-isotope tracer ratio technique, and endogenous fecal zinc (EFZ) was measured by an isotope dilution technique., Results: No group or sex differences were found. Therefore, results were combined for 43 toddlers aged 19-25 mo whose major food staple was white rice. Selected results (x+/- SD) were 1.86 +/- 0.55 mg total dietary Zn/d; 0.35 +/- 0.12 FAZ; 0.63 +/- 0.24 mg total absorbed Zn/d; 0.67 +/- 0.23 mg EFZ/d; and 65.0 +/- 8.3 microg plasma Zn/dL. The molar ratio of dietary phytate to zinc was 2.7:1., Conclusions: The mean intake and absorption of zinc in this population are low in comparison with estimated average dietary and physiologic requirements for zinc, and plasma zinc values are consistent with zinc deficiency. Intestinal losses of endogenous zinc exceed previous estimates for toddlers, and only modest evidence exists of conservation in response to low zinc intake and absorption.

Background: Poor bioavailability of zinc from high-phytate diets is an important contributory factor to zinc deficiency in low-income populations., Objective: The objective of this study was to determine the effect of low-phytate maize consumption on zinc absorption., Design: The participants were apparently healthy children from the Central Highlands of Guatemala. Sixty children (20 per group) were randomly assigned to be fed only the low-phytate maize or 1 of 2 control maizes, the isohybrid wild-type maize or a local maize, for a 10-wk period. During the final week, the fractional absorption of zinc for all meals was measured during 1 d with the use of zinc stable isotopes and a dual isotope ratio technique based on urine enrichment data., Results: Mean (+/-SD) phytate intakes for the low-phytate, wild-type, and local maize groups were 1536 +/- 563, 2056 +/- 517, and 2253 +/- 687 mg/d, respectively. Corresponding zinc intakes were 8.6 +/- 2.5, 8.1 +/- 2.0, and 9.7 +/- 2.6 mg/d, and the dietary phytate:zinc molar ratios were 18 +/- 5, 26 +/- 6, and 23 +/- 5. Corresponding fractional absorptions of zinc were 0.32 +/- 0.07, 0.28 +/- 0.07, and 0.29 +/- 0.06. The respective values for total absorbed zinc were 2.72 +/- 0.88, 2.30 +/- 0.96, and 2.78 +/- 1.04 mg/d. No significant differences in either the fractional absorption of zinc or total absorbed zinc were seen between the maize groups., Conclusion: Under the conditions of the present study, zinc absorption was not increased by the long-term use of low-phytate maize in children whose major dietary staple is maize.

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.

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.

Background: Information is needed on the fractional absorption of zinc (FAZ) and absorbed zinc (AZ) during prolonged exposure to zinc-fortified foods., Objective: The objective was to measure FAZ and AZ from diets fortified with different amounts of zinc and to determine whether zinc absorption changes over approximately 7 wk., Design: Forty-one stunted, moderately anemic children received daily, at breakfast and lunch, 100 g wheat products fortified with 3 mg Fe (ferrous sulfate) and 0 (group Zn-0), 3 (group Zn-3), or 9 (group Zn-9) mg Zn (zinc sulfate) per 100 g flour. FAZ was measured on days 2-3 and 51-52; meal-specific AZs were calculated as the product of FAZ and zinc intake., Results: For the breakfast and lunch meals combined, mean total zinc intakes were 2.14, 4.72, and 10.04 mg/d in groups Zn-0, Zn-3, and Zn-9, respectively, during the initial absorption studies; mean (+/-SD) FAZ values were 0.341 +/- 0.111, 0.237 +/- 0.052, and 0.133 +/- 0.041, respectively, on days 2-3 (P < 0.001) and did not change significantly on days 51-52 in the subset of 31 children studied twice. Mean initial AZ was positively related to zinc intake (0.71 +/- 0.18, 1.11 +/- 0.21, and 1.34 +/- 0.47 mg/d, respectively; P < 0.001); final values did not differ significantly from the initial values., Conclusions: AZ from meals containing zinc-fortified wheat products increases in young children relative to the level of fortification and changes only slightly during approximately 7-wk periods of consumption. Although consumption of zinc-fortified foods may reduce FAZ, zinc fortification at the levels studied positively affects total daily zinc absorption, even after nearly 2 mo of exposure to zinc-fortified diets.

Background: Zinc supplements are used extensively in medicine and research and for public health purposes in the prevention and treatment of zinc deficiency. However, little is known about the efficiency of zinc utilization after different doses., Objective: The objective was to determine the relation between dose of aqueous zinc and absorbed zinc (AZ) in healthy adults., Design: Eight healthy adults (3 men and 5 women) aged 33.8 +/- 9.8 y (x +/- SD) received 3 pairs of zinc doses (2 and 5, 10 and 15, and 20 and 30 mg) in random order in 3 phases (1 pair per phase). There was a 3-wk washout between phases. Aqueous zinc sulfate labeled with 70Zn or 68Zn was orally administered in the postabsorptive state on days 1 and 6, respectively; intravenous 67Zn was administered 1 h after the first oral zinc dose. Two urine samples were collected daily from days 3 to 15; zinc isotopic ratios were determined by inductively coupled plasma mass spectrometry. Fractional absorption of zinc (FAZ) was determined by dual-isotope-tracer ratio; AZ was calculated by multiplying FAZ by dose., Results: Mean (+/-SD) AZ values at doses of 2.2, 5.2, 10.4, 15.2, 20.3, and 30.1 mg ingested Zn were 1.6 +/- 0.4, 3.5 +/- 1.3, 7.4 +/- 1.0, 9.5 +/- 2.2, 11.0 +/- 4.4, and 11.2 +/- 2.1 mg, respectively. A saturable dose-response model, the Hill equation, was selected to model the relation of AZ to ingested zinc. Parameter estimation by nonlinear regression predicted a maximum zinc absorption of 13 mg for larger doses., Conclusions: Increases in aqueous zinc doses >20 mg result in relatively small and progressively diminishing increases in AZ postabsorptively in healthy adults.

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.

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.

Background: Zinc deficiency in children is an important public health concern in the developing world, and the consumption of predominantly cereal-based diets with a high phytate content may contribute to the risk. The gastrointestinal tract plays a central role in absorbing and conserving zinc, yet it has not been carefully studied in such children., Objective: This study investigated zinc homeostasis in healthy, free-living Malawian children with habitually high-phytate diets to better understand the role of the gastrointestinal tract., Design: We evaluated zinc homeostasis in 10 children aged 2-5 y who were consuming a maize-based diet (phytate:zinc molar ratio of 23:1). Zinc stable isotopes were administered orally and intravenously. The tracer and tracee were measured in urine and feces., Results: Endogenous fecal zinc was high in comparison with results for this measure in previous studies. Typical correlations seen in subjects consuming a low-phytate diet between total absorbed zinc, the size of the exchangeable zinc pool, and endogenous fecal zinc were not observed. Fractional absorption of zinc was 0.24., Conclusions: Zinc homeostasis was perturbed, particularly by large, endogenous fecal zinc losses, in this vulnerable population. The effects of interventions to improve zinc status, including dietary phytate reduction, on zinc homeostasis merit further study.

High dietary phytate content that compromises zinc nutriture is thought to be a major problem among children of the developing world. Zinc stable isotope techniques permit the quantitative assessment of the effect of phytate reduction on zinc homeostasis. We tested the hypothesis that zinc absorption would be increased in Malawian children fed a reduced-phytate corn-plus-soy diet compared with a standard high phytate diet. Twenty-three children hospitalized in Blantyre, Malawi, were enrolled. Children were selected from those recovering from tuberculosis and from well children (those with minor injuries, those awaiting elective surgery or healthy siblings). Children received a diet of corn-plus-soy porridge (either low phytate or high phytate) for a period of 3-7 d and then participated in a zinc stable isotope study. The study included the administration of oral and intravenous zinc stable isotopes and 7-d collections of urine and stool. The diet was maintained throughout the duration of specimen collection. Zinc isotopic enrichments in urine and stool were measured, and zinc fractional absorption, total zinc absorption, endogenous fecal zinc, net zinc retention and size of the exchangeable zinc pool were calculated. Among the 14 children recovering from tuberculosis, dietary phytate reduction resulted in higher fractional absorption (0.41 +/- 0.14 versus 0.24 +/- 0.09, mean +/- SD, P: < 0.05) and total zinc absorption (169 +/- 55 versus 100 +/- 46 microg/(kg. d), P: < 0.05). No effect of phytate reduction was seen in the well children (n = 9). Phytate reduction did not decrease the absolute endogenous fecal zinc, but it did decrease it relative to total absorbed zinc. These preliminary results indicate that phytate reduction may be beneficial in improving zinc nutriture in groups with increased zinc requirements who consume a cereal-based diet.

Zinc stable isotopes can be applied to the identification of populations at risk for zinc deficiency and to monitoring the effects of zinc intervention studies designed to improve zinc nutriture. Techniques using these isotopes can provide information on how effectively the intestine is absorbing exogenous dietary zinc and conserving endogenous zinc. They can also yield estimates of the quantity of readily exchangeable zinc in the body. Data derived from stable-isotope studies can provide extensive information on zinc status and the bioavailability of dietary zinc, allowing researchers to relate zinc intake to physiologic and pathologic conditions. Application of these techniques in longitudinal studies can provide quantitative data on the effectiveness of prevention programs such as simple community measures aimed at reducing dietary phytate and zinc fortification and supplementation programs. Further, judicious application of zinc stable-isotope techniques could make an important contribution to progress toward the eradication of zinc deficiency in infants and young children in the developing world.

The association between low initial plasma zinc concentration and risk of morbidity over the subsequent 3 mo was examined in a cohort of 116 children aged 12-59 mo recovering from acute diarrhea. Children with low initial plasma zinc (< or = 8.4 micromol/L) had more episodes of diarrhea [risk ratio (RR): 1.47; 95% CI: 1.03, 2.49) and severe diarrhea, defined as passage of > or = 5 liquid stools in a 24-h period, (RR: 1.70; 95% CI: 1.06, 2.72) than did children with normal plasma zinc (> 8.4 micromol/L). The mean prevalence rate of diarrhea associated with fever was 4 times higher in the zinc-deficient group (P = 0.01). Overall, the difference in the number of episodes of acute lower respiratory tract infections (ALRIs) between the two groups was not statistically significant (RR: 1.76; 95% CI: 0.88-3.53) but the mean prevalence rate of ALRIs was 3.5 times higher in children with low plasma zinc (P = 0.05). The increased risk of diarrhea and ALRIs episodes in zinc-deficient children was larger in boys than in girls. These results show that children with low plasma zinc concentrations are at risk for increased diarrheal and respiratory morbidity.