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.

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.

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.

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.

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.

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.

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.

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.

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.

Resistant starch does not affect zinc homeostasis in rural Malawian children.

OBJECTIVE: This study tested the hypothesis that Malawian children at risk for zinc deficiency will have reduced endogenous fecal zinc (EFZ) and increased net absorbed zinc (NAZ) following the addition of high amylose maize resistant starch (RS) to their diet. METHODS: This was a small controlled clinical trial to determine the effects of added dietary RS on zinc homeostasis among 17 stunted children, aged 3-5 years consuming a plant-based diet and at risk for perturbed zinc homeostasis. Dual zinc stable isotope studies were performed before and after 28 d of intervention with RS, so that each child served as their own control. The RS was incorporated into fried wheat flour dough and given under direct observation twice daily for 28 d. Changes in zinc homeostatic measures were compared using paired Student's t-tests and linear regression analysis. RESULTS: Children had a mean height-for-age Z-score of -3.3, and consumed animal source foods ≤twice per month. Their habitual diet contained a phytate:zinc molar ratio of 34:1. Children avidly consumed the RS without complaints. EFZ was 0.8±0.4mg/d (mean±SD) both before and after the intervention. Fractional absorption of zinc was 0.38±0.08 and 0.35±0.06 before and after the RS intervention respectively. NAZ was 1.1±0.5 and 0.6±0.7 before and after the RS intervention. This reduction of NAZ corresponded with diminished dietary zinc intake on the study day following intervention with RS. Regression analysis indicated no change in zinc absorption relative to dietary intake as a result of the RS intervention. CONCLUSION: Consumption of RS did not improve zinc homeostasis in rural African children without zinc deficiency. RS was well tolerated in this setting.

Zinc absorption from micronutrient powder is low but is not affected by iron in Kenyan infants.

Interference with zinc absorption is a proposed explanation for adverse effects of supplemental iron in iron-replete children in malaria endemic settings. We examined the effects of iron in micronutrient powder (MNP) on zinc absorption after three months of home fortification with MNP in maize-based diets in rural Kenyan infants. In a double blind design, six-month-old, non-anemic infants were randomized to MNP containing 5 mg zinc, with or without 12.5 mg of iron (MNP + Fe and MNP − Fe, respectively); a control (C) group received placebo powder. After three months, duplicate diet collections and zinc stable isotopes were used to measure intake from MNP + non-breast milk foods and fractional absorption of zinc (FAZ) by dual isotope ratio method; total absorbed zinc (TAZ, mg/day) was calculated from intake × FAZ. Mean (SEM) TAZ was not different between MNP + Fe (n = 10) and MNP - Fe (n = 9) groups: 0.85 (0.22) and 0.72 (0.19), respectively, but both were higher than C (n = 9): 0.24 (0.03) (p = 0.04). Iron in MNP did not significantly alter zinc absorption, but despite intakes over double estimated dietary requirement, both MNP groups' mean TAZ barely approximated the physiologic requirement for age. Impaired zinc absorption may dictate need for higher zinc doses in vulnerable populations.

Zinc deficiency in infants and children: a review of its complex and synergistic interactions.

Zinc deficiency is estimated to contribute to over half a million deaths per year in infants and children under 5 years of age. This paper reviews the features of mild-to-moderate zinc deficiency, which include growth faltering, deficits in immune function and altered integrity and function of the gastro-intestinal tract. Sub-clinical features include oxidative stress and a pro-inflammatory state. The homeostatic response to low dietary zinc intake by increasing absorption is limited, especially if the source of zinc is of poor bioavailability, and conservation of endogenous intestinal losses is a critical component of adaptation. Owing to low zinc intakes, older breastfed infants, especially those of low birthweight, are predictably at risk of zinc deficiency if complementary food choices are unfortified and/or low in zinc. Host factors such as young age, poor intra-uterine zinc accretion owing to poor maternal status and/or prematurity, and gastro-intestinal dysfunction also potently predispose to zinc deficiency. Environmental enteropathy, which is prevalent in low-resource settings, may substantially impair zinc absorption and/or increase endogenous losses, and thus lead to relatively high zinc requirements. Emerging evidence highlights common features between chronic inflammation and zinc deficiency, and each may exacerbate the other. More investigations of zinc homeostasis in populations in low-resource settings are needed to better quantify absorption capacity and losses. Effective preventive strategies must address potentially higher zinc requirements as well as the underlying context that perpetuates a vicious cycle of zinc deficiency and multiple adverse outcomes.

Newborn length predicts early infant linear growth retardation and disproportionately high weight gain in a low-income population.

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.

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.

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

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

Zinc requirements: assessment and population needs.

Reliable estimates of zinc requirements have assumed greater priority as the global public health importance of preventing zinc deficiency has gained increasing recognition. On a global public health basis, our first most evident goal is reliable estimates of average population requirements. Despite expectations of rapid advances towards simpler and more sophisticated strategies, estimations of zinc requirements continue to depend on a factorial approach. Since the Dietary Reference Intakes (DRIs) were published, there have been important advances in techniques for the factorial approach but also confusion resulting from the subsequent publication of conflicting 'international' estimates. The reasons for these differences have now been fully elucidated, removing an obstruction to continuing progress and refinements of our knowledge base. A key advance has been the development and validation of a model that can be simply applied to determine the inhibitory effects of phytate on zinc absorption. Better understanding of maternal and young child zinc requirements continues to present a challenge of special importance.

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.

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

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

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

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