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Biomedical subjects

Nancy F Krebs

Publications and source records attributed to Nancy F Krebs.

At least 19 recordsLinked to original sources

A mathematical model of zinc absorption in humans as a function of dietary zinc and phytate.

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.

Humans↗

Changes in zinc absorption during development.

Zinc (Zn) nutrition is of special practical importance in infants and young children, however relatively little is known about maturation and comparative aspects of Zn absorption. The principal objective of this paper is to compare Zn absorption of term infants, preterm infants, and adults on low phytate diets. Existing data derived from using Zn stable isotopes as extrinsic labels for an entire day were modeled with saturation kinetic analysis (saturable response model). When adjusted for differences in length of small intestine, the efficiency of Zn absorption for both term (4 months) and preterm (33 weeks post-conception) infants was comparable with that for adults, suggesting early maturation of mechanisms that regulate absorption. However, infant intestinal lengths were shorter, and Zn absorptive capacity was proportionately less. Reduced capacity was matched by lower Zn requirements for normal term infants. This favorable match, however, did not occur in the preterm infant because of relatively high Zn requirements. Although intestinal conservation of endogenous Zn in these preterm infants was appropriate in relation to the quantity of Zn absorbed, it was not optimal for achieving the retention required. Normal homeostatic mechanisms in the premature infant prevented efficient absorption of the quantity of Zn required or/and optimal conservation of endogenous Zn.

Adult↗

Zinc absorption in Guatemalan schoolchildren fed normal or low-phytate maize.

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.

Anthropometry↗

Comprehensive integration of nutrition into medical training.

Nutrition must be integrated into the medical school curriculum to train physicians who can effectively provide nutrition care for the prevention and management of chronic diseases. This article describes the comprehensive nutrition curriculum developed at the University of Colorado School of Medicine. Two fundamental principles have guided the school's approach to medical nutrition education: 1) nutrition content must be broad in nature and be vertically integrated across the preclinical and clinical years and continued through postgraduate training, and 2) active adult learning (eg, "learning by doing") should be practiced whenever possible. From our experience, we have identified several key elements important for the successful integration of nutrition into the curriculum. First, identifying a core group of committed faculty to advocate for nutrition and serve as role models and having a physician nutrition specialist at the helm provides constant momentum for the advancement of nutrition education. Second, establishing a network of linkages with other elements of the existing curriculum creates the opportunity to add nutrition content without necessarily adding time. The third key element is an emphasis on incorporating nutrition in clinical training. Students must be routinely exposed to physicians practicing nutrition for nutrition to become part of standard patient care. This can be accomplished through multiple exposures to nutrition throughout the curriculum (ie, vertical integration). Finally, a coordinator is needed to monitor the many "fronts" of the integrated nutrition curriculum and to continue networking and program implementation.

Colorado↗

Major variables of zinc homeostasis in Chinese toddlers.

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.

Child, Preschool↗

Zinc absorption during late pregnancy in rural southern Ethiopia.

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

Administration, Oral↗

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

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

Birth Weight↗

Effect of maternal consumption of lactobacillus GG on transfer and establishment of fecal bifidobacterial microbiota in neonates.

BACKGROUND: Establishment of the gut microbiota at birth provides a substantial source of microbial stimuli for the maturation of the immune system. Deviations in this process precede the development of specific diseases providing the rationale for the use of probiotics to counteract them. OBJECTIVE: This study was designed to characterize both the mother-infant bifidobacteria transfer at birth and the development of bifidobacteria microbiota during the first weeks of life in infants whose mothers received Lactobacillus rhamnosus GG or placebo. METHODS: Species-specific PCR was used to assess the fecal bifidobacterial composition of mothers before and after delivery and in infants at 5 days and 3 weeks of age. RESULTS: Bifidobacterium longum was the species most commonly found in the mothers. Bifidobacterium catenulatum was the most prevalent group in infants at 5 days of age and B. longum the predominant species at 3 weeks. At 5 days of age, infants whose mothers received L. rhamnosus GG showed a significantly higher occurrence of B. breve and lower of B. adolescentis than those from the placebo group. In addition, L. rhamnosus GG consumption increased the bifidobacterial diversity in infants and reduced the Bifidobacterium microbiota similarity between mother and infant. CONCLUSIONS: These results indicate that specific changes in the transfer and initial establishment of bifidobacteria in neonates take place as consequence of the consumption of L. rhamnosus GG by the mothers.

Adult↗

Optimizing bone health and calcium intakes of infants, children, and adolescents.

Most older children and adolescents in the United States currently do not achieve the recommended intake of calcium. Maintaining adequate calcium intake during childhood and adolescence is necessary for the development of peak bone mass, which may be important in reducing the risk of fractures and osteoporosis later in life. Optimal calcium intake is especially relevant during adolescence, when most bone mineral accretion occurs. Because of the influence of the family's diet on the diet of children and adolescents, adequate calcium intake by all members of the family is important. Assessment of calcium intake can be performed in the physician's office. A well-rounded diet including low-fat dairy products, fruits, and vegetables and appropriate physical activity are important for achieving good bone health. Establishing these practices in childhood is important so that they will be followed throughout the life span.

Adolescent↗

Measurements of zinc absorption: application and interpretation in research designed to improve human zinc nutriture.

The focus of this paper is on the application of measurements of zinc absorption in human research, especially studies designed to assess the efficacy of intervention strategies to prevent and manage zinc deficiency in populations. Emphasis is given to the measurement of quantities of zinc absorbed rather than restricting investigations to measurements of fractional absorption of zinc. This is especially important when determining absorption of zinc from the diet, whether it be the habitual diet or an intervention diet under evaluation. Moreover, measurements should encompass all meals for a minimum of one day with the exception of some pilot studies. Zinc absorption is primarily via an active saturable transport process into the enterocytes of the proximal small intestine. The relationship between quantity of zinc absorbed and the quantity ingested is best characterized by saturable binding models. When applied to human studies that have sufficient data to examine dose-response relationships, efficiency of absorption is high until approximately 50-60% maximal absorption is achieved, even with moderate phytate intakes. This also coincides approximately with the quantity of absorbed zinc necessary to meet physiologic requirements. Efficiency of absorption with intakes that exceed this level is low or very low. These observations have important practical implications for the design and interpretation of intervention studies to prevent zinc deficiency. They also suggest the potential utility of measurements of the quantity of zinc absorbed when evaluating the zinc status of populations.

Biological Availability↗

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

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

Adult↗

Longitudinal measurements of zinc absorption in Peruvian children consuming wheat products fortified with iron only or iron and 1 of 2 amounts of zinc.

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.

Biological Availability↗

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

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

Administration, Oral↗

Plasma zinc concentrations are depressed during the acute phase response in children with falciparum malaria.

Plasma concentrations of some micronutrients are altered in the setting of acute infectious or inflammatory stress. Previous studies have provided conflicting evidence concerning the extent and direction of changes in plasma zinc concentrations during the acute phase response. We carried out an observational cohort study in 689 children enrolled in a randomized trial of zinc supplementation during acute falciparum malaria in order to evaluate the relation between plasma zinc concentration and the acute phase response. Plasma zinc was measured by atomic absorption spectrophotometry. On admission, 70% of all subjects had low plasma zinc (<9.2 micromol/L). Multivariate analysis of predictors of admission plasma zinc showed that admission C-reactive protein (CRP), parasite density, and study site were the most important predictors. Predictors of changes in plasma zinc from admission to 72 h included baseline CRP, change in CRP, treatment group, study site, and baseline zinc concentration. In children with acute malaria infection, baseline plasma zinc concentrations were very low and were inversely correlated with CRP (r = -0.24, P < 0.0001) and the degree of parasitemia (r = -0.19, P < 0.0001). Even when CRP and time were taken into account, zinc supplementation increased plasma zinc concentration from admission to 72 h. When available, plasma zinc concentrations should be interpreted with concurrent measures of the acute phase response such as CRP. In children whose age, diet, and/or nutritional status place them at risk of zinc deficiency, those with low plasma zinc levels should be supplemented with oral zinc and followed for clinical and/or biochemical response.

Antimalarials↗

Failure to thrive as a manifestation of child neglect.

Failure to thrive is a common problem in infancy and childhood. It is most often multifactorial in origin. Inadequate nutrition and disturbed social interactions contribute to poor weight gain, delayed development, and abnormal behavior. The syndrome develops in a significant number of children as a consequence of child neglect. This clinical report is intended to focus the pediatrician on the consideration, evaluation, and management of failure to thrive when child neglect may be present. Child protective services agencies should be notified when the evaluation leads to a suspicion of abuse or neglect.

Child↗

Zinc homeostasis in premature infants does not differ between those fed preterm formula or fortified human milk.

The objectives of this study were to compare zinc homeostasis in premature infants enterally fed with either preterm infant formula or fortified human milk; to examine interrelationships of variables of zinc homeostasis; and to examine the findings in relation to estimated zinc requirements of preterm infants. Zinc homeostasis was studied in 14 infants (8 male), with mean gestational age of 31 wk and birth weight appropriate for gestational age, who were exclusively fed either preterm formula (n = 9) or own mother's milk with human milk fortifier (n = 5). Zinc stable isotopes were administered intravenously ((70)Zn) and orally as an extrinsic label ((67)Zn) over multiple feeds for determination of fractional absorption by dual isotope tracer ratio in urine; endogenous fecal zinc was determined by isotope dilution; and exchangeable zinc pool (EZP) size was estimated from linear regression of log-transformed urine (70)Zn enrichment data. Results indicated no significant differences in the variables of zinc homeostasis between the feeding groups; data for all subjects were thus combined. Mean (+/- SD) fractional absorption was 0.26 +/- 0.07; net absorbed zinc 0.43 +/- 0.25 mg/d (0.31 +/- 0.19 mg/kg/d). Mean EZP was 20 +/- 10 mg/kg, and was positively correlated with total absorbed zinc and with net absorbed zinc. Feeding type and total absorbed zinc were significantly related to daily weight gain (p = 0.003). Current zinc intakes from fortified human milk or formula are associated with acceptable weight gain, but whether the observed net zinc absorption was optimal in the human milk group cannot be definitively determined from these data.

Cross-Sectional Studies↗

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

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

Adult↗