Leland Miller | University of Colorado Denver (original) (raw)

Papers by Leland Miller

Pediatric Research, 2000

Low plasma zinc concentrations have been reported in approximately 30% of young infants with cyst... more Low plasma zinc concentrations have been reported in approximately 30% of young infants with cystic fibrosis identified by newborn screening. The objective of this study was to examine zinc homeostasis in this population by application of stable isotope methodology. Fifteen infants with cystic fibrosis (9 male, 6 female; 7 breast-fed, 8 formula-fed) were studied at a mean (ϮSD) age of 1.8 Ϯ 0.7 mo. On d 1, 70 Zn was administered intravenously, and 67 Zn was quantitatively administered with all human milk/formula feeds during the day. Three days later, a 3-d metabolic period was initiated, during which time intake was measured and complete urine and fecal collections were obtained. Fractional zinc absorption, total absorbed zinc, endogenous fecal zinc, and net absorbed zinc were measured; fecal fat excretion was also determined. Fractional absorption was significantly higher for the breast-fed infants (0.40 Ϯ 0.21) compared with the formula-fed group (0.13 Ϯ 0.06) (p ϭ 0.01), but with the significantly higher dietary zinc intake of the formula-fed ABSTRACT 256

Stereotactic and Functional Neurosurgery, 1982

International Journal for Vitamin and Nutrition Research, 2005

The focus of this paper is on the application of measurements of zinc absorption in human researc... more 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.

Analytical Biochemistry, 2003

Reducing water to hydrogen gas by zinc or uranium metal for determining D/H ratio is both tedious... more Reducing water to hydrogen gas by zinc or uranium metal for determining D/H ratio is both tedious and time consuming. This has forced most energy metabolism investigators to use the ''two-point'' technique instead of the ''Multi-point'' technique for estimating total energy expenditure (TEE). Recently, we purchased a new platinum (Pt)-equilibration system that significantly reduces both time and labor required for D/H ratio determination. In this study, we compared TEE obtained from nine overweight but healthy subjects, estimated using the traditional Zn-reduction method to that obtained from the new Pt-equilibration system. Rate constants, pool spaces, and CO 2 production rates obtained from use of the two methodologies were not significantly different. Correlation analysis demonstrated that TEEs estimated using the two methods were significantly correlated (r ¼ 0:925, p ¼ 0:0001). Sample equilibration time was reduced by 66% compared to those of similar methods. The data demonstrated that the Zn-reduction method could be replaced by the Pt-equilibration method when TEE was estimated using the ''Multi-Point'' technique. Furthermore, D equilibration time was significantly reduced. (B.J. Sonko).

Analytical Chemistry, 1998

A microwave digestion method to prepare human erythrocytes for measurement of Zn concentration by... more A microwave digestion method to prepare human erythrocytes for measurement of Zn concentration by atomic absorption spectrophotometry and stable isotope enrichment by mass spectrometry is described. Also described is a process for purifying digested erythrocyte samples enriched with Zn stable isotope for analysis by fast atom bombardment mass spectrometry. Microwave digestion was investigated as a way to increase sample throughput by replacing a more time-consuming conventional oven ashing/hot plate wet digestion method. Pooled red blood cells and NIST bovine liver standard reference material were digested by the two different methods and zinc recoveries compared by atomic absorption spectrophotometry. Microwave and conventional methods yielded 11.7 +/- 0.1 and 11.7 +/- 0.2 micrograms/g (wet wt), respectively, for the pooled erythrocytes, and Zn recovery from NIST bovine liver standard (certified 123 +/- 8 micrograms/g) was 128.2 +/- 1.2 and 127.4 +/- 1.3 micrograms/g, p > or = 0.282, respectively. Microwave digestion improved the processing of erythrocytes for atomic absorption spectrophotometry and mass spectrometry by reducing digestion time from 1 week to 2 h. In addition, a procedure for purifying digested erythrocyte samples by either extraction and ion-exchange chromatography in preparation for mass spectrometry analysis of Zn stable isotope enrichment is outlined.

Journal of Nutritional Biochemistry, 1995

The refinement of techniques that can accurately measure small changes in zinc stable isotope rat... more The refinement of techniques that can accurately measure small changes in zinc stable isotope ratios in biological samples provides new opportunities for advancing our understanding of human zinc metabolism. The feasibilig of utilizing more than one zinc stable isotope label simultaneously is invaluable for more complex kinetic studies. These techniques are especially valuable for investigations of the regulation of Zn homeostasis in infants and in women during the reproductive cycle in whom problems with zinc nutriture may be relatively frequent and of concern for pre-and postnatal growth and devfelopment. Initiall!, these techniques have been applied to studying the role of the intestine in the maintenance of zinc homeostasis and have served to emphasize the importance of the modulation of fecal excretion of endogenous zinc. Application of stable isotope techniques to explore zinc metabolism beyond the intestinal tract is still limited but has considerable potential for advancing our understanding of zinc metabolism in health and disease. (J. Nutr. Biochem. 6:292-301, 1995.)

Journal of Pediatrics, 2006

Zinc (Zn) nutrition is of special practical importance in infants and young children, however rel... more 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. (J Pediatr 2006;149:S64-S68)

Analytical Chemistry, 1993

Stable isotopes have gained prominence in nutrition and trace element research. Fast atom bombard... more Stable isotopes have gained prominence in nutrition and trace element research. Fast atom bombardment mass spectrometry (FAB-MS) measurement of iron isotope ratios has an accuracy of 299.7% with the stable isotopes MFe, 68Fe, and bsFe with relative standard deviations (RSDs) of 10.9%. The isolation of iron from biological matrices can be accomplished in 4 h with almost total removal of isobaric interferences caused by s9KOH, "K*H20, r&aOH, and/or 'OCa-H2O. FAB-MS isotope enrichment measurements from this method compare favorably to predicted absorption/enrichment levels.

Journal of Pediatric Gastroenterology and Nutrition, 2000

The results of earlier, nonquantitative studies suggested that absorption of zinc from a semielem... more The results of earlier, nonquantitative studies suggested that absorption of zinc from a semielemental (casein hydrolysate) formula was inferior to absorption from a cow's milk-based formula. The objective of this study was to compare fractional, total and net zinc absorption, and fecal excretion of endogenous zinc in the same healthy young infants when fed a casein hydrolysate versus cow's milk-based formula. Fractional absorption of zinc and fecal excretion of endogenous zinc were determined from measurement of cumulative fecal excretion of unabsorbed tracer and by an isotope dilution technique, respectively, after oral administration of a 70Zn tracer with all formula feedings for 1 day. Six infants were assigned randomly to receive the test or control formula, and the other formula was administered 2 to 5 weeks later. Mean (+/-SD) fractional absorption of zinc from the casein hydrolysate formula (0.47 +/- 0.17) was double that from the cow's milk-based formula (0.22 +/- 0.04; P = 0.01) with a correspondingly greater total zinc absorption (3.23 +/- 1.67 mg Zn/day vs. 1.55 +/- 0.55 mg Zn/day; P = 0.05). Because the excretion of endogenous zinc in the feces did not differ between formulas (0.90 +/- 0.44 mg Zn/day vs. 0.91 +/- 0.29 mg Zn/day), net absorption of zinc was also higher with the casein hydrolysate formula (2.33 +/- 1.65 mg Zn/day vs. 0.81 +/- 0.67 mg Zn/day; P = 0.02). Retention of zinc appeared to be adequate to meet the needs for growth during feeding with cow's milk-based formula and was more than adequate during short-term feeding with the casein hydrolysate formula.

Background: Small-for-gestational-age (SGA) infants are susceptible to postnatal zinc deficiency,... more 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 70 Zn (45 g/kg) was administered to 10 SGA infants (8 boys) with a mean (ȀSD) gestational age of 33.3 Ȁ 1.8 wk and to 11 AGA infants (8 boys) with a mean (ȀSD) gestational age of 32.4 Ȁ 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 Ȁ 0.2 kg and of the AGA infants was 1.84 Ȁ 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 Ȁ 2.8 and 25.2 Ȁ 8.1 mg; P ҃ 0.0002) and relative to body weight (10.3 Ȁ 2.5 and 13.9 Ȁ 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.

Journal of Nutrition, 2008

The quantity of total dietary zinc (Zn) and phytate are the principal determinants of the quantit... more 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 lowphytate 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

Background: Calcium fortification of maize has been achieved for millennia in Central America by ... more 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 Ȃ140 g tortillas in lieu of breakfast. On one occasion, the tortillas were prepared from maize with Ȃ60% 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 Ȁ 0.03) was significantly (P ҃ 0.003) greater than that from tortillas prepared from the control maize (0.35 Ȁ 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.

Pediatric Research, 1996

... Nancy F Krebs 1 , Carol J Reidinger 1 , Leland V Miller 1 and K Michael Hambidge 1. ... Ziegl... more ... Nancy F Krebs 1 , Carol J Reidinger 1 , Leland V Miller 1 and K Michael Hambidge 1. ... Ziegler EE, Serfass RE, Nelson SE, Figueroa-Colon R, Edwards BB, Houk RS, Thompson JJ 1989 Effect of low zinc intake on absorption and excretion of zinc by infants studied with Zn as ...

Journal of Pediatric Gastroenterology and Nutrition, 2002

Background: The aims of this study were to compare the absorption efficiency of zinc from rice ce... more Background: The aims of this study were to compare the absorption efficiency of zinc from rice cereal and meat, with and without human milk, in 7-month-old breast-fed infants and to compare the size of exchangeable zinc pools in the infants according to the assigned complementary food. Methods: Fractional absorption of zinc was measured in male infants using extrinsic labeling with a stable isotope of zinc in a test meal of either pureed beef (n ‫ס‬ 9) or iron-fortified infant rice cereal (n ‫ס‬ 9). The effect on fractional absorption of the addition of human milk to each complementary food was measured in each infant with a second oral zinc isotope. Fractional absorption was measured using fecal monitoring of isotope excretion, and exchangeable zinc pool size was calculated from isotopic enrichment in urine. Results: Fractional absorption of zinc did not statistically differ between the beef (0.41 ± 0.11) and cereal (0.36 ± 0.05) test meals, although the trend showed that beef had higher frac-tional absorption than cereal. The higher intake of zinc from the beef versus cereal test meal resulted in a 16-fold greater amount of absorbed zinc (P ‫ס‬ 0.0002). The addition of human milk caused significant decreases in fractional absorption of zinc (0.07 ± 0.02, P ‫ס‬ 0.01) and absorbed zinc (0.04 ± 0.01 mg, P < 0.0001). The size of the exchangeable zinc pool did not differ according to group but was strongly correlated with mean daily zinc intake (r ‫ס‬ 0.72, P ‫ס‬ 0.003). Conclusions: These results confirm that meat as a complementary food for breast-fed infants can provide a rich source of dietary zinc that is well absorbed. The significant positive correlation between zinc intake and exchangeable zinc pool size suggests that increasing zinc intake positively affects metabolically available zinc. JPGN 34: [35][36][37][38][39][40][41] 2002. Key Words: Zinc absorption-Zinc intake-Breast-fed infants-Complementary foods-Meat-Exchangeable zinc pool.

Little is yet known about zinc absorption in late pregnancy, and no information on absorption fro... more 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 foodcomposition 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 (ȀSD) FAZ was 0.35 Ȁ 0.11, TDZ was 6.0 Ȁ 3.2 mg/d, TAZ was 2.1 Ȁ 1.0 mg/d, phytate intake was 1033 Ȁ 843 mg/d, plasma zinc was 44.1 Ȁ 6.0 g/dL, and the exchangeable zinc pool size was 142 Ȁ 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: Identification of allelic variants in a single gene that determine the phytate conten... more 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 Ȃ60% and Ȃ80%, 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 (ȀSD) FAZ values from tortillas prepared from ND-LP, lpa1-1-LP, lpa1-1-WT, and ND-WT were 0.38 Ȁ 0.07, 0.28 Ȁ 0.04, 0.15 Ȁ 0.07, and 0.13 Ȁ 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 fractional absorption of an oral dose of zinc can . d '. Fecal collection is difficult, tedio... more The fractional absorption of an oral dose of zinc can . d '. Fecal collection is difficult, tedious, and often incomplete, and may be replaced by urine collection for the fractional absorption of zinc in groups of premature infants. Am J C/in Nutr l996;63:342-7. KEY WORDS Zinc absorption, premature infants, stable zinc isotopes I

The quantities of zinc and phytate in the diet are the primary factors determining zinc absorptio... more 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. J. Nutr. 137: 135-141, 2007.