Biomedical subjects

Leland V Miller

Publications and source records attributed to Leland V Miller.

13 recordsLinked to original sources

PubMed2007

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↗

PubMed2006

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↗

PubMed2006

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↗

PubMed2006

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↗

PubMed2005

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↗

PubMed2005

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↗

PubMed2005

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↗

PubMed2004

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↗

PubMed2004

Zinc absorption as a function of the dose of zinc sulfate in aqueous solution.

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.

Absorption↗

PubMed2003

Multi-point estimation of total energy expenditure: a comparison between zinc-reduction and platinum-equilibration methodologies.

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 CO2 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=0.925, p=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.

Adult↗

PubMed2003

Exchangeable zinc pool size in infants is related to key variables of zinc homeostasis.

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.

Homeostasis↗

PubMed2002

Zinc homeostasis during lactation in a population with a low zinc intake.

BACKGROUND: There is a major increase in endogenous zinc excretion, specifically via the mammary gland, in early human lactation. Whereas fractional absorption of dietary zinc has been reported to increase in early human lactation, it is not known to what extent adaptive mechanisms may maintain zinc homeostasis, especially when dietary zinc intake is relatively low. OBJECTIVE: The objective of this study was to quantitate major variables of zinc homeostasis during early lactation in subjects from a population whose habitual dietary zinc intake is low. DESIGN: We studied 18 free-living lactating women from a rural community of northeast China whose infants were exclusively breast-fed. The subjects were studied at approximately 2 mo of lactation with use of stable isotopes of zinc and metabolic collection techniques. Milk volume was measured with use of a deuterium enrichment method. RESULTS: The mean (+/-SD) secretion of zinc in milk was 2.01 +/- 0.97 mg/d, the intake of zinc was 7.64 +/- 1.61 mg/d, and the fractional absorption of zinc was 0.53 +/- 0.09, for a total daily zinc absorption of 4.00 +/- 0.71 mg/d. Endogenous zinc excretion in urine and feces was 0.30 +/- 0.10 and 1.66 +/- 0.97 mg/d, respectively. CONCLUSIONS: Zinc balance, including zinc secreted in breast milk, was maintained at approximately 2 mo of lactation in women whose habitual diet was low in zinc. Homeostasis was achieved by high fractional absorption of zinc and intestinal conservation of endogenous fecal zinc.

Adult↗

PubMed2002

Zinc absorption and exchangeable zinc pool sizes in breast-fed infants fed meat or cereal as first complementary food.

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 = 9) or iron-fortified infant rice cereal (n = 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 fractional 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 = 0.0002). The addition of human milk caused significant decreases in fractional absorption of zinc (0.07 +/- 0.02, P = 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 = 0.72, P = 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.

Animals↗