Leland V. Miller

The Quantity of Zinc Absorbed from Wheat in Adult Women Is Enhanced by Biofortification

Biofortification of crops that provide major food staples to large, poor rural populations offers an appealing strategy for diminishing public health problems attributable to micronutrient deficiencies. The objective of this first-stage human study was to determine the increase in quantity of zinc (Zn) absorbed achieved by biofortifying wheat with Zn. Secondary objectives included evaluating the magnitude of the measured increases in Zn absorption as a function of dietary Zn and phytate. The biofortified and control wheats were extracted at high (95%) and moderate (80%) levels and Zn and phytate concentrations measured. Adult women with habitual diets high in phytate consumed 300 g of 95 or 80% extracted wheat as tortillas for 2 consecutive days using either biofortified (41 mg Zn/g) or control (24 mg Zn/g) wheat. All meals for the 2-d experiment were extrinsically labeled with Zn stable isotopes and fractional absorption of Zn determined by a dual isotope tracer ratio technique. Zn intake from the biofortified wheat diet was 5.7 mg/d (72%) higher at 95% extraction (P < 0.001) and 2.7 mg/d (68%) higher at 80% extraction compared with the corresponding control wheat (P = 0.007). Zn absorption from biofortified wheat meals was (mean +/- SD) 2.1 +/- 0.7 and 2.0 +/- 0.4 mg/d for 95 and 80% extraction, respectively, both of which were 0.5 mg/d higher than for the corresponding control wheat (P < 0.05). Results were consistent with those predicted by a trivariate model of Zn absorption as a function of dietary Zn and phytate. Potentially valuable increases in Zn absorption can be achieved from biofortification of wheat with Zn.

Abnormalities in zinc homeostasis in young infants with cystic fibrosis.

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 (±SD) age of 1.8 ± 0.7 mo. On d 1, 70Zn was administered intravenously, and 67Zn 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 ± 0.21) compared with the formula-fed group (0.13 ± 0.06) (p = 0.01), but with the significantly higher dietary zinc intake of the formula-fed group, total absorbed zinc was higher for those receiving formula (p = 0.01). In 11 infants with complete zinc metabolic data, excretion of endogenous zinc was twofold greater for the formula-fed infants (p < 0.05); net absorption (mg zinc/d) was negative for both feeding groups: −0.04 ± 0.52 for breast-fed; −0.28 ± 0.57 for formula-fed. Endogenous fecal zinc losses correlated with fecal fat excretion (r = 0.89, n = 9, p = 0.001), suggesting interference with normal conservation of endogenously secreted zinc. These findings indicate impaired zinc homeostasis in this population and suggest an explanation for the observations of suboptimal zinc status in many young infants with cystic fibrosis prior to diagnosis and treatment.

Zinc Homeostasis in Breast-Fed Infants

The needs for dietary zinc are adequately met by most fully breast-fed infants despite relatively low zinc intakes in relation to estimated requirements. The objective of this study was to use stable isotope techniques to evaluate how zinc retention is achieved in normal fully breast-fed infants. Nine male infants, aged 2-5 mo, were fed expressed human milk labeled with70 Zn over a 24-h period. Complete fecal collections were obtained for 8 d. On d 4-7, a metabolic period was initiated which included test weighing and milk sampling, to measure zinc intake, and daily urine collections. Isotopic enrichment of fecal and urine samples was determined by fast atom bombardment mass spectrometry. Results included a mean (±SD) dietary zinc intake of 17.8 ± 6.6 μmol/d; fractional absorption of 0.54 ± 0.075; and total absorbed zinc of 9.5 ± 3.5 μmol/d. Mean endogenous fecal zinc, determined on seven infants by isotope dilution, was 4.7 ± 2.3μmol/d, which resulted in a mean net absorption of 4.8 ± 3.4μmol/d. The results of the study indicated that, for fully breast-fed infants, it is the combination of a relatively high fractional absorption and efficient conservation of intestinal endogenous zinc that results in zinc retention adequate to meet the demands of growth in the face of modest intake.

The use of stable isotope techniques to assess zinc metabolism

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 feasibility 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 preand postnatal growth and development. Initially, 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.

Dietary reference intakes for zinc may require adjustment for phytate intake based upon model predictions.

The quantity of total dietary zinc (Zn) and phytate are the principal determinants of the quantity of absorbed Zn. Recent estimates of Dietary Reference Intakes (DRI) for Zn by the Institute of Medicine (IOM) were based on data from low-phytate or phytate-free diets. The objective of this project was to estimate the effects of increasing quantities of dietary phytate on these DRI. We used a trivariate model of the quantity of Zn absorbed as a function of dietary Zn and phytate with updated parameters to estimate the phytate effect on the Estimated Average Requirement (EAR) and Recommended Daily Allowance for Zn for both men and women. The EAR predicted from the model at 0 phytate was very close to the EAR of the IOM. The addition of 1000 mg phytate doubled the EAR and adding 2000 mg phytate tripled the EAR. The model also predicted that the EAR for men and women could not be attained with phytate:Zn molar ratios > 11:1 and 15:1, respectively. The phytate effect on upper limits (UL) was predicted by first estimating the quantity of absorbed Zn corresponding to the UL of 40 mg for phytate-free diets, which is 6.4 mg Zn/d. Extrapolation of the model suggested, for example, that with 900 mg/d phytate, 100 mg dietary Zn is required to attain 6.4 mg absorbed Zn/d. Experimental studies with higher Zn intakes are required to test these predictions.

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.

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.

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

Abstract 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.

Evaluation of zinc metabolism with use of stable-isotope techniques: implications for the assessment of zinc status.

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

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.