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Background: Children in resource-limited settings remain vulnerable to zinc deficiency and its consequences., Objectives: To evaluate the effects of different doses, durations, and frequencies of zinc supplementation on the incidence of diarrhea and change in linear growth among young children., Methods: We conducted a randomized, partially double-blind, controlled, 6-arm, community-based efficacy trial in Dhaka, Bangladesh. Children aged 9-11 mo were randomly assigned to receive 1 of the following interventions for 24 wk: 1) standard micronutrient powder (MNP) containing 4.1 mg zinc and 10 mg iron, daily; 2) high-zinc (10 mg), low-iron (6 mg) (HiZn LoFe) MNP, daily; 3) HiZn (10 mg) LoFe (6 mg)/HiZn (10 mg), no-iron MNPs on alternating days; 4) dispersible zinc tablet (10 mg), daily; 5) dispersible zinc tablet (10 mg), daily for 2 wk at enrollment and 12 wk; 6) placebo powder, daily. Primary outcomes were incidence of diarrhea and change in length-for-age z-score (LAZ) over the 24-wk intervention period. Home visits were conducted twice weekly to assess diarrhea and other morbidity. Incidence and prevalence outcomes were compared among groups with Poisson regression; continuous outcomes were compared using ANCOVA., Results: A total of 2886 children were enrolled between February 2018 and July 2019. The mean incidence and prevalence of diarrhea among all participants was 1.21 episodes per 100 d and 3.76 d per 100 d, respectively. There were no differences in the incidence or prevalence of diarrhea across intervention groups. The decline in LAZ was slightly smaller among children in the daily HiZn LoFe MNP group compared with the placebo powder group (P < 0.05)., Conclusions: The dose of zinc in MNPs as well as the duration and frequency of supplementation evaluated in this trial were not effective in reducing diarrhea; however, the daily HiZn LoFe MNP formulation offered modest improvements in linear growth among young children. This trial was registered at clinicaltrials.gov as NCT03406793., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Vitamin A (VA) stores are low in early infancy and may impair development of the immune system., Objective: This study determined if neonatal VA supplementation (VAS) affects the following: 1) development of regulatory T (Treg) cells; 2) chemokine receptor 9 (CCR9) expression, which directs mucosal targeting of immune cells; and 3) systemic endotoxin exposure as indicated by changed plasma concentrations of soluble CD14 (sCD14). Secondarily, VA status, growth, and systemic inflammation were investigated., Methods: In total, 306 Bangladeshi infants were randomly assigned to receive 50,000 IU VA or placebo (PL) within 48 h of birth, and immune function was assessed at 6 wk, 15 wk, and 2 y. Primary outcomes included the following: 1) peripheral blood Treg cells; 2) percentage of Treg, T, and B cells expressing CCR9; and 3) plasma sCD14. Secondary outcomes included the following: 4) VA status measured using the modified relative dose-response (MRDR) test and plasma retinol; 5) infant growth; and 6) plasma C-reactive protein (CRP). Statistical analysis identified group differences and interactions with sex and birthweight., Results: VAS increased (P = 0.004) the percentage of CCR9+ Treg cells (13.2 ± 1.37%) relative to PL (9.17 ± 1.15%) in children below the median birthweight but had the opposite effect (P = 0.04) in those with higher birthweight (VA, 9.13 ± 0.89; PL, 12.1 ± 1.31%) at 6 and 15 wk (values are combined mean ± SE). VAS decreased (P = 0.003) plasma sCD14 (1.56 ± 0.025 mg/L) relative to PL (1.67 ± 0.032 mg/L) and decreased (P = 0.034) the prevalence of VA deficiency (2.3%) relative to PL (9.2%) at 2 y., Conclusions: Neonatal VAS enhanced mucosal targeting of Treg cells in low-birthweight infants. The decreased systemic exposure to endotoxin and improved VA status at 2 y may have been due to VA-mediated improvements in gut development resulting in improved barrier function and nutrient absorption. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610., (Published by Oxford University Press on behalf of the American Society for Nutrition 2020.)

Background: Zinc deficiency impairs immune function and is common among children in South-East Asia., Objectives: The effect of zinc supplementation on immune function in young Laotian children was investigated., Methods: Children (n = 512) aged 6-23 mo received daily preventive zinc tablets (PZ; 7 mg Zn/d), daily multiple micronutrient powder (MNP; 10 mg Zn/d, 6 mg Fe/d, plus 13 other micronutrients), therapeutic dispersible zinc tablets only in association with diarrhea episodes (TZ; 20 mg Zn/d for 10 d after an episode), or daily placebo powder (control). These interventions continued for 9 mo. Cytokine production from whole blood cultures, the concentrations of T-cell populations, and a complete blood count with differential leukocyte count were measured at baseline and endline. Endline means were compared via ANCOVA, controlling for the baseline value of the outcome, child age and sex, district, month of enrollment, and baseline zinc status (below, or above or equal to, the median plasma zinc concentration)., Results: T-cell cytokines (IL-2, IFN-γ, IL-13, IL-17), LPS-stimulated cytokines (IL-1β, IL-6, TNF-α, and IL-10), and T-cell concentrations at endline did not differ between intervention groups, nor was there an interaction with baseline zinc status. However, mean ± SE endline lymphocyte concentrations were significantly lower in the PZ than in the control group (5018 ± 158 compared with 5640 ± 160 cells/μL, P = 0.032). Interactions with baseline zinc status were seen for eosinophils (Pixn = 0.0036), basophils (Pixn = 0.023), and monocytes (P = 0.086) but a significant subgroup difference was seen only for eosinophils, where concentrations were significantly lower in the PZ than in the control group among children with baseline plasma zinc concentrations below the overall median (524 ± 44 compared with 600 ± 41 cells/μL, P = 0.012)., Conclusions: Zinc supplementation of rural Laotian children had no effect on cytokines or T-cell concentrations, although zinc supplementation affected lymphocyte and eosinophil concentrations. These cell subsets may be useful as indicators of response to zinc supplementation.This trial was registered at clinicaltrials.gov as NCT02428647., (Published by Oxford University Press on behalf of the American Society for Nutrition 2020.)

Background: Cross-sectional (CS) surveys indicate that individuals with acute inflammation have higher plasma ferritin (pF), and lower retinol-binding protein (RBP) and zinc (pZn) concentrations than those without. In populations with a high burden of infection, correction factors (CFs) or regression corrections (RCs) are applied to biomarkers to estimate the prevalence of micronutrient (MN) deficiencies adjusted for inflammation. This assumes that individuals with and without inflammation have the same nutritional status, which may not be the case., Objectives: The aim of this study was to investigate relations between short-term, longitudinal within-individual changes in acute phase proteins (C-reactive protein [CRP], α-1-acid glycoprotein [AGP]) and biomarkers of MN status (pF, soluble transferrin receptor [sTfR], RBP, and pZn), and compare them to CS differences., Methods: Two blood samples were obtained 21 d apart from 451 asymptomatic Burkinabé children aged 6-23 mo. To calculate CFs, inflammation was defined as CRP >5 mg/L or AGP >1 g/L, or both. The RC approach adjusted MN biomarkers to a presumably healthy reference point within the study population (10th percentile CRP or AGP concentration). CS CFs and RCs were estimated from a naive regression model, treating observations from the same children as independent. Longitudinal CFs and RCs, to estimate effects of within-individual changes in CRP and/or AGP, were estimated from general linear models, accounting for repeated measures., Results: In CS models, geometric mean pF and sTfR concentrations were 8-340% greater, and RBP and pZn 2-18% lower, in children with inflammation than those without. Except for sTfR, biomarker concentrations differed in the same direction and by similar magnitude within individuals whose inflammation status changed during the observation period. Although geometric mean MN concentrations differed significantly when adjusted with CS compared with longitudinal models, the estimated prevalence of MN deficiencies in CS and longitudinally adjusted models was similar., Conclusions: The CF and RC approaches to adjust MN biomarkers for inflammation between individuals in CS surveys are valid approaches for data collection and programmatic decisions in comparable populations. This study was registered at clinicaltrials.gov as NCT00944853., (Copyright © American Society for Nutrition 2019.)

Background: Pregnancy and childbirth complications and cesarean delivery are common in Bangladesh. Objective: We evaluated the effect of lipid-based nutrient supplements for pregnant and lactating women (LNS-PL) on pregnancy and childbirth complications and cesarean delivery. Methods: We conducted the Rang-Din Nutrition Study, a cluster-randomized controlled effectiveness trial within a community health program in rural Bangladesh. We enrolled 4011 pregnant women in early pregnancy. Women in 48 clusters received iron and folic acid (IFA; 60 mg Fe + 400 μg folic acid/d) and women in 16 clusters received LNS-PL (20 g/d, 118 kcal) containing essential fatty acids and 22 vitamins and minerals. Pregnancy and childbirth complications and the cesarean delivery rate were secondary outcomes of the study. Results: Women in the LNS-PL group did not differ significantly from the IFA group with respect to mean systolic blood pressure at 36 wk gestation (113 and 112 mm Hg; P = 0.17), diastolic blood pressure at 36 wk gestation (68.9 and 68.7 mmHg; P = 0.88), or mean total number of pregnancy and childbirth complications (0.32 and 0.31; P = 0.86). They also did not differ significantly with respect to the prevalence of high blood pressure at 36 wk (1.74% and 2.03%; P = 0.62), antepartum hemorrhage (0.83% and 1.39%; P = 0.21), prolonged labor (8.34% and 8.79%; P = 0.68), early rupture of membranes (9.30% and 8.45%; P = 0.43), convulsions (1.57% and 1.08%; P = 0.24), high blood pressure in labor (1.54% and 1.19%; P = 0.46), obstructed labor (2.83% and 2.91%; P = 0.90), any complications during pregnancy or childbirth (35.9% and 37.1%; P = 0.64), episiotomy (6.31% and 6.44%; P = 0.90), or cesarean delivery (15.6% and 14.2%; P = 0.48). Conclusion: Compared with IFA, antenatal LNS-PL did not increase or decrease pregnancy and childbirth complications or cesarean delivery among women in rural Bangladesh. This trial was registered at clinicaltrials.gov as NCT01715038., Competing Interests: Author disclosures: MKM, SLM, RRP, SH, MS, MH, JMP, SAV, and KGD, no conflicts of interest., (© 2017 American Society for Nutrition.)

Background: The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project is a multiagency and multicountry collaboration that was formed to improve micronutrient assessment and to better characterize anemia. Objectives: The aims of the project were to 1 ) identify factors associated with inflammation, 2 ) assess the relations between inflammation, malaria infection, and biomarkers of iron and vitamin A status and compare adjustment approaches, and 3 ) assess risk factors for anemia in preschool children (PSC) and women of reproductive age (WRA). Design: The BRINDA database inclusion criteria included surveys that 1 ) were conducted after 2004, 2 ) had target groups of PSC, WRA, or both, and 3 ) used a similar laboratory methodology for the measurement of ≥1 biomarker of iron [ferritin or soluble transferrin receptor or vitamin A status (retinol-binding protein or retinol)] and ≥1 biomarker of inflammation (α-1-acid glycoprotein or C-reactive protein). Individual data sets were standardized and merged into a BRINDA database comprising 16 nationally and regionally representative surveys from 14 countries. Collectively, the database covered all 6 WHO geographic regions and contained ∼30,000 PSC and 27,000 WRA. Data were analyzed individually and combined with the use of a meta-analysis. Results: The methods that were used to standardize the BRINDA database and the analytic approaches used to address the project's research questions are presented in this article. Three approaches to adjust micronutrient biomarker concentrations in the presence of inflammation and malaria infection are presented, along with an anemia conceptual framework that guided the BRINDA project's anemia analyses. Conclusions: The BRINDA project refines approaches to interpret iron and vitamin A biomarker values in settings of inflammation and malaria infection and suggests the use of a new regression approach as well as proposes an anemia framework to which real-world data can be applied. Findings can inform guidelines and strategies to prevent and control micronutrient deficiencies and anemia globally.

Background: A lack of information on the etiology of anemia has hampered the design and monitoring of anemia-control efforts. Objective: We aimed to evaluate predictors of anemia in preschool children (PSC) (age range: 6-59 mo) by country and infection-burden category. Design: Cross-sectional data from 16 surveys ( n = 29,293) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed separately and pooled by category of infection burden. We assessed relations between anemia (hemoglobin concentration <110 g/L) and severe anemia (hemoglobin concentration <70 g/L) and individual-level (age, anthropometric measures, micronutrient deficiencies, malaria, and inflammation) and household-level predictors; we also examined the proportion of anemia with concomitant iron deficiency (defined as an inflammation-adjusted ferritin concentration <12 μg/L). Countries were grouped into 4 categories on the basis of risk and burden of infectious disease, and a pooled multivariable logistic regression analysis was conducted for each group. Results: Iron deficiency, malaria, breastfeeding, stunting, underweight, inflammation, low socioeconomic status, and poor sanitation were each associated with anemia in >50% of surveys. Associations between breastfeeding and anemia were attenuated by controlling for child age, which was negatively associated with anemia. The most consistent predictors of severe anemia were malaria, poor sanitation, and underweight. In multivariable pooled models, child age, iron deficiency, and stunting independently predicted anemia and severe anemia. Inflammation was generally associated with anemia in the high- and very high-infection groups but not in the low- and medium-infection groups. In PSC with anemia, 50%, 30%, 55%, and 58% of children had concomitant iron deficiency in low-, medium-, high-, and very high-infection categories, respectively. Conclusions: Although causal inference is limited by cross-sectional survey data, results suggest anemia-control programs should address both iron deficiency and infections. The relative importance of factors that are associated with anemia varies by setting, and thus, country-specific data are needed to guide programs.

Background: Human milk is the subject of many studies, but procedures for representative sample collection have not been established. Our improved methods for milk micronutrient analysis now enable systematic study of factors that affect its concentrations. Objective: We evaluated the effects of sample collection protocols, variations in circadian rhythms, subject variability, and acute maternal micronutrient supplementation on milk vitamin concentrations. Methods: In the BMQ (Breast-Milk-Quality) study, we recruited 18 healthy women (aged 18-26 y) in Dhaka, Bangladesh, at 2-4 mo of lactation for a 3-d supplementation study. On day 1, no supplements were given; on days 2 and 3, participants consumed ∼1 time and 2 times, respectively, the US-Canadian Recommended Dietary Allowances for vitamins at breakfast (0800-0859). Milk was collected during every feeding from the same breast over 24 h. Milk expressed in the first 2 min (aliquot I) was collected separately from the remainder (aliquot II); a third aliquot (aliquot III) was saved by combining aliquots I and II. Thiamin, riboflavin, niacin, and vitamins B-6, B-12, A, and E and fat were measured in each sample. Results: Significant but small differences (14-18%) between aliquots were found for all vitamins except for vitamins B-6 and B-12. Circadian variance was significant except for fat-adjusted vitamins A and E, with a higher contribution to total variance with supplementation. Between-subject variability accounted for most of the total variance. Afternoon and evening samples best reflected daily vitamin concentrations for all study days. Acute supplementation effects were found for thiamin, riboflavin, and vitamins B-6 and A at 2-4 h postdosing, with 0.1-6.17% passing into milk. Supplementation was reflected in fasting, 24-h postdose samples for riboflavin and vitamin B-6. Maximum amounts of dose-responding vitamins in 1 feeding ranged from 4.7% to 21.8% (day 2) and 8.2% to 35.0% (day 3) of Adequate Intake. Conclusions: In the milk of Bangladeshi mothers, differences in vitamin concentrations between aliquots within feedings and by circadian variance were significant but small. Afternoon and evening collection provided the most-representative samples. Supplementation acutely affects some breast-milk micronutrient concentrations. This trial was registered at clinicaltrials.gov as NCT02756026.

Background: Childhood stunting usually begins in utero and continues after birth; therefore, its reduction must involve actions across different stages of early life., Objective: We evaluated the efficacy of small-quantity, lipid-based nutrient supplements (SQ-LNSs) provided during pregnancy, lactation, and infancy on attained size by 18 mo of age., Design: In this partially double-blind, individually randomized trial, 1320 women at ≤20 wk of gestation received standard iron and folic acid (IFA group), multiple micronutrients (MMN group), or SQ-LNS (LNS group) daily until delivery, and then placebo, MMNs, or SQ-LNS, respectively, for 6 mo postpartum; infants in the LNS group received SQ-LNS formulated for infants from 6 to 18 mo of age (endline). The primary outcome was child length by 18 mo of age., Results: At endline, data were available for 85% of 1228 infants enrolled; overall mean length and length-for-age z score (LAZ) were 79.3 cm and -0.83, respectively, and 12% of the children were stunted (LAZ <-2). In analysis based on the intended treatment, mean ± SD length and LAZ for the LNS group (79.7 ± 2.9 cm and -0.69 ± 1.01, respectively) were significantly greater than for the IFA (79.1 ± 2.9 cm and -0.87 ± 0.99) and MMN (79.1 ± 2.9 cm and -0.91 ± 1.01) groups (P = 0.006 and P = 0.009, respectively). Differences were also significant for weight and weight-for-age z score but not head or midupper arm circumference, and the prevalence of stunting in the LNS group was 8.9%, compared with 13.7% in the IFA group and 12.9% in the MMN group (P = 0.12). In analysis based on actual supplement provided at enrollment, stunting prevalences were 8.9% compared with 15.1% and 11.5%, respectively (P = 0.045)., Conclusion: Provision of SQ-LNSs to women from pregnancy to 6 mo postpartum and to their infants from 6 to 18 mo of age may increase the child's attained length by age 18 mo in similar settings. This trial was registered at clinicaltrials.gov as NCT00970866.

Background: Saturated fatty acids (FAs) released from triglyceride-rich lipoproteins (TGRLs) activate Toll-like receptor 2 (TLR-2) and induce the expression of proinflammatory cytokines in monocytes. Certain plant polyphenols inhibit TLR-mediated signaling pathways., Objective: We determined whether plasma free FAs (FFAs) after a moderately high-fat (MHF, 40% kcal from fat) breakfast modulate the inflammatory status of postprandial blood, and whether blueberry intake suppresses FFA-induced inflammatory responses in healthy humans., Methods: Twenty-three volunteers with a mean ± SEM age and body mass index (in kg/m(2)) of 30 ± 3 y and 21.9 ± 0.4, respectively, consumed an MHF breakfast with either a placebo powder or 2 or 4 servings of blueberry powder in a randomized crossover design. The placebo powder was provided on the first test day and the blueberry powder doses were randomized with a 2-wk washout period. Plasma concentrations of lipids, glucose, and cytokines were determined. To determine whether FFAs derived from TGRL stimulate monocyte activation, and whether this is inhibited by blueberry intake, whole blood was treated with lipoprotein lipase (LPL)., Results: The median concentrations of FFAs and cytokines [tumor necrosis factor-α, interleukin (IL)-6 and IL-8] in postprandial plasma (3.5 h) decreased compared with fasting plasma regardless of the blueberry intake (P < 0.001 for FFAs and P < 0.05 for cytokines). However, concentrations of FFAs and cytokines including IL-1β increased in LPL-treated whole blood compared with untreated blood samples from participants who consumed the placebo powder. Blueberry intake suppressed IL-1β and IL-6 production in LPL-treated postprandial blood compared with the placebo control when fasting changes were used as a covariate., Conclusions: The plasma FFA concentration may be an important determinant affecting inflammatory cytokine production in blood. Supplementation with blueberry powder did not affect plasma FFA and cytokine concentrations; however, it attenuated the cytokine production induced by ex vivo treatment of whole blood with LPL. This trial was registered at clinicaltrials.gov as NCT01594008., (© 2016 American Society for Nutrition.)

Background: Maternal undernutrition and newborn stunting [birth length-for-age z score (LAZ) <-2] are common in Bangladesh., Objective: The objective was to evaluate the effect of lipid-based nutrient supplements for pregnant and lactating women (LNS-PLs) on birth outcomes., Design: We conducted a cluster-randomized effectiveness trial (the Rang-Din Nutrition Study) within a community health program in rural Bangladesh. We enrolled 4011 pregnant women at ≤20 gestational weeks; 48 clusters received iron and folic acid (IFA; 60 mg Fe + 400 μg folic acid) and 16 clusters received LNS-PLs (20 g/d, 118 kcal) containing essential fatty acids and 22 vitamins and minerals. Both of the supplements were intended for daily consumption until delivery. Primary outcomes were birth weight and length., Results: Infants in the LNS-PL group had higher birth weights (2629 ± 408 compared with 2588 ± 413 g; P = 0.007), weight-for-age z scores (-1.48 ± 1.01 compared with -1.59 ± 1.02; P = 0.006), head-circumference-for-age z scores (HCZs; -1.26 ± 1.08 compared with -1.34 ± 1.12; P = 0.028), and body mass index z scores (-1.57 ± 1.05 compared with -1.66 ± 1.03; P = 0.005) than those in the IFA group; in adjusted models, the differences in length (47.6 ± 0.07 compared with 47.4 ± 0.04 cm; P = 0.043) and LAZ (-1.15 ± 0.04 compared with -1.24 ± 0.02; P = 0.035) were also significant. LNS-PLs reduced the risk of newborn stunting (18.7% compared with 22.6%; RR: 0.83; 95% CI: 0.71, 0.97) and small head size (HCZ <-2) (20.7% compared with 24.9%; RR: 0.85; 95% CI: 0.73, 0.98). The effects of LNS-PL on newborn stunting were greatest in infants born before a 10-wk interruption in LNS-PL distribution (n = 1301; 15.7% compared with 23.6%; adjusted RR: 0.69; 95% CI: 0.53, 0.89) and in infants born to women ≤24 y of age or with household food insecurity., Conclusion: Prenatal lipid-based nutrient supplements can improve birth outcomes in Bangladeshi women, especially those at higher risk of fetal growth restriction. This trial was registered at clinicaltrials.gov as NCT01715038., (© 2016 American Society for Nutrition.)

Background: The International Lipid-Based Nutrient Supplements Project developed a small-quantity (20 g/d) lipid-based nutrient supplement (LNS) for pregnant and lactating women., Objective: We evaluated the effects of prenatal LNS supplementation on fetal growth., Design: In a community-based, partially double-blind, individually randomized controlled trial, 1320 women ≤20 wk pregnant received 60 mg Fe/400 μg folic acid (IFA), or 1-2 Recommended Dietary Allowances of 18 micronutrients, including 20 mg Fe (MMN), or LNS with the same micronutrients as the MMN group, plus 4 minerals and macronutrients contributing 118 kcal (LNS) daily until delivery. Fetal growth was compared across groups by using intention-to-treat analysis. The primary outcome was birth length., Results: This analysis included 1057 women (IFA = 349, MMN = 354, LNS = 354). Groups did not differ significantly in mean birth length, length-for-age z score (LAZ), head circumference, or percentage low birth length but differed in mean birth weight (P = 0.044), weight-for-age z score (WAZ; P = 0.046), and BMI-for-age z score (BMIZ; P = 0.040), with a trend toward differences in low birth weight (P = 0.069). In pairwise comparisons, the LNS group had greater mean birth weight (+85 g; P = 0.040), WAZ (+0.19; P = 0.045), and BMIZ (+0.21; P = 0.035) and a lower risk of low birth weight (RR: 0.61, 95% CI: 0.39, 0.96; P = 0.032) than did the IFA group. The other group differences were not significant. The effect of intervention was modified by mother's parity, age, height, baseline hemoglobin, household food insecurity, and child sex, with parity being the most consistent modifier. Among primiparous women (IFA = 131; MMN = 110; LNS = 128), the LNS group had greater mean birth length (+0.91 cm; P = 0.001), LAZ (+0.47; P = 0.001), weight (+237 g; P < 0.001), WAZ (+0.56; P < 0.001), BMIZ (+0.52; P < 0.001), head circumference (0.50 cm; P = 0.017), and head circumference-for-age z score (+0.40; P = 0.022) than did the IFA group; similar differences were found when comparing the LNS and MMN groups among primiparous women, and no group differences were found among multiparous women., Conclusion: Prenatal LNS supplementation can improve fetal growth among vulnerable women in Ghana, particularly primiparous women. This trial was registered at clinicaltrials.gov as NCT00970866., (© 2015 American Society for Nutrition.)

Information is needed on zinc absorption from grain cultivars having higher zinc content. Total absorbed zinc (TAZ) from mixed diets containing high-zinc rice (HZnR), conventional rice (CR), or CR plus zinc fortificant (CR+Zn) was measured. Forty-two nonmalnourished preschool-aged children were enrolled in 1 of 2 groups. Using a crossover design, children in group A (n = 22) received for 1 d each a mixed diet containing 150 g CR or HZnR. Children in group B (n = 20) received HZnR on 1 d and CR+Zn on the other day. Fractional zinc absorption (FZA) was measured during each dietary period by using a dual-isotope tracer ratio technique; TAZ was calculated as the product of zinc intake [total dietary zinc (TDZ)] and FZA. TDZ was 3.83, 4.83, and 6.03 mg/d when the children were fed the CR, HZnR, and CR+Zn-containing diets, respectively. Mean FZA from the CR diet was greater than from the HZnR diet (25.1 vs. 20.1%, P < 0.001), and the mean FZA from the CR+Zn diet (18.8%) was less than from both the CR diet (P < 0.001) and the HZnR diet (P = 0.014). The mean TAZ was 0.96 ± 0.16, 0.97 ± 0.18, and 1.13 ± 0.20 mg/d from the CR, HZnR and CR +Zn diets, respectively. TAZ was not different for the CR and HZnR diets (P = 0.99) but was significantly greater from the CR+Zn diet compared with the other 2 diets (P < 0.001). Rice cultivars with higher zinc and/or lower phytate content are needed to increase TAZ by young children consuming this amount of rice.

We assessed the effect of daily consumption of orange-fleshed sweet potatoes (OFSP), with or without added fat, on the vitamin A (VA) status of Bangladeshi women with low initial VA status. Women (n = 30/group) received one of the following for 6 d/wk over 10 wk: 1) 0 μg retinol activity equivalents (RAE)/d as boiled white-fleshed sweet potatoes (WFSP) and a corn oil capsule, 2) 600 μg RAE/d as boiled OFSP and a corn oil capsule, 3) fried OFSP and a corn oil capsule, or 4) boiled WFSP and a retinyl palmitate capsule in addition to their home diets. Plasma concentrations of retinol and β-carotene and total body VA pool size were assessed before and after the 60-d intervention. Initial and final plasma retinol concentrations (mean ± SD) were 0.75 ± 0.18 μmol/L and 0.84 ± 0.19 μmol/L, respectively (P = 0.31); final means did not differ by group. Initial and final plasma β-carotene concentrations were 0.10 ± 00 μmol/L and 0.18 ± 0.09 μmol/L, respectively (P < 0.0001); final mean plasma β-carotene concentrations were higher in groups that received OFSP (P < 0.0001), and final mean plasma β-carotene was marginally higher in the group that received fried OFSP compared with boiled OFSP (P = 0.07). Initial and final total body VA pool sizes were 0.060 ± 0.047 mmol and 0.091 ± 0.070 mmol, respectively (P = 0.05, n = 110) and did not differ by group. Despite an increase in plasma β-carotene concentration, the impact of OFSP on VA status appears to be limited in Bangladeshi women residing in a resource-poor community.

The estimated average requirement (EAR) for vitamin A (VA) of adult males is based on the amount of dietary VA required to maintain adequate function and provide a modest liver VA reserve (0.07 μmol/g). In the present study, the paired-deuterated retinol dilution technique was used to estimate changes in VA pool size in Bangladeshi men from low-income, urban neighborhoods who had small initial VA pool sizes (0.059 ± 0.032 mmol, or 0.047 ± 0.025 μmol/g liver; n = 16). The men were supplemented for 60 d with 1 of 8 different levels of dietary VA, ranging from 100 to 2300 μg/d (2 men/dietary VA level). VA pool size was estimated before and after the supplementation period. The mean change (plus or minus) in VA pool size in the men was plotted against their corresponding levels of daily VA intake and a regression line was fit to the data. The level of intake at which the regression line crossed the x-axis (where estimates of VA pool size remained unchanged) was used as an estimate of the EAR. A VA intake of 254-400 μg/d was sufficient to maintain a small VA pool size (0.059 ± 0.032 mmol) in the Bangladeshi men, corresponding to a VA intake of 362-571 μg/d for a 70-kg U.S. man, which is lower than their current EAR of 625 μg/d. The data suggest that the paired-deuterated retinol dilution technique could be used for estimating the EAR for VA for population subgroups for which there are currently no direct estimates.

To assist with the evaluation of zinc (Zn) intervention programs, information is needed on the magnitude and velocity of response of plasma Zn concentration following changes in Zn intake. Our objective in this study was to measure plasma Zn concentration of healthy adult men before and after initiation and discontinuation of 1 of 2 dosages of Zn supplements or placebo. We conducted a randomized, double-blind, placebo-controlled trial in 58 apparently healthy males aged 19-54 y. Participants received 1 of 3 liquid supplements daily for 21 d: 10 or 20 mg Zn/d, as Zn sulfate, or placebo. Fasting plasma Zn concentrations were measured on 14 occasions before, during, and after supplementation. Data were analyzed using mixed-model ANCOVA. The plasma Zn concentration was related to day of study (P < 0.0001) and study group (P < 0.0001). Controlling for baseline concentrations, plasma Zn concentrations were consistently elevated above baseline by d 5 among individuals in both of the Zn-supplemented groups compared with those receiving placebo supplements, regardless of their initial plasma Zn concentration. There were no significant group-wise differences between those who received either 10 or 20 mg/d Zn. Plasma Zn concentrations of supplemented individuals declined following withdrawal of supplementation and within 2 wk no longer differed from those of the placebo group. Change in the plasma Zn concentration is a useful indicator to monitor compliance with, and possibly effectiveness of, Zn supplementation programs. To ensure accurate interpretation of the results, samples should be collected while the intervention is still in progress.

Background: Delayed onset of lactogenesis (OL) is most common in primiparas and increases the risk of excess neonatal weight loss, formula supplementation, and early weaning., Objective: We examined variables associated with delayed OL among first-time mothers who delivered at term and initiated breastfeeding (n = 431)., Design: We conducted in-person interviews during pregnancy and at days 0, 3, and 7 postpartum and extracted obstetric and newborn information from medical records. We defined OL as delayed if it occurred after 72 h and used chi-square analysis to examine its association with potential risk factors across 6 dimensions: 1) prenatal characteristics, 2) maternal anthropometric characteristics, 3) labor and delivery experience, 4) newborn characteristics, 5) maternal postpartum factors, and 6) infant feeding variables. We examined independent associations by using multivariable logistic regression analysis., Results: Median OL was 68.9 h postpartum; 44% of mothers experienced delayed OL. We observed significant bivariate associations between delayed OL and variables in all 6 dimensions (P < 0.05). In a multivariate model adjusted for prenatal feeding intentions, independent risk factors for delayed OL were maternal age > or =30 y, body mass index in the overweight or obese range, birth weight >3600 g, absence of nipple discomfort between 0-3 d postpartum, and infant failing to "breastfeed well" > or =2 times in the first 24 h. Postpartum edema was significant in an alternate model excluding body mass index (P < 0.05)., Conclusions: The risk factors for delayed OL are multidimensional. Public health and obstetric and maternity care interventions are needed to address what has become an alarmingly common problem among primiparas.

A survey indicated that high-dose vitamin A (HD-VA) supplements had no apparent effect on vitamin A (VA) status, assessed by serum retinol concentrations, of Zambian children lt 5 y of age. To explore possible reasons for the lack of response, we quantified absorption, retention, and urinary elimination of either a single HD-VA supplement (209.8 micromol; 60 mg) or a smaller dose of stable isotope (SI)-labeled VA (17.5 micromol; 5 mg), which was used to estimate VA pool size, in 3- to 4-y-old Zambian boys (n = 4 for each VA dose). A tracer dose of [(14)C(2)]-labeled VA (0.925 kBq; 25 nCi) was coadministered with the HD-VA supplement or SI-labeled VA, and 24-h stool and urine samples were collected for 3 and 7 consecutive days, respectively, and 24-h urine samples at 4 later time points. Accelerator MS was used to quantify (14)C in stool and urine. Estimates of absorption, retention, and the urinary elimination rate (UER) were 83.8 +/- 7.1%, 76.3 +/- 6.7%, and 1.9 +/- 0.6%/d, respectively, for the HD-VA supplement and 76.5 +/- 9.5%, 71.1 +/- 9.4%, and 1.8 +/- 1.2%/d, respectively, for the SI-labeled VA. Mean estimates of absorption, retention, and the UER did not differ by size of the VA dose administered. Estimated absorption and retention were negatively associated with reported fever (r = minus 0.83; P = 0.011). The HD-VA supplement and SI-labeled VA were adequately absorbed, retained, and utilized in apparently healthy Zambian preschool-age boys; absorption and retention may be affected by recent fever.

Background & Aims: Although abnormal hepatic methionine metabolism plays a central role in the pathogenesis of experimental alcoholic liver disease (ALD), its relationship to the risk and severity of clinical ALD is not known. The aim of this clinical study was to determine the relationship between serum levels of methionine metabolites in chronic alcoholics and the risk and pathological severity of ALD., Methods: Serum levels of liver function biochemical markers, vitamin B6, vitamin B12, folate, homocysteine, methionine, S-adenosylmethionine, S-adenosylhomocysteine, cystathionine, cysteine, alpha-aminobutyrate, glycine, serine, and dimethylglycine were measured in 40 ALD patients, of whom 24 had liver biopsies, 26 were active drinkers without liver disease, and 28 were healthy subjects., Results: Serum homocysteine was elevated in all alcoholics, whereas ALD patients had low vitamin B6 with elevated cystathionine and decreased alpha-aminobutyrate/cystathionine ratios, consistent with decreased activity of vitamin B6 dependent cystathionase. The alpha-aminobutyrate/cystathionine ratio predicted the presence of ALD, while cystathionine correlated with the stage of fibrosis in all ALD patients., Conclusions: The predictive role of the alpha-aminobutyrate/cystathionine ratio for the presence of ALD and the correlation between cystathionine serum levels with the severity of fibrosis point to the importance of the homocysteine transsulfuration pathway in ALD and may have important diagnostic and therapeutic implications., (Copyright 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Deficiencies of multiple micronutrients (MMN) usually coexist in developing countries, but supplements have usually provided only 1 or 2 micronutrients (MN). To inform policy, in this article we compared the relative benefits of supplying MMN vs. a placebo or 1 or 2 MN on the following: children's growth, health, and development; pregnancy outcome; nutritional status; and HIV/AIDS mortality and morbidity in adults. Sufficient data were available to perform random-effects meta-analyses of randomized controlled trials (RCT) for the effects of MMN on child growth and nutritional status. Results for other outcomes are presented as effect sizes (ES) when available. In children, MMN interventions resulted in small but significantly greater improvements in length or height (ES = 0.13; 95% CI: 0.055, 0.21) and weight (ES = 0.14; 95% CI: 0.029, 0.25), hemoglobin (ES = 0.39; 95% CI: 0.25, 0.53), serum zinc (ES = 0.23; 95% CI: 0.18, 0.43), serum retinol (ES = 0.33; 95% CI: 0.050, 0.61), and motor development. A Cochrane review reported that compared with no supplementation or a placebo, MMN supplementation during pregnancy reduced the relative risk of low birth weight (0.83), small-for-gestational age (0.92), and anemia (0.61); however, MMN were not more effective than iron + folic acid alone. There is some evidence that MMN supplementation improves CD4 counts and HIV-related morbidity and mortality in adults. The efficacy of MMN varies across trials, but overall there is evidence that outcomes are better than when providing < or =2 MN. The policy implications of these studies are discussed.

Background: Information is needed on the minimum energy density and feeding frequency of complementary foods that can provide adequate energy intakes (EIs) for healthy breastfed children., Objectives: The objectives of the study were to evaluate the effects of various energy densities and feeding frequencies of complementary foods on EI from these foods, breast milk consumption, and total EI from both sources., Design: During 9 separate, randomly ordered dietary periods lasting 3-6 d each, we measured intakes of food and breast milk by 18 healthy breastfed children 8-11 mo of age who, 3, 4, or 5 times/d, were fed porridge with a coded energy density of 0.5, 1.0, or 1.5 kcal/g. Food intake was measured by weighing the feeding bowl before and after meals, and breast milk intake was measured by test weighing., Results: The mean amounts of complementary foods consumed were inversely related to their energy density and positively related to the number of meals/d (P < 0.001 for both); EIs from foods were positively related to both factors. Breast milk intake decreased slightly but progressively, with greater energy density and feeding frequency of complementary foods; total EIs (kcal/d) increased in relation to both factors (P < 0.001 for both)., Conclusions: The energy density and feeding frequency of complementary foods affect infants' total daily EI and breast milk consumption. Recommendations can be developed for the appropriate combinations of these dietary factors that are compatible with adequate EI, although longer-term effects of complementary feeding practices on breast milk intake and breastfeeding duration need further community-based studies.

Background: No studies have examined the independent effects of current and longer-term dietary zinc intakes on zinc absorption., Objective: We determined the effects of current compared with longer-term zinc intake on fractional zinc absorption (FZA)., Design: We studied 9 men whose usual zinc intakes were >11 mg/d. FZA was measured at baseline, depletion (0.6 mg Zn/d for 1 wk and 4 mg Zn/d for 5 wk), and repletion (11 mg Zn/d for 4 wk with 20 mg supplemental Zn/d for first 7 d). During 2 successive days after each dietary period, subjects consumed either adequate-zinc meals (11 mg Zn/d) with a zinc stable isotope tracer for 1 d, followed by low-zinc meals (4 mg Zn/d) with zinc tracer, or vice versa. Five days after oral dosing, a zinc tracer was infused intravenously. FZA was measured with the use of a modified double isotope tracer ratio method with urine samples collected on days 5-7 and 10-12 of absorption studies., Results: Plasma and urinary zinc did not vary by dietary period. Mean FZA was greater from low-zinc meals than from adequate-zinc meals (60.9% +/- 13.8% compared with 36.1% +/- 8.9%; P < 0.0001), whereas mean total absorbed zinc was greater from adequate-zinc meals than from low-zinc meals (3.60 +/- 0.91 compared with 2.48 +/- 0.56; P < 0.0001), regardless of the longer-term dietary period., Conclusions: FZA was inversely related to current zinc intake, but there was no detectable effect of longer-term dietary zinc. If longer- term zinc intake does modify FZA, such changes are smaller than those caused by current zinc intake, or they occur only after more severe zinc depletion.

Background: Glutamate carboxypeptidase II (GCPII) encodes for intestinal folate hydrolase and brain N-acetylated alpha-linked acidic dipeptidase. Previous studies provided conflicting results on the effect of the GCPII 1561C-->T polymorphism on folate and total homocysteine (tHcy) concentrations., Objective: We aimed to determine the potential effects of 2 polymorphisms of GCPII on plasma folate and tHcy concentrations, cognition, anxiety, and depression in a large aging cohort of Norwegians enrolled in the Hordaland Homocysteine Study., Design: DNA samples were genotyped for the GCPII 1561C-->T and 484A-->G polymorphisms, and the results were linked to plasma folate and tHcy concentrations and to scores for cognition, anxiety, and depression., Results: The 2 polymorphisms were in linkage disequilibrium and were associated with concentrations of tHcy. After adjustment for covariates, persons in the CT or combined CT and TT groups of the 1561C-->T polymorphism had higher plasma folate concentrations and lower tHcy concentrations than did those in the CC group. Subjects with the TT genotype had lower Symbol Digit Modalities Test (SDMT) scores than did subjects with the CC genotype. Compared with abstainers, moderate alcohol drinkers had higher plasma folate concentrations and higher scores on the Mini Mental State Examination. However, women abstainers with the CT genotype had lower SDMT scores than did abstainers with the CC genotype or moderate drinkers with the CT genotype., Conclusions: The 1561C-->T polymorphism is associated with higher plasma folate and lower tHcy concentrations and with lower SDMT cognitive scores in women who abstain from alcohol.

The high prevalence of vitamin B-12 deficiency in many regions of the world is becoming recognized as a widespread public health problem, but it is not known to what extent this deficiency results from a low intake of the vitamin or from its malabsorption from food. In rural Kenya, where a previous study identified a high prevalence of inadequate vitamin B-12 intakes, this study examined whether plasma vitamin B-12 concentrations were associated with dietary sources of the vitamin at baseline and could be increased by supplementation with animal source foods (ASF). The 4 experimental groups in 503 school children were: 1) control (no food provided); 2) githeri (a maize and bean staple with added oil); 3) githeri + meat (githeri + minced beef); or 4) githeri + milk (githeri + milk). Feedings were isocaloric. Dietary data were collected at baseline, and biochemical data at baseline and after 1 and 2 y of feeding. Baseline plasma vitamin B-12 concentration was 193.6 +/- 105.3 pmol/L and correlated with % energy from ASF (r = 0.308, P < 0.001). The odds ratio for low plasma vitamin B-12 (<148 pmol/L), which occurred in 40% of children, was 6.28 [95% CI: 3.07-12.82] for the lowest vs. highest ASF intake tertile (P < 0.001). Feeding ASF (meat or milk) greatly reduced the prevalence of low plasma vitamin B-12 (P < 0.001). The high prevalence of low plasma vitamin B-12 concentrations in these children is predicted by a low intake of ASF, and supplemental ASF improves vitamin B-12 status.

Background: Zinc supplementation decreases morbidity from infections and increases growth of stunted children, but there is little information on functional responses to zinc delivered in fortified foods., Objective: The aim was to examine the effects of zinc fortification on the growth, morbidity from infections, and plasma zinc concentrations of young children., Design: We compared the physical growth, morbidity, and micronutrient status of 6-8-mo-old Peruvian children with initial length-for-age z score (LAZ) < -0.50 who were randomly assigned to receive one of the following treatments daily for 6 mo: 1) 30 g dry weight of an iron-fortified cereal porridge and a separate dose of an aqueous multivitamin (MV) supplement between meals (control group), 2) the same porridge and MV with 3 mg Zn added to the supplement dose (ZnSuppl group), or 3) the porridge with added zinc (150 mg/kg dry weight) and MV without zinc (ZnFort group)., Results: The children consumed a mean of 22-26 g dry porridge/d and 96% of the possible MV doses. After adjustment for small baseline differences in socioeconomic status and morbidity, no significant differences in weight or length increments were observed between the groups, even among the subset with an initial LAZ < -1.5, and no significant differences in the rates of common illnesses were observed. Mean plasma zinc concentrations decreased in the control group (-3.9 microg/dL), increased in the ZnSuppl group (4.3 microg/dL), and did not change significantly in the ZnFort group (-1.5 microg/dL; P < 0.001 for group-wise comparison)., Conclusions: Provision of additional zinc, either in an aqueous supplement or a fortified porridge, did not significantly affect the children's physical growth or morbidity from infections, possibly because they were not sufficiently growth-restricted or zinc-deficient initially or because the level of zinc intake or absorption was inadequate. Additional studies of the functional effect of zinc-fortified foods are needed in populations that are known to respond to zinc supplements.

Background: Information is needed to design studies of the effects of complementary feeding regimens on children's intakes of complementary foods (CFs) and breast milk., Objective: We evaluated the effects of varied energy density of CFs on the time until stabilization of dietary intakes and on total daily energy intakes (EIs) and breast-milk intakes., Design: CFs with low [0.4 kcal/g (LD)] and high [1.5 kcal/g (HD)] energy density were fed 3 times/d to 10 children (aged 9-18 mo) during 2 randomly assigned sequences of three 8-d diet periods (HD-LD-HD or LD-HD-LD) along with ad libitum breastfeeding. CF and breast-milk intakes were measured., Results: Intakes of the HD diet and breast milk did not vary by day of period, but intake of the LD diet increased progressively. During days 5-7 of the last 2 diet periods in each sequence, more of the LD than of the HD diet was consumed (752 +/- 252 and 439 +/- 111 g/d, respectively; P < 0.001), but EIs from CFs were greater with the HD diet. Breast-milk consumption was slightly less (192 +/- 115 and 234 +/- 121 g/d, respectively; P = 0.03) but total daily EI was greater (774 +/- 175 and 441 +/- 85 kcal/d, respectively; P < 0.001) during the HD than during the LD diet period., Conclusions: New information on the effects of newly introduced diets on daily intakes of these diets and of breast milk can be used to design future studies. Total daily EIs were greater with the HD diet despite its negative effects on breast-milk intakes.

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.

Background: It is not known whether daily consumption of vitamin A-containing foods is efficacious for treating nightblindness., Objective: We assessed the effect of supplementation with vitamin A from food or synthetic sources on dark adaptation and plasma retinol concentrations in nightblind pregnant Nepali women., Design: Nightblind pregnant women were randomly assigned to 1 of 6 treatment groups to receive 6 d/wk for 6 wk either 850 microg retinol equivalents/d as retinyl palmitate, vitamin A-fortified rice, goat liver, amaranth leaves, or carrots or 2000 microg retinol equivalents/d as retinyl palmitate. Dark adaptation was assessed weekly by using the pupillary threshold (PT) test; plasma retinol concentrations were measured before and after the intervention. These outcomes were also assessed in a comparison group of nonnightblind pregnant women., Results: In the nightblind women, the mean PT improved significantly (P<0.0001) from -0.71+/-0.04 to -1.42+/-0.02 log cd/m2, and the final mean PT did not differ significantly from that in the nonnightblind women (-1.43+/-0.04; P=0.55). Improvement in dark adaptation was greater in the liver group than in the vitamin A-fortified rice group (P<0.02). Plasma retinol concentrations increased significantly (P<0.0001) from 0.95+/-0.05 to 1.07+/-0.05 micromol/L. The plasma retinol response was greater in the higher-dose capsule and liver groups than in the vegetable groups and significantly greater in the liver group than in the vitamin A-fortified rice group (both: P<0.05)., Conclusion: Improvement in dark adaptation did not differ significantly between women who received vitamin A as liver, amaranth leaves, carrots, or retinyl palmitate.

Background: Recent evidence suggests that the vitamin A equivalency of beta-carotene from plant sources is lower than previously estimated., Objective: We assessed the effect of 60 d of daily supplementation with 750 microg retinol equivalents (RE) of either cooked, puréed sweet potatoes; cooked, puréed Indian spinach (Basella alba); or synthetic sources of vitamin A or beta-carotene on total-body vitamin A stores in Bangladeshi men., Design: Total-body vitamin A stores in Bangladeshi men (n = 14/group) were estimated by using the deuterated-retinol-dilution technique before and after 60 d of supplementation with either 0 microg RE/d (white vegetables) or 750 microg RE/d as sweet potatoes, Indian spinach, retinyl palmitate, or beta-carotene (RE = 1 microg retinol or 6 microg beta-carotene) in addition to a low-vitamin A diet providing approximately 200 microg RE/d. Mean changes in vitamin A stores in the vegetable and beta-carotene groups were compared with the mean change in the retinyl palmitate group to estimate the relative equivalency of these vitamin A sources., Results: Overall geometric mean (+/-SD) initial vitamin A stores were 0.108 +/- 0.067 mmol. Relative to the low-vitamin A control group, the estimated mean changes in vitamin A stores were 0.029 mmol for sweet potato (P = 0.21), 0.041 mmol for Indian spinach (P = 0.033), 0.065 mmol for retinyl palmitate (P < 0.001), and 0.062 mmol for beta-carotene (P < 0.002). Vitamin A equivalency factors (beta-carotene:retinol, wt:wt) were estimated as approximately 13:1 for sweet potato, approximately 10:1 for Indian spinach, and approximately 6:1 for synthetic beta-carotene., Conclusion: Daily consumption of cooked, puréed green leafy vegetables or sweet potatoes has a positive effect on vitamin A stores in populations at risk of vitamin A deficiency.

Background: Zinc supplements reduce childhood morbidity in populations in whom zinc deficiency is common. In such populations, deficiencies in other micronutrients may also occur., Objective: The objective was to determine whether the administration of other micronutrients with zinc modifies the effect of zinc supplementation on children's morbidity and physical growth., Design: Two hundred forty-six children aged 6-35 mo with persistent diarrhea were randomly assigned to 1 of 3 groups to receive a daily supplement of 10 mg Zn alone (Zn; n = 81), zinc plus vitamins and other minerals at 1-2 times recommended daily intakes (Zn+VM; n = 82), or placebo (n = 83) for approximately 6 mo after the diarrhea episode ended. Morbidity information was collected on weekdays. Weight, length, and other anthropometric indicators were measured monthly, and plasma zinc and other indicators of micronutrient status were measured at baseline and 6 mo., Results: Supplement consumption was high ( approximately 90%) in all groups, although slightly more vomiting was reported in the Zn+VM group (P < 0.0001, analysis of variance). The change in plasma zinc from baseline to 6 mo was greater in the 2 zinc groups (6.1, 27.3, and 16.2 micro g/dL in the placebo, Zn, and Zn+VM groups, respectively; P < 0.0001, analysis of variance). The Zn group had fewer episodes of diarrhea, dysentery, and respiratory illness and a lower prevalence of fever and cough than did the Zn+VM group and a lower prevalence of cough than did the placebo group (P = 0.05). No significant effects of supplementation on growth were observed., Conclusion: Morbidity was greater after supplementation with zinc plus multivitamins and minerals than it was after supplementation with zinc alone.

Background: Iron, zinc, and calcium can interact with each other in a way that inhibits their respective absorption. On the other hand, mineral fortification has been used to improve simultaneous iron and zinc absorption from food supplements., Objective: We evaluated the effect of a novel fortificant mixture consisting of NaFeEDTA, zinc methionine, ascorbic acid, and citric acid on iron and zinc absorption from a dry food supplement designed for preschool children., Design: The standard food supplement contained cereal and legume flour, dried milk, and a mixture of micronutrients including ferrous sulfate and zinc sulfate as sources of supplemental iron and zinc, respectively. Standard and novel food products were prepared as porridge with or without the addition of 200 mg Ca as calcium phosphate. Iron absorption and zinc absorption from the food products were evaluated simultaneously in 13 nonpregnant, adult women by extrinsically labeling the products with radioisotopes of iron and zinc and carrying out whole-body counting 7 d after the food products were consumed in random order., Results: The absorption of iron from the NaFeEDTA-containing (novel) food product was 1.7 times that from the ferrous sulfate-containing (standard) product (P = 0.015). There was no significant effect of dietary calcium on iron absorption. Zinc absorption was not associated with the form of zinc consumed, but higher dietary calcium was marginally associated with lower zinc absorption (P = 0.071)., Conclusions: A mixture of fortificants containing NaFeEDTA, zinc sulfate or zinc methionine, ascorbic acid, and citric acid, but without calcium, can improve iron and zinc absorption from food products. A cost-benefit analysis of the novel fortificant mixture needs to be performed.

Background: The risk of zinc deficiency in populations can be estimated by comparing serum zinc data with statistically defined lower cutoffs derived from a presumably healthy population. Serum zinc data are available from a large sample of the US population assessed during the second National Health and Nutrition Examination Survey (NHANES II). Although the original analysis of these data considered fasting status and the time of day of blood sampling, it did not account for potentially confounding variables that may affect the serum zinc concentration, such as age, sex, and health status., Objective: The objective was to describe variations in serum zinc concentration by age, sex, and other characteristics and to recommend lower cutoffs for presumably healthy persons., Design: Serum zinc data from NHANES II were analyzed by using analysis of variance and covariance models to identify and describe variables significantly associated with serum zinc concentration; 2.5th percentile curves were produced and used to establish age- and sex-based lower cutoffs., Results: Age and sex were significant confounders of serum zinc concentration, so separate lower cutoffs were derived for children and adolescent and adult males and females. Other minor confounding variables were identified. Tentative lower cutoffs for pregnancy and oral contraceptive use were also derived., Conclusions: The interpretation of population serum zinc data with the use of lower cutoffs should account for the age and sex of the subjects, pregnancy and oral contraceptive use, and fasting status and time of day of blood collection.

The essential design and quality control aspects of dietary assessment, randomized controlled trials (RCT) in developing countries and their subsequent meta-analysis are reviewed. Dietary assessment protocols consist of three stages: measurement of food intakes using a method appropriate for the study objectives, calculation of nutrient intakes and finally an evaluation of their nutrient adequacy. The latter may involve: 1) assessment of dietary diversity (average number of different foods consumed per day) and selected indices of dietary quality such as intakes of animal source foods (g/d); 2) percentage of energy from protein, fat and animal protein; 3) selected nutrient densities; and 4) dietary phytate:zinc molar ratio, as well as the prevalence of inadequate nutrient intakes calculated using a probability approach. To establish causality between the nutrient inadequacies identified and adverse health outcomes, RCT must be undertaken. A prerequisite of RCT is double-blind randomization, a procedure designed to eliminate biases arising from baseline confounding variables, unintended interventions and ascertainment bias. Results from existing RCT can be summarized via meta-analysis to gain a better understanding of the population relationship. Meta-analysis is a statistical technique involving linear models or generalized linear models, which can be performed after locating the individual studies, and selecting and abstracting all the necessary data.

Background: The deuterated-retinol-dilution technique provides a quantitative estimate of total-body vitamin A (TBVA) stores in adults. To apply the technique to children, information on plasma retinol kinetics in this age group is needed., Objectives: We described the plasma retinol kinetics of an oral dose of [(2)H(4)]retinyl acetate in a population of Peruvian children (12-24 mo of age) in order to examine the relation between TBVA stores and individual plasma isotopic ratios 3 d after the dose and to estimate 1) the time required for the isotope dose to mix with endogenous vitamin A, 2) the fractional catabolic rate for retinol, and 3) TBVA stores., Design: An oral dose of [(2)H(4)]retinyl acetate (14 micromol retinol equivalents) was administered to children (n = 107) to construct a population-level kinetic curve of the plasma ratio of [(2)H(4)]retinol to retinol to estimate equilibration time and the fractional catabolic rate. TBVA stores were estimated by using a modification of the isotope dilution equation for adults., Results: The dose of [(2)H(4)]retinyl acetate fully mixed with endogenous vitamin A 8 d after the dose. The fractional catabolic rate was 0.022/d (95% CI: 0.014, 0.030/d). Mean (+/- SD) TBVA stores were estimated as 0.097 +/- 0.081 mmol (range: 0.016-0.392 mmol). Plasma ratios of [(2)H(4)]retinol to retinol 3 d after the dose were correlated with the inverse of estimated TBVA stores (r = -0.74, P < 0.0001)., Conclusions: Compared with previous results in adults, the equilibration time occurred earlier and the estimated system fractional catabolic rate was higher in this population of children. The modified isotope dilution equation provided estimates of hepatic vitamin A concentration that are similar to values reported in US children at autopsy.

Background: Multiple studies have been carried out to assess the effect of zinc supplementation on children's growth. The results of these studies are inconsistent, and the factors responsible for these varied outcomes are unknown., Objective: Meta-analyses of randomized controlled intervention trials were therefore completed to assess the effect of zinc supplementation on the physical growth and serum zinc concentrations of prepubertal children., Design: A total of 33 acceptable studies with appropriate data were identified by MEDLINE (National Library of Medicine, Bethesda, MD) searches and other methods. Weighted mean effect sizes (expressed in SD units) were calculated for changes in height, weight, weight-for-height, and serum zinc concentration by using random-effects models; factors associated with effect sizes were explored by meta-regression techniques., Results: Zinc supplementation produced highly significant, positive responses in height and weight increments, with effect sizes of 0.350 (95% CI: 0.189, 0.511) and 0.309 (0.178, 0.439), respectively. There was no significant effect of zinc on weight-for-height indexes [weighted mean effect size: -0.018 (-0.132, 0.097)]. Zinc supplementation caused a large increase in the children's serum zinc concentrations, with an effect size of 0.820 (0.499, 1.14). Growth responses were greater in children with low initial weight-for-age z scores and in those aged >6 mo with low initial height-for-age z scores., Conclusions: Interventions to improve children's zinc nutriture should be considered in populations at risk of zinc deficiency, especially where there are elevated rates of underweight or stunting. The population mean serum zinc concentration is a useful indicator of the successful delivery and absorption of zinc supplements in children.