The Effect of Zinc Biofortified Wheat Produced via Foliar Application on Zinc Status: A Randomized, Controlled Trial in Indian Children.

BACKGROUND: Agronomic zinc biofortification of wheat by foliar application increases wheat zinc content and total zinc absorption in humans. OBJECTIVES: To assess the effect of agronomically biofortified whole wheat flour (BFW) on plasma zinc (PZC) compared with a postharvest fortified wheat (PHFW) and unfortified control wheat (CW) when integrated in a midday school meal scheme. METHODS: We conducted a 20-wk double-blind intervention trial in children (4-12 y, n = 273) individually randomly assigned to 3 groups to receive a daily school lunch consisting of 3 chapattis prepared with the 3 different wheat flour types. Measurements of anthropometry, blood biochemistry, and leukocyte DNA strand breaks were conducted. We applied sparse serial sampling to monitor PZC over time, and analysis was performed using linear mixed-effects models. RESULTS: Mean zinc content in BFW, PHFW, and CW were 48.0, 45.1, and 21.2 ppm, respectively (P < 0.001). Mean (standard deviation) daily zinc intakes in the study intervention in BFW, PHFW, and CW groups were 4.4 (1.6), 5.9 (1.9) and 2.6 (0.6) mg Zn/d, respectively, with intake in groups PHFW and BFW differing from CW (P < 0.001) but no difference between BFW and PHFW. There were no time effect, group difference, or group × time interaction in PZC. Prevalence of zinc deficiency decreased in the BFW (from 14.1%-11.2%), PHFW (from 8.9%-2.3%), and CW (9.8%-8.8%) groups, but there was no time × treatment interaction in the prevalence of zinc deficiency (P = 0.191). Compliance with consuming the study school meals was associated with PZC (P = 0.006). DNA strand breaks were not significantly associated with PZC (n = 51; r = 0.004, P = 0.945). CONCLUSIONS: Consumption of either PHFW or BFW provided an additional ∼1.8 to 3.3 mg Zn/d, but it did not affect PZC or zinc deficiency, growth, or DNA strand breaks. This trial was registered on clinicaltrials.gov as NCT02241330 and ctri.nic.in as CTRI/2015/06/005913.

The Molecular Basis for Zinc Bioavailability.

Zinc is an essential micronutrient, and its deficiency is perhaps the most prevalent and least understood worldwide. Recent advances have expanded the understanding of zinc's unique chemistry and molecular roles in a vast array of critical functions. However, beyond the concept of zinc absorption, few studies have explored the molecular basis of zinc bioavailability that determines the proportion of dietary zinc utilized in zinc-dependent processes in the body. The purpose of this review is to merge the concepts of zinc molecular biology and bioavailability with a focus on the molecular determinants of zinc luminal availability, absorption, transport, and utilization.

Marginal Zinc Deficiency Alters Essential Fatty Acid Metabolism in Healthy Men.

BACKGROUND: Rice biofortification with Zinc (Zn) can improve the Zn status of rice-consuming populations. However, the metabolic impact in humans consuming Zn-biofortified rice is unknown. OBJECTIVES: To determine the effects of Zn-biofortified rice on lipid metabolism in normolipidemic men. METHODS: The men consumed a rice-based diet containing 6 mg Zn/d and 1.5 g phytate (phytate/Zn ratio = 44) for 2 wk followed by a 10-mg Zn/d diet without phytate for 4 wk. An ad libitum diet supplemented with 25 mg Zn/d was then fed for 3 wk. Fasting blood samples were taken at baseline and at the end of each metabolic period for measuring plasma zinc, glucose, insulin, triglyceride (TG), LDL and HDL cholesterol, fatty acids, oxylipins, and fatty acid desaturase activities. Statistical differences were assessed by linear mixed model. RESULTS: Fatty acid desaturase (FADS) 1 activity decreased by 29.1% (P = 0.007) when the 6-mg Zn/d diet was consumed for 2 wk. This change was associated with significant decreases in HDL and LDL cholesterol. The alterations in FADS1, HDL cholesterol, and TG remained unchanged when Zn intakes were increased to 10 mg/d for 4 wk. Supplementation with 25 mg Zn/d for 3 wk normalized these metabolic changes and significantly increased LDL cholesterol at the end of this metabolic period compared with baseline. FADS1 activity was inversely correlated with FADS2 (rmcorr = -0.52; P = 0.001) and TG (rmcorr = -0.55; P = 0.001) at all time points. CONCLUSIONS: A low-zinc, high-phytate rice-based diet reduced plasma HDL cholesterol concentrations and altered fatty acid profiles in healthy men within 2 wk. Consuming 10 mg Zn/d without phytate for 4 wk did not improve the lipid profiles, but a 25-mg Zn/d supplement corrects these alterations in lipid metabolism within 3 wk.

Changes in Visceral and Ectopic Adipose Tissue Stores Across Pregnancy and Their Relationship to Gestational Weight Gain.

BACKGROUND: Excessive gestational weight gain has been associated with increased total body fat (TBF), metabolic syndrome, and abdominal obesity. However, little is known about the relationship of gestational weight gain with changes in metabolically active visceral or ectopic (hepatic and skeletal muscle) lipid stores. OBJECTIVES: In a prospective study of 50 healthy, pregnant women, we assessed whether changes in weight were associated with changes in total, visceral, and ectopic lipid stores. METHODS: Participants (ages 19-39) were primarily White (84%). The mean preconception BMI was 25.8 kg/m2 (SD, 4.5 kg/m2; min-max, 17.1-35.9 kg/m2). Measurements were completed at visits 1 and 2 at means of 16 and 34 weeks gestation, respectively, and included TBF using BOD POD; abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) using MRI; and intrahepatic lipids (IHL), intramyocellular lipids (IMCL), and extramyocellular lipids (EMCL) using magnetic resonance spectroscopy. We used paired t-tests to examine changes in adipose tissue and Pearson's correlation to examine associations of adipose tissue changes and weight changes. We also examined whether changes in adipose tissue stores differed by preconception BMI (normal, overweight, and obese), using 1-way ANOVA. RESULTS: The TBF (mean change, +3.5 kg; 95% CI: 2.4-4.6 kg), SAT (mean change, +701 cm3; 95% CI: 421-981 cm3), VAT (mean change, +275 cm3; 95% CI: 170-379 cm3), and IHL (percentage water peak; median, +0.15; IQR = -0.01 to 0.32) values increased significantly; the IMCL and EMCL values did not change. Changes varied by BMI strata, with the least increase (or, for SAT, net loss) among women with obesity. Weight change was positively correlated with changes in TBF (r = 0.83; P < 0.001), SAT (r = 0.74; P < 0.001), and VAT (r = 0.63; P < 0.001) but not significantly correlated with changes in ectopic lipids (IHL, IMCL, and EMCL; -0.14 < r < 0.26). CONCLUSIONS: Preferential deposition of adipose tissue to the viscera in pregnancy, as seen in our sample, could serve an important metabolic function; however, excessive deposition in this region could negatively affect maternal health.

Different Doses, Forms, and Frequencies of Zinc Supplementation for the Prevention of Diarrhea and Promotion of Linear Growth among Young Bangladeshi Children: A Six-Arm, Randomized, Community-Based Efficacy Trial.

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.

Zinc Kinetics Correlate With Length-for-Age z Scores in Bangladeshi Infants.

OBJECTIVES: Stunting [length-for-age z score (LAZ) <-2] has multiple causes and is prevalent in areas with low dietary zinc (Zn) intake. Zinc kinetics from non-stunted infants were used in a published model for predicting linear growth; here, we directly measure zinc kinetics in stunted infants. METHODS: Zinc kinetics were determined in 9-month-old Bangladeshi infants (n = 10), who were non-wasted [weight-for-length z score (WLZ) > -2], ranging in LAZ from -2.9 to -0.43. Stable isotopes were administered 2 hours after a meal as oral ( 70 Zn) and intravenous ( 67 Zn) tracers. After isotope administration, blood was sampled within 5 hours and all urine and feces were collected for 24 hours. Urine was sampled twice-daily out to 9 days. Data were analyzed by compartmental modeling. Daily zinc intake was estimated by the model as the sum of zinc used for growth plus that lost via urine and feces. Zinc absorbed (the amount required to maintain steady state) was the sum of zinc used for growth plus urine and endogenous fecal excretions. RESULTS: The LAZ score correlated with serum zinc concentration ( R = 0.77, P = 0.001), urinary zinc excretion ( R = 0.66, P = 0.010), and fractional zinc absorption from calculated daily intake ( R = 0.58, P = 0.030). In stunted infants (n = 8), the amount of zinc absorbed did not increase with calculated zinc intake unlike published values for non-stunted infants. CONCLUSIONS: Zinc kinetics in Bangladeshi infants correlate with LAZ and show that malabsorption of supplemental sources of zinc may occur in stunted infants.

Zinc Supplements Taken with Food Increase Essential Fatty Acid Desaturation Indices in Adult Men Compared with Zinc Taken in the Fasted State.

BACKGROUND: Zinc intake is associated with reduced risk of metabolic disease in adults, possibly due in part to zinc's role in essential fatty acid (EFA) desaturation. Although plasma zinc is the accepted indicator of zinc status, product-to-precursor activity indices of fatty acid desaturase (FADS) 1 and 2 have also been proposed as response indicators for changes in zinc intake. OBJECTIVES: To examine zinc supplement effects on plasma zinc concentration (PZC) and estimated FADS 1 and 2 activities, when zinc supplements are taken with food compared with fasted. METHODS: Apparently healthy adult men were randomly allocated to take 25 mg zinc as zinc gluconate either in the fasted state 30 min before breakfast [zinc before breakfast (ZBB)] or with breakfast [zinc with breakfast (ZWB)] daily for 13 d. Fasting PZC was measured by inductively coupled plasma optical emission spectrometry. Selected EFAs for FADS activity indices were measured by LC-MS/MS at study baseline and end. RESULTS: A total of 35 men completed the study (ZBB, n = 18; ZWB, n = 17). Mean ± SEM PZC was 86.2 ± 1.64 µg/dL at baseline. After 2 wk of zinc supplementation, the PZCs were 18% higher in the ZBB compared with the ZWB groups (105 ± 5.88 compared with 88.7 ± 2.36 µg/dL, P = < 0.05). However, the geometric mean (95% CI) FADS1 activity indices were 15% higher in the ZWB than the ZBB participants, 6.45 (5.84, 7.13) compared with 5.57 (5.05, 6.14), P < 0.05. CONCLUSIONS: These data demonstrate a lack of congruence between the effects of zinc supplements on PZC and EFA metabolism in response to whether a zinc supplement is taken with or without food. Additional research is needed to determine how absorbed zinc may be directed differently toward metabolic processes, when coabsorbed with food. This trial was registered at clinicaltrials.gov as NCT03619421.

Zinc-Biofortified Wheat Intake and Zinc Status Biomarkers in Men: Randomized Controlled Trial.

BACKGROUND: Biofortification is a novel method for improving the nutritional value of grains. Wheat is widely consumed worldwide. Thus, wheat zinc biofortification may improve the zinc status of populations. OBJECTIVES: We determined the effect of consuming zinc-biofortified wheat on plasma zinc concentrations and biomarkers of zinc-dependent functions in a controlled feeding study. METHODS: Thirty-six healthy adult men, aged 18 to 51 y, participated in a 10-wk zinc-controlled feeding trial. After a 2-wk run-in period [metabolic period (MP) 1] (9.3 mg zinc/d and 2.1 g total phytate/d) to standardize zinc status, the participants consumed bread made from zinc-biofortified wheat (10.9 mg zinc/d) with no additional phytate (0.6 g/d total phytate) for 6 wk (MP2). During the final 2 wk (MP3), half of the men took a 25-mg zinc supplement daily to determine if the supplement further altered zinc status biomarkers. Repeated-measures linear regression methods were used to compare plasma zinc concentrations, fatty acid desaturase (FADS) activities, glutathione (GSH) concentrations, and DNA strand breaks assessed at enrollment and the end of each metabolic period. RESULTS: Plasma zinc concentrations did not change throughout the study. From the end of MP1 to the end of MP2, the conversion of linoleic acid to γ-linolenic acid (FADS2 activity) increased from 0.020 to 0.025 (P = 0.02), and the conversion of dihomo-γ-linolenic acid to arachidonic acid (FADS1 activity) decreased from 6.37 to 5.53 (P = 0.01). GSH concentrations and DNA strand breaks did not change. Zinc supplementation (25 mg/d) in MP3 did not alter any of the endpoints. CONCLUSIONS: In healthy adult men, a 1.6-mg/d increase in dietary zinc from biofortified wheat modified FADS2 and FADS1 activities without changing DNA damage, plasma zinc, or GSH concentrations, demonstrating that FADS activities are more sensitive to small changes in zinc consumed with a meal. This trial was registered at clinicaltrials.gov as NCT03451214.

Maintaining Balance.

Writing this biography forced me to look back over my career as a scientist, teacher, wife, and mother. To my surprise, a lifelong theme emerged that I was unaware of, that is, the role of maintaining balance between work and family, science and teaching, mentorship and administration, and personal values and challenges. My primary mentor, Dr. Doris Calloway, demonstrated the importance of maintaining balance. My interest in nutrition started as a preschooler living on a farm where I learned firsthand the importance of balancing the expense of providing good nutrition to the livestock with potential income. In our small high school, I became acquainted with the fascinating field of chemistry, but found it critical to balance that interest with a politically correct field of study for a woman in the early 1960s. I chose dietetics for its strong roots in chemistry. As a US Army dietitian, I learned firsthand how to conduct metabolic studies and knew, immediately, that I had to balance that interest with future opportunities feasible for a dietitian. I chose the University of California, Berkeley, for my PhD because it needed to train dietitians in research to balance an emerging need to offer undergraduates a practicum in dietetics. My subsequent faculty appointment there enabled me to develop novel isotopic approaches for studying zinc and prenatal nutrition, and balance my research with teaching and administrative responsibilities. During the next 40 years, my work as a Berkeley professor led to appointments at the Western Human Nutrition Research Center and Children's Hospital Oakland Research Institute, while balancing my responsibilities as a wife and a mother to my two sons. Balance is defined as a condition in which different elements are equal or in the correct proportions. It is extremely satisfying to look back and see evidence of successfully balancing the disparate elements of my career.

More Nutrition Precision, Better Decisions for the Health of Our Nation.

Nutritional science is evolving to an enhanced emphasis on recent scientific and technological advancements supporting a transition to precision nutrition as a strategy for disease prevention and management across populations. The complexity of chronic disease, which afflicts 6 in 10 adult Americans, is highlighted in the diet-disease relation where it is apparent that there is no "one size fits all" approach to disease management. Precision nutrition is the study of how individuals respond differently to food and nutrients, and it leads to personalized or classified, evidence-based guidelines that represent the best approach for fighting chronic disease. Enhanced resources are imperative as we transition to a precision nutrition approach that will transform agriculture and nutritional science to support positive health outcomes. Both the USDA and the NIH recognize the need to prioritize research and funding on precision nutrition. Increased federal investment in this realm is critical as we look ahead; it will help lower health care costs, while supporting individual health and quality of life.

Predictors of the Size of the Exchangeable Zinc Pool Differ between Children and Adults.

BACKGROUND: The size of the rapidly exchanging pool of body zinc has been suggested as having potential utility as a biomarker of zinc status. Knowledge of the relations of exchangeable zinc pool (EZP) size to relevant variables is necessary to adequately evaluate its use as a biomarker. OBJECTIVE: We used regression analysis to investigate associations of EZP with age, sex, body size, and zinc nutrition variables. METHODS: Data were compiled from 18 isotope tracer studies of zinc absorption in 247 children and adults (248 observations) in which EZP and relevant variables (e.g., weight, age, absorbed zinc) were measured. Linear regression analyses were performed separately on data from adults and children. RESULTS: In children, EZP was most strongly associated with weight (r = 0.78). The best-fitting regression models of EZP (R2 ≥ 0.68) had weight or age and weight-for-age z score as predictors. Other variables had little effect on EZP when controlling for weight. Absorbed zinc was observed to be a predictor of EZP only in zinc intervention trials of infants. The mean EZP/wt was 4 mg/kg between 8 and 120 mo of age. In adults, EZP was observed to vary in a complex manner with (in order of importance) age, absorbed zinc, weight, sex, and plasma zinc concentration. EZP data from zinc-deprived subjects were lower than the 95% prediction interval of a model of normative data. CONCLUSIONS: EZP was observed to maintain a constant size relative to weight and was influenced only slightly by other factors in children. In contrast, EZP in adults varied with several factors, including absorbed zinc, and was statistically smaller in zinc-deprived individuals. The findings suggest that EZP may have utility as an indicator of zinc status in adults, but there is less evidence for this in children. Additional data are needed to reach a definitive conclusion.

Identification of a Hemolysis Threshold That Increases Plasma and Serum Zinc Concentration.

Background: Plasma or serum zinc concentration (PZC or SZC) is the primary measure of zinc status, but accurate sampling requires controlling for hemolysis to prevent leakage of zinc from erythrocytes. It is not established how much hemolysis can occur without changing PZC/SZC concentrations.Objective: This study determines a guideline for the level of hemolysis that can significantly elevate PZC/SZC.Methods: The effect of hemolysis on PZC/SZC was estimated by using standard hematologic variables and mineral content. The calculated hemolysis threshold was then compared with results from an in vitro study and a population survey. Hemolysis was assessed by hemoglobin and iron concentrations, direct spectrophotometry, and visual assessment of the plasma or serum. Zinc and iron concentrations were determined by inductively coupled plasma spectrometry.Results: A 5% increase in PZC/SZC was calculated to result from the lysis of 1.15% of the erythrocytes in whole blood, corresponding to ∼1 g hemoglobin/L added into the plasma or serum. Similarly, the addition of simulated hemolysate to control plasma in vitro caused a 5% increase in PZC when hemoglobin concentrations reached 1.18 ± 0.10 g/L. In addition, serum samples from a population nutritional survey were scored for hemolysis and analyzed for changes in SZC; samples with hemolysis in the range of 1-2.5 g hemoglobin/L showed an estimated increase in SZC of 6% compared with nonhemolyzed samples. Each approach indicated that a 5% increase in PZC/SZC occurs at ∼1 g hemoglobin/L in plasma or serum. This concentration of hemoglobin can be readily identified directly by chemical hemoglobin assays or indirectly by direct spectrophotometry or matching to a color scale.Conclusions: A threshold of 1 g hemoglobin/L is recommended for PZC/SZC measurements to avoid increases in zinc caused by hemolysis. The use of this threshold may improve zinc assessment for monitoring zinc status and nutritional interventions.

An Animal-Source Food Supplement Increases Micronutrient Intakes and Iron Status among Reproductive-Age Women in Rural Vietnam.

Background: Few studies have examined the impact of local animal-source foods (ASFs) on the nutritional status of reproductive-age women in developing countries.Objective: We hypothesized that a midmorning snack of local ASF for 6 mo would reduce dietary micronutrient deficiencies [usual intake less than the estimated average requirement (EAR)] and improve blood biomarkers of iron, zinc, and vitamins A and B-12 status among nonpregnant, reproductive-age women in rural Vietnam.Methods: One hundred seventeen women, 18-30 y old, were randomly assigned to receive either an ASF (mean: 144 kcal, 8.9 mg Fe, 2.7 mg Zn, 1050 µg retinoic acid equivalent vitamin A, and 5.5 µg vitamin B-12) or a control snack (mean: 150 kcal, 2.0 mg Fe, 0.9 mg Zn, 0 µg retinoic acid equivalent vitamin A, and 0 µg vitamin B-12) 5 d/wk for 6 mo. Usual nutrient intakes were estimated by repeated 24-h dietary recalls. Blood samples were collected at baseline and 3 and 6 mo. Because of the relation between nutritional status and inflammation, serum C-reactive protein, α-1-acid-glycoprotein, and urinary tract infections (UTIs) were also monitored.Results: Eighty-nine women (47 in the ASF group and 42 controls) completed the study. In the ASF group, intakes of iron and vitamins A and B-12 below the EAR were eliminated, and the prevalence of a low zinc intake was reduced to 9.6% compared with 64.7% in controls (P < 0.001). At 6 mo, a modest increase (P < 0.05) in hemoglobin and iron status occurred in the ASF group compared with the control group, but plasma zinc, retinol, and serum vitamin B-12 concentrations did not differ. UTI relative risk was 3.9 (P < 0.05) among women assigned to the ASF group who had a low whole-body iron status at baseline.Conclusions: Adding a small amount of locally produced ASF to the diets of reproductive-age Vietnamese women improved micronutrient intakes and iron status. However, the increased UTI incidence in women in the ASF group with initially lower iron stores warrants further investigation.

A Summary of Pathways or Mechanisms Linking Preconception Maternal Nutrition with Birth Outcomes.

Population, human, animal, tissue, and molecular studies show collectively and consistently that maternal nutrition in the pre- or periconception period influences fetal growth and development, which subsequently affects the individual's long-term health. It is known that nutrition during pregnancy is an important determinant of the offspring's growth and health. However, now there is evidence that the mother's nutritional status at conception also influences pregnancy outcome and long-term health. For example, the mother's nutritional status at conception influences the way energy is partitioned between maternal and fetal needs. Furthermore, placental development during the first weeks of gestation reflects maternal nutrition and establishes mechanisms for balancing maternal and fetal nutritional needs. Also, maternal nutritional signals at fertilization influence epigenetic remodeling of fetal genes. These findings all indicate that maternal parenting begins before conception. The following papers from a symposium on preconception nutrition presented at the 2015 Scientific Sessions and Annual Meeting of the ASN emphasize the importance of maternal nutrition at conception on the growth and long-term health of the child.

Biomarkers of Nutrition for Development (BOND)-Zinc Review.

Zinc is required for multiple metabolic processes as a structural, regulatory, or catalytic ion. Cellular, tissue, and whole-body zinc homeostasis is tightly controlled to sustain metabolic functions over a wide range of zinc intakes, making it difficult to assess zinc insufficiency or excess. The BOND (Biomarkers of Nutrition for Development) Zinc Expert Panel recommends 3 measurements for estimating zinc status: dietary zinc intake, plasma zinc concentration (PZC), and height-for-age of growing infants and children. The amount of dietary zinc potentially available for absorption, which requires an estimate of dietary zinc and phytate, can be used to identify individuals and populations at risk of zinc deficiency. PZCs respond to severe dietary zinc restriction and to zinc supplementation; they also change with shifts in whole-body zinc balance and clinical signs of zinc deficiency. PZC cutoffs are available to identify individuals and populations at risk of zinc deficiency. However, there are limitations in using the PZC to assess zinc status. PZCs respond less to additional zinc provided in food than to a supplement administered between meals, there is considerable interindividual variability in PZCs with changes in dietary zinc, and PZCs are influenced by recent meal consumption, the time of day, inflammation, and certain drugs and hormones. Insufficient data are available on hair, urinary, nail, and blood cell zinc responses to changes in dietary zinc to recommend these biomarkers for assessing zinc status. Of the potential functional indicators of zinc, growth is the only one that is recommended. Because pharmacologic zinc doses are unlikely to enhance growth, a growth response to supplemental zinc is interpreted as indicating pre-existing zinc deficiency. Other functional indicators reviewed but not recommended for assessing zinc nutrition in clinical or field settings because of insufficient information are the activity or amounts of zinc-dependent enzymes and proteins and biomarkers of oxidative stress, inflammation, or DNA damage.

Acute changes in cellular zinc alters zinc uptake rates prior to zinc transporter gene expression in Jurkat cells.

A coordinated network of zinc transporters and binding proteins tightly regulate cellular zinc levels. Canonical responses to zinc availability are thought to be mediated by changes in gene expression of key zinc transporters. We investigated the temporal relationships of actual zinc uptake with patterns of gene expression in membrane-bound zinc transporters in the human immortalized T lymphocyte Jurkat cell line. Cellular zinc levels were elevated or reduced with exogenous zinc sulfate or N,N,N',N-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), respectively. Excess zinc resulted in a rapid 44 % decrease in the rate of zinc uptake within 10 min. After 120 min, the expression of metallothionein (positive control) increased, as well as the zinc exporter, ZnT1; however, the expression of zinc importers did not change during this time period. Zinc chelation with TPEN resulted in a rapid twofold increase in the rate of zinc uptake within 10 min. After 120 min, the expression of ZnT1 decreased, while again the expression of zinc importers did not change. Overall, zinc transporter gene expression kinetics did not match actual changes in cellular zinc uptake with exogenous zinc or TPEN treatments. This suggests zinc transporter regulation may be the initial response to changes in zinc within Jurkat cells.

Development of a plasma zinc concentration cutoff to identify individuals with severe zinc deficiency based on results from adults undergoing experimental severe dietary zinc restriction and individuals with acrodermatitis enteropathica.

Plasma zinc concentration (PZC) is a recommended biomarker to assess zinc status and the risk of zinc deficiency in populations. However, the relation between PZC and clinical signs of zinc deficiency remains uncertain. These analyses were conducted to evaluate the relation between PZC and clinical signs of zinc deficiency and to determine a cutoff for PZC below which individuals would have an increased likelihood of having clinical signs associated with zinc deficiency. Electronic bibliographic searches were conducted of literature indexed in PubMed, Embase, CINAHL Plus, and EBSCO and related to experimental zinc depletion studies in adults and case reports in children and adults (ages <1 mo-43 y) with acrodermatitis enteropathica (AE). Data extracted included demographic characteristics, PZCs, and the presence or absence of clinical signs likely associated with zinc deficiency (e.g., dermatitis, diarrhea). Mean PZC was significantly lower among adults consuming severely zinc-restricted diets (<1 mg Zn/d) who developed clinical signs compared with those who remained asymptomatic (36.0 ± 16.8 vs. 67.9 ± 13.3 µg/dL, P < 0.034). Likewise, patients with AE had a lower mean PZC when symptomatic compared with post-treatment PZC when they were asymptomatic (38.2 ± 20.7 vs. 102 ± 34.7 µg/dL, P < 0.01). Among individuals with restricted dietary zinc intake, PZC predicted clinical signs with 82% sensitivity and 92% specificity when using a cutoff of 50 µg/dL. Among individuals with AE, PZC predicted clinical signs with 80% sensitivity and 89% specificity when applying a cutoff of 50 µg/dL. These analyses demonstrate a clear relation between PZC and the presence of clinical signs associated with zinc deficiency among presumably healthy individuals undergoing periods of dietary zinc restriction, as well as in individuals with AE, further validating the usefulness of PZC as a biomarker of severe zinc deficiency.

Effect of animal-source food supplement prior to and during pregnancy on birthweight and prematurity in rural Vietnam: a brief study description.

BACKGROUND: Maternal nutritional status is an important predictor of infant birthweight. Most previous attempts to improve birthweight through multiple micronutrient supplementation have been initiated after women are pregnant. Interventions to improve maternal nutritional status prior to conception may be more effective in preventing low birthweight and improving other infant health outcomes. OBJECTIVE: To compare the effects of maternal supplementation with animal-source food from preconception to term or from mid-gestation to term with routine prenatal care on birthweight, the prevalence of preterm births, intrauterine growth restriction, and infant growth during the first 12 months of life and on maternal nutrient status and the incidence of maternal and infant infections. METHODS: Young women from 29 rural communes in northwestern Vietnam were recruited when they registered to marry and were randomized to one of three interventions: animal-source food supplement 5 days per week from marriage to term (approximately 13 months), animal-source food supplement 5 days per week from 16 weeks of gestation to term (approximately 5 months), or routine prenatal care without supplementalfeeding. Data on infant birthweight and gestational age, maternal and infant anthropometry, micronutrient status, and infections in the infant and mother were collected at various time points. RESULTS: In a preliminary study of women of reproductive age in this area of Vietnam, 40% of the women were underweight (body mass index < 18.5) and anemic. About 50% had infections. Rice was the dietary staple, and nutrient-rich, animal-source foods were rarely consumed by women. Iron, zinc, vitamin A, folate, and vitamin B12 intakes were inadequate in about 40% of the women. The study is still ongoing, and further data are not yet available. CONCLUSIONS: The results of this study will provide important data regarding whether improved intake of micronutrient-rich animal-source foods that are locally available and affordable before and during pregnancy improves maternal and infant health and development. This food-based approach may have global implications regarding how and when to initiate sustainable nutritional interventions to improve maternal and infant health.

Pregnancy glycemia in Mexican-American women without diabetes or gestational diabetes and programming for childhood obesity.

In the present study, we estimated the association between pregnancy glucose levels and offspring body mass index (BMI) z scores at 2, 3.5, 5, and 7 years of age, as well as z score trajectories across this age range, among Mexican-American women without diabetes or gestational diabetes. Beginning in 1999-2000, the Center for the Health Assessment of Mothers and Children of Salinas prospectively followed women from Monterey County, California (52 obese and 214 nonobese women) and their children. Plasma glucose values obtained 1 hour after a 50-g oral glucose load comprised the exposure. Offspring BMIs were compared with national data to calculate z scores. Increasing pregnancy glucose levels were associated with increased offspring BMI z scores at 7 years of age; a 1-mmol/L increase in glucose corresponded to an increase of 0.11 (standard deviation = 0.044) z-score units (P < 0.05). In nonobese women only, the mean z score over this age range increased with increasing glucose levels. The average BMI z score at 4.5 years of age increased by 0.12 (standard error, 0.059) units for each 1-mmol/L increase in glucose (P = 0.04). In obese women only, increasing glucose was associated with increases in BMI z score over time (P = 0.07). Whether interventions to reduce glucose values in women free of disease could mitigate childhood obesity remains unknown.