Effects of Different Doses, Forms, and Frequencies of Zinc Supplementation on Biomarkers of Iron and Zinc Status among Young Children in Dhaka, Bangladesh.

Young children in resource-constrained settings are susceptible to zinc deficiency and its deleterious health effects. The objective of this secondary analysis was to evaluate the effects of the following six interventions on biomarkers of iron and zinc status among a subgroup of young children in Dhaka, Bangladesh, who participated in the Zinc in Powders Trial (ZiPT): (1) standard micronutrient powders (MNPs) containing 4.1 mg zinc and 10 mg iron, daily; (2) high-zinc (10 mg) and low-iron (6 mg) (HiZn LoFe) MNP, daily; (3) HiZn (10 mg) and LoFe (6 mg)/HiZn (10 mg) and no-iron MNPs on alternating days; (4) dispersible zinc tablet (10 mg), daily; (5) dispersible zinc tablet (10 mg), daily for 2 weeks at enrollment and at 12 weeks; (6) placebo powder, daily. At the end of the 24 week intervention period, children in the daily dispersible zinc tablet group exhibited a mean serum zinc concentration (SZC) of 92.5 µg/dL, which was significantly higher than all other groups except the HiZn LoFe MNP alternating group (81.3 µg/dL). MNPs containing 10 mg and 6 mg of iron had a similar impact on biomarkers of iron status, with no evidence of an adverse interaction with zinc.

Competing paradigms of obesity pathogenesis: energy balance versus carbohydrate-insulin models.

The obesity pandemic continues unabated despite a persistent public health campaign to decrease energy intake ("eat less") and increase energy expenditure ("move more"). One explanation for this failure is that the current approach, based on the notion of energy balance, has not been adequately embraced by the public. Another possibility is that this approach rests on an erroneous paradigm. A new formulation of the energy balance model (EBM), like prior versions, considers overeating (energy intake > expenditure) the primary cause of obesity, incorporating an emphasis on "complex endocrine, metabolic, and nervous system signals" that control food intake below conscious level. This model attributes rising obesity prevalence to inexpensive, convenient, energy-dense, "ultra-processed" foods high in fat and sugar. An alternative view, the carbohydrate-insulin model (CIM), proposes that hormonal responses to highly processed carbohydrates shift energy partitioning toward deposition in adipose tissue, leaving fewer calories available for the body's metabolic needs. Thus, increasing adiposity causes overeating to compensate for the sequestered calories. Here, we highlight robust contrasts in how the EBM and CIM view obesity pathophysiology and consider deficiencies in the EBM that impede paradigm testing and refinement. Rectifying these deficiencies should assume priority, as a constructive paradigm clash is needed to resolve long-standing scientific controversies and inform the design of new models to guide prevention and treatment. Nevertheless, public health action need not await resolution of this debate, as both models target processed carbohydrates as major drivers of obesity.

Implications of phytate in plant-based foods for iron and zinc bioavailability, setting dietary requirements, and formulating programs and policies.

Plant-based diets in low-income countries (LICs) have a high content of phytic acid (myo-inositol hexaphosphate [InsP6]) and associated magnesium, potassium, and calcium salts. Together, InsP6 acid and its salts are termed "phytate" and are potent inhibitors of iron and zinc absorption. Traditional food processing can reduce the InsP6 content through loss of water-soluble phytate or through phytase hydrolysis to lower myo-inositol phosphate forms that no longer inhibit iron and zinc absorption. Hence, some processing practices can reduce the need for high-dose iron fortificants in plant-based diets and alleviate safety concerns. Dietary phytate-to-iron and phytate-to-zinc molar ratios are used to estimate iron and zinc bioavailability and to identify dietary iron and zinc requirements according to diet type. The European Food Safety Authority has set adult dietary zinc requirements for 4 levels of phytate intake, highlighting the urgent need for phytate food composition data. Such data will improve the ability to estimate the prevalence of inadequate zinc intakes in vulnerable groups in LICs, which will facilitate implementation of targeted policies to alleviate zinc deficiency.

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.

Zinc homeostasis in pediatric critical illness.

OBJECTIVE: We explored the hypothesis that marked decline in plasma zinc concentrations among critically ill children is related to shifts in metallothionein expression and inflammation. DESIGN: Prospective pilot study. SETTING: Intensive care unit of tertiary care children's hospital. PATIENTS: All children (<18 yrs) with unadjusted Pediatric Risk of Mortality III score >5 or at least one organ failure admitted to the pediatric intensive care unit from March through August 2006 were eligible for enrollment. INTERVENTIONS: After consent, blood samples were collected on days 1 and 3 of illness and analyzed for serum chemistries, plasma zinc and copper levels, metallothionein isoform expression, and cytokine levels. MEASUREMENTS AND MAIN RESULTS: Twenty patients were enrolled, with median age of 2.9 yrs (interquartile range, 0.7-10.1). Male to female ratio was 1.2:1. All patients had low zinc levels (mean, 0.43; range, 0.26-0.66 mug/dL) on day 1 of pediatric intensive care unit admission, and remained low (mean, 0.51; range, 0.26-0.81 mug/dL) on day 3, even when corrected for hypoalbuminemia. In comparison, serum copper levels were normal. On day 1, there was a positive correlation between zinc levels and expression of MT-1A (p < 0.01), MT-1G (p = 0.02), and MT-1H (p = 0.03). Plasma zinc levels correlated inversely with C-reactive protein levels (r = -.75, p = 0.01) and interleukin-6 levels (r = -.53, p = 0.04) on day 3. On day 3, patients with two or more organ failures had significantly lower plasma zinc concentrations compared with patients with

Daily supplementation with iron increases lipid peroxidation in young women with low iron stores.

The aim of this study was to determine whether women with low iron stores (plasma ferritin

Use of serum zinc concentration as an indicator of population zinc status.

Assessing the prevalence and severity of zinc deficiency in populations is critical to determine the need for and appropriate targeting of zinc intervention programs and to assess their effectiveness for improving the health and well-being of high-risk populations. However, there is very little information on the zinc status of populations worldwide due to the lack of consensus on appropriate biochemical indicators of zinc status. The objective of this review was to evaluate the use of serum zinc concentration as an indicator of population zinc status. We have reviewed the response of serum zinc concentration to dietary zinc restriction and zinc supplementation. In addition, we completed pooled analyses of nine zinc intervention trials in young children to assess the relations between serum zinc concentration of individuals before treatment and their responses to zinc supplementation. Also, in updated combined analyses of previously published data, we investigated the relation between the mean initial serum zinc concentration of a study population and their mean growth responses to zinc supplementation in randomized intervention trials among children. The results from depletion/repletion studies indicate that serum zinc concentrations respond appreciably to severe dietary zinc restriction, although there is considerable interindividual variation in these responses. There is also clear evidence that both individual and population mean serum zinc concentrations increase consistently during zinc supplementation, regardless of the initial level of serum zinc concentration. By contrast, an individual's serum zinc concentration does not reliably predict that person's response to zinc supplementation. Serum zinc concentration can be considered a useful biomarker of a population's risk of zinc deficiency and response to zinc interventions, although it may not be a reliable indicator of individual zinc status.

Effect of maximal exercise on the short-term kinetics of zinc metabolism in sedentary men.

OBJECTIVE: To examine the effect of acute exhaustive exercise versus rest on short-term zinc kinetics in men. DESIGN: Crossover design, wherein all subjects were their own control. SETTING: University setting, where subjects were free living. PARTICIPANTS: 12 healthy, sedentary men, 25-35 years of age. INTERVENTIONS: (70)Zn was infused 10 min after exercise or at rest. Plasma zinc concentrations were measured at baseline and 2, 5, 10, 15, 30, 45, 60, 75, 90 and 120 min after exercise or rest. Haematocrit was measured before and after exercise to assess changes in plasma volume. MAIN OUTCOME MEASUREMENTS: Plasma zinc (primary), serum creatine kinase and serum cortisol concentrations (secondary). RESULTS: Plasma zinc concentrations decreased (p<0.05) after exercise, with a mean (SD) nadir of 13.9% (4.1%) observed at 70 min after exercise. There were increases in the size of the rapidly exchangeable plasma zinc pool (Qa; from 3.1 (0.2) to 3.6 (0.2) mg; p<0.05) and the liver zinc pool (Qb; from 10.2 (0.6) to 11.4 (0.8) mg; p = 0.12). CONCLUSION: Exercise seems to cause a shift of plasma zinc into the interstitial fluid and liver after exercise, which may reflect the acute stress response of strenuous exercise.

Iron and zinc absorption from two bean (Phaseolus vulgaris L.) genotypes in young women.

Extrinsic and intrinsic iron and zinc labels were used to test iron and zinc absorption from two bean (Phaseolus vulgaris) genotypes, containing normal (common beans, CB) or higher (HFeZnB) iron and zinc concentrations, fed in single meals to young women with low iron reserves. The women were divided into two groups, with one receiving a CB test meal (n = 12) and the other, an HFeZnB test meal (n = 11). The beans were intrinsically labeled hydroponically with (55)Fe (CB and HFeZnB) and with (70)Zn (HFeZnB). Concentrations of zinc and iron were 98 and 65% higher, respectively, in HFeZnB as compared to CB, but phytic acid contents were similar. Extrinsic labels were (59)Fe (CB and HFeZnB), (67)Zn (CB), and (68)Zn (HFeZnB). Iron and zinc percent absorption levels were calculated from radio-iron activity in red blood cells and from urinary excretion of zinc isotopes. Intrinsic and extrinsic iron absorption measures were highly correlated (R (2) = 0.986) (average extrinsic/intrinsic ratio was 1.00). Iron absorption was low (geometric mean < 2%) in both bean types, and total iron absorbed was not different between types. Intrinsic zinc absorption from the HFeZn beans was higher than extrinsic absorption (15.2% vs 13.4%, p < 0.05) (average extrinsic/intrinsic was 0.90). The correlation between intrinsic and extrinsic zinc measures was not as high as that for iron (R (2) = 0.719). Percent zinc absorption levels were similar in both bean types, but total extrinsic zinc absorbed was 90% higher (p < 0.05) from the HFeZnB meal. Thus, the less expensive and time-consuming extrinsic labeling may be used to screen various varieties of beans for iron bioavailability in humans, but it underestimates zinc absorption by approximately 10%. Selective breeding for high-zinc bean genotypes may improve zinc status. However, high-iron genotypes appear to have little effect on iron status when fed alone in single meals to women with low iron reserves.

Supplemental zinc lowers measures of iron status in young women with low iron reserves.

Zinc and iron compete during intestinal absorption, but postabsorptive interactions between these nutrients are less clear. Understanding these interactions is important to determine when supplementation with iron or zinc is proposed. The effect of zinc supplementation (22 mg Zn/d as zinc gluconate) or of iron supplementation (100 mg Fe/d as ferrous sulfate) for 6 wk on iron and zinc metabolism and absorption was evaluated in young women with low iron reserves. Young adult women (ages 20-28 y), nonanemic but with low iron stores (plasma ferritin< 20 microg/L), participated in the 70-d study. The women were divided in two groups (zinc-supplemented, n = 11; iron-supplemented, n = 12). The supplements were taken at bedtime. Iron and zinc biochemical indices and intestinal absorption were measured on d 1 and 56. Radioiron and stable isotopes of zinc were used to measure iron and zinc absorption from a test meal. In the iron-supplemented group, blood hemoglobin, plasma ferritin and the percentage of transferrin saturation increased (P < 0.01). Zinc indices did not change. In the zinc-supplemented group, plasma ferritin and the percentage of transferrin saturation decreased (P < 0.05), whereas the plasma transferrin receptor and erythrocyte zinc protoprophyrin levels increased (P < 0.05). Plasma and urinary zinc also increased (P < 0.01). Iron absorption (%) from the test meal increased (P < 0.01), whereas zinc absorption (%) decreased (P < 0.01) compared with baseline in the Zn-supplemented women. Our results indicate that the use of iron supplements in women with marginal iron status improves iron indices with no effect on zinc status. However, use of a modest zinc supplement improves zinc indices, but also appears to induce a cellular iron deficiency and, possibly, further reduce iron status.

Immune functions are maintained in healthy men with low zinc intake.

Although immunity is impaired during severe zinc deficiency, there is limited information about the effects of mild zinc depletion on immune response in humans. We evaluated the effects of a zinc-restricted diet (4.6 mg/d) on several indices of immunity in 8 healthy men. The subjects consumed zinc supplements with 9.1 mg/d during the 5-wk baseline (BL) and 5-wk repletion (RP) periods, and placebos during the 10-wk zinc-restriction (ZR) period. Leukocyte numbers and functions were studied at the end of each metabolic period. After ZR, there were reductions in the proliferation of peripheral blood mononuclear cells (PBMNC) stimulated with phytohemagglutinin (PHA, 1.2, 2.5, 5.0, 10.0 [corrected] and 20.0 mg/L; P < 0.01) and in the in vitro secretion of interleukin-2 receptor (IL-2R) (PHA, 2.5 mg/L; P = 0.058). These variables remained reduced (P < 0.05) even after 5 wk of zinc repletion. The amount of zinc consumed did not alter the numbers of circulating neutrophils, monocytes and lymphocytes, the in vitro PBMNC secretion of interferon-gamma and tumor necrosis factor-alpha or neutrophil superoxide production. The results suggest that changes in lymphocyte proliferation and IL-2R expression may be early markers of mild zinc deficiency.