The effect of zinc supplementation on glucose homeostasis: a randomised double-blind placebo-controlled trial.

AIMS: The burden and health costs of Type 2 Diabetes Mellitus continue to increase globally and prevention strategies in at-risk people need to be explored. Previous work, in both animal models and humans, supports the role of zinc in improving glucose homeostasis. We, therefore, aimed to test the effectiveness of zinc supplementation on glycaemic control in pre-diabetic adults. METHODS: We conducted a randomized, double-blind, placebo-controlled trial across 10 General Practitioner (GP) practices in NSW, Australia. The trial is known as Zinc in Preventing the Progression of pre-Diabetes (ZIPPeD)Study. Pre-diabetic (haemoglobin A1c [HbA1c] 5.7-6.4%, 39-46 mmol/mol) men and women (N = 98) were all assigned to a free state government telephone health coaching service (New South Wales Get Healthy Information and Coaching Service) and then randomised to either daily 30 mg zinc gluconate or placebo. Blood tests were collected at baseline, 1, 6 and 12 months for the primary outcomes (HbA1c, fasting blood glucose (FBG)); secondary outcomes included Homeostasis Model Assessment 2 (HOMA 2) parameters, lipids, body weight, height, waist circumference, blood pressure and pulse. RESULTS: The baseline-adjusted mean group difference at 6 months, expressed as treatment-placebo, (95% CI) was -0.02 (-0.14, 0.11, p = 0.78) for HbA1c and 0.17 (-0.07, 0.42; p = 0.17) for FBG, neither of which were statistically significant. There were also no significant differences between groups in any of the secondary outcomes. Zinc was well tolerated, and compliance was high (88%). CONCLUSION: We believe our results are consistent with other Western clinical trial studies and do not support the use of supplemental zinc in populations with a Western diet. There may still be a role for supplemental zinc in the developing world where diets may be zinc deficient. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12618001120268. Registered on 6 July 2018.

Zinc in Preventing the Progression of pre-Diabetes (ZIPPeD Study) - study protocol for a randomised placebo-controlled trial in Australia.

BACKGROUND: Diabetes is increasing in incidence, morbidity and treatment costs globally, hence prevention strategies need to be explored. Animal studies and some human data have shown that zinc can improve glycaemic control, but the impact of this effect in a pre-diabetic population remains uncertain. This study is designed to investigate whether zinc gluconate and lifestyle coaching can improve glucose handling and ultimately reduce diabetes incidence in an at-risk pre-diabetic population in Australia. METHODS/DESIGN: The study will be a randomised, placebo-controlled, double-blind clinical trial. The study will be conducted at the Hunter New England Local Health District New South Wales (NSW), Australia. Pre-diabetic (haemoglobin A1c [HbA1c] 5.7-6.4) male and female participants (n = 410) aged 40-70 years will be recruited through the Diabetes Alliance Network, a collaboration of diabetes specialists and general practitioner practices. All participants will be given routine care to encourage healthy lifestyle changes using a telephone coaching service (Get Healthy Information and Coaching Service, NSW Health) and then randomised to receive a supplement, either zinc gluconate (equivalent to 30 mg of elemental zinc) or placebo of identical appearance for 12 months. The identity of the supplements will be blinded to both research personnel and the participants. Participants will be asked to complete medical, lifestyle and dietary surveys and will have baseline and final visits at their general practitioner practice. Primary outcomes will be HbA1c and insulin sensitivity collected at baseline and at 1, 6 and 12 months; secondary outcomes will include fasting blood glucose, fasting cholesterol, blood pressure and body mass index. The primary efficacy endpoint will be judged at 6 months. DISCUSSION: This study will generate new evidence about the potential for health coaching, with or without zinc supplementation, to improve glucose handling and ultimately to reduce progression from pre-diabetes to diabetes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12618001120268 . Registered on 6 July 2018.

Modified Version of Baby-Led Weaning Does Not Result in Lower Zinc Intake or Status in Infants: A Randomized Controlled Trial.

BACKGROUND: Little is known about zinc intakes and status during complementary feeding. This is particularly true for baby-led approaches, which encourage infants to feed themselves from the start of complementary feeding, although self-feeding may restrict the intake of zinc-rich foods. OBJECTIVE: To determine the zinc intakes, sources, and biochemical zinc status of infants following Baby-Led Introduction to SolidS (BLISS), a modified version of Baby-Led Weaning (BLW), compared with traditional spoon-feeding. DESIGN: Secondary analysis of the BLISS randomized controlled trial. PARTICIPANTS/SETTING: Between 2012 and 2014, 206 community-based participants from Dunedin, New Zealand were randomized to a Control or BLISS group. INTERVENTION: BLISS participants received eight study visits (antenatal to 9 months) providing education and support regarding BLISS (ie, infant self-feeding from 6 months with modifications to address concerns about iron, choking, and growth). MAIN OUTCOME MEASURES: Dietary zinc intakes at 7 and 12 months (weighed 3-day diet records) and zinc status at 12 months (plasma zinc concentration). STATISTICAL ANALYSES PERFORMED: Regression analyses were used to investigate differences in dietary intakes and zinc status by group, adjusted for maternal education and parity and infant age and sex. RESULTS: There were no significant differences in zinc intakes between BLISS and Control infants at 7 (median: 3.5 vs 3.5 mg/day; P=0.42) or 12 (4.4 vs 4.4 mg/day; P=0.86) months. Complementary food groups contributing the most zinc at 7 months were "vegetables" for Control infants, and "breads and cereals" for BLISS infants, then "dairy" for both groups at 12 months. There was no significant difference in mean±standard deviation plasma zinc concentration between the Control (62.8±9.8 µg/dL [9.6±1.5 µmol/L]) and BLISS (62.8±10.5 µg/dL [9.6±1.6 µmol/L]) groups (P=0.75). CONCLUSIONS: BLISS infants achieved similar zinc intake and status to Control infants. However, the BLISS intervention was modified to increase iron intake, which may have improved zinc intake, so these results should not be generalized to infants following unmodified BLW.

Modifiable "Predictors" of Zinc Status in Toddlers.

Suboptimal zinc status is common in very young children and likely associated with increased risk of infection and detrimental effects on growth. No studies have determined potentially modifiable "predictors" of zinc status in toddlers from high-income countries. This cross-sectional analysis of 115 toddlers from the Baby-Led Introduction to SolidS (BLISS) study used weighed diet records (three non-consecutive days) to assess dietary intake, and a venous blood sample (trace-element free techniques) to assess plasma zinc, at 12 months of age. "Predictors" of plasma zinc were determined by univariate analysis and multiple regression. Mean (SD) plasma zinc was 9.7 (1.5) µmol/L, 60% were below the IZiNCG reference limit of <9.9 µmol/L. Median (25th, 75th percentiles) intake of zinc was 4.4 (3.7, 5.4) mg/day. Red meat intake (p = 0.004), consumption of zinc-fortified infant formula (3-6 mg zinc/100 g) (p = 0.026), and food fussiness (p = 0.028) were statistically significant "predictors" of plasma zinc at 12 months. Although higher intakes of red meat, and consumption of infant formula, are potentially achievable, it is important to consider possible barriers, particularly impact on breastfeeding, cost, and the challenges of behavior modification. Of interest is the association with food fussiness-further research should investigate the direction of this association.

Zinc-induced upregulation of metallothionein (MT)-2A is predicted by gene expression of zinc transporters in healthy adults.

The usefulness of zinc transporter and metallothionein (MT) gene expressions to detect changes in zinc intake remains unclear. This pilot study aimed to determine the effects of zinc supplementation on zinc transporter and MT gene expressions in humans. Healthy adults (n = 39) were randomised to zinc treatment (ZT), receiving 22 mg Zn/day (n = 19), or no treatment (NT) (n = 20). Blood samples were collected on Days 0, 2, 7, 14, and 21. Plasma zinc and serum C-reactive protein concentrations were analysed. Gene expression of zinc transporters and MT in peripheral blood mononuclear cells was analysed using real-time PCR. Using repeated-measures ANOVA, MT-2A gene expression and fold change were found to be higher in the ZT group (P = 0.025 and P = 0.016, respectively) compared to the NT group, specifically at Day 2 (40 ± 18 % increase from baseline, P = 0.011), despite no significant increase in plasma zinc concentration. In a multiple regression model exploring the changes in gene expressions between Days 0 and 21, the change in MT-2A gene expression was correlated with changes in all zinc transporter expressions (r (2) = 0.54, P = 0.029); the change in ZIP1 expression emerged as a univariate predictor (P = 0.003). Dietary zinc intake was predictive of zinc transporter and MT expressions (P = 0.030). Physical activity level was positively correlated with baseline ZIP7 expression (r = 0.36, P = 0.029). The present study shows that MT-2A expression is related to changing expression of zinc transporter genes, specifically ZIP1, in response to zinc supplementation. The current report adds to our understanding of MT in the coordinated nature of cellular zinc homeostasis.

TNF-α gene expression is increased following zinc supplementation in type 2 diabetes mellitus.

Chronic low-grade inflammation in type 2 diabetes mellitus (DM) can elicit changes in whole-body zinc metabolism. The interaction among the expression of inflammatory cytokines, zinc transporter and metallothionein (MT) genes in peripheral blood mononuclear cells in type 2 DM remains unclear. In a 12-week randomized controlled trial, the effects of zinc (40 mg/day) supplementation on the gene expression of cytokines, zinc transporters and MT in women with type 2 DM were examined. In the zinc-supplemented group, gene expression of tumour necrosis factor (TNF)-α tended to be upregulated by 27 ± 10 % at week 12 compared to baseline (P = 0.053). TNF-α fold change in the zinc-treated group was higher than in those without zinc supplementation (P < 0.05). No significant changes were observed in the expression or fold change of interleukin (IL)-1ß or IL-6. Numerous bivariate relationships were observed between the fold changes of cytokines and zinc transporters, including ZnT7 with IL-1ß (P < 0.01), IL-6 (P < 0.01) and TNF-α (P < 0.01). In multiple regression analysis, IL-1ß expression was predicted by the expression of all zinc transporters and MT measured at baseline (r (2) = 0.495, P < 0.05) and at week 12 (r (2) = 0.532, P < 0.03). The current study presents preliminary evidence that zinc supplementation increases cytokine gene expression in type 2 DM. The relationships found among zinc transporters, MT and cytokines suggest close  interactions between zinc homeostasis and inflammation.

Zinc supplement use and contribution to zinc intake in Australian children.

OBJECTIVE: The aims of the present study were to examine the Zn intake and characteristics of Zn supplement users and non-users and to survey Zn supplements that are commercially available. DESIGN: Cross-sectional national nutrition survey (2007 Australian Children's Nutrition and Physical Activity Survey) and a review of commercially available Zn supplements. SETTING: Australia. SUBJECTS: Children (n 4834) aged 2-16 years. RESULTS: Zn supplement use was associated with younger age, being female, having a lower BMI and consuming a vegetarian or modified diet. Supplement users had significantly higher intakes of Zn than non-users in all age and gender subgroups. Adolescent boys aged 14-16 years who did not use Zn supplements were at highest risk of inadequate Zn intake (15 % compared with 1 % of users). Conversely, children aged 2-3 years were at highest risk of exceeding the recommended upper limit of Zn intake (86-87 % of users and 64-71 % of non-users), followed by children aged 4-8 years (9-29 % of users and 3-12 % of non-users). The most common sources of Zn supplements consumed by children were multi-vitamin and mineral preparations (92 %), followed by Zn-only supplements (5 %) and Zn-containing cold and flu, or cold sore supplements (3 %). A survey of commercially available Zn supplements revealed that the median elemental Zn content was 2 and 25 mg for multi-vitamin and mineral preparations and Zn-only supplements, respectively. CONCLUSIONS: Based on these data, widespread Zn supplement use among young children is unlikely to be warranted. The impact of exceeding the upper limit of Zn intake on biomarkers of Zn toxicity requires further investigation.

Micronutrient status in female university students: iron, zinc, copper, selenium, vitamin B12 and folate.

Young women are at an increased risk of micronutrient deficiencies, particularly due to higher micronutrient requirements during childbearing years and multiple food group avoidances. The objective of this study was to investigate biomarkers of particular micronutrients in apparently healthy young women. Female students (n = 308; age range 18-35 year; Body Mass Index 21.5 ± 2.8 kg/m2; mean ± SD) were recruited to participate in a cross-sectional study. Blood samples were obtained from participants in the fasted state and analysed for biomarkers of iron status, vitamin B12, folate, homocysteine, selenium, zinc, and copper. The results show iron deficiency anaemia, unspecified anaemia, and hypoferritinemia in 3%, 7% and 33.9% of participants, respectively. Low vitamin B12 concentrations (<120 pmol/L) were found in 11.3% of participants, while 4.7% showed sub-clinical deficiency based on serum methylmalonic acid concentrations >0.34 µmol/L. Folate concentrations below the reference range were observed in 1.7% (serum) or 1% (erythrocytes) of participants, and 99.7% of the participant had erythrocyte-folate concentrations >300 nmol/L. Serum zinc concentrations <10.7 µmol/L were observed in 2% of participants. Serum copper and selenium concentrations were below the reference range in 23% and 11% of participants, respectively. Micronutrient deficiencies including iron and vitamin B12, and apparent excess of folate are present in educated Australian female students of childbearing age, including those studying nutrition. The effects of dietary behaviours and food choices on markers of micronutrient status require further investigation.

Zinc transporter gene expression and glycemic control in post-menopausal women with Type 2 diabetes mellitus.

Type 2 diabetes mellitus (DM) is associated often with underlying zinc deficiency and nutritional supplements such as zinc may be of therapeutic benefit in the disease. In a randomized, double-blind, placebo-controlled, 12-week trial in postmenopausal women (n=48) with Type 2 DM we investigated the effects of supplementation with zinc (40mg/d) and flaxseed oil (FSO; 2g/d) on the gene expression of zinc transporters (ZnT1, ZnT5, ZnT6, ZnT7, ZnT8, Zip1, Zip3, Zip7, and Zip10) and metallothionein (MT-1A, and MT-2A), and markers of glycemic control (glucose, insulin, glycosylated hemoglobin [HbA1c]). The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. No significant effects of zinc or FSO supplementation were observed on glycemic marker concentrations, HOMA-IR or fold change over 12 weeks in zinc transporter and metallothionein gene expression. In multivariate analysis, the change over 12 weeks in serum glucose concentrations (P=0.001) and HOMA-IR (P=0.001) predicted the fold change in Zip10. In secondary analysis, marginal statistical significance was observed with the change in both serum glucose concentrations (P=0.003) and HOMA-IR (P=0.007) being predictive of the fold change in ZnT6. ZnT8 mRNA expression was variable; HbA1c levels were higher (P=0.006) in participants who exhibited ZnT8 expression compared to those who did not. The significant predictive relationships between Zip10, ZnT6, serum glucose and HOMA-IR are preliminary, as is the relationship between HbA1c and ZnT8; nevertheless the observations support an association between Type 2 DM and zinc homeostasis that requires further exploration.

Inclusion of pork meat in the diets of young women reduces their intakes of energy-dense, nutrient-poor foods: results from a randomized controlled trial.

Adherence of young women to dietary recommendations has been examined predominantly by surveys. This study aimed to determine the quality of women's diets relative to the Australian Guide to Healthy Eating (AGHE); and to evaluate dietary changes during an intervention trial with pork meat or an iron supplement. A 12-week randomized trial was conducted in young women who were assigned to one of three groups. They maintained three, seven-day food diaries while continuing their routine diet (CG); taking an iron supplement (SG); or incorporating into their diets 500 g/week of pork (PG). Participants (n = 58) provided dietary information on 1218 diary-days. The serves consumed from the vegetable, fruit and dairy groups were lower (p < 0.001), and from the meat and alternatives group greater (p < 0.001) than the recommended serves. PG consumed significantly fewer (p < 0.001) serves of "extra" foods, and ate fruit more frequently (p < 0.001) than CG and SG. The participants' dietary self-assessment showed poor agreement with the AGHE description of "serve". The inclusion of pork in the diets of young women is associated with the reduced consumption of energy-dense nutrient-poor "extra" foods and increased frequency of fruit intake. The effect may be explained by diverse factors such as increased food knowledge, cooking skills and the effect of pork on satiety.

Biological variability and impact of oral contraceptives on vitamins B(6), B(12) and folate status in women of reproductive age.

Vitamins B(6), B(12) and folate play crucial metabolic roles especially during the reproductive years for women. There is limited reporting of within-subject variability of these vitamins. This study aimed to determine the within and between subject variability in serum vitamins B(6), B(12), folate and erythrocyte folate concentrations in young women; identify factors that contribute to variability; and determine dietary intakes and sources of these vitamins. Data were obtained from the control group of a trial aimed at investigating the effect of iron on the nutritional status of young women (age 25.2 ± 4.2 year; BMI 21.9 ± 2.2 kg/m2). The coefficients of variability within-subject (CVI) and between-subject (CVG) for serum vitamins B(6), B(12)and folate, and erythrocyte folate were calculated. Food frequency questionnaires provided dietary data. CVI and CVG were in the range 16.1%-25.7% and 31.7%-62.2%, respectively. Oral contraceptive pill (OCP) use was associated (P = 0.042) with lower serum vitamin B12 concentrations. Initial values were 172 ± 16 pmol/L and 318 ± 51 pmol/L for OCP and non-OCP users, respectively; with differences maintained at four time points over 12 weeks. BMI, age, physical activity, alcohol intake and haematological variables did not affect serum or erythrocyte vitamin concentrations. Vitamin B12 intakes were derived from traditional and unexpected sources including commercial energy drinks. Young women using OCP had significantly lower serum vitamin B12 concentrations. This should be considered in clinical decision making and requires further investigation.

Inflammation markers predict zinc transporter gene expression in women with type 2 diabetes mellitus.

The pathology of type 2 diabetes mellitus (DM) often is associated with underlying states of conditioned zinc deficiency and chronic inflammation. Zinc and omega-3 polyunsaturated fatty acids each exhibit anti-inflammatory effects and may be of therapeutic benefit in the disease. The present randomized, double-blind, placebo-controlled, 12-week trial was designed to investigate the effects of zinc (40 mg/day) and α-linolenic acid (ALA; 2 g/day flaxseed oil) supplementation on markers of inflammation [interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP)] and zinc transporter and metallothionein gene expression in 48 postmenopausal women with type 2 DM. No significant effects of zinc or ALA supplementation were observed on inflammatory marker concentrations or fold change in zinc transporter and metallothionein gene expression. Significant increases in plasma zinc concentrations were observed over time in the groups supplemented with zinc alone or combined with ALA (P=.007 and P=.009, respectively). An impact of zinc treatment on zinc transporter gene expression was found; ZnT5 was positively correlated with Zip3 mRNA (P<.001) only in participants receiving zinc, while zinc supplementation abolished the relationship between ZnT5 and Zip10. IL-6 predicted the expression levels and CRP predicted the fold change of the ZnT5, ZnT7, Zip1, Zip7 and Zip10 mRNA cluster (P<.001 and P=.031, respectively). Fold change in the expression of metallothionein mRNA was predicted by TNF-α (P=.022). Associations among inflammatory cytokines and zinc transporter and metallothionein gene expression support an interrelationship between zinc homeostasis and inflammation in type 2 DM.

Effect of vegetarian diets on zinc status: a systematic review and meta-analysis of studies in humans.

Plant-based diets contain less saturated fat and cholesterol and more folate, fibre and phytochemicals than omnivorous diets, but some micronutrients, especially zinc, are poorly bioavailable. The findings of studies exploring the zinc intake and zinc status in populations that habitually consume vegetarian diets are inconsistent. This study aims to investigate the effects of plant-based diets on dietary zinc intake and status in humans using systematic review and meta-analysis techniques. Thirty-four studies were included in the systematic review. Of these, 26 studies (reporting 48 comparisons) compared males and/or females consuming vegetarian diets with non-vegetarian groups and were included in meta-analyses. Dietary zinc intakes and serum zinc concentrations were significantly lower (-0.88 ± 0.15 mg day(-1), P < 0.001 and -0.93 ± 0.27 µmol L(-1), P = 0.001 respectively; mean ± standard error) in populations that followed habitual vegetarian diets compared with non-vegetarians. Secondary analyses showed greater impact of vegetarian diets on the zinc intake and status of females, vegetarians from developing countries and vegans. Populations that habitually consume vegetarian diets have low zinc intakes and status. Not all vegetarian categories impact zinc status to the same extent, but a lack of consistency in defining vegetarian diets for research purposes makes dietary assessment difficult. Dietary practices that increase zinc bioavailability, the consumption of foods fortified with zinc or low-dose supplementation are strategies that should be considered for improving the zinc status of vegetarians with low zinc intakes or serum zinc concentrations at the lower end of the reference range.

Iron supplementation decreases plasma zinc but has no effect on plasma fatty acids in non-anemic women.

Limited information is available on the role of iron in fatty acid metabolism in humans. We hypothesized that iron supplementation will increase desaturase activity, and so, the aim of this study was to determine the effect of iron supplementation on fatty acid desaturase activity in young women. Participants were randomly assigned to a control group (CG) or supplementation group (SG) who were provided with 37.4 mg of elemental iron daily for 12 weeks. Forty women completed the trial, n = 19 in CG and n = 21 in SG. The mean ages were 25.2 and 24.6 years, and body mass indices were 21.8 and 21.2 (kg/m(2)) in CG and SG, respectively. Serum ferritin concentrations increased significantly (P < .01) in subjects assigned to SG but were unchanged in CG. Serum iron concentrations were not significantly changed. Plasma zinc concentrations at the end of the intervention were similar to baseline values for individuals in CG but were decreased significantly (P = .004) in SG. Plasma fatty acids, phospholipid fatty acids, and desaturase activities, expressed as precursor-to-product ratios, were not significantly affected by the intervention, although in SG the concentration of serum ferritin was correlated positively (P < .05) with Δ6-desaturase activity. Supplementing non-anemic women with low dose iron improves iron status but has no significant effect on desaturase activity. The lack of a clear effect on an indirect indicator of desaturase activity may be related to the antagonism between iron and zinc, as illustrated by the decrease in plasma zinc concentrations in women who were supplemented with iron.

Zinc and glycemic control: a meta-analysis of randomised placebo controlled supplementation trials in humans.

BACKGROUND: Impaired zinc metabolism is prominent in chronic disorders including cardiovascular disease and diabetes. Zinc has the potential to affect glucose homeostasis in animals and humans and hence impact the risk of type 2 diabetes mellitus. METHODS: A systematic review and meta-analysis of randomised placebo controlled trials was conducted to determine the effect of zinc supplementation on fasting blood glucose, HbA1c, serum insulin and serum zinc concentrations. Relevant studies for inclusion were identified from a literature search of electronic databases up to July 2011. RESULTS: Fourteen reports (n=3978 subjects) were included in the meta-analysis. In the overall analysis, a small but statistically significant reduction in fasting glucose concentrations was observed (-0.19±0.08mmol/L, P=0.013) after zinc supplementation. HbA1c tended to decrease in zinc-supplemented individuals (-0.64±0.36%, P=0.072). No significant effect was observed for serum insulin concentrations. Plasma zinc concentrations increased significantly following supplementation (+4.03±0.81µmol/L, P=0.001). In secondary analyses of participants with chronic metabolic disease (types 1 and 2 diabetes mellitus, metabolic syndrome and obesity), zinc supplementation produced a greater reduction in glucose concentrations (-0.49±0.11mmol/L, P=0.001) compared to the effect that was observed in healthy participants. CONCLUSION: The significant albeit modest reduction in glucose concentrations and tendency for a decrease in HbA1c following zinc supplementation suggest that zinc may contribute to the management of hyperglycemia in individuals with chronic metabolic disease.

A randomized controlled trial in young women of the effects of consuming pork meat or iron supplements on nutritional status and feeling of well-being.

OBJECTIVES: Limited information is available on the role of pork meat in influencing iron status. The aim of this study was to determine the effect of consuming pork meat as compared to iron supplementation on nutritional status and feeling of well-being. METHODS: Young women were randomly assigned to a control diet (CG), a pork-containing diet (PG), or a control diet with iron supplementation (SG) for 12 weeks. Sixty-five women aged 24.6 ± 4.4 years (mean ± SD) completed the trial. RESULTS: Serum ferritin concentrations were increased significantly (p = 0.001) in participants assigned to the SG as compared with the other groups, as assessed by repeated-measures analysis of variance. At week 12, hemoglobin concentrations were significantly higher in PG and SG as compared with CG. Plasma zinc concentrations at the end of the intervention were similar to baseline concentrations for individuals in the CG and PG but were decreased significantly (p < 0.05) in SG. Plasma-, erythrocyte-folate, and serum vitamin B6 and B12 concentrations were not significantly affected by the intervention, although the concentrations of vitamins B6 and B12 tended to increase in PG. Well-being, as measured using the Health Survey Short Form (SF-36) and its 8 multi-item scales, showed significant improvement in vitality in SG (p < 0.05) and bodily pain in PG (p < 0.05). No significant relationships were observed between these health concept scores and biomarkers of nutritional status. CONCLUSIONS: Consumption of pork meat by young women maintains hemoglobin levels to the same extent as low-dose iron supplementation and enhances the components of well-being, mainly their perception of bodily pain.

Zinc intake and its dietary sources: results of the 2007 Australian National Children's Nutrition and Physical Activity Survey.

The current Australian Nutrient Reference Values (NRV) use different Estimated Average Requirements (EAR) for zinc for adolescent boys and girls compared to the previous recommendations. The adequacy of zinc intakes of 2-16 years old children (n = 4834) was examined in the 2007 Australian National Children's Nutrition and Physical Activity Survey. Zinc intakes were estimated from two 24-h recalls and compared with age- and gender-specific NRV. Food sources of zinc were assessed and compared with those of the 1995 National Nutrition Survey. The mean (SD) zinc intake was 10.2 (3.0) mg/day for all children. Nearly all children met the EAR for zinc except for 14-16 years old boys (29% did not meet EAR). Children (2-3 years) were at highest risk of excessive zinc intakes with 79% exceeding the Upper Level of Intake. Meat and poultry; milk products; and cereals and cereal products contributed 68% of total zinc intake. The contribution of cereals to total zinc intake has increased significantly since 1995, due to the greater market-availability of zinc-fortified breakfast cereals. We conclude that sub-groups of Australian children are at-risk of inadequate (boys 14-16 years) or excessive (children 2-3 years) zinc intakes, and monitoring of zinc status is required.

Zinc and regulation of inflammatory cytokines: implications for cardiometabolic disease.

In atherosclerosis and diabetes mellitus, the concomitant presence of low-grade systemic inflammation and mild zinc deficiency highlights a role for zinc nutrition in the management of chronic disease. This review aims to evaluate the literature that reports on the interactions of zinc and cytokines. In humans, inflammatory cytokines have been shown both to up- and down-regulate the expression of specific cellular zinc transporters in response to an increased demand for zinc in inflammatory conditions. The acute phase response includes a rapid decline in the plasma zinc concentration as a result of the redistribution of zinc into cellular compartments. Zinc deficiency influences the generation of cytokines, including IL-1ß, IL-2, IL-6, and TNF-α, and in response to zinc supplementation plasma cytokines exhibit a dose-dependent response. The mechanism of action may reflect the ability of zinc to either induce or inhibit the activation of NF-κB. Confounders in understanding the zinc-cytokine relationship on the basis of in vitro experimentation include methodological issues such as the cell type and the means of activating cells in culture. Impaired zinc homeostasis and chronic inflammation feature prominently in a number of cardiometabolic diseases. Given the high prevalence of zinc deficiency and chronic disease globally, the interplay of zinc and inflammation warrants further examination.

Zinc and redox signaling: perturbations associated with cardiovascular disease and diabetes mellitus.

Cellular signal transduction pathways are influenced by the zinc and redox status of the cell. Numerous chronic diseases, including cardiovascular disease (CVD) and diabetes mellitus (DM), have been associated with impaired zinc utilization and increased oxidative stress. In humans, mutations in the MT-1A and ZnT8 genes, both of which are involved in the maintenance of zinc homeostasis, have been linked with DM development. Changes in levels of intracellular free zinc may exacerbate oxidative stress in CVD and DM by impacting glutathione homeostasis, nitric oxide signaling, and nuclear factor-kappa B-dependent cellular processes. Zinc ions have been shown to influence insulin and leptin signaling via the phosphoinositide 3'-kinase/Akt pathway, potentially linking an imbalance of zinc at the cellular level to insulin resistance and dyslipidemia. The oxidative modification of cysteine residues in zinc coordination sites in proteins has been implicated in cellular signaling and regulatory pathways. Despite the many interactions between zinc and cellular stress responses, studies investigating the potential therapeutic benefit of zinc supplementation in the prevention and treatment of oxidative stress-related chronic disease in humans are few and inconsistent. Further well-designed randomized controlled trials are needed to determine the effects of zinc supplementation in populations at various stages of CVD and DM progression.

Effects of zinc on plasma lipoprotein cholesterol concentrations in humans: a meta-analysis of randomised controlled trials.

BACKGROUND: Studies in humans and animals suggest that zinc has the potential to affect lipoprotein metabolism and hence impact cardiovascular disease risk. METHODS: A meta-analysis of controlled clinical trials was conducted to determine the effect of zinc supplementation on plasma cholesterol and triglyceride concentrations in humans. Potentially relevant studies were identified from a literature search covering the period 1980-2008 (inclusive), and additional citation searches. RESULTS: Thirty three interventions (n=14,238 subjects) were included in the random effects meta-analysis. No overall significant effects of zinc supplementation were observed for plasma cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol or plasma triglyceride concentrations. Plasma zinc concentrations increased significantly (+2.42+/-0.25 micromol/L, P<0.001; n=14,047). Secondary analyses in individuals classified as healthy revealed that zinc supplementation is associated with a significant decrease in plasma HDL cholesterol concentrations (-0.10+/-0.02 mmol/L, P<0.001; n=13,215), equivalent to a 7% decrease from baseline. CONCLUSION: No effect of zinc supplementation on plasma lipoproteins was detected in the overall analysis. In individuals classified as healthy, zinc supplementation is associated with a decrease in HDL cholesterol concentrations and thus contributes to an increased risk of coronary heart disease.