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To our knowledge, no randomized study has shown whether zinc replacement therapy is effective for hyperammonemia in liver cirrhosis; therefore, we performed a double-blind, placebo-controlled trial to examine efficacy and safety of the zinc replacement therapy. Patients with liver cirrhosis and hyperammonemia (at or above the institutional reference value) and hypozincemia (≤65 μg/dL) were enrolled in the outpatient units of the participating institutions and were randomly divided to receive placebo (P group) or zinc acetate preparation at a dose of 3 capsules/d for a total zinc content of 150 mg/d (Z group) by the envelope method. Of the 18 enrolled patients, 6 dropped out; thus, the analyses included 12 patients (5 in the P group and 7 in the Z group). Variations in blood concentrations of zinc and ammonia as well as liver function test results were compared. Blood zinc levels significantly increased in the Z group (P = 0.0037; Friedman test) but not the P group. Blood ammonia levels significantly decreased in the Z group (P = 0.0114; Friedman test) but not the P group. The percent change in blood ammonia level also revealed significant reduction at the eighth week in the Z group (P = 0.0188: Mann-Whitney test). No serious adverse events attributable to the zinc preparation were noted. Although this study is preliminary and includes a small sample, it is, to our knowledge, the first randomized controlled trial to show that zinc supplementation for 3 mo seems effective and safe for treating hyperammonemia in liver cirrhosis. Studies with a larger sample size are needed to confirm our findings.

Background: In hemodialysis (HD) patients, zinc depletion caused by inadequate intake, malabsorption, and removal by HD treatment leads to erythropoiesis-stimulating agent (ESA) hyporesponsiveness. This study investigated the effects of zinc supplementation in HD patients with zinc deficiency on changes in the erythropoietin responsiveness index (ERI). Methods: Patients on HD with low serum zinc levels (<65 μg/dL) were randomly assigned to two groups: The polaprezinc group (who received daily polaprezinc, containing 34 mg/day of zinc) (n = 35) and the control group (no supplementation) (n = 35) for 12 months. All the 70 patients had been taking epoetin alpha as treatment for renal anemia. ERI was measured with the following equation: Weekly ESA dose (units)/dry weight (kg)/hemoglobin (g/dL). Results: There were no significant changes in hemoglobin levels within groups or between the control and polaprezinc groups during the study period. Although reticulocyte counts were increased immediately after zinc supplementation, this change was transient. Serum zinc levels were significantly increased and serum copper levels were significantly decreased in the polaprezinc group after three months; this persisted throughout the study period. Although there was no significant change in the serum iron or transferrin saturation levels in the polaprezinc group during the study period, serum ferritin levels significantly decreased following polaprezinc treatment. Further, in the polaprezinc group, ESA dosage and ERI were significantly decreased at 10 months and nine months, respectively, as compared with the baseline value. Multiple stepwise regression analysis revealed that the change in the serum zinc level was an independent predictor of lowered ERI. Conclusions: Zinc supplementation reduces ERI in patients undergoing HD and may be a novel therapeutic strategy for patients with renal anemia and low serum zinc levels.

The Brazilian Amazon region has selenium (Se)-rich soil, which is associated with higher Se levels in populations fed locally grown produce. Brazil nuts are a major source of dietary Se and are included with meals offered to children enrolled in public preschool in Macapá. The aim of this study was to examine Se intake and status of these children. The Macapá group consisted of 41 children from a public preschool who received 15 to 30 g of Brazil nuts 3 d/wk. The control group included 88 children from the nearby city of Belém who did not receive Brazil nut–enriched meals. In both groups, school meals comprised ≥90% of the children's total food consumption. Selenium was assessed using hydride generation quartz tube atomic absorption spectroscopy in plasma, erythrocytes, nails, hair and urine. Dietary intakes (macronutrients and Se) were evaluated using the duplicate-portion method. Both groups received inadequate intakes of energy and macronutrients. Selenium intake was excessive in both groups (155.30 and 44.40 μg/d, in Macapá and Belém, respectively). Intake was potentially toxic in Macapá on days when Brazil nuts were added to meals. Although biomarkers of Se exposure exceeded reference levels in the Macapá group, no clinical symptoms of Se overload (selenosis) were observed. The inclusion of Brazil nuts in school meals provided to children with already high dietary Se intakes increased Se levels and may result in an increased risk for toxicity. As selenosis is associated with some chronic diseases, we recommend continued monitoring of Se intake and status in this population. •Brazil nuts can be used as a dietary selenium supplement.•Children from an Amazonian school fed a Brazil nut–enriched diet had high levels of selenium.•These children were asymptomatic, but at risk for toxicity.•Children not receiving a supplemented diet had normal levels of selenium.•Selenium supplementation should be preceded by assessment of selenium levels in the recipients.

The aim of the study was to evaluate the effect of selenium supplementation on the expression of genes associated with glucose metabolism in humans, in order to explain the unclear relationship between selenium and the risk of diabetes. For gene expression analysis we used archival samples of cDNA from 76 non-diabetic subjects supplemented with selenium in the previous study. The supplementation period was six weeks and the daily dose of selenium was 200 µg (as selenium yeast). Blood for mRNA isolation was collected at four time points: before supplementation, after two and four weeks of supplementation, and after four weeks of washout. The analysis included 15 genes encoding selected proteins involved in insulin signaling and glucose metabolism. In addition, HbA1c and fasting plasma glucose were measured at three and four time points, respectively. Selenium supplementation was associated with a significantly decreased level of HbA1c but not fasting plasma glucose (FPG) and significant down-regulation of seven genes: INSR, ADIPOR1, LDHA, PDHA, PDHB, MYC, and HIF1AN. These results suggest that selenium may affect glycemic control at different levels of regulation, linked to insulin signaling, glycolysis, and pyruvate metabolism. Further research is needed to investigate mechanisms of such transcriptional regulation and its potential implication in direct metabolic effects.

Concern has been expressed recently that Se may increase the risk of type 2 diabetes, but this has not been tested in a randomised-controlled trial (RCT) in pregnant women. We took advantage of having stored plasma samples from the Se in Pregnancy Intervention (SPRINT) RCT of Se supplementation in pregnancy to test the effect of Se supplementation on a marker of insulin resistance in UK pregnant women. Because our blood samples were not fasted, we measured plasma adiponectin concentration, a recognised marker of insulin resistance that gives valid measurements in non-fasted samples, as diurnal variability is minor and there is no noticeable effect of food intake. In SPRINT, 230 primiparous UK women were randomised to treatment with Se (60 μg/d) or placebo from 12 weeks of gestation until delivery. We hypothesised that supplementation with Se at a nutritional level would not exacerbate the fall in adiponectin concentration that occurs in normal pregnancy, indicating the lack of an adverse effect on insulin resistance. Indeed, there was no significant difference between the two groups in the change in adiponectin from 12 to 35 weeks (P=0·938), nor when the analysis was restricted to the bottom or top quartiles of baseline whole-blood Se (P=0·515 and 0·858, respectively). Cross-sectionally, adiponectin concentration was not associated with any parameter of Se status, either at 12 or 35 weeks. It is reassuring that a nutritional dose of Se had no adverse effect on the concentration of adiponectin, a biomarker of insulin resistance, in pregnant women of modest Se status.

This study explored the effects of four-week multi-vitamin and mineral (MVM) supplementation on mood and neurocognitive function in healthy, young adults. Fifty-eight healthy adults, 18–40 years of age (M = 25.82 years, SD = 4.87) participated in this randomised, double-blind, placebo-controlled trial, in which mood and blood biomarkers were assessed at baseline and after four weeks of supplementation. Compared to placebo, MVM supplementation was associated with significantly lowered homocysteine and increased blood B-vitamin levels (p < 0.01). MVM treatment was also associated with significantly improved mood, as measured by reduced scores on the “depression-dejection” subscale of the Profile of Mood States (p = 0.018). These findings suggest that the four weeks of MVM supplementation may have beneficial effects on mood, underpinned by elevated B-vitamins and lowered homocysteine in healthy young adults.

The relation of zinc (Zn) nutriture to brain development and function has been elucidated. The purpose of this study is to examine whether Zn supplementation improves mood states in young women. The study used a double-blind, randomized and placebo-controlled procedure. The major outcomes were psychological measures, somatic symptoms and serum Zn. Thirty women were placed randomly and in equal numbers into two groups, and they ingested one capsule containing multivitamins (MVs) or MV and 7 mg Zn daily for 10 weeks. Women who took MV and Zn showed a significant reduction in anger–hostility score (P=0.009) and depression–dejection score (P=0.011) in the Profile of Moods State (POMS) and a significant increase in serum Zn concentration (P=0.008), whereas women who took only MV did not. Our results suggest that Zn supplementation may be effective in reducing anger and depression.

Despite a high content of saturated fat, evidence from observational studies indicates that the consumption of dairy products may have a neutral effect or may be inversely associated with the risk of CVD. We aimed to examine whether milk minerals modify the effect of saturated fat on serum lipid profile. We present data from two studies. Study I had a randomised, blinded, parallel design (n 24 pigs) with a 10 d adaptation period during which a high-fat diet was fed to the pigs and a 14 d intervention period during which the same diet either enriched with milk minerals (MM group) or placebo (control group) was fed to the pigs. Study II had a randomised cross-over design (n 9 men) where the subjects were fed either a high-fat diet enriched with milk minerals (MM period) or a regular diet (control period). In both the studies, blood variables were measured before and after the intervention and faecal and urine samples were collected at the end of the dietary periods. The increase in plasma total cholesterol and LDL-cholesterol concentrations but not in HDL-cholesterol concentration was markedly lowered by milk minerals in both the studies. In the animal study, baseline adjusted total cholesterol and LDL-cholesterol concentrations in the MM group were 11 % (P= 0·004) and 13 % (P= 0·03) lower compared with those in the control group after the intervention. Similarly in the human study, baseline adjusted total cholesterol and LDL-cholesterol concentrations were 6 % (P= 0·002) and 9 % (P= 0·03) lower after the MM period compared with those in the control period. HDL-cholesterol concentration was not lowered by milk minerals. These short-term studies indicate that the addition of milk minerals to a high-fat diet to some extent attenuates the increase in total cholesterol and LDL-cholesterol concentrations, without affecting HDL-cholesterol concentration.

In Vietnam, nutrition interventions do not target school children despite a high prevalence of micronutrient deficiencies. The present randomised, placebo-controlled study evaluated the impact of providing school children (n 403) with daily multiple micronutrient-fortified biscuits (FB) or a weekly Fe supplement (SUP) on anaemia and Fe deficiency. Micronutrient status was assessed by concentrations of Hb, and plasma ferritin (PF), transferrin receptor (TfR), Zn and retinol. After 6 months of intervention, children receiving FB or SUP had a significantly better Fe status when compared with the control children (C), indicated by higher PF (FB: geometric mean 36·9 (95 % CI 28·0, 55·4) μg/l; SUP: geometric mean 46·0 (95 % CI 33·0, 71·7) μg/l; C: geometric mean 34·4 (95 % CI 15·2, 51·2) μg/l; P < 0·001) and lower TfR concentrations (FB: geometric mean 5·7 (95 % CI 4·8, 6·52) mg/l; SUP: geometric mean 5·5 (95 % CI 4·9, 6·2) mg/l; C: geometric mean 5·9 (95 % CI 5·1, 7·1) mg/l; P = 0·007). Consequently, body Fe was higher in children receiving FB (mean 5·6 (sd 2·2) mg/kg body weight) and SUP (mean 6·1 (sd 2·5) mg/kg body weight) compared with the C group (mean 4·2 (sd 3·3) mg/kg body weight, P < 0·001). However, anaemia prevalence was significantly lower only in the FB group (1·0 %) compared with the C group (10·4 %, P = 0·006), with the SUP group being intermediate (7·4 %). Children receiving FB had better weight-for-height Z-scores after the intervention than children receiving the SUP (P = 0·009). Vitamin A deficiency at baseline modified the intervention effect, with higher Hb concentrations in vitamin A-deficient children receiving FB but not in those receiving the SUP. This indicates that vitamin A deficiency is implicated in the high prevalence of anaemia in Vietnamese school children, and that interventions should take other deficiencies besides Fe into account to improve Hb concentrations. Provision of biscuits fortified with multiple micronutrients is effective in reducing anaemia prevalence in school children.

Background/Objective: To assess the effectiveness of iron supplements administered to school children through a longitudinal school health intervention in terms of child haemoglobin concentration and anaemia prevalence. Subjects/Methods: Children and adolescents aged 5–17 years were selected from 30 schools in north-west Pakistan for a longitudinal iron supplement intervention. Children received once-weekly iron supplements (200 mg ferrous sulphate containing 63 mg of elemental iron) for 24 weeks ( n =352); or the same supplements twice-weekly for 12 weeks ( n =298) or received no tablets ( n =298). Haemoglobin concentration was estimated in finger-prick blood samples at baseline, 12 and 24 weeks. Follow-up samples were taken at 36 weeks. Results: A non-significant increase in haemoglobin concentration was observed in children receiving iron supplements after 12 weeks (mean 1.4 g/l s.d. 15.0 g/l in once-weekly versus 2.5 g/l s.d. 14.5 g/l in twice-weekly) compared with the group receiving no iron supplements. There was no significant reduction in the prevalence of anaemia in the once-weekly or twice-weekly group compared with the unsupplemented group. The prevalence of anaemia increased in all three groups during the follow-up period (24–36 weeks). Conclusions: Once-weekly and twice-weekly iron supplements were not associated with significant increases in haemoglobin concentration compared with unsupplemented children. In all groups, baseline haemoglobin concentration was the strongest predictor of haemoglobin increase. The lack of improvement may stem from the moderate baseline prevalence of anaemia (33%); other micronutrient deficiencies; variable compliance; or the worsening of haemoglobin status owing to seasonal changes in dietary iron and other nutrients.