A double-blind trial of zinc supplementation in pregnancy

A double-blind randomised trial of oral zinc supplementation was carried out during the last two trimesters of pregnancy. Fifty-six women at risk of delivering a small-for-gestational-age baby received either zinc supplement (22.5 mg daily) or placebo. Twenty-nine of the women were compliant. Zinc significantly reduced the incidence of intrauterine growth retardation, and most measured indices of labour and fetal health were better in the supplemented group. Larger studies are now needed to confirm a role for selective zinc supplementation in at-risk pregnancies.     

Randomized controlled trial of the effect of zinc supplementation on the mental development of Bangladeshi infants

BACKGROUND: Zinc deficiency is thought to be common in young children in developing countries and some data suggest that it may detrimentally affect children's development. OBJECTIVE: Our goal was to assess the effect of zinc supplementation on the developmental levels and behavior of Bangladeshi infants. DESIGN: This was a randomized, double-blind, controlled trial conducted in Dhaka, Bangladesh. Three hundred one infants aged 1 mo were randomly assigned to receive either 5 mg elemental Zn or placebo daily for 5 mo, and subsequent growth and morbidity were observed. For the present study, developmental levels were assessed in a subsample of 212 infants at 7 and 13 mo of age with use of the Bayley Scales of Infant Development, and the infants' behavior during the tests was observed. The children's social backgrounds, weights, and lengths were also recorded. RESULTS: The children's nutritional status was generally poor. The zinc-treated group had slightly lower scores on the mental development index of the Bayley Scales than did the placebo group (beta = 3.7, SE = 1.3, P < 0.005). This effect remained significant when nutritional status and social background were controlled for. No other significant differences between groups were noted. CONCLUSIONS: The mental development index scores of the zinc-treated group were slightly but significantly lower than those of the placebo group. This finding may have been due to micronutrient imbalance. Caution should be exercised when supplementing undernourished infants with a single micronutrient.     

Iron and/or zinc supplementation did not reduce blood lead concentrations in children in a randomized, placebo-controlled trial

There is increasing interest in the interaction of nutritional deficiencies with toxic metals. Iron deficiency and elevated blood lead concentrations (PbB) reportedly occur together, and zinc also plays an important role in lead metabolism. The objective was to evaluate the effect of zinc and/or iron supplementation on PbB of children attending schools in the neighborhood of a smelter complex for 6 mo. We conducted a double-blind, placebo-controlled field trial in 9 elementary schools located within a 3.5-km radius of a metal foundry in Torreón, Mexico. Of the 602 first-graders enrolled, 517 completed supplementation and had initial and final PbBs. Children were given either 30 mg of iron, 30 mg of zinc, both, or a placebo daily for 6 mo. Baseline and final measures included nutritional status and PbB. The overall prevalence of iron and zinc deficiencies was 12.1 and 30.3%, respectively, and 10.3% were anemic. The PbB concentration decreased in all experimental groups (P < 0.05). After controlling for initial PbB, groups administered zinc and/or iron did not have lower PbB concentrations than the placebo group (P < 0.05). In conclusion, iron supplementation of lead-exposed children significantly improved iron status but did not reduce PbBs. Zinc supplementation did not reduce PbBs independently of zinc nutritional status. Neither iron nor zinc can be recommended as the sole treatment for lead-exposed school children.     

Iron supplementation during pregnancy, anemia, and birth weight: a randomized controlled trial

BACKGROUND: The need for prophylactic iron during pregnancy is uncertain. OBJECTIVE: We tested the hypothesis that administration of a daily iron supplement from enrollment to 28 wk of gestation to initially iron-replete, nonanemic pregnant women would reduce the prevalence of anemia at 28 wk and increase birth weight. DESIGN: Between June 1995 and September 1998, 513 low-income pregnant women in Cleveland were enrolled in the study before 20 wk of gestation. Of these, 275 had a hemoglobin concentration >/= 110 g/L and a ferritin concentration >/= 20 micro g/L and were randomly assigned to receive a monthly supply of capsules containing either 30 mg Fe as ferrous sulfate or placebo until 28 wk of gestation. At 28 and 38 wk of gestation, women with a ferritin concentration of 12 to < 20 micro g/L or < 12 micro g/L received 30 and 60 mg Fe/d, respectively, regardless of initial assignment. Almost all the women received some supplemental iron during pregnancy. We obtained infant birth weight and gestational age at delivery for 117 and 96 of the 146 and 129 women randomly assigned to receive iron and placebo, respectively. RESULTS: Compared with placebo, iron supplementation from enrollment to 28 wk of gestation did not significantly affect the overall prevalence of anemia or the incidence of preterm births but led to a significantly higher mean (+/- SD) birth weight (206 +/- 565 g; P = 0.010), a significantly lower incidence of low-birth-weight infants (4% compared with 17%; P = 0.003), and a significantly lower incidence of preterm low-birth-weight infants (3% compared with 10%; P = 0.017). CONCLUSION: Prenatal prophylactic iron supplementation deserves further examination as a measure to improve birth weight and potentially reduce health care costs.     

Evaluation of oral zinc sulfate effect on obsessive-compulsive disorder: a randomized placebo-controlled clinical trial

ObjectiveObsessive–compulsive disorder is a common neuropsychiatric condition. Although various pharmaceutical agents are available for the treatment of obsessive–compulsive disorder, psychiatrists often find that many patients cannot tolerate the side effects of these medications, the patients do not respond properly to the treatment, or the medications lose their effectiveness after a period of treatment. The augmentation with safe supplementation of medication, such as with trace elements, may be a solution to some of these problems.MethodsThis study was a prospective, double-blinded, 8-wk trial. Twelve patients were given fluoxetine (20 mg/d) plus zinc (440 mg/d) and 11 patients were given fluoxetine plus placebo for 8 wk.ResultsBoth groups showed a decrease in the mean Yale–Brown Obsessive–Compulsive Scale score. Based on t tests, in weeks 2 and 8, patients treated with fluoxetine plus zinc had significantly lower scores than those treated with fluoxetine plus placebo.ConclusionThe results show that zinc, as adjuvant agent for obsessive–compulsive disorder, produces improved outcomes.     

A randomized placebo-controlled trial of iron supplementation in breastfed young infants initiated on complementary feeding: effect on haematological status

To combat iron deficiency manifesting around six months of age, iron-fortified complementary feeding has been recommended. In developing countries, in view of the poor bioavailability of iron from predominantly cereal-based diets and the high cost of fortification, medicinal iron supplementation is an alternative intervention. This double-blind randomized placebo-controlled trial was conducted from April 1999 to March 2000 in the Out-patient Department of a tertiary hospital in New Delhi, India, to evaluate the haematological effects of medicinal iron supplementation to breastfed young infants initiated on complementary feeding. One hundred healthy non-low birth-weight, predominantly breastfed infants aged 4-6 months were randomized into two groups to receive either iron (2 mg/kg/day) (IS group; n=49) or placebo drops (P group; n=51) beginning with the initiation of home-based non-fortified complementary feeding. Haematological parameters and anthropometry of mothers and infants were measured at baseline and repeated for infants after four and eight weeks of recruitment. Seventy-one subjects (35 in the IS group and the 36 in P group) came for the first follow-up, and of these, 43 (19 in the IS group and 24 in the P group) reported for the second visit. The adjusted (for maternal and baseline infant ferritin) serum ferritin levels were significantly higher in the IS group at both the follow-ups (p=0.006). The adjusted (for maternal ferritin and baseline infant ferritin) change in haemoglobin was significantly higher only at the second follow-up (0.7 g/dL; 95% confidence interval [CI] 0.3-1.0 g/dL). The adjusted rise in haemoglobin was higher in initially anaemic infants (at second follow-up by 1 g/dL; 95% CI 0.5-1.6 g/dL). Medicinal iron supplementation, at the time of initiating complementary feeding, to breastfed young infants resulted in an elevation of serum ferritin and haemoglobin. The response was higher in initially anaemic infants. From a programmatic perspective, evidence needs to be generated on the relative merits of selective (anaemic) versus general supplementation and daily versus weekly supplementation.     

Effect of zinc on liver cirrhosis with hyperammonemia: A preliminary randomized,placebo-controlled double-blind trial

ObjectiveTo 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.MethodsPatients 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.ResultsBlood 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.ConclusionAlthough 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.     

Effect of zinc supplementation on growth in West African children: a randomized double-blind placebo-controlled trial in rural Burkina Faso

OBJECTIVE: To analyse the effects of zinc supplementation on growth parameters in a representative sample of young children in rural Burkina Faso. Design Randomized, double-blind, placebo-controlled efficacy trial. Setting Eighteen villages in rural northwestern Burkina Faso. Subjects In all, 709 children aged 6-31 months were enrolled; 685 completed the trial. Intervention Supplementation with zinc (12.5 mg zinc sulphate) or placebo daily for 6 days a week for 6 months. Outcomes Weight, length/height, mid-arm circumference, and serum zinc. RESULTS: In a representative subsample of study children, 72% were zinc-deficient at baseline. After supplementation, serum zinc increased in zinc-supplemented but not in control children of the subsample. No significant differences between groups were observed during follow-up regarding length/height, weight, mid-arm circumference, and z scores for height-for-age, weight-for-age, and weight-for-height. CONCLUSIONS: We conclude that zinc supplementation does not have an effect of public health importance on growth in West African populations of young children with a high prevalence of malnutrition. Multinutrient interventions are likely to be more effective.     

The effect of fish oil supplementation on serum phospholipid fatty acids profile during pregnancy: A double blind randomized controlled trial

Omega-3 fatty acids (FAs) are essential unsaturated long-chain FAs necessary for proper health and growth. The objective of the authors in this study was to evaluate the effect of fish oil supplementation in pregnancy on maternal serum FA profiles. Participants (n = 150 pregnant women aged 18–35 years in Tabriz, Iran) were randomly assigned to receive either 1,000 mg fish oil supplements daily containing 120 mg docosahexanoic acid (DHA) and 180 mg eicosapentaenoic acid (EPA), or placebo from week 21 of pregnancy to delivery. The primary outcome measures were mean serum DHA and EPA proportion of total FAs at weeks 35–37 of pregnancy. Analyses were based on intention-to-treat. No significant differences were observed between the groups in consumption of fish and serum FAs levels at baseline. Fish oil supplementation significantly increased the mean DHA proportion of total FAs in the intervention compared to the placebo group at weeks 35–37 [adjusted Mean Difference (aMD) = 0.15; 95% CI 0.08–0.23]. The mean EPA proportion of total FAs also increased in the intervention group, but the difference between the groups was not significant (aMD = 0.04; 95% CI ?0.01 to 0.08). The dietary recommendation for consumption of 1,000 mg/day fish oil supplements during pregnancy seems beneficial for better serum FA composition.     

Glutamine supplementation in infants with gastrointestinal disease: a randomized, placebo-controlled pilot trial

OBJECTIVE: Glutamine (Gln) is a non-essential amino acid that plays an important role in energy metabolism for gastrointestinal epithelia and other cells with rapid turnover. We evaluated the effects of enteral supplementation with Gln in infants undergoing surgery for congenital or acquired gastrointestinal disease. METHODS: This was a randomized, double-masked, controlled clinical trial. RESULTS: Twenty infants were randomly assigned to receive Gln (n = 9) or placebo amino acid (n = 11), with a goal of supplemental amino acid intake of 0.4 g.kg(-1).d(-1). Infants were weaned from parenteral nutrition, and enteral feeds were started according to a standardized feeding protocol. Median (interquartile range) durations of parenteral nutrition were 39 d (12 to 99) in the Gln group and 21 d (6 to 59) in the control group (P = 0.201). Median (interquartile range) durations needed to reach 80% of the US recommended dietary allowance for energy with enteral nutrition were 24 d (8 to 55) in the Gln group and 12.5 d (5 to 32) in the control group (P = 0.313). There were no differences in the occurrence of infections between groups. Among all infants enrolled, significant correlations were found between duration of parenteral nutrition and residual small bowel length, peak concentrations of direct bilirubin, and alanine aminotransferase. Peak direct bilirubin was associated with longer duration of parenteral nutrition, shorter gestation, older age before feeds were started, shorter bowel length, and larger amounts of parenteral energy and protein intake. CONCLUSIONS: In this pilot trial, enteral Gln supplementation was well tolerated among infants with surgical gastrointestinal disease. There was no effect observed on the duration of parenteral nutrition, tolerance of enteral feeds, or intestinal absorptive or barrier function. Larger, multicenter trials in infants with surgical gastrointestinal disease are needed due to the variability in important outcome measurements.     

孕期补锌对新生儿健康影响随机对照试验meta分析

目的 采用meta分析方法系统定量评价健康孕妇孕期补锌对新生儿出生体重、出生身长、出生头围、早产、低出生体重和围生期死亡的影响,为孕妇合理补锌提供充分的科学依据。方法 检索Pubmed、OVID、EMBASE、WOK、SCOPUS和万方、中国生物医学文献数据库等多个中英文数据库的相关文献,收集所有关于孕妇孕期补充锌与新生儿出生体重、出生身长、出生头围、早产、低出生体重和围生期死亡关系的随机对照试验原始研究数据,应用Rev Man 5.2软件进行meta分析。结果 共纳入符合要求的原始文献15篇,包括14篇英文文献和1篇中文文献;meta分析结果显示,孕期补锌对出生体重影响的MD=18.13(95%CI=-26.72~62.99),对出生身长影响的MD=-0.10(95%CI=-0.24~0.03),对出生头围影响的MD=-0.04(95%CI=-0.13~0.05),对早产影响的相对危险度RR=0.84(95%CI=0.74~0.96),对低出生体重影响的RR=0.85(95%CI=0.66~1.11),对围生期死亡影响的RR=1.27(95%CI=0.68~2.38);孕期干预组单独补充锌对出生体重影响的MD=-30.73(95%CI=-86.82~25.35),对早产影响的RR=0.89(95%CI=0.71~1.11),对低出生体重影响的RR=0.77(95%CI=0.44~1.37);而含锌的多种微量营养素联合补充对出生体重影响的MD=38.13(95%CI=-20.60~96.85),对出生身长影响的MD=-0.08(95%CI=-0.24~0.08),对出生头围影响的MD=-0.02(95%CI=-0.18~0.13),对早产影响的RR=0.78(95%CI=0.64~0.95),对低出生体重影响的RR=0.80(95%CI=0.51~1.26)。结论 孕期单独补充锌可降低早产的发生,但对新生儿出生体重、出生身长、出生头围、低出生体重和围生期死亡无影响。     

Vitamin A supplementation reduces measles morbidity in young African children: a randomized, placebo-controlled, double-blind trial

The effects of vitamin A supplementation on measles morbidity are unclear. Sixty hospitalized children aged 4-24 mo with complicated measles received a World Health Organization--(WHO) recommended dose of vitamin A or placebo. The two groups were comparable in known covariants of measles severity: weight-for-age percentiles, overcrowding, rash, total lymphocytes, and serum concentrations of zinc, albumin, prealbumin, retinol-binding protein, and vitamins A and E. Ninety percent of the patients had hyporetinemia. Integrated morbidity scores, determined by severity of condition (eg, diarrhoea, herpes, and respiratory-tract infection) were assigned on day 8 and 6 wk and 6 mo; these were reduced by 82%, 61%, and 85%, respectively, in the supplemented group, which was mainly due to reduced respiratory-tract infection. There was one death in the placebo group. At 6 wk weight gain was significant in the supplemented group. Despite the selected sample, attention to multiple covariates enhances the validity of the data obtained and supports the current WHO recommendations for vitamin A supplementation during measles.     

Oral magnesium supplementation in asthmatic children: a double-blind randomized placebo-controlled trial

OBJECTIVE: To investigate the long-term effect of oral magnesium supplementation on clinical symptoms, bronchial reactivity, lung function and allergen-induced skin responses in children and adolescents with moderate persistent asthma. DESIGN: A double-blind randomized parallel placebo-controlled study. SETTING AND SUBJECTS: The patients were recruited from the Pediatric Outpatient Clinic, Division of Pulmonology, Allergy and Immunology, and followed at the Center for Investigation in Pediatrics at State University of Campinas Hospital, Brazil. Thirty-seven out of 72 patients met the study criteria. There were no dropouts. INTERVENTION: The 37 patients (aged 7-19 years, 19 males) were randomized in two groups: magnesium (n=18, 300 mg/day) and placebo (n=19), during 2 months. Both patient groups received inhaled fluticasone (250 microg twice a day) and salbutamol as needed. The primary outcome was bronchial reactivity evaluated with methacholine challenge test (PC20). RESULTS: After a follow-up of 2 months, the methacholine PC20 for testing bronchial reactivity has augmented significantly in the magnesium group only. The skin responses to recognized antigens have also decreased in patients treated with magnesium. The forced vital capacity (FVC), the forced expiratory volume at first second (FEV1), the forced expiratory flow at 25-75 and the FEV1/FVC ratio were similar in both groups. The magnesium group presented fewer asthma exacerbations and used less salbutamol compared to the placebo group. CONCLUSIONS: Oral magnesium supplementation helped to reduce bronchial reactivity to methacholine, to diminish their allergen-induced skin responses and to provide better symptom control in pediatric patients with moderate persistent asthma treated with inhaled fluticasone.     

Effect of fish-oil supplementation on mental well-being in older subjects: a randomized, double-blind, placebo-controlled trial

BACKGROUND: It is suggested that a low intake of fish and/or n-3 PUFA is associated with depressed mood. However, results from epidemiologic studies are mixed, and randomized trials have mainly been performed in depressed patients, yielding conflicting results. OBJECTIVE: We investigated the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on mental well-being in a double-blind, placebo-controlled trial. DESIGN: Independently living individuals (n = 302) aged > or =65 y were randomly assigned to consume 1800 mg/d EPA+DHA, 400 mg/d EPA+DHA, or placebo capsules for 26 wk. Changes in mental well-being were assessed as the primary outcome with the Center for Epidemiologic Studies Depression Scale (CES-D), Montgomery-Asberg Rating Scale (MADRS), Geriatric Depression Scale (GDS-15), and Hospital Anxiety and Depression Scale (HADS-A). RESULTS: Plasma concentrations of EPA+DHA increased by 238% in the high-dose and 51% in the low-dose fish-oil group compared with the placebo group, reflecting excellent compliance. Baseline CES-D scores ranged from 5.9 to 6.8 in the 3 groups and were not significantly different between groups. Mean changes in CES-D scores after 26 wk were -0.2, 0.2, and -0.4 (P = 0.87) in the high-dose fish oil, low-dose fish oil, and placebo groups, respectively. Treatment with neither 1800 mg nor 400 mg EPA+DHA differentially affected any of the measures of mental well-being after 13 or 26 wk of intervention compared with placebo. CONCLUSIONS: In this randomized, double-blind, placebo-controlled trial we observed no effect of EPA+DHA supplementation for 26 wk on mental well-being in the general older population studied. This trial was registered at clinicaltrials.gov as NCT00124852.     

Short-term supplementation with zinc and vitamin A has no significant effect on the growth of undernourished Bangladeshi children.

BACKGROUND: Several vitamin A supplementation trials have failed to improve the growth rate in children. Addition of zinc to vitamin A might result in enhanced growth. OBJECTIVE: This study evaluated the effect on growth in children of simultaneous supplementation with zinc and vitamin A. DESIGN: This was a randomized, double-blind, placebo-controlled intervention trial. Six hundred fifty-three children aged 12-35 mo were randomly assigned to 1 of 4 intervention groups: 20 mg Zn/d for 14 d (Z group), 60000 retinol equivalents (200000 IU) vitamin A on day 14 (A group), zinc plus vitamin A (ZA group), or placebo syrup and placebo capsule (placebo group). Weight and length were measured at enrollment and again after 3 and 6 mo. RESULTS: Gains in weight and length during the 6-mo follow-up period were not significantly different among the 4 groups by analysis of variance. Catch-up growth also did not differ significantly among the groups. The proportions of children whose weight-for-age z scores did not change or decreased were 57% in the Z group, 46% in the A group, 50% in the ZA group, and 54% in the placebo group (NS). The proportions of children whose length-for-age z scores did not change or decreased were 42% in the Z group, 48% in the A group, 53% in the ZA group, and 46% in the placebo group (NS). CONCLUSION: Combined short-term zinc supplementation and a single dose of vitamin A has no significant effects on weight and length increments in children over a 6-mo period.     

Effects of galactooligosaccharide and long-chain fructooligosaccharide supplementation during pregnancy on maternal and neonatal microbiota and immunity--a randomized, double-blind, placebo-controlled study

BACKGROUND: Galactooligosaccharides (GOS) and long-chain fructooligosaccharides (lcFOS) proliferate bifidobacteria in infant gut microbiota. However, it is not known how GOS and FOS influence the microbiota of pregnant women and whether a potential prebiotic effect is transferred to the offspring. OBJECTIVES: We aimed to test how supplementation with GOS and lcFOS (GOS/lcFOS) in the last trimester of pregnancy affects maternal and neonatal gut microbiota. Variables of fetal immunity were assessed as a secondary outcome. DESIGN: In a randomized, double-blind, placebo-controlled pilot study, 48 pregnant women were supplemented 3 times/d with 3 g GOS/lcFOS (at a ratio of 9:1) or maltodextrin (placebo) from week 25 of gestation until delivery. Percentages of bifidobacteria and lactobacilli within total bacterial counts were detected by fluorescent in situ hybridization and quantitative polymerase chain reaction in maternal and neonatal (days 5, 20, and approximately 182) stool samples. Variables of fetal immunity were assessed in cord blood by using flow cytometry and cytokine multiplex-array analysis. RESULTS: The proportions of bifidobacteria in the maternal gut were significantly higher in the supplemented group than in the placebo group (21.0% and 12.4%, respectively; P = 0.026); the proportion of lactobacilli did not differ between the groups. In neonates, bifidobacteria and lactobacilli percentages, diversity and similarity indexes, and fetal immune parameters did not differ significantly between the 2 groups. Mother-neonate similarity indexes of bifidobacteria decreased over time. CONCLUSIONS: GOS/lcFOS supplementation has a bifidogenic effect on maternal gut microbiota that is not transferred to neonates. The increased maternal bifidobacteria did not affect fetal immunity as measured by a comprehensive examination of cord blood immunity variables.