Randomized controlled trial of zinc supplementation for persistent diarrhea in adults with HIV-1 infection.

Department of Epidemiology, University of Washington, Seattle, WA 98104, USA.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.39). 10/2006; 43(2):197-201. DOI: 10.1097/01.qai.0000242446.44285.b5
Source: PubMed

ABSTRACT In children, zinc supplementation reduces the incidence and severity of diarrhea.
HIV-infected adults with > or =7 days of diarrhea recruited at 3 tertiary hospitals in Lima, Peru, received a zinc sulfate capsule containing 50 mg of elemental zinc twice daily or an identical placebo for 14 days. Outcomes included persistence of diarrhea at day 14 and time until cessation of diarrhea.
The 81 subjects randomized to zinc and 78 randomized to placebo were comparable at baseline, except for higher prevalences of certain enteric pathogens in the zinc group; complete follow-up rates were 62% and 69%, respectively. Zinc concentrations were consistent with zinc deficiency at follow-up in 94% of placebo recipients and 66% of zinc recipients (P = 0.01). Persistence of diarrhea at day 14 according to follow-up interview (60% for zinc-treated patients and 57.4% for placebo-treated patients) or to patient diary (42.2% vs. 31.9%) did not differ significantly. Adjusting for enteric pathogens and CD4 count, the hazard ratio (HR) for zinc supplementation and cessation of diarrhea (according to the diaries) was 0.91 (95% confidence interval [CI]: 0.50 to 1.64).
Supplemental zinc had no significant effect on the duration or remission of diarrhea in HIV-infected adults.

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    ABSTRACT: To evaluate clinical data indicating the benefits of oral zinc supplementation to prevent and/or treat diarrhea in children and extend these findings to adults. Zinc plays an important role in modulating host resistance to infectious agents and reducing the risk, severity, and duration of diarrheal diseases. Zinc is important in the developing world and in low-income and middle-income countries where mild-to-moderate zinc deficiency is highly prevalent.The WHO/UNICEF recommendations for zinc supplementation are based on meta-analyses of randomized, controlled intervention trials on children: 20 mg zinc/day for 10-14 days for children with acute diarrhea and 10 mg/day for infants under 6 months of age. Effective forms include sulfate, gluconate, or acetate. No similar studies have been conducted on adults. Thus, carefully conducted clinical trials are necessary to ascertain the efficacy of zinc in prevention of acute and persistent diarrhea in adults. Faced with rising antibiotic resistance and the lack of effective antidiarrheal vaccines, oral zinc provides substantial benefit in the reduction of stool output and disease duration combined with safety, selectivity of action, and low cost. Thus, oral zinc supplementation is a practical therapeutic intervention for the treatment of diarrhea in children, and by extension, should be provided to adults.
    Current Opinion in Clinical Nutrition and Metabolic Care 12/2008; 11(6):711-7. DOI:10.1097/MCO.0b013e3283109092 · 3.97 Impact Factor
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    ABSTRACT: Background Diarrhoea causes around two million child deaths annually. Zinc supplementation could help reduce the duration and severity of diarrhoea, and is recommended by the World Health Organization and UNICEF.Objectives To evaluate oral zinc supplementation for treating children with acute or persistent diarrhoea.Search strategyIn November 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 4), MEDLINE, EMBASE, LILACS, CINAHL, mRCT, and reference lists. We also contacted researchers.Selection criteriaRandomized controlled trials comparing oral zinc supplementation (≥ 5 mg/day for any duration) with placebo in children aged one month to five years with acute or persistent diarrhoea, including dysentery.Data collection and analysisBoth authors assessed trial eligibility and methodological quality, extracted and analysed data, and drafted the review. Diarrhoea duration and severity were the primary outcomes. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD) with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses (using the fixed- or random-effects model) and assessed heterogeneity.Main resultsEighteen trials enrolling 6165 participants met our inclusion criteria. In acute diarrhoea, zinc resulted in a shorter diarrhoea duration (MD -12.27 h, 95% CI -23.02 to -1.52 h; 2741 children, 9 trials), and less diarrhoea at day three (RR 0.69, 95% CI 0.59 to 0.81; 1073 children, 2 trials), day five (RR 0.55, 95% CI 0.32 to 0.95; 346 children, 2 trials), and day seven (RR 0.71, 95% CI 0.52 to 0.98; 4087 children, 7 trials). The four trials (1458 children) that reported on diarrhoea severity used different units and time points, and the effect of zinc was less clear. Subgroup analyses by age (trials with only children aged less than six months) showed no benefit with zinc. Subgroup analyses by nutritional status, geographical region, background zinc deficiency, zinc type, and study setting did not affect the results' significance. Zinc also reduced the duration of persistent diarrhoea (MD -15.84 h, 95% CI -25.43 to -6.24 h; 529 children, 5 trials). Few trials reported on severity, and results were inconsistent. No trial reported serious adverse events, but vomiting was more common in zinc-treated children with acute diarrhoea (RR 1.71, 95% 1.27 to 2.30; 4727 children, 8 trials).Authors' conclusionsIn areas where diarrhoea is an important cause of child mortality, research evidence shows zinc is clearly of benefit in children aged six months or more.Plain Language SummaryOral zinc supplementation for treating diarrhoea in childrenIn developing countries, millions of children suffer from severe diarrhoea every year. This is due to infection and malnutrition, and many die from dehydration due to the diarrhoea. Giving fluids by mouth (using an oral rehydration solution) has been shown to save children's lives, but it seems to have no effect on the length of time the children suffer with diarrhoea. Children in developing countries are often zinc deficient. Zinc supplementation is a possible treatment for diarrhoea though it can have adverse effects if given in high doses. The review of trials identified 18 trials involving 6165 children of all ages. Zinc reduced the time that children over the age of six months suffered from symptoms of acute or persistent diarrhoea. However, there were insufficient data to see any impact on the number of children who died. More children vomited when given zinc, but it was considered that the benefits outweighed these adverse effects. Zinc seemed to have no impact on children aged less than six months. In areas where diarrhoea is an important cause of child mortality, research evidence shows zinc is clearly of benefit in children aged six months or more with diarrhoeal diseases.
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