Use Of Zinc Supplementation Research Articles

Oral zinc for treating diarrhoea in children.

BackgroundIn developing countries, diarrhoea causes around 500,000 child deaths annually. Zinc supplementation during acute diarrhoea is currently recommended by the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF).ObjectivesTo evaluate oral zinc supplementation for treating children with acute or persistent diarrhoea.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library 2016, Issue 5), MEDLINE, Embase, LILACS, CINAHL, mRCT, and reference lists up to 30 September 2016. We also contacted researchers.Selection criteriaRandomized controlled trials (RCTs) that compared oral zinc supplementation with placebo in children aged one month to five years with acute or persistent diarrhoea, including dysentery.Data collection and analysisBoth review authors assessed trial eligibility and risk of bias, extracted and analysed data, and drafted the review. The primary outcomes were diarrhoea duration and severity. 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 either a fixed‐effect or random‐effects model) and assessed heterogeneity.We assessed the certainty of the evidence using the GRADE approach.Main resultsThirty‐three trials that included 10,841 children met our inclusion criteria. Most included trials were conducted in Asian countries that were at high risk of zinc deficiency.Acute diarrhoeaThere is currently not enough evidence from well‐conducted RCTs to be able to say whether zinc supplementation during acute diarrhoea reduces death or number of children hospitalized (very low certainty evidence).In children older than six months of age, zinc supplementation may shorten the average duration of diarrhoea by around half a day (MD −11.46 hours, 95% CI −19.72 to −3.19; 2581 children, 9 trials, low certainty evidence), and probably reduces the number of children whose diarrhoea persists until day seven (RR 0.73, 95% CI 0.61 to 0.88; 3865 children, 6 trials, moderate certainty evidence). In children with signs of malnutrition the effect appears greater, reducing the duration of diarrhoea by around a day (MD −26.39 hours, 95% CI −36.54 to −16.23; 419 children, 5 trials, high certainty evidence).Conversely, in children younger than six months of age, the available evidence suggests zinc supplementation may have no effect on the mean duration of diarrhoea (MD 5.23 hours, 95% CI −4.00 to 14.45; 1334 children, 2 trials, low certainty evidence), or the number of children who still have diarrhoea on day seven (RR 1.24, 95% CI 0.99 to 1.54; 1074 children, 1 trial, low certainty evidence).None of the included trials reported serious adverse events. However, zinc supplementation increased the risk of vomiting in both age groups (children greater than six months of age: RR 1.57, 95% CI 1.32 to 1.86; 2605 children, 6 trials, moderate certainty evidence; children less than six months of age: RR 1.54, 95% CI 1.05 to 2.24; 1334 children, 2 trials, moderate certainty evidence).Persistent diarrhoeaIn children with persistent diarrhoea, zinc supplementation probably shortens the average duration of diarrhoea by around 16 hours (MD −15.84 hours, 95% CI −25.43 to −6.24; 529 children, 5 trials, moderate certainty evidence).Authors' conclusionsIn areas where the prevalence of zinc deficiency or the prevalence of malnutrition is high, zinc may be of benefit in children aged six months or more. The current evidence does not support the use of zinc supplementation in children less six months of age, in well‐nourished children, and in settings where children are at low risk of zinc deficiency.12 April 2019Up to dateAll studies incorporated from most recent searchAll eligible published studies found in the last search (30 Sep, 2016) were included and two ongoing studies have been identified (see 'Characteristics of ongoing studies' section)

Zinc and Taste Disturbances in Older Adults: A Review of the Literature.

According to the National Health and Nutrition Examination Survey III, 35% to 45% of adults 60 years of age or older had zinc intakes below the estimated average requirement of 6.8 mg/day for elderly females and 9.4 mg/day for elderly males. Zinc deficiency may lead to loss of appetite, impaired immune function, weight loss, delayed healing of wounds, eye and skin lesions, and smell and taste disturbances. Older adults are especially affected by changes in taste sensations because of age-related gustatory dysfunction, use of multiple medications, increased frailty, and zinc deficiency. This article reviews the finding of clinical studies investigating the use of zinc supplementation for improvement with taste disturbances in older adults.

Zinc Intake Is Associated with Lower Cadmium Burden in US Adults1–3

Background: Cadmium is a toxic transition metal whose absorption and accumulation might depend on zinc intake.Objective: We sought to determine whether zinc intake and serum zinc would be inversely associated with cadmium exposure.Methods: This study used data from NHANES 2003–2012, from which there were 6678 and 6488 participants with urinary and blood cadmium data, respectively, and 1195 participants with serum zinc data. Mean blood and urinary cadmium were reported by quintiles of zinc intake and by the dose and duration of zinc supplement use. The associations between zinc intake from diet and supplements, serum zinc, and blood and urinary cadmium were determined using multiple regression. Analyses were adjusted for age, body mass index, race/ethnicity, gender, income-to-poverty ratio, education, smoking status, and mean intakes of energy, calcium, and iron.Results: Urinary cadmium concentrations were 0.04 <g/g creatinine lower among participants in the highest compared with lowest quintile of total zinc intake (P-trend = 0.0041). Zinc supplement dose and duration were inversely associated with blood cadmium (P = 0.0372) and serum zinc (P-trend = 0.0017), respectively. In adjusted regression models, a 10% increase in total zinc intake corresponded to a predicted decrease in blood cadmium of 0.42% (95% CI: −0.79%, −0.06%; P = 0.0260) and in urinary cadmium of 0.42% (95% CI: −0.81%, −0.04%; P = 0.0340). A 10% increase in serum zinc was associated with a predicted 1.99% (95% CI: −3.17%, −0.81%; P = 0.0012) decrease in blood cadmium and a predicted 4.09% (95% CI: 2.14%, 6.04%, P = 0.0001) increase in urinary cadmium.Conclusions: Dietary and serum zinc in US adults are associated with cadmium exposure, presumably by influencing the absorption and accumulation of cadmium. Whether the degree of reduction in cadmium exposure from greater zinc intake and status is causal or relevant from a public health perspective needs further investigation.

Zinc supplementation for the prevention of type 2 diabetes mellitus in adults with insulin resistance.

Diabetes is associated with long-term damage, dysfunction and failure of various organs, especially the eyes, kidneys, nerves, heart and blood vessels. The risk of developing type 2 diabetes increases with age, obesity and lack of physical activity. Insulin resistance is a fundamental aspect of the aetiology of type 2 diabetes. Insulin resistance has been shown to be associated with atherosclerosis, dyslipidaemia, glucose intolerance, hyperuricaemia, hypertension and polycystic ovary syndrome. The mineral zinc plays a key role in the synthesis and action of insulin, both physiologically and in diabetes mellitus. Zinc seems to stimulate insulin action and insulin receptor tyrosine kinase activity. To assess the effects of zinc supplementation for the prevention of type 2 diabetes mellitus in adults with insulin resistance. This review is an update of a previous Cochrane systematic review published in 2007. We searched the Cochrane Library (2015, Issue 3), MEDLINE, EMBASE, LILACS and the ICTRP trial register (from inception to March 2015). There were no language restrictions. We conducted citation searches and screened reference lists of included studies. We included studies if they had a randomised or quasi-randomised design and if they investigated zinc supplementation compared with placebo or no intervention in adults with insulin resistance living in the community. Two review authors selected relevant trials, assessed risk of bias and extracted data. We included three trials with a total of 128 participants in this review. The duration of zinc supplementation ranged between four and 12 weeks. Risk of bias was unclear for most studies regarding selection bias (random sequence generation, allocation concealment) and detection bias (blinding of outcome assessment). No study reported on our key outcome measures (incidence of type 2 diabetes mellitus, adverse events, health-related quality of life, all-cause mortality, diabetic complications, socioeconomic effects). Evaluation of insulin resistance as measured by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) showed neutral effects when comparing zinc supplementation with control (two trials; 114 participants). There were neutral effects for trials comparing zinc supplementation with placebo for total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides (2 studies, 70 participants). The one trial comparing zinc supplementation with exercise also showed neutral effects for total cholesterol, HDL and LDL cholesterol, and a mean difference in triglycerides of -30 mg/dL (95% confidence interval (CI) -49 to -10) in favour of zinc supplementation (53 participants). Various surrogate laboratory parameters were also analysed in the included trials. There is currently no evidence on which to base the use of zinc supplementation for the prevention of type 2 diabetes mellitus. Future trials should investigate patient-important outcome measures such as incidence of type 2 diabetes mellitus, health-related quality of life, diabetic complications, all-cause mortality and socioeconomic effects.

Is there randomized controlled trial evidence to support the use of zinc supplementation in children for preventing mortality, morbidity, and growth failure?

Is there randomized controlled trial evidence to support the use of zinc supplementation in children for preventing mortality, morbidity, and growth failure?

Infectious diarrhea: an overview.

Diarrheal disease, which is most often caused by infectious pathogens, is a significant cause of morbidity and mortality worldwide, especially in children. This is particularly true in developing countries. Recent outbreaks of infectious diarrhea in developed countries, including the USA, are often attributed to food handling and distribution practices and highlight the need for continued vigilance in this area. Another common cause of infectious diarrhea, Clostridium difficile infection (CDI), has historically been associated with the use of antibiotics and exposure to a health-care setting but is now increasingly common in the community in persons who lack the typical risk factors. Recent scientific advances have also led to new and proposed new therapies for infectious diarrhea, including fecal microbiota transplant (FMT) for recurrent C. difficile infection (RCDI), probiotics for prevention of antibiotic-associated diarrhea (AAD) and CDI, and the use of zinc supplementation in the treatment of acute diarrhea in children. Other therapies that have been in use for decades, such as the oral rehydration solution (ORS), continue to be the targets of scientific advancement in an effort to improve delivery and efficacy. Finally, post-infectious irritable bowel syndrome (PI-IBS) is an increasingly recognized occurrence. Attempts to understand the mechanism behind this phenomenon are underway and may provide insight into potential treatment options.

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

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. Cross-sectional national nutrition survey (2007 Australian Children's Nutrition and Physical Activity Survey) and a review of commercially available Zn supplements. Australia. Children (n 4834) aged 2-16 years. 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. 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.

Hair Zinc Levels and the Efficacy of Oral Zinc Supplementation in Patients with Atopic Dermatitis

Zinc deficiency in patients with atopic dermatitis (AD) and the use of zinc supplementation is still controversial. We measured hair zinc levels in 58 children with AD and 43 controls (age range 2-14 years). We also investigated the efficacy of oral zinc supplementation in AD patients with low hair zinc levels by comparing eczema assessment severity index (EASI), transepidermal water loss (TEWL), and visual analogue scales for pruritus and sleep disturbance in patients receiving zinc supplementation (Group A) and others not receiving supplementation (Group B). At baseline, the mean zinc level was significantly reduced in AD patients (113.1 μg/g vs. 130.9 μg/g, p = 0.012). After 8 weeks of supplement, hair zinc level increased significantly in Group A (p < 0.001), and EASI scores, TEWL, and visual analogue scales for pruritus improved more in Group A than in Group B (p = 0.044, 0.015 and < 0.001, respectively). Thus, oral zinc supplementation may be effective in AD patients with low hair zinc levels.

A Question Mark on Zinc Deficiency in 185 Million People in Pakistan—Possible Way Out

This paper reviews research published in recent years concerning the effects of zinc deficiency, its consequences, and possible solutions. Zinc is an essential trace element necessary for over 300 zinc metalloenzymes and required for normal nucleic acid, protein, and membrane metabolism. Zinc deficiency is one of the ten biggest factors contributing to burden of disease in developing countries. Populations in South Asia, South East Asia, and sub-Saharan Africa are at greatest risk of zinc deficiency. Zinc intakes are inadequate for about a third of the population and stunting affects 40% of preschool children. In Pakistan, zinc deficiency is an emerging health problem as about 20.6% children are found in the levels of zinc, below 60 μg/dL. Signs and symptoms caused by zinc deficiency are poor appetite, weight loss, and poor growth in childhood, delayed healing of wounds, taste abnormalities, and mental lethargy. As body stores of zinc decline, these symptoms worsen and are accompanied by diarrhea, recurrent infection, and dermatitis. Daily zinc requirements for an adult are 12–16 mg/day. Iron, calcium and phytates inhibit the absorption of zinc therefore simultaneous administration should not be prescribed. Zinc deficiency and its effects are well known but the ways it can help in treatment of different diseases is yet to be discovered. Improving zinc intakes through dietary improvements is a complex task that requires considerable time and effort. The use of zinc supplements, dietary modification, and fortifying foods with zinc are the best techniques to combat its deficiency.

Comparison of the Serum Concentration of Zinc in Patients With Bronchiectasis and Control Group

BackgroundBronchiectasis is an abnormal and permanent dilatation of bronchi. Infection plays a major role in causing and perpetuating bronchiectasis, as reducing the microbial load and attendant mediators are cornerstone of therapy. Zinc, as an integral micronutrient is involved in the immune reactions including response to infection. In several previous studies, mild zinc deficiency has been described in many infectious diseases such as abscess, cellulitis, chronic diarrhea, pneumonia, tuberculosis (TB), etc.ObjectivesThe purpose of this study was to determine serum zinc level in a series of patients suffering from bronchiectasis and to compare it with healthy control group.Patients and MaterialsThis analytical cross-sectional study was performed on thirty four patients with proven bronchiectasis and twenty nine healthy control subjects referred to Rasoul-e-Akram Hospital, Tehran, Iran, between March 2005 and March 2007. Serum concentration of the zinc was measured for all of the subjects and other information was completed according to their medical records. Both groups (case and control) were frequently matched regarding their age groups.ResultsPatients included 11 (32.4%) males and 23 (67.6%) females with the average age of 55.03 (SD = 17.06) yr. The mean level of serum zinc in the case and control groups were 94.06 (SD = 20/96) mcg/dl and 103.7 (SD = 11.96) mcg/dl, respectively. Independent T-test analysis showed that serum zinc concentration in the case group of bronchiectasis patients was significantly lower than control group (P = 0.02).ConclusionsThe results of our study show that serum zinc level in bronchiectasis patients was lower than the control group and the difference was statistically significant. It seems that the use of zinc supplement can reduce progression of the infectious disease regarding its role in improving the immune system reactions and some unknown mechanisms. Therefore, prophylactic and therapeutic use of zinc must be evaluated in further trials.

Canadian program targets diarrhea-related child deaths in India

A new Canadian program aims to save the lives of about 150 000 children in three states in India by scaling up the use of zinc supplementation and oral rehydration salts. The Zinc Alliance for Child Health (ZACH) is a movement of Canadian organizations led by UNICEF Canada and Teck Resources Limited

Zinc deficiency induces production of the proinflammatory cytokines IL-1β and TNFα in promyeloid cells via epigenetic and redox-dependent mechanisms

The deprivation of zinc, caused by malnutrition or as a consequence of aging or disease, strongly affects immune cell functions, causing higher frequency of infections. Among other effects, an increased production of reactive oxygen species (ROS) and proinflammatory cytokines has been observed in zinc-deficient patients, but the underlying mechanisms were unknown. The aim of the current study was to define mechanisms explaining the increase in proinflammatory cytokine production during zinc deficiency, focusing on the role of epigenetic and redox-mediated mechanisms.Interleukin (IL)-1β and tumor necrosis factor (TNF)α production was increased in HL-60 cells under zinc deficiency. Analyses of the chromatin structure demonstrated that the elevated cytokine production was due to increased accessibilities of IL-1β and TNFα promoters in zinc-deficient cells. Moreover, the level of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) oxidase-produced ROS was elevated under zinc deficiency, subsequently leading to p38 mitogen-activated protein kinase (MAPK) phosphorylation. The increased activation of p38 MAPK appeared to be necessary for posttranscriptional processes in IL-1β and TNFα synthesis.These data demonstrate that IL-1β and TNFα expression under zinc deficiency is regulated via epigenetic and redox-mediated mechanisms. Assuming an important role of zinc in proinflammatory cytokine regulation, this should encourage research in the use of zinc supplementation for treatment of inflammatory diseases.

Knowledge and Use of Zinc Supplementation in the Management of Childhood Diarrhoea among Health Care Workers in Public Primary Health Facilities in Benin-City, Nigeria

Zinc supplementation reduces the severity, duration and recurrence of childhood acute diarrhoea. These beneficial effects of zinc in the treatment of diarrhoea led to the inclusion of a 10-14 days treatment regimen by the WHO/UNICEF. This study assessed the level of knowledge and use of zinc supplementation in the management of childhood diarrhoea among health care workers in public primary health facilities in Benin-City, Nigeria.Methodology:This cross-sectional study was carried out among the total population of health care providers in public primary health facilities in Benin-City. Data collection was done using a pre-tested, structured, self-administered questionnaire and data was analyzed using SPSS version 15.0.Results:A total of 168 health care workers participated in the study. Two-thirds of them were aware of zinc supplementation but specific knowledge of zinc supplementation in the management of childhood acute diarrhoea was poor. Thirty-five percent of them prescribed zinc when managing childhood diarrhoea and only 10% of these do so for every case of childhood diarrhoea. About 84.6% of them prescribed the correct dose of zinc while less than half of them prescribe it for the correct duration. All but one of them prescribed zinc in addition to ORS in line with the WHO guideline.Discussion:The study revealed a gap in the knowledge and practice of use of zinc supplementation in the management of childhood diarrhoea. It is recommended that nationwide campaigns should be embarked on to promote the use of zinc supplementation in the clinical management of childhood diarrhoea.

The effect of zinc supplementation on diarrheal diseases in children in the Niger Delta Sub-Region of Nigeria

This study evaluated the trend of diarrheal diseases managed with zinc supplementation by comparing it with diarrheal diseases managed without zinc supplementation at the University of Port Harcourt Teaching hospital (UPTH), Nigeria. The study was a descriptive retrospective study done at the Diarrhea Training Unit (DTU) of UPTH to determine the effect of zinc supplementation in the management of diarrhea in children under 5 years. Out of the 134 case records studied, of children aged 0 to 59 months who presented with diarrhea at the DTU, 57 children did not receive zinc supplementation between October and December, 2007 and 77 children received zinc supplementation between October and December 2009. The results showed that (74) 96.1% of patients who received zinc supplementation, and (48) 84.2% of those who did not, had no repeat diarrheal episodes when seen at the follow up clinic. On the other hand, 1.3% of those who received zinc supplementation and 1.8% of those who did not, had increased episodes of diarrhea when seen at the follow up clinic. Of those who received, and those who did not receive zinc supplementation, 2.6% and 14% respectively, had reduced episodes of diarrhea. These findings clearly demonstrate the effectiveness of zinc supplementation in halting the course of diarrheal diseases in children aged 0 to 59 months. We therefore advocate for the use of zinc supplementation in the management of diarrhea in Nigeria

Roles of Zinc in the Pathophysiology of Acute Diarrhea

Zinc has caught wide scientific attention for the conceptual promise it has to offer for prevention, control and treatment of acute diarrhea. This review focuses on the mechanisms by which zinc might contribute to the pathogenesis of acute diarrhea and the degree of success achieved in diarrhea control and treatment by zinc supplementation. Animal and in vitro studies have continued to fascinate the scientific fraternity and form a solid basis for the potential use of zinc supplementation against diarrhea. However, emerging evidence in terms of controlled studies in humans beckons a more complete understanding of the mechanistic basis for zinc supplementation. Current evidence indicates that studies specifically addressing the variability in response to zinc supplementation need to be undertaken to better comprehend these mechanisms.

What zinc supplementation does and does not achieve in diarrhea prevention: a systematic review and meta-analysis

BackgroundPrevention of diarrhea has presented indomitable challenges. A preventive strategy that has received significant interest is zinc supplementation. Existing literature including quantitative meta-analyses and systematic reviews tend to show that zinc supplementation is beneficial however evidence to the contrary is augmenting. We therefore conducted an updated and comprehensive meta-analytical synthesis of the existing literature on the effect of zinc supplementation in prevention of diarrhea.MethodsEMBASE®, MEDLINE ® and CINAHL® databases were searched for published reviews and meta-analyses on the use of zinc supplementation for the prevention childhood diarrhea. Additional RCTs published following the meta-analyses were also sought. Effect of zinc supplementation on the following five outcomes was studied: incidence of diarrhea, prevalence of diarrhea, incidence of persistent diarrhea, incidence of dysentery and incidence of mortality. The published RCTs were combined using random-effects meta-analyses, subgroup meta-analyses, meta-regression, cumulative meta-analyses and restricted meta-analyses to quantify and characterize the role of zinc supplementation with the afore stated outcomes.ResultsWe found that zinc supplementation has a modest beneficial association (9% reduction) with incidence of diarrhea, a stronger beneficial association (19% reduction) with prevalence of diarrhea and occurrence of multiple diarrheal episodes (28% reduction) but there was significant unexplained heterogeneity across the studies for these associations. Age, continent of study origin, zinc salt and risk of bias contributed significantly to between studies heterogeneity. Zinc supplementation did not show statistically significant benefit in reducing the incidence of persistent diarrhea, dysentery or mortality. In most instances, the 95% prediction intervals for summary relative risk estimates straddled unity.ConclusionsDemonstrable benefit of preventive zinc supplementation was observed against two of the five diarrhea-related outcomes but the prediction intervals straddled unity. Thus the evidence for a preventive benefit of zinc against diarrhea is inconclusive. Continued efforts are needed to better understand the sources of heterogeneity. The outcomes of zinc supplementation may be improved by identifying subgroups that need zinc supplementation.

Situational analysis of infant and young child nutrition policies and programmatic activities in the Islamic Republic of Mauritania.

Progress towards reducing mortality and malnutrition among children <5 years of age has been less than needed to achieve related Millennium Development Goals (MDGs), so several international agencies joined to 'reposition children's right to adequate nutrition in the Sahel', starting with an analysis of current activities related to infant and young child nutrition (IYCN). The main objectives of the situational analysis are to compile, analyse, and interpret available information on infant and child feeding, and the nutrition and health situation of children <2 years of age in Mauritania as one of the six target countries (Burkina Faso, Chad, Mali, Mauritania, Niger, Senegal). These findings are available to assist countries in identifying inconsistencies and filling gaps in current programming. Between August and November of 2008, key informants responsible for conducting IYCN-related activities in Mauritania were interviewed, and 46 documents were examined on the following themes: optimal breastfeeding and complementary feeding practices, prevention of micronutrient deficiencies, prevention of mother-to-child transmission of human immunodeficiency virus (HIV), management of acute malnutrition, food security, and hygienic practices. Mauritania is on track to reaching the MDG of halving undernutrition among children <5 years of age by 2015. National policy documents, training guides, and programmes address nearly all of the key IYCN topics, specifically or generally. Exceptions are the use of zinc supplements in diarrhoea treatment, prevention of zinc deficiency, and dietary guidelines for preventing mother-to-child transmission of HIV. Substantial infrastructure capacity building was also recently implemented in nutritionally high-risk regions, and increases were reported in exclusive breastfeeding rates among children <6 months. The recent National Behaviour Change Communication Strategy is intended to address the needs of adapting programme activities to local needs. Despite these noteworthy accomplishments, the prevalence of acute malnutrition remains high, mortality rates did not decrease as malnutrition rates decreased, the overall prevalence of desirable nutrition-related practices is low, and human resources are reportedly insufficient to carry out all nutrition-related programme activities. Very little nutrition research has been conducted in Mauritania, and key informants identified gaps in adapting international programmes to local needs. Monitoring and evaluation reports have not been rigorous enough to identify which programme activities were implemented as designed or whether programmes were effective at improving nutritional and health status of young children. Therefore, we could not confirm which programmes might have been responsible for the reported improvements, or if other population-wide changes contributed to these changes. The policy framework is supportive of optimal IYCN practices, but greater resources and capacity building are needed to (i) support activities to adapt training materials and programme protocols to fit local needs, (ii) expand and track the implementation of evidence-based programmes nationally, (iii) improve and carry out monitoring and evaluation that identify effective and ineffective programmes, and (iv) apply these findings in developing, disseminating, and improving effective programmes.

Randomized, Controlled Clinical Trial of Zinc Supplementation to Prevent Immunological Failure in HIV‐Infected Adults

Adequate zinc is critical for immune function; however, zinc deficiency occurs in >50% of human immunodeficiency virus (HIV)-infected adults. We examined the safety and efficacy of long-term zinc supplementation in relation to HIV disease progression. A prospective, randomized, controlled clinical trial was conducted involving 231 HIV-infected adults with low plasma zinc levels (<0.75 mg/L), who were randomly assigned to receive zinc (12 mg of elemental zinc for women and 15 mg for men) or placebo for 18 months. The primary end point was immunological failure. HIV viral load and CD4(+) cell count were determined every 6 months. Questionnaires, pill counts, and plasma zinc and C-reactive protein levels were used to monitor adherence to study supplements and antiretroviral therapy. Intent-to-treat analysis used multiple-event analysis, treating CD4(+) cell count <200 cells/mm(3) as a recurrent immunological failure event. Cox proportional hazard models and the general-linear model were used to analyze morbidity and mortality data. Zinc supplementation for 18 months reduced 4-fold the likelihood of immunological failure, controlling for age, sex, food insecurity, baseline CD4(+) cell count, viral load, and antiretroviral therapy (relative rate, 0.24; 95% confidence interval, 0.10-0.56; P<.002). Viral load indicated poor control with antiretroviral therapy but was not affected by zinc supplementation. Zinc supplementation also reduced the rate of diarrhea by more than half (odds ratio, 0.4; 95% confidence interval, 0.183-0.981; P=.019), compared with placebo. There was no significant difference in mortality between the 2 groups. This study demonstrated that long-term (18-month) zinc supplementation at nutritional levels delayed immunological failure and decreased diarrhea over time. This evidence supports the use of zinc supplementation as an adjunct therapy for HIV-infected adult cohorts with poor viral control. Trial registration. ClinicalTrials.gov identifier: NCT00149552.

Therapeutic Value of Zinc Supplementation in Acute and Persistent Diarrhea: A Systematic Review

BackgroundFor over a decade, the importance of zinc in the treatment of acute and persistent diarrhea has been recognized. In spite of recently published reviews, there remain several unanswered questions about the role of zinc supplementation in childhood diarrhea in the developing countries. Our study aimed to assess the therapeutic benefits of zinc supplementation in the treatment of acute or persistent diarrhea in children, and to examine the causes of any heterogeneity of response to zinc supplementation.Methods and FindingsEMBASE®, MEDLINE ® and CINAHL® databases were searched for published reviews and meta-analyses on the use of zinc supplementation for the prevention and treatment of childhood diarrhea. Additional RCTs published following the meta-analyses were also sought. The reviews and published RCTs were qualitatively mapped followed by updated random-effects meta-analyses, subgroup meta-analyses and meta-regression to quantify and characterize the role of zinc supplementation with diarrhea-related outcomes. We found that although there was evidence to support the use of zinc to treat diarrhea in children, there was significant unexplained heterogeneity across the studies for the effect of zinc supplementation in reducing important diarrhea outcomes. Zinc supplementation reduced the mean duration of diarrhea by 19.7% but had no effect on stool frequency or stool output, and increased the risk of vomiting. Our subgroup meta-analyses and meta-regression showed that age, stunting, breast-feeding and baseline zinc levels could not explain the heterogeneity associated with differential reduction in the mean diarrheal duration. However, the baseline zinc levels may not be representative of the existing zinc deficiency state.ConclusionsUnderstanding the predictors of zinc efficacy including the role of diarrheal disease etiology on the response to zinc would help to identify the populations most likely to benefit from supplementation. To improve the programmatic use of zinc, further evaluations of the zinc salts used, the dose, the frequency and duration of supplementation, and its acceptability are required. The significant heterogeneity of responses to zinc suggests the need to revisit the strategy of universal zinc supplementation in the treatment children with acute diarrhea in developing countries.

Targeting Hypoxia in Cancer Cells by Restoring Homeodomain Interacting Protein-Kinase 2 and p53 Activity and Suppressing HIF-1α

BackgroundThe tumor suppressor homeodomain-interacting protein kinase-2 (HIPK2) by phosphorylating serine 46 (Ser46) is a crucial regulator of p53 apoptotic function. HIPK2 is also a transcriptional co-repressor of hypoxia-inducible factor-1α (HIF-1α) restraining tumor angiogenesis and chemoresistance. HIPK2 can be deregulated in tumors by several mechanisms including hypoxia. Here, we sought to target hypoxia by restoring HIPK2 function and suppressing HIF-1α, in order to provide evidence for the involvement of both HIPK2 and p53 in counteracting hypoxia-induced chemoresistance.Methodology/Principal FindingsUpon exposure of colon and lung cancer cells to hypoxia, by either low oxygen or cobalt, HIPK2 function was impaired allowing for increased HIF-1α expression and inhibiting the p53-apoptotic response to drug. Cobalt suppressed HIPK2 recruitment onto HIF-1α promoter. Hypoxia induced expression of the p53 target MDM2 that downregulates HIPK2, thus MDM2 inhibition by siRNA restored the HIPK2/p53Ser46 response to drug. Zinc supplementation to hypoxia-treated cells increased HIPK2 protein stability and nuclear accumulation, leading to restoration of HIPK2 binding to HIF-1α promoter, repression of MDR1, Bcl2, and VEGF genes, and activation of the p53 apoptotic response to drug. Combination of zinc and ADR strongly suppressed tumor growth in vivo by inhibiting HIF-1 pathway and upregulating p53 apoptotic target genes.Conclusions/SignificanceWe show here for the first time that hypoxia-induced HIPK2 deregulation was counteracted by zinc that restored HIPK2 suppression of HIF-1 pathway and reactivated p53 apoptotic response to drug, underscoring the potential use of zinc supplementation in combination with chemotherapy to address hypoxia and improve tumor treatment.