锌缺乏与艾滋病

综述了锌缺乏与艾滋病发病机理之间的关系,认为锌缺乏导致的机体免疫功能下降或改变对HIV感染具有重要影响,并认为适当补锌对恢复HIV感染者免疫能力有一定作用。     

Zinc and copper: proposed fortification levels and recommended zinc compounds

Micronutrient fortification of foods is now a highly relevant tool worldwide for overcoming micronutrient deficiency. Recent data show that subclinical zinc deficiency is widespread; in Mexico a national survey showed that 25% of children less than age 11 y had plasma zinc concentrations below 10.0 micromol/L (65 microg/dL). Copper deficiency in populations is unknown but copper supplementation is recommended to accompany zinc supplementation. Of the foods available for fortification, staple cereals are very good candidates for reducing micronutrient deficiencies. Because of its higher stability and lower cost, we recommend fortification of cereal flours with zinc oxide, which is absorbed as well as the less stable and more expensive forms of zinc. Depending on the amount of the food that is expected to be eaten, zinc fortification of staple foods could be 20-50 mg/kg of flour. For copper fortification the safer compound is copper gluconate. Copper sulfate is significantly less expensive, but an evaluation of potential physicochemical reactions that affect the final food product is recommended. The suggested amount of copper added to staple foods is 1.2-3.0 mg/kg of flour. For food supplements designed as part of supplementation programs to reduce micronutrient deficiency in children less than age 3 y, a dose of the final product (usually approximately 40-50 g) should contain approximately 4-5 mg of zinc and approximately 0.2-0.4 mg of copper depending on the habitual diet, magnitude of deficiencies and period of supplementation.     

Zinc deficiency in low‐ and middle‐income countries: prevalence and approaches for mitigation

This review addresses the prevalence of zinc deficiency in Low‐ and Middle‐income Countries (LMICs) and assesses the available strategies for its alleviation. The paucity of national‐level data on the zinc deficiency in LMICs is partially a result of the lack of a reliable biomarker. Zinc deficiency appears to be a public health problem in almost all the LMICs, irrespective of the recommended indicators (plasma zinc concentration, dietary zinc adequacy and stunting prevalence) used. Based on plasma/serum zinc concentration (PZC), which is the most appropriate indicator at present, the prevalence of zinc deficiency in LMICs is of concern. Among the 25 countries for which national PZC data were available, 23 had a zinc deficiency prevalence of >20% for at least one physiological group. Zinc supplementation is largely restricted as an adjunct therapy for diarrhoea management in children, and the best platform and the most effective way of preventive zinc supplementation delivery remains to be established. Impact assessment for current zinc fortification programmes in LMICs and the effectiveness of zinc supplementation as part of a multi‐micronutrient powder is to be determined. Dietary diversification, though promising for LMICs, is in the nascent stages of development at present. Inclusion of meat and animal products can be an important way of improving zinc status. Programmatic experience with the promotion of home processing techniques to increase absorbable zinc in the diet is lacking. Conventional biofortification techniques are gaining recognition in LMICs; however, transgenic biofortification as a strategy remains controversial.     

Zinc and childhood infectious disease morbidity and mortality

Zinc is an essential mineral and deficiency results in abnormal immune function and higher rates of infectious diseases. Randomized controlled trials of zinc supplementation have been conducted in children in developing countries to determine effects on infectious disease morbidity and mortality. Zinc-supplemented children have been found to have lower rates of diarrhea, pneumonia and malaria in comparison with children not given zinc. Zinc used as an adjunct to fluid and dietary management of acute and persistent diarrhea has been found to reduce diarrheal duration and severity. Preliminary evidence suggests that zinc supplementation in children in poor developing country settings may also reduce infant mortality, but larger trials are needed to address this important issue. Preventive and therapeutic interventions should be implemented in developing countries where zinc deficiency is likely to be prevalent.     

Zinc and diarrheal disease: current status and future perspectives

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.     

Zinc Supplementation with or without Additional Micronutrients Does Not Affect Peripheral Blood Gene Expression or Serum Cytokine Level in Bangladeshi Children

Preventive zinc supplementation provided as a stand-alone dispersible tablet, or via home fortification as multiple micronutrient powders (MNPs), has been considered a potential strategy to prevent zinc deficiency and improve health (including immune) outcomes among children in low- and middle-income countries. However, the impact of zinc supplementation on immune profiles has not been well characterized. We sought to define the effect of zinc supplementation on peripheral blood gene expression and cytokine levels among young children in Dhaka, Bangladesh. In a sub-study of a large randomized, controlled, community-based efficacy trial where children 9–11 months of age received one of the following interventions on a daily basis for 24 weeks: (1) MNPs containing 10 mg of zinc; (2) dispersible tablet containing 10 mg zinc; or (3) placebo powder, we used RNA sequencing to profile the peripheral blood gene expression, as well as highly sensitive multiplex assays to detect cytokine profiles. We profiled samples from 100 children enrolled in the parent trial (zinc MNPs 28, zinc tablets 39, placebo 33). We did not detect an effect from either zinc intervention on differential peripheral blood gene expression at the end of the intervention, or an effect from the intervention on changes in gene expression from baseline. We also did not detect an effect from either intervention on cytokine concentrations. Exploratory analysis did not identify an association between undernutrition (defined as stunting, underweight or wasting) and peripheral blood gene expression. Zinc interventions in children did not produce a gene expression or cytokine signature in the peripheral blood. However, this study demonstrates a proof of principle that sensitive multi-omic techniques can be applied to samples collected in field studies.     

Zinc and protein metabolism in chronic liver diseases

The capacity to metabolize proteins is closely related to the hepatic functional reserve in patients with chronic liver disease, and hypoalbuminemia and hyperammonemia develop along with hepatic disease progression. Zinc deficiency, which is frequently observed in patients with chronic liver disease, significantly affects protein metabolism. Ornithine transcarbamylase is a zinc enzyme involved in the urea cycle. Its activity decreases because of zinc deficiency, thereby reducing hepatic capacity to metabolize ammonia. Because the glutamine-synthesizing system in skeletal muscles compensates for the decrease in ammonia metabolism, hyperammonemia does not develop in the early stages of chronic liver disease. However, branched-chain amino acids (BCAAs) are consumed with the increase in glutamine-synthesizing system reactions, leading to a decreased capacity to synthesize proteins, including albumin, due to amino acid imbalance. Upon further disease progression, skeletal muscle mass decreases because of nutritional deficiency, as well as the further decreased capacity to metabolize ammonia in the liver, whereby the capacity to detoxify ammonia reduces as a whole, resulting in hyperammonemia. BCAA supplementation therapy for nutritional deficiency in liver cirrhosis improves survival by correcting amino acid imbalance via recovery of the capacity to synthesize albumin, while zinc supplementation therapy improves the capacity to metabolize ammonia in the liver. Here, the efficacy of a combination of BCAA and zinc preparation for nutritional deficiency in liver cirrhosis, as well as its theoretical background, was reviewed.     

Mobilization Of Hepatic Vitamin A By Zinc Supplementation In Zinc Deficiency Associated With Protein-Energy Malnutrition

Short-term supplementation with oral zinc increased circulating vitamin A and retinol-binding protein levels in children with protein-energy malnutrition and presumed zinc deficiency, but not in children with a predominantly dietary vitamin A deficiency.     

The Relevance of the Colon to Zinc Nutrition

Globally, zinc deficiency is widespread, despite decades of research highlighting its negative effects on health, and in particular upon child health in low-income countries. Apart from inadequate dietary intake of bioavailable zinc, other significant contributors to zinc deficiency include the excessive intestinal loss of endogenously secreted zinc and impairment in small intestinal absorptive function. Such changes are likely to occur in children suffering from environmental (or tropical) enteropathy (EE)—an almost universal condition among inhabitants of developing countries characterized by morphologic and functional changes in the small intestine. Changes to the proximal gut in environmental enteropathy will likely influence the nature and amount of zinc delivered into the large intestine. Consequently, we reviewed the current literature to determine if colonic absorption of endogenous or exogenous (dietary) zinc could contribute to overall zinc nutriture. Whilst we found evidence that significant zinc absorption occurs in the rodent colon, and is favoured when microbially-fermentable carbohydrates (specifically resistant starch) are consumed, it is unclear whether this process occur in humans and/or to what degree. Constraints in study design in the few available studies may well have masked a possible colonic contribution to zinc nutrition. Furthermore these few available human studies have failed to include the actual target population that would benefit, namely infants affected by EE where zinc delivery to the colon may be increased and who are also at risk of zinc deficiency. In conducting this review we have not been able to confirm a colonic contribution to zinc absorption in humans. However, given the observations in rodents and that feeding resistant starch to children is feasible, definitive studies utilising the dual stable isotope method in children with EE should be undertaken.     

Oral Zinc Supplementation for the Treatment of Acute Diarrhea in Children: A Systematic Review and Meta-Analysis

Evidence supporting the impact of therapeutic zinc supplementation on the duration and severity of diarrhea among children under five is largely derived from studies conducted in South Asia. China experiences a substantial portion of the global burden of diarrhea, but the impact of zinc treatment among children under five has not been well documented by previously published systematic reviews on the topic. We therefore conducted a systematic literature review, which included an exhaustive search of the Chinese literature, in an effort to update previously published estimates of the effect of therapeutic zinc. We conducted systematic literature searches in various databases, including the China National Knowledge Infrastructure (CNKI), and abstracted relevant data from studies meeting our inclusion and exclusion criteria. We used STATA 12.0 to pool select outcomes and to generate estimates of percentage difference and relative risk comparing outcomes between zinc and control groups. We identified 89 Chinese and 15 non-Chinese studies for the review, including studies in 10 countries from all WHO geographic regions, and analyzed a total of 18,822 diarrhea cases (9469 zinc and 9353 control). None of the included Chinese studies had previously been included in published pooled effect estimates. Chinese and non-Chinese studies reported the effect of therapeutic zinc supplementation on decreased episode duration, stool output, stool frequency, hospitalization duration and proportion of episodes lasting beyond three and seven days. Pooling Chinese and non-Chinese studies yielded an overall 26% (95% CI: 20%−32%) reduction in the estimated relative risk of diarrhea lasting beyond three days among zinc-treated children. Studies conducted in and outside China report reductions in morbidity as a result of oral therapeutic zinc supplementation for acute diarrhea among children under five years of age. The WHO recommendation for zinc treatment of diarrhea episodes should be supported in all low- and middle-income countries.     

Zinc supplementation and psychosocial stimulation: effects on the development of undernourished Jamaican children

BACKGROUND: Undernourished children have poor levels of development that benefit from stimulation. Zinc deficiency is prevalent in undernourished children and may contribute to their poor development. OBJECTIVE: We assessed the effects of zinc supplementation and psychosocial stimulation given together or separately on the psychomotor development of undernourished children. DESIGN: This was a randomized controlled trial with 4 groups: stimulation alone, zinc supplementation alone, both interventions, and control (routine care only). Subjects were 114 children aged 9-30 mo and below -1.5 z scores of the National Center for Health Statistics weight-for-age references who were recruited from 18 health clinics. Clinics were randomly assigned to receive stimulation or not; individual children were randomly assigned to receive zinc or placebo. The stimulation program comprised weekly home visits during which play was demonstrated and maternal-child interactions were encouraged. The supplementation was 10 mg Zn as sulfate daily or placebo. Development (assessed by use of the Griffiths Mental Development Scales), length, and weight were measured at baseline and 6 mo later. Weekly morbidity histories were taken. RESULTS: Significant interactions were found between zinc supplementation and stimulation. Zinc benefited the developmental quotient only in children who received stimulation, and benefits from zinc to hand and eye coordination were greater in stimulated children. Zinc supplementation alone improved hand and eye coordination, and stimulation alone benefited the developmental quotient, hearing and speech, and performance. Zinc supplementation also reduced diarrheal morbidity but did not significantly improve growth. CONCLUSION: Zinc supplementation benefits development in undernourished children, and the benefits are enhanced if stimulation is also provided.     

补充锌剂对儿童生长发育影响的研究

目的：了解补充锌剂对不同年龄儿童生长发育的影响。方法：对济宁市4446名4－12岁儿童采用配对双盲分组的方法进行补锌实验。结果：市区儿童缺严重，缺锌率达54．7％，补充锌剂和儿童生长育有密切相关性。结论：不同年龄的儿童补充锌剂对生长发育影响不尽相同，补锌应结合其生理规律适时适量补充。     

儿童补锌与生长发育相关性研究

目的:探讨儿童补锌对血锌水平的影响及与儿童体重、身高、智商等发育的相关关系。方法:用分层加单纯随机抽样的方法对抽取的168例儿童进行体格检查、血锌浓度测定、智商测定,并问卷调查儿童饮食、补锌等情况,采用SPSS10.0版统计软件进行多元线性回归分析。结果:①本组168例儿童血锌平均浓度为58.98μmol/L,正常血锌儿童占75.0%,低血锌儿童占25.0%。②儿童血锌水平与性别无关,与年龄有高度显著性差异(χ2=20.08,P<0.01),3~6岁儿童缺锌比例较7~12岁儿童高。③血锌水平影响儿童体重、身高发育,低血锌儿童体重、身高发育指标低于正常的比例高(χ2=24.52,P<0.01,χ2=29.03,P<0.01,)。④影响血锌水平的因素主要为饮食与补锌情况。⑤影响智商的因素为血锌水平与补锌情况。结论:正常饮食儿童低血锌比例低,偏食、挑食、厌食是引起血锌偏低的主要因素,血锌水平影响智商高低。科学对待儿童缺锌与补锌,理性对待广告宣传,纠正不良饮食习惯是保障儿童锌营养的关键。     

Crosstalk between Zinc Status and Giardia Infection: A New Approach

Zinc supplementation has been shown to reduce the incidence and prevalence of diarrhea; however, its anti-diarrheal effect remains only partially understood. There is now growing evidence that zinc can have pathogen-specific protective effects. Giardiasis is a common yet neglected cause of acute-chronic diarrheal illness worldwide which causes disturbances in zinc metabolism of infected children, representing a risk factor for zinc deficiency. How zinc metabolism is compromised by Giardia is not well understood; zinc status could be altered by intestinal malabsorption, organ redistribution or host-pathogen competition. The potential metal-binding properties of Giardia suggest unusual ways that the parasite may interact with its host. Zinc supplementation was recently found to reduce the rate of diarrhea caused by Giardia in children and to upregulate humoral immune response in Giardia-infected mice; in vitro and in vivo, zinc-salts enhanced the activity of bacitracin in a zinc-dose-dependent way, and this was not due to zinc toxicity. These findings reflect biological effect of zinc that may impact significantly public health in endemic areas of infection. In this paper, we shall explore one direction of this complex interaction, discussing recent information regarding zinc status and its possible contribution to the outcome of the encounter between the host and Giardia.     

Zinc deficiency in pregnancy and fetal outcome

Maternal zinc deficiency during pregnancy has been related to adverse effects on progeny, and there are data showing that mild to moderate zinc deficiency (as assessed by available indicators) is quite common in the developing world. Observational data relating zinc deficiency to adverse fetal outcome have produced conflicting results, mainly because of the lack of a valid indicator of zinc deficiency in pregnancy. Studies of human pregnancy and zinc supplementation, including those from developing countries, have failed to document a consistent beneficial effect on fetal growth, duration of gestation, and early neonatal survival. Preliminary results from unpublished studies in developing countries have also proven to be discouraging. However, recent data and some preliminary findings indicate a beneficial effect of maternal zinc supplementation on neonatal immune status and infant morbidity from infectious diseases, and there is also preliminary evidence that, zinc supplementation may prevent congenital malformations (cleft lip/palate). With respect to neurobehavioral development, the evidence is conflicting, with only one study reporting a positive outcome. More research is required to assess the benefits of the large-scale introduction of zinc supplementation during pregnancy on congenital malformations, immune functions, neurobehavior, and overall neonatal survival in countries where zinc deficiency is a problem. Currently available information does not support the routine use of zinc supplementation to improve pregnancy outcome.     

Micronutrients and Child Health: Studies in International Nutrition and HIV Infection

Increasing data link micronutrient deficiencies to excess childhood morbidity and mortality, and similar relationships have been noted in the study of nutrition and HIV infection. We review epidemiologic studies that have examined the relationship between micronutrient deficiencies and health outcomes in childhood and HIV infection, as well as clinical trials of micronutrient supplementation. Vitamin A supplementation among communities at risk of deficiency effectively reduces mortality and morbidity in children younger than age 5, and vitamin A may be especially effective in HIV-infected children. Vertical transmission of HIV has not to date been affected by maternal micronutrient supplementation. In children with poor dietary zinc intake and/or bioavailability, zinc supplementation reduces the incidence and severity of diarrheal diseases, as well as the occurrence of pneumonia. Vitamin A therapy has not been associated with improved growth, whereas some trials have shown that zinc supplementation is associated with greater increments in height. Further trials of micronutrient supplementation are warranted.     

Zinc and cognitive development

Cognition is a field of thought processes by which an individual processes information through skills of perception, thinking, memory, learning and attention. Zinc deficiency may affect cognitive development by alterations in attention, activity, neuropsychological behavior and motor development. The exact mechanisms are not clear but it appears that zinc is essential for neurogenesis, neuronal migration, synaptogenesis and its deficiency could interfere with neurotransmission and subsequent neuropsychological behavior. Studies in animals show that zinc deficiency during the time of rapid brain growth, or during the juvenile and adolescent period affects cognitive development by decreasing activity, increasing emotional behavior, impairing memory and the capacity to learn. Evidence from human studies is limited. Low maternal intakes of zinc during pregnancy and lactation were found to be associated with less focused attention in neonates and decreased motor functions at 6 months of age. Zinc supplementation resulted in better motor development and more playfulness in low birth weight infants and increased vigorous and functional activity in infants and toddlers. In older school going children the data is controversial but there is some evidence of improved neuropsychological functions with zinc supplementation. Additional research is required to determine the exact biological mechanisms, the critical periods, the threshold of severity and the long-term effects of zinc deprivation on cognitive development.     

Identifying Populations at Risk of Zinc Deficiency: The Use of Supplementation Trials

Zinc supplementation trials assessing the response of growth and immunity have assisted in identifying populations at risk of zinc deficiency and the factors that contribute. A recent trial in Ethiopia demonstrated a high risk of zinc deficiency among young children, particularly among those who were stunted.     

Zinc tolerance tests in zinc deficient and zinc supplemented diets

Seven men consumed a low-zinc (3.3 mg/day) diet for 8 wk, followed by zinc-repletion (+15 mg/day) for 12 days. Zinc tolerance tests (50 mg) were administered initially and following depletion and repletion periods. Plasma zinc after 2 h in the zinc tolerance test was marginally higher after both the depletion (p less than 0.06) and repletion (p less than 0.001) periods as compared to the initial test. No changes were seen in parotid zinc tolerance tests or fasting levels of zinc in plasma or parotid saliva. In a subsequent study, zinc tolerance tests were given to normal subjects before and after 12 days of zinc supplementation (15 mg/day). Again, zinc levels in plasma were increased following zinc supplementation at the 2nd h post-zinc dose, but levels in saliva did not change. The elevation of plasma zinc curves with both zinc deficiency and supplementation suggests that this test is not a reliable indicator of zinc status.