Zinc Deficiency
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Zinc Deficiency |
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Zinc Deficiency Global Prevalence – Kenneth Brown Zinc and Growth Barbara E Golden. University of Aberdeen, Scotland, United KingdomThere is now overwhelming evidence that zinc deficiency commonly limits weight gain. However, the details remain unclear. The effect of a zinc supplement on a patient or a population is still relatively unpredictable. This is in part due to the lack of an easy test of zinc status or a test sensitive or specific to change in zinc status. It is also due to the numerous other factors which affect growth. These are both dietary and host factors, many of which interact with zinc. Zinc itself has effects on key functions other than growth. Several recent papers would suggest that its major role in public health is in diminishing the effects of infections. Its role in improving growth is seen as secondary to this. Finally, in spite of tight homeostatic control of zinc within body compartments, there is some evidence of deleterious effects of too much zinc. That said, failure to thrive, or weight faltering, in early childhood is still a major global problem. It is usually associated with poverty. The more severe, the higher the short term morbidity and mortality. For those who survive, complete catch up in height is unusual and the subsequent short heights are associated with impaired physical and mental capacities. In circumstances in which poverty is followed by affluence, a further twist is emerging: failure to thrive in early childhood is associated with chronic disease in adulthood leading to premature death. Clearly, there is an urgent need to delineate the role of zinc in treatment and prevention of failure to thrive in early childhood. The questions above need to be answered so that clinicians and public health programmes are sufficiently informed to know when to prescribe zinc, how much to prescribe and whether it needs to be part of a nutrient package as recommended, for example, for the treatment of severe malnutrition. Evaluation of Zinc and Vitamin A on Synergistic Effects in Child Health. S.K. Roy . R. Begum, A. Begum. ICDDR,B Mohakhali, Dhaka, Bangladesh.Most of the children in developing countries who suffer from diarrhoea also have malnutrition and are likely to have deficiency in micro-nutrients including vitamin A and zinc. Diarrhoea has been globally recognised as one of the most important causes of morbidity and mortality in children, which effects millions of young children and annually cause > 3 million deaths in children aged under 5 years (Gracey, 1999). The interactions between diarrhoeal disease and nutritional status are complex and synergistic. Among the essential micro-nutrients for growth and reduced morbidity, zinc has been known for a long time to be present in more than 100 metalloenzymes which are regularly needed for protein synthesis, bone mineralisation, physical growth and biological functions including immunocompetence (Prasad, 1979). It is essential for the synthesis of retinol-binding protein, which is required for mobilisation of vitamin A from liver. Malnourished children have a higher risk of diarrhoea, which worsens the malnutrition and leads to high mortality. Vitamin A and zinc may play a key role in modulating the sequence of events of diarrhoea especially in the malnourished children. Role of zinc on growth and morbidity In a pooled analysis of multiple country studies, it was shown that zinc supplementation in children in developing countries is associated with substantial reductions in the rates of diarrhoea and pneumonia, the two leading causes of death (Bhutta et al, 1999). Supplementation of zinc during acute diarrhoea enabled a 25% increase in linear growth up to 10 weeks after acute diarrhoea (Roy et al, 1999). In a study it has been shown that improving zinc status reduces morbidity from diarrhoea and respiratory infection (Tomkins, 2000). In an another study it was also shown that there was a significant reduction in the duration of persistent diarrhoea in selected sub-groups of zinc supplemented patients (Roy et al, 1998). The mean net increase in length in group receiving zinc was 4.14 cm, vitamin A was 3.26 cm and combined supplementation group was 3.71cm (Table 1). Table 1: Monthly increase in length (cm) of study children in different treatment groups after the first dose ( n, mean ± SD)
In Bangladesh, a double-blind randomised trial on zinc or placebo in a multivitamin syrup was conducted among 4-24 months old children suffering from acute diarrhoea for less than 3 days. 20 mg of elemental zinc per day was administered for two weeks. Significant reduction in median stool weight during recovery was noticed among the hypozincaemic (279 vs 329 g, p<0.04) and shorter children (328 vs 325 g, p<0.05) who were zinc supplemented compared to their placebo counterparts (Table 2). Table 2: Impact of zinc supplementation on stool output in children during acute diarrhoea
In another study, 90 patients with persistent diarrhoea, aged 3-24 months, were given a placebo or zinc (20 mg/day) for two weeks. The duration of clinical recovery was significantly reduced by zinc supplementation among children who were underweight (< 70% wt/age, p<0.01) (Roy et al 1998) (Table 3). Table 3: Impact of zinc supplementation on duration of acute diarrhoea in days. Mean ± SD (95% CI)
In pooled analysis of randomised controlled trials it has been shown that supplementation with zinc reduces incidence of pneumonia by 41%. Acute diarrhoea trials from Indonesia, India and Bangladesh show 15% earlier recovery (95% CI 6 to 22%) and persistent diarrhoea trials from Peru, Bangladesh and Pakistan show 29% faster recovery in children (Bhutta et al, 1999). It has also been reported that when zinc supplementation is given to children following diarrhoea, improved catch- up growth was seen compared to a non-supplementation group (Behrens et al, 1990). Zinc deficiency syndrome of acrodermatitis enteropathica, associated with low plasma zinc, low alkaline phosphatase level and reduced urinary excretion of zinc reversed to normal after zinc therapy. Role of zinc in immunity Micro-nutrients such as zinc can influence several components of innate immunity (Erickson et al, 2000). More severe nutritional status and impairment of cellular immunity are related to the persistence of diarrhoea (Taniguchi et al, 1999). Compared with immunocompetent children, immunodeficient children had about twice the risk of developing persistent diarrhoea (Baqui et al, 1993). The immunological consequences of zinc deficiency may be responsible for decreased cell mediated immune functions and inflammatory reactions in zinc deficient subjects. Zinc influence immunity, tissue regeneration and promote protein synthesis. The effect of zinc deficiency on the immune response was studied in an experimental model of human recently (Prasad, 2000). Zinc deficiency causes imbalance between TH1 and TH2 functions and the production of INFg , IL-2 and TNFa (products of TH cells) are decreased (Prasad 2000, Prasad 1998). Zinc supplementation increases IL-2 and INFg production. As a result of zinc deficiency, the ratio of CD4+ CD45RA+ to CD4+CD45RO+ was decreased suggesting that zinc may be required for the new CD4+ T cells. Zinc deficiency caused decreased serum thymulin activity, which could be restored by zinc supplementation (Prasad 1998). Zinc deficiency also decreased the percentage of CD8+ CD73+ T cells those are the precursor cells of cytotoxic T cells. IL-1b is involved in the zinc deficiency induced mucosal damage. Intestinal cell proliferation was also reduced by zinc deficiency. In one of our study, 147 children were observed, among them 45 children received elemental zinc (40/per day), 37 children received vitamin A, 35 children received zinc + vitamin A and 34 receive placebo. In this study there was no significant difference in production of IL-2 and IL-10 in any group before and after supplementation. Table 4:Comparison of Interleukin production (pg/mL) within groups before and after supplementation of zinc and /or vitamin A (median/range)
Table 5: Comparison of weight gain (kg) within groups after 8 weeks follow up (Mean ± SD)
Incidence of diarrhoeal episodes was significantly lower in the zinc supplementation children only (p=0.02). Number of dysenteric attack were less in vitamin A group compared to zinc and placebo group (p=0.03) and ear infection were less in group receiving vitamin A (p=0.002) (Table 6). Table 6: Comparison of illness episodes between groups during 8 weeks follow-up (Mean ± SEM)
Zinc vs placebo p=0.02* (diarrhoea) Role of vitamin A on child health In recent years, different studies have shown association between clinical vitamin A deficiency and increased morbidity. Vitamin A supplementation have reduced the mortality from measles and other infectious diseases (Tidsskr NL, 2000). Effect of vitamin A on infection may be mediated through two major ways: one through improving the epithelial repair and the other through immunological protection. Weekly supplementation of low dose vitamin A reduced 46% death but did not reduce morbidity in children (Rahmatullah et al, 1990). West et al showed 47% reduction in pregnancy related death in Nepal (West et al, 1991). Ghana VAST study (1993) showed that vitamin A supplemented children had fewer attendance at clinics (p=0.001), hospital admissions (p=0.02) and deaths than children who received placebo (Ghana, 1993). Barreto et al showed that the overall diarrhoeal episode was significantly lower in the vitamin A supplemented group (Mauricio et al, 1994). In Bangladesh, a case control study at ICDDR,B demonstrated that protein energy malnutrition was associated with four times higher risk and persistent diarrhoea was associated with 3.5 times higher risk of vitamin A deficiency (Mahalanabis, 1991). A study in northern India showed that there was 18.8% reduction in diarrhoeal episodes in children who received 2,00,000 IU vitamin A in a double blind randomised trial (Agarwal et al, 1994). In a another study in Bangladesh showed a significantly earlier clinical recovery from shigellosis in the vitamin A supplementation group than control group (Hossain et al, 1998). Supplementation studies of vitamin A among children in developing world settings have demonstrated a substantial reduction in diarrhoeal mortality. In Madurai in southern India, the effect of weekly doses of vitamin A on diarrhoeal mortality was >50% reduction (RR=0.48, CI 0.24-0.96) (Rahmatullah et al, 1990). Vitamin A supplementation showed improved cell-mediated immunity (CMI) in malnourished infants below 6 months of age who were given 15 mg vitamin A in 3 doses at monthly interval (Rahman et al, 1997). Combined effect of zinc and vitamin A Effects of supplementation of vitamin A and / or zinc on height and weight gains have been recently described by Smith and his colleagues (Smith et al, 1999). Height and weight gains were significantly increased in the subjects who received a single weekly supplement 3030 RE of vitamin A. In a double- blind, controlled trial study, 684 patients aged between 6-24 months, were randomly assigned to 4 groups to receive: (a) vitamin A (b) zinc (c) both vitamin A + zinc and (d) placebo. Patients were observed in the hospital for 24 hours and followed up at home for 15 days. Zinc supplementation was associated with a reduced duration of diarrhoea (13 %, p = 0.03) and markedly reduced rate (43%, p = 0.017) of prolonged diarrhoea (> 7 days). Vitamin A supplementation was associated with a non-significant trend for reduced rate of prolonged diarrhoea (p = 0.089). They concluded that zinc supplementation as adjunct therapy had a substantial impact on the rate of prolonged diarrhoea and some impact on duration and may be beneficial in children with diarrhoea in developing countries (Faruque et al, 1999) Another double blind randomised control trial study was conducted on the children who were moderately malnourished and aged between 6-36 months. Children were randomly allocated into three groups- zinc, vitamin A and zinc + vitamin A. The mean net increase in body weight in group receiving zinc was 1.07 kg, Vitamin-A was 0.88kg and combined supplementation group was 1.00kg (Tables 8, 9). Table 7: Diarrhoea duration following intervention and proportion of patients with diarrhoea lasting for more than 4, 7 or 16 days in groups supplementation with zinc or vitamin A.
p=0.01a Table 8: Monthly increase in body weight (kg) of study children in different treatment groups after the first dose (n, mean ± SD)
Table 9: Monthly increase in body weight (g/kg) of study children in different treatment groups after the second dose (n, mean ± SD)
*Zinc Vs Vitamin A and combined group Vs Vitamin A were significantly different at 0.05 level Conclusion While being underweight or stunted is recognised as an important factor for increased prevalence and severity of infection and high mortality rates, there is increasing evidence for an independent role for micro-nutrient deficiency. Several studies have shown beneficial effects of zinc supplementation in malnourished children with acute and persistent diarrhoea. Children with PEM are often deficient in zinc and vitamin A. Micronutrient deficiency such as zinc deficiency may be a possible factor for increasing diarrhoeal severity, incidence and growth retardation. Although supplementation of one micronutrient may be beneficial to the subject, its effect on and interaction with other micronutrients needs to be evaluated. Zinc supplementation is therefore a strategy to improve growth. There is also evidence that zinc plays an important role in preventing attacks of diarrhoea and respiratory infection. These evidences together offer zinc supplementation to be a key strategy for improving growth and reducing morbidity in malnourished children of the community where zinc deficiency is present. Improving vitamin A status reduces mortality among older infants and young children and reduces pregnancy-related mortality; it also reduces the prevalence of severe illness and clinic attendance among children and improving zinc status reduces morbidity from diarrhoeal and respiratory infection (Tomkins, 2000). Dietary supplementation or therapeutic treatment with vitamin A and zinc may be a cheap yet effective means of preventing or treating infections in highly susceptible populations. References
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