For many years it was considered improbable that zinc deficiency in humans could lead to significant adverse health effects. The idea that zinc deficiency occurred in humans remained very controversial for over a decade. However, in 1974, the National Research Council of the National Academy of Sciences declared zinc as an essential element for humans and established a recommended dietary allowance (RDA) for zinc (1). The clinical manifestations of zinc deficiency, are growth retardation, hypogonadism, rough skin, poor appetite, mental lethargy and infections. The World Health Organization (WHO) estimate that that nearly two billion people in the developing world may have nutritional deficiency of zinc. In the developing world the diet consists of mainly cereal proteins with high phytate content which complexes zinc and decreases its availability. Zinc deficiency has been reported in patients with liver disease; chronic alcoholism, malabsorption syndrome, chronic renal disease, and other chronic diseases (2). A severe deficiency of zinc is seen in patients with acroder-matitis enteropathica (AE). AE is a lethal, autosomal, recessive trait that usually occurs in infants of Italian, Armenian or Iranian lineage (3). The disease develops in the early months of life soon after weaning from breast feeding leading to bullous dermatitis, growth retardation, neuropsychiatric symptoms and severe cell-mediated immune dysfunction resulting in infections.
Data clearly indicates that even a mild deficiency of zinc in humans affects chemical, bio-chemical and immunological functions adversely impacting upon multiple organ systems such as a decreased serum testosterone level, sperm development, decreased natural killer cell activity, decreased activity of Th1 cells, decreased serum thymulin activity, decreased dark adaptation and decreased lean body mass (4-6).
Zinc has, relatively speaking, no toxicity and is non-teratogenic, thus it can be given to subjects of all ages including pregnant women.
Sources of zinc
A wide variety of foods contain zinc. Oysters contain more zinc per serving than any other food, but red meat and poultry provide the majority of zinc in the diet. Other good sources include beans, nuts, certain types of seafood (such as crab and lobster), whole grains, fortified breakfast cereals and dairy products.
Phytates, which are present in whole grain breads, cereals, legumes, and other foods, bind with zinc and inhibit its absorption. Thus, the bioavailability of zinc from grains and plant foods is lower than that from animal foods, although many grain-and grain based foods are still good sources of zinc.
Zinc in health and disease
Several studies have shown that zinc supplementation to infants and children with acute diarrhoea, decreases both diarrhoea morbidity and mortality (7,8). Zinc therapy has saved lives of millions of children worldwide and the WHO is currently using zinc therapy for acute diarrhoea in nearly seventy countries.
Zinc deficiency is also correlated with the risk of respiratory tract infections in young children, and zinc supplementation has been shown to benefit those children who have severe infections and are zinc deficient.
The common cold is one of the most frequently occurring dis-eases in the world. Annually adults develop a common cold 2–4 times a year and children may develop colds 6–8 times in a year. Zinc lozenges have been used for the treatment of the common cold since 1984 (9). Two studies (10,11) evidence the efficacy of zinc lozenges for the treatment of the common cold. Each zinc lozenge contained 13–14 mg elemental zinc and it was taken every 3 h during the waking period. Compared with the placebo group, the zinc group had shorter overall duration of cold symptoms (4.5 days versus 8.1 days) and duration of cough and nasal discharge. A significantly decreased total severity score for all symptoms was also observed.
It has been suggested that in order for the zinc acetate lozenges to be effective in the treatment of common cold, the treatment with zinc must be started within 24 h of its onset. The total daily dose of elemental zinc should be >75 mg. The chemical formulation of the lozenges must be optimal such that zinc is ionized in the oral cavity at pH 7.4. Zinc acetate and zinc gluconate are commonly used; however, if citric acid, glycine, tartrate and other binders are added to the formulation, zinc is prevented from ionization. A meta-analysis of zinc trials was recently reported by Cochrane Library has confirmed these results (12).
Zinc competes with copper for similar binding sites and oral zinc decreases uptake of copper very efficiently. Zinc has now been developed as a very efficient therapeutic agent for the treatment of Wilson’s disease and this has been approved by the FDA (13,14). For maintenance therapy, zinc is the drug of choice.
Sickle Cell Disease
Studies have documented the occurrence of zinc deficiency in adult sickle cell disease (SCD) patients (15,16). Growth retardation, hypogonadism in males, hyperammonemia, abnormal dark adaptation, and cell-mediated immune dysfunction in SCD patients have been related to a deficiency of zinc. SCD patients have persistent hemolysis and this results in excessive loss of zinc in the urine. These patients also have lack of appetite and their zinc intake is not optimal. A placebo controlled trial of zinc supplementation showed that the zinc supplemented subjects had a decreased incidence of infections, decreased incidence of pain-crises, decreased oxidative stress, decreased generation of inflammatory cytokines and the zinc supplementation improved Th1 cell function [23,24]. A recent Cochrane review has concluded that at the present time oral zinc supplementation is the only agent which decreases incidence of infection and incidence of pain-crises in SCD patients (17).
Age Related Macular Degeneration
Age related macular degeneration (AMD) affects nearly 25% of individuals older than 65 years of age, and late stage disease account for nearly 50% legal blindness in Europe and USA. Newsome et al. (18) demonstrated that concentrations of zinc are reduced in human eyes with signs of AMD and suggested that zinc deficiency may lead to oxidative stress and retinal damage. The Age Related Eye Disease Study Group (AREDS) supported by National Eye Institute of NIH conducted a 11-center double blind clinical trial in patients with dry type AMD (19,20). The average follow up period was 6.3 years in 3640 subjects. Participants were randomly assigned to one of the following: (1) antioxidants (Vitamin C 500 mg, Vitamin E 400 IU and beta-carotene 15 mg); (2) zinc 80 mg as zinc oxide and copper 2 mg as oxide to prevent copper deficiency induced by zinc; (3) antioxidants plus zinc; or (4) placebo. In the group receiving antioxidant plus zinc, the risk of developing advanced AMD was reduced by ∼25% and vision loss by ∼19%. In the group taking zinc alone, the risk of developing advanced AMD was reduced by ∼21% and vision loss by ∼11%. In the group taking the vitamins alone, the risk of developing advanced AMD was decreased by 17% and vision loss was decreased by 10%. This study confirmed the antioxidant effect of zinc in humans and interestingly, only the zinc supplemented group showed increased longevity. The risk of mortality was reduced by 27% in the AREDS studies in subjects aged 55–81 years who received only therapeutic zinc daily. Later analysis revealed that the reduction in mortality was due to decreased deaths related to cardiac events(21).
Since zinc deficiency and susceptibility to infections due to cell-mediated immune dysfunction have been observed in the elderly, a randomized placebo-controlled trial of zinc supplementation in healthy elderly subjects of both sexes and all ethnic groups was performed. Zinc supplementation consisted of 45 mg elemental zinc (as gluconate) daily for 12 months (22-24). The mean incidence of infection per subject in 12 months was significantly lower in the zinc supplemented group than in the placebo group.
Zinc affects the monocytes/macrophages in several ways. Zinc is required for the development of monocytes/macrophages and regulates their functions such as phagocytosis and pro inflammatory cytokine production. Zinc deficiency affects Th1 functions adversely (25,26). Serum thymulin activity and generation of Th1 cytokines were affected within 8–12 weeks of institution of a zinc restricted diet (3–5 mg/d) in human volunteers, whereas plasma zinc decreased only after 20–24 weeks of the institution of the zinc deficient diet. This suggests that Th1 cells are very sensitive to zinc restriction. Thus in zinc deficiency there is a shift from Th1 to Th2 functions and cell-mediated immune functions are impaired. Zinc deficiency also leads to oxidative stress and activation of macrophages-monocytes resulting in increased generation of inflammatory cytokines.
Zinc is secreted into the seminal plasma by the prostate gland. In addition it has been demonstrated that zinc concentration is an excellent indicator of prostatic secretory function. Seminal plasma zinc concentration has been reported to be an important factor in the regulation of fertility, although the exact mechanisms are unclear. Low seminal zinc levels have been correlated with decreased fertility potential in the male. Furthermore, treatment with zinc sulphate has been reported to improve fertility potential and serum zinc levels were reported to correlate well with serum testosterone and inversely with serum luteinizing hormone. (27)
Findings indicate: (1) low dose zinc androgen therapy increases seminal zinc concentrations and sperm motility when pre-treatment seminal zinc concentrations are low; (2) the efficacy of low-dose androgen therapy can be improved by the concomitant administration of zinc sulphate (28).
Changes in the level of the trace element zinc are known to be associated with the functioning of different organs (breast, colon, stomach, liver, kidney, prostate, and muscle). One study estimated and compared the zinc levels in the prostate tissue, plasma, and urine obtaine from patients diagnosed with BPH. In BPH, there was a 61% decrease in mean tissue zinc as compared to normal tissues. Both these values were statistically significant. The plasma zinc in prostate cancer patients showed an 18% decrease (P < 0.01) as compared to BPH. The urine zinc/creatinine (ratio) was significantly increased by 20% in BPH as compared to normal subjects. It is evident from this study that BPH may be associated with a reduction in the levels of tissue zinc, plasma zinc, and an increase in urine zinc/creatinine (29).
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- Singh M, Das R. Zinc for the common cold. Cochrane Syst Rev 2011;2:1–58.
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- Prasad AS, Beck FWJ, Bao B, Fitzgerald JT, Snell DC, et al. Am J Clin Nutr 2007;85:837–44.[
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Key words:-zinc, diarrhoea, common cold, sickle cell disease, wilsons disease, age related macular degeneration, infection, fertility, prostate health