Version August 2025
INTRODUCTION —
Zinc is an essential trace element that plays a role in growth, tissue repair and wound healing, intestinal mucosal integrity, synthesis of testicular hormones, and the immune response. Because zinc intake is closely related to protein intake, zinc deficiency is common in many resource-limited settings and is an important component of nutrition-related morbidity worldwide.
Symptoms attributable to severe zinc depletion include growth failure, diarrhea, skin disease, alopecia, impaired taste and smell, poor appetite, and impaired immunity and resistance to infection. Mild deficiency may be asymptomatic or can be characterized by feeding difficulties and poor growth. Zinc supplementation or food fortification in populations at risk for zinc deficiency appears to have beneficial effects on the incidence and outcome of serious childhood infectious diseases.
This topic review will discuss the causes, clinical manifestations, and treatment of zinc deficiency in children, followed by a review of clinical application of zinc supplementation and underlying evidence. Zinc metabolism, actions, and clinical aspects in adults are discussed separately. (See "Overview of dietary trace elements", section on 'Zinc' and "Nutrition in pregnancy: Dietary requirements and supplements".)
The use of zinc for cold symptoms, including potential side effects, is discussed separately. (See "The common cold in children: Management and prevention", section on 'Unproven therapies'.)
CHEMISTRY AND BIOLOGIC FUNCTIONS —
Zinc has major catalytic and structural functions in hundreds of enzymes and transcription factors involved in nucleic acid metabolism, cellular proliferation and differentiation, apoptosis, and signal transduction. Zinc also participates in oxidation-reduction reactions through the combined biochemistry of zinc and sulfur-containing proteins such as glutathione. Zinc is vital to normal anabolic activity including growth, tissue integrity, and wound healing, and, as a result, deficiency predominantly affects rapid turnover areas including skin, intestinal mucosa, gonads, and immune cells. It is essential for neuronal synaptic transmission, cell adhesion and migration, cytoskeleton formation, and acid-base balance. It plays an additional role in insulin-like growth factor 1 levels and function, independent from adequate caloric intake.
RECOMMENDED INTAKE
Recommended dietary allowance — The recommended dietary allowance for zinc ranges from 2 mg/day in young infants to 9 mg/day in adolescent females and 11 mg/day in adolescent males (table 1) [1]. Requirements are slightly higher during pregnancy and lactation.
For premature infants, the recommended target for enteral intake is 2 to 3 mg/kg/day, based on expert opinion [2].
Upper tolerable limit — The upper tolerable limit (UL) describes the upper threshold for chronic zinc intake that avoids adverse effects. We prefer the ULs set by the World Health Organization (WHO) [3,4], which range from 13 mg/day in older infants, 23 to 34 mg/day in school-aged children, 34 to 36 mg/day in female adolescents and adults, and 40 to 48 mg/day in male adolescents and adults.
These ULs set by the WHO are considerably higher than those established by the National Academy of Medicine (NAM) in the United States more than 20 years ago because they are based on different concerns:
●NAM – The NAM based their UL on the concern that zinc competes with copper for absorption in the intestine and chronic intake of high doses of zinc may be associated with copper deficiency [5]. Of note, typical zinc intakes for toddlers in many countries, including the United States, exceed the NAM's UL for this age group.
●WHO – The WHO based their UL on estimates of the threshold at which zinc intake alters laboratory measures of copper sufficiency. These ULs are well above the dietary zinc intake for most individuals but could be exceeded if high-dose zinc is taken as a supplement [6]. The International Zinc Nutrition Consultative Group also supports higher ULs than those set by the NAM [7].
Doses higher than the UL that are used for acute treatment of zinc deficiency or diarrhea are safe and have not been associated with adverse effects on copper status or other metabolic indicators. (See 'Treatment' below.)
DIETARY SOURCES —
Primary dietary sources of zinc include animal products such as meat/flesh and shellfish and certain plant products including chickpeas, cashews, and pumpkin seeds (table 2). Among plant products, fortified ready-to-eat cereal is a common source of zinc [8]. Sufficient dietary zinc sources are available in a typical mixed diet. Lacto-ovo-vegetarians, especially in the pediatric age range, need more fortified grains or whole grains, legumes, milk, eggs, nuts, and seeds to achieve adequate levels. This is in part because grains and legumes have relatively high concentrations of phytates, which inhibit zinc absorption, as described below [1,9]. In addition, the zinc content of most fruits and vegetables is low. (See "Vegetarian diets for children".)
ZINC DEFICIENCY —
Zinc deficiency is typically related to inadequate dietary intake or underlying medical conditions that primarily impact the gastrointestinal tract. Because there are no substantial stores of zinc in the body, regular intake is essential and mild deficiency is relatively easily precipitated. The gastrointestinal tract has the largest role in zinc homeostasis, both through a saturable absorption process and controlled endogenous excretion that is responsive to zinc status. Reliable, sensitive tests for zinc deficiency are lacking, and an empiric trial of zinc supplementation is generally safe and often the most valuable tool for assessment of zinc status in children with suspected zinc deficiency. (See 'Underlying medical conditions' below.)
Causes
Dietary zinc deficiency — Inadequate dietary zinc intake is an important worldwide health problem, primarily but not exclusively affecting children in resource-limited settings. The true prevalence of mild zinc deficiency is not known, because of the nonspecificity of symptoms and imprecise diagnostic methods. On the basis of proxy indicators for populations (dietary intake, serum zinc concentrations, and prevalence of stunting), the prevalence of zinc deficiency is probably >25 percent in many resource-limited settings, with the highest rates in South and Southeast Asia and sub-Saharan Africa.
Risk factors for dietary zinc deficiency include:
●Prolonged exclusive breastfeeding – Symptomatic mild zinc deficiency occurs in infants who are exclusively or predominantly breastfed and with limited introduction of zinc-rich complementary foods beyond six months of age. This is due to the sharp physiologic decline in human milk zinc concentration during the first few months postpartum [10]. Other risk factors for more severe deficiency include malabsorptive disease including intestinal failure. The clinical presentation of zinc deficiency in infants and young children includes nonspecific symptoms or signs such as growth faltering (linear and ponderal), poor appetite, and frequent infections [11-14].
●Prematurity – Premature infants are born with lower absolute zinc stores and have higher urinary zinc excretion and diminished capacity for absorption of dietary zinc compared with full-term infants [15]. As a result, human milk fortifiers and preterm formulas routinely supply zinc but may still not meet the needs of some infants (see 'Resource-abundant settings' below). The increasing use of donor human milk further increases the risk of zinc deficiency because donor human milk tends to come from mothers who are several months postpartum, when zinc concentrations are much lower than age-matched mother's own milk [16,17]. (See "Approach to enteral nutrition in the premature infant", section on 'Nutrient requirements'.)
●Transient neonatal zinc deficiency – This condition is caused by a pathogenic variant in the zinc transporter ZnT-2 gene (SLC30A2), potentially impacting approximately 1 in 2300 newborns [18,19]. Lactating people with this variant have very low zinc concentration in their breast milk and subsequent zinc deficiency in their breastfed infant [20]. An increasing number of clinical cases and gene abnormalities of the zinc transporter gene have been identified. This condition should be considered in the differential diagnosis of exclusively or partially breastfed infants presenting with signs of moderate to severe zinc deficiency, including growth failure, dermatitis, and diarrhea.
●Complementary foods with low zinc content – Many complementary foods traditionally offered to infants and small children, such as natural grains and fruits and vegetables, have low zinc contents. Increasingly, weaning foods are fortified, but this practice is not widespread, especially in resource-limited countries [21]. The health consequences of subclinical zinc deficiency in infants and young children and the benefits of zinc supplementation in this population are discussed below (see 'Supplementation and food fortification' below). Introduction of meat (1 to 2 oz/day) as an early complementary food and continued through the first two years of life may provide a practical solution to enhancing zinc as well as iron status for breastfed infants and toddlers. (See 'Prevention' below.)
●Coingestion with phytates – Dietary phytates, which are present in cereal grains and legumes, interfere with zinc absorption and can contribute to zinc deficiency. This mechanism is seen in populations with diets high in grains and low in meats, such as areas of Africa, the Middle East, and Southeast Asia [22]. As an example, zinc deficiency was first described in adolescent males in Iran and Egypt [23,24]. The depletion was caused by inadequate zinc intake and poor zinc absorption because of the binding of ingested zinc to phytates in unleavened bread; in some cases, this was exacerbated by ingestion of clay (eating of earth, a form of pica). Affected patients suffered from severe growth retardation, anemia, hypogonadism, rough skin, and apathy or lethargy, which responded to zinc supplementation.
Acrodermatitis enteropathica — Acrodermatitis enteropathica (MIM #201100) is a recessively inherited partial defect in intestinal zinc absorption. It is the result of mutations in the SLC39A4 gene, which encodes the ZIP4 protein, resulting in a partial block of intestinal zinc absorption [25,26]. Global incidence rate of acrodermatitis enteropathica has been estimated at 1 per 500,000 births.
Affected infants develop an erythematous and vesiculobullous dermatitis (picture 1), alopecia, diarrhea, ophthalmic disorders (including corneal scarring, cataract formation, retinal degeneration, and optic atrophy [27]), severe growth retardation, delayed sexual maturation, neuropsychiatric manifestations, and frequent infections (table 3). The syndrome is associated with severe zinc depletion and is fatal without treatment. It responds to oral supplementation with pharmacologic doses of zinc, which are required for life.
Underlying medical conditions — Reduced serum zinc levels, at times symptomatic, have been reported in several other conditions. However, serum zinc is impacted by many factors including inflammation, postprandial state, and collection method, confounding its clinical utility, as detailed below.
●Crohn disease and ulcerative colitis – Low serum zinc concentrations are common in inflammatory bowel disease. Annual assessment of serum zinc has been recommended in pediatric patients with active disease, but specific benefits and the need for empiric supplementation are uncertain [28-30]. Clinicians should have a low threshold for checking zinc status and/or initiating an empiric course of zinc supplementation for patients with symptoms suggestive of deficiency, substantial mineral losses (eg, high-volume diarrhea or ostomy losses), and/or markedly low serum alkaline phosphatase concentration, which can be associated with zinc deficiency. Otherwise, the evidence for routine supplementation is lacking, particularly for patients with well-controlled disease. (See "Important health maintenance issues for children and adolescents with inflammatory bowel disease", section on 'Micronutrient deficiencies'.)
Evidence for zinc deficiency in inflammatory bowel disease and strategies for management are discussed separately. (See "Vitamin and mineral deficiencies in inflammatory bowel disease", section on 'Zinc'.)
●Celiac disease – Low serum zinc concentrations have been reported in approximately 50 to 60 percent of children and adults with newly diagnosed celiac disease, likely due to malabsorption [31-33]. Treatment with a gluten-free diet usually resolves the mucosal injury and zinc malabsorption, provided that the new diet includes meat or other source of zinc (gluten-free grain products often contain minimal zinc) [34]. However, partially treated celiac disease (ie, ongoing low-grade intestinal injury due to incomplete adherence to a gluten-free diet) is likely to increase zinc requirements.
●Cystic fibrosis – Dermatitis caused by zinc deficiency can be a presenting feature of cystic fibrosis in infants [35-37]. The dermatitis resembles acrodermatitis enteropathica, consistent with severe zinc deficiency, but may be multifactorial and may not respond to zinc supplementation alone [38]. Zinc deficiency in this population is related to malabsorption and increased endogenous fecal zinc losses related to fat malabsorption, as demonstrated by studies in infants prior to initiation of pancreatic enzyme therapy [39]. Concomitant deficiencies in essential fatty acids or protein-energy malnutrition also may contribute to the dermatitis. An empiric trial of zinc supplementation has been suggested for cystic fibrosis patients with symptoms that may be attributable to zinc deficiency (eg, characteristic dermatitis, growth retardation, increased susceptibility to infections, delayed sexual maturation, anorexia), as outlined in consensus guidelines [40]. (See "Cystic fibrosis: Nutritional issues", section on 'Zinc'.)
●Sickle cell disease – Low zinc levels can occur in children and adolescents with sickle cell disease, particularly in those with poor growth [41,42]. Zinc depletion in this population appears to reflect increased urinary excretion caused by a renal tubular defect and perhaps chronic hemolysis or impaired absorption, not only inadequate dietary intake [42,43]. Whether zinc deficiency contributes to adverse events in children with sickle cell disease is unclear [44]. A Cochrane review has found evidence of decreases in sickle cell crisis events with zinc supplementation [45]. A randomized clinical trial of children with sickle cell disease did not find a benefit of zinc supplementation on incidence of infections, although most children in the treatment arm had persistently low serum zinc concentrations, suggesting that higher doses may be necessary [46].
●Liver disease – Low plasma zinc concentrations in children and adults with severe chronic liver disease may be related to hypoalbuminemia, reduced intake, and increased urinary excretion [47-49]. There is some evidence indicating that zinc supplementation in patients with hepatic encephalopathy improved cognitive function [50]. If liver transplantation is performed, the low zinc concentration and the increased urinary excretion correct within seven days [47,48].
●Parenteral nutrition/intestinal failure – Infants and children receiving parenteral nutrition for intestinal failure are at risk for zinc deficiency if the parenteral nutrition has insufficient zinc concentrations (eg, due to a shortage of injectable zinc). They are also at risk for zinc deficiency after stopping the parenteral nutrition if they have ongoing zinc malabsorption due to the underlying intestinal disease [51]. In a case series of children with intestinal failure weaned off of parenteral nutrition, 67 percent had low measured zinc concentrations, indicating that intestinal failure alone can be the sole cause, potentially due to impaired absorption and/or increased endogenous losses [52]. A separate case series described three premature infants with cholestasis who developed clinical zinc deficiency consisting of diaper dermatitis, perioral erosions, and bullae on the dorsal surface of the hands and feet due to insufficient parenteral zinc concentrations [53]. (See "Parenteral nutrition in premature infants", section on 'Trace minerals'.)
●Kidney disease – Zinc deficiency can complicate nephrotic syndrome in children due to increased urinary losses [54]. In addition, uremic patients are often deficient in zinc, probably because of reduced dietary intake, zinc malabsorption, and/or removal of zinc during dialysis, particularly continuous kidney replacement therapy [55,56].
Clinical manifestations — Numerous signs and symptoms have been associated with zinc depletion (table 3).
●Mild zinc deficiency is associated with anorexia and growth impairment, depressed immunity, impaired taste and smell, onset of night blindness (related to interaction with vitamin A homeostasis), and, sometimes, a mild psoriasiform dermatitis.
●Severe zinc deficiency is characterized by dermatitis (typically erythematous, scaly, vesiculobullous, or pustular lesions, distributed initially in the perioral and perianal areas or on extensor surfaces of the limbs), severely depressed immune function, frequent infections, diarrhea, and alopecia (picture 2) [57-59]. (See "Overview of dietary trace elements", section on 'Deficiency'.)
The importance of zinc in immune function is suggested by studies showing benefits of zinc for treatment or prevention of diarrhea or pneumonia in children in resource-limited settings, as discussed below. (See 'Likely beneficial effects' below.)
Diagnosis — Although many biomarkers have been tested, none completely reflects zinc status, in part due to the diversity of its biologic functions and incorporation in nearly all tissues of the body. In our clinical practice, we do not routinely find benefit from checking serum zinc levels. Rather, evaluating the clinical context, dietary habits, medical history, and physical examination have a greater influence on the decision to provide empiric zinc supplementation.
Evidence to support a diagnosis of zinc deficiency may include:
●Serum/plasma zinc concentrations – This is the most useful laboratory test for zinc deficiency, despite limited sensitivity and specificity. In general, its use should be limited to clear clinical indications and results interpreted based on the underlying reason for the evaluation.
•Technique – If this test is performed, precautions must be taken to avoid contamination of the sample by careful cleaning of skin, use of zinc-free gloves, and use of a zinc-free collection tube. Low serum zinc has been defined as <60 micrograms/dL (<9.2 micromol/L) [60]. However, for morning samples, it may be appropriate to use a higher threshold of 65 or 70 micrograms/dL (9.9 or 10.7 micromol/L) [61,62].
•Limitations – Zinc levels are depressed during inflammatory conditions and during pregnancy. If inflammation is a concern, measuring a marker of inflammation such as C-reactive protein may be helpful to assess the inflammatory state and interpret the serum zinc result [63]. Conversely, serum zinc concentrations increase with acute catabolic states [64]. Moreover, sensitivity is limited since patients with mild zinc deficiency may have normal serum levels [65].
In patients with hypoalbuminemia, measured zinc levels are typically decreased because most serum zinc is bound to albumin. However, in clinical practice, we do not attempt to correct measured zinc levels for hypoalbuminemia. Instead, we treat patients with low serum zinc levels empirically with zinc supplements regardless of albumin levels.
Zinc levels may also be measured in neutrophils, lymphocytes, or erythrocytes, but these assays generally have poor sensitivity and are not considered reliable biomarkers of status [1,63,66].
●Clinical response – In selected clinical cases in which the zinc level is normal, a clinical response to zinc supplementation (eg, with improved appetite or growth) may confirm a diagnosis of zinc deficiency. In other situations, the diagnosis of zinc depletion is inferred by the response to zinc supplementation in placebo-controlled intervention. (See 'Supplementation and food fortification' below.)
●Alkaline phosphatase – Depressed serum alkaline phosphatase activity for age has been proposed to provide supportive evidence for zinc deficiency. However, this test does not reliably reflect zinc intake or zinc status and is not considered to be a sensitive biomarker [63,67].
Treatment
●Deficiency due to inadequate intake or underlying conditions – For zinc deficiency due to inadequate oral intake, a typical oral replacement dose is 1 to 2 mg/kg/day of elemental zinc [68,69]. Resolution usually requires at least four to six weeks of therapy, depending on the etiology and severity. Routine maintenance supplementation may also be appropriate for patients with underlying diseases that predispose to zinc deficiency, such as active Crohn disease, cystic fibrosis, liver disease, or sickle cell disease. Note that it is acceptable if these short-term replacement doses exceed the upper tolerable limit (UL) for zinc, which refer to chronic intake of zinc (see 'Upper tolerable limit' above). It is not usually necessary to coadminister copper unless the zinc dose exceeds 2 mg/kg/day on a chronic basis and if serum copper levels are reduced.
Infants receiving long-term parenteral nutrition or those with intestinal failure may need additional zinc added to their parenteral nutrition or given orally, with close monitoring of serum zinc levels [52]. (See "Parenteral nutrition in infants and children", section on 'Trace elements and minerals' and "Parenteral nutrition in premature infants", section on 'Trace minerals'.)
●Acrodermatitis enteropathica – For acrodermatitis enteropathica, higher replacement doses are recommended: approximately 3 mg elemental zinc/kg/day (13.2 mg/kg/day of zinc sulfate or 10.1 mg/kg/day of zinc acetate) [70,71]. We suggest measuring zinc levels every three to six months and adjusting the dose up or down as needed; serum copper should also be monitored. Patients with acrodermatitis enteropathica require these high doses to overcome the defect in intestinal zinc absorption. (See 'Acrodermatitis enteropathica' above.)
Toxicity from zinc supplementation is rare, although long-term administration of high doses (>50 mg zinc/day) may lead to copper deficiency, reduced immune function, and lower high-density lipoprotein cholesterol levels. High intakes are also associated with nausea, gastric distress, vomiting, and loss of appetite [64]. (See 'Adverse effects' below.)
Prevention — Local foods that are naturally rich in zinc may prevent dietary zinc depletion and its health consequences (table 2). For infants, the use of pureed meats as a complementary food may provide a practical solution in resource-limited countries, although the relative expense of animal source foods is a major impediment to broad implementation [21]. This approach was explored in two studies of healthy breastfed infants in the United States, in which infants were randomized to be fed with either fortified cereal or beef as a first complementary food from age four to nine months [72,73]. Both diets provided estimated requirements of zinc and iron, and there were no differences in infant tolerance or acceptance or in serum zinc levels. These findings suggest that 1 to 2 oz of pureed meat per day may provide a practical preventive strategy for zinc and iron deficiencies in resource-limited countries, if social, cultural, and economic barriers to this practice can be addressed by public health initiatives. The World Health Organization (WHO), American Academy of Pediatrics, and 2020-2025 Dietary Guidelines for Americans have all endorsed the potential value of meats as an early complementary food [74-76].
SUPPLEMENTATION AND FOOD FORTIFICATION
Resource-limited settings — Zinc deficiency, which is associated with impaired immunity and propensity to infection, is common in resource-limited countries, where it may contribute to the high rates of serious infections among children. Accordingly, zinc supplementation has been evaluated as a therapeutic agent and prophylactic agent in children in these populations [77].
In population interventions or studies, zinc is often provided via fortified foods including weaning foods. Large-scale food fortification reduces the incidence of zinc deficiency in high-risk populations [78,79]. In many places, however, the fortification of foods is done with multiple micronutrients, so reported beneficial effects may not reflect an independent effect of zinc supplementation.
Likely beneficial effects
Treatment of acute or persistent diarrhea — We agree with the World Health Organization (WHO) recommendation of zinc supplementation for children with acute diarrhea in resource-limited settings [80]. Dosing, supporting evidence, and other considerations are discussed separately. (See "Approach to the child with acute diarrhea in resource-limited settings", section on 'Vitamins and minerals'.)
Few data are available regarding the role of zinc in recovery from acute diarrhea in resource-abundant settings. Available data suggest that there is little or no benefit, but much larger and well-controlled trial data are needed [81].
Prevention of diarrhea — Numerous studies in resource-limited countries have shown that routine oral zinc supplementation reduces the incidence of diarrheal disease and diarrhea-related mortality in populations with high risk for zinc deficiency [82-90]. A meta-analysis found that supplementation modestly reduced the incidence of diarrhea in children 6 months to 12 years of age (39 studies; risk ratio 0.91, 95% CI 0.90-0.93) [91]. A few trials in infants also suggest that zinc supplementation may have a small protective effect on the risk for diarrhea [90,92,93]. One placebo-controlled study found that two weeks of zinc supplementation in infants aged 6 to 11 months in India reduced the frequency of diarrheal episodes by 39 percent and duration of the episodes by 36 percent [92], while a separate study in Bangladesh found no effect of zinc supplementation on diarrhea duration or frequency [77].
Zinc supplementation given to pregnant women reduces the frequency of diarrhea in their offspring during infancy. In a placebo-controlled trial in Peru, infants whose mothers received prenatal zinc supplementation had a 34 percent lower risk of prolonged diarrheal episodes compared with controls [94]. In a similar trial in Bangladesh, prenatal zinc supplementation reduced the infants' risk for acute diarrhea by 16 percent and dysentery by 64 percent [95].
Prevention of pneumonia — A meta-analysis found that zinc supplementation given to children between two months and five years of age in resource-limited settings reduced the incidence of clinically confirmed pneumonia by approximately 20 percent (risk ratio 0.79, 95% CI 0.71-0.88) [88,96]. The included studies were performed in Bangladesh, India, Peru, and South Africa. One study found a shorter course of pneumonia in children under five years of age in Mexico [97].
Enhancement of growth — In populations with high rates of zinc deficiency, zinc supplementation enhances growth in young infants and has modest effects on growth in older children. A meta-analysis that focused on multinutrient supplementation also showed only modest growth benefits [98]. Of note, zinc has no effect on growth in individuals without an underlying zinc deficiency (ie, it has no pharmacologic effect on growth) [99,100]. Thus, a growth response to supplemental zinc is considered evidence of a preexisting zinc deficiency.
The growth effect of zinc supplementation appears to depend on the dose, age group, and presence of other micronutrients such as iron:
●Young infants – A meta-analysis of studies conducted in infants less than six months of age in resource-limited settings found that oral zinc supplements improved growth, as measured by weight-for-age and weight-for-length Z-scores [101]. This meta-analysis was limited to a few studies, with substantial dropouts and other limitations noted. Further studies would be needed to assess this population before supplements could be recommended for this population.
●Older infants – A study of over 2000 infants in Bangladesh ages 9 to 11 months found beneficial effects on linear growth of a micronutrient powder with zinc (10 mg) and iron (6 mg) compared with zinc alone or lower doses of zinc [77]. These results are in contrast with a large randomized trial that studied infants up to 18 months of age in Tanzania, in which zinc supplementation alone (5 mg daily) had a slight negative effect on growth, while the combination of zinc with a multivitamin supplement (without iron) had a small positive effect on weight gain [102]. In this population, zinc or multivitamin supplementation had no effect on measures of cognition at 15 months of age [103].
●Young children – A meta-analysis focusing on children younger than five years of age from resource-limited settings found modest positive effects of zinc on linear growth, but this effect was attenuated in children given concurrent iron supplementation [104]. The doses of zinc used in these trials varied from 1 to 20 mg/day of elemental zinc, with a median of 10 mg/day. A subsequent meta-analysis also reported modest benefits of zinc supplementation on height and weight, with greater effects among children two to five years of age compared with those under two years of age [105].
●School-aged children – A systematic review of more than 80 randomized trials from resource-limited settings found modest positive effects of zinc supplementation on height in children between 6 months and 12 years of age, although the benefits were greater for older children (>5 years) compared with younger children and infants [89]. Zinc supplementation had negative effects on copper status and increased risk for vomiting.
Unclear or marginal benefits
Adjunctive treatment for pneumonia or other bacterial infection — Studies conflict regarding the utility of adjunctive zinc for children with pneumonia. A meta-analysis showed a potential small benefit on length of hospitalization but no impact on recovery time [106]. Most evaluated studies took place in resource-limited settings where children are already at high risk of zinc deficiency. The authors concluded that empiric zinc supplementation in children with pneumonia could not be supported.
By contrast, a study in 700 young infants (7 to 120 days old) in India with serious bacterial infections (pneumonia, sepsis, and diarrhea) suggests a beneficial effect of adjunctive zinc [107]. All subjects were treated with antibiotics according to a standardized protocol. Infants who were also treated with zinc (5 mg twice daily by mouth) had significantly less treatment failure as compared with those treated with placebo (10 versus 17 percent, respectively); treatment failure was defined as a need to change antibiotics within seven days of randomization or a need for intensive care, or death at any time within 21 days. The absolute risk reduction was 6.8 percent (95% CI 1.5-12.0). The population in this study had a high rate of underlying nutritional zinc deficiency, and whether adjunctive zinc treatment for bacterial infection is beneficial in other populations has not been established.
Prevention or treatment of malaria — Several meta-analyses have failed to show an effect on malaria parasitemia of zinc supplementation alone or in combination with other micronutrients [108,109].
Although zinc levels tend to decrease in children with acute falciparum malaria [110], this is an artifact of the acute phase response and zinc supplementation does not appear to have a beneficial effect when used as an adjunct to treatment of the disease [111]. (See "Treatment of uncomplicated falciparum malaria in nonpregnant adults and children" and "Treatment of severe malaria".)
Resource-abundant settings
●Supplementation – Routine zinc supplementation is not necessary or recommended for healthy infants and children in resource-abundant settings, where the risk of zinc deficiency is low. In these settings, zinc supplementation is generally limited to individuals with suspected or confirmed zinc deficiency. Targeted testing for zinc deficiency or empiric supplementation may be appropriate for patients with an increased risk for zinc deficiency due to an underlying medical condition, as outlined above. (See 'Underlying medical conditions' above.)
Similarly, in these resource-abundant settings, empiric zinc supplementation does not appear to be beneficial for children with acute or persistent diarrhea, pneumonia, idiopathic growth failure, or other conditions [81]. This is in contrast with the case for children in resource-limited settings. (See 'Resource-limited settings' above.)
One exception is for premature infants, in whom zinc appears to have beneficial effects on growth. Premature infants have lower zinc stores and higher needs compared with term infants [112]. Multiple large randomized controlled trials and meta-analyses have shown beneficial effects of zinc supplementation on growth in premature infants [113,114]. Positive effects have been demonstrated for not only weight gain but also linear growth and possibly head growth that persists after discharge from the neonatal intensive care unit [115]. Both formula-fed and human milk-fed infants appear to have improved growth outcomes with zinc supplementation, suggesting that neither feeding regimen provides adequate zinc in this vulnerable population [114]. Human milk fortifiers and preterm formulas routinely supply zinc supplements around 2 mg/kg/day. This is probably sufficient for larger preterm infants but may not fully meet zinc needs for infants <1500 g (estimated requirements for these small infants are approximately 2.7 to 3 mg/kg/day) [2]. Whether there are additional benefits of higher doses has not been established. (See "Nutritional composition of human milk and preterm formula for the premature infant", section on 'Other vitamins and minerals'.)
Benefits of zinc supplementation are also seen for mortality (low-certainty evidence) but have not been demonstrated for other conditions including sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia, in part due to limited studies [114].
●Fortification – For most children, adequate zinc is supplied by widespread fortification of commonly used foods, such as breakfast cereals. As an example, among older infants enrolled in the Special Supplemental Nutrition Program in the United States, only 2 percent had inadequate zinc intake due to zinc fortification of foods provided by this program [116].
ADVERSE EFFECTS —
Zinc supplementation at typical doses (eg, 1 to 2 mg/kg/day for dietary deficiency) is generally well tolerated. The main side effect is vomiting, which is more common with higher doses (eg, 20 mg daily) or when taken on an empty stomach [117].
Chronic intake of high doses of zinc (eg, >60 mg/day) may be associated with copper deficiency because zinc inhibits intestinal absorption of copper. (See 'Recommended intake' above.)
The acute ingestion of 1 to 2 g zinc sulfate produces nausea and vomiting associated with irritation and corrosion of the gastrointestinal tract [118]. Large doses of zinc compounds also can produce acute kidney failure caused by tubular necrosis or interstitial nephritis [119]. (See "Acute kidney injury in children: Clinical features, etiology, evaluation, and diagnosis".)
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Vitamin deficiencies".)
SUMMARY AND RECOMMENDATIONS
●Dietary sources of zinc – Primary dietary sources of zinc include animal products such as meat, seafood, milk, and fortified foods such as breakfast cereal (table 2). Sufficient dietary zinc sources are available in a typical mixed diet. Adequate zinc can also be obtained from a balanced lacto-ovo-vegetarian diet that includes foods rich in zinc, including zinc-fortified cereals, legumes, nuts, seeds, eggs, and milk. (See 'Recommended intake' above.)
●Clinical manifestations – Symptoms attributable to severe zinc depletion include anorexia, growth impairment, impaired taste and smell, impaired immunity, and night blindness (which is related to impaired vitamin A homeostasis) (table 3). Severe zinc deficiency is characterized by dermatitis (typically in the perioral and perianal areas), diarrhea, alopecia, and severely depressed immune function with frequent infections (picture 2). (See 'Clinical manifestations' above.)
●Causes of zinc deficiency
•Dietary deficiency – Zinc depletion primarily occurs in resource-limited settings, where complementary foods typically provide inadequate amounts of bioavailable zinc. Symptomatic zinc deficiency can also occur in infants who are exclusively or predominantly breastfed who are not fed zinc-rich complementary foods by six months of age. It is especially common in premature infants. Zinc deficiency in a breastfed newborn also may be precipitated by a maternal genetic variant that impairs zinc transport into breast milk. (See 'Dietary zinc deficiency' above.)
•Genetic disorders – Acrodermatitis enteropathica is a recessively inherited partial defect in intestinal zinc absorption. Affected infants develop an erythematous and vesiculobullous dermatitis (picture 1), alopecia, ophthalmic disorders, diarrhea, and severe growth retardation. The syndrome responds to oral supplementation with pharmacologic doses of zinc. (See 'Acrodermatitis enteropathica' above and 'Treatment' above.)
•Medical conditions – Reduced serum zinc concentrations, at times symptomatic, have been reported in malabsorptive conditions (Crohn disease, celiac disease, cystic fibrosis, intestinal failure), sickle cell disease, severe liver disease, kidney disease (nephrotic syndrome), and children maintained on parenteral nutrition without zinc supplementation. (See 'Underlying medical conditions' above.)
●Diagnosis – Serum or plasma zinc concentrations are the most useful laboratory test for zinc deficiency, despite limited sensitivity and specificity. However, in practice, we often decide whether to initiate zinc supplementation based on the clinical context and symptoms rather than on laboratory testing. In addition, a normal serum zinc concentration in a patient with risk factors does not rule out zinc deficiency. A low serum zinc concentration usually is defined as a value less than 60 to 65 mcg/dL. Zinc concentrations can be reduced in patients with inflammation or hypoalbuminemia and increased in acute catabolic states. (See 'Diagnosis' above.)
●Treatment – For infants and young children with suspected zinc deficiency, replacement doses of zinc are 1 to 2 mg/kg/day of elemental zinc for at least four to six weeks, while observing for a clinical response. A longer observation period may be warranted in older children. (See 'Treatment' above.)
●Approach in resource-limited settings
•Routine supplementation – Zinc deficiency is common in children in resource-limited countries, and zinc deficiency appears to contribute to the risk of diarrhea and pneumonia in these populations. Routine oral zinc supplementation, often done via food fortification, reduces the incidence of these disorders. (See 'Resource-limited settings' above.)
•Acute diarrhea – Zinc administration is indicated for treatment of acute or persistent diarrhea in children from populations in which zinc deficiency is common. Dosing, supporting evidence, and other considerations are discussed separately. (See "Approach to the child with acute diarrhea in resource-limited settings", section on 'Vitamins and minerals'.)
●Adverse effects – Zinc supplementation at typical doses (eg, 1 to 2 mg/kg/day for dietary deficiency) is generally well tolerated. The main side effect is vomiting, which is more common with higher doses (eg, 20 mg daily) or when taken on an empty stomach. Because intestinal absorption of copper is inhibited by zinc, chronic intake of very high doses of zinc (eg, >60 mg/day) may cause copper deficiency. (See 'Adverse effects' above.)
