Essential micronutrients in children and adolescents with a focus on growth and development: a narrative review

Overview: role of micronutrients

Understanding recommended micronutrient intake levels is helpful for evaluating nutritional adequacy and planning appropriate interventions. Table 1 presents the Korean Dietary Reference Intakes of the micronutrients discussed in this review [3]. These reference values provide important benchmarks for assessing nutritional requirements across different age groups and serve as a reference for the following review of each micronutrient. The Dietary Reference Intakes (DRIs) used in Table 1 include several reference values, the definitions of which are as follows. The Estimated Average Requirement (EAR) represents the median daily nutrient intake level that meets the requirements of 50% of healthy individuals and is usually used to assess the nutrient intakes of groups of people and to plan nutritionally adequate diets for them, although it can also be used to assess individual nutrient intakes. The Recommended Nutrient Intake (RNI) is set at two standard deviations above the EAR, meets the requirements of 97% to 98% of healthy individuals, and is often used to plan nutritionally adequate diets. RNI is the term used in Korean DRIs and is equivalent to the Recommended Dietary Allowance in the United States DRI system. The Adequate Intake (AI) is established when evidence is insufficient to determine EAR based on the median intake levels of healthy individuals from experimental or observational studies, although the extent to which this meets the requirements of the target population is uncertain [3].

Table 1.

Korean Dietary Reference Intakes for selected essential micronutrients by age group

To aid clinical practice, Table 2 summarizes the primary physiological roles, key deficiency symptoms, high-risk groups, and prevalence data of these six micronutrients.

Table 2.

Summary of each essential micronutrient for growth and development in children and adolescents

Iron

Iron exists primarily in two forms: heme iron from animal sources with higher bioavailability (15%–35%) and nonheme iron from plant sources with lower bioavailability (2%–20%). The absorption of nonheme iron is significantly affected by dietary components, with factors such as phytic acid, polyphenols, calcium, and proteins found in milk, eggs, and soybeans inhibiting absorption. Conversely, enhancers such as ascorbic acid can facilitate the conversion of ferric iron to ferrous iron, thereby promoting iron absorption [4].

The fundamental roles of iron include hemoglobin formation, oxygen transport, myoglobin function, and neural development [5]. Iron deficiency (ID) can manifest with or without anemia. While functional alterations may be present even without anemia, the most severe impairments typically occur with iron deficiency anemia (IDA) [6]. Common causes of ID include an insufficient intake of bioavailable iron, increased demand during rapid growth or menstruation, gastrointestinal blood loss, and impaired absorption [7].

Assessment of iron relies on serum ferritin levels (reflecting storage), transferrin saturation, and hemoglobin levels. Ferritin levels of <12–15 ng/mL typically indicate depleted iron stores, although ferritin levels can be elevated during inflammation. In children and adolescents, IDA is often suspected if the hemoglobin level is <11 g/dL up to 11 years of age and <12 g/dL thereafter [8].

IDA is the most common type of anemia in children and adolescents and one of the most widespread nutritional deficiencies globally [9]. ID can negatively affect motor, cognitive, socioemotional, and neurophysiological development in infants, children, and adolescents in both the short and long term [10]. The impact of iron on fetuses is also significant; ID can lead to changes in hippocampal energy metabolism, striatal dopamine metabolism, and a decrease in myelination, adversely affecting the developing brain behavioral system in fetuses and newborns. Maternal ID is the most common cause of fetal ID [11].

Prevalence data from the Korea National Health and Nutrition Examination Survey (KNHANES) showed higher rates in females, particularly adolescents; boys aged 10 to 14 years had an ID prevalence of 6.8% versus 18.6% in girls, with an IDA prevalence of 1.0% and 2.6%, respectively. Among adolescents aged 15 to 17 years, 3.2% of males had ID, whereas 34.7% and 9.0% of females had ID and IDA, respectively [12]. In the United States, National Health and Nutrition Examination Survey (NHANES) data showed ID, anemia, and IDA prevalence rates of 7.1%, 3.2%, and 1.1%, respectively, in children aged 1 to 5 years, with higher rates in ages of 1 to 2 years. Among females aged 12 to 21 years, the prevalence of ID was 38.6%, and that of IDA was 6.3%, similar to Korean patterns [13].

For these at-risk groups, it is essential to monitor ID and ensure appropriate surveillance. For infants, it is important to introduce complementary foods at the appropriate time and pay careful attention to their diets to ensure adequate iron intake. Nutritional ID occurs when a diet fails to provide sufficient iron to meet the physiological needs of the body. Populations that primarily consume repetitive plant-based diets with minimal meat intake tend to experience reduced bioavailability of dietary iron. This is especially prevalent in diets low in meat, since meat is known to have higher heme iron content, and thus better bioavailability [14]. Incorporating animal-based foods rich in heme iron and coupling them with fresh vegetables and fruits loaded with ascorbic acid can enhance the overall intake and absorption of iron.

A Cochrane Review of 26 studies involving 2,726 preterm and low-birthweight infants found that enteral iron supplementation (≥1 mg/kg/day) reduced the risk of ID [15]. The American Academy of Pediatrics (AAP) recommends iron supplementation of 2 mg/kg/day for preterm infants aged 1 to 12 months who are fed breast milk. For exclusively or primarily breastfed full-term infants, the AAP advises 1 mg/kg of daily iron supplementation from the age of 4 months until they begin consuming iron-containing complementary foods [16]. The European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) recommends that breastfed preterm infants up to 6 months of age receive 2 to 3 mg/kg/day of iron supplements [17].

Meta-analyses and systematic reviews have shown that iron supplementation does not significantly affect the growth of children and adolescents. Some studies have shown that while iron treatment significantly improves hemoglobin levels, it does not significantly affect other anthropometric measures, such as weight, height, mid-upper arm circumference, skinfold thickness, and head circumference [18-20]. In terms of development, iron supplementation has shown positive results in reducing cognitive and motor developmental deficits and improving memory and learning in iron-deficient or anemic children and adolescents [18]. A systematic review indicated that while iron interventions are effective in improving iron status and anemia, there is no evidence that iron status and anemia affect or are associated with the attention, intelligence, or memory of adolescents, nor does iron supplementation improve memory recall or intelligence [21]. Iron plays a crucial role in the growth and development of children and adolescents; however, the effects of iron supplementation can vary based on individual conditions, age, health status, and other variables. Therefore, the approach to iron supplementation should be considered carefully, assessing each child’s iron and nutritional status and providing appropriate iron supplementation when needed.

Zinc

Zinc is abundantly found in meat, fish, and seafood, with oysters notably high in content; meat, particularly beef, accounts for 20% of intake owing to its higher consumption rate. Eggs and dairy also contain zinc. Plant-based sources such as beans, nuts, and whole grains also contain zinc, but their bioavailability is low because of the presence of phytates, which form insoluble complexes that inhibit zinc absorption [22]. Zinc plays a vital role in enzyme catalysis, enhancing immune functions, protein and DNA synthesis, cell signaling, division, growth, tissue repair, and wound healing. It is also involved in lipid and glucose metabolism and in responses to immunity and infection [23]. Zinc supports growth by promoting growth hormone (GH) receptor binding and regulating the expression of GH receptors and insulin-like growth factor 1 (IGF-1) genes in the liver [24].

Symptoms of zinc deficiency vary with age. Diarrhea is a common issue in infants and young children. As children grow older, they may experience growth delays, alopecia, and frequent infections. Additionally, zinc deficiency can affect taste and smell [25]. Acrodermatitis enteropathica is an inherited form of zinc deficiency resulting from impaired absorption and occurs due to an autosomal recessive mutation in the SLC39A4 gene. This condition often becomes symptomatic in infancy after breastfeeding ceases, with clinical symptoms including alopecia, diarrhea, growth impairment, and characteristic skin lesions that predominantly appear as burn-like psoriasiform lesions around the mouth, anus, gluteal region, perineum, and extremities [26].

Typically, serum zinc levels <70 μg/dL for women and <74 μg/dL for men are considered indicative of insufficient zinc status [23]. The International Zinc Nutrition Consultative Group suggests cutoff values for zinc deficiency of <65 µg/dL (9.9 µmol/L) in the morning and <57 µg/dL (8.7 µmol/L) in the afternoon for children under 10 years old [27]. However, these serum values have limitations, as zinc concentrations can vary based on sex, age, and time of day (morning vs. evening); therefore, interpretation requires caution [28].

In the United States, <1% of children aged 2 to 8 years have a zinc intake below the EAR; however, among adolescents aged 14 to 18 years, only 1% of boys fall short compared to 20.9% of girls. The NHANES (2011–2014) further indicates that 3.8% of children <10 years old, 8.6% of males ≥10 years old, and 8.2% of females have serum zinc levels below the sufficiency cutoff, suggesting that adolescents are at potential risk of zinc deficiency [29]. In contrast, Korean data (KNHANES 2016–2019) show that children aged ≥1 year have a zinc intake of 147.4% of the EAR, with those <5 years old consuming more than twice the EAR, suggesting that zinc deficiency is rarely observed in Korea [30].

Several groups should be mindful of zinc inadequacy. Approximately 15% to 40% of individuals with inflammatory bowel disease (IBD) experience zinc deficiency due to inflammation, poor intake, and malabsorption [31]. Children and adolescents receiving parenteral nutrition for long-term intestinal failure are at risk of zinc deficiency if their nutrition lacks adequate zinc [32]. In cystic fibrosis, dermatitis caused by zinc deficiency can be the initial presenting symptom [33]. Vegetarians may encounter zinc inadequacy because the bioavailability of zinc in their diets is low [34]. Additionally, older infants who are exclusively breastfed are at risk of zinc deficiency. The zinc content in breast milk is the highest in the first month after birth and declines by approximately 75% by the ninth month. Therefore, infants older than 6 months who are exclusively breastfed without adequate complementary foods may not receive sufficient zinc [35].

For individuals at risk of zinc deficiency or showing signs or symptoms of zinc deficiency, an assessment of zinc status is necessary. Preventatively, consuming zinc-rich foods such as meat, fish, and seafood are advised. Zinc supplementation is not routinely required for healthy children and adolescents in low-risk environments. Zinc is available in supplements containing only zinc, in combination with other ingredients, and in many multivitamin/mineral products. These supplements contain various forms of zinc, with the amount of elemental zinc indicated on the product label [36]. Regarding gut health, zinc deficiency can alter the composition of the gut microbiome, favoring pathogenic over beneficial bacteria. Adequate zinc levels support intestinal barrier integrity, immune functionality, and overall microbiome health [37]. Studies suggest that zinc, alone or in combination with other treatments, can effectively reduce the duration of diarrhea in children, particularly in low- and middle-income countries [38,39]. The World Health Organization (WHO) recommends a short course (10–14 days) of zinc supplementation to treat diarrhea in children [40]. A recent meta-analysis of the effects of zinc supplementation on growth patterns in healthy children revealed that zinc supplementation significantly enhanced height, weight, and height-for-age in individuals [41]. The positive effects of zinc on weight and height may be related to its effects on GH metabolism. Zinc supplementation increases the levels of IGF-1 and IGF-binding protein-3 in healthy children [42].

Vitamin A

Vitamin A refers to a group of fat-soluble retinoids, most notably retinol and retinyl esters. It is involved in immune responses, growth and development, and reproductive health and aids in the cellular growth and differentiation necessary for the healthy formation and maintenance of vital organs, such as the heart and lungs. Additionally, vitamin A is important for vision, acting as a crucial element of rhodopsin, a light-sensitive protein in the retina, and contributing to the normal differentiation and function of the conjunctival membranes and cornea [43,44].

Humans must obtain vitamin A from their diet either as preformed vitamin A or provitamin A carotenoids. Animal sources such as dairy, eggs, fish, and organ meat provide preformed vitamin A. Provitamin A carotenoids, which are abundant in green leafy vegetables, sweet potatoes, and carrots, are converted into vitamin A in the intestine. In wealthier nations, the majority of vitamin A intake comes from preformed vitamin A, whereas in low-income countries, people primarily consume provitamin A [43].

The first symptom of vitamin A deficiency is night blindness, caused by low retinal rhodopsin levels. The most common clinical manifestation is xerophthalmia, which occurs due to low plasma retinol levels and depletion of vitamin A reserves in the eyes. In extreme cases, long-term vitamin A deficiency can lead to hyperkeratosis of the ocular epithelial tissue and eventually permanent blindness, which is the most common cause of blindness in developing countries [45]. Chronic vitamin A deficiency is also associated with abnormal lung development, pneumonia, increased risk of anemia, and increased mortality [46].

For assessment of vitamin A status, plasma retinol measurement is the standard diagnostic tool, with concentrations of ≤0.70 µmol/L and ≤0.35 µmol/L indicating moderate-severe deficiency, respectively [43]. Although vitamin A deficiency is uncommon in developed countries, it remains a significant public health concern in developing nations, where economic constraints and dietary customs often limit access to both animal-derived foods with preformed vitamin A and plant-based foods rich in provitamin A carotenoids [43]. According to a 2009 WHO report, vitamin A deficiency affected more than 190 million preschool-aged children worldwide, particularly in developing countries [47]. By 2013, the prevalence among children aged 6 to 59 months in low- and middle-income countries was estimated at 29% [48]. In contrast, a 2007 regional study in Korea found that only 2.4% of children aged 2 to 6 years were vitamin A deficient, based on plasma retinol concentrations <0.70 µmol/L [49]. The authors attributed this low prevalence to dietary patterns that rely heavily on plant-based provitamin A carotenoids and the generally good health and balanced nutrition of Korean children [49].

While vitamin A deficiency primarily affects infants and children in low- and middle-income countries, certain individuals, such as preterm infants and those with malabsorptive conditions, including IBD, are also at risk. Premature infants can be vulnerable due to inadequate hepatic vitamin A reserves at birth, with their plasma retinol levels frequently remaining below optimal levels throughout the first year of life. This deficiency is particularly concerning in preterm infants because it increases the risk of developing ocular complications and chronic pulmonary disease [50].

Vitamin D

Vitamin D is synthesized primarily (80%–90%) in the skin upon ultraviolet-B (290–320 nm) exposure, influenced by factors such as skin type, latitude, season, age, and obesity [51]. Only a small portion of vitamin D is provided by the diet, mainly fatty fish (e.g., salmon and mackerel), cod liver oil, and egg yolks, whereas mushrooms contain ergocalciferol [52]. Once produced or ingested, vitamin D binds to vitamin D-binding protein, is hydroxylated in the liver to form 25-hydroxy vitamin D (25(OH)D), and is converted in the kidneys to its active form, 1,25-dihydroxy vitamin D (1,25(OH)D) [53]. Vitamin D aids in calcium absorption in the intestine, maintains adequate calcium and phosphate levels for bone formation, and prevents hypocalcemia. It is also critical for bone remodeling, immune function, and glucose metabolism [54].

In Korea, while the Ministry of Health and Welfare and osteoporosis guidelines consider ≥20 ng/mL as appropriate for skeletal health, clinical practice commonly adopts the criteria of <10 ng/mL for deficiency and <30 ng/mL for insufficiency. The criteria for vitamin D status varies internationally [55]. The U.S. National Institutes of Health considers serum 25(OH)D concentrations <12 ng/mL as deficient, 12 to 20 ng/mL as potentially inadequate, and ≥20 ng/mL as sufficient for most people, with levels >50 ng/mL potentially associated with adverse effects [56].

Vitamin D deficiency is a significant public health concern across various countries and age groups. Data from the KNHANES (2008–2011) demonstrated that among adolescents aged 10 years to 18 years, the prevalence of vitamin D deficiency (<20 ng/mL) and insufficiency (20–29.9 ng/mL) was 73.3% and 24.4%, respectively [57]. Similar patterns were observed in other Asian countries. Studies from Japan have indicated that among 2-year-old children, 24.7% were classified as vitamin D deficient and 51.3% showed insufficient levels [58]. A Chinese study revealed that approximately 66% of children and adolescents aged 6 to 17 years had a suboptimal vitamin D status, using 20 ng/mL as the cutoff value [59]. In the United States, 70% of children and adolescents had suboptimal vitamin D levels (9% deficient and 61% insufficient) [60].

These deficiencies can result from low dietary intake, inadequate sun exposure, impaired renal conversion, or malabsorption. Severe deficiency may cause rickets in children and osteomalacia in adolescents [61]. The risk of vitamin D deficiency is influenced by multiple factors, such as dark skin pigmentation, geographical location (northern latitudes) during winter, consistent use of high sun protection factor sunscreen, cultural practices involving extensive body coverage with clothing, air pollution exposure, and a predominantly indoor lifestyle [62]. These risk factors are likely to be relevant to Korean adolescents.

Children and adolescents who are obese are known to be at risk for vitamin D deficiency or insufficiency [63]. Recent meta-analyses have also confirmed the association between obesity and vitamin D deficiency in adolescents [64]. However, these findings do not conclusively determine whether obesity causes vitamin D deficiency or vice versa. Possible mechanisms include subcutaneous fat-sequestering of vitamin D (limiting its bioavailability), obesity-related leptin pathways inhibiting renal activation, decreased sun exposure, and inadequate dietary intake [65,66]. Some studies have suggested that vitamin D deficiency contributes to obesity through its potential effects on insulin sensitivity and lipid metabolism [67,68]. Obese populations may require higher doses of oral vitamin D supplements [65]; however, the effects of these supplements on metabolic and cardiovascular outcomes remain uncertain. Meta-analyses in adults suggest possible reductions in body mass index and waist circumference with supplementation [69], while pediatric studies (children 6–14 years old) have generally indicated no significant changes in body composition [70,71].

Lactating mothers and their exclusively breastfed infants are considered at high risk for vitamin D deficiency, as human milk typically contains limited amounts of vitamin D (≤25–78 IU/L), with concentrations heavily influenced by maternal vitamin D status [72]. The WHO recommends 200 IU/day of vitamin D for infants [73], and the AAP recommends vitamin D supplementation of 400 IU/day for all infants from birth, including exclusively and partially breastfed infants, continuing until they consume at least 1,000 mL/day of vitamin D-fortified formula or whole milk [72]. The ESPGHAN guidelines recommend oral vitamin D supplementation at 400 IU/day for all infants [74]. The Korean Society of Pediatric Endocrinology suggests a higher supplementation of 400 to 600 IU/day for infants [75]. While sunlight exposure can facilitate vitamin D production in infants, the AAP recommends protecting infants under 6 months of age from direct sunlight through protective clothing and limited sunscreen use when sun exposure cannot be avoided [76].

Iodine

Iodine is a critical component of the thyroid hormones thyroxine (T4) and triiodothyronine (T3). Thyroid function is mainly regulated by thyroid-stimulating hormone (TSH), also known as thyrotropin, which is secreted by the pituitary gland. Iodine deficiency can cause a continuous increase in TSH levels, leading to the development of goiter [77]. Earth’s soil contains varying amounts of iodine, which affects the iodine content of crops. Iodine-deficient soils are common in some areas, increasing the risk of iodine deficiency in people consuming local foods. Salt iodization programs have significantly reduced the global prevalence of iodine deficiency globally [35]. Seaweed such as kelp and nori is among the best food sources of iodine. Other seafood and eggs also contain iodine [78].

Iodine status is most effectively evaluated through urinary iodine concentration (UIC), which serves as a sensitive biomarker of current iodine intake because approximately 90% of absorbed iodine is excreted in the urine [79]. While other assessment methods include measuring thyroid size and serum thyroid hormone levels, spot urine measurements are particularly useful as population-level indicators [80]. According to the WHO classification, a median UIC of 100 to 199 μg/L in school-aged children indicates adequate iodine status, while levels <100 μg/L suggest deficiency [81]. Global estimates indicate that 29.8% of school-aged children have insufficient iodine intake [82]. In Korea, an analysis of KNHANES data from 2013 to 2015 showed that only 6.6% of adolescents aged 10 to 18 years had inadequate iodine levels [83].

Iodine deficiency disorders arise when the body cannot produce an adequate level of thyroid hormones owing to insufficient iodine. Their impact can range from mild developmental issues to severe conditions, such as congenital iodine deficiency syndrome, characterized by severe intellectual impairment, hearing loss, muscle spasticity, restricted growth, and delayed sexual development [78]. Prolonged or profound deficiencies can have irreversible effects, particularly during pregnancy or infancy. Consuming <10 to 20 μg of iodine per day may cause hypothyroidism, with goiter often an early sign. In women who are pregnant, deficiency increases the risk of fetal neurodevelopmental deficits, growth retardation, miscarriage, and stillbirth [77].

A meta-analysis showed that lower maternal iodine status in the first trimester was associated with lower verbal intelligence quotient (IQ) in children aged 1.5 to 8 years [84]. Even a mild-to-moderate lack of iodine during pregnancy can compromise fetal development and is linked to a higher incidence of attention deficit hyperactivity disorder in offspring [85]. A meta-analysis found that children (≤5 years old) of iodine-deficient mothers could score 6.910.2 IQ points lower than those of iodine-replete mothers [86]. Research also suggests the partial reversibility of deficits in older children. Two RCTs indicated significant cognitive gains when iodine was provided to school-aged children with mild-to-moderate deficiency (10–12 years in Albania and 10–13 years in New Zealand), indicating that the adverse effects of deficiency may be mitigated, at least until early adolescence [87,88].

Although mild-to-moderate iodine deficiency can adversely affect neurodevelopment, the current evidence remains uncertain as to whether supplementation yields clear benefits in such cases. One RCT found no significant improvements in children’s neurodevelopment by the ages of 5 to 6 years [89], and a systematic review likewise deemed the current data insufficient to establish definitive benefits [90]. Nevertheless, the WHO advises 150 μg/day of iodine for women of childbearing age, rising to 250 μg/day throughout pregnancy and lactation [91]. These guidelines aim to prevent severe deficiencies and mitigate the potential long-term consequences on children’s development, especially in regions without adequate iodized salt programs.

Folate

Folate, an essential water-soluble B vitamin, is found in various foods and is available as a supplement. It plays a crucial role in protein metabolism and DNA and RNA synthesis. Folate participates in two key biochemical processes, converting homocysteine to methionine and methylating deoxyuridylate to form thymidylate, which are critical for DNA synthesis and cell division [92]. Natural food sources of folate include vegetables (particularly spinach, asparagus, and Brussels sprouts), fruits, meat, seafood, dairy products, and liver [92].

Folate status is typically assessed based on serum and red blood cell (RBC) folate levels. Serum folate levels reflect recent dietary or supplemental intake, making them useful for identifying current folate consumption patterns and detecting early signs of folate deficiency. In contrast, RBC folate level reflects long-term status because it remains stable over the 120-day lifespan of erythrocytes and correlates with liver folate stores. This biomarker is commonly used to evaluate chronic folate deficiencies and diagnose conditions associated with folate insufficiency, such as megaloblastic anemia [93]. Folate deficiency is defined as serum levels <6.8 nmol/L, whereas marginal deficiency ranges from 6.8 to 13.4 nmol/L [94]. RBC folate concentrations of <317 nmol/L have been considered indicative of folate deficiency [93].

The prevalence of folate deficiency varies considerably across countries, with reported rates ranging from 1.5% to 40.2% among children and adolescents [95]. In Korea, according to the KNHANES 2013–2015, the prevalence of folate deficiency (<6.8 nmol/L) was 8.6% in males and <2% in females aged ≥10 years [96].

Folate deficiency is relatively rare but is usually seen in conjunction with other nutrient deficiencies, often resulting from poor diet, absorption disorders, or conditions with high cell turnover [92]. Common manifestations of folate deficiency in children include weight loss, headaches, behavioral changes, and stunted growth [97]. Both folate and vitamin B12 are essential for RBC formation and their deficiencies lead to megaloblastic anemia [97]. Insufficient folate intake during pregnancy significantly increases the risk of neural tube defects in infants and is associated with low birth weight, preterm delivery, and fetal growth retardation [92].

To prevent folate deficiency, individuals, especially those in high-risk groups, should consume diets rich in green leafy vegetables and fruits. Daily supplementation with 1 mg of folic acid is typically sufficient for prevention in these populations [98]. Women of childbearing age are strongly recommended to consume folate-rich foods and supplement with at least 0.4 mg of folic acid daily to mitigate the risk of pregnancy complications and fetal anomalies [99].