Nutrients are defined as having nutritive values (they participate in the metabolism building structures of cells) and being presumed to be safe to the human body also. Nutrients are classified into three macronutrients (carbohydrate, protein and fat) and the rest of the unclassified micronutrients are required in very small quantities, yet pose important influence on metabolism and health [1]. Micronutrients are of two types, trace elements (inorganic elements) and vitamins (complex organic molecules). These micronutrients are necessary for the optimal utilization of the three macronutrients. Trace elements contribute less than 0.01% to body weight and a human nutritional requirement has been established for iron, iodine, zinc, copper, chromium, selenium, molybdenum, manganese, and cobalt [2]. Cotzias defined essential trace elements as having the following five characteristics: 1) present in healthy tissues of all living things, 2) maintain a constant tissue concentration, 3) withdrawal leads to reproducible functional abnormalities, 4) addition of the element prevents abnormalities, 5) biochemical change is prevented or cured with clinical abnormality [3].

Biological effect of any trace element depends on the dose; problems may result from intakes that are too low or too high.

The etiology of trace element deficiency is varied. First, inadequate intake situations are associated with increased requirements, losses during food processing, poor bioavailability, local deficiencies in the geochemical environment, protein energy malnutrition, and synthetic diets including intravenous feeding. Variations in bioavailability are major factors that determine the adequacy of dietary intake of some trace elements [4]. It is especially important for infants who depend on one major food staple. Second, other circumstances are associated with prematurity (small reservoirs), impairment of intestinal absorption, and inborn errors of trace element metabolism [5]. Recently, the increasing use of synthetic diets in medical practice, including those used in intravenous feeding, has provided some of the most dramatic examples of acquired trace element deficient states. Deficiencies of zinc, copper, chromium, molybdenum, and selenium have been documented in association with long-term intravenous feeding [6].

Quantitative measurement of trace elements which are present in a very small amount is difficult. Laboratory analysis and the detection of trace elements use the atomic absorption spectrophotometry. Even when the analytic data are accurate, interpretation of the data frequently becomes a problem. Recently, hair analysis was introduced and misused as a diagnostic tool. Currently, the application of chemical analysis of hair in clinical practice is extremely limited [7,8].

In this article, we review various trace element deficiency states such as zinc, copper, and selenium and briefly discuss the use of dietary supplements.

Diet zinc deficiency syndrome showing hypogonadism, anemia, and growth retardation was reported in 1961 [9]. Acrodermatitis enteropathica, an autosomal recessive disorder of gastrointestinal zinc absorption, resulted in severe acro-orificial dermatitis and diarrhea in infants [10]. After the 1990s, the importance of zinc as an essential nutrient for humans was documented through large scale trials [11-13].

Copper is an essential nutrient for humans and a component of many enzymes that regulate various metabolic processes. Copper deficiency is rare in humans. Since the first report on hypochromic anemia as a manifestation of copper deficiency in 1964, copper deficiency has been documented in patients with prolonged severe malabsorption, severe malnutrition, and parenteral nutrition without copper supplementation, and in premature infants [23]. Copper is absorbed mostly in the small intestine and distributed in high concentrations in the liver and brain. Copper is transported to the liver and incorporated into ceruloplasmin and then released into the peripheral tissue. Copper is mostly excreted through bile [24].

Selenium is used for the synthesis of selenocysteine to be incorporated into mammalian proteins. About 25 selenoproteins have been revealed for their own functions of antioxidant enzymes, putative antioxidant proteins, and other metabolic functioning enzymes [32]. A wide spectrum of biochemical functions of selenium leads to broad clinical manifestations.

Neutraceutical is a concentrated matrix of bioactive agent from food and a dietary supplement that makes us fitter and healthier. The purposes of using dietary supplements to children are as follows: 1) optimization of growth and development, 2) correcting the dietary inadequacy, and 3) prevention and treatment of childhood diseases [39]. When dietary supplements are used in children, there are a few special considerations. First, each nutrient competes for absorption in the body, thus high dose supplementation with single nutrients can be toxic and dangerous. Diet supplementation may lead to interference with other drugs or medications. Second, nutraceutical products are sometimes inconstant in dosage listed on the label and can be contaminated. Third, there is a lack of research or established evidence of intake for children [40]. The most commonly used dietary supplements are multivitamins and minerals to make up for the inadequacies in a child's diet. There are no benefits for healthy children with a regular adequate diet. However, if the dietary intake of nutrients is chronically inadequate, the use of multivitamin and mineral supplements may be advisable. Physicians should obtain the history of supplement use from pediatric patients and monitor the adverse reactions.

Micronutrients are provided ideally in a normal diet, because the gut normally acts to regulate absorption in response to demand. However, in special situations, such as synthetic diet, long term parenteral nutrition with incomplete formula, and lack of reservoirs (preterm infants, low birth weight, and malnutrition state), trace element deficiency can be developed. The diagnosis of micronutrient deficiency syndrome is difficult but careful analysis of clinical manifestations and laboratory findings are essential and sufficient. Infants are vulnerable toward micronutrient deficiency syndrome because of their rapid postnatal growth, low initial stores and ingestion of foods with low concentration of micronutrients. And supplements of neutraceuticals in children are required careful consideration for a thorough understanding of overdose toxicity and interference with other nutrients and drugs for proper treatment of patients with micronutrient deficiency.