bubble_chart Overview

Zinc is one of the essential trace elements for the human body, widely participating in various metabolic activities as a component of many enzymes. Zinc deficiency can lead to anorexia, stunted growth, delayed sexual maturation, weakened immune function, skin rashes, and alopecia areata, among other symptoms. In 1961, Ananda S. Prasad and others reported "Iranian village disease," characterized by short stature, underdeveloped reproductive organs, iron-deficient hepatosplenomegaly, lethargy, and geophagia, with zinc treatment proving highly effective. Subsequently, similar cases were discovered in Egypt. Developed countries have also reported cases of zinc nutritional deficiency confirmed by experiments, and it was found that zinc treatment is highly effective for acrodermatitis enteropathica. Since the late 1970s, there have been numerous reports of zinc deficiency diseases across China, with children being the most commonly affected.

bubble_chart Etiology

1. Insufficient Intake Plant-based foods such as grains contain less zinc than animal-based foods like meat, eggs, and dairy, making vegetarians prone to zinc deficiency. During periods of growth, development, and malnutrition, as well as the {|###|}stage of convalescence{|###|}, the relative demand for zinc increases. Pregnant and lactating women also require more zinc. Insufficient intake can lead to zinc deficiency in both mothers and their fetuses or infants. Total parenteral nutrition without adequate zinc supplementation can result in severe zinc deficiency. During infections and {|###|}fever{|###|}, zinc requirements rise while appetite declines, reducing intake and increasing the risk of zinc deficiency.

2. Poor Absorption Various causes of {|###|}diarrhea{|###|} can reduce zinc absorption, especially chronic diarrhea such as in malabsorption syndromes, steatorrhea, and cystic fibrosis. Grains contain high levels of phytates and crude fiber, which hinder zinc absorption. Although cow's milk contains zinc levels similar to breast milk (approximately 45.9–53.6 μmol/L or 300–350 μg/dL), zinc absorption from cow's milk is {|###|}deficient{|###|} compared to breast milk.

3. Excessive Loss Conditions such as repeated {|###|}loss of blood{|###|}, hemolysis, trauma, and burns can lead to significant zinc loss through bodily fluids. Liver cirrhosis, chronic uremia, and other conditions causing hypoalbuminemia result in hyperzincuria. Certain medications, such as long-term use of metal chelators (e.g., penicillamine) and repeated intravenous infusions of glutamate, bind zinc and promote its excretion in urine, leading to zinc deficiency.

4. Genetic Defects A rare autosomal recessive disorder, acrodermatitis enteropathica (AE), results from a defect in {|###|}small intestine{|###|} zinc absorption, leading to reduced zinc levels in the body. Plasma (serum) zinc, red blood cell zinc, muscle zinc, hair zinc, and urinary zinc are all decreased. Symptoms include acral skin lesions, intractable {|###|}diarrhea{|###|}, alopecia, growth retardation, and impaired immunity, increasing susceptibility to infections.

Zinc's Generation, Transformation, and Physiological Functions Over 100 enzymes in the human body contain zinc or are zinc-dependent, such as RNA and DNA polymerases, carbonic anhydrase, alkaline phosphatase, and lactate dehydrogenase. These enzymes primarily function in nucleic acid metabolism and protein synthesis, as well as in the metabolism of carbohydrates, lipids, and vitamin A. Zinc stabilizes cell {|###|}membrane{|###|} structures, reducing damage from lipid peroxidation and other free radicals. It promotes lymphocyte mitosis and cell transformation, maintaining T-cell immune function. Zinc assists the liver in synthesizing retinol-binding protein (RBP), mobilizing stored vitamin A into the blood to maintain normal vitamin A levels. Zinc is essential for cell proliferation and human growth and development, making children and young animals require relatively higher amounts of zinc.

bubble_chart Clinical Manifestations

1. Anorexia   Zinc deficiency leads to reduced taste bud function, decreased taste acuity, loss of appetite, and reduced food intake. The activity of digestive enzymes such as carboxypeptidase A is also diminished, impairing digestion.

2. Growth Retardation   Zinc deficiency hinders nucleic acid and protein synthesis and reduces food intake, affecting children's growth and development. Zinc-deficient children often have lower height and weight compared to their healthy peers, with severe cases leading to dwarfism. Studies show that zinc supplementation in deficient children accelerates recovery in height and weight. Zinc deficiency can also impair cognitive development, with severe cases causing mental disorders, all of which respond well to zinc supplementation.

3. Delayed Pubertal Development   Manifestations include underdeveloped male genitalia (small testes and penis), low testosterone levels, and impaired sexual function; delayed breast development and menstruation in females; and late appearance of pubic hair in both sexes. Zinc supplementation leads to the emergence of secondary sexual characteristics within weeks to months, alleviating or resolving these symptoms.

4. Infantile Paroxia   Zinc-deficient children may exhibit pica, craving substances like dirt, wall plaster, paper, coal cinders, or other non-food items. Zinc supplementation is effective in treating this condition.

5. Susceptibility to Infections   Zinc-deficient children may experience reduced cellular and humoral immune function, increasing their vulnerability to infections, including diarrhea.

6. Skin and Mucous Membrane Manifestations   Severe zinc deficiency can cause various rashes, bullous dermatitis, recurrent oral ulcers, chronic shank ulcers that fail to heal, and varying degrees of alopecia.

7. Fetal Growth Retardation and Multiple Malformations   Severe zinc deficiency in pregnant women or animals can lead to fetal growth retardation and various malformations, including neural tube defects. Labor may be prolonged due to uterine inertia, resulting in excessive bleeding.

8. Others   Symptoms may include mental disorders or lethargy, as well as impaired vitamin A metabolism, leading to reduced serum vitamin A levels, prolonged dark adaptation time, and night blindness. {|107|}

bubble_chart Diagnosis

Diagnosis relies on medical history, symptoms, signs, and laboratory tests. When necessary, the efficacy of zinc supplementation can assist in diagnosis.

1. Medical history and physical examination: Assess feeding history, such as low zinc content in the diet or long-term malabsorption (e.g., chronic diarrhea). Reduced taste sensitivity and appetite, delayed growth and development, and other aforementioned symptoms and signs of varying degrees.

2. Laboratory diagnosis: Plasma (or serum) zinc levels are below the normal range, specifically under the lower limit of 10.0–10.7 μmol/L (65–70 μg/dL). Generally, serum zinc is slightly higher than plasma zinc because some zinc is released from red blood cells and platelets. The longer the interval between blood collection and testing, the higher the zinc measurement tends to be. Plasma should be separated and tested immediately after blood collection. Avoid hemolysis during blood collection, as red blood cell zinc is over 10 times higher than plasma zinc. Prevent sample contamination; rubber stoppers and adhesive tapes contain zinc and should be avoided. Plasma (serum) zinc levels are influenced by recent dietary zinc intake. Liver and kidney diseases, acute or chronic infections, and stress conditions can all lower plasma (serum) zinc levels.

Hair zinc can serve as a reference indicator for chronic zinc deficiency. However, hair zinc is affected by factors such as hair growth rate, environmental contamination, washing methods, and collection site, and it does not closely correlate with plasma zinc. Thus, it is not a reliable diagnostic marker for zinc deficiency.

Zinc participates in the formation of the active center of alkaline phosphatase, so serum alkaline phosphatase activity can help reflect zinc nutritional status in infants and young children. It decreases during zinc deficiency and rises after zinc supplementation.

Leukocyte zinc is a sensitive indicator of human zinc nutritional status, but the test requires a large blood sample (currently at least 5 mL in China) and is complex to perform, making it difficult to widely adopt in clinical practice.

In recent years, domestic and international researchers have explored using stable isotope methods to measure zinc metabolic pool size and metallothionein concentration to assess zinc nutritional status, though these methods are still under investigation.

3. Therapeutic trial: If zinc deficiency is suspected, a single zinc supplementation trial can be conducted. A rapid therapeutic response can help confirm the diagnosis.

bubble_chart Treatment Measures

Zinc deficiency in infants, preschoolers, and preadolescent children affects growth and development. Oral zinc supplements (calculated as elemental zinc) can be administered daily at 0.5–1.5 mg/kg, or double the recommended daily zinc intake, with a maximum daily dose of 20 mg. The treatment course is 3 months, which can be shorter for mild cases. Zinc sulfate, zinc gluconate, or zinc acetate can be used. For secondary zinc deficiency, the dosage varies depending on the severity of malabsorption and excessive loss. An initial dose of 1 mg/kg daily may be used. To meet rapid growth needs, infants with continued excessive loss may increase to 2 mg/kg daily, but plasma zinc levels should be closely monitored.

For parenteral zinc supplementation in cases of acrodermatitis enteropathica, the recommended doses are: 0.4 mg/kg daily for premature infants, 0.2 mg/kg daily for full-term infants under 3 months, 0.1 mg/kg daily for older infants and toddlers, and 0.05 mg/kg daily for children. Dosage should be increased if zinc loss is excessive, especially from the gastrointestinal tract. Plasma zinc levels should be monitored regularly. In cases of severe zinc deficiency, intravenous zinc at 0.3–0.5 mg/kg daily may be administered until skin lesions resolve and plasma zinc levels normalize. Excessive zinc intake may lower plasma copper levels.

To enhance zinc absorption, oral zinc supplements are best taken 1 to 2 hours before meals.

For zinc deficiency-induced anorexia or infantile pica, improvements are typically seen within 2–4 weeks of zinc supplementation, while growth delays may take 1–3 months to improve. Zinc supplementation is ineffective for non-zinc deficiency cases. During zinc therapy, efficacy and side effects should be monitored, along with plasma zinc levels, while increasing zinc-rich foods in the diet. Except for specific conditions like acrodermatitis enteropathica or total parenteral nutrition, zinc therapy should be discontinued promptly. Common side effects of zinc sulfate and other zinc supplements include gastrointestinal symptoms such as nausea, vomiting, and diarrhea, which may be reduced by taking them after meals.

bubble_chart Prevention

Human colostrum contains a high level of zinc, up to 306 μmol/L (2000 μg/dl), and the absorption and utilization of zinc in breast milk are also high. Therefore, breastfeeding is beneficial for preventing zinc deficiency in infants. However, as the child grows, complementary foods should be introduced on time, such as egg yolks, lean meat, fish, animal organs, beans, and nuts, which are rich in zinc, and should be appropriately included in the daily diet. For formula-fed infants without breast milk, it is best to feed them infant formula or milk powder fortified with an appropriate amount of zinc.

In 1988, the Chinese Nutrition Society recommended the following daily zinc (element) supply:

Birth to 6 months: 3 mg; 6 months to 1 year: 5 mg

1 year to 10 years: 10 mg; over 10 years: 15 mg

Pregnant and lactating women: 20 mg

Currently, there are various zinc-fortified foods on the market. Pay attention to their zinc content, as long-term consumption of multiple zinc-fortified foods may lead to excessive zinc intake and poisoning. Excessive zinc intake can cause acute zinc poisoning, with gastrointestinal symptoms such as vomiting and diarrhea. Inhalation of zinc fumes may cause low-grade fever and common cold-like symptoms. Chronic zinc poisoning may lead to anemia and iron deficiency, and animal experiments have shown it can impair liver and kidney function as well as immunity.