I. Mechanisms of Zinc Metabolic Abnormalities in Infantile Anorexia
Infantile anorexia is characterized by long-term decreased appetite and food intake, with 30%–45% of anorexic children exhibiting reduced serum zinc concentration (<70 μg/dL). Zinc plays a central role in taste formation and appetite regulation:
Maintenance of taste receptor function: Zinc is an essential cofactor for gustin, a protein that maintains taste function by regulating taste bud cell renewal (cycle ~10 days) and sensitivity of taste receptors (e.g., TAS1R3). Zinc deficiency downregulates the zinc transporter ZnT-7 in taste bud cells, reducing gustin synthesis and increasing the sensory threshold for sweet and salty tastes by 1.5–2 times in children.
Regulation of hypothalamic appetite centers: Zinc modulates feeding behavior by influencing the secretion of hypothalamic neuropeptides (e.g., neuropeptide Y/NPY, pro-opiomelanocortin/POMC). Zinc deficiency increases NPY mRNA expression in the hypothalamus of rats by 22%, promoting appetite-suppressing signals while inhibiting the insulin-like growth factor-1 (IGF-1)-mediated appetite-stimulating pathway.
II. Pharmacological Properties and Action Advantages of Zinc Gluconate
As an organic zinc preparation, zinc gluconate (C₁₂H₂₂O₁₄Zn) offers unique advantages due to its molecular structure:
Significantly higher bioavailability than inorganic zinc: In the intestinal pH environment, gluconate ions form stable chelates with zinc, reducing competitive binding to phytic acid (a major antinutrient binding zinc) in food. Clinical studies show that zinc absorption rate in 6–12-year-old children taking oral zinc gluconate (3 mg/kg/d) reaches 39%, a 77% increase compared to zinc sulfate (22%).
Superior gastrointestinal safety: Zinc gluconate has low dissociation (pKa=3.5) and minimal gastric mucosal irritation. A trial involving 200 anorexic children showed that the nausea incidence in the zinc gluconate group (1.5 mg/kg/d) was 2.3%, significantly lower than 11.7% in the zinc sulfate group.
III. Core Mechanisms and Evidence of Clinical Intervention
1. Repair of Intestinal Mucosa and Digestive Enzyme Activity
Reconstruction of intestinal mucosal barrier function: Zinc is involved in the synthesis of intestinal epithelial tight junction proteins (e.g., claudin-1, occludin). Zinc deficiency leads to intestinal villus atrophy (villus height reduced by 30%) and increased crypt depth. After 8 weeks of zinc gluconate intervention (1 mg/kg/d), anorexic children show a 28% increase in intestinal alkaline phosphatase (IAP) activity and a 40% decrease in the urinary lactulose/mannitol ratio (an index of intestinal permeability), promoting nutrient absorption.
Regulation of digestive enzyme activity: As a cofactor for carboxypeptidase A and α-amylase, zinc directly affects protein and carbohydrate digestion. Supplementation with zinc gluconate increases salivary amylase activity in children from (120±15) U/L to (185±20) U/L and fecal lipase excretion by 35%.
2. Regulation of Immune and Inflammatory Status
Regulation of anti-inflammatory factor balance: Anorexic children often have mild chronic inflammation, with serum IL-6 levels increased by 15%–20%. Zinc gluconate reduces IL-6 and TNF-α levels by 22% and 18%, respectively, through inhibiting the NF-κB pathway, decreasing inflammation-mediated suppression of appetite centers.
Enhancement of thymus development and immune function: Zinc deficiency causes thymus atrophy (weight reduced by 25%) and T-cell subset imbalance (CD4⁺/CD8⁺ ratio decreased by 0.3). Zinc gluconate intervention increases the thymus index (thymus weight/body weight) in children under 6 years old by 18%, restoring CD4⁺ cell proportions to normal levels.
3. Evidence-Based Medical Evidence of Clinical Efficacy
Short-term appetite improvement: A multicenter randomized controlled trial (RCT) showed that after 2 weeks of oral zinc gluconate (1.5 mg/kg/d) in 3–6-year-old anorexic children, daily food intake increased from (125±20) g to (180±25) g, and the appetite score (using Visual Analog Scale VAS) rose from 3.2±0.8 to 5.8±1.2 (out of 10).
Long-term growth catch-up: After 12 weeks of continuous intervention, the weight gain rate of children increased from (0.21±0.03) kg/week to (0.35±0.04) kg/week, height growth was 1.2 cm more than the placebo group, and serum IGF-1 levels rose from (180±25) ng/mL to (265±30) ng/mL, approaching those of healthy children of the same age.
IV. Standardized Protocols for Clinical Application
1. Dosage and Course Optimization
Age-stratified administration:
1–3 years: 10–15 mg daily (calculated as zinc element, same below), taken twice;
4–6 years: 15–20 mg daily;
7–12 years: 20–30 mg daily.
The course is usually 4–8 weeks, and severe zinc deficiency (serum zinc <60 μg/dL) can be extended to 12 weeks, with serum zinc monitoring (target 80–110 μg/dL).
2. Combined Intervention Strategies
Synergistic application with probiotics: Zinc gluconate (1 mg/kg/d) combined with Lactobacillus reuteri (1×10⁹ CFU/d) increases intestinal Bifidobacterium count by 2.1 log CFU/g feces and serum short-chain fatty acids (SCFAs) by 35% in anorexic children, improving appetite response by 15% compared to monotherapy.
Dietary behavior intervention: Zinc supplementation combined with behavior therapy (e.g., fixed meal times, snack restriction) increases clinical efficacy from 68% to 85%. A crossover trial showed that children in the combined intervention group extended meal duration from (12±3) minutes to (25±5) minutes and reduced picky eating by 40%.
3. Key Points for Safety Monitoring
High-dose risks: Exceeding the recommended dose by 2 times (e.g., >40 mg daily for 6-year-olds) may cause copper deficiency (serum copper <70 μg/dL), requiring trace element testing every 4 weeks.
Drug interactions: Avoid concurrent use with tetracyclines (interval >2 hours) and calcium supplements to prevent insoluble complex formation and reduced absorption. In vitro experiments show zinc absorption decreases by 23% when the zinc-to-calcium molar ratio exceeds 1:2.
V. Special Populations and Extended Applications
1. Premature and Low Birth Weight Infants
Premature infants with intrauterine zinc deficiency (birth weight <2000 g) are more prone to feeding difficulties, often with serum zinc <50 μg/dL. Early supplementation with zinc gluconate (0.5 mg/kg/d) reduces the incidence of feeding intolerance from 45% to 22% and shortens the time to full enteral feeding by 3.5 days.
2. Adjuvant Therapy for Anorexia Secondary to Chronic Diseases
For children with recurrent respiratory tract infections (RRI) complicated by anorexia, zinc gluconate (1 mg/kg/d) combined with vitamin A (1500 IU/d) reduces RRI episodes from (3.2±0.8)/6 months to (1.5±0.5)/6 months and increases appetite scores by 42%, with mechanisms related to enhancing respiratory mucosal immune barriers.
VI. Existing Challenges and Future Directions
Development of biomarkers for precision zinc supplementation: Current reliance on serum zinc testing may shift to red blood cell zinc (reflecting intracellular zinc status) and zinc transporter ZnT-1 gene polymorphisms (e.g., rs10883725) as more precise efficacy predictors. Preliminary studies show children with ZnT-1 mutant types respond 30% better to zinc gluconate than wild types.
Formulation innovation and compliance optimization: Orange-flavored chewable tablets (5 mg zinc/tablet) developed for young children have a taste acceptance rate of 92%, significantly higher than oral liquids (75% compliance). Application of nanocrystal technology increases the dissolution rate of zinc gluconate by 2.3 times, suitable for children with swallowing difficulties.
Zinc gluconate has become a first-line intervention for infantile anorexia by correcting zinc deficiency and repairing taste-appetite regulatory pathways. Combined with individualized dosing and multimodal interventions, its clinical value in improving nutritional status and promoting growth and development in children is increasingly strengthened by evidence-based medical evidence.
