What is the role of zinc supplementation in anorexia refeeding?

Zinc Supplementation in Anorexia Nervosa Refeeding

Zinc supplementation should be included in the treatment protocol for anorexia nervosa patients during refeeding, as it enhances the rate of recovery by increasing weight gain and improving anxiety and depression levels.

Role of Zinc in Anorexia Nervosa

Zinc deficiency is commonly observed in patients with anorexia nervosa and shares many clinical manifestations with the disorder itself. The relationship between zinc status and anorexia nervosa is bidirectional:

Zinc Status in Anorexia Nervosa Patients

• Patients with anorexia nervosa frequently present with zinc deficiency 1
• Studies have shown depressed serum zinc concentrations and significantly lower urinary zinc excretion in anorexia nervosa patients compared to healthy controls 2
• By dietary history, anorexic patients consume only about 6.46 mg/day of zinc, well below the Recommended Dietary Allowance 2

Clinical Manifestations of Zinc Deficiency Relevant to Anorexia

• Reduced food consumption (anorexia) is a major manifestation of zinc deficiency 2
• Other symptoms include growth retardation, delayed sexual development, impaired immune function, and altered taste perception (hypogeusia) 3
• Zinc deficiency may act as a "sustaining factor" for abnormal eating behavior in certain eating disorder patients 2

Evidence Supporting Zinc Supplementation

The strongest evidence comes from randomized controlled trials:

1. A double-blind, placebo-controlled trial demonstrated that zinc supplementation (100 mg zinc gluconate daily) resulted in a rate of BMI increase twice that of the placebo group (p = 0.03) 4

2. Multiple randomized, double-blind controlled clinical trials indicate that zinc therapy enhances recovery by:

   • Increasing weight gain
   • Improving levels of anxiety and depression 5

3. Even after short-term weight recovery, zinc deficiencies often persist, suggesting the need for supplementation beyond initial refeeding 1

Mechanism of Action

Zinc may improve anorexia nervosa outcomes through several mechanisms:

• Zinc is an allosteric modulator of NMDA receptors, essential for glutamatergic functioning 6
• Chronic zinc deficiency leads to overactivation and upregulation of NMDA receptors, which may contribute to pathological glutamate levels 6
• Zinc deficiency affects taste perception (hypogeusia), which may contribute to reduced food intake 3
• Zinc plays important roles in immune function and inflammation regulation 3

Recommended Supplementation Protocol

Based on the available evidence:

1. Dosage:

   • 50-100 mg of zinc gluconate daily during refeeding 5, 4
   • Continue supplementation until significant weight recovery is achieved (at least 10% increase in BMI) 4

2. Monitoring:

   • Assess zinc status before and after supplementation
   • Monitor serum zinc levels and urinary zinc excretion 2

3. Duration:

   • Continue supplementation beyond initial weight recovery, as deficiencies often persist even after short-term refeeding 1

Potential Pitfalls and Considerations

1. Accurate Assessment of Zinc Status:

   • Plasma zinc decreases significantly during inflammation (when CRP exceeds 20 mg/L), complicating interpretation of results 3
   • Consider using multiple markers including serum zinc, urinary zinc excretion, and dietary intake assessment

2. Toxicity Concerns:

   • Zinc has a relatively low toxicity profile at therapeutic doses 5
   • However, chronic excessive supplementation can interfere with copper metabolism
   • Symptoms of toxicity typically appear only when ingestion exceeds 1-2g of zinc 3

3. Comprehensive Approach:

   • Zinc supplementation should be part of a comprehensive nutritional rehabilitation program
   • Address other potential nutritional deficiencies concurrently

Special Considerations

• Vegetarian/vegan patients may require higher supplementation due to reduced zinc bioavailability from plant sources 3
• Patients with comorbid conditions affecting zinc absorption (e.g., inflammatory bowel disease) may require adjusted dosing

By incorporating zinc supplementation into anorexia nervosa treatment protocols, clinicians can potentially enhance recovery rates and improve both physical and psychological outcomes for these patients.