What is the role and appropriate dosing of zinc in treating dengue fever in otherwise healthy adults and children?

Zinc Has No Established Role in Dengue Fever Treatment

Based on current evidence, zinc supplementation cannot be recommended for dengue fever treatment, as the single randomized controlled trial showed no significant reduction in fever duration, and the mechanism of action remains unclear. While zinc deficiency is common in children with dengue (46-47% prevalence), supplementation has not demonstrated meaningful clinical benefits on the primary outcomes that matter most: morbidity and mortality 1, 2.

Evidence from Clinical Trials

The only randomized controlled trial of zinc supplementation in dengue fever enrolled 50 Thai children and found:

• No significant reduction in fever duration: Mean defervescence time was 29.2 hours with zinc versus 38.1 hours with placebo (p=0.270), which is not statistically significant 1
• Modest reduction in hospital stay: 62.5 hours versus 84.7 hours (22.2 hour difference, p=0.010), though this secondary outcome is less clinically meaningful than fever resolution 1
• No severe dengue cases occurred in either group, making it impossible to assess impact on the outcomes that truly matter—preventing hemorrhagic complications, shock, or death 1

This single small trial is insufficient to support routine zinc supplementation for dengue fever.

Zinc Deficiency in Dengue Patients

While zinc deficiency is highly prevalent in children with dengue infection (46-47%), this may be a consequence rather than a cause of disease severity:

• Low serum zinc levels are documented in Thai children hospitalized with dengue 1, 2
• Boys appear at higher risk for zinc deficiency than girls (OR=7.3) 2
• Zinc levels increase during recovery regardless of supplementation, though the increase is greater with zinc treatment (26.4 μg/dL versus 14.4 μg/dL) 1

The critical caveat: Association does not prove causation, and correcting zinc deficiency has not been shown to improve the clinical outcomes that matter most in dengue—preventing progression to severe disease, shock, or death.

Mechanistic Considerations

Laboratory studies suggest zinc chelation (zinc depletion) may actually inhibit dengue virus replication through activation of antiviral immune responses:

• Zinc chelation with TPEN inhibited dengue and Japanese encephalitis virus infection in epithelial cells 3
• The mechanism involves inducing ER stress and activating NF-κB, leading to interferon signaling 3
• This suggests zinc may facilitate viral replication, and removing it triggers host antiviral defenses 3

This creates a paradox: If zinc depletion activates antiviral immunity, why would zinc supplementation help? The laboratory data actually suggest zinc supplementation could theoretically worsen dengue infection, though this has not been demonstrated clinically 3, 4.

Practical Recommendations

Do not routinely supplement zinc for dengue fever treatment. The evidence does not support this practice for improving fever duration, preventing severe disease, or reducing mortality 1, 5.

If zinc supplementation is considered despite limited evidence:

• Dosing used in the trial: Bis-glycinate zinc administered three times daily for 5 days or until fever resolution 1
• Monitor for zinc deficiency in high-risk populations (malnourished children, developing countries) 2
• Ensure adequate copper intake if supplementing zinc, maintaining an 8:1 to 15:1 zinc-to-copper ratio to prevent copper deficiency 6

Common Pitfalls to Avoid

• Do not delay proven supportive care (fluid management, monitoring for warning signs of severe dengue) in favor of unproven micronutrient supplementation
• Do not assume zinc deficiency causes severe dengue—the relationship may be correlative rather than causal 2
• Do not extrapolate from other viral infections—zinc's role varies dramatically by virus, being beneficial for some (common cold, herpes) but potentially harmful for others based on viral replication requirements 7, 4

The Bottom Line

The evidence for zinc in dengue fever is insufficient and contradictory. One small trial showed no benefit on fever duration, laboratory studies suggest zinc depletion may be antiviral, and no studies have demonstrated impact on severe disease or mortality 1, 3, 5. Standard supportive care remains the only evidence-based approach to dengue management.