Different doses of vitamin A supplementation as adjuvant treatment for pneumonia in children: a network meta-analysis of randomized controlled trials

Abstract

While previous meta-analyses have established a link between vitamin A supplementation and outcomes in children with pneumonia, the efficacy and safety of different dosing regimens remain unclear. Existing evidence is predominantly based on single-dose trials, creating a critical knowledge gap. We systematically searched PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang and VIP databases from their inception to December 2025. Study searches were independently carried out in December 2025 by two reviewers. Two researchers used the Cochrane risk of bias tool to independently assess the quality of the included studies. Data analysis was conducted through the "netmeta" package in R software (version 4.3.3). Twenty-five trials involving 3116 patients were included. Network meta-analysis revealed that medium-dose vitamin A supplementation was most effective in reducing the duration of fever and cough. Low-to-medium doses were consistently associated with better clinical outcomes than high-dose regimens. However, evidence regarding safety outcomes remained limited and inconclusive.

Conclusion: Low-to-medium dose vitamin A supplementation appears superior to high-dose regimens for alleviating clinical symptoms in children with pneumonia. However, the evidence is limited by high heterogeneity, indirect comparisons between dose groups, and poor reporting of adverse events. Future trials should prioritize direct dose-comparisons and rigorous safety monitoring to refine dosing guidelines.

What is known: • Pneumonia poses a significant threat to the health and lives of children. Vitamin A supplementation plays an adjuvant role in the treatment of pneumonia in children. • There are currently divergent conclusions in the research regarding the optimal dosage of vitamin A, particularly with regard to the safety of high-dose supplementation and the effectiveness of low-dose supplementation.

What is new: • This study revealed that medium-to-low-dose vitamin A supplementation appears to be more effective than high-dose therapy in alleviating the primary symptoms of childhood pneumonia. • This study also suggests that children in developed regions have higher baseline serum retinol levels, which may diminish the marginal benefits of high-dose supplementation and may even predispose them to its immunosuppressive effects.

Keywords: Children; Dose; Network meta-analysis; Pneumonia; Vitamin A.