Comparative Effectiveness of Oral Nutritional Supplements in Preventing Respiratory Tract Infections among Adults A Systematic Review and Network Meta-Analysis
Zhixin Zhu, Xiaoxia Zhu, Yanru Chu, Bing Zhang, Yi Chen
Background Different nutritional supplements may prevent respiratory tract infections (RTIs) in adults, but their comparative effectiveness remains unclear. We aimed to evaluate the effectiveness of oral nutritional supplements in preventing RTIs and reducing their symptom duration and severity.
Methods We searched for randomized controlled trials (RCTs) assessing oral micronutrients, flavonoids, probiotics, or synbiotics in adults for the prevention of RTIs in PubMed, Embase, Cochrane Central Register, and ClinicalTrials.gov from inception to February 25, 2025. We performed network meta-analyses using frequentist random-effects models to compare interventions through direct and indirect evidence. We used the CINeMA framework to rate the overall certainty of evidence. Primary outcomes were the incidence of RTIs. Secondary outcomes were upper respiratory tract infections (URTIs) or common cold, COVID-19 or influenza, RTI symptom duration, RTI symptom severity, and adverse events. The study was registered with PROSPERO (CRD420250653276).
Findings We identified 127 eligible trials involving 155 126 adults. Compared with placebo, flavonoids (risk ratio, RR=0.72, 95% CI: 0.59, 0.87), probiotics (RR=0.88, 95% CI: 0.83, 0.93), multiple micronutrient supplements (RR=0.87, 95% CI: 0.80, 0.95), and moderate-dose vitamin C (RR=0.92, 95% CI: 0.86, 0.98) most effectively reduced RTI incidence. For COVID-19 or influenza prevention, high-dose vitamin D showed intermediate effectiveness (RR=0.60, 95% CI: 0.44, 0.81). Probiotics were most effective in shortening RTI symptom duration (standard mean difference, SMD=-0.24, 95% CI: -0.36, -0.12). Probiotics (SMD=-0.19, 95% CI: -0.32, -0.06) and synbiotics (SMD=-0.41, 95% CI: -0.77, -0.06) most effectively alleviated symptom severity. The quality of the above evidence ranged from moderate to high. Adverse events showed no significant differences across interventions.
Interpretation Flavonoids appear to be among the best measures for preventing RTIs, while probiotics and synbiotics most effectively alleviate symptoms. These findings provide evidence-based guidance for nutritional supplement selection in RTI prevention.
Declarations Ethical Approval statement Not applicable.
Consent for publication Not applicable.
Competing interests The authors declare that they have no competing interests" in this section.
Authors' contributions YC and ZXZ designed the study. ZXZ, XXZ, YRC, BZ and YC conducted the literature search and literature screening. ZXZ and XXZ extracted the data. ZXZ analyzed the data and wrote the first draft of the paper. All authors interpreted the data, read the manuscript, and approved the final version.
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