Comparative effectiveness of oral nutritional supplements in preventing respiratory tract infections among adults: a systematic review and network meta-analysis.

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

In this systematic review and network meta-analysis, 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. Studies with participants under 18 years, immunodeficiencies, non-oral administration, or a therapeutic rather than preventive focus were excluded. We performed network meta-analyses (NMA) 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. The primary outcome was the incidence of RTIs. The 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 is registered with PROSPERO, CRD420250653276.

FINDINGS

We identified 120 eligible trials, among which 107 trials involving 101,751 adults were included in the network meta-analysis. Compared with placebo, catechin (RR = 0.79, 95% CI: 0.66, 0.95; n = 5; high certainty), (RR = 0.79, 95% CI: 0.63, 0.99; n = 3; moderate certainty), and multi-strain probiotics (RR = 0.90, 95% CI: 0.82, 0.98; n = 16; moderate certainty) were the most effective interventions for reducing RTI incidence. For COVID-19 or influenza prevention, high-dose vitamin D was highly effective (RR = 0.66, 95% CI: 0.51, 0.86; n = 9; moderate certainty). Catechin (MD = -2.64 days/RTI, 95% CI: -4.92, -0.35; n = 2; moderate certainty) and multi-strain probiotics (MD = -0.97 days/RTI, 95% CI: -1.78, -0.16; n = 4; high certainty) most effectively shortened RTI symptom duration. Multi-strain probiotics (SMD = -0.33, 95% CI: -0.51, -0.14; n = 6; moderate certainty) also showed superior performance in alleviating RTI symptom severity. None of the interventions increased the risk of adverse events versus placebo.

INTERPRETATION

Based on the current evidence, catechin, , and multi-strain probiotics show relatively better effects in preventing adult RTI compared to other nutritional supplements. For COVID-19 or influenza prevention, high-dose vitamin D supplementation may be more effective. This study is limited by the lack of head-to-head comparisons between interventions (particularly across major categories) and heterogeneity from varied administration methods (e.g., capsules, beverages, mouthwashes), impacting the consistency and overall estimation of the NMA. Future high-quality studies are needed to provide direct evidence on the optimal intervention type, frequency, and form/dose of administration to guide clinical practice effectively.

FUNDING

This work was supported by the Ningbo Top Medical and Health Research Program and the Zhejiang Provincial Disease Prevention and Control Science and Technology Plan.