Respiratory Track Infection Network Meta-Analysis (ignores 5+ factors)

Comparative efficacy of nutritional supplements for the prevention of respiratory tract infections in children: a systematic review and network meta-analysis

BMC Infectious Diseases May 2026 https://doi.org/10.1186/s12879-026-13567-1

Background: This study employs a network meta-analysis to compare the effectiveness of multiple nutritional supplements in preventing childhood respiratory infections.

Methods: Systematically searched PubMed, Embase, Cochrane Library, Web of Science from their inception to 1 September 2025. Included studies were randomized controlled trials evaluating nutritional supplements for preventing respiratory infections in children under 18 years old. The primary outcome was the incidence of respiratory infections. Traditional meta-analysis and Bayesian network meta-analysis were conducted using random-effects models to calculate odds ratios (OR) and their 95% credible intervals (CrI). The cumulative sorted rank curve area (SUCRA) was used to rank the efficacy of each intervention. The Cochrane risk of bias tool was applied to assess the quality of included studies.

Results: A total of 19 articles involving 11,576 children were included. Direct comparison meta-analysis showed no statistically significant differences between low-dose vitamin D, vitamin A, vitamin A combined with zinc, zinc, and placebo. Network meta-analysis formed a closed-loop network, and local inconsistency tests revealed no significant differences in either direct or indirect comparisons. The league table indicated a trend toward reduced risk of childhood respiratory infections with high-dose vitamin D (HVD) compared to placebo [OR = 0.76, 95% CrI (0.61, 0.94)]. The cumulative ordered probability (SUCRA) for each intervention was: HVD (82.44%) > LVD (64.81%) > Iron (57.2%) > VA_Zinc (54.56%) > Probiotics (52.49%) > Zinc (42.5%) > VA (23.31%).

Conclusion: This study indicates that among the various nutritional interventions included, HVD demonstrated the greatest potential effect in preventing respiratory infections in children. Direct comparison meta-analyses revealed no statistically significant differences between LVD, VA, VA_Zinc, zinc, and placebo. A network meta-analysis further supported these findings, with league table and SUCRA rankings indicating HVD may offer the optimal efficacy among all interventions.

PDF

Claude AI Deep Research summary for a high school graduate PDF

Meta-analyses, including network, often ignore dose size, dose duration, dose form, age, and weight

Related in Vitamin D Life

15,400 studies of "network meta-analysis" and Vitamin D as of May 2026

Google Scholar Health problems include:

  • sarcopenia
  • preeclampsia
  • cardiovascular disease
  • rickets
  • CPAP use
  • type 2 diabetes mellitus
  • HIV
  • Multiple Sclerosis

Top 20 Health Problems in Recent Vitamin D Network Meta-Analyses (2021–2026)

Claude AI Entire PDF

Where available, each row reports:

  • Representative NMA: first author / year / journal
  • k / N: number of RCTs / participants in the synthesis
  • Vitamin D rank: SUCRA (Surface Under the Cumulative Ranking curve) or pooled effect
  • Certainty: GRADE rating from the source NMA where reported

Ranking table 1-20 + 10 more

# Condition Representative NMA k / N Vitamin D rank or effect Certainty
1 Type 2 diabetes / insulin resistance Deng 2025, Front Nutr (exercise + vitamin NMA) Multi-arm; separate dose NMA: 40 RCTs EHDS (≥4000 IU/d) rank 91.2% for 25(OH)D; HbA1c best with LDS Mod–Low
2 Falls / fractures / osteoporosis Tan 2024, BMC Geriatr 35 / 58,937 800–1000 IU/d: RR 0.85 (0.74–0.95) vs placebo Moderate
3 Depression (incl. postpartum, geriatric) Ghaemi 2024, Psychol Med (dose-response) 31 / 24,189 −0.32 SMD per 1000 IU/d; peak at 8000 IU/d (SMD −2.04) Moderate
4 Gestational diabetes mellitus (GDM) Di 2025, Front Endocrinol (dietary intervention NMA) + Luo 2026, Front Med 28 / 2,666 (NMA); 20 / 1,737 (MA) Vitamin D reduced FPG SMD −1.01; insulin SMD −0.64 Low–Mod
5 Obesity / metabolic syndrome / lipid profile Multi-NMA cluster; umbrella meta-analysis 14 MAs — BMI −0.11 kg/m², WC −0.79 cm vs control Low–Mod
6 Polycystic ovary syndrome (PCOS) Ma 2023, Front Endocrinol (nutritional NMA) 41 / 2,362 Vitamin D not top-ranked; carnitine/inositol/probiotics > on weight; chromium top for HOMA-IR Low
7 COVID-19 (mortality, ICU, intubation) Zhang 2024, Front Nutr 21 / 4,553 Continuous-dose, deficient-baseline subgroups: significant mortality and ICU benefit Low–Mod
8 Sarcopenia Cheng 2021, Nutrients (original NMA); Zhao 2025 update 35 / 2,331 (2025) Protein + vitamin D + exercise top for grip strength; vitamin D alone shortened chair-stand time Low
9 Knee osteoarthritis (KOA) Zhang 2025, Nutrients (7 supplements) 42 / 4,599 Vitamin D mid-ranked; curcumin/Boswellia higher on WOMAC pain Low
10 Multiple sclerosis (relapse, fatigue, disability) Zhang 2026, Front Neurol (RCTs to April 2025) Multiple Linear dose-response with annualized relapse rate; supplementation reduced relapse risk Low–Mod
11 Atopic dermatitis / eczema Nielsen 2024, Nutrients 11 / 686 SCORAD/EASI: SMD −0.41 (95% CI −0.67 to −0.16) vs control Moderate
12 Psoriasis Chen 2025, Front Nutr (8 supplements NMA) 21 / 1,463 Vitamin D ↓PASI MD −3.29; vitamin D + NB-UVB top for IL reduction; XP-828L top for DLQI/PGA Low–Mod
13 Hashimoto's thyroiditis Peng 2024, Front Endocrinol (NMA selenium/vit-D/myo-inositol) 10 quantitative MAs Selenium > vitamin D for TPO-Ab/Tg-Ab reduction at 6 months Low
14 Asthma & COPD (FEV1, exacerbations) Wang 2022, J Glob Health (still most-cited MA); updated 2024+ 30 / 3,208 Asthma FEV1/FVC improved; COPD FEV1% improved; mixed exacerbation data Low–Mod
15 Cardiovascular disease & hypertension Multiple MAs; few true NMAs Heterogeneous ≈10% lower CV event risk per 10 ng/mL 25(OH)D in observational pooling Low
16 Chronic kidney disease (CV outcomes, mortality) Saleem 2025, Cureus (RCTs only); plus 20-cohort MA 11 RCTs (NMA); 20 cohorts (MA) RCTs: RR 0.39 (0.22–0.69) for adverse CV events; cohorts: 26% lower all-cause mortality Low
17 Respiratory tract infections (general) ScienceDirect/Lancet NMA 2025 (oral nutritional supplements) — High-dose vitamin D > comparators for COVID-19 / influenza prevention Low
18 Preeclampsia Kartasurya 2025, AIMS Public Health 24 / 52,372 Supplementation reduced preeclampsia incidence (pooled OR <1) Low–Mod
19 Tuberculosis (prevention + adjunct) Liu 2025, Biomol Biomed; IPD-MA 2019 Multiple RCTs TB risk aOR 1.48 in deficient; 4.28 in severe deficiency + HIV; supplementation effect inconsistent Low
20 Inflammatory bowel disease (Crohn's, UC) Valvano 2024, IBD 12 RCTs Reduced clinical relapse risk, especially in Crohn's in remission Low

Honorable mentions (top 21–30)

# Condition Notes
21 Obstructive sleep apnea / CPAP Many MAs on OSA–25(OH)D association and CPAP's effect on vitamin D; few true NMAs. Pooled OSA d+ = −0.74 for 25(OH)D (Loh 2023)
22 Dementia / Alzheimer's / cognitive impairment Huang 2025, Front Neurol: 22 studies, 53,122 participants; lowest vs highest vitamin D: RR 1.49
23 Rheumatoid arthritis Multiple MAs on CRP, VAS, disease activity
24 Critical illness / ICU mortality Zheng 2025, Front Nutr: 19 RCTs / 2,754 patients; mortality RR 0.83 (0.70–0.98)
25 Systemic lupus erythematosus (SLE) El Kababi 2025, Nutrients: 3,177 adults; disease-activity reduction in 12/15 studies
26 Periodontitis Liang 2023, BMC Oral Health: lower 25(OH)D in periodontitis; mixed RCT data
27 Traumatic brain injury medRxiv 2025: GCS-score forest plot favoring vitamin D
28 Anxiety Often paired with depression NMAs; under-powered as primary outcome
29 Irritable bowel syndrome (IBS) Few NMAs; pairwise MA shows IBS-SSS WMD −84.21
30 Cancer survival (pooled across sites) Chen 2022, Nutrients: post-diagnosis supplementation OS HR 0.87

Methodological gaps for the Vitamin D Life audience

  1. Baseline 25(OH)D stratification is rarely required for inclusion. Most NMAs pool RCTs without regard to whether participants were deficient at entry. The Zhang 2024 COVID-19 NMA is one of the few to subgroup by 25(OH)D <30 ng/mL — and it found benefit only in that subgroup. This pattern likely explains many null NMAs.
  2. Dose heterogeneity swamps signal. Pooling 400 IU/d with 60,000 IU/wk arms produces uninterpretable pooled effects. Bayesian dose-response NMAs (e.g., Zhuang 2023 for 25(OH)D elevation; Ghaemi 2024 for depression) are the methodological frontier.
  3. D2 vs D3 vs calcifediol vs calcitriol are usually collapsed. The 17 RCTs of calcifediol in stroke and CKD demand separate synthesis.
  4. SII (Systemic Immune-Inflammation Index) and other inflammatory mediators are almost never modeled as the causal pathway in NMAs. Mediation analysis — as in Xu 2026 on MCR — is the gap worth filling.
  5. Adoption-relevant outcomes (Medicare Advantage cost reduction, LTC fall rates, IHS clinic uptake) are not in any NMA. Translational/implementation NMAs would be a novel contribution.
  6. Profitable-ignorance bias: Cochrane and ACP NMAs frequently exclude vitamin D and calcium arms by protocol, then conclude that pharmacologic agents are uniquely effective. The ACP 2024 osteoporosis NMA is the canonical example.

Caveats

  • Google Scholar counts are inflated and unstable; the same query run a week apart can vary by 5–15%.
  • "Network meta-analysis" in title/abstract does not guarantee proper NMA methodology — many self-described NMAs are actually pairwise meta-analyses with subgroup ranking.
  • The top-20 ranking here is by research volume, not clinical impact. Rickets has enormous clinical impact globally despite producing few NMAs.
  • Numbers in the k/N column reflect the cited representative NMA only, not the total literature for that condition.
  • Compiled from PubMed/PMC, Frontiers, MDPI, BMC, Springer, Lancet, and Cureus indices, May 2026. Where a 2026-dated paper is cited, it reflects the journal's online-first publication date.