ID,Citation,Year,Journal,Evidence Class,Study Design,Research Area,Population / Model,N,Baseline 25(OH)D,Vitamin D Form,Dose / Regimen,Duration,Comparator,Immune Endpoint(s),Clinical Endpoint(s),Main Finding,Key Statistical Result,Evidence Direction,Key Limitations / Notes,PMID,DOI,PubMed / Source URL,ImmuneForward Use
H01,"Li-Ng et al., 2009",2009,Epidemiology and infection,Human RCT,"Randomized, placebo-controlled",Respiratory infection,Adults,162,~63–64 nmol/L,Vitamin D3,"2,000 IU/day",12 weeks,Placebo,—,"Symptomatic URI incidence, duration, severity","No reduction in URI incidence, duration, or severity despite increased 25(OH)D.",URI 48 vs 50; P=0.57; duration P=0.86,Neutral / Negative,Winter trial; baseline vitamin D status generally not severely deficient.,19296870,10.1017/S0950268809002404,https://pubmed.ncbi.nlm.nih.gov/19296870/,Qualifies claims that supplementation prevents respiratory infections.
H02,"Urashima et al., 2010",2010,The American journal of clinical nutrition,Human RCT,"Randomized, double-blind, placebo-controlled",Influenza,Schoolchildren,334,Not extracted,Vitamin D3,"1,200 IU/day",Dec 2008–Mar 2009,Placebo,—,Laboratory/physician-diagnosed influenza A,Lower incidence of influenza A in vitamin D group.,10.8% vs 18.6%; RR 0.58 (95% CI 0.34–0.99); P=0.04,Positive,Specific pediatric population and influenza season; outcome-specific.,20219962,10.3945/ajcn.2009.29094,https://pubmed.ncbi.nlm.nih.gov/20219962/,Supports possible infection-specific benefit in children.
H03,"Laaksi et al., 2010",2010,The Journal of infectious diseases,Human RCT,"Randomized, double-blind",Respiratory infection,Young Finnish men,Not extracted,Not extracted,Vitamin D3,Daily supplementation,Winter study,Placebo,—,Acute respiratory tract infection,Trial tested vitamin D for prevention of ARTI in young men; include in respiratory RCT evidence base.,See primary publication,Mixed / requires full extraction,PubMed metadata verified; no abstract available in the retrieved record. Full numerical extraction requires primary-article review before claim-level use.,20632889,10.1086/654881,https://pubmed.ncbi.nlm.nih.gov/20632889/,Respiratory-infection RCT evidence.
H04,"Camargo et al., 2012",2012,Pediatrics,Human RCT,"Cluster randomized, double-blind comparison",Respiratory infection,Mongolian schoolchildren with marked vitamin D deficiency,247,Median 7 ng/mL,Vitamin D3,300 IU/day in fortified milk,~3 months winter,Unfortified milk,—,Parent-reported ARI,Vitamin D-fortified milk reduced reported ARIs.,Rate ratio 0.52 (95% CI 0.31–0.89); adjusted RR 0.50 (0.28–0.88),Positive,Subset of larger cluster trial; very low baseline 25(OH)D; parent-reported outcome.,22908115,10.1542/peds.2011-3029,https://pubmed.ncbi.nlm.nih.gov/22908115/,Supports benefit in severely deficient children.
H05,"Murdoch et al., 2012 (VIDARIS)",2012,JAMA,Human RCT,"Randomized, double-blind, placebo-controlled",Respiratory infection,Healthy adults,322,Mean 29 ng/mL,Vitamin D3,"200,000 IU initial + 200,000 IU at 1 month, then 100,000 IU monthly",18 months,Placebo,—,"URTI incidence, duration, severity, missed work",High-dose monthly vitamin D did not reduce incidence or severity of URTIs.,RR 0.97 (95% CI 0.85–1.11) for URTIs/person,Neutral / Negative,Bolus regimen; participants not markedly deficient at baseline.,23032549,10.1001/jama.2012.12505,https://pubmed.ncbi.nlm.nih.gov/23032549/,Strong negative evidence for intermittent high-dose supplementation.
H06,"Bergman et al., 2012",2012,BMJ open,Human RCT,"Randomized, double-blind, placebo-controlled",Respiratory infection,Adults with frequent RTIs and/or antibody deficiency,140,Not extracted,Vitamin D3,"4,000 IU/day",1 year,Placebo,Antimicrobial/immune context,"Infectious symptoms, antibiotic use",Daily vitamin D produced favorable infection-related outcomes in a selected high-risk population.,See primary publication,Positive,Selected clinical population; not generalizable to healthy adults.,23242238,10.1136/bmjopen-2012-001663,https://pubmed.ncbi.nlm.nih.gov/23242238/,Supports possible benefit in selected high-risk patients.
H07,"Rees et al., 2013",2013,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,Human RCT,Randomized controlled trial / secondary infection analysis,Respiratory infection,Adults aged 45–75 with prior colorectal adenoma,2259,≥12 ng/mL,Vitamin D3,"1,000 IU/day",Multi-year parent trial,Placebo / calcium factorial,—,"Winter URTI, colds, influenza-like illness","No significant reduction in winter URTI, colds, or influenza-like illness.",URTI RR 0.93 (95% CI 0.79–1.09),Neutral / Negative,Respiratory outcomes were secondary; diary subset n=759.,24014734,10.1093/cid/cit549,https://pubmed.ncbi.nlm.nih.gov/24014734/,Negative evidence in generally healthy midlife/older adults.
H08,"Goodall et al., 2014",2014,BMC infectious diseases,Human RCT,Randomized controlled trial,Respiratory infection,University students,600,Not extracted,Vitamin D3,Not extracted,Not extracted,Placebo,—,Clinical and laboratory-confirmed URTI,"Clinical URTI reduction was not statistically significant, but laboratory-confirmed URTI was lower with vitamin D.",Clinical RR 0.79 (95% CI 0.61–1.03); lab-confirmed RR 0.54 (0.34–0.84),Mixed / Positive for lab-confirmed endpoint,Factorial trial also tested gargling; completion varied.,24885201,10.1186/1471-2334-14-273,https://pubmed.ncbi.nlm.nih.gov/24885201/,Shows endpoint-dependent respiratory findings.
H09,"Urashima et al., 2014",2014,Food & function,Human RCT,"Randomized, double-blind, placebo-controlled",Influenza,Japanese high-school students,247,Not extracted,Vitamin D3,"2,000 IU/day",2 months,Placebo,—,Influenza A during 2009 H1N1 pandemic,No reduction in influenza A incidence.,13.5% vs 12.1%,Neutral / Negative,Specific pandemic season; contrasts with earlier pediatric influenza trial.,25088394,10.1039/c4fo00371c,https://pubmed.ncbi.nlm.nih.gov/25088394/,Balances positive influenza findings.
H10,"Grant et al., 2015",2015,"Acta paediatrica (Oslo, Norway : 1992)",Human RCT,"Randomized, double-blind, placebo-controlled",Respiratory infection,Pregnancy/infancy supplementation cohort,Not extracted,Not extracted,Vitamin D3,Pregnancy and infancy dosing arms,Infancy follow-up,Placebo,—,Primary-care ARI visits,Vitamin D supplementation was associated with reduced primary-care respiratory infection visits in the trial follow-up.,See primary publication,Positive,Maternal/infant intervention; population and dosing differ from adult supplementation.,25283480,10.1111/apa.12819,https://pubmed.ncbi.nlm.nih.gov/25283480/,Pediatric/perinatal respiratory evidence.
H11,"Konijeti et al., 2016",2016,The Journal of clinical endocrinology and metabolism,Human RCT / ancillary,Double-blind randomized dose comparison,T-cell function,Vitamin-D-deficient adults with untreated pre/early hypertension,38,Vitamin D deficient,Vitamin D3,"400 vs 4,000 IU/day",6 months; immune endpoint at 2 months,Low-dose vitamin D,CD4+ T-cell activation / intracellular ATP after stimulation,Not measured as a clinical outcome,"Higher-dose vitamin D reduced stimulated CD4+ T-cell ATP release versus the lower dose; this is immune modulation, not enhanced protection.",38 participants; immune testing at 2 months; OR 3.43 for lower ATP release. The abstract confidence interval appears typographically inconsistent and is not reproduced.,Mechanistically Positive,Small ancillary study; low-dose active comparator rather than placebo.,26653112,10.1210/jc.2015-3599,https://pubmed.ncbi.nlm.nih.gov/26653112/,Direct human evidence that supplementation can modulate T-cell function.
H12,"Sharifi et al., 2016",2016,Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association,Human RCT,Randomized placebo-controlled,Cathelicidin / inflammation,Ulcerative colitis patients in remission,90,Not extracted,Vitamin D,"300,000 IU intramuscular once",90 days,Saline placebo,"Cathelicidin hCAP18 expression, hs-CRP, ESR",Inflammatory biomarkers,Vitamin D increased cathelicidin gene expression and reduced hs-CRP and ESR versus placebo.,hs-CRP P=0.023; ESR P<0.001; hCAP18 increased,Positive mechanistic,Disease-specific population; very large bolus; not evidence of general immune benefit.,27488327,10.4103/1319-3767.187606,https://pubmed.ncbi.nlm.nih.gov/27488327/,Mechanistic human evidence for antimicrobial peptide/inflammation pathways.
H13,"Loeb et al. / Vietnam trial, 2019",2019,Influenza and other respiratory viruses,Human RCT,"Randomized, placebo-controlled",Respiratory viral infection,Children and adolescents in Vietnam,1300,~65 nmol/L,Vitamin D,Trial supplementation,Not extracted,Placebo,—,RT-PCR influenza and non-influenza respiratory viruses,No reduction in influenza; moderate reduction in non-influenza respiratory viral infection and all respiratory viruses combined.,Influenza HR 1.18 (0.79–1.78); non-influenza HR 0.76 (0.61–0.94); all viruses HR 0.81 (0.66–0.99),Mixed,Benefit depended on virologic endpoint; baseline vitamin D not severely low.,30328294,10.1111/irv.12615,https://pubmed.ncbi.nlm.nih.gov/30328294/,Demonstrates pathogen-specific heterogeneity.
H14,"Ganmaa et al., 2020",2020,The New England journal of medicine,Human RCT,"Randomized, double-blind, placebo-controlled",Tuberculosis / respiratory infection,Vitamin-D-deficient Mongolian schoolchildren,"~8,800",Deficient,Vitamin D3,Weekly supplementation,3 years,Placebo,TB infection (QFT),TB infection/disease; ARI hospitalization,"Vitamin D substantially raised 25(OH)D but did not reduce tuberculosis infection, TB disease, or ARI hospitalization.",QFT adjusted RR 1.10 (0.87–1.38); TB disease RR 0.87 (0.49–1.55),Neutral / Negative,"Large, long-duration trial; highly relevant negative evidence despite correction of deficiency.",32706534,10.1056/NEJMoa1915176,https://pubmed.ncbi.nlm.nih.gov/32706534/,Strong negative evidence for TB prevention.
H15,"Jolliffe et al., 2022 (CORONAVIT)",2022,BMJ (Clinical research ed.),Human RCT,Phase 3 open-label randomized controlled trial,Respiratory infection / COVID-19,UK adults ≥16 years,6200,Test-and-treat threshold <75 nmol/L,Vitamin D3,"800 or 3,200 IU/day when <75 nmol/L",6 months,No offer of testing/supplementation,—,All-cause ARI and COVID-19,Test-and-treat vitamin D strategy did not establish prevention of all-cause ARI or COVID-19.,See primary publication,Neutral / Negative,Open-label; intervention was an offer/test-and-treat strategy rather than simple blinded supplementation.,36215226,10.1136/bmj-2022-071230,https://pubmed.ncbi.nlm.nih.gov/36215226/,Large modern trial relevant to ARI/COVID prevention.
H16,"Jolliffe et al., 2022 (CORONAVIT vaccine substudy)",2022,Nutrients,Human RCT substudy,Nested randomized trial substudies,Vaccination,UK adults with suboptimal vitamin D status,2808 / 1853 / 100 across substudies,<75 nmol/L entry criterion,Vitamin D3,"800 or 3,200 IU/day",During vaccination follow-up,No offer,"Anti-Spike IgGAM, neutralizing antibodies, IFN-γ cellular response",Breakthrough SARS-CoV-2 infection,Supplementation raised 25(OH)D but did not improve vaccine immunogenicity or efficacy.,Breakthrough aHR 1.28 and 1.17 vs no offer; no antibody/IFN-γ benefit,Neutral / Negative,Nested substudies; SARS-CoV-2 vaccines specifically.,36145196,10.3390/nu14183821,https://pubmed.ncbi.nlm.nih.gov/36145196/,Strong negative evidence against routine vitamin D to boost SARS-CoV-2 vaccine response.
H17,"Camargo et al., 2024 (VITAL URI analysis)",2024,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,Human RCT,Prespecified analysis of randomized placebo-controlled trial,Respiratory infection,Generally healthy older adults,"15,804",Mean 31 ng/mL; 2.4% <12 ng/mL,Vitamin D3,"2,000 IU/day",1 year primary URI analysis,Placebo,—,Self-reported recent URI,Daily vitamin D3 did not significantly lower self-reported recent upper respiratory infection risk in older adults.,OR 0.96 (95% CI 0.86–1.06); primary endpoint at 1 year.,Neutral / Negative,Predominantly vitamin-D-sufficient population; URI self-report.,38113446,10.1093/cid/ciad770,https://pubmed.ncbi.nlm.nih.gov/38113446/,Large daily-dose trial in older adults.
H18,"A. Laaksi et al., 2024",2024,Open forum infectious diseases,Human RCT + observational follow-up,Randomized placebo-controlled,Respiratory infection / cathelicidin,Young men; follow-up cohort 412,RCT N not extracted; cohort 412,Insufficiency defined <50 nmol/L,Vitamin D3,20 µg/day (800 IU/day),14 weeks,Placebo,Cathelicidin,ARI and days off,Supplementation had no effect on ARI or days off; baseline insufficiency was associated with more ARI and lower cathelicidin.,Baseline insufficiency ARI OR 2.1 (1.2–3.7); supplementation null,"Mixed: RCT neutral, observational association",Important distinction between association and supplementation effect.,39301110,10.1093/ofid/ofae482,https://pubmed.ncbi.nlm.nih.gov/39301110/,Excellent example of observational association not translating into RCT benefit.
H19,"Clerico et al., 2025",2025,European journal of nutrition,Human RCT,Randomized clinical trial,Respiratory infection,Children aged 6–8 years,200 randomized; 189 with complete infection questionnaires,79.8 ± 17.2 nmol/L,Vitamin D,20 µg/day (800 IU/day) vitamin D3,24 weeks,Control,—,Acute respiratory tract infections,Fewer days with acute respiratory infection and with febrile respiratory infection; no difference in other measured outcomes.,Sick days RR 0.83 (95% CI 0.76–0.90); febrile sick days RR 0.57 (0.48–0.67); both P<0.001.,Mixed / Positive,"Secondary analysis of a factorial Danish trial; generally vitamin-D-replete, white children aged 6–8; illness reported by parents. This measures sick days, not universal infection prevention.",40310565,10.1007/s00394-025-03674-1,https://pubmed.ncbi.nlm.nih.gov/40310565/,Recent pediatric RCT.
H20,"Rastgoo et al., 2025",2025,Frontiers in Immunology,Human RCT,"Randomized, double-blind, four active-treatment groups",Immune aging / cellular senescence,Vitamin-D-deficient older adults in Iran,88; 22 per group,Vitamin D deficient,Vitamin D,"1,000 or 5,000 IU/day, with or without NAC 600 mg/day",8 weeks,"1,000 IU/day vitamin D; no untreated placebo","PBMC p16, p21, IL6, TNF; SA-β-gal activity; serum IL-6, CRP, NLR",No clinical infection or vaccine outcome,"5,000 IU/day reduced selected PBMC senescence-associated markers versus 1,000 IU/day; some NAC combinations also changed markers. Serum IL-6, CRP and NLR did not differ significantly between groups.",88 completed; p21 changes were not significant. See corrected full text for endpoint-specific tests.,Positive mechanistic,"Short biomarker trial with active comparators; does not establish whole-system immune rejuvenation. 5,000 IU/day exceeds the usual adult upper intake level. Corrigendum PMID 40510343 corrects a 50,000/5,000 IU table-label typo.",40421021,10.3389/fimmu.2025.1570441,https://pubmed.ncbi.nlm.nih.gov/40421021/,Direct but preliminary human immune-aging-marker evidence from the supplied ImmAge document.
H21,"Zhu et al., 2025 (VITAL telomere substudy)",2025,American Journal of Clinical Nutrition,Human RCT substudy,Ancillary study of a randomized double-blind factorial trial,Aging biomarkers / telomeres,US men ≥50 and women ≥55 years,"1,031 participants with telomere measurements",Not selected for deficiency,Vitamin D3,"2,000 IU/day",4 years,Placebo,Leukocyte telomere length,No direct immune-function or infection endpoint in this analysis,Vitamin D reduced leukocyte telomere attrition compared with placebo. This biomarker result does not establish immune rejuvenation.,"Between-group difference in attrition 0.14 kb (95% CI 0.007–0.27), P=0.039.",Positive biomarker,Ancillary analysis; telomere measurement is not a clinical immunity outcome; differs from the negative monthly-dose D-Health study.,40409468,10.1016/j.ajcnut.2025.05.003,https://pubmed.ncbi.nlm.nih.gov/40409468/,Adds aging-biomarker context without claiming a younger immune system.
H22,"Rahman et al., 2023 (D-Health telomere substudy)",2023,"The Journal of Nutrition, Health & Aging",Human RCT substudy,Ancillary analysis of randomized double-blind trial,Aging biomarkers / telomeres,"Australian adults aged 60–84 years, largely vitamin D replete","1,519",Largely vitamin D replete,Vitamin D3,"60,000 IU monthly",Telomeres measured 4 or 5 years after randomization,Placebo,Relative leukocyte telomere length,No immune-function endpoint in this analysis,Monthly supplementation did not change relative telomere length.,Adjusted T/S-ratio difference −0.001 (95% CI −0.02 to 0.02).,Neutral / Negative,No baseline telomere change measurement in this comparison; monthly regimen and population differ from VITAL.,37702332,10.1007/s12603-023-1948-3,https://pubmed.ncbi.nlm.nih.gov/37702332/,Balances positive VITAL biomarker evidence.
A01,"Bruce et al., 2009",2009,International immunology,Animal Study,VDR knockout infection model; young and old mice,Immune aging / Listeria infection,Young and old VDR-KO and WT mice,Not extracted,N/A,VDR genetic deletion,VDR knockout,Primary and secondary infection,Wild-type controls,"Memory T cells, cytokines, antibodies",Listeria monocytogenes clearance,"VDR-KO mice cleared primary and secondary Listeria infections, with somewhat delayed kinetics; old VDR-KO mice had fewer memory T cells but elevated nonspecific cytokine/antibody responses.",Complete clearance despite altered immune phenotype,Mixed / Mechanistic,Important aging model: amplified immune responses did not translate into better pathogen clearance.,19088060,10.1093/intimm/dxn129,https://pubmed.ncbi.nlm.nih.gov/19088060/,Shows VDR effects on immune aging and regulation without simple loss of antimicrobial competence.
A02,"Mathieu et al., 2001",2001,Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research,Animal Study,VDR knockout immune phenotyping,Innate & adaptive immunity,VDR-KO and wild-type mice,Not extracted,N/A,VDR genetic deletion,VDR knockout,In vivo/in vitro,Wild-type,"Anti-CD3 proliferation, macrophage chemotaxis, phagocytosis/killing",Graft rejection; streptozotocin diabetes,"VDR-KO mice showed lower anti-CD3 proliferation and impaired macrophage chemotaxis, but several abnormalities normalized when calcium homeostasis was corrected.",Anti-CD3 SI 13±4 vs 24±9; macrophage chemotaxis 41±19% vs 60±18%,Mixed / Mechanistic,Highlights major calcium-homeostasis confounding in VDR-KO models.,11697802,10.1359/jbmr.2001.16.11.2057,https://pubmed.ncbi.nlm.nih.gov/11697802/,Cautions against attributing every VDR-KO immune phenotype directly to vitamin D signaling.
A03,"Wu et al., 2010",2010,The American journal of pathology,Animal Study,VDR knockout + Salmonella infection,Bacterial infection / NF-κB,VDR-/- and VDR+/+ mice,Not extracted,N/A,VDR genetic deletion,VDR knockout,Acute infection,Wild-type,"Intestinal NF-κB, IL-6, epithelial responses",Salmonella burden and mortality,VDR deletion produced a pro-inflammatory intestinal phenotype and increased Salmonella burden and mortality.,See primary publication,Negative effect of VDR loss,"Genetic receptor model; demonstrates VDR-dependent host regulation, not supplementation efficacy.",20566739,10.2353/ajpath.2010.090998,https://pubmed.ncbi.nlm.nih.gov/20566739/,Supports VDR/NF-κB and mucosal host-defense mechanisms.
A04,"Ryz et al., 2012",2012,American journal of physiology. Gastrointestinal and liver physiology,Animal Study,Calcitriol treatment during enteric infection,Citrobacter / Th17,C. rodentium-infected mice,Not extracted,N/A,"1,25(OH)2D3",Active vitamin D treatment,During infection,Vehicle/control,"Th17, Th1, Treg, REG3γ","Pathogen burden, tissue pathology",Active vitamin D suppressed mucosal Th17 responses and REG3γ and increased pathogen burden and pathology.,See primary publication,Adverse / Mechanistically informative,Important negative animal result: immune suppression can impair host defense.,23019194,10.1152/ajpgi.00320.2012,https://pubmed.ncbi.nlm.nih.gov/23019194/,Balances claims that vitamin D immune modulation is universally beneficial.
A05,"Ooi et al., 2013",2013,The Journal of nutrition,Animal Study,Vitamin D/VDR/CYP27B1 deficiency and DSS colitis,Microbiome / colitis,"WT, VDR-KO and Cyp27b1-KO mice",Not extracted,N/A,"1,25(OH)2D3 / VDR",Dietary treatment in Cyp KO,Experimental colitis,WT / untreated,"Tolerogenic dendritic cells, E-cadherin, microbiota",DSS colitis severity,"Vitamin D/VDR deficiency caused dysbiosis and greater colitis susceptibility; 1,25(OH)2D3 treatment reduced colitis severity in Cyp-KO mice.",See primary publication,Positive mechanistic,Complex microbiome-mediated model; not direct human evidence.,23966330,10.3945/jn.113.180794,https://pubmed.ncbi.nlm.nih.gov/23966330/,Supports vitamin D–microbiome–mucosal immunity interactions.
A06,"Liu et al., 2013",2013,The Journal of clinical investigation,Animal Study,Epithelial VDR transgenic/rescue colitis models,Mucosal immunity / colitis,Multiple mouse colitis models,Not extracted,N/A,VDR signaling,Epithelial VDR expression/rescue,Experimental colitis,WT / VDR-deficient,Epithelial barrier and inflammatory responses,Colitis severity and survival,Intestinal epithelial VDR expression protected against several experimental colitis models and rescued severe disease in VDR-null mice.,See primary publication,Positive mechanistic,Tissue-specific genetic model; not supplementation evidence.,23945234,10.1172/JCI65842,https://pubmed.ncbi.nlm.nih.gov/23945234/,Supports epithelial VDR as a regulator of mucosal inflammation.
A07,"Reeme & Robinson, 2016",2016,"Journal of immunology (Baltimore, Md. : 1950)",Animal Study,Dietary vitamin D3 in experimental tuberculosis,Tuberculosis / immunopathology,C3HeB/FeJ mice infected with M. tuberculosis,3–4/group/timepoint,N/A,Vitamin D3,Vitamin-D-high vs deficient diet,Up to 92 days post-infection,Vitamin-D-low diet,"IL-12/23p40, IFN-γ, T-cell accumulation, myeloid cells",M. tuberculosis burden; pulmonary pathology,Vitamin-D-replete diet reduced late pulmonary inflammation and immunopathology but did not significantly reduce bacterial burden.,Lung burden P=0.1444; spleen P=0.6109,Mixed / Positive immunopathology,Strong example that immune modulation and pathogen killing are distinct outcomes.,26729807,10.4049/jimmunol.1500931,https://pubmed.ncbi.nlm.nih.gov/26729807/,Supports anti-inflammatory effects without claiming antimycobacterial efficacy.
A08,"Penkert et al., 2016",2016,Clinical and vaccine immunology : CVI,Animal Study,Vitamin A/D deficiency and live attenuated influenza vaccination,Vaccination / mucosal antibody,Vitamin-deficient mice,Not extracted,N/A,Vitamins A and D,Supplementation at immunization,Vaccination study,Deficient controls,Mucosal antibody responses,Influenza vaccine immunogenicity,"Vitamin D deficiency alone had limited effects, while combined A+D deficiency further reduced respiratory antibody responses; supplementation restored responses dose-dependently.",See primary publication,Mixed / Combination evidence,Combined nutrient model prevents attribution of rescue solely to vitamin D.,26740391,10.1128/CVI.00739-15,https://pubmed.ncbi.nlm.nih.gov/26740391/,Animal vaccine evidence; clearly label combined vitamin A/D intervention.
A09,"Zhang et al., 2016",2016,Scientific reports,Animal Study,Vitamin D treatment in TNBS and oxazolone colitis,Th1/Th17 / colitis,C57BL/6 mice,Not extracted,N/A,Vitamin D,Pretreatment,Experimental colitis,Vehicle,"Th1, Th17, Th2, Treg cytokines",Colitis pathology,"Vitamin D attenuated TNBS-induced colitis and suppressed Th1/Th17-related cytokines, but did not improve oxazolone colitis.",See primary publication,Mixed / Model-dependent,Effect differed by immune/pathologic model.,27620138,10.1038/srep32889,https://pubmed.ncbi.nlm.nih.gov/27620138/,Shows immune effects depend on inflammatory context.
A10,"Cantorna et al., 2019",2019,Frontiers in immunology,Animal Study,Vitamin D regulation of colonic Tregs and microbiota,Treg / microbiome / colitis,Vitamin-D-sufficient and deficient mice; germ-free recipients,Not extracted,N/A,"Vitamin D / 1,25(OH)2D",Dietary status and treatment,Development + colitis,Vitamin-D-deficient,FoxP3+ and RORγt/FoxP3+ Tregs,Colitis susceptibility,Vitamin-D-sufficient mice had more colonic regulatory T cells and were less susceptible to colitis; microbiota transfer reproduced aspects of the phenotype.,See primary publication,Positive mechanistic,Microbiota-dependent; developmental timing mattered.,31417552,10.3389/fimmu.2019.01772,https://pubmed.ncbi.nlm.nih.gov/31417552/,Supports vitamin D–microbiome–Treg axis.
A11,"Yamamoto et al., 2020",2020,Nutrients,Animal Study,Oral 25(OH)D3 supplementation before influenza challenge,Influenza infection,Influenza A-infected mice,Not extracted,N/A,25-hydroxyvitamin D3,High-dose dietary 25(OH)D3,Prophylactic feeding,Standard diet,Inflammatory/antiviral lung responses,Pulmonary viral titers,25(OH)D3-fed mice had significantly lower lung viral titers than standard-fed controls.,See primary publication,Positive preclinical,High-dose metabolite in mice; cannot be generalized to standard human D3 supplementation.,32635656,10.3390/nu12072000,https://pubmed.ncbi.nlm.nih.gov/32635656/,Preclinical antiviral evidence.
A12,"Cantorna group, 2022",2022,Nutrients,Animal Study,"Vitamin D deficiency, CYP27B1 KO, H1N1 and SARS-CoV-2 models",Respiratory viral infection,Mice and hamsters,Not extracted,N/A,"Vitamin D / 1,25(OH)2D",Deficiency/sufficiency; supplementation,Infection studies,Sufficient WT controls,"Lung inflammation, vitamin D activation","Survival, viral gene expression, weight recovery","Deficiency or inability to generate 1,25(OH)2D worsened H1N1 outcomes; supplementation reduced inflammation in mice, but viral replication was not consistently reduced and hamster results differed.",See primary publication,Mixed / Positive host tolerance,Species- and endpoint-dependent; distinguishes inflammation/survival from viral replication.,35893921,10.3390/nu14153061,https://pubmed.ncbi.nlm.nih.gov/35893921/,Modern respiratory-virus animal evidence with important limitations.
A13,"Meehan & DeLuca, 2002",2002,Archives of biochemistry and biophysics,Animal Study,VDR requirement for calcitriol suppression of EAE,Autoimmunity / EAE,EAE mice with/without functional VDR,Not extracted,N/A,"1,25(OH)2D3",Calcitriol,EAE course,Vehicle / genotype controls,Autoimmune T-cell responses,EAE severity,Calcitriol suppressed EAE through the canonical vitamin D receptor; VDR was required for the effect.,See primary publication,Positive mechanistic,"Pharmacologic active hormone in autoimmune model, not nutritional supplementation.",12464272,10.1016/s0003-9861(02)00580-5,https://pubmed.ncbi.nlm.nih.gov/12464272/,Establishes VDR dependence of calcitriol's autoimmune effects.
A14,"Mayne et al., 2011",2011,European journal of immunology,Animal Study,T-cell-specific VDR targeting in EAE,Autoimmunity / T cells,EAE mice with conditional VDR targeting,Not extracted,N/A,"1,25(OH)2D3 / VDR",Calcitriol / genetic targeting,EAE course,Controls,"Pathogenic CD4+ T cells, Foxp3+ Tregs",EAE severity,Calcitriol acted directly through T-cell VDR to inhibit EAE; Foxp3+ proportions were not the key mechanism in this model.,See primary publication,Positive mechanistic,Disease model and pharmacologic calcitriol; not general immune-health evidence.,21287548,10.1002/eji.201040632,https://pubmed.ncbi.nlm.nih.gov/21287548/,Direct evidence for T-cell VDR-mediated immunoregulation.
R01,"Martineau/Jolliffe et al., 2019 IPD meta-analysis",2019,"Health technology assessment (Winchester, England)",Systematic Review / Meta-analysis,Individual participant data meta-analysis of 25 RCTs,Respiratory infection,Participants aged 0–95 years,11321,Stratified including <25 nmol/L,D2/D3,Multiple regimens,Multiple,Placebo,—,ARI,Overall protection was reported; stronger effects were observed with daily/weekly dosing without bolus and among very deficient participants in those regimens.,aOR 0.88 (0.81–0.96); daily/weekly aOR 0.81; <25 nmol/L subgroup aOR 0.30,Positive meta-analytic evidence,Based on older trial set; later larger meta-analyses changed the overall inference.,30675873,10.3310/hta23020,https://pubmed.ncbi.nlm.nih.gov/30675873/,Historical synthesis explaining earlier positive interpretation.
R02,"Jolliffe et al., 2021",2021,The lancet. Diabetes & endocrinology,Systematic Review / Meta-analysis,Aggregate-data meta-analysis,Respiratory infection,43 trials; ages 0–95,48488,Stratified,D2/D3/25(OH)D,Multiple,Various,Placebo/low-dose,—,ARI,"Small overall reduction in ARI was reported, with heterogeneity; no significant interaction by prespecified modifiers.",OR 0.92 (0.86–0.99),Small Positive / heterogeneous,Superseded by newer 2025 update with additional large trials.,33798465,10.1016/S2213-8587(21)00051-6,https://pubmed.ncbi.nlm.nih.gov/33798465/,Shows evolution of evidence over time.
R03,"Cho et al., 2022",2022,Nutrients,Systematic Review / Meta-analysis,Meta-analysis of RCTs,ARI prevention,30 RCTs,30263,Various,Vitamin D,Various,Various,Control,—,ARI prevention,No significant overall prevention; apparent daily/short-term subgroup effects disappeared in high-quality-study subgroup analyses.,RR 0.96 (0.91–1.01),Neutral / Mixed,Subgroup heterogeneity; quality-sensitive results.,35215468,10.3390/nu14040818,https://pubmed.ncbi.nlm.nih.gov/35215468/,Supports cautious infection-prevention conclusion.
R04,"Cho et al., 2022 treatment meta-analysis",2022,Nutrients,Systematic Review / Meta-analysis,Meta-analysis of 18 RCTs,ARI treatment,18 RCTs,3648,Various,Vitamin D,Various,Various,Control,—,ARI treatment outcomes,Small statistical signal overall was not clinically substantial and disappeared in high-quality RCTs.,Overall RR 1.07 (1.01–1.13); high-quality RR 1.02 (0.98–1.06),Neutral / Not clinically effective,Publication bias observed; treatment rather than prevention.,35334804,10.3390/nu14061144,https://pubmed.ncbi.nlm.nih.gov/35334804/,Supports distinction between mechanistic plausibility and clinical treatment efficacy.
R05,2024 dose-response ARI meta-analysis,2024,Nutrition journal,Systematic Review / Meta-analysis,43-RCT dose-response/pairwise meta-analysis,ARI prevention,43 RCTs,49320,Various,Vitamin D,Multiple,Multiple,Control,—,ARI,No significant overall preventive effect; some subgroup signals for daily dosing and seasonal windows.,Overall RR 0.99 (0.97–1.01),Neutral / Mixed,Subgroup findings require caution given null overall result.,39143549,10.1186/s12937-024-00990-w,https://pubmed.ncbi.nlm.nih.gov/39143549/,Modern synthesis before 2025 update.
R06,"Jolliffe et al., 2025",2025,The lancet. Diabetes & endocrinology,Systematic Review / Meta-analysis,Updated meta-analysis of stratified aggregate RCT data,ARI prevention,40 placebo-controlled comparisons in primary analysis,61589,Stratified,Vitamin D,Multiple regimens,Multiple,Placebo,—,ARI,"Updated evidence found no statistically significant overall reduction in ARI and no evidence of effect modification by age, baseline vitamin D status, dosing frequency, or dose size.","OR 0.94 (0.88–1.00), P=0.057",Neutral / Not established,Most current major synthesis; funnel-plot asymmetry noted.,39993397,10.1016/S2213-8587(24)00348-6,https://pubmed.ncbi.nlm.nih.gov/39993397/,Primary current synthesis for overall ARI claim.
R07,"Wang et al., 2025",2025,BMC pediatrics,Systematic Review / Meta-analysis,Pediatric RCT systematic review/meta-analysis,Pediatric ARI,17 pediatric RCTs,18372,Various,Vitamin D,Various,Various,Placebo/no treatment,—,"ARI incidence, hospitalization, recovery, mortality","No significant reduction in pediatric ARI incidence, hospitalization duration, recovery time, or mortality.",ARI RR 0.82 (0.64–1.06),Neutral,Pediatric-specific; substantial heterogeneity possible across trials.,41387808,10.1186/s12887-025-06361-6,https://pubmed.ncbi.nlm.nih.gov/41387808/,Current pediatric synthesis.
R08,"Hewison, 2011",2011,Vitamins and hormones,Major Review,Narrative mechanistic review,Innate & adaptive immunity,Human/experimental literature,—,—,Vitamin D metabolites,—,—,—,"CYP27B1/VDR, antimicrobial activity, antigen presentation, T/B-cell function",—,Review describes intracrine/paracrine vitamin D signaling in innate and adaptive immunity.,—,Mechanistic Review,"Review, not primary clinical evidence.",21419266,10.1016/B978-0-12-386960-9.00002-2,https://pubmed.ncbi.nlm.nih.gov/21419266/,Core mechanistic background.
R09,"Kongsbak et al., 2013",2013,Frontiers in immunology,Major Review,Narrative review,T-cell biology,T-cell / mechanistic literature,—,—,"1,25(OH)2D3 / VDR",—,—,—,"VDR expression, T-cell development, differentiation, effector function",—,Summarizes VDR regulation and its role in T-cell development and effector function.,—,Mechanistic Review,Review; use primary studies for specific clinical claims.,23785369,10.3389/fimmu.2013.00148,https://pubmed.ncbi.nlm.nih.gov/23785369/,T-cell mechanism background.
R10,"Kamen & Tangpricha, 2010",2010,"Journal of molecular medicine (Berlin, Germany)",Major Review,Narrative review,Innate/adaptive immunity,Human/experimental literature,—,—,Vitamin D,—,—,—,"Macrophages, antimicrobial peptides, dendritic cells, T/B cells",—,Summarizes immunomodulatory effects including antimicrobial peptide induction and adaptive immune regulation.,—,Mechanistic Review,Review-level evidence.,20119827,10.1007/s00109-010-0590-9,https://pubmed.ncbi.nlm.nih.gov/20119827/,General immune mechanism background.
R11,"Carlberg & Velleuer, 2024",2024,Nutrients,Major Review,Narrative mechanistic review,Immune aging,Human immune aging / molecular literature,—,—,"Vitamin D3 / 1,25(OH)2D3 / VDR",—,—,—,"VDR epigenome/transcriptome, myeloid cells, immunocompetence",Healthy aging / disease context,Proposes a central role for VDR-dependent immune-cell programming in immunocompetence and aging.,—,Mechanistic / Aging Review,Conceptual review; does not establish that supplementation reverses immunosenescence.,38337682,10.3390/nu16030398,https://pubmed.ncbi.nlm.nih.gov/38337682/,"Immune-aging context; supports mechanistic discussion, not rejuvenation claims."
M01,"Liu et al., 2006",2006,Science,Human cell / mechanistic study,Laboratory experiments in human macrophages,Antimicrobial pathways,Human macrophages; ex vivo / in vitro,Not a clinical trial,Serum-dependent experiments,Vitamin D metabolites,Laboratory conditions,Laboratory experiments,Experimental control conditions,"TLR activation, VDR, CYP27B1, cathelicidin and intracellular mycobacterial killing",No clinical infection-prevention endpoint,TLR activation induced a vitamin-D-dependent antimicrobial pathway in human macrophages.,Mechanistic experiments; not a supplementation trial.,Mechanistically Positive,"Cell experiments establish a pathway, not that supplements prevent tuberculosis or respiratory infections in people.",16497887,10.1126/science.1123933,https://pubmed.ncbi.nlm.nih.gov/16497887/,Primary human-cell evidence underlying the mechanism explanation.