Table 1.
Characteristics of the 25 eligible trials and their participants
| Reference | Setting (study duration) | Participants (male:female) | Mean (SD) age, years (range) | 25(OH)D | No in intervention:control group | Oral dose of vitamin D3 | ARTI | No entering primary analysis/No randomised (%) | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Assay, EQA scheme | Mean (SD) baseline level, nmol/L (range) | Baseline level <25 nmol/L (%) | Definition | Outcome type | |||||||
| Li-Ng 200941 | USA (3 months) | Healthy adults (34:128) | 57.9 (13.6) (21.4-80.6) | RIA (DiaSorin), DEQAS | 63.7 (25.5) (16.0-156.0) | 3/150 (2.0) | 84:78 | 50 µg daily, placebo | URTI: ≥2 URTI symptoms in absence of allergy symptoms | Primary | 157/162 (96.9) |
| Urashima 201027 | Japan (4 months) | Schoolchildren (242:188) | 10.2 (2.3) (6.0-15.0) | -- | ND | -- | 217:213 | 30 µg daily, placebo | URTI: influenza A/B diagnosed by RIDT or RIDT-negative ILI | Primary | 334/430 (77.7) |
| Manaseki-Holland 201042 | Afghanistan (3 months) | Preschool children with pneumonia (257:196) | 1.1 (0.8) (0.1-3.3) | -- | ND | -- | 224:229 | 2.5 mg bolus once, placebo | LRTI: repeat episode of pneumonia—age-specific tachypnoea without wheeze | Secondary | 453/453 (100.0) |
| Laaksi 201037 | Finland (6 months) | Military conscripts (164:0) | 19.1 (0.6) (18.0-21.0) | EIA (IDS OCTEIA) | 75.9 (18.7) (41.9-129.0) | 0/73 (0.0) | 80:84 | 10 µg daily, placebo | ARTI: medical record diagnosis | Primary | 164/164 (100.0) |
| Majak 201143 | Poland (6 months) | Children with asthma (32:16) | 10.9 (3.3) (6.0-17.0) | RIA (BioSource Europe), RIQAS | 88.9 (38.2) (31.5-184.7) | 0/48 (0.0) | 24:24 | 12.5 µg daily, placebo | ARTI: self report | Secondary | 48/48 (100.0) |
| Trilok-Kumar 201144 | India (6 months) | Low birthweight infants (970:1109) | 0.1 (0.0) (0.0-0.3) | -- | ND | ND | 1039:1040 | 35 µg weekly, placebo | ARTI: medical record diagnosis of events resulting in hospital admission | Secondary | 2064/2079 (99.3) |
| Lehouck 201215 | Belgium (1 year) | Adults with COPD (145:37) | 67.9 (8.3) (48.0-86.0) | RIA (Diasorin), DEQAS | 49.8 (29.2) (9.0-159.7) | 31/182 (17.0) | 91:91 | 2.5 mg bolus monthly, placebo | URTI: self report | Secondary | 175/182 (96.2) |
| Manaseki-Holland 201235 | Afghanistan (1.5 years) | Infants (1591:1455) | 0.5 (0.3) (0.0-1.0) | -- | ND | ND | 1524:1522 | 2.5 mg bolus 3-monthly, placebo | LRTI: pneumonia confirmed by chest radiography | Primary | 3011/3046 (98.9) |
| Camargo 201221 | Mongolia (7 weeks) | 3rd/4th grade schoolchildren (129:118) | 10.0 (0.9) (7.0-12.7) | LC-MS/MS, DEQAS | 18.9 (9.7) (3.3-61.2) | 192/245 (78.4) | 143:104 | 7.5 µg daily, placebo | ARTI: parent reported “chest infections or colds” | Secondary | 244/247 (98.8) |
| Murdoch 201222 | New Zealand (1.5 years) | Healthy adults (81:241) | 48.1 (9.7) (18.0-67.6) | LC-MS/MS, DEQAS | 72.1 (22.1) (13.0-142.0) | 5/322 (1.6) | 161:161 | 2×5 mg bolus monthly then 2.5 mg bolus monthly, placebo | URTI: assessed with symptom score | Primary | 322/322 (100.0) |
| Bergman 201245 | Sweden (1 year) | Adults with increased susceptibility to ARTI (38:102) | 53.1 (13.1) (20.0-77.0) | CLA (DiaSorin), DEQAS | 49.3 (23.2) (8.0-135.0) | 15/131 (11.45) | 70:70 | 100 µg daily, placebo | URTI: assessed with symptom score | Secondary | 124/140 (88.6) |
| Marchisio 201346 | Italy (6 months) | Children with recurrent acute otitis media (64:52) | 2.8 (1.0) (1.3-4.8) | CLA (DiaSorin), ISO9001 | 65.3 (17.3) (24.7-120.6) | 2/116 (1.7) | 58:58 | 25 µg daily, placebo | URTI: doctor diagnosed acute otitis media | Primary | 116/116 (100.0) |
| Rees 201323 | USA (13 months, average) | Adults with previous colorectal adenoma (438:321*) | 61.2 (6.6) (47.1-77.9) | RIA (IDS), DEQAS | 62.5 (21.3) (30.2-171.6) | 0/759 (0.0) | 399:360 | 25 µg daily, placebo | URTI: assessed from daily symptom diary | Secondary | 759/759 (100.0) |
| Tran 201425 | Australia (1 year) | Healthy older adults (343:301) | 71.7 (6.9) (60.3-85.2) | CLA (DiaSorin), DEQAS | 41.7 (13.5) (12.6-105.0) | 66/643 (10.3) | 430:214 | 0.75 mg bolus v 1.5 mg bolus monthly, placebo | URTI: self reported cold | Secondary | 594/644 (92.2) |
| Goodall 201447 | Canada (8 weeks) | Healthy university students (218:382) | 19.6 (2.2) (17.0-33.0) | -- | ND | -- | 300:300 | 0.25 mg weekly (factorial with gargling), placebo | URTI: self reported cold | Primary | 492/600 (82.0) |
| Urashima 201426 | Japan (2 months) | High school students (162:85) | 16.5 (1.0) (15.0-18.0) | -- | ND | -- | 148:99 | 50 µg daily, placebo | URTI: influenza A diagnosed by RIDT or RIDT negative ILI | Primary | 247/247 (100.0) |
| Grant 201448 | New Zealand (9 months: 3 months in pregnancy + 6 months in infancy) | Pregnant women and offspring (0:260 (mothers) 121:128 (offspring)) | unborn | LC-MS/MS, DEQAS | 54.8 (25.8) (8.0-128.0) | 30/200 (15.0) | 173:87 (mothers) 164:85 (offspring) | Mothers: 25 µg v 50 µg daily Infants: 10 µg v 20 µg daily, placebo | ARTI: doctor diagnosed ARTI precipitating primary care consultation | Secondary | 236/260 (90.8) |
| Martineau 2015a16 (ViDiCO) | UK (1 year) | Adults with COPD (144:96) | 64.7 (8.5) (40.0-85.0) | LC-MS/MS, DEQAS | 46.1 (25.7) (0.0-160.0) | 50/240 (20.8) | 122:118 | 3 mg bolus 2-monthly, placebo | URTI: assessed from daily symptom diary | Coprimary | 240/240 (100.0) |
| Martineau 2015b49 (ViDiAs) | UK (1 year) | Adults with asthma (109:141) | 47.9 (14.4) (16.0-78.0) | LC-MS/MS, DEQAS | 49.6 (24.7) (0.0-139.0) | 36/250 (14.4) | 125:125 | 3 mg bolus 2-monthly, placebo | URTI: assessed from daily symptom diary | Coprimary | 250/250 (100.0) |
| Martineau 2015c50 (ViDiFlu) | UK (1 year) | Older adults and their carers (82:158) | 67.1 (13.0) (21.4-94.0) | LC-MS/MS, DEQAS | 42.9 (23.0) (0.0-128.0) | 60/240 (25.0) | 137:103 | Older adults: 2.4 mg bolus 2-monthly+10 µg daily. Carers: 3 mg 2-monthly, older adults: placebo+10 µg daily. Carers: placebo | URTI and LRTI, both assessed from daily symptom diary | Coprimary | 240/240 (100.0) |
| Simpson 201551 | Australia (17 weeks) | Healthy adults (14:20) | 32.2 (12.2) (18.0-52.0) | LC-MS/MS, DEQAS | 67.9 (23.0) (32.0-132.0) | 0/33 (0.0) | 18:16 | 0.5 mg weekly, placebo | ARTI assessed with symptom score | Primary | 34/34 (100.0) |
| Dubnov-Raz 201536 | Israel (12 weeks) | Adolescent swimmers with vitamin D insufficiency (34:20) | 15.2 (1.6) (12.9-18.6) | RIA (DiaSorin), DEQAS | 60.4 (11.9) (28.0-74.6) | 0/54 (0.0) | 27:27 | 50 µg daily, placebo | URTI assessed with symptom score | Primary | 25/54 (46.3) |
| Denlinger 201652 | USA (28 weeks) | Adults with asthma (130:278) | 39.2 (12.9) (18.0-85.0) | CLA (DiaSorin), VDSP | 47.0 (16.9) (10.0-74.6) | 55/408 (13.5) | 201:207 | 2.5 mg bolus then 100 µg daily, placebo | URTI assessed with symptom score | Secondary | 408/408 (100.0) |
| Tachimoto 201624 | Japan (6 months) | Children with asthma (50:39) | 9.9 (2.3) (6.0-15.0) | RIA (DiaSorin), CAP | 74.9 (24.6) (20.0-187.2) | 1/89 (1.1) | 54:35 | 20 µg daily, first 2 months, placebo | URTI: assessed with symptom score | Secondary | 89/89 (100.0) |
| Ginde, 201653 | USA (1 year) | Older care home residents (45:62) | 80.7 (9.9) (60.0-95.0) | LC-MS/MS, VDSP | 57.3 (22.7) (11.7-106.1) | 12/107 (11.2) | 55:52 | 2.5 mg bolus monthly+≤25 µg per day equivalent, placebo+10-25 µg per day equivalent | ARTI: medical record diagnosis | Primary | 107/107 (100.0) |
25(OH)D=25-hydroxyvitamin D; RIDT=rapid influenza diagnostic test; COPD=chronic obstructive pulmonary disease; D3, vitamin D3 (cholecalciferol); ARTI=acute respiratory tract infection; CAP=College of American Pathologists; CLA=chemiluminescent assay; DEQAS=Vitamin D External Quality Assessment Scheme; EIA=enzyme immunoassay; EQA=external quality assessment; LC-MS/MS=liquid chromatography tandem-mass spectrometry; RIA=radioimmunoassay; URTI=upper respiratory tract infection; LRTI=lower respiratory tract infection; ILI=influenza-like illness; RIQAS=Randox International Quality Assessment Scheme; VDSP=Vitamin D Standardisation Program of the Office of Dietary Supplements, National Institutes of Health, USA.
1 µg vitamin D3=40 international units (IU); 25(OH)D concentrations reported in ng/mL were converted to nmol/L (multiplying by 2.496)
*Sex missing for two participants randomised to intervention arm and subsequently excluded from analysis owing to lack of outcome data.