. 2024 Aug 14;23:92. doi: 10.1186/s12937-024-00990-w

Table 1.

Main characteristics of the included studies and their participants

Author name, publication year	Number of participants in intervention and control groups^a	Participants (male %); mean age at baseline in years (age range of inclusion)	Disease specific population	Mean baseline 25(OH)D levels, nmol/L (SD) Percentage of participants with 25(OH)D deficiency (%) with study definition	Oral dose of vitamin D3 in the intervention group (IU) [average daily dose (IU/day)]	Mean 25(OH)D levels after intervention nmol/L (SD)	Country, city Climatic zone	Trial duration Season (from-to)	ARI definition	ARI outcome
Li-Ng et al., 2009 [28]	Intervention = 84 Control = 78	162 (male 21.0%) 57.9 (18–80 years)	No	Intervention 64.3 (25,4) Control 63.0 (25,8) NR	2,000 IU daily vs placebo [2,000 IU/day]	88.5 (23,2)	USA, New York, Temperate	3 Months Winter-Spring	URI: ≥ 2 symptoms and absence of allergy symptoms	Primary
Laaski et al., 2010 [29]	Intervention = 80 Control = 84	164 (male 100%) 19.1 (18–28 years)	No	Intervention 78.7 (14.9) Control 74.4 (20.8) NR	400 IU daily vs placebo [400 IU/day]	71.6 (22.9)	Finland, Huovinrinne, Temperate	6 Months Autumn–Winter	ARI: any acute respiratory tract infection recorded in medical records	Primary
Manaseki-Holland et al., 2010 [30]	Intervention = 224 Control = 229	453 (male 56.7%) 1.1 (1–36 months)	Pneumonia	NM	100,000 IU bolus once vs placebo [1,111 IU/day]	NM	Afghanistan, Kabul, Temperate	3 Months Winter-Spring	LRI: repeat episode of pneumonia (age-specific tachypnoea + no wheeze)	Secondary
Urashima et al., 2010 [31]	Intervention = 217 Control = 213	430 (male 56.3%) 10.2 (6–15 years)	No	NM	1,200 IU daily vs placebo [1,200 IU/day]	NM	Japan, NA, Temperate	4 Months Winter-Spring	URI: RIDT-positive influenza A or B or RIDT- negative influenza like illness	Primary + Secondary
Kumar et al., 2011 [32]	Intervention = 1039 Control = 1040	2079 (male 46.7%) 0.1 (0–48 h)	Low birthweight term infants	NM	1,400 IU weekly vs placebo [200 IU/day]	55.0 (22.5)	India, New Delhi, Temperate	6 Months All year	ARI: episodes leading to hospital admission obtained from medical record	Secondary
Majak et al., 2011 [33]	Intervention = 24 Control = 24	48 (male 50.0%) 10.9 (5–18 years)	Asthma and allergy	Intervention 90.1 (34.7) Control 87.6 (42.2) NR	500 IU daily vs placebo [500 IU/day]	93.9 (32.7)	Poland, Lodz, Temperate	6 Months Autumn-Spring	ARI: self-reported symptoms	Secondary
Bergman et al., 2012 [34]	Intervention = 70 Control = 70	140 (male 27.1%) 53.1 (18–75 years)	Susceptibility to respiratory infections	Intervention 51.5 (NR) Control 46.9 (NR) NR	4,000 IU daily vs placebo [4000 IU/day]	133.4 (NR)	Sweden, Flemingsburg Temperate	12 Months All year	ARI: assessed with questionnaire	Secondary
Camargo et al., 2012 [35]	Intervention = 143 Control = 104	247 (male 52.2%) 10.0 (NR)	No	Intervention 18.0 (3.6) Control 17.1 (3.8) 245/247 (99.2%) (serum 25(OH)D < 50 nmol/L)	300 IU daily vs placebo [300 IU/day]	49.1 (15,1)	Mongolia, Ulaanbaatar, Temperate	7 Weeks Winter-Spring	ARI: parent- reported symptomatic chest infections or colds lasting ≥ 24 h	Secondary
Lehouck et al., 2012 [36]	Intervention = 91; Control = 91	182 (79.7%) 67.9 (> 50 years)	COPD	Intervention 49.9 (30.0) Control 49.9 (27.5) 30/182 (16,5%) (serum 25(OH)D < 25 nmol/L)	100,000 IU bolus monthly vs placebo [3571 IU/day]	128.8 (44.7)	Belgium, Leuven, Temperate	12 Months All year	LRI: self-reported episodes	Secondary
Manaseki- Holland et al., 2012 [37]	Intervention = 1524 Control = 1522	3046 (male 52.2%) 0.5 (1–11 months)	No	NM	100,000 IU bolus every 3 months vs placebo [1111 IU/day]	32.7 (17.1)	Afghanistan, Kabul, Temperate	18 Months All year	LRI: radiologically confirmed pneumonia	Primary
Murdoch et al., 2012 [38]	Intervention = 161 Control = 161	322 (male 25,2%) 48.1 (> 18 years)	No	Intervention 72.4 (22.5) Control 69.9 (22.5) 5/322 (1.6%) (serum 25(OH)D < 25 nmol/L)	200,000 IU bolus every 2 months then 100.000 IU bolus monthly vs placebo [3704 IU/day]	123.6 (27,5)	New Zealand, Christchurch, Temperate	18 Months All year	URI: assessed with questionnaire	Primary
Marchisio et al., 2013 [39]	Intervention = 58 Control = 58	116 (male 55.2%) 2.8 (1–5 years)	History of repeated acute otitis media	Intervention 90.4 (21.2) Control 46.7 (17.7) NR	1,000 IU daily vs placebo [1000 IU/day]	114.6 (19.5)	Italy, Milan, Temperate	6 Months Winter-Spring	URI: doctor diagnosed acute otitis media episodes	Primary
Rees et al., 2013 [40]	Intervention = 401 Control = 360	759 (male 57.7%) 61.2 (45–75 years)	Previous colorectal adenoma (removed)	Intervention 61.9 (20.7) Control 63.2 (22.0) 0 (no definition provided)	1,000 IU daily vs placebo [1000 IU/day]	186.9 (455.1)	USA, NA Temperate	13 Months All year	URI: assessed from patient’s diary	Secondary
Goodall et al., 2014 [41]	Intervention = 300 Control = 300	600 (male 36.3%) 19.6 (> 17 years)	No	NM	10,000 IU weekly vs placebo [1429 IU/day]	NM	Canada, Hamilton, Temperate	8 Weeks Autumn	URI: self-reported symptomatic cold	Primary
Grant et al., 2014 [42]	Intervention Group 1 = 87 Group 2 = 86 Control = 87	249 (male 48.6%) unborn at baseline	No	NR	Group 1: 400 IU Group 2: 800 IU daily vs placebo [G1: 400 IU/day] [G2: 800 IU/day]	Group 1 85.2 (34.7) Group 2 101.1 (46.8)	New Zealand, Auckland, Temperate	6 Months All year	ARI: doctor diagnosed ARI during primary care visits	Secondary
Tran et al., 2014 [43]	Intervention Group 1 = 215 Group 2 = 215 Control = 214	644 (male 53.3%) 71.7 (60–84 years)	No	Group 1: 41.5 (12.8) Group 2: 41.5 (14.1) Control 41.9 (13.2) 61/620 (9.8%) (serum 25(OH)D < 25 nmol/L)	Group 1:30,000 IU Group 2:60,000 IU bolus monthly vs placebo [G1: 1000 IU/day] [G2: 2000 IU/day]	Group 1 64.0 (16.8) Group 2 77.9 (19.9)	Australia, Queensland, New South Wales, Victoria, Tasmania Temperate	12 Months All year	URI: assessed with questionnaire and medical records	Secondary
Urashima et al., 2014 [44]	Intervention = 148 Control = 99	247 (male 65.6%) 16.5 (15–18 years)	No	NM	2,000 IU daily vs placebo [2000 IU/day]	NM	Japan, Tokyo, Temperate	2 Months Winter	URI: RIDT-positive influenza A or RIDT- negative influenza like illness	Primary
Dubnov-Raz et al., 2015 [45]	Intervention = 28 Control = 27	54 (male 63%) 15·2 (12–21 years)	No	Intervention 60.7 (12.2) Control 60.9 (11.7) 11/54 (20.4%) (serum 25(OH)D < 50 nmol/L)	2,000 IU daily vs placebo [2000 IU/day]	74.6 (16.2)	Israel, Petah-Tikva, Temperate	3 Months Winter	URI: assessed with symptom score	Primary
Martineau et al., 2015, ViDiAs Trial, [46]	Intervention = 125 Control = 125	250 (male 43.6%) 47.9 (16–78 years)	Asthma	Intervention 49.8 (25.2) Control 49.4 (24.2) 36/250 (14·4%) (serum 25(OH)D < 25 nmol/L)	120,000 IU bolus once every 2 months vs placebo [2000 IU/day]	69.4 (21.0)	England, London, Temperate	12 Months All year	URI: assessed from daily symptom scores diary	Coprimary
Martineau et al., 2015, ViDiCO Trial, [47]	Intervention = 122 Control = 118	240 (male 60%) 64.7 (> 40 years)	COPD	Intervention 45.4 (27.9) Control 46.7 (23.3) 50/240 (20.8%) (serum 25(OH)D < 25 nmol/L)	120,000 IU bolus every 2 months vs placebo [2000 IU/day]	67.4 (27.5)	England, London, Temperate	12 Months All year	URI: assessed from patient’s diary	Coprimary
Martineau et al., 2015, ViDiFlu Trial [48]	Intervention = 137 Control = 103	240 (male 34.2%) 67.1 (21.4–94.0 years)	No	Intervention 42.4 (23.4) Control 43.6 (22.6) 60/240 (25%) (serum 25(OH)D < 25 nmol/L)	Resident: 96,000 IU bolus every 2 months + 400 IU daily; Carers: 120,000 IU bolus every 2 months vs controls [2000 IU/day]^d	82.8 (4.4)	England, London, Temperate	12 Months All year	URI and LRI: both assessed from daily symptom diary	Primary + Secondary
Simpson et al., 2015 [49]	Intervention = 18 Control = 16	34 (male 41.2%) 32.2 (18–52 years)	No	Intervention 60.5 (13.9) Control 76.4 (27.3) 8/34 (23.5%) (serum 25(OH)D < 50 nmol/L) 4/34 (11.8%) (serum 25(OH)D < 40 nmol/L)	20,000 IU weekly vs placebo [2857 IU/day]	100.7 (23.9)	Australia, Hobart, Temperate	17 Weeks Autumn-Spring	ARI: assessed with symptom score	Primary
Denlinger et al., 2016 [50]	Intervention = 201 Control = 207	408 (male 31.9%) 39.2 (18–85 years)	Asthma	Intervention 45.1 (12.5) Control 49.2 (12.5) 111/203 (54.7%) (serum 25(OH)D < 50 nmol/L)	Once 100,000 IU bolus, then 4,000 IU daily vs placebo [4000 IU/day]	104.6 (4.5)	USA, NA, Temperate	7 Months Winter-Summer	URI: assessed with symptom score	Secondary
Gupta et al., 2016 [51]	Intervention = 162 Control = 162	324 (male 69.8%) 1.4 (0.5–5 years)	Severe pneumonia	Intervention 35.9 (19.5) Control 38.2 (19.1) 126/324 (38.9%) (serum 25(OH)D < 30 nmol/L)	One 100,000 IU bolus vs placebo [556 IU/day]	NA	India, New Delhi, Temperate	6 Months All year	ARI: physician confirmed recurrent pneumonia	Coprimary
Aglipay et al., 2017 [52]	Intervention = 349 Control = 354	703 (male 57.5%) 2.7 (1–5 years)	No	Intervention 89.6 (30.7) Control 92.1 (29.2) NM	2,000 IU daily vs 400 IU daily [2000 IU/day]	121.6 (4.5)	Canada, Toronto, Temperate	4–8 Months Autumn-Spring	URI: laboratory confirmed	Primary
Ginde et al., 2017 [53]	Intervention = 55 Control = 52	107 (male 42.1%) 80.7 (60–95 years)	No	Intervention 57.4 (21.0) Control 57.4 (24.7) 37/107 (34.6%) (serum 25(OH)D < 50 nmol/L)	100,000 IU bolus monthly vs 12,000 IU bolus monthly (or Placebo + 400–1,000 IU per day equivalent) [3333 IU/day]	81.4	USA, Aurora, Temperate	12 Months All year	ARI: medical record diagnosis by nurse or physician assessment and/or new prescribed treatment	Primary
Hibbs et al., 2018 [54]	Intervention = 153 Control = 147	300 (male 55.3%)^b unborn at baseline	No	Intervention 47.7 (NR) Control 52.4 (NR)^c 0% (serum 25(OH)D < 25 nmol/L)	400 IU daily vs placebo [400 IU/day]	NA	USA, Cleveland, Temperate	12 Months All year	ARI: self-reported URI or LRI, assessed by questionnaire	Secondary
Lee et al., 2018 [55]	Intervention = 31 Control = 31	62 (male 48.4%) 9.9 (3–20 years)	Sickle cell disease	Intervention 37.4 (17.5) Control 33.9 (15.5) 48/62 (77.4%) (serum 25(OH)D < 50 nmol/L)	100,000 IU bolus monthly vs 12,000 IU bolus monthly [3333 IU/day]	90.1 (NM)	USA, New York, Temperate	24 Months All year	Self-reported respiratory events, including ARI	Primary
Rosendhal et al., 2018 [56]	Intervention = 492 Control = 495	987 (male 50.2%) unborn at baseline	No	Intervention 81.3 (24.0) Control 81.7 (27.8) 41/955 (4.3%) (serum 25(OH)D < 50 nmol/L)	1,200 IU daily vs 400 IU daily [1200 IU/day]	117.7(26.1)	Finland, Helsinki, Temperate	24 Months All year	Parent-reported infections, including ARI	Coprimary
Shimizu et al., 2018 [57]	Intervention = 126 Control = 126	252 (male 32.5%) 53.1 (45–74 years)	No	Intervention 49.2 (13.8) Control 48.9 (13.0) 121/215 (56.3%) (serum 25(OH)D < 50 nmol/L)	400 IU daily vs placebo [400 IU/day]	114.6 (32.7)	Japan, Tokyo, Yokohama, Temperate	4 Months Winter-Summer	ARI: self-reported assessed by questionnaire	Primary
Aloia et al., 2019 [58]	Intervention = 130 Control = 130	260 (male 0%) 68.2 (65.4–72.5 years)	No	Intervention 53.7 (16.2) Control 55.4 (17.2) NM	2,000 IU daily vs placebo [2000 IU/day]	117.3 (28.0)	USA, New York, Temperate	3 Months All year	ARI: self-reported common cold or influenza	Secondary
Arihiro et al., 2019 [59]	Intervention = 119 Control = 118	237 (male 61.6%) 44.7 (18–80 years)	Ulcerative Colitis or Crohn’s Disease	Intervention 57.4 (18.2) Control 59.7 (25.5) 77/223 (34.5%) (serum 25(OH)D < 50 nmol/L)	500 IU daily vs placebo [500 IU/day]	80.4 (NR)	Japan, Tokyo, Temperate	6 Months Winter-Spring	ARI: laboratory confirmed influenza, URI: diagnosed by clinician	Primary + Secondary
Hauger et al., 2019 [60]	Intervention Group 1 = 44 Group 2 = 43 Control = 43	130 (male 46.9%) 6.7 (4–8 years)	No	Group 1: 56.9 (12.7) Group 2: 58.1 (13.5) Control 55.2 (10.8) NM	Group 1: 400 IU Group 2: 800 IU daily vs placebo [G1: 400 IU/day] [G2: 800 IU/day]	Group 1 61.8 (10.6) Group 2 75.8 (11.5)	Denmark, Copenhagen, Temperate	5 Months Autumn-Spring	ARI: self-reported	Secondary
Loeb et al., 2019 [61]	Intervention = 650 Control = 650	1300 (male 47.8%) 8.5 (3–17 years)	No	Intervention 65.7 (16.7) Control 65.2 (16.9) 6/1300 (0.5%) (serum 25(OH)D < 25 nmol/L)	14,000 IU weekly vs placebo [2000 IU/day]	91.8 (23.6)	Vietnam, Hanoi, Tropical	8 Months All year	ARI: RT-PCR confirmed influenza A or B	Primary
Bischop-Ferrari et al., 2020 [62]	Intervention = 1076 Control = 1081	2157 (male 38.3%) 74.9 (70–95 years)	No	Intervention 55.9 (21.0) Control 55.9 (21.2) 241/2140 (11.3%) (serum 25(OH)D < 30 nmol/L)	2,000 IU daily vs placebo [2000 IU/day]^e	93.9 (NR)	Switzerland, France, Austria, Germany, Portugal, NA, Temperate	3 Years All year	ARI: self-reported and verified by independent physician	Coprimary
Camargo et al., 2020 [63]	Intervention = 2558 Control = 2552	5056 (male 58%) 66.4 (50–84)	No	Intervention 63.7 (23.6) Control 63.0 (23.5) 89/5056 (2.0%) (serum 25(OH)D < 25 nmol/L)	200,000 IU bolus followed by a monthly 100, 000 IU vs placebo, [3300 IU/day]	135 (NA)	New Zealand, NA, Temperate	3 Years All year	Self-reported: cold, runny nose, sore throat, flu-like illness, or chest infection	Secondary
Ganmaa et al., 2020 [64]	Intervention = 4418 Control = 4433	8851 (male 51%) 9.4 (6–13)	No	Intervention 29.7 (10.5) Control 29.7 (10.5) 2813/8846 (31.8%) (serum 25(OH)D < 25 nmol/L)	14,000 IU weekly vs placebo, [2000 IU/day]	77.4 (22.7)	Mongolia, Ulaanbaatar, Temperate	3 Years All year	Self-reported	Secondary
Mandlik et al., 2020 [65]	Intervention = 135 Control = 150	244 (male 53%) 8.0 (6–12)	No	Intervention 60.2 (11.9) Control 57.7 (10.0) NA	1,000 IU daily vs placebo, [1000 IU/day]	80.0 (23.3)	India, Pune, Tropical	6 Months Summer–Winter	Self-reported	Primary
Rake et al., 2020 [66]	Intervention = 395 Control = 392	787 (male NA) NA (65–84)	No	NA 127/781 (16.3%) (serum 25(OH)D < 25 nmol/L)	100,000 IU bolus monthly vs placebo, [3300 IU/day]	109.2 (NR)	England, NA, Temperate	2 Years All year	Reported by general practitioner	Secondary
Jadhav et al., 2021 [67]	Intervention = 155 Control = 155	298 (male 61.3%) 3.0 (1–5)	Recurrent ARI	NM	120,000 IU bolus vs placebo [667 IU/day]	NM	India, Karad, Tropical	6 Months All year	ARI: self-reported	Primary
Pham et al., 2021 [68]	Intervention = 8000 Control = 8000	15,373 (male 54.3%) NA 60–84)	No	NM	60,000 IU bolus monthly vs placebo, [2000 IU/day]	114.8 (30.0)	Australia, NA, Temperate	5 Years All year	Self-reported: cold, runny nose, sore throat, the flu	Secondary
Huang et al., 2022 [69]	Intervention = 135 Control = 113	248 (male 69.3%) 3.9 (2–5)	No	NM	2000 IU daily vs placebo [2000 IU/day]	NM	Taiwan, North and South, Temperate + Tropical	6 Months All year	ARI: lab-confirmed influenza illness	Primary
Villasis-Keever et al., 2022 [70]	Intervention = 161 Control = 160	321 (male 30%) 37.5 (NR)	No	Intervention 18.3 (NR) Control 17.1 (NR)^c 215/321 (67.0%) (serum 25(OH)D < 50 nmol/L)	4000 IU daily vs placebo [4000 IU/day]	67.4 (NR)	Mexico, Mexico City, Tropical	45 Days Summer–Winter	ARI: positive laboratory result for SARS-CoV-2 infection	Primary

Author name, publication year

Number of participants in intervention and control groups^a

Participants (male %); mean age at baseline in years (age range of inclusion)

Disease specific population

Mean baseline 25(OH)D levels, nmol/L (SD)
Percentage of participants with 25(OH)D deficiency (%) with study definition

Oral dose of vitamin D3 in the intervention group (IU) [average daily dose (IU/day)]

Mean 25(OH)D levels after intervention nmol/L (SD)

Country, city
Climatic zone

Trial duration
Season
(from-to)

ARI definition

ARI outcome

Li-Ng et al.,

2009 [28]

Intervention = 84 Control = 78

162 (male 21.0%)

57.9 (18–80 years)

Intervention 64.3 (25,4)

Control 63.0 (25,8)

2,000 IU daily vs placebo

[2,000 IU/day]

88.5

(23,2)

USA, New York,

Temperate

3 Months

Winter-Spring

URI: ≥ 2 symptoms and absence of allergy symptoms

Primary

Laaski et al.,

2010 [29]

Intervention = 80 Control = 84

164 (male 100%)

19.1 (18–28 years)

Intervention 78.7 (14.9)

Control 74.4 (20.8)

400 IU daily vs placebo

[400 IU/day]

71.6

(22.9)

Finland, Huovinrinne,

Temperate

6 Months

Autumn–Winter

ARI: any acute respiratory tract infection recorded in medical records

Primary

Manaseki-Holland et al.,

2010 [30]

Intervention = 224 Control = 229

453 (male 56.7%)

1.1 (1–36 months)

Pneumonia

100,000 IU bolus once vs placebo [1,111 IU/day]

Afghanistan, Kabul,

Temperate

3 Months

Winter-Spring

LRI: repeat episode of pneumonia (age-specific tachypnoea + no wheeze)

Secondary

Urashima et al., 2010 [31]

Intervention = 217 Control = 213

430 (male 56.3%)

10.2 (6–15 years)

1,200 IU daily vs placebo

[1,200 IU/day]

Japan, NA,

Temperate

4 Months

Winter-Spring

URI: RIDT-positive influenza A or B or RIDT- negative influenza like illness

Primary

Secondary

Kumar et al.,

2011 [32]

Intervention = 1039

Control = 1040

2079 (male 46.7%)

0.1 (0–48 h)

Low birthweight term infants

1,400 IU weekly vs placebo [200 IU/day]

55.0

(22.5)

India, New Delhi,

Temperate

6 Months

All year

ARI: episodes leading to hospital admission obtained from medical record

Secondary

Majak et al.,

2011 [33]

Intervention = 24 Control = 24

48 (male 50.0%)

10.9 (5–18 years)

Asthma and allergy

Intervention 90.1 (34.7)

Control 87.6 (42.2)

500 IU daily vs placebo

[500 IU/day]

93.9

(32.7)

Poland, Lodz,

Temperate

6 Months

Autumn-Spring

ARI: self-reported symptoms

Secondary

Bergman et al., 2012 [34]

Intervention = 70 Control = 70

140 (male 27.1%)

53.1 (18–75 years)

Susceptibility to respiratory infections

Intervention 51.5 (NR)

Control 46.9 (NR)

4,000 IU daily vs placebo

[4000 IU/day]

133.4

(NR)

Sweden, Flemingsburg

Temperate

12 Months

All year

ARI: assessed with questionnaire

Secondary

Camargo et al., 2012 [35]

Intervention = 143

Control = 104

247 (male 52.2%)

10.0 (NR)

Intervention 18.0 (3.6)

Control 17.1 (3.8)

245/247 (99.2%)

(serum 25(OH)D < 50 nmol/L)

300 IU daily vs placebo

[300 IU/day]

49.1

(15,1)

Mongolia, Ulaanbaatar,

Temperate

7 Weeks

Winter-Spring

ARI: parent- reported symptomatic chest infections or colds lasting ≥ 24 h

Secondary

Lehouck et al.,

2012 [36]

Intervention = 91; Control = 91

182 (79.7%)

67.9 (> 50 years)

COPD

Intervention 49.9 (30.0)

Control 49.9 (27.5)

30/182 (16,5%)

(serum 25(OH)D < 25 nmol/L)

100,000 IU bolus monthly vs placebo [3571 IU/day]

128.8

(44.7)

Belgium, Leuven,

Temperate

12 Months

All year

LRI: self-reported episodes

Secondary

Manaseki-

Holland et al.,

2012 [37]

Intervention = 1524 Control = 1522

3046 (male 52.2%)

0.5 (1–11 months)

100,000 IU bolus every 3 months vs placebo

[1111 IU/day]

32.7

(17.1)

Afghanistan, Kabul, Temperate

18 Months

All year

LRI: radiologically confirmed pneumonia

Primary

Murdoch et al., 2012 [38]

Intervention = 161

Control = 161

322 (male 25,2%)

48.1 (> 18 years)

Intervention 72.4 (22.5)

Control 69.9 (22.5)

5/322 (1.6%)

(serum 25(OH)D < 25 nmol/L)

200,000 IU bolus every 2 months then 100.000 IU bolus monthly vs placebo [3704 IU/day]

123.6

(27,5)

New Zealand, Christchurch,

Temperate

18 Months

All year

URI: assessed with questionnaire

Primary

Marchisio et al., 2013 [39]

Intervention = 58

Control = 58

116 (male 55.2%)

2.8 (1–5 years)

History of repeated acute otitis media

Intervention 90.4 (21.2)

Control 46.7 (17.7)

1,000 IU daily vs placebo

[1000 IU/day]

114.6

(19.5)

Italy, Milan,

Temperate

6 Months

Winter-Spring

URI: doctor diagnosed acute otitis media episodes

Primary

Rees et al.,

2013 [40]

Intervention = 401 Control = 360

759 (male 57.7%)

61.2 (45–75 years)

Previous colorectal adenoma (removed)

Intervention 61.9 (20.7)

Control 63.2 (22.0)

0 (no definition provided)

1,000 IU daily vs placebo

[1000 IU/day]

186.9

(455.1)

USA, NA

Temperate

13 Months

All year

URI: assessed from patient’s diary

Secondary

Goodall et al.,

2014 [41]

Intervention = 300 Control = 300

600 (male 36.3%)

19.6 (> 17 years)

10,000 IU weekly

vs placebo [1429 IU/day]

Canada, Hamilton,

Temperate

8 Weeks

Autumn

URI: self-reported symptomatic cold

Primary

Grant et al.,

2014 [42]

Intervention

Group 1 = 87

Group 2 = 86

Control = 87

249 (male 48.6%)

unborn at baseline

Group 1: 400 IU

Group 2: 800 IU

daily vs placebo

[G1: 400 IU/day]

[G2: 800 IU/day]

Group 1

85.2 (34.7)

Group 2

101.1 (46.8)

New Zealand, Auckland,

Temperate

6 Months

All year

ARI: doctor diagnosed ARI during primary care visits

Secondary

Tran et al.,

2014 [43]

Intervention

Group 1 = 215

Group 2 = 215

Control = 214

644 (male 53.3%)

71.7 (60–84 years)

Group 1: 41.5 (12.8)

Group 2: 41.5 (14.1)

Control 41.9 (13.2)

61/620 (9.8%)

(serum 25(OH)D < 25 nmol/L)

Group 1:30,000 IU

Group 2:60,000 IU

bolus monthly vs placebo

[G1: 1000 IU/day]

[G2: 2000 IU/day]

Group 1

64.0 (16.8)

Group 2

77.9 (19.9)

Australia, Queensland,

New South Wales, Victoria, Tasmania

Temperate

12 Months

All year

URI: assessed with questionnaire and medical records

Secondary

Urashima et al., 2014 [44]

Intervention = 148 Control = 99

247 (male 65.6%)

16.5 (15–18 years)

2,000 IU daily vs placebo

[2000 IU/day]

Japan, Tokyo,

Temperate

2 Months

Winter

URI: RIDT-positive influenza A or RIDT- negative influenza like illness

Primary

Dubnov-Raz et al., 2015 [45]

Intervention = 28

Control = 27

54 (male 63%)

15·2 (12–21 years)

Intervention 60.7 (12.2)

Control 60.9 (11.7)

11/54 (20.4%)

(serum 25(OH)D < 50 nmol/L)

2,000 IU daily vs placebo

[2000 IU/day]

74.6

(16.2)

Israel, Petah-Tikva,

Temperate

3 Months

Winter

URI: assessed with symptom score

Primary

Martineau et al., 2015, ViDiAs Trial, [46]

Intervention = 125

Control = 125

250 (male 43.6%)

47.9 (16–78 years)

Asthma

Intervention 49.8 (25.2)

Control 49.4 (24.2)

36/250 (14·4%)

(serum 25(OH)D < 25 nmol/L)

120,000 IU bolus once every 2 months

vs placebo [2000 IU/day]

69.4

(21.0)

England, London,

Temperate

12 Months

All year

URI: assessed from daily symptom scores diary

Coprimary

Martineau et al., 2015, ViDiCO Trial, [47]

Intervention = 122 Control = 118

240 (male 60%)

64.7 (> 40 years)

COPD

Intervention 45.4 (27.9)

Control 46.7 (23.3)

50/240 (20.8%)

(serum 25(OH)D < 25 nmol/L)

120,000 IU bolus every 2 months vs placebo

[2000 IU/day]

67.4

(27.5)

England, London,

Temperate

12 Months

All year

URI: assessed from patient’s diary

Coprimary

Martineau et al., 2015, ViDiFlu Trial [48]

Intervention = 137

Control = 103

240 (male 34.2%)

67.1 (21.4–94.0 years)

Intervention 42.4 (23.4)

Control 43.6 (22.6)

60/240 (25%)

(serum 25(OH)D < 25 nmol/L)

Resident: 96,000 IU bolus every 2 months + 400 IU daily; Carers: 120,000 IU bolus every 2 months vs controls [2000 IU/day]^d

82.8

(4.4)

England, London,

Temperate

12 Months

All year

URI and LRI: both assessed from daily symptom diary

Primary

+ Secondary

Simpson et al.,

2015 [49]

Intervention = 18

Control = 16

34 (male 41.2%)

32.2 (18–52 years)

Intervention 60.5 (13.9)

Control 76.4 (27.3)

8/34 (23.5%)

(serum 25(OH)D < 50 nmol/L)

4/34 (11.8%)

(serum 25(OH)D < 40 nmol/L)

20,000 IU weekly vs placebo [2857 IU/day]

100.7

(23.9)

Australia, Hobart,

Temperate

17 Weeks

Autumn-Spring

ARI: assessed with

symptom score

Primary

Denlinger et al., 2016 [50]

Intervention = 201

Control = 207

408 (male 31.9%)

39.2 (18–85 years)

Asthma

Intervention 45.1 (12.5)

Control 49.2 (12.5)

111/203 (54.7%)

(serum 25(OH)D < 50 nmol/L)

Once 100,000 IU bolus, then 4,000 IU daily vs placebo [4000 IU/day]

104.6

(4.5)

USA, NA,

Temperate

7 Months

Winter-Summer

URI: assessed with symptom score

Secondary

Gupta et al.,

2016 [51]

Intervention = 162

Control = 162

324 (male 69.8%)

1.4 (0.5–5 years)

Severe pneumonia

Intervention 35.9 (19.5)

Control 38.2 (19.1)

126/324 (38.9%)

(serum 25(OH)D < 30 nmol/L)

One 100,000 IU bolus vs placebo [556 IU/day]

India, New Delhi,

Temperate

6 Months

All year

ARI: physician

confirmed

recurrent

pneumonia

Coprimary

Aglipay et al.,

2017 [52]

Intervention = 349

Control = 354

703 (male 57.5%)

2.7 (1–5 years)

Intervention 89.6 (30.7)

Control 92.1 (29.2)

2,000 IU daily vs 400 IU daily [2000 IU/day]

121.6

(4.5)

Canada, Toronto,

Temperate

4–8 Months

Autumn-Spring

URI: laboratory

confirmed

Primary

Ginde et al.,

2017 [53]

Intervention = 55

Control = 52

107 (male 42.1%)

80.7 (60–95 years)

Intervention 57.4 (21.0)

Control 57.4 (24.7)

37/107 (34.6%)

(serum 25(OH)D < 50 nmol/L)

100,000 IU bolus monthly vs 12,000 IU bolus monthly

(or Placebo + 400–1,000 IU

per day equivalent)

[3333 IU/day]

81.4

USA, Aurora,

Temperate

12 Months

All year

ARI: medical record diagnosis by nurse or physician assessment and/or new prescribed treatment

Primary

Hibbs et al.,

2018 [54]

Intervention = 153

Control = 147

300 (male 55.3%)^b

unborn at baseline

Intervention 47.7 (NR)

Control 52.4 (NR)^c

(serum 25(OH)D < 25 nmol/L)

400 IU daily vs placebo

[400 IU/day]

USA, Cleveland,

Temperate

12 Months

All year

ARI: self-reported

URI or LRI, assessed by questionnaire

Secondary

Lee et al.,

2018 [55]

Intervention = 31

Control = 31

62 (male 48.4%)

9.9 (3–20 years)

Sickle cell disease

Intervention 37.4 (17.5)

Control 33.9 (15.5)

48/62 (77.4%)

(serum 25(OH)D < 50 nmol/L)

100,000 IU bolus monthly

vs 12,000 IU bolus monthly

[3333 IU/day]

90.1

(NM)

USA, New York,

Temperate

24 Months

All year

Self-reported

respiratory events,

including ARI

Primary

Rosendhal et al., 2018 [56]

Intervention = 492

Control = 495

987 (male 50.2%)

unborn at baseline

Intervention 81.3 (24.0)

Control 81.7 (27.8)

41/955 (4.3%)

(serum 25(OH)D < 50 nmol/L)

1,200 IU daily vs 400 IU daily [1200 IU/day]

117.7(26.1)

Finland, Helsinki,

Temperate

24 Months

All year

Parent-reported

infections,

including ARI

Coprimary

Shimizu et al.,

2018 [57]

Intervention = 126

Control = 126

252 (male 32.5%)

53.1 (45–74 years)

Intervention 49.2 (13.8)

Control 48.9 (13.0)

121/215 (56.3%)

(serum 25(OH)D < 50 nmol/L)

400 IU daily vs placebo

[400 IU/day]

114.6

(32.7)

Japan, Tokyo, Yokohama,

Temperate

4 Months

Winter-Summer

ARI: self-reported

assessed by questionnaire

Primary

Aloia et al.,

2019 [58]

Intervention = 130

Control = 130

260 (male 0%)

68.2 (65.4–72.5 years)

Intervention 53.7 (16.2)

Control 55.4 (17.2)

2,000 IU daily vs placebo

[2000 IU/day]

117.3

(28.0)

USA, New York,

Temperate

3 Months

All year

ARI: self-reported common cold or influenza

Secondary

Arihiro et al.,

2019 [59]

Intervention = 119

Control = 118

237 (male 61.6%)

44.7 (18–80 years)

Ulcerative Colitis or Crohn’s Disease

Intervention 57.4 (18.2)

Control 59.7 (25.5)

77/223 (34.5%)

(serum 25(OH)D < 50 nmol/L)

500 IU daily vs placebo

[500 IU/day]

80.4

(NR)

Japan, Tokyo,

Temperate

6 Months

Winter-Spring

ARI: laboratory confirmed influenza, URI: diagnosed by clinician

Primary + Secondary

Hauger et al.,

2019 [60]

Intervention

Group 1 = 44

Group 2 = 43

Control = 43

130 (male 46.9%)

6.7 (4–8 years)

Group 1: 56.9 (12.7)

Group 2: 58.1 (13.5)

Control 55.2 (10.8)

Group 1: 400 IU

Group 2: 800 IU

daily vs placebo

[G1: 400 IU/day]

[G2: 800 IU/day]

Group 1

61.8 (10.6)

Group 2

75.8 (11.5)

Denmark, Copenhagen,

Temperate

5 Months

Autumn-Spring

ARI: self-reported

Secondary

Loeb et al.,

2019 [61]

Intervention = 650

Control = 650

1300 (male 47.8%)

8.5 (3–17 years)

Intervention 65.7 (16.7)

Control 65.2 (16.9)

6/1300 (0.5%)

(serum 25(OH)D < 25 nmol/L)

14,000 IU weekly vs placebo [2000 IU/day]

91.8

(23.6)

Vietnam, Hanoi,

Tropical

8 Months

All year

ARI: RT-PCR

confirmed

influenza A or B

Primary

Bischop-Ferrari

et al.,

2020 [62]

Intervention = 1076

Control = 1081

2157 (male 38.3%)

74.9 (70–95 years)

Intervention 55.9 (21.0)

Control 55.9 (21.2)

241/2140 (11.3%)

(serum 25(OH)D < 30 nmol/L)

2,000 IU daily vs placebo

[2000 IU/day]^e

93.9

(NR)

Switzerland, France, Austria, Germany, Portugal, NA,

Temperate

3 Years

All year

ARI: self-reported

and verified by

independent

physician

Coprimary

Camargo et al.,

2020 [63]

Intervention = 2558

Control = 2552

5056 (male 58%)

66.4 (50–84)

Intervention 63.7 (23.6)

Control 63.0 (23.5)

89/5056 (2.0%)

(serum 25(OH)D < 25 nmol/L)

200,000 IU bolus followed by a monthly 100, 000 IU vs placebo, [3300 IU/day]

135

(NA)

New Zealand, NA,

Temperate

3 Years

All year

Self-reported: cold, runny nose, sore throat, flu-like illness, or chest infection

Secondary

Ganmaa et al.,

2020 [64]

Intervention = 4418

Control = 4433

8851 (male 51%)

9.4 (6–13)

Intervention 29.7 (10.5)

Control 29.7 (10.5)

2813/8846 (31.8%)

(serum 25(OH)D < 25 nmol/L)

14,000 IU weekly vs placebo, [2000 IU/day]

77.4

(22.7)

Mongolia, Ulaanbaatar,

Temperate

3 Years

All year

Self-reported

Secondary

Mandlik et al.,

2020 [65]

Intervention = 135

Control = 150

244 (male 53%)

8.0 (6–12)

Intervention 60.2 (11.9)

Control 57.7 (10.0)

1,000 IU daily vs placebo, [1000 IU/day]

80.0

(23.3)

India, Pune,

Tropical

6 Months

Summer–Winter

Self-reported

Primary

Rake et al.,

2020 [66]

Intervention = 395

Control = 392

787 (male NA)

NA (65–84)

127/781 (16.3%)

(serum 25(OH)D < 25 nmol/L)

100,000 IU bolus monthly vs placebo, [3300 IU/day]

109.2

(NR)

England, NA,

Temperate

2 Years

All year

Reported by general practitioner

Secondary

Jadhav et al.,

2021 [67]

Intervention = 155

Control = 155

298 (male 61.3%)

3.0 (1–5)

Recurrent ARI

120,000 IU bolus vs placebo [667 IU/day]

India, Karad, Tropical

6 Months

All year

ARI: self-reported

Primary

Pham et al.,

2021 [68]

Intervention = 8000

Control = 8000

15,373 (male 54.3%)

NA 60–84)

60,000 IU bolus monthly vs placebo, [2000 IU/day]

114.8

(30.0)

Australia, NA,

Temperate

5 Years

All year

Self-reported: cold, runny nose, sore throat, the flu

Secondary

Huang et al.,

2022 [69]

Intervention = 135

Control = 113

248 (male 69.3%)

3.9 (2–5)

2000 IU daily vs placebo

[2000 IU/day]

Taiwan, North and South,

Temperate + Tropical

6 Months

All year

ARI: lab-confirmed

influenza illness

Primary

Villasis-Keever

et al., 2022 [70]

Intervention = 161

Control = 160

321 (male 30%)

37.5 (NR)

Intervention 18.3 (NR)

Control 17.1 (NR)^c

215/321 (67.0%)

(serum 25(OH)D < 50 nmol/L)

4000 IU daily vs placebo

[4000 IU/day]

67.4

(NR)

Mexico, Mexico City,

Tropical

45 Days

Summer–Winter

ARI: positive laboratory result for

SARS-CoV-2 infection

Primary

25(OH)D 25-hydroxyvitamin D, ARI Acute respiratory infection, NA Not applicable, NM Not measured, NR Not reported, RIDT Rapid influenza diagnostic test, URI Upper respiratory infections

^aBased on the intention-to-treat original study number

^bSex was missing for one participant

^cReported the median with interquartile range, not the mean and standard deviation

^dControls: carers assumed placebo; residents assumed placebo + 400 IU of 25(OH)D

^eTrial design: Vitamin D (2 × 2 × 2 factorial with omega-3 fatty acid supplementation and strength training exercise)