Table 1 Characteristics of studies included in the meta-analysis
Study | Year | Study design | Country | Disease | Totle, CD/UC/control | Female, CD/UC/control | Matching or adjustment | Maturity (CD/UC/control) | Vitamin D assessment tool | Vitamin D deficiency definition (ng/mL for 25(OH)D, pg/mL 1,25(OH)2D) | Vitamin D supplementation | Quality score |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Driscoll [25] | 1982 | Case–control | US | CD | 82/–/40 | NR/–/NR | NR | > 18 | CPBA | Normal: 15.1–27.9 | Yes | 5 |
Harries [26] | 1985 | Case–control | Wales | CD and UC | 40/20/9 | 21/9/6 | NR | 38.75 ± 15.42/45 ± 17/– | RIA | NR | No | 5 |
Westarp [69] | 1987 | Case–control | Canada | CD | 39/–/64 | 25/–/37 | NR | 9.3 ± 0.3 | CPBA | NR | No | 5 |
Martin [70] | 1994 | Case–control | Italy | CD | 20/–/12 | 0/–/0 | Age | 38.8 ± 9.94/–/43 ± 14 | HPLC | NR | No | 6 |
Pollak [27] | 1998 | Case–control | Israel | CD and UC | 63/41/– | 23/21/– | Age, sex | 37.7 ± 14.5 (IBD)/34.6 ± 11.2 | RIA | Normal: 10–45 | No | 4 |
Gokhale [28] | 1998 | Case–control | US | CD and UC | 58/37/– | 22/17/– | NR | 14.3 ± 2.9/13.7 ± 3.5/– | CPBA | 25(OH)DNormal: 10–60; 1,25(OH)2DNormal (2–12 years): 10.8–90.2 | No | 5 |
Ardizzone [29] | 2000 | Case–control | Italy | CD and UC | 51/40/30 | 30/15/16 | Age, sex | 38.7 ± 13.2/34.4 ± 12.5/39.4 ± 11.6 | RIA | 25(OH)DNormal: 15–40; 1,25(OH)2DNormal: 14–50 | No | 7 |
Jahnsen [30] | 2002 | Cross-sectional | Norway | CD and UC | 60/60/– | 36/36/– | Age, sex | 36 ± 16.5/38 ± 13.5/– | HPLC + RIA | 25(OH)DNormal: 12–44; 1,25(OH)2DNormal: 19–56 | No | 7 |
Haderslev [31] | 2003 | Case–control | Denmark | CD and UC | 42/–/384 | 24/–/NR | NR | 50.3 ± 12.3 | RIA | Deficiency: < 15 | No | 4 |
Tajika [32] | 2004 | Case–control | Japan | CD and UC | 33/11/15 | 8/5/7 | Age, sex | 37.6 ± 7.5/47.6 ± 12.4/37.7 ± 10.0 | CPBA + RIA | 25(OH)DNormal: 10–55; deficiency: ≤ 10; 1,25(OH)2DNormal: 20–60 | No | 6 |
Duggan [33] | 2004 | Case–control | Ireland | CD | 44/–/44 | 29/–/29 | NR | 36.9 ± 11.1/–/36.7 ± 11.0 | ELISA | NR | 6.7 ± 5.1/6.7 ± 4.8 μg | 6 |
Abreu [34] | 2004 | Cohort | US | CD and UC | 138/29/96 | 63/12/NR | NR | 37.7 ± 1.1/38.1 ± 3.3/40.0 ± 1.0 | CPBA | Elevated 1,25(OH)2D: > 60; normal 1,25(OH)2D: < 60 | No | 6 |
McCarthy [35] | 2005 | Case–control | Ireland | CD | 44/–/44 | 29/–/29 | Age, sex | 36.9 ± 11.1/–/36.7 ± 11.1 | ELISA | Insufficiency: < 32; sufficiency: > 32; replete: > 20; mild deficiency: 10–20; moderate deficiency: 5–10; severe deficiency: < 5 | 2.5–20 μg/day | 6 |
Gilman [36] | 2006 | Cross-sectional | Ireland | CD and UC | 47/26/73 | NR/NR/NR | Age, sex | > 18 | ELISA | Deficiency: < 20 | No | 5 |
Pappa [37] | 2006 | Cross-sectional | US | CD and UC | 94/36/– | 43/20/– | NR | 15 ± 3/14 ± 4/– | NR | Deficiency: ≤ 15; severe deficiency: ≤ 8 | Yes | 3 |
Sinnott [38] | 2006 | Cohort | US | CD and UC | 30/18/– | 14/9/– | Age, sex | 48.0 ± 12.0/48.9 ± 15.7/– | NR | NR | No | 4 |
Vagianos [39] | 2007 | Cross-sectional | canada | CD and UC | 84/42/– | 52/25/– | NR | 37.6 ± 14.3/36.6 ± 12.9/– | CPBA | Normal: 14–80; deficiency: 20–30 | Yes | 4 |
Kuwabara [40] | 2008 | Cross-sectional | Japan | CD and UC | 29/41/– | 9/17/– | NR | 32.2 ± 6.7/39.3 ± 14.6/– | RIA | Deficiency: < 20; insufficiency: 21–29 | No | 3 |
Leslie [41] | 2008 | Cohort | Canada | CD and UC | 56/45/– | NR/NR/– | NR | > 18 | RIA | Optimal: > 30; marginally deficient: 20–30; insufficiency: 10–19; deficiency: < 10 | No | 6 |
Souza [71] | 2008 | Cohort | Brazil | CD and UC | 39/37/40 | 18/25/24 | NR | 32.1 ± 8.7/35.0 ± 8.5/34.0 ± 7.0 | RIA | No | 6 | |
Joseph [42] | 2009 | Case–control | India | CD and UC | 34/34/– | 10/10/– | Age, sex | 39.2 ± 12.9/38.9 ± 13.4 (IBS) | RIA | Deficiency: < 20; insufficiency: 20–32; adequate: > 32 | No | 6 |
Kumari [43] | 2010 | Prospective case–control | Georgia | CD | 4/–/4 | 0/–/0 | Age | 35.5 ± 9.75/–/42.40 ± 5.13 | ELISA | Insufficiency: < 30 | 240.50 ± 119.92/211.60 ± 132.11 (IU) | 6 |
EI-Matary [44] | 2011 | Cross-sectional | Canada | CD and UC | 39/21/56 | 20/11/31 | Age, sex, ethnicity | 12.2 ± 3.2/12.4 ± 3.7/11.3 ± 4.2 | CPBA | Optimum: ≥ 32 | No | 3 |
Levin [45] | 2011 | Cross-sectional | Australia | CD and UC | 70/8/– | NR/NR/– | NR | 12.6 ± 3.5 | CLIA | NR | No | 3 |
Pappa [47] | 2011 | Cross-sectional | US | CD and UC | 288/143/– | 127/78/– | Age, sex, ethnicity | 15.9 ± 3.1/15.4 ± 3.3/– | CLIA | Optimum: ≥ 32 | Yes | 4 |
Atia [48] | 2011 | Cross-sectional | US | CD and UC | 43/80/– | 3/7/– | NR | 61.4 ± 14.7/66.5 ± 11.5/– | CLIA | Deficiency: < 20; insufficiency: < 30 | No | 2 |
EI-Hodhod [46] | 2012 | Case–control | Egypt | CD and UC | 20/27/50 | 2/13/9 | Age, sex | 10.49 ± 3.34/12.77 ± 1.71/12.8 ± 3.77 | RIA | Deficiency: < 15; severe deficiency: < 8 | No | 6 |
Suibhne [49] | 2012 | Case–control | Ireland | CD | 81/–/70 | 48/–/42 | Age, sex,socio-economic status. | 36.43 ± 11.00/–/36.34 ± 9.53 | RIA | 2cut-points: (1) deficiency: < 20; (2) deficiency: < 32 | 200–400 IU; ≥ 800 IU | 5 |
Hassan [50] | 2012 | Cohort | Iran | CD and UC | 26/34/– | 7/10/– | NR | 34 ± 18/30 ± 11/– | RIA | Sufficiency: ≥ 30; insufficiency: 11–29; deficiency: ≤ 10 ng/mL | No | 7 |
Chatu [51] | 2012 | Retrospective cohort | UK | CD and UC | 107/61/– | NR/NR/– | NR | 34.98 ± 14.36(IBD)/– | CPBA | Normal: ≥ 20; deficiency: < 20; severe: < 10 | No | 4 |
Fu [52] | 2012 | Cohort | Canada | CD and UC | 40/60/– | 18/32/– | NR | 40 ± 13.2/42.1 ± 13.9/– | RIA | Hypovitaminosis: < 20 | No | 5 |
Salacinski [53] | 2012 | Cohort | US | CD | 19/–/19 | 10/–/10 | Age, sex | 44.16 ± 10.28/–/41.68 ± 11.19 | HPLC | Low 25(OH)D levels: < 20 ng/mL; insufficient: 20–32 ng/mL | No | 3 |
Garg [54] | 2013 | Cohort | Australia | CD and UC | 40/31/23 | 18/14/13 | Sunlight exposure | 41 ± 13.25/44 ± 15/42 ± 11.5 | CLIA | Sufficiency: ≥ 30; insufficiency: 20–30; deficiency: < 20 | 795/927/473(UI) | 6 |
Prosnitz [55] | 2013 | Cohort | US | CD | 78/–/221 | 34/–/109 | Anthropometry, body composition, pubertal development weight and height | 12.7 ± 2.8/–/13.5 ± 4.4 | RIA | Deficiency: < 20 | No | 7 |
Miznerova [56] | 2013 | Cohort | Slovakia | CD and UC | 46/30/– | 25/15/– | NR | 36 ± 12.75/47 ± 13.5/– | ECLIA | Deficiency: < 30; very low: < 10 | No | 4 |
Grunbaum [17] | 2013 | Case–control | Canada | CD and UC | 34/21/48 | 21/13/38 | Age, sex, ethnicity, weight | 39.9 ± 12.3/44.2 ± 13.7/39.6 ± 13.8 | RIA | Replete: ≥ 30; insufficiency: 20–29; deficiency: < 20; severely deficiency: < 10 | 932.4/1020.8 (IU) | 6 |
Jorgensen [72] | 2013 | Cross-sectional | Denmark | CD | 182/–/62 | 57/–/52 | NR | 36 ± 10.2/–/32 ± 11 | LC–MS | Deficiency: < 20 | Yes | 5 |
Middleton [57] | 2013 | Cross-sectional | US | CD | 52/–/40 | 20/–/25 | NR | 17.0 ± 0.9/–/11.0 ± 2.5 | CLIA + LC–MS | Deficiency: ≤ 15; insufficiency: < 32 | No | 5 |
Lorinczy [58] | 2013 | Cross-sectional | Hungary | CD and UC | 128/41/– | NR/NR/– | Age, sex | 35.8 ± 12.0 | CLIA | NR | No | 5 |
Alkhouri [59] | 2013 | Case–control | US | CD and UC | 46/12/61 | 14/6/31 | Age, sex | 12.1 ± 4.1/12.3 ± 3.5/12.1 ± 3.6 | NR | Deficiency: < 12; severely deficiency: < 4 | No | 4 |
Bruyn [60] | 2014 | Prospective case–control | Netherlands | CD | 98/–/43 | 68/–/NR | NR | 36 ± 10.2/–/32 ± 7.3 | CLIA | Normal: ≥ 30; insufficiency: 20–30; deficiency: < 20 | Yes | 5 |
Dumitrescu [61] | 2014 | Prospective case–control | Romania | CD and UC | 14/33/94 | 6/16/44 | Age, sex | 36 ± 9/42 ± 14/42 ± 12 | HPLC | Sufficiency: ≥ 30; insufficiency: 20–30; deficiency: < 20 | No | 7 |
Tan [62] | 2014 | Case–control | China | CD and UC | 107/124/122 | 61/39/55 | Age, sex | 38.0 ± 15.3/39.6 ± 14.4/39.43 ± 12.71 | ELISA | Sufficiency: ≥ 20; insufficiency: 10–20; deficiency: < 10 | No | 7 |
Oikonomou [63] | 2014 | Case–control | Greece | CD | 44/–/20 | 22/–/14 | NR | 31 ± 8/–/30 ± 6.75 | CLIA | NR | No | 4 |
Veit [64] | 2014 | Cohort | US | CD and UC | 40/18/116 | 16/11/67 | Age | 16.61 ± 2.20/16.13 ± 1.99/14.56 ± 4.35 | CPBA | Sufficiency: ≥ 30 ng/mL; insufficiency: 20–29.9; deficiency: < 20 ng/mL | No | 7 |
Basson [65] | 2015 | Cross-sectional | South Africa | CD | 186/–/199 | NR/–/NR | NR | 47.35 ± 14.20/–/34.11 ± 15.16 | CLIA | Deficiency: ≤ 20 or 29 ng/mL | No | 7 |
Thorsen [66] | 2016 | Case–control | Danish | CD and UC | 155/210/384 | 69/114/196 | NR | 13.65 ± 2.24/14.30 ± 4.48/NS | LC–MS | NR | No | 7 |
Schäffler [67] | 2017 | Cohort | Germany | CD and UC | 123/85/– | NR/NR/– | NR | NR | NR | Deficiency: < 50 nmol/mL; insufficiency: < 75 nmol; normal: ≥ 75 nmol | No | 4 |
Opstelten [68] | 2018 | Multicenter cohort | UK | CD and UC | 72/169/144 338 | 56/82/112 164 | Age, sex | 49.55 ± 4.62/51.63 ± 2.20/48.94 ± 3.37; 51.61 ± 1.96 | LCMS | Deficiency: ≤ 50 nmol/mL; insufficiency: 50–75 nmol/mL; sufficiency: ≥ 75 nmol/mL | No | 5 |
Scotti [73] | 2018 | Cohort | Italy | CD and UC | 126/174/– | 56/76/– | Age, sex | 51 ± 16.7/51 ± 17.9/– | ELISA | Severe deficiency: ≤ 10 ng/mL; deficiency: 11–20 ng/mL; insufficient levels 21–30 ng/mL; adequate levels > 30 ng/mL | No | 6 |
Garg [74] | 2018 | Cohort | Australia | UC | –/17/8 | –/7/3 | Age, sex | –/47.26 ± 11.55/50.75 ± 8.95 | LCMS | Deficiency: < 50 nmol/mL | 40000 IU/week | 7 |
Caviezel [75] | 2018 | Cross-sectional | Switzerland | CD and UC | 99/57/– | 48/31/– | Age, sex | 41.2 ± 14.5/41.5 ± 13.6/– | CPBA | Deficiency: < 50 nmol/mL | NO | 7 |
Kyoung [18] | 2018 | Retrospective cohort | Korea | CD and UC | 42/45/– | 17/13/– | Age, sex | 40.9 ± 15.6/48.5 ± 13.7/– | CLIA | Deficiency: < 20 ng/mL | No | 6 |
Strisciuglio [76] | 2018 | Cohort | Italy | CD and UC | 12/21/18 | 17/8 | Age, sex | 11 ± 3.25 (IBD)/9.2 ± 2.5 | ELISA | NR | No | 7 |
Grag [77] | 2019 | Cohort | Australia | CD and UC | 20/15/14 | 8/5/7 | Age, sex | 43.75 ± 11.75/42.75 ± 11.75/48.25 ± 13.56 | NR | NR | Yes | 8 |