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Table 1 Characteristics of studies included in the meta-analysis

From: Vitamin D deficiency associated with Crohn’s disease and ulcerative colitis: a meta-analysis of 55 observational studies

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
  1. CPBA competitive protein binding assay, RIA radioimmunoassay, ECLIA electrochemiluminescence immunoassay, ELISA enzyme-linked immunosorbent assay, CLIA chemiluminescence, HPLC high performance liquid chromatography, LC–MS liquid chromatograph mass spectrometer, NR not reported