Vitamin D and Inflammatory Bowel Disease

Table 2

Vitamin D versus disease activity and outcome in IBD (chronological order).

Author	Year	Population	Methodology	Main findings
Harries et al. [50]	1985	U.S.A; 40 CD; 20 UC; 9 HC	Single-center cohort; CD divided into 2 groups (undernourished and well nourished); 2 control groups: 20 well-nourished UC and 9 HC	25(OH)D3 significantly lower in CD with active disease versus inactive disease ( < 0.05)
Tajika et al. [46]	2004	Japan; 33 CD,; 11 UC,; 15 HC	Single-center cohort; 25(OH)D3 and disease activity assessed by CDAI and IOIBD score	Serum 25(OH)D3 significantly related to disease duration ( = 0.46, = 0.003), CDAI ( = 0.44, = 0.005), IOIBD score ( = 0.30, < 0.05), serum ferritin ( = 0.34, = 0.03), CRP ( = 0.34, = 0.03)
Joseph et al. [52]	2009	India; 34 CD,; 34 HC	Single-center cohort; disease activity evaluated by HBI in CD	Serum 25(OH)D3 in CD significantly lower versus controls ( < 0.05). Disease activity correlated negatively with 25(OH)D3 level ( < 0.004). 25(OH)D3 levels were comparable to controls in mild CD but were significantly lower in moderate and severe CD
Nakajima et al. [68]	2011	Japan; 47 CD, 40 UC, 41 HC	Single-center cohort; disease activity measured using CAI/CDAI scores	No decrease 1,25(OH)2D3 in CD with high CDAI; No significant correlation between serum 1,25(OH)2D3 levels and CAI or CDAI in UC or CD
Ulitsky et al. [59]	2011	U.S.A.; 504 IBD (403 CD, 101 UC)	Single-center cohort; retrospective observational study; HRQOL measured with SIBDQ, disease activity measured using HBI/UCDI scores	25(OH)D3 deficiency significantly associated with lower SIBDQ ( = 0.002) and higher mean HBI/UCDI ( = 0.002) in IBD versus vit D sufficient patients. Analyzed separately, vit D deficiency associated with lower HRQOL scores only in CD ( = 0.04), not in UC
El-Matary et al. [54]	2011	Canada; 60 IBD (39 CD, 21 UC)	Cross-sectional pediatric study. Disease activity measured by PCDAI e PUCAI	No correlation between PCDAI and serum 25(OH)D3. Marginal evidence against the null hypothesis ( = 0.05) between serum 25(OH)D3 and PUCAI, but without statistical significance
Hassan et al. [60]	2013	Iran; 60 IBD (34 UC, 26 CD)	Cross-sectional study. Disease activity measured by CDAI and Truelove index	Serum vit D lower in active versus inactive disease (non significantly). VitD deficiency was not associated with IBD activity (also considering CD and UC separately), however was associated with a history of IBD related intestinal surgery
Ananthakrishnan et al. [81]	2013	U.S.A.; 3,217 IBD (55% CD, 45% UC)	Multicenter cohort; 25(OH)D3: Normal (>30 ng/mL), Insufficient (20–29.9 ng/mL) or; Deficient (<20 ng/mL)	IBD-related surgery: CD: 10% patients never vitamin D deficient versus 13% vitamin D insufficient versus 17% vitamin D deficient. UC: vitamin D deficiency associated with elevated risk of surgery and hospitalization with effect similar to CD; no statistical significance in patients vitamin D insufficient.; Normalization of 25(OH)D3 associated with reduction in the risk of related surgery but not in UC
Zator et al. [92]	2014	U.S.A.; 101 IBD (74 CD, 27 UC)	Retrospective single-center cohort; patients on anti-TNF therapy evaluated for loss of response; 25(OH)D3 insufficiency: <30 ng/mL	Patients with insufficient vitamin D demonstrated earlier cessation of anti-TNF- therapy ( = 0.04). This effect was significant in patients who stopped treatment for loss of response, stronger for CD than UC ( = NS)
Ananthakrishnan et al. [91]	2014	U.S.A.; 3188 IBD patients (45% UC, 55% CD)	Retrospective multi-center analysis of 25(OH)D3 in 35 patients who developed CDI	25(OH)D3 level was significantly lower in IBD who developed CDI compared to non-CDI-IBD ( = 0.002). Levels below 20 ng/mL were associated with a two-fold increase in risk of CDI.; 25(OH)D3 level was an independent predictor of CDI
Ham et al. [93]	2014	U.S.A.; 37 CD	Prospectively collected samples for 25(OH)D3 analysis; assessment of HBI and CRP; PBMC tested for VDR, Cyp	25(OH)D3 levels lower in patients with active disease versus inactive disease, 25(OH)D3 correlated with HBI (not with CRP); PBMC: mean gene expression of VDR and CypB1 higher in active disease
Garg et al. [90]	2013	Australia; 40 CD; 31 UC; 23 HC	Assessment of 25(OH)D3, fecal calprotectin and CRP	Inverse correlation between serum 25(OH)D3 and fecal calprotectin in CD and UC patients, but not with CRP
Hlavaty et al. [82]	2014	Slovakia; 141 CD; 49 UC	SIBDQ assessment in vitamin D sufficient or -deficient patients and in vitamin supplement (800 IU/day for 3 months) patients	SIBDQ was significantly better in vitamin D-sufficient patients; vitamin D supplements did not influence vitamin D status or sIBDQ
Govani et al. [88]	2015	U.S.A.; 67,751 CD	Retrospective, national, analysis of UV exposure and inpatient surgery risk	UV exposure protective for inpatients surgery

Abbreviations: CD: Crohn’s disease; UC: ulcerative colitis; HC: healthy controls; IBS: irritable bowel syndrome; IBD: inflammatory bowel disease; CDAI: Crohn’s Disease Activity Index; IOIBD: international organization for the study of inflammatory bowel disease score; CAI: Lichtiger’s clinical activity index; 25(OH)D₃: 25-Hydroxycholecalciferol; 1,25(OH)₂D₃: 1,25dihydroxycholecalciferol; SIBDQ: Short IBD Questionnaire; HBI: Harvey-Bradshaw index; UCDI: Ulcerative colitis disease activity index; HRQOL: health-related quality of life; PCDAI: pediatric Crohn’s disease activity index; PUCAI: pediatric ulcerative colitis activity index; CDI: Clostridium difficile infection; CRP: C-reactive protein; UV: ultraviolet; TNF: tumor necrosis factor; PBMC: peripheral blood mononuclear cells; Cyp: Cyp27b1 gene; VDR: vitamin D receptor.