Effectiveness of Vitamin D Supplementation on Disease Course in Inflammatory Bowel Disease Patients: Systematic Review With Meta-Analysis

Abstract

Background The vitamin D role in bone metabolism is well known; however, recent evidence suggests the impact of vitamin D in immune modulation and its implications in immune-mediated diseases, including inflammatory bowel disease (IBD). Method We performed a systematic review with meta-analysis by a specific protocol (PROSPERO: CRD42022311184; March 2022, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=311184). Randomized clinical trials involving IBD patients treated with vitamin D supplementation, compared with placebo, that evaluated the risk of clinical relapse and disease activity were included. Literature search was performed using Medline, Scopus, and Cochrane CENTRAL through January 2022. Results Out of 1448 articles, 12 (11 full-texts and 1 abstract) were included. Seven randomized clinical trials reported data on the clinical relapse as dichotomous outcome, while 7 studies reported data on disease activity expressed as continuous variables. The pooled risk ratio of clinical relapse was 0.64 (95% confidence interval, 0.46-0.89; I2 = 25%) among 458 IBD patients. However, this seems to be solid only in Crohn’s disease (CD) patients. In fact, only 2 studies, involving 67 patients with ulcerative colitis, were included in the analysis. CD patients in clinical remission had a strong significant risk reduction in clinical relapse (risk ratio, 0.47; 95% confidence interval, 0.27-0.82; I2 = 0%), suggesting that it could be a specific subgroup with maximum clinical benefit of vitamin D supplementation. Conclusions This meta-analysis shows that vitamin D supplementation can reduce the risk of clinical relapse in IBD patients, especially in CD patients in clinical remission. In a subgroup analysis, it was not significant (due to small number of studies and low number of patients), and well-powered studies are needed, in particular for ulcerative colitis patients.

Adjunctive therapeutic effects of micronutrient supplementation in inflammatory bowel disease

“…At present, micronutrients for which more clinical trials have been conducted in the IBD population are vitamin D and iron. Vitamin D supplementation in patients with IBD reduces inflammation and the risk of clinical relapse ( 12 , 14 ), improves responsiveness to anti-TNF therapy ( 15 ), prevents upper respiratory tract infections in winter and spring ( 17 ), and may have a positive effect on mental health ( 18 ). However, comparisons between studies are complicated by the wide variation in dose and follow-up of existing clinical trials, and no uniform recommended supplementation dose is currently available.…”

“…High-dose vitamin D supplementation can reduce the expression of proinflammatory cytokines (12), but whether it can alleviate disease activity remains controversial. There is randomized controlled trial (RCT) suggesting that vitamin D supplementation may attenuate disease activity in UC patients (13), but this effect was not observed in the clinical trial conducted by Bendix et al (12) in 40 CD patients. Moreover, a Meta-analysis conducted by Valvano et al ( 14) suggested that vitamin D supplementation can reduce the risk of clinical relapse in IBD patients, especially in CD patients in clinical remission.…”

“…Moreover, a Meta-analysis conducted by Valvano et al. ( 14 ) suggested that vitamin D supplementation can reduce the risk of clinical relapse in IBD patients, especially in CD patients in clinical remission. Supplementation with vitamin D in IBD patients has also shown some other benefits.…”

Vitamin D and malabsorptive gastrointestinal conditions: A bidirectional relationship?

“…In another pooled analysis of 17 trials with 1127 IBD patients, oral vitamin D supplementation effectively increased the concentration of serum 25(OH)D and decreased serum CRP levels, but it did not decrease ESR, disease activity index, and relapse rate [101]. In another recent systematic review with meta-analysis including 12 RCTs, the risk of clinical relapse and disease activity in IBD patients treated with vitamin D supplementation compared with placebo was evaluated [102]. Vitamin D supplementation reduced the overall risk of clinical relapse in IBD patients (ITT: RR, 0.64; CI 0.46-0.89; I 2 = 25% and PP: RR, 0.62; CI 0.41-0.92; I 2 = 18%), especially in CsD patients in clinical remission (RR, 0.47; 95% CI, 0.27 to 0.82; I 2 = 0%).…”

“…Simply put, patients should be given as much vitamin D as they need to achieve satisfactory levels of circulating 25(OH)D. In a recent meta-analysis, an attempt was made to define a daily vitamin D dosage that is most likely to yield significant results, assuming its effectiveness as adjuvant therapy. Meta-regression suggested that vitamin D dose may indeed influence treatment effectiveness, and it is to be expected to observe this effect with high dose vitamin D regimens [102].…”