Effects of vitamin D supplementation on intestinal permeability, cathelicidin and disease markers in Crohn's disease: Results from a randomised double‐blind placebo‐controlled study

Abstract

Background: Vitamin D (vitD) supplementation may prolong remission in Crohn's disease (CD); however, the clinical efficacy and mechanisms are unclear. Aim: To determine changes in intestinal permeability (IP), antimicrobial peptide (AMP) concentrations and disease markers in CD, in response to vitD supplementation. Methods: In a double-blind randomised placebo-controlled study, we assigned 27 CD patients in remission to 2000 IU/day vitD or placebo for 3 mos. We determined IP, plasma cathelicidin (LL-37 in ng/mL), human-beta-defensin-2 (hBD2 in pg/mL), disease activity (Crohn's Disease Activity Index (CDAI)), C-reactive protein (CRP in mg/L), fecal calprotectin (mg/g), Quality of Life (QoL) and serum 25-hydroxyvitamin D (25(OH)D in nmol/L) at 0 and 3 mos. Results: At 3 mos., 25(OH)D concentrations were significantly higher in those whom were treated (p < 0.001). Intra-group analysis showed increased LL-37 concentrations (p ¼ 0.050) and maintenance of IP measures in the treated group. In contrast, in the placebo group, the small bowel (p ¼ 0.018) and gastro-duodenal permeability (p ¼ 0.030) increased from baseline. At 3 mos., patients with 25(OH)D 75 nmol/L had significantly lower CRP (p ¼ 0.019), higher QoL (p ¼ 0.037), higher LL-37 concentrations (p < 0.001) and non-significantly lower CDAI scores (p ¼ 0.082), compared to those with levels <75 nmol/L. Conclusion: Short-term treatment with 2000 IU/day vitD significantly increased 25(OH)D levels in CD patients in remission and it was associated with increased LL-37 concentrations and maintenance of IP. Achieving 25(OH)D 75 nmol/l was accompanied by higher circulating LL-37, higher QoL scores and reduced CRP. Registered at ClinicalTrials.gov (NCT01792388).

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

“…Focusing solely on fortifying the gut, there are many nutrients that may strengthen the integrity of the intestinal barrier. For example, Zinc, Vitamin D, and Magnesium are all known to improve the health of the intestinal mucosa lining [201][202][203] . Interestingly, all of these nutrients have been…”

Is vitamin D supplementation a viable treatment for Crohn’s disease?

“…[19] Vitamin D as therapy -possible biological mechanisms in CD There is plausible evidence from animal models that vitamin D reduces intestinal inflammation, [20,21] supresses tumor necrosis factor-alpha and interferon gamma (IFNγ) and induces IL-10. [20] Consistent with this, increased IL-10 and reduced IFNγ (for review, see [3,4]) has been documented in human CD; however, others [10] failed to detect changes in cytokine profiles in response to vitamin D treatment. Recently, direct effects of vitamin D action on the intestinal barrier and junctional proteins have been reported primarily in animal models [22] although preliminary work in human CD [10] may support this hypothesis.…”

“…This study was of good size (n, 98), but showed fewer relapses than anticipated by the authors at 12 months, of note also was the relatively high 25OHD levels at enrolment, as discussed later, and while clinical relapse is an important end point, endoscopic score or fecal calprotectin would be of interest in future studies. A recent pilot RCT [10] (n = 28) showed that 3 months administration of 2000 IU oral vitamin D 3 daily appeared to prevent deterioration in intestinal permeability in the treated group; however, longer follow-up would be required to determine effects on clinical relapse.…”

“…[16,17] In current RCTs, [9,10] mean post-treatment 25OHD was between 90 and 100 nmol/L, with baseline levels reasonable on enrolment in these studies. Targeting the level of 25OHD, rather than focussing on a fixed uniform dose, similar to Yang et al, [11] in a randomized controlled manner, would be informative.…”

“…Published RCTs to date were amongst patients with reasonable baseline 25OHD concentration at study enrolment (69 nmol/L for both Jorgensen et al [9] and Raftery et al [10], where ≤50 is considered suboptimal [14]). It is plausible that supplementation in a vitamin D deficient CD group would show greater benefit compared to a replete group.…”