Can Vitamin D Replacement Correct Chronic Disease Anemia?

Overview

This prospective, single-arm interventional pilot study evaluated whether vitamin D supplementation alone improves iron status in adults with inflammatory bowel disease (IBD) who are in clinical remission and have concurrent vitamin D deficiency. Because vitamin D can suppress hepcidin-a key regulator that inhibits iron absorption-the investigators hypothesized that correcting vitamin D deficiency might improve iron parameters. Adult IBD patients (Crohn's disease or ulcerative colitis) in clinical remission with serum 25-hydroxyvitamin D \<20 ng/mL, ferritin \<40 µg/L, and no anemia received oral cholecalciferol (50,000 IU weekly for 8 weeks, followed by 2,000 IU daily) and were reassessed at 3 months. The primary outcome was the within-subject change in iron parameters (serum iron, ferritin, and transferrin saturation) from baseline to 3 months. The study also examined the change in 25(OH)D and explored differences by IBD subtype and biologic therapy use.

Background and Rationale Vitamin D acts as an immunomodulator and can reduce hepcidin, the principal regulator of iron metabolism that inhibits intestinal iron absorption and iron release from stores. Lower hepcidin levels may therefore increase iron availability. The investigators sought to determine whether correcting vitamin D deficiency alone could improve iron parameters. The corrective effect of vitamin D on iron parameters had previously been demonstrated in pediatric IBD patients but had not been prospectively examined in non-anemic adults. The investigators hypothesized that vitamin D replacement would significantly improve serum iron, ferritin, and transferrin saturation within 3 months, potentially through hepcidin suppression and modulation of TNF-α-dependent pathways. Study Design and Setting This was a prospective, single-arm, single-center interventional pilot study conducted at the Inflammatory Bowel Disease outpatient clinic of the Department of Internal Medicine, Division of Gastroenterology, Gazi University Hospital, Ankara, Turkey, between September 2022 and March 2023. Participants Eligible participants were adults (≥18 years) diagnosed with Crohn's disease or ulcerative colitis who were in clinical remission and had laboratory evidence of concurrent vitamin D deficiency \[25(OH)D \<20 ng/mL\]. Clinical remission was defined as a Harvey-Bradshaw Index \<5 for Crohn's disease and a partial Mayo Score ≤1 (with no individual subscore \>1) for ulcerative colitis. Patients with vitamin D or iron allergy, anemia, active disease, or fever were excluded. Intervention All eligible participants received the same standardized regimen: oral cholecalciferol 50,000 IU once weekly for 8 weeks (cumulative loading dose 400,000 IU), followed by oral cholecalciferol 2,000 IU daily as maintenance until the 3-month follow-up visit. No iron supplementation was administered as part of the protocol. Outcome Measures The primary outcome was the within-subject change in iron parameters (serum iron, ferritin, and transferrin saturation) from baseline to the 3-month follow-up visit. Secondary outcomes included the within-subject change in serum 25(OH)D from baseline to follow-up, and pre-specified subgroup analyses by IBD subtype (Crohn's disease vs. ulcerative colitis) and by biologic therapy use (yes vs. no). Statistical Analysis No a priori sample size calculation was performed; all consecutive eligible patients during the recruitment period were enrolled. Normality of continuous variables was assessed with the Kolmogorov-Smirnov and Shapiro-Wilk tests, and within-subject changes in non-normally distributed variables were analyzed using the Wilcoxon signed-rank test. Given the exploratory nature of the subgroup analyses and the small sample size, no correction for multiple comparisons was applied. A two-sided p-value \<0.05 was considered statistically significant. Enrollment Of 1,292 IBD patients screened, 43 met all eligibility criteria and were enrolled; 32 completed the 3-month follow-up.