A Prospective Open-Label Dose–Response Study to Correct Vitamin D Deficiency in Cirrhosis

Chip A. Bowman, Kian Bichoupan, Shai Posner, Emily Schonfeld, Alexis Pappas, Mark Woodward, Thomas Schiano, Andrea D. Branch

Research output: Contribution to journalArticlepeer-review


Background: Patients with advanced liver disease often have vitamin D deficiency, but the daily dosages of vitamin D3 needed to raise their serum 25-hydrodroxyvitamin D [25(OH)D] concentrations are unknown. Objective: We aimed to establish the dose–response relationship between vitamin D3 and 25(OH)D in patients with liver cirrhosis. Design: An open-label study of orally-administered vitamin D3 (gelcaps) was conducted in patients with liver cirrhosis using a tiered-dosing regimen: 4,000 IU/d for baseline 25(OH)D ≤ 15 ng/mL and 2,000 IU/d for baseline 25(OH)D > 15 to ≤ 25 ng/mL (NCT01575717). Supplementation continued for 6 months, or until liver transplantation. Changes in 25(OH)D were measured after ≥ 3 months. Dose–response data on 48 patients (21 receiving 4000 IU/d and 27 receiving 2,000 IU/d) reporting ≥ 80% adherence were analyzed using generalized estimating equations (GEE). Results: Among the 48 patients, 39 (81%) had 25(OH)D > 20 ng/mL while on supplements, and none experienced hypercalcemia. The magnitude of the increase in 25(OH)D was approximately twofold greater in patients receiving the higher dose. The mean incremental increase was 5.1 ng/ml ± 3.9 of 25(OH)D per 1000 IU/d of vitamin D3. Multivariable models demonstrated a significant positive relationship between baseline 25(OH)D and serum albumin (p < 0.01) and hemoglobin (p = 0.01), and a negative relationship with the MELD score (p < 0.01) and total bilirubin (p < 0.01). Conclusions: A two-tiered dosing regimen of daily oral vitamin D3supplementation safely raised 25(OH)D concentrations in the majority of adults with liver cirrhosis who were adherent to supplement use. Graphical Abstract: (Figure presented.)

Original languageEnglish
Pages (from-to)1015-1024
Number of pages10
JournalDigestive Diseases and Sciences
Issue number3
StatePublished - Mar 2024


  • Cholecalciferol
  • Cirrhosis
  • Supplementation
  • Transplant
  • Vitamin D


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