Daily Vitamin D3 Versus Stoss Vitamin D3 for Correction of 25OHD Deficiency in Children with Inflammatory Bowel Disease, a Randomised Controlled Trial.

2025-02-28
Digestive diseases and sciences 70(5)
- Jonathan E M O'Donnell
- Steven T Leach
- Nerissa L Bowcock
- Siying Chen
- Nitin Gupta
- Kevin Jiang
- Robert N Lopez
- Rachel Messenger
- Lily Nahidi
- Amanda Shapiro
- Andrew S Day
- Daniel A Lemberg

PubMed: 40021606
DOI: 10.1007/s10620-025-08913-3

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 74
Population: 74 children aged 5-18 years with Paediatric Inflammatory Bowel Disease and 25OHD deficiency (< 50 nmol/L)
Methods: Randomised controlled trial comparing 2000 IU oral vitamin D3 daily to a stoss protocol (400,000 IU for 3-12 years or 800,000 IU for >12 years)
Duration: 12 months

Rigorous Journal

Introduction

Vitamin D deficiency is common in Paediatric Inflammatory Bowel Disease (PIBD) and has been implicated in disease pathogenesis and disease exacerbation. Current guidelines recommend oral vitamin D supplementation when 25OHD levels are below 50 nmol/L. Supplementation comes in two forms: either a daily supplement of a low dose of vitamin D3 (2000 IU) for several months or a single high dose of oral vitamin D3-termed 'stoss' therapy, with no consensus regarding optimum treatment.

Methods

A randomised controlled trial was conducted in children with a prior diagnosis of PIBD with 25OHD deficiency (< 50 nmol/L), comparing 2000 IU oral D3 daily to a stoss protocol (oral D3 dosage 400,000 IU for 3-12 years of age or 800,000 IU for > 12 years). Children were followed for 12 months, with biochemistry (25OHD, calcium, magnesium, phosphate, parathyroid hormone, haemoglobin, haematocrit, platelets, albumin), stool markers (calprotectin, S100A12), anthropometrics (weight, height, body mass index) as well as clinical disease indices (Paediatric Crohn's Disease Activity Index, Paediatric Ulcerative Colitis Activity Index) and medication use collected at 3, 6, 9 and 12 months.

Results

74 children aged 5-18 years completed the study. Both 2000 IU daily and stoss protocol significantly increased 25OHD from baseline values at 3, 6, 9 and 12 months. One patient randomised to stoss protocol had a 25OHD level of 263 nmol/L with normal serum calcium. There was no difference in biochemical, stool or clinical markers between groups at any time point, nor was there any correlation between 25OHD level and calprotectin or 25OHD level and clinical disease activity scores.

Conclusion

Stoss protocol was non-inferior to 2000 IU daily vitamin D3 in raising 25OHD levels at 12 months. There was also no difference between 25OHD levels at 3, 6 and 9 months between groups.

Research Insights

Vitamin D→Changed Albumin Level
There was no difference in biochemical, stool or clinical markers between groups at any time point
Effect
Neutral
Effect size
Small
Dose
2000 IU daily or 400,000 IU (3-12 years) or 800,000 IU (>12 years) single dose
Vitamin D→Changed Anthropometric Measure
There was no difference in biochemical, stool or clinical markers between groups at any time point
Effect
Neutral
Effect size
Small
Dose
2000 IU daily or 400,000 IU (3-12 years) or 800,000 IU (>12 years) single dose
Vitamin D→Changed Magnesium Level
There was no difference in biochemical, stool or clinical markers between groups at any time point
Effect
Neutral
Effect size
Small
Dose
2000 IU daily or 400,000 IU (3-12 years) or 800,000 IU (>12 years) single dose
Vitamin D→Changed Parathyroid Hormone Level
There was no difference in biochemical, stool or clinical markers between groups at any time point
Effect
Neutral
Effect size
Small
Dose
2000 IU daily or 400,000 IU (3-12 years) or 800,000 IU (>12 years) single dose
Vitamin D→Changed Phosphate Level
There was no difference in biochemical, stool or clinical markers between groups at any time point
Effect
Neutral
Effect size
Small
Dose
2000 IU daily or 400,000 IU (3-12 years) or 800,000 IU (>12 years) single dose
Vitamin D→Changed Serum Calcium Level
There was no difference in biochemical, stool or clinical markers between groups at any time point
Effect
Neutral
Effect size
Small
Dose
2000 IU daily or 400,000 IU (3-12 years) or 800,000 IU (>12 years) single dose
Vitamin D→Improved Clinical Disease Activity
There was no difference in biochemical, stool or clinical markers between groups at any time point, nor was there any correlation between 25OHD level and clinical disease activity scores
Effect
Neutral
Effect size
Small
Dose
2000 IU daily or 400,000 IU (3-12 years) or 800,000 IU (>12 years) single dose
Vitamin D→Increased Hemoglobin Levels
There was no difference in biochemical, stool or clinical markers between groups at any time point
Effect
Neutral
Effect size
Small
Dose
2000 IU daily or 400,000 IU (3-12 years) or 800,000 IU (>12 years) single dose
Vitamin D→Increased Platelet Count
There was no difference in biochemical, stool or clinical markers between groups at any time point
Effect
Neutral
Effect size
Small
Dose
2000 IU daily or 400,000 IU (3-12 years) or 800,000 IU (>12 years) single dose
Vitamin D→Reduced Fecal Calprotectin
There was no difference in biochemical, stool or clinical markers between groups at any time point, nor was there any correlation between 25OHD level and calprotectin
Effect
Neutral
Effect size
Small
Dose
2000 IU daily or 400,000 IU (3-12 years) or 800,000 IU (>12 years) single dose
Vitamin D→Reduced S100A12 Level
There was no difference in biochemical, stool or clinical markers between groups at any time point
Effect
Neutral
Effect size
Small
Dose
2000 IU daily or 400,000 IU (3-12 years) or 800,000 IU (>12 years) single dose
Vitamin D→Reduced Vitamin D Deficiency
Both 2000 IU daily and stoss protocol significantly increased 25OHD from baseline values at 3, 6, 9 and 12 months.
Effect
Beneficial
Effect size
Moderate
Dose
400,000 IU (3-12 years) or 800,000 IU (>12 years) single dose