Vitamin D3 (Cholecalciferol)

Why it happens in Crohn’s disease

Vitamin D is fat-soluble, so anything that impairs fat absorption impairs it. Crohn’s does this in several ways at once: proximal small bowel inflammation reduces uptake directly; ileal disease or resection interrupts bile acid recycling, and without an adequate bile salt pool fat-soluble vitamins are not solubilised at all. Corticosteroids accelerate vitamin D catabolism. Chronic inflammation, fatigue and photosensitivity from drugs also reduce sun exposure. What makes vitamin D distinctive is the reverse arrow: the vitamin D receptor is expressed on intestinal epithelium and on T cells, where calcitriol supports antimicrobial peptide production, tight-junction integrity and regulatory T cell development. Low vitamin D may therefore worsen the disease that caused it.

Who is most at risk

• Extensive small bowel disease or resection
• Loss of the terminal ileum and the resulting bile salt depletion
• Repeated or prolonged corticosteroid courses
• Higher latitude, winter months, darker skin pigmentation
• Low body weight and reduced adipose storage

Symptoms of deficiency

• Often completely silent until bone disease is advanced
• Bone and muscle aching, especially in the hips, pelvis and thighs
• Proximal muscle weakness — difficulty rising from a chair or climbing stairs
• Fatigue that persists even when disease activity and haemoglobin are controlled
• Osteomalacia, osteopenia and fracture risk in prolonged deficiency

Many of these overlap with Crohn’s disease itself, which is exactly why deficiencies are missed. Fatigue attributed to active disease is frequently anaemia, and neuropathy attributed to medication is sometimes B12.

How it is tested

Measure serum 25-hydroxyvitamin D, not 1,25-dihydroxyvitamin D — the latter is tightly regulated and stays normal well into deficiency. Below 30 nmol/L (12 ng/mL) is deficient, 30–50 nmol/L insufficient. Testing at diagnosis and then annually, ideally at the end of winter, is standard practice in IBD clinics. Pair with calcium, phosphate, alkaline phosphatase and parathyroid hormone when levels are very low.

Replenishment protocols

Replacement in Crohn’s typically needs higher doses than in the general population because absorption is the limiting step. Common practice is a loading regimen (for example 50,000 IU weekly for 6–8 weeks) followed by 1,000–4,000 IU/day maintenance, retested after 3 months and titrated to a target of 75–100 nmol/L. The randomised evidence for using vitamin D to change disease course is suggestive but unproven: the Jørgensen trial gave 1,200 IU/day to patients in remission and saw relapse at 12 months of 13% versus 29% on placebo — a result that did not reach statistical significance in an underpowered study. A later trial of high-dose vitamin D did not prevent post-operative recurrence. Correcting a documented deficiency is uncontroversial; treating Crohn’s disease with vitamin D is not established.

Amounts reflect what gastroenterology literature and guidelines describe. The right dose for you depends on your test results, absorption and surgical history, so test first and work with your care team to personalise it.

Medication interactions

Prednisone and other corticosteroids increase vitamin D catabolism and independently drive bone loss, so anyone on repeated steroid courses should be on vitamin D and calcium as a matter of routine. Cholestyramine, used for bile acid diarrhoea after ileal resection, binds fat-soluble vitamins and should be dosed hours apart from supplements. Orlistat and long-term mineral oil have the same effect.

Sources

1. 1

   Review article: vitamin D and inflammatory bowel diseases

   Mouli VP, Ananthakrishnan AN. · Alimentary Pharmacology & Therapeutics · 2014 · PMID 24236989

2. 2

   Clinical trial: vitamin D3 treatment in Crohn’s disease — a randomized double-blind placebo-controlled study

   Jørgensen SP, Agnholt J, Glerup H, et al. · Alimentary Pharmacology & Therapeutics · 2010

3. 3

   High-dose vitamin D does not prevent postoperative recurrence of Crohn’s disease in a randomized placebo-controlled trial

   de Bruyn JR, Bossuyt P, Ferrante M, et al. · Clinical Gastroenterology and Hepatology · 2020