Vitamin B12 (Cobalamin)

Why it happens in Crohn’s disease

Vitamin B12 absorption is the most anatomically specific process in the gut. Dietary B12 binds intrinsic factor produced by gastric parietal cells, and the resulting complex is taken up by cubilin receptors found only in the terminal ileum. There is no backup site. Crohn’s disease is ileal in the majority of patients, so inflammation, stricturing or surgical removal of that exact segment eliminates the receptor population outright — this is why B12 deficiency tracks disease location more tightly than any other nutrient. Bacterial overgrowth in a strictured or blind loop compounds the problem, because luminal bacteria consume B12 before the host can absorb it.

Who is most at risk

• Ileal or ileocolonic Crohn’s disease (as opposed to colonic-only disease)
• Prior ileocaecal resection — risk rises sharply above 20 cm of ileum removed
• Small intestinal bacterial overgrowth, especially with strictures or a blind loop
• Long-term proton pump inhibitor or metformin use
• Vegetarian or vegan diet layered on top of malabsorption

Symptoms of deficiency

• Fatigue and exertional breathlessness from macrocytic anaemia
• Paraesthesia — numbness, pins and needles, typically starting in the feet
• Loss of proprioception and balance, worse in the dark
• Sore, smooth, beefy-red tongue (glossitis)
• Cognitive slowing, low mood, irritability — sometimes the first sign
• Subacute combined degeneration of the spinal cord in prolonged untreated 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

Serum B12 is the usual first test but is insensitive in the low-normal range. Where B12 sits between roughly 150 and 400 pmol/L, methylmalonic acid (MMA) and homocysteine detect functional deficiency that serum B12 misses — a meaningful proportion of Crohn’s patients. Guidelines recommend annual screening in ileal disease and after any ileal resection. Check folate at the same time: correcting folate alone in combined deficiency can precipitate neurological deterioration.

Replenishment protocols

Standard replacement is intramuscular hydroxocobalamin or cyanocobalamin, typically 1,000 mcg on a loading schedule then every 1–3 months indefinitely where the ileum is absent or badly diseased. High-dose oral B12 (1,000–2,000 mcg/day) also works for many patients, because roughly 1% of an oral dose crosses the entire small intestine by passive diffusion independent of intrinsic factor and ileal receptors — an effect documented specifically in Crohn’s patients. Oral therapy requires monitoring to confirm it is actually working; parenteral dosing remains the safer default after extensive ileal resection. Neurological symptoms warrant parenteral replacement and urgent specialist review.

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

Metformin reduces B12 absorption and is commonly co-prescribed for steroid-induced diabetes in patients on Prednisone. Long-term proton pump inhibitors reduce the gastric acid needed to liberate protein-bound B12 from food. Neither interacts with Humira, Remicade, Stelara, Skyrizi or Entyvio, but biologics that fail to heal ileal inflammation leave the underlying absorptive defect in place — controlling the disease is itself part of correcting the deficiency.

Sources

1. 1

   Prevalence of and risk factors for vitamin B12 deficiency in patients with Crohn’s disease

   Headstrom PD, Rulyak SJ, Lee SD. · Inflammatory Bowel Diseases · 2008 · PMID 17886286

2. 2

   Vitamin B12 deficiency in inflammatory bowel disease: prevalence, risk factors, evaluation, and management

   Battat R, Kopylov U, Szilagyi A, et al. · Inflammatory Bowel Diseases · 2014 · PMID 24859298

3. 3

   Third European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: Part 1: Diagnosis and medical management

   Gomollón F, Dignass A, Annese V, et al. · Journal of Crohn’s and Colitis (ECCO) · 2017 · PMID 27660341