Prevalence and Risk Factors for Functional Vitamin B12 Deficiency in Patients with Crohn's Disease

Crohn's disease (CD) is a risk factor for vitamin B12 deficiency due to frequent involvement of the terminal ileum. Conventional screening for B12 deficiency with serum B12 is relatively insensitive and measures total B12 concentration, of which a minority is present in a biologically active form. Holotranscobalamin (holoTC) combined with methylmalonic acid (MMA) is believed to be more accurate in identifying impaired B12 status. We evaluated the prevalence and risk factors for B12 deficiency using holoTC supported by MMA among patients with CD.

We performed a single-center service evaluation of 381 patients with CD who underwent B12 assessment (holoTC/MMA) and compared them with 141 patients with ulcerative colitis. Eighty-nine patients with CD underwent paired serum B12 and holoTC. Among patients with CD, risk factors including terminal ileal resection length, ileal inflammation on endoscopy, and disease characteristics on magnetic resonance imaging were recorded.

Prevalence of B12 deficiency among patients with CD was 33% compared with 16% in ulcerative colitis (P < 0.0001). In 89 patients who underwent paired tests, conventional testing identified B12 deficiency in 5% of patients with CD, which increased to 32% using holoTC/MMA. Independent risk factors for B12 deficiency were ileal resection length ≤20 cm (odds ratio: 3.0, 95% confidence interval, 1.5-6.0, P = 0.002) and >20 cm (odds ratio: 6.7, 95% confidence interval, 3.0-14.7, P < 0.0001) and ileal inflammation (odds ratio: 3.9, 95% confidence interval, 2.2-6.9, P < 0.0001). On magnetic resonance imaging, active terminal ileal inflammation (P = 0.02) and an increased disease burden (≥1 skip lesion, P = 0.01 and prestenotic dilatation >3 cm, P = 0.01) were associated with B12 deficiency.

Vitamin B12 deficiency is common in patients with CD. holoTC supported by MMA identifies patients with B12 deficiency considered replete on conventional testing.