Systematic Review and Pragmatic Clinical Approach to Oral and Nasal Vitamin B12 (Cobalamin) Treatment in Patients with Vitamin B12 Deficiency Related to Gastrointestinal Disorders

Abstract

The objective of this review is to provide an update on the effectiveness of oral and nasal vitamin B12 (cobalamin) treatment in gastrointestinal (GI) disorders. Relevant articles were identified by PubMed and Google Scholar systematic search, from January 2010 and June 2018, and through hand search of relevant reference articles. Additional studies were obtained from references of identified studies, the Cochrane Library and the ISI Web of Knowledge. Data gleaned from reference textbooks and international meetings were also used, as was information gleaned from commercial sites on the web and data from CARE B12 research group. For oral vitamin B12 treatment, 4 randomized controlled trials (vs. intramuscular), 4 narrative and 4 systematic reviews, and 13 prospective studies fulfilled our inclusion criteria. These studies concerned patients with vitamin B12 deficiency related to: food-cobalamin malabsorption (n = 6), Biermer's disease (n = 3), veganism or vegetarianism (n = 1), total gastrectomy after Roux-en-Y gastric bypass (n = 2) and Crohn's disease (n = 1). Four prospective studies include patients with vitamin B12 deficiency related to the aforementioned etiologies, except veganism or vegetarianism. The systematic present review documents that oral vitamin B12 replacement, at a daily dose of 1000 μg (1 mg), was adequate to normalize serum vitamin B12 levels and cure main clinical manifestations related to vitamin B12 deficiency, in GI disorders, and thus, with safety profile. For nasal vitamin B12 treatment, only one preliminary study was available. We conclude that oral vitamin B12 is an effective alternative to intramuscular vitamin B12 (except in patients presenting with severe neurological manifestations). Oral vitamin B12 treatment avoids the discomfort, contraindication (in patients with anticoagulation), and cost of monthly injections.

Keywords: Biermer’s disease; Cobalamin; food-cobalamin malabsorption; nasal vitamin B12 treatment; oral vitamin B12 treatment; vitamin B12.

Figure 1

Flowchart of the reference research.

Figure 2

Structure and metabolism of the vitamin B12, with a focus on gastrointestinal disorders responsible for vitamin B12 deficiency. The digestive step of the metabolic of cobalamin (cbl) begins with nutrient intake to its intestinal absorption. Endocytic receptors and proteins responsible for vitamin B12 intestinal absorption include cubilin (CUBN), amnionless (AMN), receptor-associated protein and megalin (MGA1). The membrane megalin/transcobalamin II (TCII)-receptor complex allows the cellular uptake of cbl. Lysosomal-mediated degradation of TCII and subsequent release of free-cbl is essential for vitamin B12 metabolic functions. MS, methonine synthase; THF, tetrahydrofolate; MTHFR, methylene tetrahydrofolate reductase; MCM, methylmalonyl CoA mutase.

Figure 3

Pragmatic clinical approach to oral vitamin B12 treatment in patients with vitamin B12 deficiency related to gastrointestinal disorders [14,40].