Phase II Study of a Multi-center Randomized Controlled Trial to Evaluate Oral Vitamin B12 Treatment for Vitamin B12 Deficiency After Total Gastrectomy in Gastric Cancer Patients

Anticancer Res. 2022 Aug;42(8):3963-3970. doi: 10.21873/anticanres.15891.


Background/aim: This prospective multi-central randomized phase II trial evaluated the efficacy and safety of oral Vitamin B12 500 μg/day replacement compared with oral Vitamin B12 1,500 μg/day in patients with Vitamin B12 deficiency after total gastrectomy for gastric cancer.

Patients and methods: Patients were randomly assigned to receive oral Vitamin B12 500 μg/day or Vitamin B12 1,500 μg/day in a 1:1 ratio with a minimization method. The primary endpoint was the incidence of a normal serum Vitamin B12 level at three months after treatment.

Results: From January 2018 to December 2021, 3 institutions collaborated with the present study, and 74 patients were registered from these 3 institutions. The study was prematurely closed due to poor accrual after reaching almost 50% of its goal. Among the 74 recruited patients, 36 were allocated to the Vitamin B12 500 μg/day arm and 38 to Vitamin B12 1,500 μg/day arm. The incidences of patients with a normal Vitamin B12 level at 3 months (serum Vitamin B12 level >200 pg/ml) were 91.7% (33/36) in the Vitamin B12 500 μg/day arm and 100% (38/38) in the Vitamin B12 1,500 μg/day arm (p=0.3587). The types of clinical symptoms with Vitamin B12 deficiency that improved with Vitamin B12 treatment and the degree of improvement were also similar.

Conclusion: Although the primary endpoint of the present study was not met, it was found that oral Vitamin B12 500 μg/day replacement is as effective and safe as oral Vitamin B12 1,500 μg/day replacement for Vitamin B12 deficiency.

Keywords: Vitamin B12; deficiency; gastric cancer; oral treatment; randomized controlled trial; total gastrectomy.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Gastrectomy / adverse effects
  • Humans
  • Prospective Studies
  • Stomach Neoplasms* / complications
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / surgery
  • Vitamin B 12 / therapeutic use
  • Vitamin B 12 Deficiency* / drug therapy
  • Vitamin B 12 Deficiency* / etiology


  • Vitamin B 12