What is the protocol for oral (per os) vitamin B12 replacement?

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Last updated: April 11, 2025View editorial policy

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From the Guidelines

Oral vitamin B12 replacement is a viable alternative to intramuscular injections for most patients with B12 deficiency, with a recommended oral dosage of 1200 mg/d, as shown in a retrospective open-label non-randomized study of 36 patients with CD 1.

Key Considerations

  • The effectiveness of oral therapy is supported by a study that demonstrated the oral route to be effective in treating vitamin B12 deficiency in patients with Crohn's disease 1.
  • High-dose oral B12 is effective due to passive diffusion, allowing adequate B12 levels to be maintained with daily supplementation.
  • Patients should be monitored with B12 levels after 1-3 months of therapy to ensure adequate replacement.
  • Oral therapy offers advantages including convenience, cost-effectiveness, and avoidance of injection-related pain and anxiety.

Special Considerations

  • Patients with severe neurological symptoms, significant malabsorption syndromes, or poor medication adherence may still benefit from initial parenteral therapy.
  • The decision to start oral or intramuscular vitamin B12 replacement should be based on individual patient factors, including the presence of neurological symptoms and the severity of malabsorption.

Monitoring and Maintenance

  • Patients with more than 20 cm of ileum resected should receive 1000 mg of vitamin B12 prophylactically every month and indefinitely 1.
  • Patients with a clinical deficiency should receive 1000 mg of vitamin B12 by intramuscular injection every other day for a week and then every month for life 1.

From the Research

Per Os B12 Replacement

  • Per os B12 replacement, also known as oral vitamin B12 supplementation, has been studied as an alternative to intramuscular injections for treating vitamin B12 deficiency and pernicious anemia 2, 3, 4, 5.
  • Research suggests that high oral doses of vitamin B12, such as 1000-2000 mcg daily, can be as effective as intramuscular administration in achieving hematological and neurological responses 3, 4, 5.
  • A prospective cohort study found that oral vitamin B12 supplementation at a dosage of 1000 μg/d was effective in improving vitamin B12 deficiency in patients with pernicious anemia, with significant improvements in plasma vitamin B12, homocysteine, and methylmalonic acid concentrations 5.
  • Another study found that oral vitamin B12 replacement at 1000 μg daily was adequate to replace vitamin B12 levels in patients with pernicious anemia, and that patients should be offered this alternative after an informed discussion on the advantages and disadvantages of both treatment options 3.

Dosage and Frequency

  • The recommended dosage for oral vitamin B12 replacement varies, but studies suggest that 1000-2000 mcg daily can be effective 3, 4, 5.
  • The frequency of laboratory tests and clinical monitoring for patients on oral vitamin B12 replacement is not well established, but regular follow-up is recommended to ensure that the treatment is effective and to monitor for any potential side effects 3.

Comparison to Intramuscular Injections

  • Oral vitamin B12 supplementation has been compared to intramuscular injections in several studies, with results suggesting that oral supplementation can be as effective as intramuscular injections in achieving hematological and neurological responses 3, 4, 5.
  • However, more research is needed to fully establish the efficacy and safety of oral vitamin B12 supplementation compared to intramuscular injections 3, 4, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Vitamin B12 replacement therapy: how much is enough?

Wisconsin medical journal, 1994

Research

Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency.

The Cochrane database of systematic reviews, 2005

Research

Oral vitamin B12 supplementation in pernicious anemia: a prospective cohort study.

The American journal of clinical nutrition, 2024

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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