What are the effects of Vitamin B12 (Cobalamin) deficiency?

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Last updated: April 17, 2025View editorial policy

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From the Guidelines

Vitamin B12 deficiency should be treated with supplementation, typically starting with intramuscular injections for severe cases followed by oral maintenance therapy, as this approach has been shown to effectively manage the condition and prevent long-term neurological damage 1. For severe deficiency, begin with hydroxocobalamin or cyanocobalamin injections 1000 mcg given every other day for 1-2 weeks, then weekly for 4-8 weeks, and monthly thereafter. For less severe cases or maintenance, oral supplementation of 1000-2000 mcg daily is effective. Common symptoms of deficiency include:

  • Fatigue
  • Weakness
  • Pale skin
  • Numbness or tingling in extremities
  • Balance problems
  • Depression
  • Memory issues
  • Glossitis Diagnosis requires blood tests measuring serum B12 levels, methylmalonic acid, and homocysteine. Risk factors include strict vegetarian/vegan diets, pernicious anemia, gastrointestinal disorders, certain medications (metformin, proton pump inhibitors), and age over 60. Untreated B12 deficiency can lead to permanent neurological damage, so prompt treatment is essential. Dietary sources include animal products like meat, fish, eggs, and dairy. Vegans should take B12 supplements regularly to prevent deficiency, as evidenced by studies showing the effectiveness of B vitamins in reducing the risk of stroke 1. It is also important to note that vitamin B12 deficiency is associated with an extensive range of neuromuscular symptoms, which become more severe as deficiency progresses, including paraesthesia, and numbness in the trunk, muscle weakness, abnormal reflexes, tendon jerks, spasticity, gait ataxia, myelopathies and myelo-neuropathies 1. Therefore, early detection and treatment of vitamin B12 deficiency are crucial to prevent long-term complications and improve quality of life.

From the FDA Drug Label

PRECAUTIONS General Vitamin B12 deficiency that is allowed to progress for longer than 3 months may produce permanent degenerative lesions of the spinal cord. Doses of folic acid greater than 0. 1 mg per day may result in hematologic remission in patients with vitamin B12 deficiency. Neurologic manifestations will not be prevented with folic acid, and if not treated with vitamin B12, irreversible damage will result. Information for Patients Patients with pernicious anemia should be informed that they will require monthly injections of vitamin B12 for the remainder of their lives. Failure to do so will result in return of the anemia and in development of incapacitating and irreversible damage to the nerves of the spinal cord Also, patients should be warned about the danger of taking folic acid in place of vitamin B12, because the former may prevent anemia but allow progression of subacute combined degeneration.

Vitamin B12 Deficiency can lead to permanent degenerative lesions of the spinal cord if left untreated for more than 3 months.

  • Key points:
    • Folic acid may mask the symptoms of vitamin B12 deficiency but will not prevent neurologic manifestations.
    • Untreated vitamin B12 deficiency can result in irreversible damage to the spinal cord.
    • Patients with pernicious anemia require monthly injections of vitamin B12 for life to prevent recurrence of anemia and nerve damage.
    • A vegetarian diet without animal products can lead to vitamin B12 deficiency, and patients should be advised to take oral vitamin B12 regularly.
    • Pregnancy and lactation increase the need for vitamin B12, and deficiency has been recognized in infants of vegetarian mothers who were breastfed 2.

From the Research

Vitamin B12 Deficiency Overview

  • Vitamin B12 deficiency is a common cause of megaloblastic anemia, various neuropsychiatric symptoms, and other clinical manifestations 3.
  • The deficiency can affect individuals at all ages, but most particularly elderly individuals, infants, children, adolescents, and women of reproductive age are also at high risk of deficiency in populations where dietary intake of B12-containing animal-derived foods is restricted 4.

Risk Factors and Screening

  • Screening average-risk adults for vitamin B12 deficiency is not recommended, but screening may be warranted in patients with one or more risk factors, such as gastric or small intestine resections, inflammatory bowel disease, use of metformin for more than four months, use of proton pump inhibitors or histamine H2 blockers for more than 12 months, vegans or strict vegetarians, and adults older than 75 years 3.
  • Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency 5.

Diagnosis and Laboratory Assessment

  • Initial laboratory assessment should include a complete blood count and serum vitamin B12 level 3.
  • Measurement of serum methylmalonic acid should be used to confirm deficiency in asymptomatic high-risk patients with low-normal levels of vitamin B12 3.
  • Diagnostic biomarkers for B12 status include decreased levels of circulating total B12 and transcobalamin-bound B12, and abnormally increased levels of homocysteine and methylmalonic acid 4.

Treatment and Management

  • Oral administration of high-dose vitamin B12 (1 to 2 mg daily) is as effective as intramuscular administration for correcting anemia and neurologic symptoms 3.
  • Intramuscular therapy leads to more rapid improvement and should be considered in patients with severe deficiency or severe neurologic symptoms 3.
  • Oral vitamin B12 supplementation at 1000 μg daily was adequate to replace vitamin B12 levels in patients with pernicious anemia 6, 7.
  • The use of high-dose oral B12 at different frequencies may be considered for long-term treatment 5.
  • Prophylactic B12 supplementation should be considered for specific high-risk groups, such as patients who have had bariatric surgery, who should receive 1 mg of oral vitamin B12 per day indefinitely 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Vitamin B12 Deficiency: Recognition and Management.

American family physician, 2017

Research

Vitamin B12 deficiency.

Nature reviews. Disease primers, 2017

Research

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

The American journal of clinical nutrition, 2024

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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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