When should a vitamin B12 (Vit B12) test be ordered?

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Last updated: June 28, 2025View editorial policy

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From the Guidelines

A vitamin B12 test should be ordered when patients show symptoms of deficiency, such as fatigue, weakness, pale skin, numbness or tingling in hands and feet, balance problems, confusion, memory issues, or depression, particularly in high-risk individuals including older adults, vegetarians and vegans, those with gastrointestinal disorders, people taking certain medications, and those with autoimmune conditions like pernicious anemia.

Key Considerations for Testing

  • Testing is crucial for patients with malabsorption conditions or those on long-term medications that affect B12 absorption, as indicated by 1.
  • The test measures serum B12 levels, with values below 200 pg/mL generally indicating deficiency.
  • Early detection of deficiency is important as some neurological damage from prolonged deficiency can be irreversible, even after treatment begins.

High-Risk Groups

  • Older adults
  • Vegetarians and vegans
  • Those with gastrointestinal disorders (like Crohn's disease, celiac disease, or after gastric surgery)
  • People taking certain medications (metformin, proton pump inhibitors, or H2 blockers)
  • Those with autoimmune conditions like pernicious anemia

Testing Approach

  • Use either total B12 (serum cobalamin) or active B12 (serum holotranscobalamin) as the initial test for suspected vitamin B12 deficiency, as recommended by 1.
  • Consider a further test to measure serum MMA concentrations in people who have symptoms or signs of vitamin B12 deficiency and an indeterminate total or active B12 test result, based on very low certainty evidence from 1.

Importance of Timely Testing

  • Vitamin B12 deficiency is a complex condition with significant variability in the type and severity of symptoms, as noted by 1.
  • Timely testing is essential to identify people with a clinical deficiency and achieve a diagnosis, while avoiding unnecessary testing in those unlikely to be deficient, as emphasized by 1.

From the FDA Drug Label

Hematocrit, reticulocyte count, vitamin B12, folate and iron levels should be obtained prior to treatment.

A Vitamin B12 test should be ordered:

  • Prior to treatment of patients with pernicious anemia
  • For patients with neurologic manifestations that may be related to vitamin B12 deficiency
  • For patients with folate deficiency to rule out vitamin B12 deficiency
  • For patients with increased need for vitamin B12, such as those who are pregnant or lactating
  • For patients who are at risk of vitamin B12 deficiency, such as those with a vegetarian diet or who have been taking certain medications that may interfere with vitamin B12 absorption 2

From the Research

When to Order a Vitamin B12 Test

A vitamin B12 test should be ordered in the following situations:

  • When a patient presents with unexplained anemia and/or neurological symptoms, as vitamin B12 deficiency can cause megaloblastic anemia and various neuropsychiatric symptoms 3, 4
  • In patients with risk factors for vitamin B12 deficiency, such as:
    • Gastric or small intestine resections 3
    • Inflammatory bowel disease 3
    • Use of metformin for more than four months 3
    • Use of proton pump inhibitors or histamine H2 blockers for more than 12 months 3
    • Vegans or strict vegetarians 3, 4
    • Adults older than 75 years 3
  • In patients who have had bariatric surgery, as they are at risk of vitamin B12 deficiency due to impaired absorption 5, 6
  • In children with neurological symptoms, as vitamin B12 deficiency can cause a range of neurological symptoms, including headache, seizure, and developmental delay 7

Laboratory Assessment

Initial laboratory assessment should include:

  • A complete blood count 3
  • Serum vitamin B12 level 3, 4
  • Measurement of serum methylmalonic acid to confirm deficiency in asymptomatic high-risk patients with low-normal levels of vitamin B12 3

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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