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Which laboratory tests are recommended for diagnosing vitamin B12 deficiency in primary care?

Answer

Guideline-Aligned (High Confidence)
Generated by iatroX. Developer: Dr Kola Tytler MBBS CertHE MBA MRCGP (General Practitioner).
Last reviewed: 22 August 2025

Recommended laboratory tests for diagnosing vitamin B12 deficiency in primary care:

  • Use either total vitamin B12 (serum cobalamin) or active vitamin B12 (serum holotranscobalamin) as the initial test for suspected vitamin B12 deficiency in most cases 1.
  • Use active vitamin B12 as the initial test during pregnancy 1.
  • If vitamin B12 deficiency is suspected due to recreational nitrous oxide use, use plasma homocysteine or serum methylmalonic acid (MMA) as the initial test; plasma homocysteine testing requires referral to secondary care phlebotomy services 1.
  • Take blood samples for diagnostic tests before starting vitamin B12 replacement therapy 1.
  • Interpret total or active B12 test results using defined thresholds or local laboratory reference ranges: less than 180 ng/L (133 pmol/L) total B12 or less than 25 pmol/L active B12 indicates confirmed deficiency; intermediate values require further assessment 1.
  • Consider measuring serum MMA concentrations if symptoms/signs of deficiency are present but initial total or active B12 test results are indeterminate 1.
  • Use laboratory reference ranges to interpret serum MMA and plasma homocysteine results, considering other factors that may affect homocysteine levels such as folate deficiency 1.

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This content was generated by iatroX. Always verify information and use clinical judgment.