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How should I interpret the results of serum B12 and folate levels in the context of macrocytic anaemia?

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Guideline-Aligned (High Confidence)
Generated by iatroX. Developer: Dr Kola Tytler MBBS CertHE MBA MRCGP (General Practitioner).
Last reviewed: 16 August 2025

Interpreting serum vitamin B12 and folate levels in macrocytic anaemia:

Serum vitamin B12 and folate levels are essential to identify the cause of macrocytic anaemia, which is often due to deficiency of either vitamin B12 or folate. A low serum vitamin B12 level (less than 180 nanograms/L or 133 pmol/L) confirms vitamin B12 deficiency, while levels between 180 and 350 nanograms/L (133–258 pmol/L) are indeterminate and may require further testing such as serum methylmalonic acid (MMA) or plasma homocysteine to clarify deficiency status. Levels above 350 nanograms/L (258 pmol/L) suggest vitamin B12 deficiency is unlikely. For folate, low serum folate indicates folate deficiency contributing to macrocytosis.

In cases of confirmed vitamin B12 deficiency, treatment should be started promptly, especially if neurological symptoms are present, without waiting for further test results. If initial B12 treatment does not improve anaemia, serum folate should be checked to exclude concurrent folate deficiency, which can mask or coexist with B12 deficiency. After 8 weeks of treatment, blood counts and mean cell volume should normalize; at this point, iron and folate levels should be reassessed to detect any masked deficiencies.

Interpretation must consider factors affecting test results, such as prior vitamin B12 supplementation, medications, and ethnicity. If results are indeterminate or symptoms persist despite normal or borderline levels, further testing with MMA or homocysteine is advised. Referral to a dietician is recommended if deficiency is thought to be due to poor diet.

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