Which lab assesses vitamin B12 and folate levels?

Laboratory Assessment of Vitamin B12 and Folate Status

Vitamin B12 and folate status should be assessed through serum/plasma measurements for recent status and red blood cell folate for long-term status, with additional metabolic markers to improve diagnostic accuracy. 1

Primary Laboratory Tests for B12 and Folate

• Serum/plasma folate reflects recent dietary intake and should be measured with normal levels being ≥10 nmol/L 1, 2
• Red blood cell (RBC) folate reflects long-term folate status (preceding 3 months) and tissue stores, with normal levels being ≥340 nmol/L 1, 2, 3
• Serum/plasma vitamin B12 measures both intake and stores, with levels below 150 pmol/L indicating deficiency 1, 3
• Holotranscobalamin (vitamin B12 bound to transcobalamin) is an increasingly recognized marker for early depletion of vitamin B12 1, 2

Supplementary Metabolic Markers

• Plasma homocysteine is a functional marker for both folate and vitamin B12 status, as both vitamins are involved in homocysteine metabolism 1, 2, 3
• Methylmalonic acid (MMA) is specific for vitamin B12 deficiency and helps differentiate it from isolated folate deficiency 1, 2, 3
• Combined measurement of these metabolites increases diagnostic sensitivity, as they may be elevated even when vitamin levels are in the low-normal range 1

Analytical Methods

• Microbiological assay (MBA) using Lactobacillus rhamnosus is considered the gold standard for folate measurement 1, 2
• Protein binding assays are available but have different affinities for different folate forms 1
• Liquid chromatography-mass spectrometry (LC-MS) can quantify different folate forms with good sensitivity but requires specialized equipment and expertise 1, 2

Clinical Considerations and Pitfalls

• Always measure both folate and vitamin B12 simultaneously, as deficiency symptoms overlap 1
• Folic acid supplementation can mask B12 deficiency by correcting the anemia while allowing neurological damage to progress 4, 5
• Vitamin B12 deficiency left untreated for more than 3 months may produce permanent degenerative lesions of the spinal cord 4, 5
• Certain medications and conditions can affect test results:
  • Most antibiotics, methotrexate, and pyrimethamine can invalidate folate and B12 diagnostic assays 4, 5
  • Colchicine, para-aminosalicylic acid, and heavy alcohol intake can affect vitamin B12 absorption 4, 5

Testing Frequency

• In patients with macrocytic anemia or at risk of malnutrition, folate status should be measured at baseline and repeated within 3 months after supplementation 1
• For diseases known to increase folate needs, measure every 3 months until stabilization, then annually 1
• For vitamin B12, regular monitoring is essential, particularly in patients with pernicious anemia who require lifelong supplementation 4, 5

Interpretation of Results

• Low serum folate with normal RBC folate suggests recent dietary inadequacy 1
• Low RBC folate suggests chronic folate deficiency 1
• Elevated homocysteine with normal MMA suggests folate deficiency 1, 3
• Elevated homocysteine and elevated MMA suggest vitamin B12 deficiency 1, 3

Following these laboratory assessment guidelines will help accurately diagnose vitamin B12 and folate deficiencies, allowing for appropriate treatment to prevent potentially irreversible neurological complications.