Which folate level should I order to assess a patient's folate status?

Folate Testing: Serum vs. Red Blood Cell Folate

For assessing a patient's folate status, both serum folate and red blood cell (RBC) folate should be ordered, with serum folate being the preferred first-line test for most clinical scenarios. 1

Recommended Testing Approach

First-Line Testing

• Serum folate: Measures short-term folate status and recent intake
  • More cost-effective and faster to perform 1, 2
  • Less influenced by analytical variables 2
  • Normal levels: ≥10 nmol/L 1

Second-Line Testing (When Indicated)

• RBC folate: Measures long-term folate status (past 3-4 months)
  • More time-consuming and costly 2
  • Normal levels: ≥340 nmol/L 1
  • Provides information about tissue stores

When to Order Folate Testing

Folate testing is indicated in the following scenarios:

• Patients with macrocytic anemia 3
• Patients at risk of malnutrition 3
• Patients with diseases known to increase folate needs 3
• When investigating unexplained elevated homocysteine levels 1

Important Considerations

Testing Method

• Folate status should be assessed using methods validated against the microbiological assay (gold standard) 3
• Analysis of homocysteine at the same time improves interpretation of laboratory measurements 3

Clinical Interpretation

• Serum folate levels under 8 μg/L (18 nmol/L) should be considered as a decision limit for folate depletion as this correlates with elevated homocysteine levels 4
• Always check vitamin B12 levels when assessing folate status to avoid masking B12 deficiency 1

Monitoring

• After initiating supplementation, folate levels should be repeated within 3 months to verify normalization 3
• In diseases that increase folate needs, measure every 3 months until stabilization, then annually 3

Advantages of Serum Folate Testing

1. Analytical reliability: Fewer pre-analytical variables affect serum folate compared to RBC folate 2
2. Cost and efficiency: Serum folate testing is less expensive and faster to perform 2
3. Clinical utility: Serum folate often shows higher correlation with homocysteine, a sensitive marker of deficiency 2
4. Response monitoring: Serum folate provides better assessment of response to supplementation 2

Pitfalls to Avoid

• Don't rely solely on RBC folate: While historically considered the gold standard, recent evidence suggests serum folate may be equally or more reliable 2
• Don't forget to check B12 simultaneously: Always check vitamin B12 levels before initiating folate treatment to avoid masking megaloblastic anemia and worsening neurological manifestations 1
• Don't ignore borderline results: Serum folate levels between 8-14 μg/L may indicate early depletion and warrant clinical correlation 4
• Don't miss pre-analytical variables: Sample storage conditions can affect folate measurements; non-hemolyzed blood samples are best stored at 4°C 5

In summary, while both tests have value, serum folate represents the most practical first-line test for assessing folate status in most clinical scenarios, with RBC folate providing complementary information about long-term status when needed.