Folate (vitamin B9) is essential for red blood cell production and DNA synthesis. The folate test measures folate in blood, helping evaluate macrocytic anemia and other conditions. Folate deficiency was historically common but has decreased in the US since folic acid fortification of grain products beginning in 1998. This guide covers folate testing and interpretation.
Serum vs RBC folate
Two forms of folate testing:
Serum folate: Reflects recent intake. Can be normal even with chronic deficiency if patient has eaten folate recently.
Red blood cell (RBC) folate: Reflects long-term folate status (over the lifetime of red cells, ~120 days). More reliable for chronic deficiency.
Reference ranges
- Serum folate: above 4 ng/mL (varies)
- RBC folate: above 280 ng/mL (varies)
Causes of folate deficiency
- Inadequate intake (poor diet)
- Alcoholism
- Malabsorption (celiac, Crohn’s)
- Increased demand (pregnancy)
- Medications (methotrexate, sulfasalazine, phenytoin)
- Hemolytic anemia (increased turnover)
Folate vs B12 deficiency
Both cause macrocytic anemia. Distinguishing matters because B12 deficiency causes neurological complications that folate doesn’t, and folate replacement alone in B12 deficiency can mask the anemia while neurological damage progresses.
When evaluating macrocytic anemia, check both folate and B12. The standard of care is to ensure B12 isn’t deficient before initiating folate replacement.
Folate in pregnancy
Adequate folate is critical for preventing neural tube defects in early pregnancy. Recommendations:
- 400 mcg daily for women of reproductive age
- 600 mcg daily during pregnancy
- Higher doses (4 mg) for women with prior NTD-affected pregnancies
Folic acid supplementation should ideally start before conception.
MTHFR variants
MTHFR gene variants affect folate metabolism. Some companies promote testing and methylated folate supplements. Mainstream guidance:
- MTHFR variants are very common (about 25% of population)
- Clinical significance is generally limited
- Standard folic acid supplementation is adequate for most patients
- Methylated folate (5-MTHF) supplementation isn’t routinely necessary
Frequently Asked Questions
Should I test folate if I’m anemic?
For macrocytic anemia, yes — alongside B12.
Do I need to fast for folate testing?
RBC folate doesn’t require fasting. Serum folate may be affected by recent meals.
Should pregnant women get folate tested?
Generally not necessary if appropriate prenatal vitamin supplementation is taken. Testing reserved for specific concerns.
Should I take methylated folate?
Generally not necessary for most patients. Standard folic acid is adequate.
Is folate deficiency common in the US?
Less common since fortification began in 1998. Specific risk groups (alcoholism, malabsorption, certain medications) remain at risk.
The bottom line on the folate test
Folate testing helps evaluate macrocytic anemia and folate deficiency. RBC folate is more reliable than serum folate for chronic deficiency. B12 must be checked alongside folate to avoid masking neurological complications. Discuss results with your healthcare provider for appropriate interpretation.