How is folate deficiency treated?

Treatment of Folate Deficiency

Folate deficiency should be treated with oral folic acid 5 mg daily for a minimum of 4 months, with treatment continuing until the underlying cause of deficiency is corrected. 1

Diagnostic Considerations Before Treatment

• Always rule out vitamin B12 deficiency before initiating folate treatment, as folic acid supplementation can mask B12 deficiency while allowing neurological damage to progress 1, 2
• Assess folate status through:
  • Serum folate measurements (normal ≥10 nmol/L) for short-term status 3, 1
  • Red blood cell folate (normal ≥340 nmol/L) for long-term status 3, 1
  • Consider measuring homocysteine levels as a functional marker of folate status 3

Treatment Protocol

Standard Treatment

• First-line treatment: Oral folic acid 5 mg daily for at least 4 months 1, 4
• Continue treatment until the underlying cause of deficiency is corrected 1
• For maintenance after normalization:
  • 0.1 mg for infants 4
  • Up to 0.3 mg for children under 4 years 4
  • 0.4 mg for adults and children 4+ years 4
  • 0.8 mg for pregnant and lactating women 4
  • Never less than 0.1 mg/day 4

Alternative Administration Routes

• If oral treatment is ineffective or not tolerated, folic acid can be administered subcutaneously, intravenously, or intramuscularly at 0.1 mg/day 1
• Parenteral administration is not generally advocated but may be necessary for patients receiving parenteral or enteral alimentation 4

Special Populations

Pregnant Women

• Women of childbearing age should consume 400 μg (0.4 mg) of folic acid daily to prevent neural tube defects 3
• Women with previous neural tube defect-affected pregnancies should take 4 mg daily starting at least 1 month before conception and continuing through the first trimester 3, 1

Patients with Comorbidities

• Higher maintenance doses may be needed in the presence of:
  • Alcoholism 4
  • Hemolytic anemia 4
  • Anticonvulsant therapy 4
  • Chronic infection 4

Monitoring Response to Treatment

• Recheck folate levels within 3 months after supplementation to verify normalization 1
• In diseases known to increase folate requirements, monitor folate status every 3 months until stabilization, then annually 1

Clinical Pitfalls to Avoid

• Never initiate folic acid treatment without first ruling out vitamin B12 deficiency - this can mask B12 deficiency while allowing neurological damage to progress 1, 2
• Do not discontinue treatment prematurely - the full 4-month course is necessary to replenish folate stores 1
• Avoid exceeding 1 mg/day without medical supervision unless specifically indicated (as in pregnancy with prior NTD history), as excess is excreted unchanged in the urine and higher doses do not enhance the hematologic effect 4
• Be aware that doses greater than 1 mg may complicate the diagnosis of vitamin B12 deficiency 3

Causes Requiring Specific Attention

• For folate deficiency due to medications (e.g., methotrexate, trimethoprim, anticonvulsants), consider dose adjustment or alternative medications when possible 5
• In alcoholism, emphasize abstinence along with supplementation 5
• For malabsorption syndromes, higher doses or parenteral administration may be necessary 4