How is folate deficiency treated?

Treatment of Folate Deficiency

For most patients with folate deficiency, oral folic acid 1 mg daily is the standard treatment, with doses up to 5 mg daily reserved for specific high-risk situations such as malabsorption, pregnancy after neural tube defects, or medication-induced deficiency. 1

Standard Treatment Approach

General Population Dosing

• Oral folic acid 1 mg daily is the usual therapeutic dose for adults and children of all ages with documented folate deficiency 1
• Doses greater than 1 mg do not enhance the hematologic effect, and most excess is excreted unchanged in urine 1
• Oral administration is preferred even in malabsorption states, as most patients who cannot absorb food folates can still absorb synthetic folic acid 1

Maintenance Therapy

Once clinical symptoms resolve and blood parameters normalize, transition to maintenance dosing 1:

• Infants: 0.1 mg daily
• Children under 4 years: up to 0.3 mg daily
• Adults and children ≥4 years: 0.4 mg daily
• Pregnant and lactating women: 0.8 mg daily
• Never use less than 0.1 mg daily 1

Special Populations Requiring Higher Doses

Medication-Induced Deficiency

Patients on methotrexate should receive 2:

• 5 mg once weekly, given 24-72 hours after methotrexate dose, OR
• 1 mg daily for 5 days per week

Patients on sulfasalazine require supplementation due to folate malabsorption 2

• Both folic acid (15 mg) and folinic acid (15 mg) restore folate stores, though folinic acid is more efficient 2

Pregnancy and High-Risk Situations

Women with prior neural tube defect-affected pregnancy 2, 3:

• 4-5 mg (4000-5000 μg) daily
• Begin at least 1-3 months before conception
• Continue through first trimester

Standard pregnancy supplementation 2:

• 400 μg (0.4 mg) daily for women without prior NTD history
• Begin before conception and continue throughout pregnancy

Inflammatory Bowel Disease

IBD patients with active disease, on sulfasalazine, or with macrocytosis should be tested for folate deficiency (serum and RBC concentrations) 2

• Pregnant IBD patients require regular monitoring of folate levels with supplementation for any deficiency 2

Conditions Requiring Increased Maintenance

The maintenance dose may need to be increased in 1:

• Alcoholism
• Hemolytic anemia
• Anticonvulsant therapy
• Chronic infection

Route of Administration

Oral vs. Parenteral

• Oral route is preferred for nearly all patients 1
• Parenteral administration (IM) is rarely necessary but may be required for patients on parenteral/enteral nutrition 1
• Doses >0.1 mg should not be used until vitamin B12 deficiency is ruled out or adequately treated 1

Critical Safety Consideration

Before initiating folate therapy >0.1 mg, vitamin B12 deficiency must be excluded or simultaneously treated 1. This is essential because:

• Folate can mask the hematologic manifestations of B12 deficiency while allowing neurologic damage to progress 4
• Folate deficiency and B12 deficiency can coexist, particularly in elderly patients 5
• Elevated homocysteine can result from either deficiency, but methylmalonic acid (MMA) is elevated only in B12 deficiency 2

Monitoring and Follow-up

• Patients should be kept under close supervision 1
• Adjust maintenance levels if relapse appears imminent 1
• For IBD patients with ileal involvement: yearly screening for both B12 and folate deficiency 2
• Serum folate should be ≥10 nmol/L and RBC folate ≥340 nmol/L 2

Alternative Formulations

5-methyltetrahydrofolate (5-MTHF) may be preferred over folic acid in specific situations 6, 7:

• Patients with MTHFR polymorphisms who cannot efficiently convert folic acid to active folate
• Concerns about unmetabolized folic acid (UMFA) accumulation with high-dose folic acid
• Better bioavailability unaffected by gastrointestinal pH or metabolic defects 7