What is the preferred route of administration for folic acid (oral vs intravenous (IV)) in patients with suspected or confirmed folic acid deficiency?

From the Guidelines

Oral administration is the preferred route for folic acid supplementation in patients with suspected or confirmed folate deficiency. The typical dosage for adults is 1-5 mg daily, depending on the severity of deficiency and underlying condition, as recommended by the espen micronutrient guideline 1. Treatment usually continues for about 4 months to fully replenish body stores, though lifelong supplementation may be necessary for patients with ongoing risk factors such as malabsorption disorders or certain medications. Oral folic acid is preferred because it is highly bioavailable, cost-effective, convenient for patients, and associated with fewer adverse effects compared to IV administration. IV folic acid is generally reserved for specific situations such as patients with severe malabsorption disorders, those who cannot take oral medications, or in emergency situations like severe megaloblastic anemia with neurological symptoms, as noted in the espen micronutrient guideline 1.

Some key points to consider when administering folic acid include:

• Checking and treating for vitamin B12 deficiency before initiating folic acid treatment to avoid precipitation of subacute combined degeneration of the spinal cord, as recommended by the british obesity and metabolic surgery society guidelines 1
• Using oral folic acid 5 mg daily for a minimum of 4 months to treat folic acid deficiency, as recommended by the british obesity and metabolic surgery society guidelines 1
• Being aware of the potential risks of folic acid supplementation, including increased cancer risk and progression, insulin resistance in children, interaction with epilepsy medication, masking of vitamin B12 deficiency, and hepatotoxicity, as noted in the espen micronutrient guideline 1
• Monitoring patients for adverse effects and adjusting the dosage as needed to minimize the risk of neurological complications in vitamin B12-deficient individuals, as recommended by the espen micronutrient guideline 1.

Overall, oral folic acid supplementation is a safe and effective treatment for patients with suspected or confirmed folate deficiency, and oral administration is the preferred route due to its high bioavailability, cost-effectiveness, and convenience.

From the FDA Drug Label

Oral administration is preferred. Although most patients with malabsorption cannot absorb food folates, they are able to absorb folic acid given orally. Parenteral administration is not advocated but may be necessary in some individuals (e.g., patients receiving parenteral or enteral alimentation). DOSAGE AND ADMINISTRATION: Parenteral Administration: IM, IV and SC routes may be used if the disease is exceptionally severe or if gastrointestinal absorption may be, or is known to be, impaired.

The preferred route of administration for folic acid is oral. However, intravenous (IV) administration may be necessary in some cases, such as:

• Patients with severe disease
• Impaired gastrointestinal absorption
• Patients receiving parenteral or enteral alimentation 2 3 Key points:
• Oral administration is preferred due to its ability to be absorbed by patients with malabsorption
• Parenteral administration, including IV, is not the first line of treatment but may be necessary in certain situations

From the Research

Folic Acid Administration Routes

The preferred route of administration for folic acid in patients with suspected or confirmed folic acid deficiency is oral.

• Oral folic acid is generally regarded as safe for normal humans, but it may cause neurological injury when given to patients with undiagnosed pernicious anemia 4.
• There is no evidence to suggest that intravenous (IV) administration of folic acid is necessary or preferred over oral administration for patients with folic acid deficiency.
• Studies have shown that oral folic acid can correct or prevent the anemia of pernicious anemia, but it may mask the underlying disease and allow the development or progression of neurological deterioration if diagnosis depends on the presence of anemic symptoms 5.
• High intakes of folic acid from fortified food and dietary supplements may exacerbate anemia and worsen cognitive symptoms in individuals with vitamin B12 deficiency 6.

Comparison of Oral and IV Folic Acid

• There is limited research comparing the efficacy and safety of oral versus IV folic acid administration.
• One study found that large daily doses of oral folic acid were well tolerated without any evidence of toxic effects, and the minimum folate absorption in the gut ranged from 10.1 to 45.7 percent 7.
• The American College of Obstetricians and Gynecologists recommends a daily multivitamin with folic acid for all women of childbearing potential to prevent neural tube defects, and this can be achieved through oral supplementation 8.