Can methyl folate be used instead of folic acid (Vitamin B9) for treating folate deficiency anemia?

From the Guidelines

Methylfolate can be used as an alternative to folic acid for treating folate deficiency anemia, but it is crucial to first rule out vitamin B12 deficiency to avoid masking its symptoms and potentially precipitating subacute combined degeneration of the spinal cord. The decision to use methylfolate instead of folic acid should be based on individual patient needs and preferences, considering factors such as the presence of MTHFR gene mutations, which can affect the body's ability to convert folic acid into its active form 1. Methylfolate is the active form of folate that the body uses, bypassing the need for conversion by the MTHFR enzyme, which may be beneficial for individuals with genetic mutations affecting this enzyme.

For patients with folate deficiency anemia, the typical dose of methylfolate could range from 1-5 mg daily until blood counts normalize, followed by a potential maintenance dose of 400-800 mcg daily. However, it's essential to work with a healthcare provider to determine the appropriate dosage and duration of treatment, as they will need to monitor blood counts to ensure the anemia is resolving and adjust treatment accordingly. The guidelines recommend treating folic acid deficiency with 5 mg of folic acid orally daily for a minimum of 4 months, but this can be adjusted based on the patient's response and the presence of any underlying conditions that may affect folate metabolism 1.

Key considerations in choosing between methylfolate and folic acid include:

• The patient's genetic profile, particularly the presence of MTHFR gene mutations
• The cost and availability of methylfolate supplements compared to folic acid
• The potential benefits of using the active form of folate, especially in patients with known difficulties in converting folic acid to its active form
• The importance of monitoring and adjusting treatment under the guidance of a healthcare provider to ensure effective management of folate deficiency anemia and to prevent complications associated with untreated vitamin B12 deficiency 1.

From the Research

Methyl Folate as an Alternative to Folic Acid

• Methyl folate, also known as 5-methyltetrahydrofolate (5-MTHF), can be used instead of folic acid for treating folate deficiency anemia, as it has several advantages over synthetic folic acid 2.
• 5-MTHF is well absorbed even when gastrointestinal pH is altered and its bioavailability is not affected by metabolic defects, making it a better option for individuals with certain genetic polymorphisms or gastrointestinal issues 2.
• Using 5-MTHF instead of folic acid reduces the potential for masking haematological symptoms of vitamin B12 deficiency and reduces interactions with drugs that inhibit dihydrofolate reductase 2.

Benefits of Methyl Folate in Specific Populations

• Individuals with methylenetetrahydrofolate reductase (MTHFR) polymorphisms may benefit from supplementation with 5-MTHF, as it can bypass the metabolic defects caused by these polymorphisms 3.
• Patients with increased folate demand, such as those undergoing anti-folate therapies, may also benefit from pharmacogenetics-based therapy choices that include 5-MTHF supplementation 3.
• In healthy individuals, the MTHFR C677T polymorphism, folate deficiency, and vitamin B12 deficiency are associated with elevated serum total homocysteine levels, and supplementation with folic acid and vitamin B12 may help prevent diseases associated with homocysteine accumulation 4.

Clinical Implications

• Screening for MTHFR polymorphisms and folate cycle status may help identify patients who are most likely to benefit from MYC-targeting therapies, and supplementation with 5-MTHF may enhance the effects of these therapies 5.
• Folate restriction and deficiency of the MTHFR enzyme can induce resistance to MYC-targeting therapies, and supplementation with 5-MTHF can abrogate this effect 5.