From the Guidelines
Folic acid supplementation is recommended over methylfolate for treating folate deficiency anemia, with a dose of 5 mg daily for a minimum of 4 months, as suggested by the British Obesity and Metabolic Surgery Society guidelines 1. The guidelines emphasize the importance of checking and treating vitamin B12 deficiency before initiating folic acid treatment to avoid precipitation of subacute combined degeneration of the spinal cord. Key points to consider when treating folate deficiency anemia include:
- Checking for vitamin B12 deficiency before starting folic acid treatment
- Using folic acid 5 mg orally daily for a minimum of 4 months
- Investigating further if there is suspicion of malabsorption
- Being aware that high doses of unmetabolized folic acid may mask vitamin B12 deficiency symptoms while allowing neurological damage to progress, although this is more relevant to the choice between folic acid and methylfolate in specific patient populations, such as those with MTHFR gene mutations. However, the provided evidence does not specifically compare the effectiveness of methylfolate and folic acid in treating folate deficiency anemia, but it does provide guidance on the treatment of folic acid deficiency, which is to use folic acid 5 mg daily for a minimum of 4 months 1. Additionally, the WHO defines folate deficiency as serum folate < 10 nmol/L or red blood cell folate < 305 nmol/L, and recommends daily allowances of 0.4 to 1 mg of folate per day 1. It's also important to note that the treatment should continue until blood counts normalize and underlying causes are addressed, usually 1-3 months. In terms of side effects, folic acid is generally well-tolerated, but high doses may cause gastrointestinal symptoms. Overall, while methylfolate may be beneficial in certain cases, such as in individuals with MTHFR gene mutations, the current evidence suggests that folic acid is a suitable and effective treatment for folate deficiency anemia, and its use is supported by guidelines and recommendations from reputable sources 1.
From the FDA Drug Label
L-METHYLFOLATE CALCIUM Tablets may be less likely than folic acid to mask vitamin B12 deficiency. Folate therapy alone is inadequate for the treatment of a B12 deficiency. Folic acid is effective in the treatment of megaloblastic anemias due to a deficiency of folic acid (as may be seen in tropical or nontropical sprue) and in anemias of nutritional origin, pregnancy, infancy, or childhood.
Methyl folate may be a better option for treating folate deficiency anemia because it is less likely to mask vitamin B12 deficiency compared to folic acid 2. However, it is essential to note that folate therapy alone is inadequate for the treatment of a B12 deficiency.
- Folic acid is effective in treating megaloblastic anemias due to folic acid deficiency, but it may obscure the detection of B12 deficiency 3. It is crucial to address both folate and vitamin B12 deficiencies to effectively treat folate deficiency anemia.
From the Research
Folate Deficiency Anemia Treatment
The treatment of folate deficiency anemia can be approached through supplementation with either methyl folate or folic acid. The effectiveness of these supplements depends on various factors, including genetic predispositions and the presence of certain polymorphisms.
- Methyl Folate vs. Folic Acid: A study published in the Journal of Clinical Medicine 4 found that supplementation with folic acid is sufficient to maintain adequate folate levels in individuals with normal MTHFR activity. However, individuals with low MTHFR activity require methyl folate to overcome metabolic defects caused by polymorphisms in their MTHFR genes.
- Genetic Predisposition: Research has shown that the MTHFR C677T polymorphism is associated with elevated serum total homocysteine levels, which can be mitigated by folic acid and vitamin B12 supplementation 5.
- Folic Acid Fortification: Mandatory folic acid fortification of enriched cereal grains has been shown to nearly eliminate folate-deficiency anemia in older US adults 6.
- Iron-Folic Acid Treatment: A longitudinal study found that iron-folic acid treatment is effective in reducing anemia prevalence and improving iron status in women of reproductive age 7.
- Folate Deficiency and Liver Diseases: While folate deficiency can induce liver disorders, excessive use of folic acid has also been reported to have adverse effects on the liver 8.
Key Considerations
When considering supplementation for folate deficiency anemia, it is essential to take into account individual genetic predispositions and the presence of certain polymorphisms. Additionally, the effectiveness of folic acid fortification and iron-folic acid treatment in preventing and treating anemia should be considered.