From the FDA Drug Label
L-METHYLFOLATE CALCIUM Tablets may be less likely than folic acid to mask vitamin B12 deficiency. The answer to whether methylfolate (MTHF) is more effective than folic acid (Vitamin B9) is not directly addressed in the provided drug label. However, it can be noted that:
- Methylfolate may have an advantage over folic acid in terms of not masking vitamin B12 deficiency. No direct comparison of effectiveness between methylfolate and folic acid is provided in the label 1.
From the Research
Methylfolate is more effective than folic acid for improving folate status, particularly in individuals with MTHFR gene mutations or those who cannot efficiently convert folic acid to its active form, as evidenced by the most recent study in 2022 2. When considering the effectiveness of methylfolate (MTHF) versus folic acid, it's essential to understand the role of folate in the body and how these two forms of folate are utilized. Methylfolate is the already-activated form of folate that the body can immediately use, bypassing the conversion process required for folic acid.
Key Points to Consider
- Methylfolate supplements are generally available in doses similar to folic acid (400-1000 mcg daily) and have the advantage of being directly bioavailable.
- Folic acid, on the other hand, requires enzymatic conversion in the body, which can be a concern for individuals with certain genetic variants or those taking medications that interfere with folate metabolism.
- The most recent and highest quality study, published in 2022 2, suggests that (6S)5-MTHF supplementation is preferred over folic acid for its ability to bypass the block in folic acid metabolism linked to enzymatic polymorphism.
- Another study from 2024 3 highlights the need for more clinical studies to establish 5-MTHF as a safe and effective therapeutic approach comparable with folic acid, but acknowledges the potential value of 5-MTHF as an alternative to folic acid.
Recommendations
- For most healthy individuals, standard folic acid supplements (typically 400-800 mcg daily) may work effectively, but those with MTHFR mutations, certain digestive disorders, or those taking medications that interfere with folate metabolism may benefit from taking methylfolate instead.
- If concerned about folate absorption or having known genetic variants affecting folate metabolism, consider discussing methylfolate supplementation with a healthcare provider, as supported by studies such as 4, 5, and 6.