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Understanding Methylated Folate: Forms and Benefits Explained

Dive into the world of methylated folate, exploring key forms such as 5-MTHF, L-methylfolate, and (6S)-5-Methyltetrahydrofolate. Learn about their bioavailability and benefits, especially for those with MTHFR gene polymorphisms or metabolic issues.


  • What forms of methylated folate?

  • Methylated folate, primarily known as 5-methyltetrahydrofolate (5-MTHF), is a biologically active form of folate that is often preferred over traditional folic acid due to better bioavailability and reduced risk of masking vitamin B12 deficiency1. Key forms of methylated folate include:

    1. 5-Methyltetrahydrofolate (5-MTHF): Also known as L-5-MTHF, methylfolate, or L-methylfolate, this is the predominant form of folate in the blood and is readily available for transport and metabolism without needing further reduction1.
    2. L-methylfolate: A commonly used supplemental form of 5-MTHF, particularly beneficial for individuals with MTHFR gene polymorphisms2.
    3. (6S)-5-Methyltetrahydrofolate: This variant is specifically noted for its stereochemistry, ensuring the active form of the supplement2.

    These forms are beneficial, especially for individuals with metabolic issues or genetic variations that impair the conversion of folic acid to active folate.

    Footnotes

    1. Office of Dietary Supplements - Folate 2

    2. Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health 2

  • What is quatrefolic?

  • Quatrefolic is a patented, glucosamine salt form of L-5-methyltetrahydrofolate (5-MTHF), developed by Gnosis by Lesaffre12. This form of 5-MTHF offers several benefits over traditional folic acid and other forms of folate due to its improved solubility and enhanced bioavailability12.

    Key Points about Quatrefolic:

    1. High Bioavailability: Quatrefolic is designed to be directly used by the body without the need for additional metabolic conversion, which is beneficial for individuals with metabolic or genetic impairments, such as MTHFR polymorphisms1.
    2. Improved Solubility: The glucosamine salt formulation of Quatrefolic improves its solubility and absorption in the gastrointestinal tract, making it more effective than other folate supplements2.
    3. Direct Action: As the active form of folate, Quatrefolic participates directly in crucial biological processes, including DNA synthesis and repair, and the conversion of homocysteine to methionine1.

    Using Quatrefolic in supplements and prenatal vitamins can ensure that individuals receive an efficient and reliable source of folate, supporting various health needs without the potential risks associated with unmetabolized folic acid.

    Footnotes

    1. Lorena Carboni, "Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health," PubMed Central, 2023. 2 3 4

    2. Niccolò Miraglia, "Enhanced oral bioavailability of a novel folate salt: comparison with folic acid and a calcium folate salt in a pharmacokinetic study in rats," PubMed Central, 2024. 2 3

  • What does the glucosamine salt in quatrefolic do?

  • The glucosamine salt in Quatrefolic serves several important functions that enhance the efficacy and stability of the active folate, L-5-methyltetrahydrofolate (L-5-MTHF):

    1. Improved Solubility: Adding glucosamine to L-5-MTHF significantly increases its solubility in water. This enhanced solubility facilitates better absorption in the gastrointestinal tract, making the active folate more available for the body to use12.

    2. Enhanced Bioavailability: Research has shown that Quatrefolic offers superior bioavailability compared to other forms of folate, such as folic acid and calcium-based L-5-MTHF. The glucosamine salt form achieves higher peaks in plasma folate levels, ensuring more efficient and rapid uptake by the body2.

    3. Stability: The glucosamine salt form provides enhanced chemical stability to L-5-MTHF. Folate molecules in their free form can be unstable and susceptible to degradation. The glucosamine form helps protect the integrity of the folate molecule until it is absorbed2.

    4. Avoidance of Metabolic Steps: Quatrefolic, being a ready-to-use form of folate, bypasses the need for enzymatic conversion steps required by other forms such as folic acid. This is particularly beneficial for individuals with genetic mutations like MTHFR polymorphisms, which could impair the conversion of folic acid to its active form1.

    These benefits make Quatrefolic a highly effective form of folate supplementation, especially for individuals with specific metabolic needs or absorption challenges.

    Footnotes

    1. Lorena Carboni, "Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health," PubMed Central, 2023. 2

    2. Niccolò Miraglia, "Enhanced oral bioavailability of a novel folate salt: comparison with folic acid and a calcium folate salt in a pharmacokinetic study in rats," PubMed Central, 2024. 2 3

  • What is the equivalent of quatrefolic to 7.5mg l-methylfolate?

  • Quatrefolic, a glucosamine salt form of L-5-methyltetrahydrofolate (L-5-MTHF), can be directly compared with other forms of L-methylfolate based on bioavailability and activity. While specific studies detailing exact equivalency conversions between Quatrefolic and standard L-methylfolate doses might be limited, general guidelines from folate supplementation indicate that bioavailability and efficacy are considered similar when the compounds are in their bioactive forms12.

    Given the structural and functional similarities, a direct 1:1 replacement is often assumed for practical purposes:

    • Quatrefolic 7.5mg = L-methylfolate 7.5mg

    Here, 7.5mg of Quatrefolic would be equivalent to 7.5mg of L-methylfolate. The enhanced bioavailability and stability offered by the glucosamine salt form (Quatrefolic) should provide at least similar, if not superior, biological effects compared to standard L-methylfolate23.

    Footnotes

    1. Lorena Carboni, "Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health," PubMed Central, 2023.

    2. Niccolò Miraglia, "Enhanced oral bioavailability of a novel folate salt: comparison with folic acid and a calcium folate salt in a pharmacokinetic study in rats," PubMed Central, 2024. 2

    3. Dominique Turck, "Conversion of calcium-l-methylfolate and (6S)-5-methyltetrahydrofolic acid glucosamine salt into dietary folate equivalents," PubMed Central, 2024.

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