March 2, 2024

What are the types of Methylfolate?

What is Methylfolate?

The active form of folate is Methylfolate that can cross the blood-brain barrier and penetrate your brain. Many factors such as; stress, MTHFR gene mutation, and other biological changes can reduce the body’s ability to transform folate or folic acid into an active form. Consequently, unmetabolized folic acid accumulates in your body, disturbing the metabolism efficacy. Methylfolate supplements are available to replenish its deficiency. 


What are the types of Methylfolate?

Methylfolate is available in various forms and has different names that create confusion. However, it is necessary to understand the variation among all forms and which form is most suitable for you. Let’s walk together and try to resolve this mystery for you.

Terms mostly used for Methylfolate are;

  • L-Methylfolate
  •  L-MTHF
  • Levomefolic acid
  • L-Methylfolate Calcium
  • Metafolin
  • D-methylfolate
  • D-5-Methylfolate
  • 5-Methylfolate
  • 5-Methyltetrahydrofolate
  • L-5-Methylhydrofolate
  • L-5-MTHF
  • 6(S)-5-Methyltetrahydrofolate
  •  6(S)-5-MTHF
  • 6(R)-5-MTHF
  • 6(R)-5-methyltetrahydrofolate
  • (6S)-5-methyltetrahydrofolate
  • Quatrefolic

If you think these, all terms are the same; you are wrong. Some terms are interchangeable and synonyms for each other, but other terms are different. Similar terms are combined together, such as; 

  • L-5-methyltetrahydrofolate, L-5-MTHF, 6(S)-L-MTHF

6 (S)-L-methyltetrahydrofolateare the same and most suitable forms.

  • Similarly, Levomefolic acid, Metafolin, and L-Methylfolate Calcium are the same and best forms.
  • D-5-methyltetrahydrofolate, D-5-MTHF, 6(R)-L-MTHF, and 6(R)-L-Methyltetrahydrofolate are not suitable forms of methylfolate.

You are perplexed; what are D, L, S, R letters, and why used here? Wait! 


This term is not common but biologically, it has much significance. Stereoisomerism means molecules have the exact same molecular formula, bounded atoms, but their orientation in space (three-dimensional) is different. Due to different orientations, their chemical properties are different from each other. Two forms of stereoisomerism are;

1. Enantiomers:

Molecules that are mirror-images of each other like your hand and exhibit the same physical properties but may have variations in biological effects are known as Enantiomers.

2. Diastereoisomers:

The diastereoisomers are not mirror images like enantiomers and exhibit the same physical properties but have different biological effects. 

The letters D, R, S, and L are used in stereoisomers to distinguish the structures and designate the properties of molecules.

Hence, methylfolate possesses stereoisomers in the form of Diastereoisomers. 

The biologically active and inactive form of Methylfolate:

Active forms of methylfolate areL or 6(S)”,and also known as;

The other forms that hold the prefix “D, or 6(R)” are biologically inactive (not functional) forms of methylfolate. So, think before purchasing these forms. 

Any other form of methylfolate that does not carry the prefix L or 6(S) isomer of methylfolate (like methylfolate, 5-methylfolate, 5-methyltetrahydrofolate) may or may not be 99% pure biologically active form of methylfolate. 

If methylfolate forms are labeled as 6RS-5-MTHF or DL-5-MTHF, that indicates more than 1% of the 6R or D isomer form of methylfolate (nearly 50% of the inactive D form). 

Therefore, before purchasing the methylfolate supplements, please carefully read the packaging details of the bottles. 

The internationally registered brands of l- methylfolate are; 

  • Quatrefolic: Amorphous glucosamine salt of methylfolate having limited stability and high bioavailability. 
  • Metafolin: Crystalline calcium salt of l-methylfolate, prescribed along with antidepressant drugs 
  • Extrafolate S: Amorphous calcium salt of 6(S)-5-methyltetrahydrofolate but less stable. 
  • Magnafolate PRO: It is a crystalline calcium salt form of pure 6(S) isomer of methylfolate and has high stability.



Methylfolate is available in different forms, and various terms are used for methylfolate that creates confusion which form is biologically active or inactive. It’s necessary to have knowledge of multiple forms of methylfolate. Those forms that specify L or 6S are biologically active forms of methylfolate, and others labeled as D or 6(R)are inactive forms of methylfolate. Therefore, care should be taken before buying the methylfolate. 


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