L-Methylfolate, Methylfolate, 5-MTHF, L-5-MTHF. Why many variations? (2024)

L-methylfolate has many different names which adds to confusion.

Those with MTHFR mutations scan labels, read websites or listen to their doctors rattle of conflicting terms for a nutrient they really need.

Update June 26, 2019:

Note how the label below illustrates:
Folate (this is where you need to pay attention – inside the paranthesis).

See how it shows (as Quatrefolic (6S) etc)?

That is the best form of methylfolate.

This is what you want.

I used to use Merck’s L-5-MTHF from calcium but I switched to Gnosis.

—

Be careful about other types of L-methylfolate are out there.

There are quite a few.

Understanding which form of methylfolate is best must be clear.

Why all the confusion?

Because there are so many different terms used for methylfolate.

By the end, you will understand everything you need to know about methylfolate.

More significantly – you will understand how to pick the right form of methylfolate.

Terms often used for methylfolate are:

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

Are these forms of methylfolate all the same?
No.

Are any of these forms of methylfolate the same?
Yes. The same forms are grouped together here. These forms are synonymous with each other:

1. L-5-MTHF = L-5-Methyltetrahydrofolate = 6(S)-L-MTHF = 6(S)-L-Methyltetrahydrofolate
   • Good forms which are well absorbed
2. L-Methylfolate Calcium = Metafolin = Levomefolic Acid
   • Good forms which are all well absorbed
3. D-5-MTHF = D-5-Methyltetrahydrofolate = 6(R)-L-MTHF = 6(R)-L-Methyltetrahydrofolate
   • Avoid these (learn why soon…)

Then what are the other forms of methylfolate?

The other forms of methylfolate may or may not be 99% pure biologically active methylfolate.

• 5-MTHF
• 5-Methylfolate
• 5-Methyltetrahydrofolate

How come these may or may not be 99% pure biologically active methylfolate?
These forms do not specify the L form (or 6(S) form) of methylfolate; therefore, you do not know what you are ingesting.

The forms of methylfolate not specifying L or 6(S) likely contain more than 1% of the D form of methylfolate.

What is the difference between D and L forms of Methylfolate?
In organic chemistry, one learns compounds may have the exact same molecular formula and sequence of bonded atoms but differ three dimensionally. These compounds are known as steroisomers.[1]

There are two common forms of sterioisomers:

1. Enantiomers:
   • mirror images of each other, such as our hands.
   • same physical properties
   • may have different biological effects
2. Diastereoisomers:
   • not mirror images of each other
   • rarely have same physical properties
   • have different biological effects

Methylfolate has stereoisomers in the form of diastereoisomers.

The forms of methylfolate that are biologically active are:

• L forms
• 6(S) forms
• L-5 forms
• Metafolin
• L-Methylfolate Calcium
• Levomefolic Acid
• Quatrefolic

The forms of methylfolate that are NOTbiologically active are:

• D forms
• 6(R) forms

The forms of methylfolate that may or may not be biologically active are the:

• forms which do not specify L, 6(S) or trademarked name of Metafolin
• 5-MTHF
• 5-methylfolate
• 5-methyltetrahydrofolate

From the package insert of Metanx, a prescription drug using biologically active Metafolin[2]:
“L-methylfolate or 6(S)-5-methyltetrahydrofolate [6(S)-5-MTHF], is the primary biologically active diastereoisomer of folateand the primary form of folate in circulation.It is also the form which is transported across membranes into peripheral tissues,particularly across the blood brain barrier.In the cell, 6(S)-5-MTHF is used in the methylation of hom*ocysteine to form methionine and tetrahydrofolate (THF).THF is the immediate acceptor of one carbon units for the synthesis of thymidine-DNA, purines (RNA and DNA) and methionine.About 70% of food folate and cellular folate is comprised of 6(S)-5-MTHF. Folic acid, the synthetic form of folate, must undergo enzymatic reduction by methylenetetrahydrofolate reductase (MTHFR) to become biologically active.Genetic mutations of MTHFR result in a cell’s inability to convert folic acid to 6(S)-5-MTHF.

Metafolin® (L-methylfolate calcium) is a substantially diastereoisomerically pure source of L-methylfolate containing not more than 1% D-methylfolate which results in not more than 0.03 milligrams of D-methylfolate inMetanx^®

D-methylfolate or 6(R)-5-methyltetrahydrofolate [6(R)-5-MTHF] is the other diastereoisomer of folate. Studies administering doses of 2.5 mg per day or higher resulted in plasma protein binding of D-methylfolate higher than L-methylfolate causing a significantly higher renal clearance of L-methylfolate when compared to D-methylfolate.Further, D-methylfolate is found to be stored in tissues in the body, mainly in the liver. D-methylfolate is not metabolized by the body and has been hypothesized to inhibit regulatory enzymes related to folate and hom*ocysteine metabolism and reduces the bioavailability of L-methylfolate.”

Example of why all this is important to know
A supplement company has a supplement called, “5-MTHF”

Let’s say this supplement states it contains 10 mg of 5-MTHF.

One assumes this contains 10 mg of biologically active L-methylfolate.

Don’t assume.

The likelihood of it containing 99% of the biologically active form of L-methylfolate is slim to none.

Why?

Prescription drugs such as Deplin contain 99% active L-methylfolate as Metafolin. Deplin provides two potencies of L-methylfolate: 7.5 mg and a 15 mg

This much L-methylfolate is VERY potent and must be prescribed by a physician.

Merck does not allow any supplement company to provide more than 1 mg of their L-methylfolate in a stand-alone supplement. If L-methylfolate, as Metafolin, is included in a formula along with other nutrients, then a maximum of 800 mcg is allowed.

What amount of this 10 gram 5-MTHF supplement actually contains the biologically active L-methylfolate?
It is not known without requesting a lab report.

The likelihood of it containing a significant amount of the inactive D form of methylfolate is high.

Remember, the D form of methylfolate is undesirable and actually may reduce the bioavailability of L-methylfolate.

What to do?
Two things:

1. Request a prescription from their physician to obtain drugs containing Metafolin.
2. Look for supplements specifying the amount of active L-methylfolate.

Drugs containing Metafolin are:

• Metanx
• Deplin
• Cerefolin
• CerefolinNAC
• Neevo
• NeevoDHA

Supplements with Methylfolate
One must carefully evaluate supplements specifying the use of Metafolin, Quatrefolic or the L form.

If the supplement does not specify on the label that it uses Metafolin, Quartrefolic or the L form of methylfolate, then it is not recommended to use without first inquiring directly to the manufacturer. A manufacturer may have named their product as 5-MTHF and use the pure L form of methylfolate; however, one must inquire to be certain.

Quatrefolic: What is this?
This is a new form of methylfolate that uses glucosamine instead of calcium to bind the L-methylfolate. Quatrefolic is also a quality form of L-methylfolate.

This is the form of methylfolate that I use in all my formulations.

Key Points about Methylfolate:

1. Not all methylfolate is the same
2. The D form of methylfolate actually is undesired and should be avoided
3. The L form of methylfolate is the desired form
4. There are many names for the same thing. Understand them.

___________________

Supplements using the pure form of L-Methylfolate

Seeking Health uses purely the L-methylfolate as Quatrefolic by Gnosis.

by Dr. Ben Lynch on April 5, 2012 in MTHFR Mutations