What is the Best Form of Methylfolate for People with an MTHFR Gene Mutation?

Those with an MTHFR gene mutation may already know the importance of supplementing with methylfolate. Methylfolate plays a pivotal role in the methylation process, which is crucial for the proper operation of many bodily functions.

Increasing awareness of MTHFR mutations and their prevalence has seen a rise in the number of methylfolate supplements available. Not all forms of methylfolate are the same, and some are more efficient than others.

People with MTHFR mutation have an increased risk of developing mental health issues, fatigue, cardiovascular problems, migraines, and certain types of cancer. Pregnant women with MTHFR who have low folate levels also face a higher risk of having children with neural tube defects.

This article will discuss the different forms of folate, and how folic acid differs from methylfolate. We will also explain how to understand the registered brand names for different forms of methylfolate.

Folic acid and methylfolate are both vitamin B9, but they are in different forms.

The first thing to understand about the MTHFR mutation is that it impairs your body’s ability to process folic acid. The Methylenetetrahydrofolate-reductase enzyme is required to convert folic acid into an active form the body can use, but the MTHFR variant results in a lack of this enzyme.

This means taking folic acid supplements will be ineffective—like putting diesel into a petrol engine.

You may see “L-” and “D-” forms of methylfolate. These letters refer to the three-dimensional orientations of their atoms in space—i.e., their structure.

The most biologically active forms of methylfolate are (6S)-5-methyltetrahydrofolate or (6S)-5-MTHF, also known as “L” forms. These may be labeled as:

The (6R)/D is the unnatural form, while the [6S] is the natural, active form used by the body. 

Experts recommend choosing active forms of methylfolate (the L form or 6(S)) form over the inactive D form as natural bioidentical forms of vitamins are superior in bioavailability and absorption.

The appropriate salt form of a nutrient can improve its overall therapeutic and pharmaceutical effects. Both calcium and glucosamine salt-based L-methylfolate can cross the blood-brain barrier for immediate utilization in the brain cells.

Major internationally registered brands of L-Methylfolate include Quatrefolic®, Metafolin®, Extrafolate S®, and Magnafolate® PRO.

Quatrefolic® is the glucosamine salt of 5-methyltetrahydrofolate. Some studies have found that the glucosamine salt form has higher bioavailability than other forms of methylfolate.

However, the results of high-performance liquid chromatography coupled with ultraviolet detection analysis indicated that the crystal form C of 6S-5-methyltetrahydrofolate calcium salt has better stability than 6S-5-methyltetrahydrofolate glucosamine salt.

It has also been suggested that a glucosamine salt must be taken at a higher dose because this form is heavier than calcium.

Metafolin® is the manufactured calcium salt of L-methylfolate and the main component of Deplin®, a prescription-only “medical food.” 

It is the crystalline form of the “L” isomer of a specific type of calcium salt, which is an essential requirement for maintaining supplement stability. This ensures greater potency over time.

Extrafolate-S® is an amorphous calcium salt of L-methylfolate, usually labeled as (6S)-5-methyltetrahydrofolate. Amorphous salt forms may be less stable and more likely to lose potency over time than crystalline salt forms.

Like Metafolin®, Magnafolate® PRO is a patented type C crystalline calcium salt of L-5-methyltetrahydrofolate.

Tested as ~99% pure, Magnafolate® C maintains stability for 36 months at room temperature.

Methylfolate’s role in the body cannot be underestimated. As a cofactor in the methylation cycle, it contributes to numerous bodily processes required for normal function.

Those who cannot metabolize folic acid due to the MTHFR gene mutation must supplement with methylfolate, preferably a glucosamine or calcium salt form.

Crystalline salt forms have shown greater stability and potency over time. When choosing a methylfolate supplement, check the label carefully.

A good place to start is with Methyl-Life®. Designed specifically for those with MTHFR gene mutations, Methyl-Life® products are made only with Magnafolate® PRO: the revolutionary type C crystalline calcium salt form with clinically proven stability and purity.

Methyl-Life® has chosen this form of methylfolate after carefully reviewing other leading brands, and their best-selling Methylfolate range now has a loyal customer base all over the world.