Cerebrofolate Vs Other Methylfolates


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Cerebrofolate vs other methylfolates: How does it compare?

Written By:
 Katie Stone - Naturopath

Medical Reviewer:
Dr. Conor Sheehy - PharmD, BCPS

Edited By:
Kari Asadorian - RN

Updated On:

Sep 1, 2024

Key Takeaways

 L-methylfolate supplements available OTC can vary considerably in terms of their potency, stability, and purity.

 Cerebrofolate™ has been tested as the most bioavailable and therapeutic source of L-methylfolate available without a prescription.

 Both Cerebrofolate™ and Metafolin® have the highest free L-methylfolate levels, indicating greater efficacy.

As you probably know, L-methylfolate (5-MTHF) is the active, readily-absorbed form of folate. It’s more bioavailable than folic acid, and also clinically proven to be more effective for boosting folate levels in the body than folic acid.

You might also know that L-methylfolate is available either on prescription as Deplin®, or as an over-the-counter nutritional supplement. Deplin® uses the patented brand Metafolin®, while OTC supplements may use any number of branded or trademarked L-methylfolates. Some of the highest-quality brands include Cerebrofolate™, Quatrefolic®, Metafolin®, and Magnafolate®.

Metafolin® and Cerebrofolate™ are both crystalline (6S)-5-MTHF calcium salts (with a Type I molecular structure) which are renowned for quality and purity. Quatrefolic®’s chemical structure is an amorphous glucosamine salt.

Cerebrofolate™ has been demonstrated as the most potent and therapeutic source of L-methylfolate on the market. This high-potency L-methylfolate is chemically identical to Metafolin and exclusively available from Methyl-Life®.


So, what makes Cerebrofolate™ the best?

Types of methylfolate can vary considerably in terms of their potency, stability, and purity. If you’re looking for the best L-methylfolate, you’ll need to know how these major brands compare to one another - and which is the most effective.


A recent study from Cyntax Health Projects compared all three of the above leading brands: Metafolin®, Quatrefolic®, and Cerebrofolate™. Each brand was tested for stability, impurities, water content, and L-methylfolate potency, specifically measuring their free L-methylfolate levels over 90 days.


Purity refers to the percentage of the product that comprises the active element; in this case, how much of the raw ingredient is made up of “pure or free L-methylfolate”. The more L-methylfolate available by percentage in a raw ingredient, the more “pure” it is considered to be.

Cerebrofolate™ has tested as the top brand with a total of 80.7% potency, the highest percentage of pure “free L-methylfolate” in the study.

Impurities are the contaminants or degradation by-products present in the raw ingredient, which may occur during the processing or storage. Per USP standards, the sum of all impurities may not exceed 2.0% for L-methylfolate. The total impurities measured for Cerebrofolate™ was 0.8%.

How did they stack up?

First, let’s explain a bit more about USP standards and ‘free L-methylfolate levels’.


The United States Pharmacopeia (USP) is the organization that sets the standards of quality for medicines, dietary supplements, and foods as recognized by the government.


“Free methylfolate” refers to the concentration of pure L-methylfolate in a nutrient after carriers have been removed, leaving the portion that’s readily available for direct absorption and utilization by the body. It’s essential for assessing the potency, stability, and effectiveness of a supplement.


In the study, Quatrefolic® and the generic brand declined sharply in free L-methylfolate levels compared to the other two crystalline calcium salt type brands. Over the 90-day period, Metafolin® and Cerebrofolate™ showed only minimal changes.


In fact, free L-methylfolate levels were highest for Cerebrofolate™ followed by Metafolin® right through to Day 90. By contrast, free L-methylfolate levels declined sharply for the generic brand (17.6%) and moderately for Quatrefolic® (4.5%).

Product Recommendation

Consider L-methylfolate to improve mood?

Sale Off
L Methylfolate 15 mg - A Mood-Boosting Supplement - Methyl-Life® Supplements
$44.00

  • Puest Bioactive Form of Folate
  • Enhanced Mood
  • 90 Chewable mint tablets

The result?

Cerebrofolate™ was clearly ranked as the most potent sample by the end of the study. Cerebrofolate™ is considered the purest methylfolate available to consumers as it has the highest percentage of pure L-methylfolate of any methylfolate type tested. Quatrefolic® ranked the lowest. Review the study results.


What’s more, Cerebrofolate™ and Metafolin® were found to be chemically identical, more stable, and of higher potency than both the amorphous form of L-5-MTHF Calcium salt and the patented glucosamine salt form. Over the 90-day testing period, Cerebrofolate™ and Metafolin® both showed minimal change in physical appearance, chemical composition, total water content, and total impurities.

Most importantly, both Cerebrofolate™ and Metafolin® showed higher free L-methylfolate levels compared to the other samples, indicating greater purity, potency, stability and therefore greater efficacy.

The takeaway

When choosing a supplement, you expect it to support your health needs. When it comes to a vital nutrient such as L-methylfolate, you expect it to meet quality standards and remain effective over time.
As per USP standards, Cerebrofolate™ is shown to be the purest and most potent of any other OTC L-methylfolate available. It has the highest concentration of free methylfolate, which means it offers the highest efficacy.
Learn more about Cerebrofolate™ and Methyl-Life’s® products here.

About the Author

Katie is a qualified naturopath (BNatMed) and freelance writer from New Zealand. She specializes in all things health and wellness, particularly dietary supplements and nutrition. Katie is also a dedicated runner and has completed more half-marathons than she can count!

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