What Is The Best Methylfolate? Methylfolate Benefits Explained!

Are you taking the best methylfolate in the world? How do you know?

You know you want the highest quality in a supplement if you’re going to put it into your body, the question is, how can you verify that quality? Stay with me and we’ll talk about the methylfolates on the market today and how they stack up.

Our Customer Success Story: 

"I have been selling methylfolate since 2012, long before most people had ever heard of it. I learned about it through a doctor who was able to save his son’s life using the nutrient. I was convinced not only by the science I learned from Dr. Rawlins, but also by my own personal journey as well as the responses my customers had with the nutrient. I went from 85 to 136 in terms of serotonin levels within a 3 month period, taking approximately 6 mg of methylfolate a day (the normal range for serotonin is 125-185). Methylfolate has changed my life and that’s why I became an expert and am obsessed with ensuring the methylfolate I take every day has the best chemistry, quality and is the purest on the planet."

1. Patented or not? Does it have to be in order to be the best? 

The answer is technically no, but historically, probably yes. If a company is going to take the time to file patents for a nutrient, you know they’re doing testing with it, which means they’re investing in its long-term future and they believe it’s got some solid wins. If it’s not patented, it may be fine, but it might be a cheaper copy-cat which hasn’t gotten a complete quality copy. I take a patented methylfolate (and make my products with this patented version), not because it’s patented, but because when I dug under the covers chemically and quality-wise, I found it to be the absolute best in the market.

2. How is our methylfolate best in class, you ask? 

First of all, the manufacturer has innovated and created the purest version of methylfolate you can buy, meaning they’ve created a proprietary process for micronizing the molecule size for optimal absorption by using sonification instead of the typical grinding process which the rest of the industry uses. This means that Magnafolate® PRO has the lowest impurities amount when measured against all of the others. The industry USP standard says no more than 2.5% impurities for methylfolate and many leading brands test at 0.9% impurities when measured, which is a lot better than 2.5%, however, our methylfolate averages 0.2-0.3% total impurities which is 3 times more pure than the other leading versions available today.

3. Okay, but what about chemically, how does it stand up? 

Well when you compare it to the industry leaders, all of the 3 patented methylfolates use only a version with the pure 6S isomer (it’s also labeled as L or 6S which is chemically identical – the science world refers to chiral molecules as either 6S or L or their chiral opposite versions as 6R or D). So what I'm saying is that it should have no inactive 6R isomer in it (but be careful of any non-patented version as it will likely be copy-cat created - and may actually contain this inactive part of methylfolate). Some companies create cheap methylfolate in a racemic form where they don't isolate the 6S isomer for consumption and throw out the 6R inactive part (they leave both parts in the nutrient you ingest), so it’s only ½ of the active ingredient and up to ½ of an inactive ingredient that actually competes for the same receptors in your body that the active ingredient needs. DL-5-Methylfolate is the chemical term for a racemic version which is only partially active (but many will not label their methylfolate with these details - so ask to see a Certificate of Analysis if you're curious and the methylfolate is too cheap to be true). Often the raw ingredient is 4+ times less expensive, so that could be why you’re getting a ‘cheap’ product.

4. What about stability and potency, that matters doesn’t it?

Absolutely, our methylfolate is built on a crystalline calcium salt molecule structure which makes it the most stable in the industry. Only two patented methylfolates are built on this same structure. Our Magnafolate® PRO is built on a Type C molecule which shows in the lab to be slightly more absorptive than the Type I molecule that the pharmaceutical version is built on. Both have excellent stability, and potency loss occurs at a super slow rate of 1-2% per year, whereas amorphous salt versions can lose up to 16% potency per year. One of the industry leaders has built their ingredient on a much less stable molecule type. We attempted an anecdotal test where we compared our Magnafolate® PRO to an industry leader by leaving both out in the open air under the same conditions. And after being left out in the open air for 30 days, we found our Magnafolate® PRO remained pretty much the same, a cream-based color, but when we compared it to the other industry leader’s methylfolate left out in the same open air for the same 30 days in the same conditions, we found it turned black in color – clearly oxidizing and not proving stable in the open air.

5. And the salt type, does that matter? 

Well it might possibly for some people. Glucosamine salt is one salt type and calcium salt is the other. Maybe a digestive upset or a rash, etc. could happen more with one of the other salt types, so it could be worth trying the other type if you have a reaction to one type of methylfolate. We moved to using the calcium salt based methylfolate in our products because it’s more stable and similar to the pharmaceutical brand. We also seemed to have less customer complaints regarding rashes or stomach & digestive issues when taking it. I think the moral of the story here is, if you are having a negative reaction to your methylfolate (and you know you took a version that was specifically glucosamine salt based), you may want to try a version built on the calcium salt type in case you find you tolerate it better (and vice versa of course) - at least before you give up on methylfolate altogether.

6. What about having a super long shelf life, would that be a good thing?

Well it would certainly prove the nutrient is stable and potent. We had the 35-year folate chemical specialist formerly from Merck test a number of our Methyl-Life products that were literally 5-year-old, just to see how they held up. And we found that they showed outstanding potency – the products were still fully potent according to the Supplement Facts, even after sitting for a full 5 years on the shelf. The other industry leader’s 5-year old products did not prove to still be fully potent, the results came in showing that the amount in the bottle no longer met the potency statements listed on the back of the bottle in the Supplement Facts panel.

7. Lastly, who do you want to trust with your methylfolate?

A company that sells vitamins, or an individual who is passionate about and has been taking methylfolate since 2011 and has made it their passion to understand the nutrient inside and out? 

I have a genetic condition requiring me to take the nutrient for the rest of my life and so I wanted to ensure that I'm taking the very best type of methylfolate that can produced on this planet. I spent a lot of time researching and trying different methylfolates and finally landed on what I believe is the very best one - this one I take each and every day of my life, so I don't want to overlook anything like impurities or potency. I also wanted to share my discoveries with folks like me, who are dealing with a genetic condition that requires a high quality nutrient that doesn't break the bank, and allows them to get some some life-changing health benefits.

If you're looking for a game-changing methylfolate, check us out, Methyl-Life is a family-owned business that "takes its own medicine" and sells products with the best methylfolate on the planet.

Are There Other Names for L-methylfolate?

There are many different names used for L-methylfolate supplements. It’s important to understand which form of methylfolate is best for you. 

Methylfolate is often known or labeled as: 

  • L-MTHF 
  • L-5-Methylfolate 
  • L-5-Methylenetetrahydrofolate
  • L-5-MTHF 
  • (6S)-5-Methylfolate 
  • (6S)-5-Methylenetetrahydrofolate

However, other terms can include: 

  • L-Methylfolate Calcium 
  • D-Methylfolate 
  • DL-Methylfolate
  • D-5-Methyltetrahydrofolate 
  • DL-5-Methylenetetrahydrofolate
  • 5-MTHF 
  • 5-Methylfolate
  • (6R)-5-Methylfolate
  • (6S)/(6R)-5-Methyltetrahydrofolate

NOTE: L or (6S) refers to the active isomer of methylfolate which your body uses. D or (6R) refers to the inactive isomer of methylfolate which your body does not use and more typically competes with the active isomer for the receptor. 

The D or (6R) form of methylfolate can block your folate receptors and is NOT recommended by doctors. Be aware of companies who may be using these inactive (and cheaper) forms of methylfolate in their products and not labeling them properly.

Some well-known L-Methylfolate raw ingredients found in products include: Metafolin®, Extrafolate®, Quatrefolic®, Magnafolate®.

Some well-known ‘medical foods’ (or prescription nutrition products which contain L-Methylfolate) are: Deplin®, Enlyte®, Metanx®, Cerefolin®, Neevo®.

What is Deplin? What is Deplin Algal Oil?

Deplin is a prescription medication that is classified as a “medical food” rather than a drug. 

It is essentially folate that has already been converted to L-methylfolate, so it is readily available for making serotonin, norepinephrine, and dopamine in the brain. 

Deplin comes in 7.5 mg and 15 mg dosage levels.

What is Deplin Used For?

Deplin is used to treat people who have conditions related to folate deficiency. It’s particularly effective for those with major depressive disorder, schizophrenia, or hyperhomocysteinemia related to folate deficiency.

Folate is required for the synthesis of key brain chemical messengers including serotonin, norepinephrine, and dopamine. Low levels of these chemicals are implicated in major depression and other psychiatric disorders.  

This is why folate deficiency is linked with depression. However, nearly half the US population can’t properly convert synthetic folic acid into the form that the body can use: L-methylfolate.

Only L-methylfolate can pass through the “blood-brain barrier” and enter the central nervous system. For many people, ingesting plain folate or folic acid is ineffective because it can't get through to the brain. This is why L-methylfolate supplements may help those with mood disorders. 

Recent research has found that combining Deplin with a serotonin reuptake inhibitor (such as Zoloft or Paxil) can improve the response rate to the antidepressant by more than two-fold. 

Using Deplin and an antidepressant together has also been shown to improve symptoms by up to 84 percent over using the antidepressant alone.

What are the Active Ingredients in Deplin?

Each DEPLIN® capsule contains 7.5 mg or 15 mg of L-methylfolate (from Metafolin®)* and 90.314 mg of Algae-S powder (Schizochytrium).

What is the Difference Between Deplin and Deplin Algal Oil? 

Deplin ingredients are a combination of the trademarked L-methylfolate (Metafolin®) and an algae called Schizochytrium, or algal oil. 

Algal oil is made from marine algae. It is a source of important omega-3 fatty acids including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Algal oil is used in foods and as a medicine. 

Taking DHA during pregnancy and/or lactation has been found to improve gestation in high-risk pregnancies, increase overall size, and enhance visual acuity, hand and eye coordination, attention, problem solving and information processing.

What is the Difference Between L-Methylfolate vs Deplin?

Deplin® is a prescription medication but is classified as a “medical food” rather than a drug. It is generally prescribed to those with distinct nutritional requirements due to suboptimal L-methylfolate levels in the CSF, plasma, and/or red blood cells. 

Deplin® is essentially folate that has already been converted into L-methylfolate, so it is readily available for making serotonin, norepinephrine, and dopamine in the brain. Those with major depressive disorder are often prescribed Deplin® if they have had no favorable response to antidepressant medications. 

L-Methylfolate is a supplement that can be purchased over-the-counter. It is often used as a Deplin® over the counter equivalent, and is also recommended for those with folate deficiency or treatment-resistant depression. 

What is the Difference between L-Methylfolate and Prescription Deplin®?

Deplin® is regulated by the US Food and Drug Administration (FDA). It can only be purchased with a prescription from your doctor. 

If you are looking for a Deplin® substitute or Deplin® OTC, your best bet is to try high-quality L-methylfolate supplements. 

These are available online and in health stores. There are many brands manufacturing L-methylfolate supplements and each formula may vary in terms of potency, quality, and the range of ingredients

Is L-Methylfolate the Over-the-Counter Equivalent to Deplin®? Can it be a Substitute for Deplin®?

L-Methylfolate (7.5 mg and 15 mg) may be an effective Deplin® OTC equivalent. It has been shown in several studies to enhance antidepressant response. 

One double-blind, placebo-controlled trial of L-methylfolate among folate-deficient patients with major depression found that adding L-methylfolate 7.5 mg or 15 mg to standard treatment significantly improved patients’ recovery, both clinically and socially.

There are some highly effective Deplin® alternatives available over-the-counter. 

Some of the best-selling methylfolate supplements for depression are the Methyl-Life™ product range, including Methylfolate 7.5+, Methylfolate 10, Methylfolate 15 and Methylfolate 15+. These formulas are designed to support the body’s requirements for energy production and neurotransmitter synthesis while restoring healthy levels of folate. 

Methyl-Life’s™ Methylfolate 15 contains a high dose (15 mg) of internationally-patented Magnafolate® PRO which recently proved to be 3x more pure than the other leading patented brands in a 60-day open air comparison study

This internationally-patented L-5-Methylfolate is crystalline calcium salt-based for superior stability and absorption. It is especially effective in people with an increased need for bioavailable folate due to genetic (MTHFR) defects, dietary deficiencies or those taking warfarin, coumadin, metformin, etc.

EnLyte® vs Deplin®

Deplin® is a medical food containing L-methylfolate, the active dietary form of the vitamin B9 (folate). 

EnLyte®, is also an FDA-regulated prescription medication. It also holds the FDA USP for dissolution and degradation of folates. This is an FDA standard claimed by only about a third of folate supplements.


Deplin® also contains L-methylfolate calcium, while EnLyte® contains L-methylfolate magnesium. EnLyte® also contains folinic acid and citrated folacin, which are the three forms of folate proven effective in treating depression as cited in the Fava study.

Deplin® vs Metanx®

Deplin® contains L-methylfolate (from Metafolin®) and Algae-S powder (Schizochytrium).

Metax® contains L-methylfolate calcium (as Metafolin®), algae-S powder (Schizochytrium), pyridoxal-5'-phosphate (active B6), and methylcobalamin (active B12).

Both are prescription medical foods given to patients to treat conditions related to folate deficiency. Metanx® is generally used to treat patients with diabetic peripheral neuropathy. It is specially formulated to meet the distinctive nutritional requirements for this condition.

Deplin®, on the other hand, is used for the clinical dietary management of depression and schizophrenia.

Deplin® vs Generic Folate

The cost of Deplin® and other prescription medications can make it unaffordable for some, especially those who don't have health insurance. And even many who do have insurance afford it through the pharmacy (due to its ‘medical food’ and not ‘drug’ classification).

There are numerous alternatives to Deplin® available in the form of supplementary folate or L-Methylfolate. It’s important to examine the ingredient lists of these products carefully to understand the form of L-methylfolate used, the potency, and any other ingredients they may contain. 



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