The Different Types of Folate: Which One is Right for You?

Blog Cover_Folate Types

Folate, or Vitamin B9, has many different names and comes in multiple forms. This adds to the confusion around which type of folate you might need.

To complicate the issue, the web is filled with confusing labels, websites, and misguided healthcare professionals. 

So, how do you know what type of folate is best for you? In this article, we’re going to cover folate basics, the different forms of folate, and how to choose the best form. 

Why is Folate Important? 

Folate is a synonym for the essential micronutrient vitamin B9. In this article, we will discuss the many forms and synonyms for “folate.”

This water-soluble B vitamin is arguably one of the most important nutrients for cognition, heart health, mood, fertility, and healthy fetal spine and brain development. You need folate to form building blocks of DNA. Essentially, humans would not exist without folate! It is well known that folate is necessary for the formation of red blood cells, amino acids such as methionine, and proper cell division.* 

Folate is essential for methylation, a process that uses “methyl” groups from folate to grow, change, and transform many functions in your body. Methylation even helps your genes to properly express themselves by transferring a “methyl group” onto your DNA to literally turn it “on” or “off” wow!

Folate Deficiency

Folate deficiency can lead to neural tube defects such as spina bifida and anencephaly, elevated homocysteine levels (increased risk of adverse effects on cardiovascular health), and can play a role in cognitive disabilities. (1, 2, 3) 

Folate deficiency ranges from less than 5 percent in high-income economies to more than 20 percent in lower-income economies, especially in women of childbearing age. (4) 

Dietary Folates

Folates from food sources, such as dark leafy greens and legumes, are absorbed through your intestinal wall. After being absorbed, dietary food folates must go through several enzymatic steps before becoming usable by your body. There are a number of dietary folate food forms; however, it may be challenging to get enough folate from your daily food intake, mainly because most individuals do not eat adequate amounts of leafy vegetables every day.

Dietary Folate_Vitamin B9_Foods

Folate RDA

The RDA (recommended dietary allowance), or simply, the recommended amount for folate in adults is 400 mcg DFE per day set by the National Institute of Health. (5) One serving of spinach contains about 160 mcg of folate. (6) However, many folate supplements will contain upwards of 1000 mcg per serving, as deficiencies may require much higher doses.

It also appears that supplemental folates are more bioavailable compared to food sources of folates.* (7)

MTHFR & Folate

In addition, an enzyme called methyltetrahydrofolate reductase (MTHFR) is a vital step in the production of bioactive folate. You may already be familiar with the MTHFR gene, which can cause the enzyme to become dysfunctional when mutated on a genetic level. This means if you have an MTHFR mutation,  you may not be producing bioactive folate in the amounts that you need. 

Folate-Pathway

Your Folate Pathway

Besides MTHFR, there are many other enzymes in your folate production process, called the folate pathway. These enzymes can contain genetic variations which increase your susceptibility to low folate levels. Even without genetic mutations in the folate or methylation pathways, your enzymes that help produce and utilize folate can become stressed and “dirty.” 

Folate Supplementation

Therefore, folate supplementation may be necessary, considering that food folates are not as bioavailable nor are they present in high enough amounts for those who require more, such as pregnant women or those with MTHFR gene mutations. This makes it an essential nutrient for prenatal formulas and anyone at risk for folate deficiency.

However, the type of folate that you consume matters. Forms like the human-made form, folic acid, are not well utilized in your body and may be problematic.* 

Folic Acid vs. Methylfolate

As we learned, functioning folate and methylation pathways are essential for growth, development, cognition, cardiovascular health, and many other aspects of health. In order for your methylation pathway to be functioning, it needs folate in the form of methylfolate. Methylfolate is attached to something called a “methyl group” and it is a preferred form of folate by your body. Methylfolate supports your methylation such as genetic expression which is an essential process that needs to be working optimally for your body to feel its best. 

However, there are forms of folate on the market now that are not well utilized by the body, such as the man-made, synthetic form called folic acid. This form of folate is used in food fortification to replenish folates lost through grain processing, such as in breakfast cereals and pasta. This form of vitamin B9 has low bioavailability (how “usable” it is by your body). Folic acid can even slow your MTHFR enzyme and other enzymes in your folate production process! 

MTHFR-cofactors-inhibitors

Ironic, right? 

It can be shocking to learn that folic acid can actually reduce your ability to get usable folate in your body!

Folic acid, as you will learn later, is not identical to folate, though it is used interchangeably. It’s one of the most common forms found in dietary supplements. Folic acid supplements are cheap and a popular prescription from many doctors for things such as pregnancy, low mood, and high homocysteine levels. But the body cannot properly use it, and therefore unmetabolized folic acid can be floating around in your body, blocking important enzymes, and slowing your body’s ability to get active folate. 

Besides folic acid, other forms are not utilized by the body, even some forms of methylfolate! We’ll get to that in a bit. But first, let’s talk about reading Supplement Facts panels.

How to Identify GOOD Folate

Adding insult to injury, some labels do not disclose what type of folate is in the product.  They just list “folate.”

Here is an example of how folate is illustrated on our Seeking Health L-5-MTHF Lozenge Supplement Facts panel:

L-5-MTHF-Lozenge-Supplement-Facts-Panel

Okay, now this is very important: See where it states “Folate” on the label? Look inside of the brackets which reads: “[as Quatrefolic® (6S)-5-methyltetrahydrofolate, glucosamine salt]”. 

Quatrefolic® (6S)-5-methyltetrahydrofolate is the most bioavailable form of methylfolate on the market for supporting methylation processes (especially supporting a dirty MTHFR gene).*  

There are a few other bioactive, high-quality forms as well. For example, if you are sensitive to methylated nutrients, you will most likely want to take the non-methylated form of folate called folinic acid. This is a bioactive and natural form that often appears on supplement labels as Folate, or may be written as “folinic acid” or “calcium folinate.”

Calcium Folinate_Supplement Facts Panel

The above examples are clear, transparent, and the best forms of folate. 

But not all dietary supplements contain these bioavailable, natural forms of folate. In fact, many supplements will not even state the form of folate on the label!

This is something you want to be extremely careful about there are a multitude of folate forms out there. If you are someone who is taking a folate supplement or folate-containing supplement, it is extremely important to ask the dietary supplement company what form is in your product.  And before you can do that, you need to understand what forms you should look for and avoid.

The Different Types of Folate

There is an exhaustive number of folate synonyms and forms. It’s important to know which are synonyms and which are completely different forms. 

Terms often used for folate include:

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

Are these forms of folate all the same?

No, not all of them. However, some are used interchangeably. Below are the synonyms bunched together.

Folates forms and their synonyms:

  • L-5-MTHF = L-5-Methyltetrahydrofolate = 6(S)-L-MTHF = 6(S)-L-Methyltetrahydrofolate
    • Good forms which are all well absorbed*
  • L-Methylfolate Calcium = Metafolin = Levomefolic Acid
    • Good forms which are all well absorbed*
  • Folinic acid = Calcium folinate
    • This is a non-methylated form of folate that is excellent for those who are sensitive to methylated folate.*
  • D-5-MTHF = D-5-Methyltetrahydrofolate = 6(R)-L-MTHF = 6(R)-L-Methyltetrahydrofolate
    • Avoid these (for reasons explained below)*
  • Folic acid
    • Avoid this COMMONLY used form, for reasons explained below.* It’s important to note that “folic acid” is often used interchangeably with “folate” on many dietary supplement labels.

Methylfolate Forms: “D” vs. “R” vs. “L” vs “6(S)”

When looking for methylfolate, you want the “L” or “6(S)” form these are most biologically active. 

The “D” or “R” forms of methylfolate are not as good because they are less bioavailable.

Thus, it’s important to look closely at the form of methylfolate on your supplement label. Perhaps you’ve heard it’s important to take methylfolate or 5-MTHF. You look at the supplement label and it reads “methylfolate” or “5-MTHF.” You’re good, right?

Not necessarily.

Supplement labels that do not specify the form of methylfolate, may or may not be biologically active. The active forms of methylfolate include the L form or the 6(S) form. If your supplement label does not specify the form of methylfolate (i.e. L or 6(S)), it likely contains the inactive, “D” form of methylfolate. 

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

What is Quatrefolic®?

Quatrefolic® is a superior form of methylfolate that uses glucosamine instead of calcium to bind the L-methylfolate. The glucosamine salt may be superior and more bioavailable than the calcium salt, however both forms are excellent.* Quatrefolic® is the form of methylfolate that Seeking Health uses in most of our methylated multivitamins, B vitamins, and prenatal formulations! (8)

The Problem with Folic Acid

Folic-acid-chemistryAs we learned earlier, folic acid is the human-made form of folate. It is popular with physicians and often found in cheaper dietary supplements and fortified foods such as pasta and bread. It was originally released to replace folate that was stripped away from wheat and other grains when making processed foods. It is cheap, easy, and known as the supplemental form of folate.

Seeking Health’s founder, Dr. Ben Lynch, has spent over a decade researching MTHFR gene mutations and other genes associated with the methylation cycle, all of which rely upon folate. His research uncovered that folic acid is not molecularly identical to natural folate. Folic acid supplementation can even block folate absorption and further slow your MTHFR enzyme (NOT good if you already have a variation in your MTHFR gene that is slowing your enzymes).* 

Research even shows that women who consume folic acid to support fertility or pregnancy may not actually be lowering their risk of birth defects or miscarriage. In contrast, bioactive forms of methylfolate raise blood levels of folate more effectively than folic acid, to support healthy fertility and pregnancy.* (9, 10, 11)

The Best and Worst Forms of Folate 

To summarize what we’ve discussed, here are the forms of folate to look for and avoid in your supplements.

Best Forms of Folate:*

  • L, 6(S), or L-5 forms: L-methylfolate, L-5-MTHF, L-5-methyltetrahydrofolate, (6S)5-MTHF glucosamine salt (often under the trademark Quatrefolic)
  • L-Methylfolate Calcium, Metafolin, or Levomefolic Acid
  • Folinic acid or calcium folinate

Worst Forms of Folate:*

  • Folic acid
  • D forms and 6(R) forms of methylfolate
  • Note that if you see just the “5” in front of the name, like “5-MTHF”, “5-methylfolate”, or “5-methyltetrahydrofolate”, this may or may NOT be a biologically active form. In this case, you will always want to reach out to the dietary supplement company or manufacturer and ask whether it’s the “D/6R” form or the “L/6S” form.
Form of Folate Methyfolate Folinic Acid Food Folates Folic Acid*
AKA L-5-MTHF
L-methylfolate
Folate
Vitamin B9
Calcium folinate
5-formyltetrahydrofolate
Folate
Vitamin B9
Vitamin B9
Folate
Vitamin B9
Folate
Seeking Health Products L-5-MTHF capsules
L-5-MTHF lozenges
Active B12 with L-5-MTHF
HomocysteX Plus
B Complex Plus
Optimal Prenatal capsules
Optimal Prenatal Protein Powder
Prenatal Essentials
Optimal Multivitamin Methyl One
Plus many others
Folinic Acid capsules
Folinic Acid lozenges
Hydroxo B12 with Folinic Acid
B Complex Plus Methyl-Free
Optimal Multivitamin Minus One
Optimal Prenatal Methyl-Free
Prenatal Essentials Methyl-Free
Plus many others!
None None
Methylated Yes No Sometimes No
Bioavailability* High Medium Variable Low
Great for supporting MTHFR gene* Best Yes Yes NOT recommended by Dr. Ben Lynch
Great for supporting Healthy Pregnancies* Best Yes Yes Not recommended by Dr. Ben Lynch
Side Effects May be sensitive to methyl groups: nervousness/rapid heartbeat/headaches None known None known May mask B12 deficiency, slow the MTHFR enzyme and other enzymes in the folate pathway, may block folate receptors
Safe for Pregnancy Yes Yes Yes Not recommended by Dr. Ben Lynch
How is it made? Synthetic form, but bioidentical Synthetic form, but bioidentical Natural dietary folates from foods Human-made synthetic form, not bioidentical
Sources/Where can you find Found in food and supplements Found in supplement form Food sources such as leafy greens and legumes Added to fortified foods and many dietary supplements
Blocks folate pathway? No No No Yes, blocks receptors
Number of Enzymatic Steps before Active form 0 3 Varies (~1-7) ~7

Superior Folate Supplements*

At Seeking Health, we’ve done the work and the research for you. Seeking Health folate supplements are formulated by Dr. Ben Lynch, founder of Seeking Health, naturopathic doctor, and creator of the StrateGene DNA Kit. Each product is carefully third-party tested, free from toxic and harsh fillers, and without artificial preservatives and sweeteners. 

If you want to support a healthy pregnancy, fertility, mood, cognition, and homocysteine metabolism, then we’ve got you covered with high-quality and bioactive forms of methylfolate that your body prefers and loves.*

L-Methylfolate Supplements

Standalone Methylfolate Supplements

L5MTHF-60-LOZ

  • L-5-MTHF: This potent formula contains the most bioactive form of folate on the market available in capsules and lozenges. The capsules contain 1700 mcg DFE per serving and are great for those needing a simple, convenient option. The lozenges support optimal, quicker absorption of the folate, and contain 1000 mcg DFE per serving .*
Multivitamins

  • Optimal Multivitamin:  A comprehensive, nutrient-dense multivitamin with plants, bioflavonoids, and herbs.
  • Optimal Multivitamin Plus:  A comprehensive, nutrient-dense multivitamin with plants, bioflavonoids, and herbs. Added liver, cognition, and vision blends for those looking for additional support.*
  • Optimal Multivitamin Chewable: A delicious, chewable multivitamin with active folate and chelated minerals. Great for kids and adults four years of age and older.*
  • Optimal Multivitamin Powder: A natural cherry-flavored powder that makes for delicious and nutritious smoothies!
  • Optimal Multivitamin Methyl One: Looking for a simple, single capsule serving size? This lower-strength multivitamin is convenient and has added antioxidants.
  • Kids Optimal Multivitamin: A nutrient-dense multivitamin for kids and teens. In a capsule format, and free from iron and copper.
Prenatal Vitamins

Optimal Prenatal capsules

  • Optimal Prenatal: Our original Optimal Prenatal capsules are designed for women with high nutritional needs. This top-selling product is formulated without iron for easy dose customization.
  • Optimal Prenatal Protein Powder: The same formula as our Optimal Prenatal capsules, but in a plant-based protein powder base. With a chocolate or vanilla option, this makes for a delicious and nutritious morning smoothie!
  • Prenatal Essentials: A concise prenatal formula that is great for those with an already healthy diet and lifestyle, and needing a cost-effective option. Prenatal Essentials is also available in a methyl-free formula.
  • Optimal Prenatal Chewable: A concise prenatal formula in a delicious chewable option! This is great for those with an already healthy diet and lifestyle and who need a cost-effective option. 

B Complexes

Active B12 with L-5-MTHF

  • B Complex Plus: A full, potent B complex formula containing all essential B vitamins, plus choline! Choline is an essential nutrient that acts similarly to a B vitamin, and is needed for proper cognition and liver health.*
  • HomocysteX Plus: Want to support healthy homocysteine metabolism? This product contains four essential B vitamins plus trimethylglycine for optimal methylation support and breakdown of homocysteine.*
  • Active B12 with L-5-MTHF: Our top-selling B12 and folate product in a delicious lozenge format for optimal absorption.*

Methyl-Free Folate Supplements

If you have tried methylated B vitamins in the past and experienced side effects such as nervousness or rapid heartbeat that can be attributed to the methyl groups, consider methyl-free options! Formulated for people sensitive to methylated supplements, these options utilize bioactive forms of B12 and folate, and are free from other methylated nutrients such as inositol and choline.*

Methyl-Free Standalone Folate

Folinic Acid capsules

  • Folinic Acid: Available in both capsule and lozenge formats, folinic acid is a non-methylated form of folate that converts quickly into the active L-5-MTHF form within the body. This potent formula contains 800 mcg DFE of folinic acid per capsule, and 1,360 mcg DFE per delicious lozenge.

Methyl-Free Prenatal Vitamins

Optimal Prenatal Methyl-Free

Methyl-Free Multivitamins

Optimal Multivitamin Minus One

  • Optimal Multivitamin Minus One: A single capsule serving multivitamin for those who need a convenient option. Free from all methylated nutrients, and instead uses a bioactive, methyl-free form of folate, folinic acid.

Methyl-Free B Complexes

Hydroxo B12 with Folinic Acid

  • B Complex Plus Methyl-Free: A one-of-a-kind formula containing your essential B vitamins, using non-methylated forms of B12 and folate.

The Bottom Line

Folate is an essential B vitamin, and arguably one of the most important for healthy mood, cognition, nervous system health, heart health, and pregnancy. Folate deficiency can increase your risk for a multitude of health issues, including risk of neural tube defects in fetuses.*

There are many forms of folate on the market and not all folates are the same. Methylfolate is known as the superior form of folate. However, it’s important to realize that not all forms of methylfolate are the same either!

There are many synonyms for folate as well as names that are not synonyms, but completely different forms that may do more harm than good. For example, folic acid is the man-made version of folate that is used in grain products to replenish folate that has been stripped out during food processing. Folic acid fortification of common foods has added to confusion of what folate really is.  The reality is that folic acid may actually block folate receptors, making it more difficult to correct a deficiency.* 

Adding confusion to the matter, many food and supplement labels will state “folate” without specifying the form. Some labels on dietary supplements don’t even tell you which form is in the bottle, making it important to inquire with the manufacturers about the specific form of folate contained in their product. Food sources of folate may not give you the folate intake that you need, due to most standard diets being low in leafy greens, vegetables, and legumes.

The best forms of folate are L-5-methyltetrahydrofolate (glucosamine or calcium salt versions), and folinic acid.* You will only find these superior forms in Seeking Health’s folate-containing  supplements. When it comes to choosing the best form of folate for you, education is key!

Shop Folate Supplements Here


References

  1. https://pubmed.ncbi.nlm.nih.gov/23482308/
  2. https://pubmed.ncbi.nlm.nih.gov/30570998/
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799525/
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282622/
  5. https://ods.od.nih.gov/HealthInformation/Dietary_Reference_Intakes.aspx
  6. https://fdc.nal.usda.gov/fdc-app.html#/food-details/1197933/nutrients
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257685/
  8. https://www.quatrefolic.com/index.php
  9. https://pubmed.ncbi.nlm.nih.gov/29882091/
  10. https://academic.oup.com/ajcn/article/84/1/156/4633186
  11. https://academic.oup.com/ajcn/article/87/3/517/4633283

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

† This information is for educational purposes only. No product results are implied.

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Comments (1)

  • Avatar

    Barbara Krall

    |

    THANK YOU, DR LYNCH for this comprehensive yet very understandable article! I have been a fan of Seeking Health products and your website for several years. Methylation and MTHRF can be complicated subjects to understand — I have read extensively about it, think I understand it but have never been able to explain it simply to someone else.

    Luckily, I have one of the mildest varieties of MTHFR (hetero C677T). Although, when initially starting folate supplementation, even my functional medicine PCP way overdid it with 2 mg of (6S)-5-Methyltetrahydrofolic acid glucosamine salt. After my body ramped up its methylation cycle and then ran out of potassium to feed the increased rate of cell division, I eventually had “panic attacks” (really low potassium attacks).

    I am one that does much better with the non-methylated folinic acid / calcium folate.

    Reply

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