The Differences Between Folic Acid, Folate, L-Methylfolate, etc.

Folate is absolutely essential for a healthy brain and body. Most people I talk to have heard about folic acid. A few know that it is an important vitamin for pregnancy because it reduces neural tube defects in newborns. Primarily for this reason, the US government started mandating the addition of folic acid in cereal products in order to reduce the number of neural tube defects. The plan worked, because the incidence of neural tube defects apparently went down from 3.5% to about 1% after folic acid fortification.

However, despite the success in lowering neural tube defects, scientists started noticing negative effects from the fortification of folic acid in food products. Increased colon cancer and the masking of anemia were the primary concerns, and evidence of increased autism and epilepsy were other concerns.

Additionally, people have started noticing a myriad of health problems can be remedied by taking supplements of functional folate (not folic acid). I’ll explain the difference between functional folate and folic acid below.

Folic acid is just one specific form of a class of molecules collectively called “folates”. Folates are essential to health and life, and are an essential vitamin. It is important to remember that folate is a generic term for many types of compounds similar to folic acid. Folic acid is an artificial folate chemically pieced together in the lab using smaller chemicals. Strictly speaking, folic acid is synthetic and virtually nonexistent in nature. Folic acid is a bare-bones vitamin that needs several “upgrades” or “additions” in order for it to actually function in your body. Think of folic acid as a car without wheels or gasoline. Even though it has potential, when the rubber meets the road (pun intended) folic acid just doesn’t work in your body until it gets “fixed up”. Even though folic acid isn’t fully assembled, your liver has some limited capacity to “correct” the folic acid by attaching the wheels and filling the gas tank, so to speak. In contrast with folic acid, however, methylated folate (known as L-methylfolate, 5-methylfolate, 5-MTHF, prescription Deplin, 5-CH3-H4folate, or simply methylfolate) is primed and ready to function in your body. It has all four wheels and gasoline and is ready to work in your body.

The Major Types of Folate

Front WheelsBack WheelsGasoline
Folic AcidNoNoNo
DihydrofolateYesNoNo
TetrahydrofolateYesYesNo
5-formyltetrahydrofolate (Folinic Acid)YesYesNot quite
5,10-methylenetetrahydrofolateYesYesNot quite
5-methyltetrahydrofolate (L-methylfolate or 5-MTHF)YesYesYes

The problem with folic acid (and it’s a major problem), especially if you have particular MTHFR genetic mutations, is that the liver can have a very hard time upgrading folic acid into functional L-methylfolate. Thus, even if someone has enough “folate” they may not have enough methylated folate (folate with wheels and gasoline) so the folate is doing them no good. They don’t produce enough neurotransmitters (they’re depressed), they aren’t protected against cancer, Alzheimer’s, fatigue, and more.

It’s extremely important to get folate in the most reduced (with wheels) and methylated (with gasoline) form you can.

The good news is that L-Methylfolate is the primary form of folate found in nature and, naturally, in most fresh, unprocessed food. The L-methylfolate in food is fully built with all four wheels and the gas tank is full.

References

Powers HJ. Folic acid under scrutiny. Br J Nutr. 2007 Oct;98(4):665-6. Epub 2007 Aug 13. PubMed PMID: 17697404.

Choi JH, Yates Z, Veysey M, Heo YR, Lucock M. Contemporary issues surrounding folic Acid fortification initiatives. Prev Nutr Food Sci. 2014 Dec;19(4):247-60. doi: 10.3746/pnf.2014.19.4.247. Epub 2014 Dec 31. Review. PubMed PMID: 25580388; PubMed Central PMCID: PMC4287316.

Cornelia M. Witthoft, Karin Forsskn, Lena Johannesson and Margaretha Jagerstad. Folates – food sources, analyses, retention and bioavailability. Scandinavian Journal of Nutrition/Naringsforskning Vol 43:138-146, 1999.

About Nicholas Hundley, MS, CNS

Nicholas Hundley is a nutritional biochemist and certified nutrition specialist. He is the main author here at MindWhale.com. He practices nutrition and can be found at NicholasHundley.com

8 thoughts on “The Differences Between Folic Acid, Folate, L-Methylfolate, etc.”

    • Hi Nancy. Great question. If broccoli contains about 100 mcg of folate per cup, then it would take 150 cups of broccoli to have the amount of folate contained in 15mg deplin. If sprouts contain about 750mcg of folate per 100g, then it would take 2kg of sprouts to have the amount of folate contained in 15mg deplin. I bet it would take even more citrus to reach 15mg methylfolate.

      That’s a lot of greens.

      Deplin is a pharmaceutical strength folate product and contains a much higher dose than the body normally needs for functioning. It is important to note that there are many nutrients besides folate involved in a healthy methylation cycle for optimal brain and body functioning.

      Reply
  1. In your response to Nancy Roberts you said “Deplin is a pharmaceutical strength folate product and contains a much higher dose than the body NORMALLY needs for functioning.”
    What if your body (brain, in my case) isn’t functioning “normally?” I have massive hydrocephalus from an acquired traumatic brain injury, a shunt, and a handful of prescriptions for depression, sleep and movement disorders that are most likely at least partially related to my TBI. I’ve been taking 15 mg Deplin for a couple years now. I’m 55, eat fresh fruits/vegetables and protein (not much fat), walk every day. I’m not working anymore & would like a less expensive option, but know without Deplin I need an even longer nap and have even less energy. Thanks for any guidance you’re comfortable providing.

    Reply
    • Hi Howard,
      If you’re noticing a benefit from 15mg of Deplin, there’s a chance (and this is not medical advice) you may really be needing adjunctive methylation support. This includes but is not limited to:

      1. Phosphatidyl choline
      2. Methyl-B12
      3. 1-5mg nutritional lithium orotate
      4. Omega-3 EPA+DHA
      5. Minerals, including magnesium, zinc, electrolytes
      6. Quality multi

      Those may lessen your need for so much methylfolate and also dramatically support brain healing and emotional health. If you decide to try them, start low, one at a time, and work up the dose. There are a lot of other nuances but that’s a good place to start. Happy holidays!

      Reply
  2. It is recommended that I take L-methylfolate because I am homozygous MTHFR but also heterozygous for VDR. I am also homozygous COMT. Both the VDR and COMT indicate I should avoid methyl donors. Can I take the L-methylfolate? Should I use hydroxy B12?

    Thank You!

    Reply
  3. Hi Nicholas,
    I need your expert advise. What is the major difference between EnLyte and Deplin.
    They both sound great for helping to produce serotonin and decreasing depression.
    If you had to choose one over the other which one would you take? I am faced with making this decision this week.
    Grateful for your advise,
    Barbara

    Reply
    • I would take Enlyte because it’s a more dynamic product with supporting nutrients (zinc, magnesium, other B vitamins) and not just L-methylfolate. However, there are a lot of non-prescription options for methylfolate supplements as well.

      Reply

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