MTHFR Methylfolate vs. Folic Acid Facts and Myths

In today’s post, Dr. Albert Mensah and I address the facts and myths surrounding MTHFR methylfolate, folic acid, and folinic acid.

Folic acid supplements, also called Vitamin B-9, are a way to take concentrated amounts of folate, which is naturally found in many foods including green leafy vegetables, and fortified in pastas and breads. Folic acid helps us utilize proteins in our bodies, form new blood cells, and create new DNA. Many medical studies have promoted folic acid supplements for the prevention of neural tube defects in infants as well as prevention for heart disease, depression, Alzheimer’s disease, and type 2 diabetes.

Proponents of folic acid supplements often think that more is better, both in dose amount and duration of supplementation. For many years now, we have seen negative side effects from the use of all forms of folic acid supplementation. A new study finally confirms what we’ve known all along: folic acid is not a supplement that should be taken long term without specific biochemical laboratory testing and evaluation due to the very negative side effects that could arise. It is not only important to know who would benefit from taking folic acid and how much is beneficial, but there is also a need to understand which form is best for each individual.

What many people fail to understand is the duality of folic acid activity. In the cytoplasm (outside the nucleus), it’s a donor of methyl, so for an undermethylated individual, the thinking is that MTHFR methylfolate is the appropriate course of treatment. In actuality, that’s not correct because, in the nucleus, which is the command center of the cell, where we are trying to affect change, folic acid removes 10 times more methyl than it donates. This can alter many cellular mechanisms including detoxification, enzymes, hormones, and neurotransmitters. This is because all forms of folic acid (including folinic, MTHFR methylfolate, and plant-based whole food sources) strip methyl at the level of DNA.

Again, whatever form of folic acid you take works differently outside the nucleus of the cell where it actually donates some methyl into the system and this is why MTHFR methylfolate has become so popular.

Yes, MTHFR Methylfolate Works Faster

Many people have come to believe that methylated folate is the best form of folate to take for optimal health, regardless of their methylation status and other biochemical imbalances. This is not accurate.

Let’s address a few issues regarding methylfolate and folic acid that have been circulating the internet lately, and hopefully, help our patients understand the purpose of methylated folate and when it should not be the preferred choice of folic acid supplements.

Faster is not always better, although some folks think that using methylfolate is a better option because methylated folate is assimilated by the body faster. The different forms of folate/folic acid, in general, will be converted to the same end product overall. However, a person who is overmethylated would not want to take methylated folate because it will add a small amount of methyl before it removes methyl.

Folic Acid Supplements: Why Process Doesn’t Matter As Much

Most folks misunderstand the process involved in the metabolism of folic acid versus methylfolate. This is the key to understanding the difference between how folate gets into the cell, or the time it takes to do that, versus the end goal of having a physiological effect from taking the particular form of folate you have ingested.

Folic acid doesn’t have to be de-methylated, but methylated folate does. Even though methylfolate gets into the system faster, it doesn’t actually begin to work faster than folic acid would, because there is the extra step of de-methylation before it can be utilized. It is only absorbed faster. It still needs processing. Quicker absorption has to go through longer processing and can ultimately take longer to complete the utilization process.

It’s like the difference between taking a direct flight to a city and taking a connecting flight to the same city. There are more steps, more delays when you take a connecting flight that re-routes you through another city. One way takes longer. One way is more direct. Once something enters a cell there is a whole lot that goes on. Whether you take a direct route or a re-routed path makes little difference in the end. By the time it is all said and done these pieces are all moving in the same direction. The only difference we are talking about is the rate at which they are moving.

The Dangers of Methylfolate

Methylated folate is not a one size fits all folic acid supplement. For some, it can have adverse effects, and unless you are tested for your methylation status, you do not know whether or not it will be beneficial or detrimental to you.

What do you think happens to that methyl contained in methylated folate? That methyl is going to get absorbed into your body. If you are giving that methyl to a person who is overmethlyated it is like adding kerosene to put out a fire. You’ll make your methylation imbalance worse. Overmethylated patients should use folic acid that is not methylated. If you are overmethylated do not take methylated folate or any other product that is methylated.

But Folic Acid is Synthetic, and That’s Bad, Right?

Folic acid is synthetic, yes but this does not make it unhealthy. It works, and it works better than natural forms in most cases. Folic acid is used to fortify foods and is found in most dietary supplements, simply because it is more stable and bioavailable than natural folates. Historically, since the days of Carl Pfeiffer, the pioneer in orthomolecular medicine, we have traditionally used folic acid for our patients and it has shown to be extremely efficient and effective. The notion that folic acid is synthetic and is not effective is incorrect. Anytime you take something out of nature and take it into a lab, it is synthetic. The truth is that folic acid works.

Folinic acid is metabolically active, which is correct. This means that folinic acid does not require enzymatic conversion before it can be utilized. Folinic acid can be found naturally in foods, but in order to benefit from folinic acid, it has to be prescribed in therapeutic doses for our patients. There are times when we may prefer the use of folinic acid to folic acid when we work with certain patient populations. Folinic acid has its best utility in autism, as we have seen over the years of research and clinical practice at Pfeiffer Treatment Center, now closed, the Walsh Research Institute, and at the Mensah Medical Clinic.

Much discussion surrounding methylated folate comes from genetic testing and the MTHFR paradigm, which is neither an accurate assessment nor an appropriate guide for true methylation disorders. MTHFR testing has significance in the realm of autism and multiple sclerosis, however, in the area of mental health, it is strikingly inconsistent and dubious at best.

Click here to listen to episode 3 of my Eat for Life podcast where Dr. Mensah and I discuss how the body processes all forms of folic acid and the myths surrounding MTHFR testing. In episode 14, we dive into the dangers of folic acid use and high folate diets for breast cancer patients.

We have seen clinically time and again that people who are truly undermethylated do not do well on methylated folate after two to three months. In fact, to the contrary, many people report worsening of symptoms. In summary, we have three decades of research and patient outcomes (a biochemical database of over 3 million chemical assays) that support all we’ve been discussing regarding the benefits of the different forms of folic acid and their appropriate usage as well as challenges.

Please remember everyone is unique so let’s not generalize regarding folic acid supplement use. There is only one you. Even if you are a twin, there is still only one epigenetic you. Do you think you have MTHFR Symptoms? Click the link below to see how I can help you.


38 thoughts on “MTHFR Methylfolate vs. Folic Acid Facts and Myths”

    1. Folinic acid is metabolically active, which means that it does not require enzymatic conversion before it can be utilized. Methylfolate requires the extra step of de-methylation before it can be utilized.

      1. Im confused so confused. I hade a test done that said i had the mthr gene mutation. So what do I take ????

    1. Over 40 years of human research and clinical patient outcomes by Dr. Albert Mensah, MD, and William Walsh PhD, about the benefits of different forms of folic acid and their appropriate usage override what you’ve shared. I encourage you to read this post in its entirety, especially the section where synthetic folic acid is specifically addressed. Folic acid is extremely efficient and effective. The notion that folic acid is synthetic and is not effective is incorrect. Anytime you take something out of nature and take it into a lab, it is synthetic. Methylfolate is not a better form. In fact, as this post explains, it is not a good option for both over and undermethylated individuals.

  1. Hello Samantha,

    I am currently being treated by a practicioner who has been trained by Walsh so I will also bring up this question to her.

    I was tested being overmethylated and having (mild) pyroluria. I am on a regimen that includes methylfolate atm and I am not doing any better so far. I am feeling very tense a lot of times and certain supplements seem to make things worse.

    Now that I read your post, I am thinking of changing methylfolate for folic acid, but I am wondering if the dosage has to remain the same.

    Thanks for your answer.

    Best regards,


    1. I’m overmethylated and use folinic acid. (I am also treated by Dr. Mensah.)
      I have an MFTHR snp and read about staying away from folic acid.

      1. As shared in this article that Dr. Mensah and I wrote together, folic acid isn’t bad and works quite well for patients that need it. Folinic is more metabolically active so we use it as well, again depending on the patient’s need and chemistry.

  2. Hi, I might want to recommend your recipes for our customers, but are your recipes for people with the biotype “undermethylation” all low-folate?
    One comment: According to Walsh, folate act as a serotonin reuptake promoter, driving serotonin activity even lower, and the benefits from improving methylation (if any) are overwhelmed by weakened serotonin neurotransmission for these persons. We have noticed mild depression from taking only 100-200 mcg of methylfolate for extended periods, so taking several hundreds or even thousands of mcg on a daily basis does not sound good. Still it is prescribed for many depressives with MTHFR. However I see some advantage of helping in the conversion of homocysteine to methionine, and other functions, but more is not better.

  3. I am 8 weeks pregnant and an undermethylator. I had been avoiding folate for myself, but understand from Dr. Walsh’s writings that for the first trimester I should be taking methylfolate for the benefit of my developing baby, while continuing Sam-e and L-methionine for myself. I have been taking 400mcg of methylfolate and getting additional through foods. Do I need to revisit this? I have not been able to find a Walsh or Mensah trained practitioner in my area.

  4. So what about a doctor who prescribes high doses of folic acid to women, like myself, when they are pregnant very early on in the pregnancy to prevent birth defects, and then we have a child with severe ADHD, on the autism spectrum, etc. Could this have contributed to that? I have no clue what my methylation status was at the time or is now.

    1. Autism is an epigenetic disorder, meaning that one or both parents contributed mutations that created the condition. It is important to take folic acid in the beginning to protect your child, but not throughout pregnancy if you are undermethylated, as it can have negative effects. I encourage you both to get properly tested. Autism and ADHD are treatable, especially when caught early on.

      1. I am reading up on the these old posts. Can you please describe what specific tests you think the parents should have done?

  5. I am an under methylator (apparently down 40%.) I took folic acid prior to pregnancy and miscarried 3 times. This is one of the problems of taking folic acid for under methylation. Early 2017 I took a Genova test (Optimal Nutrition Evalutaion) which recommended I need 1200mcg of methylfolate. I have been doing this for 8 months now and feel great! Have also increased green leafy veg intake.

  6. Hi Samantha

    I’ve read your articles with great interest since reading Nutrient Power. I am going to be tested by a Walsh practitioner in Ireland (certified from WRI site so legitimate as I know many claim to be but are not) so I’m not looking for individual advice as I will get that in a few weeks once my tests are conducted and results come in. I just wondered generally about your opinion on the following

    Ive heard Walsh say bloods are only part of the picture and in the books many traits are listed for each biotype -specifically referring to depression chapter. I feel I have traits from both under and overmethylated lists so to me tests are the only way to truly tell.

    What I wondered is I had some tests on our national health service in the UK and have low folate at under 2.2 acceptable range seemed to be from 2.4- so lets say in theory I receive my Walsh tests back and and Im found to be an undermethylated person. Does this mean I should NOT attempt to increase my folates to an acceptable level as I know from reading the book undermethylaters should avoid folates.

    Secondly and this is just out of interest how often do you have clients who seem to have traits from many of the biotypes? As I get the impression this is part of the decision making process Ive even heard Mensah and Bowman say in webinars they suspect what tests results will be before they come back and are normally correct. Whereas to me the bloods will reveal the true picture and when they come back the traits become irrelevant scientifically speaking as they are just generalisations vs chemical proof.

    Thanks 🙂

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