Folate: Friend or Foe?

By Samantha Gilbert, FNC, CHNP, CNC     Last updated on September 4th, 2022

Yesterday, while perusing my fitness magazines, I couldn’t help but notice dietitians and doctors preaching about the importance of folate; they’re recommending that everyone consume more folate in both food and supplement forms.

This got me thinking. Here in the United States, we are one of the wealthiest nations in the world, yet we experience higher rates of disease and injury, and we die sooner than people in other high-income countries.

Let’s understand how folate and folic acid impact the brain and body.

What is Folate?

Folate is a B-vitamin that is required for many biological activities. These vary from the creation of nucleic acids (DNA + RNA) and neurotransmitters including dopamine, adrenalin, noradrenaline, and serotonin to the detoxification of the master antioxidant, glutathione. It is essential for immunological health and is necessary for the generation of healthy red blood cells (which is vital in the prevention of megaloblastic anaemia) as well as platelet production.

Is Folate Good for You?

Well, this depends on your biochemistry. For those of us that are undermethylated, any form of folate, folic or folinic acid will function the same over time, regardless of whether it comes from food or supplements. This is because folate acts as a demethylating agent. The opposite is true for overmethylated individuals that require folate to reduce an overload of methyl groups.

Practitioners often tell their clients they need folate every day, but depending on your chemistry, the answer could be yes or no.

Fortified Foods and Folate

It all began during the Industrial Revolution when we decided to remove the bran from the germ of grains through milling and mass refining. Grain products could then sit on store shelves much longer without spoiling.

At the end of World War II, bakeries in America began using large amounts of chemicals, additives, bleaches, and preservatives (as many as 25 different chemicals are added to refined grain and bread products) to create an even longer shelf life. Because this process strips away all of the natural vitamins and minerals, foods must be “fortified and enriched” with vitamin and mineral forms our bodies do not recognize.

And at the top of the fortified and enriched list? Yep, you guessed it, folic acid.

What’s even worse is that in the United States and Canada, folic acid fortification became a mandatory practice in 1998.

Folate Versus Folic Acid

Folate is a general term that denotes a group of water-soluble b-vitamins (B-9), while folic acid stands for the synthetic compound used in supplements and to fortify foods. Much has been said about these two forms, with the general consensus being that it’s safe in food form and as supplemental methylfolate, but not as supplemental folic acid.

Folic acid is a manufactured molecule that is not present in nature. It’s more stable in tablet form, which is why it’s used for supplementation. Folic acid works in different ways depending on its location in the cell. The part we’re most concerned with is the cell nucleus because that’s where methyl loss and excessive stripping of methyl by all forms of folate and folic acid (even food-based) occurs.

Are There Side Effects to Folate Fortification?

An increase in conditions such as autism, depression, bipolar disorder, autoimmune diseases and diabetes were noticed once fortification became mandatory (along with chemicals such as glyphosate and atrazine, potent endocrine disruptors). Studies also continue to emerge linking folic acid supplementation to illnesses such as breast cancer and colon cancer.

Researchers involved in the treatment of cancer have found that too much folic acid is directly related to increased cancer rates. Methotrexate, a drug used to treat cancer, fights cancer by inhibiting the metabolism of folic acid. When folic acid was added after treatment, cancer rates increased. This explains why undermethylated people do worse on folates and have a greater propensity to develop cancer.

What is Methylation?

Methylation is a fundamental metabolic process for our bodies to properly function. It’s essential for detoxification, immune function, DNA synthesis, energy, mood regulation, and inflammation management. Many chronic diseases are caused by impaired methylation.

In a methyl group, one carbon is attached to three hydrogens. But, since carbon can link to a total of four atoms, the methyl group has one empty site where something else can attach.

In methylation, another molecule joins the methyl group at its empty receptor site and creates a biological switch which can activate or deactivate certain bodily functions. It can be used to “turn off” DNA. While methylation is responsible for gene silencing, folate can turn on deviant genes in undermethylated individuals.

How Are Methylation and Folate Related?

As I shared in this post, there is a duality to all forms of folate and folic acid activity when it comes to the methylation cycle.

Methylation status is determined by a tug of war between enzymes for undermethylation versus enzymes for overmethylation. Whoever wins this tug of war determines your methylation status, not one enzyme. You may have a particular SNP (single-nucleotide polymorphism) but it doesn’t mean that that SNP is causing you any trouble.

Outside the nucleus of the cell (the cytoplasm), folate and folic acid donor some methyl, but in the nucleus, which is the command center of the cell, where all of our instructions are made and where we are trying to affect change, it steals 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 such as spinach and avocados) steal methyl at the level of DNA.

Undermethylation and Folate

If you are undermethylated, it’s important to be very careful with folate and folic acid because they are serotonin reuptake promoters, (anti-depressants [SSRI’s] are reuptake inhibitors and undermethylated persons generally respond well to these medications). This explains why my years as a raw vegan on a high folate diet yielded devastating results for me.

Keep in mind that any form of folate, folic, or folinic acid (including methylfolate) will function the same over time, regardless of whether it comes from food or supplements. And when it comes to methylfolate, it’s not a better form, it’s simply a different form.

Nutrients give our genes their marching orders and are required for balanced methylation. SAMe is one of the most important methylating nutrients; therefore, anything that depletes SAMe reduces methylation. SAMe is depleted in undermethylated individuals and anything that interferes with ATP production (such as diet, alcohol, and stress). SAMe requires important nutrients such as B6, B12, and methionine (a precursor to SAMe) to function optimally. These are important supplements for undermethylation.

Overmethylation and Folate

Undermethylators have low amounts of important neurotransmitters (dopamine, norepinephrine, and serotonin), whereas overmethylators have high levels of these important neurotransmitters.

Low folate disorder is another name for overmethylation, which can manifest as ADD, OCPD (obsessive compulsive personality disorder), depression, high anxiety, and even schizophrenia. Overmethylated individuals need folate to balance out an excess of methyl; as I shared previously, folate is a powerful demethylating agent. Overmethylation supplements include folic acid, folinic acid, and folate from foods, as well as vitamin B6. Keep in mind methylfolate is contraindicated in those with overmethylation.

Nutrition Counseling To Help You Thrive

In order to heal methylation disorders, I aim to identify and address the root biochemical causes and imbalances of your symptoms.

I offer a free 1:1 consultation to help you disconnect from the hype and the marketing jargon, and address the true source(s) of your discomfort. It’s time for your healing journey to truly begin.

References

Is folic acid good for everyone?
Folic Acid and Risk of Prostate Cancer: Results From a Randomized Clinical Trial 
Mensah, Albert. MTHFR and Mental Health: Understanding The Overall Effect of Individual Genetic Mutations (SNPs)
Too Much Folate in Pregnant Women Increases Risk for Autism (Johns Hopkins Study) 
Science Daily: Researchers found too much folic acid was just as detrimental as too little 
23 & Me article about MTHFR (with research links) 
MTHFR ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing 

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93 thoughts on “Folate: Friend or Foe?”

  1. Thanks for the article.
    One doubt, for one who small dosages of methyl-b12 or folate rich foods (watercress, liver) gives insomnia and more nervousness, also with histamine intolerance, is it supposed to be in the under or in the over-methylation part?

    Homocysteine 11.4 blood test.
    Zn lower limit
    B12 ok
    Folate 10.4

    Thanks!

  2. How do you explain this? Is this article not stating that people with depression have a deficiency in folate and that taking folate (along with SSRI’s) helps with this?

    “Without the participation of 5-MTHF in this process, SAMe and neurotransmitter levels decrease in the cerebrospinal fluid, contributing to the disease process of depression.”

    “Depressed individuals with low serum folate also tend to not respond well to selective serotonin reuptake inhibitor (SSRI) antidepressant drugs. Correcting the insufficiency by dosing folate along with the SSRI results in a significantly better antidepressant response.”

    https://pubmed.ncbi.nlm.nih.gov/18950248/

    Here is another one.

    “Folate supplements especially levomefolic acid (L-5-methylfolate) demonstrated improvement in clinical outcomes in certain mental health conditions, such as in major depressive disorder (including postpartum and post-menopausal depression), schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder and bipolar affective disorder. Daily dosage range is 50 microgram to 15 mg orally daily depending on the clinical diagnosis and clinical presentation.”

    https://www.sciencedirect.com/science/article/pii/S0753332221013287

    Where is the proof that folate is a Serotonin reuptake promotor in research studies?

    1. Hi Melissa, as an undermethylated depressive I can attest to the horrible effect that folates have on my mind, it’s no joke. I was scared/reluctant to avoid folates at first because there is so much literature about how important they are. But, even after years on a nearly pure carnivore diet, my RBC Folate and my hemoglobin levels stay high. This is despite the fact that my serum folates are low since the serum only represents recent folate exposure.

      I have an upregulated CBS gene that causes me to have higher than normal levels of sulfates in my urine. I’ve concluded that in my personal case, this is the genetic cause of my undermethylation, not an MTHFR mutation. Since sulfur gets pulled out of the methylation cycle by the CBS gene, I’m peeing out part of my sulfur and it doesn’t get recycled like it should. It leaves my methionine and SAMe levels very low.

      In my bloodwork, my fasting levels of all my sulfur-based amino acids (including Methionine and Homocysteine) are quite low. I don’t know if this causes me to have lower than normal folate requirements, or if I just recycle folate very efficiently. But either way, my homocysteine is always low and my red blood cells are normal so there isn’t any functional deficiency of folates despite the fact that I avoid them like the plague.

      I’ve read for years that folates are SERT promoters. I don’t think it’s true because I’ve read studies that say that high dose SAMe has little effect on serotonin or it’s transporters. It did increase dopamine by over 1000% though 🙂 But nonetheless, folates are powerful demethylating agents. I believe the proof lies in this study from 2011.

      “The fact that folate participates in the enzymatic demethylation of histones provides an opportunity for this micronutrient to play a role in the epigenetic control of gene expression.”

      https://pubmed.ncbi.nlm.nih.gov/21510664/

      Exactly what is being demethylated hasn’t been proven by anyone, there are only theories. My personal guess is that undermethylated people gradually develop over-expressed (upregulated) monoamine receptor sites in their brain. All monoamine receptor types (5-HT1a, 5-HT2b, D1, D2, etc…) are under epigenetic influence, not just the transporters (SERT, DAT, etc…). There are studies that show highly upregulated serotonin binding sites in the prefrontal cortex in a subset of depressed suicides. The more serotonin receptors someone has, the less responsive they become to a static level of serotonin. This is generally true for all neurotransmitter receptor types. It’s just a theory though.

      I totally believe it’s true that major depression is an epigenetic illness. The genetic predisposition, combined with constant stress or an environmental insult, is likely what puts things into motion. SSRIs use brute force to try to down-regulate serotonin receptors by flooding them with too many neurotransmitters for them to handle. The problem is that it’s a hammer approach that ultimately causes it’s own form of dysregulation.

      The only reason I am chiming in is only to confirm for anyone reading that folates do in fact cause severe mental destabilization in some people. The reason why hasn’t been totally flushed out, but the phenomenon is completely real. I can also confirm that prior to my initial mental breakdown in my 30s, I never knowingly had a negative reaction to folates. If I did, I never made the association.

      SORRY FOR THE LONG POST!!!

    1. Hi Lisa – No, methylation status is determined via testing, but undermethylation is commonly seen in fibromyalgia.

  3. Hello. Are there any legumes that are lower folate? I am dairy, gluten and egg free due to food Intolerances. I feel like I am running out of food options.

    1. Hi Joanne – I wish I could share some low folate legumes with you, but there aren’t any. Animal proteins are your best source of low folate, bioavailable sources of zinc, and other important nutrients such as B6, which is needed for hormone and neurotransmitter balance.

  4. Sorry I meant to say b complex that has no copper, and has the UN methylated versions of b12 and calcium folinate (I read this version is better than folic acid because it is converted better ?)

  5. Hi Sami,
    I did the DHA package test (Pyrolle, Zinc, Copper, Ceruloplasma and histamines) and am wondering a few things.

    1. Is over methylation status determined solely by histamin level? If not, what else? I just want to know the test names please?

    For example, can someone just have false over methylation status because they were supplementing with methylated folate for a long time? It makes sense that if you are taking folate then your test will show you have low histamine due to the body taking methylated folate?

    2. For borderline overmethylated folks what version of b12 is best? I know it can’t be methycobalamine so which one?
    What brand Bcomplex do you recommend what has the correct b12 and folate for over methylated folks? I can’t for the love of god find one that has no copper, plus in methylated b12 and calcium colonic acid!
    Please help!

  6. Hi Samantha!

    Thanks for writing this article. They are very helpful when it comes to methylation! This week I’m about to get my histamine results, but since I have OCD (Pure O) I guess I’m an undermethylator. Therefore I’ve already supplemented with Sam-e. I took 800 mg a day. The first 5 weeks it worked very well, but this week I don’t feel the effects anymore. Do you know perhaps what’s the reason because of this? Thanks in advance!

    1. Hi Sarah – nutrient therapy requires a wide range of antioxidants and other important nutrients to create change at the level of DNA. SAMe on its own is wonderful for UM’s but we need much more than that for lasting change to occur. In addition to methylation, I also look at copper, zinc, and pyrrole levels to name a few. You may also have one or more of these conditions, something I commonly see in my clinic.

      1. Hi Samantha,

        Thanks for your reply. Today I’ve received my blood results of the histamine test and turns out I’m probably an overmethylator with a histamine of 23. Could that be possible with Pure OCD? Could you help me out? I’m still taking the Sam-e, but now I feel very emotional.

  7. Heather Brusseau

    Hi Samantha!

    I am an undermethylator who also has the MTHFR deficiency. I take L-methyl folate. I’m confused as to how my body can run the methylation cycle if I do not take l-methyl folate? How can I avoid taking folate when it’s needed for the methyl cycle to function properly?

    Thank you in advance for your advice.

    Heather B.

  8. Hi Samantha,

    i would really like to ask please, if someone is homogenous 677T, and subsequently has a folate deficiency (which i think means that he should take folate to correct this deficiency), but he is also an undermethylator (which means he shouldn’t take folate), what happens in this situation?
    Thank you in advance.

  9. Hi Samantha, I have bipolar disorder and when I take B vitamins or a multivitamin then I end up feeling worse off. Could it be from the folate? A multivitamin gives me some energy but it also makes me feel a little off so im not sure if it could be interacting with one of my meds(latuda, lamictal, clonazepam)? Also even if I take a vitamin d supplement then it makes me really tired and off. I can take a b12 sublingual and thats about it. Im very sensitive to supplements. But i do think i need to take a low dose multi because of the lamictal depleting vitamin mineral content. Have you ever came across any of this before? Thank you

    1. Hi Scott! This is difficult to answer without lab testing but I see this a lot with leaky gut/dysbiosis. Without proper testing, there’s no way to determine your specific nutrient requirements. Keep in mind you don’t have to have GI symptoms to have gut inflammation.

  10. Hi. loved this article. i’m wondering: If you are undermethylating and take too much folate. how long will it take after stopping folate for the symptoms of too much folate go away? are we talking days or months?

    how long after you quit your raw vegan lifestyle did you notice improvements especially with cognitive problems ?

  11. Hi Sami, this is interesting… I have been supplementing sam-e for a few years, because methyl folate b complex and lots of green juices made me depressed over time. However, I currently have low serum levels of folate, and clinical signs of b vitamin deficiency such as sore red tongue, lips, sores on side of mouth. Not to mention extremely elevated anxiety right now. I had a 7 hr surgery 4 weeks ago, so that hasn’t helped my levels. Sam-e at low doses or high doesn’t seem to help anxiety. I have been prescribed a B complex from my naturopath that includes semi-active vitamins. BUT Im scared to take. Not sure what to do…all i know is I am feeling very undermethylated. Should I take sam-e and B-vits too in order to replenish the b levels? Or will Sam-e inhibit methyl folate reductase enzyme and make me lower?

  12. Hi Sami,

    Thanks so much for this great article. It is very informative! I am homozygous for mthfr c677t and I get terrible anxiety/a racing heart with any methylated vitamins. However, I felt great after taking regular folic acid several years ago. Do you know why this might be? I know you said that all folates act the same way over time, but did the folic acid have some initial effect that made me feel better?

    Thank you

  13. I think this is what’s happened to me. I’ve supplemeneted b12/folate for years as needed. It recently has thrown me into terrible anxiety attacks and panic. Worst 2 weeks of my life. I finally started feeling better 2 weeks out, yesterday had some spinach and all my symptoms started coming back. Now I know. Not even food folate. Is there anyway to move this out of my system fast??

  14. my questions were: how does one become a mensah patient? it sounds like you’re down with the walsh biotypes, is that right? what do the acronyms by your name stand for?

  15. Hi,

    I am fairly new to this nutritional approach.
    I have a patient with low folate, who has treatment resistant depression.
    He is an undermethylator (high histamine, low zinc) and has high pyrroles.

    Due to the low folate – would there be a role of some supplementation with l-methylfolate? (He had a poor response to SSRIs – they made him worse).

    I read some studies that show l-methylfolate can be helpful in treatment resistant.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869616/

    Thoughts?

    Thanks..

  16. Could i please ask something? What if someone with a homogenous c677t is an undermethylator, but has also tested for low blood folic acid?

  17. Don’t veggies have duality of folate and methyl donors? Don’t spinach have several times more methyl donors than folate?

    I understand the need to not supplement folate if one is undermethylated. But as an undermethylator, I actually feel great eating veggies absorbing methyls that way and just forgoing excess folate supplementation.

    I also supplement DMG or TMG or SAMe. I’ve lost 10 lbs within a months time on a methyl rich veggie diet along with protein and fats and some healthy carbs.

    1. I’m glad you are doing well Ted, and I trust you were properly tested. Plants do not provide appropriate methyl donors for undermethylated individuals. Plant-based diets may feel good initially, but over time, can create a decline for the undermethylated person. Of course, it’s always important to be sure other levels are tested, such as homocysteine, which does require folic acid to reduce, and would be used in a very target dose for a specific amount of time until levels are normalized.

  18. I am completely depleted in all my B vitamins except for B9 (weird) according to my NutrEval test from Genova last month. A also have 2 copies of C677T for the genetic MTHFR mutation. I have also suffered life long depression and anxiety. My thinking is that if I am so depleted in these vitamins due to a “faulty” methylation system, then why, upon taking Active B-12 with L-5-MTHF along with a b complex (minus b12 and folate), do I feel so much worse with depression and fatigue? How do I replete these vitamins if I cannot tolerate them? I have even been eating lots of healthy dark greens in the hopes of helping this. I am completely lost and feel very sick! What would be the next logical step to take if a patient came to you with this info? Thanks in advance so very much!

    1. Hi Beth,
      The testing methods you mention are neither an accurate assessment nor an appropriate guide for true methylation disorders in the area of mental health, so I encourage you to get properly tested. Click here to schedule a complimentary session with me to see how I can help.

      1. Thank you but I only mentioned one test – NutrEval from Genova. What tests to you recommend for proper testing?

      2. Lastly, do you follow Dr Walsh’s protocol and order the appropriate tests as well as interpret them? I understand you are a nutritional expert? Thanks again.

  19. I’m a little confused. Isn’t dietary folate a methyl-donor? So if a person is over-methylated, Dr. Walsh says the person should take folate since Overmethylated individuals have too much methyl and folate is a powerful demethylating agent.

    Even Dr. Ben Lynch says that when a person is overmethylated with Mb12 and methyfolate, s/he should take niacin to “mop up” the methyls.

    My question is, how is folate a powerful demethylating agent, when I read other statements saying that folate is a methyl-donor?

    1. What many people (especially practitioners) fail to understand is folic acid’s role of duality. In one area, it’s a donor of methyl, so for an undermethylator, they think folic acid or methylfolate is a great thing. In actuality, that’s not correct because in the nucleus where we’re trying to affect change, where the command center is, folic acid removes methyl, which can inhibit any detoxification process. This is because all forms of folate strip methyl at the level of DNA. DNA level is in the nucleus of the cell where all the instructions are made. That same folic acid works differently outside the nucleus of the cell where it actually gives lots of methyl into the system.

  20. Great read! What about those people who are undermethylated and wanting to become pregnant? Ordinarily doctors would recommend taking a pre-natal multi V with folate to prevent birth defects. Is this the case with U.M. individuals? Also, are there B-complex supplements on the market available without B9? Other B’s are quite important and I struggle to find supplementation without folate.

  21. Hi there

    Due to epilepsy I took 5mg of folic acid for a few years during conception/pregnancy etc. My blood levels remain very high and don’t seem to have gone down despite having not taken folic acid for at least a year. I’ve been taking methyl folate on and off. Would this be indicative of being an overmethylater and therefore being more consistent with my methyl folate would help clear it? Thanks!

    1. Hi Rebecca,
      Thanks for your comment, but this is impossible to answer without proper testing and assessment from a qualified practitioner.

  22. Hi Sami G,

    Interesting reading these comments. Another consideration for individuals not doing so well on a vegan/vego diet could be that these diets are high in copper and lower in Zinc, and also essential proteins. High copper, low zinc can contribute to negative mental states, also protein deficiencies. Is it possible that these factors are an issue rather than excessive folate?

    1. Hi Bec,
      Yes, there is also a connection with high copper, low zinc, and protein deficiency. However, folate is a primary factor with methylation imbalances and must be taken into consideration for proper treatment.

      1. Thanks for your reply Sami! I have a similar story to you: Undermethylated, copper overload. Also have pyroluria, and a number of secondary issues. I have had a consult with a “walsh” practioner, however they recommended 1,000 mcg of methyl folate amongst other things and more red meat, protein based diet as apparently I am a fast oxidizer and “para-sympathetic” metabolic type. I have spent a small fortune on trying to feel well, with some results but certainly not enough to substantiate the cost involved. Like yourself I have tried acupuncture, vegan, aromatherapy, several naturopath’s, and a hundred other outlets. But I think you may have a few missing pieces to the puzzle for me. Since I dont have the energy to study a masters degree, I would love to consult with you and gain further insight 🙂

      2. Hi Bec,
        I look forward to speaking with you soon. Please note the practitioner you mentioned in your booking is not Walsh trained.

    2. Hi my name is Tyler,
      I recently had a blood histimine test done and it was high 86 and a homo cysteine test also high 8.6 so I know I’m undermethylated starting methyl B12 and B6 was told to take Methyl folate is that a no- no any thoughts?

      1. Hi Tyler,
        Unfortunately, I cannot provide specific guidance without consulting with you but with your numbers, I would be very cautious with methylfolate.

  23. Second question is… to work as a nutritionist in functional medicine do you have any study recommendations? Here in New Zealand I could do a two year diploma in Nutrition but i’m not sure if that will be enough preparation to study functional medicine & nutrient therapy. I would like to work as a nutritionist alongside a functional medicine doctor or as a private consultant/health coach focused on nutrient therapy. Essentially what you do. Any thoughts?

    1. Hi Erika,
      I recommend a masters degree program from an accredited institution that focuses on functional medicine and human nutrition.

  24. Hi Sami, Brilliant article – thanks. A question on the folate. I was told that over methylators should avoid methyl-folate because of the ‘methyl’ and instead supplement with Folic Acid. I have read about the risks with folic acid and would prefer a natural form of supplementation. What are your thoughts and recommendations on this?

    The same with B12 – is it true that over-methylators should avoid methylcobalamin? if so what other form is best?

    Can you recommend any further reading on optimum diets for under and over methylators – fascinating stuff.

    Thanks so much for the work you do,
    Erika.

    1. Hi Erika,
      Thanks for your post, I’m glad you enjoyed my article. Yes, overmethylators should avoid methylated nutrients. Keep in mind that all forms of folic acid perform the same over time.

      1. In other words, every overmethylator is unique and functional testing along with an in-depth assessment will reveal what is and isn’t needed.

  25. Hello. I am quite new to learning about methylation. I just stumbled across it because I was researching info in regards to MTHFR gene mutations. I’ve recently found out some relatives have them and so now I’m interested in testing to see if I do too. That might explain a few things for me. 🙂
    But in what I’ve researched, which isn’t all that much at this point :), I’m pretty stumped about something. If I understand correctly- if one has an MTHFR gene mutation then it is folate that they need to help or correct it. Other key nutrients too, but folate is the main/most important according to everything I’ve read about it so far. It seems it is definitely “needed” for those with MTHFR mutations. But then I also read that many (but not all) MTHFRs are undermethylators as well. And then from what I’ve read above by you and on a couple other sites- if you’re undermethylated, you must avoid folate as much as possible. It’s very confusing. Maybe I completely misunderstood something? I’d appreciate it if you can help me to understand please. 🙂 Also, do you offer/do testing for both? *I have to say, based on typical symptoms I feel like I’m 50/50 under and over- methylated. 🙂

    Thank you,
    Lyn

    1. Hi Lyn,
      Thank you for your comment, I get this question a lot. The thing about genetic tests is that they have no way of determining the net effect of what the SNPs are actually doing in your body at the present time. I use functional tests (blood, urine and hair) to determine methylation status and other deficiencies and overloads. This is how your biotype is determined. If you’d like to set up a complimentary session to see how I can help, you can book one.

    1. Hi Mike,
      My diet varies depending on my workout and travel schedules, but one thing remains: I thrive on a high protein diet and since I workout a lot, I also make sure to get adequate fat and starches such as yams and MCT oil. I’m also mindful of not consuming too many high folate vegetables. It’s amazing how much better I feel without green leafy things. 🙂

  26. Hi Sami,
    Thanks for the info on folate. It seems to be a wild card in all things methylation.

    I had krypto test at 15 and histamine test at 70. Might of had some limited light exposure but mostly low light after and into freezer quickly. Sounds like should focus on pyroll first, then retest wbc?

    Folate is confusing, had high end homocyeistine
    levels and was told to take methlated folate. When folate blood test came back high, seemed odd to take more of it. So thanks again for the extra detail. Have seen web info for trimethylglycine helping with homocyeistine and under methyl.

    Is b12 in methylated form good for undermethylation?

    Have you found that once things were stabilized could you have limited amounts of foods with copper? I think avacodos are high in copper too.

    If a person avoided most processed foods and then any supps with folate then would some greens a few times per week balancing things out?

    1. Hi Steve,
      You are most welcome. I do enjoy high copper foods once in a while such as an ounce of raw dark chocolate and a few almonds here and there, but for the most part, I stay away from them. It’s important to stay on a low folate diet.

      1. Dear Sami,
        What would be other high copper foods you would suggest one to avoid if suffering from a copper overload?
        Thank you in advance!
        Kind regards,
        Dorina

  27. Hi Sami. I’ve been ayi g around with supplements since getting my 23&Me resumts back. Good results with SAM-e, added more supps to support but now am needing help to fine tune. Still need to get tested for histamine and copper and the rest.

    My question is this: is it possible that with SAM-e and too many other supplements I pushed into overmethylation? I ask because one night I woke with really busy thoughts (as usual) and thought it felt like overstimulation due to excess neurotransmitters (I have homozyg MAOA) so I took 800mcg Metafolin, chewed it up and held it under my tongue and the mind calmed down in minutes.

    I know I am an undermethylator, although I have symptoms of overmethylation too, so thjs didn’t make sense to me. I worry that I take too many supps and am now in strange new territory.

    Also, do you trust Doctor’s Data for testing or is it best to stay with Direct Healthcare?

    Thank you.

    1. Hi Simon,
      I don’t recommend taking nutrients without testing first. The overstimulation could be from a variety of things, so it’s difficult to know without a thorough assessment. Keep in mind that under and over methylation symptoms can be misconstrued, especially if you have pyrrole disorder.

      1. Hi Bob,
        It’s not possible to eliminate dietary folate, but yes, I do maintain a low folate diet with occasional greens/romaine, etc. I do love a good caesar salad!

  28. I’m really confused … is there a simple comprehensive explanation to all this. I am overwhelmed even at this stage.

    1. Hi Julietta,
      I completely understand how you feel! This is very complex and at times confusing science. The best way I can break this down is that if you struggle with any kind of cognitive issue, it’s best to get properly tested before taking any form of folate (from food or supplements). Depending on your biotype, it may make you feel worse (if you are already low in serotonin) or better (if you have an abundance of it) because folate itself lowers serotonin. I trust this is helpful.

  29. I don’t understand how folate from spinach and other veggies could be bad for undermethylated individuals. Why would folate deplete methyl when I’ve read over and over again that it is critical not only in methylation, but also in the production of glutathione and neurotransmitters, for regulating DNA, for keeping toxic homocysteine levels down, for determining which genes get turned on/off, for preventing diseases and depression, etc.? If I were to cut folate-rich vegetables from my diet, I would think my mental and physical health would suffer, not improve.

    1. Hi Kara,
      I discussed this in my post and in the comments (see my reply to Cindy), and I am happy to reiterate:

      Folate is a serotonin reuptake promoter. You can treat a methylation imbalance with folate, but If your body doesn’t make enough methyl (undermethylation) and you struggle with depression/cognitive impairments, it will strip more methyl than it provides and make you feel worse. Antidepressants (SSRI’s) are reuptake inhibitors and undermethylated persons respond well to these medications.

      On the other hand, if you are an overmethylator, folate is a good nutrient for you.

      I have many clients that saw a major decline in cognitive performance after embarking on a high vegetarian, folate-rich diet. Functional testing revealed them to be undermethylated, and they saw great improvements after eliminating trigger foods and incorporating an appropriate nutrient therapy protocol. This was my experience as well and why folate-rich (vegan/vegetarian) diets don’t work for everyone.

      You can still enjoy vegetables, however, if you are undermethylated, it’s important to be mindful of those that are high in folates.

      1. I feel like you’re promoting SSRI’s for the undermethylaters but that doesn’t work long-term, it creates problems for instance with sleep, etc. What other solutions do you offer for your patients for undermethylation? I had to get off SSRI’s, they weren’t working. Lithium Orotate helps me, but there’s got to be other choices.

      2. No where in this post, nor any other, do I promote SSRI’s. And I’ve been very clear in other posts about the nasty side-effects of them and why advanced nutrient therapy (a non-drug approach) is the key.

    2. Folate has at least 6 different forms and methylfolate, which recycles methionine to make SAMe is only one part of the several very important jobs that folate does. After methylfolate recycles homocysteine into methionine it becomes tetrahydrofolate, which can be used in several reactions. One of these reactions takes place in the nucleus of the cell by an enzyme called LSD1, or lysine specific demethylase 1. This enzyme takes a methyl group off of certain parts of histones, which control how our DNA is expressed, and transfers it to tetrahydrofolate, which then becomes another form of folate.

      If in an individual person the ability of demethylate these histones is stronger than the person’s ability to methylate them, which depends upon many other factors, then they can have undermethylated histones in their DNA and this may cause symptoms.

      Why do I know so much about this? Because I have a son with schizophrenia and another with depression and they are both undermethylated (and have pyrrole disorder) and so I have done a lot of studying about this. My son with depression became depressed a couple of months after starting high dose folate. Any type of folate has the same effect on him and he is now on a folate limited diet.

      1. Hi Kim, you have done your studies, have you ever read articles on Carl C. Pfeiffer, Ph.D…, i learned of these articles years ago. Very interesting stuff. I think i have too much histamine and have felt very depressed and anxious.

      2. hi kim im not sure you will get this but I also have 2 sons exact same situation and would love to talk with you.

    3. I agree, Im really surprised by these findings but intrigued and need to know more. I live in Oz so can’t have a consult with you directly. I am working with a couple of practitioners who have trained with MTHFR.net

      This goes against everything I’ve read on the topic prior to now.
      Not that I don’t believe you I’m just incredulous that this seems to go against whats being discussed in sites like MTHFR.net

      I think I’m an undermethylator (although I don’t think Ive had tests to test methylations status- what tests are those?), have high histamine levels (2), folate was normal, am heterozygous for C667T, and am trying for a baby….

      How does one find out if they are an under or over methylator?

      1. Hi Angela,
        Genetic testing has no way of determining methylation status. We use a whole blood histamine and/or SAM/SAH ratio, but it needs to be performed with the right lab and specified protocol for accurate results. Keep in mind other testing is also essential in determining biotype status.

      2. Coming late to this thread. Do you have any contacts in the uk who practice similarly? What should I be searching for? Walsh-institute trained? Functional medicine doctor?

  30. Hi there,

    Just ran across your site and you sound like “just the women I need to talk to!” I have been trying to learn everything I can about this very subject. I had anxiety all my life and after being put on a SSRI and ambien when I was struggling with major stress in my life and peri menopause, I literately “lost it”. A horrible story with a wonderful ending though! It was my divine meltdown so to speak. Anyway much too long of story but I ended up having some genetic testing by a Functional Med doctor here in Walnut Creek, CA ( I live in the Bay area too! noticed you are in Marin 🙂 and he found I had a homogygeous 1298 MTHFR mutation plus a lot of others and from that finding he said I needed a methyl-folate. But then I “rediscovered” a formula that I had taken 15 years ago that helped me from an Integrative Psychiatrist here in Danville. Ive been off ALL those meds and only use this one supplement and it does have methyl folate and folic acid but I feel fabulous!! And 1000’s of people for over the last 2 decades have had the same results of being able to take this and get off all meds and feel wonderful. I would love your take on this? Do you have an office to go to or are you just available by phone or email?

    How do you determine who is a overmethylated or undermethylated person? I thought I read the the MTHFR 677 mutations tend to be more of the OCD and the 1298 the opposite? Why again does Dr. Walsh call methylfolate a “suicide nutrient”??

    Thanks!!!

    1. Hi Cindy,
      Thank you for sharing your story. I currently work with clients via phone and Skype, as well as on-line and in-person group programs.

      Please keep in mind that genetic tests have no way of determining how much methyl is present, so we use functional testing to determine methylation status.

      Dr. Walsh calls methylfolate a suicide nutrient because it “loses its identity very quickly” in the methylation cycle. If your body doesn’t make enough methyl (undermethylation) and you struggle with depression/cognitive impairments, it will strip more methyl than it provides and make you feel worse. Antidepressants (SSRI’s) are reuptake inhibitors and undermethylated persons respond well to these medications.

      1. I think that he calls it a suicide nutrient because it just gets used once as methylfolate and then it becomes tetrahydrofolate and enters the general folate pool.

        It wouldn’t make any sense to call methylfolate a suicide nutrient in particular when other forms of folate have the same effect on serotonin reuptake, and when it can be helpful for overmethylated people with depression.

      2. Hi Kim,
        Yes, that’s true, but giving an overmethylated individual more methyl is not recommended. This is why folic acid is best.

      3. I agree totally, Sami….. I’m a (borderline) overmethylator per your tests, and I had a horrible experience with methylfolate before I started working with you. It was severe for me, like I was being poisoned.

      4. Thank you for sharing your thoughts Lorraine! I’m so excited you are doing better. Keep up the great work! 🙂

      5. So this is an old thread, but what type of folate for an overmethylated person, then? And what is the right type of B12 for an over methylators?

        Struggling to find an answer to this!

        Thanks 🙂

      6. Overmethylators must stay away from anything methylated included methylB12. The right form of nutrients is determined after biochemical testing and evaluation.

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