Folate: Friend or Foe?

Yesterday I was perusing my fitness magazines and couldn’t help but notice all the dietitians touting the importance of including more folate, from both food and supplements, for everyone.

And this got me thinking about how we are one of the wealthiest nations in the world, yet experience higher rates of disease and injury, and die sooner than people in other high-income countries.

So how did we get this way?

Well, it all started during the Industrial Revolution when removing the bran from the germ of grains through milling and mass refining seemed like a good idea because it meant that grain products could sit on store shelves much longer without spoiling.

Then at the end of World War II, bakeries in America began using large amounts of chemicals, additives, bleaches, and preservatives (as much as 25 different chemicals are added to refined grain and bread products) to create even longer shelf life. Because this process strips all the vitamin and mineral content from the original source, these foods are “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, fortification became a mandatory practice in the 1990’s.

And the result of this practice?

Higher rates of cancer and a massive increase in things like autism, depression, bipolar disorder, autoimmune diseases and diabetes to name a few. You can read more about that here and here.

Or to put it another way, we began experiencing changes to our DNA in the form of genetic mutations or SNPs (pronounced snips) that create disease states. And you can thank the holy heavens most of these are epigenetic is nature, which means that with diet, lifestyle and nutrient therapy, we can correct these imbalances. By the way, we all have SNPs, they just manifest differently for each of us.

So what is folate?

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 ok in food form, but not so much in supplement form.

And herein lies the problem.

For those of us, that struggle with cognitive impairments, any form of folate, folic or folinic acid will function the same over time, regardless of whether it comes from food or supplements.

And when it comes to methyl folate, it’s not a better form, it’s simply a different form.

In other words, if you are undermethylated, you need to be very careful with folate because it is a serotonin reuptake promoter, (anti-depressants (SSRI’s) are reuptake inhibitors and undermethylated persons respond well to these medications) so it will make you feel worse. This explains why my years as a raw vegan on a high folate diet yielded devastating results for me.

Now I know what all that green juice was really doing to my body. And why one man’s food is another man’s poison.

Overmethylated individuals, however, thrive on folates because they have too much methyl and folate is a powerful demethylating agent.

Folic acid works in different ways in different parts of the cell. The part we need to be concerned about is the nucleus because it’s inside the cell that we see methyl loss, and folic acid strips more methyl than it provides. 1

Researchers involved in the treatment of cancer now realize that folic acid is directly related to an increase in cancer rates. Methotrexate, a drug used to treat cancer, acts by inhibiting the metabolism of folic acid. It’s a great cancer agent, but unfortunately, the patient’s got worse and many died because folic acid was added back in. This is a good indicator as to why undermethylated persons have a greater propensity to develop cancer and do worse on folates. 2

If you know of someone who could benefit from this post, please share it. It is through sharing that we create community, eliminate guilt and shame, and bring about healing.

Love,
SamiSig

 

 

 

[1] [2] Mensah, Albert. MTHFR and Mental Health: Understanding The Overall Effect of Individual Genetic Mutations (SNPs)

Comments 71

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  1. 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!!!

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      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.

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          Hi Kim,
          Yes, that’s true, but giving an overmethylated individual more methyl is a bad idea and can lead to suicidal ideation. This is why regular folic acid is best.

          1. 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.

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

          3. 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 🙂

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

  2. 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.

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      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.

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          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.

    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?

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        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.

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      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.

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          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!

  3. 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.

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      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.

  4. 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?

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      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

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      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. 🙂

  5. 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

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      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 that here.

  6. 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.

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      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.

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

  7. 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?

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

  8. 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?

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      Hi Bec,
      Yes, there is also a connection with high copper, low zinc, and protein deficiency, which I’ve gone into great detail here. 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 🙂

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

  9. 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!

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

  10. 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.

  11. 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?

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      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.

  12. 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!

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      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.

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      1. 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.

  13. 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.

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      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.

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

  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..

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  16. 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?

  17. 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??

  18. 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

  19. 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?

  20. 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 ?

  21. 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.

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