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I Can’t Take Folate – Now What?

We all know that MTHFR mutations are differences in the way your body processes folate, so obviously the answer is to take more or better folate supplements like 5-LMTHF or folinic acid just like every doctor out there talks about. It’s so exciting to have a solution to the health issues that you’ve been struggling with! The problem is, there is a significant chunk of MTHFR folks out there who just don’t tolerate folate and never will. Truly, never. If you’re not sure why not being able to tolerate folate would matter in MTHFR, then read the Start Here Guide to MTHFR.

Who Can’t Take Folate?

Typically these people are in the group of MTHFR folks who tend toward undermethylation. Undermethylators make up about 45% of the population and while some of them do tolerate folate in low doses in foods or even a very tiny dose in a supplement, many of them don’t tolerate any folate at all, not even in food. There are exceptions, of course including low-serotonin overmethylators.

Now How Do I Deal With MTHFR Issues?

You’ll recall that the whole methylation cycle is mostly accomplishing two goals. One is converting homocysteine to methionine (to avoid homocysteine buildup), and the other is making SAMe (a methyl-donor).

the MTHFR lifestyle matters because of the way these cycles all interconnect.
the MTHFR lifestyle matters because of the way these cycles all interconnect.

Bypass the Cycle

So, if you can’t convert homocysteine to methionine, and you can’t make SAMe, you can still get the cycle and all related processes going by taking methionine and SAMe. It’s a bit of a cheat, but it helps to solve that one very basic problem and for most people, boosts their mood tremendously.

But Why Is This Happening In The First Place?

For most undermethylators who don’t tolerate folate, it’s happening because their serotonin is just so low. This can happen to overmethylators too, but it’s far less common. The key issue is typically LOW SEROTONIN and folate of any kind makes the depressive symptoms of low serotonin worse.

The basic trouble is that folate, 5-LMTHF, and folinic acid (also folic acid, but I know you don’t allow any of that into your body because of this) have an epigenetic effect on the SERT transporter.

The SERT Transporter

The SERT transporter helps to re-uptake serotonin after it has been released, This is the target for the popular antidepressants called SSRIs – that stands for Selective Serotonin Reuptake Inhibitor (it’s essentially a SERT inhibitor).

Taking an SSRI or inhibiting SERT doesn’t change the amount of serotonin you have, but it changes how long it stays out there as a signal. The longer it’s out there, the more effect it has and the happier you feel.

folate vs. SSRI for people who can't take folate
Folate boosts serotonin production, but also speeds up reuptake so may actually net decrease the amount of benefit (happiness) you get from that serotonin.

Folate in all of it’s forms actually boosts SERT function so even though folate helps your body manufacture more serotonin through the BH4 pathway, it boosts re-uptake more, so the net effect feels like lower serotonin.

Boosting Serotonin Naturally (Or Less Naturally)

The great news is that often the people who don’t respond well to folate, do typically respond really well to supplements and often drugs that boost serotonin. These include:

  • St. John’s Wort
  • SAMe (so if depression is your primary concern, focus on finding the optimal dose of SAMe before you add other serotonin boosters).
  • Melatonin (which boosts serotonin indirectly by both helping sleep and also reducing serotonin conversion to melatonin.)
  • Tryptophan
  • SSRI Medications (although you may still experience side-effects).

Where Do I Start?

Here's what to do if you can't take folate
Here’s what to do if you can’t take folate
  1. Folic Acid – Like everyone else with MTHFR issues, start at the beginning, which is getting the toxic folic acid out of your diet. If you don’t tolerate high-folate foods or folate supplements, then foods fortified with folic acid are extra harmful to you.
  2. HIgh natural-folate foods – you might find you can tolerate some high-folate foods once the folic acid is gone. If not, that’s fine too, but it’s worth it to try. This gets you out of stage 1 of MTHFR balancing, which is the general stuff that is typically good for all mutants. If you want more detail, check here.
  3. Other B vitamins – a B supplement or multivitamin that doesn’t include folate or B12. The only ones I know of are from Seeking Health and can be purchased from Fullscript using the sidebar link. This is an affiliate link so I will get a small commission on the referral and I will offer you a 10% discount.
  4. Methionine – 500 mg at bedtime can make a world of difference on its own.
  5. SAMe – this can help with depression and energy levels so it’s a good next choice. (Methionine and SAMe can also be purchased from the link on the side, but they are also pretty easy to find in local health food stores.) As with everything else with MTHFR, start at a lower dose, and increase slowly. A good starting dose is 200 mg twice daily.
  6. Move to Stage 3 of MTHFR balancing – this is all working with your own individual symptom picture, so it very much depends on what you are working with right now.

What If Low Serotonin Doesn’t Sound Like Me?

Sometimes, even without low serotonin some MTHFR folks just don’t do well with high-folate foods or supplements like 5-LMTHF. In this scenario, it is still a good idea to try the steps above and if low serotonin (which usually feels like depression) isn’t the issue then you might be able to try a tiny dose of folinic acid, which for some reason is better tolerated in this situation. It still might not be right, but it is worth a try to see if we can get that cycle moving just a little bit. Otherwise, follow the Start Here for MTHFR guide.

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MTHFR is a common genetic mutation that can contribute to anxiety, depression, fatigue, chronic pain, infertility, and more serious conditions like breast implant illness, heart attack, stroke, chronic fatigue syndrome, and some types of cancer. If you know or suspect you have an MTHFR variant, schedule a free 15-minute meet-and-greet appointment with MTHFR expert Dr. Amy today.

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Amy Neuzil
Amy Neuzil

Dr. Amy Neuzil, N.D. is a leading expert in MTHFR and epigenetics, and she is passionate about helping people achieve optimal health and wellness for their genetic picture. She has helped thousands of people overcome health challenges using a simple, step-by-step approach that starts with where they are today. Dr. Neuzil's unique approach to wellness has helped countless people improve their energy levels, lose weight, and feel better mentally and emotionally. If you're looking for a way to feel your best, Dr. Amy Neuzil can help. Contact her today to learn more about how she can help you achieve optimal health and wellness.

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    • Hi Sam,
      Not at all – some of us with MTHFR really need B12, it just depends on what type of B12 we’re talking about. Methylcobalamin can be a bit too quickly metabolized for some people and make them feel speedy, so it’s about choosing the right B12 for you. For a lot of MTHFR folks, a tydroxycobalamin can be a better choice. We’ll be doing a whole post on it – hopefully this quarter so keep an eye out!

  1. So where do undermethylated MTHFR folks who cannot tolerate folate (foods or supplements get their folate from?

    • Hi Lori,
      It’s a great question and honestly, I have a small handful of clients who really can’t do the foods or supplements of any kind (although it’s a small handful – most people tolerate food sources at least in small amounts). Even if you can’t get any folate from food or supplements, your gut bacteria do make a small amount, which is wonderful. Between that and some other methylation driver (SAMe or choline are the most likely ones if you don’t tolerate any folate), then we can usually get your methylation balanced.

  2. Amy you are a superhero! Blessings to you.
    now I have my gene profile [ MTHFR AC & CT pairing – loved your emoticon explanation ] everything I am reading on your site makes the most sense to me re longterm gut-systemic issues.
    I know I do well on B complex capsules but lost this habit again months ago due to a brand supply issue.
    As I am now in the super-reactive-sensitive category my first step will be to again test the known brand.
    Otherwise I don’t currently fit the worst case symptom pictures – more like a roller coaster of swinging from feeling very good body-mind-energy to weak and in pain-discomfort -so I know I have good potential to recover.

    Thankyou again for this collection of resources

    • Hi Eme,
      I am so glad you’re here and enjoying the posts – that is great news. And yes, you’re absolutely right. Even with known brands it helps to really listen to your body and test things out because we can have reactions with all kinds of things. IT does make it easier if you know you do well on Bs though – that’s great news. And I feel you – the roller coaster is real. You have amazing potential to recover and you’re taking great steps in that direction. Let me know if you have any questions!

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