Methylfolate Side Effects - Dr Lynch (2024)



Methylfolate is a remarkable nutrient yet it can create significant side effects.

Those who have MTHFR mutations (especially the C677T MTHFR mutation) learn that methylfolate is critical to take. The issue is methylfolate can cause more harm than good if not started at the right time or tapered up slowly in amount.

UPDATEDecember 7, 2014:

Pleaseread this article on how to prevent methylfolate side effectsin addition to this one. I’ve since learned how to reduce the incidence of side effects even more.

There appear to be three types of responses to methylfolate:
FIRST: A person who can jump on methylfolate and feel absolutely wonderful. The only down side they experience is why didn’t they know about methylfolate before?!
SECOND: A person starts methylfolate has an amazingly incredible week where they are happy, interacting and alert. Then the second week comes and they switch to wanting to hide in a room by themselves or literally throw dishes across the room out of anger. Or they may become bed ridden from muscle aches, intense headaches or joint pain.
THIRD: A person takes a small amount of methylfolate and feels all the methylfolate side effects right out the gate.

Methylfolate Side Effects:

  • irritability
  • insomnia
  • sore muscles
  • achy joints
  • acne
  • rash
  • severe anxiety
  • palpitations
  • nausea
  • headaches
  • migraines

Why does methylfolate create such an amazing week and then create such severe side effects so soon after?
It has to do with methylation, pre-existing inflammation and other genetic mutations which exist yet you’ve no idea they do.
This gets complicated quickly so I am going to keep it simple.
If you experience any of the above methylfolate side effects, I highly recommend you discuss it with your physician and get your dose of methylfolate reduced significantly or stopped for a week or two before reintroducing it.

UPDATE November 25, 2014

There aretwothreefour things you can do toquicklyquench most of the methylfolate side effects:

  1. Consider50 to 100 mg of niacinas nicotinic acid. Why? Niacin is broken down by SAMe. This means that excessive SAM is quenched by taking niacin.Niacin also helps transform folates – especially unreduced folates. There are many other things niacin does as well – beyond my understanding. I continue to look for them and will update this as I learn more.
    • NOTE: Youmayexperience flushing for 20 to 30 minutes. This is not harmful. It simply makes you feel ‘warm’ everywhere.
  2. Considerliposomal curcumin to help quench inflammation. If one takes methylfolate before inflammation is controlled, the methylfolate will worsen it. One may consider taking 2 capsules of Optimal Turmeric three times a day during times of inflammation.
  3. ConsiderHydroxocobalaminas it is an excellent sponge for reducing nitric oxide levels. Methylfolate increases nitric oxide levels – which is why it is so effective in reducing headaches, pain, cardiovascular disease risk, thrombosis, preeclampsia, periodontal disease, etc – but at the same time, excessive nitric oxide levels are harmful as they end up producing serious radical damage via peroxynitrite. Hydroxocobalamin quenches nitric oxide quite effectively. Hydroxocobalamin also works to reduce hydrogen sulfide levels (great for those with high sulfate-reducing bacteria or sulfur-smelling stools/diarrhea).
  4. Limit intake of leafy greens until side effects go away. This is because leafy green also contain methylfolate and nitrates.
  5. Electrolytes – as methylfolate increases, so does cell division and when that happens, electrolyte deficiency can occur.
  6. Glutathione – as cells divide with more methylfolate, glutathione levels get further depleted. Restoring levels can help significantly. Do it SLOWLY, though.

“If Icannot tolerate methylfolate or methylcobalamin, what forms of each could I tolerate?”

I get this question a ton.

If this is the case, perhaps you need to just stop taking any form of folate and B12 for a while. You’ll need to evaluate with your healthcare professional.
The other option is to take other active forms of folate and vitamin B12 which are not methylated.
Since you are not tolerating methylfolate or methylcobalamin, then perhaps you’d do well without the methylated forms.
This is possible.

Folinic acidis an active form of folate that is not methylated.
Hydroxocobalaminis a recognized natural form of vitamin B12 that is not methylated.
You can get them separately or in acombination Hydroxocobalamin and Folinic acid lozenge.
The lozenge allows you to cut it into smaller pieces, easier to use as you don’t have to swallow a pill and more importantly, it allows you to dissolve the nutrients slowly which has the benefit of getting into your system better.
Another benefit? It allows you to remove the lozenge from your mouth if you’re not getting desirable effects – ie side effects. If you swallow a pill – that’s it. You cannot take it out. A lozenge you can.
As with any nutritional supplement, you need to talk with your healthcare professional. Some are more educated in nutritional biochemistry than others.

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  • Methylfolate Side Effects - Dr Lynch (1)Jennifer says:

    July 22, 2022 at 11:55 am

    Hi Dr.Lynch, I’m curious if you have a more recent update for this article, thanks.


  • Methylfolate Side Effects - Dr Lynch (2)Silvana says:

    April 22, 2022 at 4:47 pm

    Great information thanks! I started methyl folate and I am feeling exactly that you write


  • Methylfolate Side Effects - Dr Lynch (3)Gala Copping says:

    October 23, 2021 at 11:00 am

    Please Dr Lynch, what happens if you can’t tolerate the methyl forms yet are compound heterozygous for MTFHR? Is it ok to take folic acid?
    Thank you!


    • Methylfolate Side Effects - Dr Lynch (4)Benjamin Lynch says:

      September 20, 2022 at 11:20 am

      Hi Gala –

      Use Folinic Acid instead. You’re not alone. Many people cannot tolerate much methylfolate. This is why I formulate many things with just folinic acid and don’t use methylfolate. We have ‘methyl-free supplements’ here.


  • Methylfolate Side Effects - Dr Lynch (5)Ashley Nicole Larson says:

    August 16, 2021 at 4:20 pm

    I am currently take Mary Ruths B complex drops and it list Vitamin B9 (Folate as Folonic Acid) 400 mcg DFE.
    Is this the same as Folic Acid?? I have been taking this regularly and I am a hom*ozygoeus A1298C – now I am concerned that I am doing more damage??! Is Folonic Acid okay or should I avoid this form?


    • Methylfolate Side Effects - Dr Lynch (6)Benjamin Lynch says:

      September 20, 2022 at 11:23 am

      Folinic acid is good. Folic acid is bad. 🙂


  • Methylfolate Side Effects - Dr Lynch (7)Marcia says:

    October 26, 2020 at 4:35 pm

    It just gets more and more complicated.
    My doc charges $600/ hour and insurance doesn’t cover her.
    After at least ten years if hurried cryptic advice, I feel no bettet and actually worse.
    Big Picture Please!


    • Methylfolate Side Effects - Dr Lynch (8)Paula Fox says:

      June 20, 2022 at 10:10 am

      I feel the same way. I got my DNA tested, got the results with a functional medicine doctor, and I’ve learned more from research on my own than I ever learned from her. Right now I am battling high iron, I consulted her, she said she’d get back to me and that was two months ago. So I’m on a quest to figure out why all of a sudden I am absorbing more iron than ever. Frustrating.


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