Methylfolate Side Effects


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.

UPDATE December 7, 2014:

Please read this article on how to prevent methylfolate side effects in 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 are two three four things you can do to quickly quench most of the methylfolate side effects:

  1. Consider 50 to 100 mg of niacin as 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: You may experience flushing for 20 to 30 minutes. This is not harmful. It simply makes you feel ‘warm’ everywhere.
  2. Consider liposomal 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. Consider Hydroxocobalamin as 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 I cannot 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 acid is an active form of folate that is not methylated.
Hydroxocobalamin is a recognized natural form of vitamin B12 that is not methylated.
You can get them separately or in a combination 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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  • Jennifer says:

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

  • Silvana says:

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

  • Gala Copping says:

    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!

  • Ashley Nicole Larson says:

    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 homozygoeus A1298C – now I am concerned that I am doing more damage??! Is Folonic Acid okay or should I avoid this form?

  • Marcia says:

    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!

    • Paula Fox says:

      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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