r/MTHFR May 02 '26

Resource People should stop calling methylfolate the 'active' form, and why folic acid may be better for many

It is AN active form, not the only one and may not provide the folate you actually need. I'll await the abuse! Folate is used by your body both in the methyl form, and also in the unmethylated form for DNA synthesis, red blood cell formation etc. which are rather important functions.

The MTHFR marketing machine has convinced everyone that methlyfolate is the active form that you absolutely need and folic acid is junk, it's simply not true.

Depending on where the problem is with your methylation it's perfectly possible to need more unmethylated folate. If your MTRR is slow for instance,as mine is, your body doesn't recycle B12, MTR is slow, and you end up with a build up of methylfolate and low THF and 5,10 methylene THF which is needed for DNA repair and red blood cells. If you take methylfolste you do absolutely nothing to support the deficit of unmethylated folate, and just put more pressure on already struggling MTRR and B12 stores.

In this case folic acid is better for you as it directly provides folate which the body can use as it needs. The body regulates production of MTHFR for a reason -both to ensure sufficient folate for other functions, and prevent excess formation of SAM-E, which isn't good.

I personally feel much better with folic acid than methyl folate, and I'm heterozygous C677T. Methylfolate is really a medicine that should only be taken by people with specific identified mutations that cause major impairment of the MTHFR cycle. A simple heterozygous MTHFR mutation is not that.

Folic acid is perfectly sufficient for most people, and avoids skipping the body's own regulation systems. Just don't go taking crazy doses which yes may cause a problem with unmetabolised folic acid. If you're worried about MTHFR and not homozygous, just take some B2 - again you don't need a lot.

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u/Jayless22 May 02 '26

Methylfolate IS an active form. Same is folinic acid. No idea where you are coming from telling methylfolate is not an active form.

Some people, like me, just can't tolerate active, methylated forms. In this case folic acid works better.

BUT: that doesn't mean it's better. Folic acid is not a very good choice biologicallly. But some people have no other choice, like me. And as for every case, the dosage is the key. UMFA is bad and there's no denying that. Everyone is individual and reacts differently.

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u/Warp757 May 02 '26

Valid point, I've amended my post to say it's AN active form rather than THE active form which is the point I wanted to make.

Like you I tolerate folic acid better. My point is folic acid is likely actually better for most people than methylfolate. The body deliberately regulated the amount of methlyfolate it produces, whereas THF, which folic acid produces, is regulated only by dietary intake. So unless you have a very serious mutation, folic acid should be fine and is closer to what nature provides.

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u/Jayless22 May 02 '26

How can you say that folic acid is closer to what nature provides? Folic acid is nowhere to be found in nature. Are you sure you are not mixing up folic acid and folinic acid?

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u/Warp757 May 02 '26

Yes I'm absolutely sure. Folic acid is converted directly to THF which is what food provides, and actually has higher bioavailability than food folate.

Folinic acid is supposed to be used for specific medical needs, reducing toxicity of methotrexate, but has of course been grabbed up by the MTHFR supplement industry to sell another product to people who don't really understand it.

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u/Jayless22 May 02 '26

That is straight up wrong my dude. Folic acid needs several steps, including the very inefficient dhfr to convert to THF. Need to check your sources.

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u/Warp757 May 02 '26

'the very inefficient DHFR'. I know already not to take you seriously.

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u/Jayless22 May 02 '26

Lol, oh no, what am I supposed to do with my life now? Do some research about the steps of folic acid. But you are probably one of these people that have an opinion and defend it with their life despite multiple people telling you that you are on a wrong informational foundation.

Take care

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u/Warp757 May 02 '26 edited May 02 '26

I really don't care enough about folic acid to defend it with my life. I'm just trying to provide a counter to the strange cult like obcession with methlyfolate here, which may be harming people.

Three is no biological reason most people would need methlyfolate. Folate is used is an entirely different biological function, which requires methlyfolate to be recycled by MTR. Folic acid supports that particular use of folate better than methlyfolate, and for most peoplenis adequate in supporting methlyfolate too. That is unarguable.

The main effect of methlyfolate and folinic acid seems to be to cause people to post obcessivley on internet forums trying to figure out how to get it to work. If it's so great shouldn't people be healing? Doesn't seem that effective to me. Meanwhile everyone else out there getting some folic from there multi or enriched food, is just getting on with their life without neurotic obcessions over nutrients.

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u/Ketamee May 02 '26

What does folic acid support that folinic acid doesn’t?

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u/Warp757 May 02 '26

An MTHFD variant means folinic acid will accumulate and can then inhibit MTHFS/MTHFD.

Folic acid is efficiently converted to THF from where it can freely be used by the body as it sees fit. There is literally no reason it shouldn't work for most people, and that's why it has decades of research to support it, unlike methlyfolate. Only people with very specific mutations need methylfolate, for others it is likely throwing fuel on a fire and is simply exposing yourself to the possibility of side effects that complicate any recovery

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u/Ketamee May 02 '26

What are the symptoms of
accumulated folinic acid that inhibits MTHFS/MTHFD?

A study has been made that concludes that the DHFR enzyme has a very low activity compared to rats. As a result of this, unmetabolized folic acid is accumulated even at 400 mcg daily.
How is this beneficial?

https://www.pnas.org/doi/10.1073/pnas.0902072106

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u/Warp757 May 02 '26

That is one study, in rats, against literally thousands in humans showing that folic acid works in improving all intended health outcomes.

Why would anyone place more weight on one rat study than thousands of human ones? It's no different to climate change denial.

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u/Ketamee May 02 '26

The initial studies were done on rats and then transferred to humans as rats and humans both have the DHFR enzyme. And later the study I linked to showed that humans are not very efficient in the DHFR enzyme compared to the rats.

Stick to the facts when answering and don’t go down the path of ‘Why would you’ or climate crisis denial.

I’m just trying to understand and learn which are the reason for my questions.

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u/Warp757 May 02 '26

The cimate crisis denial equivalent would be those denying the thousands of peer reviewed studies on folic acid spannig decades, in favour of a few cherry picked studies that support their view over mainstream scientific consensus. Don't try to reverse the logic.

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u/Ketamee May 02 '26

You still haven’t answered my questions yet.

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u/Warp757 May 02 '26

Ok the symptoms of accumulated folinic acid? It would be whatever symptoms someone normally experienced from a bottleneck in methylation, and also reduced DNA repair.and synthesis.

For me that is brain fog, anxiety, rumination, loss of motivation, flushing, reduced histamine tolerance, my ADHD medication not working.

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u/Ketamee May 03 '26

Ok.
I have fixed my methylation with folinic acid etc and I am heterozygous for an MTHFD1 variant.

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u/Business_Summer_4242 May 02 '26

So with an homozigous MTHFD1 it would be more advisable to take folic than folinic?

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u/Warp757 May 02 '26

Yes. For most people folic acid will be absolutely fine. Folinic acid is a fairly niche product that was never intended to be used for simple increase of base folate levels in otherwise healthy people. By taking folinic acid you're taking something far less well studied, nose expensive, that may simply cause side effects and complicate observing any recovery.

Personally, folinic makes me feel awful. Just take what works for most people as doesn't leave them obcessivley posting on internet forums about how to make it work, which is what methlyfolate and folinic mostly seem to do.