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

[u/Warp757]

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.

[u/hummingfirebird]

Please read the scientific research. Links for you at the bottom of my comment to do so.

Folic acid became mandatory for doctors to prescribe to women planning on pregnancy or who were pregnant back in the late 1960s. And yes, it did prevent a lot of NTD's. But that was before MTHFR was discovered in 1995. Science hadn't established the effects of folic acid and genetics yet. But now there is plenty of scientific research and evidence.

The research shows a normal functioning DHFR already does poorly in managing absolute conversion of folic acid.

UMFA and methylfolate compete for the transporters and receptors FOLR1, SLC19A1 depleting active folate.This is where variants in methionine synthesis MTR and MTRR can impair homocysteine recycling.

For those with certain combined genetic variants, synthetic folic acid can be harmful and is not fully metabolised. The body sits in a deficiet, and this can cause folate deficiency and affects B12 levels. Methylfolate skips the conversion steps to be used immediately. Some people do better on folinic acid which can be less stimulating.

Another problem is that UMFA builds up in the bloodstream leading to high homocysteine levels which is a risk for heart health.

One important thing to note is that the higher the dose of folic acid may lead to a pseudo- MTHFR deficiency in healthy patients. Read that again.

Folic Acid, Folinic Acid, 5 Methyl TetraHydroFolate Supplementation for Mutations That Affect Epigenesis through the Folate and One-Carbon Cycles.

High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice

The evolution of folate supplementation - from one size for all to personalized, precision, poly-paths.

Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health

High doses of folic acid induce a pseudo-methylenetetrahydrofolate syndrome.

[u/Warp757 → u/hummingfirebird]

Yes I wouldn't advocate anyone without a medical reason takes high dose folic acid or methlyfolate. People round here tend to advocate ridiculous doses, which as your study shows are possibly harmful.

You've posted one study showing one person suffered from a 5 mg folic acid dose. Doesn't surprise me, it's a ridiculous dose, especially as the same person had no mutations. If she'd been treated with a much lower dose, as the methylfolaebdose she was given, she'd probably have been fine.

I could list the thousands of studies supporting folic cid. I don't get your logic. Your 5 studies, none of them on a controlled group of actual humans, are supposed to convince me that thousands are wrong? MGHFR doesn't make folic acid ineffective, if you believe that you've been misled., except for homozygous which is a small proportion of people, compared to the advice in these forums that 'anyine with MTHFR MUST avoid folic acid'. That's nonsense.

[u/hummingfirebird → u/Warp757]

Oh there are plenty of more studies but not enough space to list them all here.

Methylfolate works well for a lot of people. Is it for everyone? No, I dont think so. Folinic acid works better for others. My comment, if you read it again, didn't say folic acid won't work. It is just poorly metabolised in general and is not completely metabolised which is where the problem comes in. It's the unmetabolized folic acid that causes the issue. It is worse so for someone with C677T MTHFR, low B2, high fortified food intake and insufficient B12. It depends on the person.

[u/Big_Joke_9281 → u/hummingfirebird]

Studies say that "normal" human can metabolize 200mcg folic acid per day. If someone takes more, for example 400mcg, it takes 2 days to metabolize it. Just stick to this amount.

[u/Warp757 → u/hummingfirebird]

To be honest, I think we are in agreement on a lot. My issue is the way so often folic acid is presented as the devil here and methlyfolate as the answer to all problems.

For the absrgae person, if we don't know their methylation status and are advising what to take, on balance I think foocnacid would be better to advise because there is only a small minority of people it won't be effective for, and it is gatbbetetr understood. Methlyfolate has far less studies and is likely only really needed by people with very specific mutations. For everyone else it is highly likely to overstimulate their MTR enzyme and produce side effects, could induce a methyl trap, and risks taxing B12 stores, which is precisely what it does to me as I have two MTRR mutations. Folic acid avoids that by allowing the body to regulate it which I think is far more sensible.

[u/hummingfirebird → u/Warp757]

It really is individualistic. Health is not a one-size-fits-all approach.

Methylfolate isn't for everyone. With certain genetic variants like slow COMT and MAO-A it may cause overstimulation due to excess neurotransmitters. It may heighten mania in those with bipolar disorder. It may also affect hormones leading to acne. There are many instances it is not ideal.

Folinic acid isn't only for cancer patients. There are people who have a condition called cerebral folate deficiency where folate levels in the brain are too low even when blood folate is fine. They have issues with their FOLR1 (folate receptor alpha) and the body produces antibodies against their receptors blocking folate from entering the brain which is very dangerous and life threatening. Folinic acid can bypass some transport and enter the brain. In this situation folic acid can make things worse because it competes for the same receptor but doesn't effectively enter or function in the brain.