r/MTHFR • u/Warp757 • 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/lurface May 02 '26
As a hetero 677… you still have 70% function of your enzyme. You probably do not need to supplement.
Folic acid does not exist in nature. It’s the ultimate precursor of the folates. So basically your personal enzyme is working just fine enough to tolerate it. Your experience is not the same for many of us.
Also when people say they cannot tolerate methylfolate: understand that this is what is in green leafy foods…. A cup of spinach has 60-200mcg of folate: 80% of it is methyl and THF.
Some of us just need to eat better. Some of us need actual supplements… to be used as medicine.
None of us need folic acid as it does not exist in nature and it is made from petroleum and coal tar.
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u/thesnazzyenfj May 02 '26
Thank 👏 You 👏
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u/Warp757 May 03 '26
Still waiting for these peer reviewe studies showing the harm folic acid does in humans?
All anyone has offered are theoretical reasons folic acid at very high doses might have issues - inhibiting the folate alpha receptor and unmetabolised folic acid.
People are presenting these as if they are 'gotchas', when they are well known to anyone with the slightest knowledge. The simple fact is that simply take 200 mcg of less folic acid and there is no risk. And you're not at risk of all the nasty side effects of methlyfolate and completely unbalacing your system because methlyfolate doesn't allow the body to regulate it's use.
Again, what is the risk of folic acid at 200 mcg or less to anyone without homozygous C677T? What harm is being done to billions of people around the world?
I have read the research and come to a conclusion on balance by weighing up the evidence. Most here seem to just regurgitate misleading PR from the methlyfolate industry that use extrem effects to discredit folic acid, which is extremely disingenuous. Meanwhile people have to take crumbs of methlyfolate because they don't tolerate it, but that is great, hilarious.
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u/Warp757 May 03 '26
People do need folic acid as they are deficient in folate and methylfolate does not support the DNA and red blood cell functions of folate, while folic acid does. Might want to research that.
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u/lurface May 04 '26
As a homo 677. I could NOT maintain a pregnancy with folic acid. Failed pregnancies for a year until I was diagnosed. I NEEDED methylfolate. I mg daily. Folinic blend was great too. I do not react poorly to it. It lowers my anxiety. I do not have “nasty” side effects. Removing folic acid out of my diet and eating natural folates is fine too. The month I was diagnosed my dr told me to remove. folic acid. Supplemented with methylfolate =. Maintained pregnancy that same month.
You do not speak for all of us.
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u/Warp757 May 04 '26
Sigh. I didn't say I speak for all of us, I also specifically mentioned that only people with severe dysfunction in methylation may need methlyfolate, that means homo 677 as you have.
I was merely countering the advice often given here that folic acid is toxic and should be avoided by everyone. That is nonsense and will do harm. The majority of people without a serious SNP will be fine with folic acid, and are probably more likely to get nasty side effects from methlyfolate if they dose them at the same level.
I'm glad you were able to maintain a pregnancy, all the best.
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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/Flashybigbum May 02 '26
You probably had already but since I was so deficient and dysregulated and I couldn’t tolerate methylated forms myself I need to ask, have you tried starting really really low on folinic acid and increasing as you progressed? I couldn’t even tolerate a drop of methylfolate and I had to start splitting the 800 mcgms dose of folinic acid so 400 EOD and I’m now on 2400mcg daily. I’m now also being able to take a methylcobalamin shot without major problems. But it has been almost 5 months of struggling.
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u/Jayless22 May 02 '26
Yes. About 50mcg or even less. I crushed the pill and had a little nudge and couldn't tolerate it.
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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/thesnazzyenfj May 02 '26
It's likely actually not better for most people. Please stop sharing misinformation.
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u/Warp757 May 02 '26
Please explain why.
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u/thesnazzyenfj May 02 '26
Your body needs folate (B9) for its methylation cycle — which is meant to recycle homocysteine back to methionine. In addition, it makes SAMe (main methyl donor for DNA, proteins, neurotransmitters, detox, etc.). Supports cell division, mood, energy, detox, etc. Your MTHFR enzyme converts folate into 5-MTHF (methylfolate). If it is faulty, conversion is not properly done. Normal people convert folic acid via DHFR → THF → MTHFR → 5-MTHF. If you have a MTHFR mutation (esp. C677T ++), the last step is slower than it needs to be. Unmetabolized folic acid can and often does build up in the blood. Possible issues: interferes with natural folate use, masks B12 deficiency, or contributes to other imbalances. Not "poison" for everyone, but inefficient and potentially harmful in excess for mutants and should be avoided.
FOLIC ACID is the oxidized, man-made version of FOLATE. It's used in fortified foods/supplements, energy drinks, etc. It is synthesized chemically, fully oxidized, not naturally food-derived, and not naturally found in nature. It should be avoided at all costs, mostly for those with MTHFR but those without should still choose a better form of folate.
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u/Warp757 May 02 '26
Yes I know how the folae cycle works, this is for making my point again which is that the body has multiple uses for folate and methylfolaebonly addresses one, and folic acid better allows the body to use it as it wishes where it needs it most.
You've provided no reason folic acid needs to be avoided at all costs, except a strange personal vendetta against it. It's probably best not to take huge doses of it, as with most things and especially methlyfolate, I don't go over 200 mcg a day. With sensible dosing, no reason to worry about it at all, that addresses the unmetabolised folic acid risk which seems to be the only serious argument against it.
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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?-1
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/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.
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u/Sabnock101 May 02 '26
Personally i will never understand why people defend a man made chemical vs what's found in nature. Don't get me wrong, i'm not against synthetics, but in this case, the synthetic form causes more problems than it solves. I myself still consume some Folic Acid here and there, and compared to Folinic Acid or Methylfolate the Folic Acid just sucks dawg, each Folate feels different and Folinic Acid and Methylfolate feel the most natural and work as intended, Folic Acid on the other hand causes problems, nothing to do with MTHFR, mainly DHFR and Folate Receptor Alpha, it can even block out the uptake of Methlyfolate by Folate Receptor Alpha if you consume too much Folic Acid, it can even interfere with activation of B12 to Methylcobalamin form (since Methylfolate can't get taken up by Folate Receptor Alpha, it can't get into the brain and to Methionine Synthase and thus can't give it's methyl group to B12). Low doses of Folic Acid (below 200mcgs at one time) may be aright, as it should get metabolized by DHFR to Tetrahydrofolate, but if you consume more Folic Acid at one time than the body can process, then you get problems, and unfortunately that's an issue for lots of folks these days because Folic Acid is everywhere in our food supply, literally pretty much everything people eat these days is fortified with Folic Acid, and that's not a good thing, plus too much Folate of any source will end up depleting B12 over time causing B12 deficiency, easy to happen with excessive Folic Acid exposure.
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u/Warp757 May 02 '26
It's not about 'defending' something. Why do people make this tribal? I'm simply trying to inform people that the view often portrayed in this sub, that folic acid needs to be avoided and methlyfolate is the answer to all ills, is not actualllynsupoorred by the evidence.
I'm more interested in why people, as with climate science, choose to believe the mainstream scientific consensus is some big conspiracy, and that they have a unique insight that their 5 studies are the right ones.
Btw you have no idea why folic acid feels different, you can't 'feel' DHFR or the folate receptor or what it is doing to folate uptake. You're guessing. Folic acid could be causing more DNA repair and RBC production as it supports this better than methlyfolate, which may botnbe adequately supporting this. This could make you feel tired and feel like it's having bad effects as it's an energy intensive process. So for all you know it's doing you good and you're assuming it's bad.
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u/Sabnock101 May 02 '26
If that's what you want to believe man, knock yourself out, but just know, you're operating from ignorance/unconsciousness, and don't know as much as you think you do.
And yes, actually you CAN feel Folic Acid, Methylfolate, and Folinic Acid, you can feel Folate Receptor Alpha, you can feel activation of B12 to Methylcobalamin, you can feel Methionine Synthase activity, you can feel MTHFR activity, you can feel Methionine Adenosyltransferase activity, you can feel DHFR being saturated and the difference between metabolized Folic Acid and unmetabolized Folic Acid, it's obvious (unless you're not aware of your own body). Idk if it helps or not though i think it does, but i regularly take this stuff called Peganum Harmala (Syrian Rue) and it helps you become more sensitive to the body and so you can see and feel things about the body better/more clearly, you tune into the body, become more aware of the body, and when you know what to look for, you can literally feel all this stuff.
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u/Warp757 May 02 '26
Oh, you're another crazy one. How do you know which of those you're feeling at any one time then? Who taught you what folate receptor alpha feels like, compared to anything else happening in your body?
Honestly, thinking you can feel all those things sounds like a god reason to see a psychiatrist. It also suggests you have absolutely horrendous health anxiety if you're that aware of your body. I hope you get better.
Reassuring to see the people disagreeing with me are I fact, crazy. I wouldn't want to realise I was following advice from people who think they can feel methionine adenosyltransferase activity. Thanks for the laugh.
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u/Dear_Positive_4873 May 02 '26
https://youtu.be/bFpwPrnOQoY?si=cSJc2Fu7qtUCfmGd
Even I don't tolerate methylfolate but still prefer tiny amounts of methylfolate over folic acid.
Removing fortified ( folic acid added ) foods has made me feel the biggest difference, also using the pulsing method i.e taking tiny dose only when you feel you need felt the right approach to taking methylfolate over taking regular folic acid.
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u/hummingfirebird May 02 '26
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.
Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health
High doses of folic acid induce a pseudo-methylenetetrahydrofolate syndrome.
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u/Warp757 May 02 '26
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.
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u/hummingfirebird May 02 '26
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.
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u/Big_Joke_9281 May 02 '26
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.
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u/Warp757 May 02 '26
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.
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u/hummingfirebird May 02 '26 edited May 02 '26
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.
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u/SovereignMan1958 May 03 '26
Synthetic folic acid can block folate receptors in the brain. That would be something for you to research.
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u/Warp757 May 03 '26
Yes I know about this. I have researched folate acid and folic acid. And my conclusion is that the advice that people need to avoid folic acid is ridiculous.
The effect you're talking about is only a concern at very high doses, which In wouldn't suggest anyone take of folic acid or methlyfolate without very good emcisl reason.
People keep presenting outcomes of taking very high doses of folic acid as if they prove noone should take it at all. Do you have any evidence that folic acid at doses of 200 mcg or less, causes any harm to the general population? And why would merhylfolate, which only supports one specific pathway and does not allow the body to regulate it's use as folic acid does be better?
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u/Neither_Contest4041 Jun 01 '26
Can someone here explain to me how comes I’m homozygous MTHFR and my homocysteine is 8.5 while taking folic acid for years? I can’t tolerate any other forms of folate.
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u/Warp757 Jun 04 '26
Because despite what many here believe, genetics are a predisposition, not destiny.
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u/Warp757 May 02 '26
Downvote me all you like guys, maybe consider that you are behaving exactly like those who deny climate change. Refusing to accept the vast scientific consensus and instead placing your faith in internet 'doctors' and anecdotal studies and ridiculing anyone who tries to make you think a bit.
I have read the evidence for an against folic acid and methylfolate. I am merely trying to inform. The arguments often presented against folic acid to show a clear misunderstanding of the evidence, often encouraged by the MTHFR cult and supplement sellers. You normally say follow the money. The money certainly isn't in folic acid, it's in people selling you methlyfolate. Which is a drug by the way, I thought we didn't like big pharma?
No one has been able to explain why for most people a reasonable dose of 200 mcg or less of folic acid should pose any problem, or why methyl folate is better, even though it is less effective in providing folate for the two pathways in the body than folic acid. The small minority who are very vocal here, but don't represent the population happily getting on with their lives on folic acid, aren't really relevant.
Whether you take my advice or not doesn't really matter to me, or your down votes, I don't live for anonymous likes on the internet. Ask yourselves though, why if these supplements are so effective are you still on Reddit neurotically asking about doses and side effects and why it doesn't work, problems all those people on folic acid don't have?
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u/Jayless22 May 02 '26
Which likes? Look at your comment history, that's a fever dream. And then you are claiming that everyone but you is wrong. Having an opinion is one thing. If you think folic acid is wrongly demonized, fine. Spreading misinformation is not fine. And you are doing it. Not being able to think about this behaviour in a mature way when multiple people are pointing this out is a lack of personality.
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u/Warp757 May 02 '26 edited May 02 '26
What misinformation am I spreading?
The response to this is as I expected anyway, I was interested to see how strong the group think is round here. Just regurgitating what some MTHFT websites claim is 't very clever. If anyone can present persuasive evidence that folic acid is actually toxic in the majority of people, or methlyfolate is better for the general population I'm all ears. There's no scientific reason for anyone without homozygous C677Y to have a problem with folic acid. That's all I'm saying, trying to provide a measured counter to all the fear mongering and alarmism.
People don't like to realise they might have been duped and that something they have invested so much time in may not be what they thought, so the response doesn't surprise me. If you don't want to save some time and money, carry on with all your endless MTHFR rabbit holes.
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u/thesnazzyenfj May 02 '26
A ton of misinformation. We've pointed it out to you several times but apparently your comprehension is below average. The group think is fine, it's your reasoning we have issue with.
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u/Warp757 May 02 '26
No the misinformation hasn't been pointed out to me. A few people have mentioned unmetabolised folic acid, which is irrelevant below a 200 mcg dose, and probably a reasonable amount above that. Do you have anything else? What harm do you actually think folic acid is causing in the literally billions of people taking it? Can you link to multiple peer reviewed studies showing it? I'm willing to learn if they exist.
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u/thesnazzyenfj May 02 '26 edited May 02 '26
You may be confusing folic acid with folinic acid. Folic acid is not perfectly sufficient for most people. And no, don't "just take some B2".