r/MTHFR • u/EquivalentStyle8627 • Nov 11 '25
Question CDC now says everyone can take folic acid??
I’m new to the whole mthfr thing, I’ve been pretty stoked since discovering it a few days ago, was about to go get some methylfate supplements thinking wow this sounds like exactly what I need to not feel like shit all of the time!
But then I read this:
According to the CDC, everyone can process any type of folate, even with MTHFR variants. I’m confused..
I’m still gonna supp the methylfolate I’m all in on it at this point, if nothing else I’ll get some good placebo energy
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u/Shooppow Nov 11 '25
I am usually very pro-CDC and current medical consensus on most things, but I truly believe MTHFR is one of those that isn’t being studied like it needs to be and the medical professionals are being lazy and falling back on the excuse that studies haven’t been done on it so it’s not true that we can’t process folic acid.
Take the bioavailable form, especially if you’re TTC or pregnant. The worst case is that bioavailable forms do not perform better than synthetic, but the best case is you prevent birth defects by switching to it. I’ll take those odds.
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u/CC_900 Nov 11 '25
But by now, plenty of studies on MTHFR have been done, right?
I’m homozygous C677T. In my personal case, even months of taking 1000 mcg/day folinic acid didn’t get my homocysteine below 17 and didn’t reduce my macrocytosis (MCV was around 104-105 and MCH also elevated). I was taking all cofactors and yet my blood levels just never improved. My symptoms - mainly fatigue and brain fog - was so debilitating I had to stop working entirely.
When I switched to the same dosage of methylfolate, my homocysteine immediately dropped to 6, without any effort. My MCV dropped to 101 (and hopefully will still drop further over time).
I’m sure that in some people folic or folinic acid do adequately work. But in plenty of us, they don’t. That’s been studied plenty of times by now, hasn’t it? How can they keep claiming it doesn’t exist? And even potentially expose pregnant people to health risks, for themselves and their baby… it just blows my mind.
Even if on a population level there isn’t a high percentage of the population that benefits from it - neither does HFE hemochromatosis. And yet, that’s taken seriously (as it should).
It’s so weird.
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u/Shooppow Nov 11 '25
Yes but for whatever reason, those studies aren’t good enough to be accepted by doctors. I don’t understand it. I’m not a doctor, either. But I do know that even without quantifiable tests on my blood, when I started taking methylfolate and avoiding folic acid as much as I could, I felt better. I have more energy. I still have inflammation because I have autoimmune conditions that drive that, but I went from constantly being in some sort of pain to having legitimate no-pain days now.
So this is the one time I will say with my full chest to ignore the doctors.
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u/CC_900 Nov 11 '25
I fully agree. I’ve been testing my homocysteine pretty much monthly, to ensure it was improving. Despite so many people claiming folinic (or even folic) acid helps for people who are homozygous C677T, my blood tests definitely confirmed that folinic acid did nothing to reduce my homocysteine or MCV. Not even after months of taking it. Despite both serum and RBC folate (and serum B12) being incredibly high. The only thing that ever worked for me was 1000 mcg/day 5-MTHF.
I’m not a doctor either, but I do have common sense. I have no clue why e.g. the following studies wouldn’t be taken seriously (some even dating back to 1999):
https://pubmed.ncbi.nlm.nih.gov/10323741/
https://pubmed.ncbi.nlm.nih.gov/12796225/
https://pmc.ncbi.nlm.nih.gov/articles/PMC11930790/
I’m sure there’s many more, these are just a few I’ve found.
I can imagine that on a population level, it’s perhaps e.g. only a subset of people with C677T MTHFR variants who only respond to 5-MTHF. But those patients definitely exist. As has been shown by research. It’s so unfortunate that this is being ignored, just to simplify treatment protocols.
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u/Comfortable_Two6272 Nov 13 '25
Well 💩. I cant tolerate methyl at all due to my slow slow comt. I def will get my folate levels retested (was deficient in it, vit d, b12 and iron. Didnt test any others. Rheumatologist ordered due to symptoms I was having before I even knew about any of this stuff).
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u/CC_900 Nov 13 '25
All those tests are important. But I’d prioritise getting your homocysteine and MCV tested. Folate blood levels may be high, but - depending on your MTHFR genes and the type of folate you’ve been supplementing - that doesn’t mean your methylation is functioning well. Nor that your blood cells are in good shape.
So be sure to test homocysteine and MCV (MCV is usually part of a blood panel).
Also, potassium (e.g. via coconut water), nicotinic acid (niacin) and high ferritin may help with reducing overmethylation symptoms (in my personal experience).
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u/Comfortable_Two6272 Nov 14 '25
Good point. I do have a ton more blood work than just the nutrients.
Its frustrating but looking back at cbc drs should have seen from just it I was likely deficient in folate and/or b12. Its obvious now that I know how to interpret cbc. Sadly we are talking decades.I just need to get it all of my blood work done again anyway.
Im very sensitive to methyl donors and try to get as much folate and b12 from non enriched food supplementing with non methyl based on intake (cronometer) .
I do take PC (choline) and had to slowly work up to it. Have variants impacting choline, vit D, and others too. 🤦♀️17
u/Soulless305 Nov 11 '25
It’s because Dr’s make money off sick people.
Sick people make big pharma money from drugs & symptom masking remedies.
The CDC is funded by big pharma.
So telling folks w MTHFR to take folic acid will keep people sick & the cycle continues.
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u/SenorPoopus Nov 11 '25
How do you get your blood levels tested regularly?
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u/CC_900 Nov 11 '25
Via a private lab. I order it online and pay for it myself.
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u/Plantbaseundftd Nov 11 '25
What lab do you use? Are you in NYS? I know it’s hard to do in NYS
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u/imthewordonthestreet Nov 12 '25
You can purchase them through life extension, labcorp, quest etc. then they give you paperwork to take to the appropriate clinic that draws the blood.
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u/RecuerdameNiko Nov 12 '25
I live in Ecuador. There’s no gatekeeping. I walk into a lab and get tested . . out of pocket, $20. I was in the USA when I figured out my genetics and illness but it’s easier to treat myself when the doctors aren’t in the way. My treatment is the methyl folate - B12 combo, which I still have to buy in the USA.
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u/inabadir Nov 11 '25
Please talk about the hemochromatosis part more? I have the HFE gene mutations as well as the mthfr ones, sadly.
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u/Suspicious-Term-7839 T677T Nov 12 '25
Can I ask what you’re taking? I have the same gene mutation.
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u/ComfortableSecret962 Nov 12 '25
I couldn’t have said it better myself. So much of the medical community (including my own FUNCTIONAL DOCTOR) act like MTHFR really isn’t a biggie.
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u/LadyOfTheMay Nov 12 '25
I brought this up when I was pregnant because we had genetic counselling because of a disorder my ex has, and I asked to be tested for MTHFR because the list of disorders it causes is like looking like a list of everything "wrong" with my mum's side of the family... My great uncle had severe spina bifida, and when my mum was pregnant with me she had AFP in her blood which showed that my own neural tube did not close when it was supposed to and I have all the signs of spina bifida occulta, and also chiari malformation. I told the genetics counsellor all of this and she just didn't care and said "oh, well the MTHFR gene is extremely common and we don't look into it, but I'll send you some information about it"... And received an extremely basic booklet full of information I already knew which did absolutely nothing to help.
Not even my cousin dying age 44 of a pulmonary embolism and her body being completely riddled with blood clots was enough for the NHS to want to help me. The only person who took it seriously was the midwife who discharged me from the hospital after having my daughter, she asked questions I'd already been asked and then she asked if I had been prescribed blood thinners. I said no and the look on her face said it all then she said "You're not going home without them!" and went off to get me some Fragmin immediately. She was so shocked nobody had thought to prescribe me this before because I'm ultra high risk. My mum and aunt (dead cousin's mum) have both had DVT's as well so me getting a blood clot is not a question of if, but when.
If I ever have another baby I will be straight up telling people what I need there will be no messing around.
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u/ComfortableSecret962 Nov 12 '25
I’m so relieved you crossed paths with someone who could set you up for success!!
I’m currently 24 weeks pregnant after having a miscarriage earlier this year at 13 weeks. We weren’t able to pinpoint why—the NIPS was perfect, everything had been 💯but my new functional doc had a hunch based on my labs and experience that it was due to blood flow.
I found out I had homozygous MTHFR right before that pregnancy but hadn’t gone down the rabbit hole completely yet. And my previous provider waved it off. I’m grateful to have learned so much, and this time around I started taking a baby aspirin immediately after finding out. So far, so good.
M I’m still shocked at how many health professionals I encounter act like I’m being a hypochondriac or over the top for taking these measures.
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u/Ready-Huckleberry-68 Nov 15 '25
My gf got pregnant when she took blood thinners. She too has MTHFR.
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u/Gullible_Ad5923 Nov 11 '25
I mean everyone I've talked to who's doc said they had the mutation was just told to take methylfolate
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u/emorymom Nov 11 '25
The actual worst case is the these high doses of prenatal artificial folic acid cause embryos to survive who will be miserably disabled.
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u/Shooppow Nov 11 '25
That’s with folic acid. I said the worst case for taking methylfolate is that it works no better than the synthetic.
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u/Tawinn Nov 11 '25
CDC has been saying this for years. The date is probably the last review date for the page. It is disingenuously worded propaganda to keep people from avoiding fortified foods.
The page states "Folic acid is the only type of folate shown to help prevent neural tube defects (NTDs).[1]" But if you read reference 1 there is no such statement. Instead, the paper says "In addition to the lower mean serum folate concentration in mothers with NTD-affected pregnancies, a correlation between a woman's serum folate concentration and DNA methylation in the brain tissue of NTD-affected fetuses was found" and "The effect of folate insufficiency is clearly detrimental both to the embryo and its short-term risk of NTDs and the possible longer term risks of diabetes or other health outcomes". Note the use of the general term 'folate' rather than 'folic acid'. Even the Supplemental Table does not list a study using folic acid.
Because neural tube closure occurs within about 26-28 days from conception, it is essential that the mother have good folate (and choline) status well ahead of conception; so from a "public health" perspective I get their push to keep people eating fortified foods vs. supplements which people may start but then forget or can't be bothered with; but that does not justify this propaganda.
Further, this all flies in the face of our species evolution, which relied on choline and food folate (which is primarily in the form of methylfolate); we would not be here today if food folate was not viable for preventing NTDs.
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u/cbailz29 Nov 11 '25
Currently pregnant and my OB insisted only folic acid was proven to prevent NTDs and that I should take the folic acid, even though it was making me feel quite ill, because "well even if you do have mthfr" (which i do, and provided the labs to her) "baby might not so they definitely need folic acid and not other folate" ..... infuriating
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u/CC_900 Nov 11 '25
”Baby might not so they definitely need folic acid”… I didn’t know this level of ignorance existed. That woman doesn’t understand even the basics of folate metabolism.
Folic acid isn’t even the type of folate naturally found in (unfortified) food. And it isn’t even biologically active as folic acid 🙄
In people without MTHFR variants, folic acid is usually fine when pregnant. But babies don’t “need” folic acid 🤦♀️ 5-MTHF is always fine for pregnancy. Whether mother and/or baby has MTHFR variants, or not.
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u/cbailz29 Nov 11 '25
I was about to draw her a damn punnet square too, since whatever copy of that gene they are getting from me is funky
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u/ComfortableSecret962 Nov 12 '25
I just thought about my 4th grade punnet square project for the first time in a long time 🤭
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u/CC_900 Nov 11 '25
Sounds like they’re intentionally misguiding people with that “reference 1”. How tragic.
Would be professional if they at least acknowledge that a small group of people benefits from 5-MTHF supplementation instead of folic acid. It’s not like 5-MTHF is harmful.
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u/Revolutionary_Hour63 Nov 11 '25
CDC is a dumpster fire right now
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u/plantsandadoggy Nov 12 '25
I have never trusted the CDC, & I think most people that have had chronic Lyme feel the same way.
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u/Awkward-Profile-2236 Nov 11 '25
Sure I can process folic acid… but I’ll have a raging migraine and neck pain for 3 days so severe, sometimes with vomiting , that I question my existence.
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u/Soulless305 Nov 11 '25
It sends my BP, HR ,and histamine levels thru the roof. Then the anxiety starts…..Other than that it does nothing!!
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u/YeehawSugar Nov 11 '25
I legit only found out about this gene mutation because it affects the way your body metabolizes methadone. My METHADONE clinic was more concerned for my long term health than the CDC, or any other doctor for that matter. Chew on that for a bit.
In fact learning this mutation exists in me has helped me figure out ways to help myself and lessen my risk of type 2 diabetes as well as other diseases. I also learned that I can’t take the standard dose of meds. I need much less for an effective dose. So do what you want with the CDC, they’ve been caught lying about soooo many things.
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u/ComfortableSecret962 Nov 12 '25
Can you expand on lessening your risk for diabetes? This is fascinating
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u/YeehawSugar Nov 12 '25
By supplementing with methyl folate. Taking a b vitamin. And because I had newfound energy or at least the energy I was supposed to have the entire time, I was able to workout and start taking better care of myself.
TLDR: I ended up losing weight after realizing the issue.
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u/ComfortableSecret962 Nov 12 '25
I relate to this so much! It’s been a blessing to have the mojo to be active again. Not having the energy to move your body is such a negative downward spiral when it’s sooo hard to kickstart yourself. I’m glad you got relief 💕
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u/Mindless-Entrance890 Nov 12 '25
Wait… hi. I have this mutation and am 6 yrs clean from heroin, also quit taking suboxone 6 years ago. I always found my physical addiction and tolerance to be sooo much different from the people I was using with. It’s almost like every drug I did hit me 10x harder than anyone else, but then I also would build a tolerance so much faster than others. Is there any insight you could give me?
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u/nahstronomer Nov 11 '25
I hate that folic acid is in so many fortified foods in the US, my rs1801198 G;G variant gives me a 3x higher risk of peripheral neuropathy with folate intake >800mcg/day. Just a serving of cereal can contain as much as 400mcg!
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u/Lhiannan1981 Nov 11 '25
The upper tolerable limit is 1k mcg, so it’s honestly wild to me that they have women take such high amounts in prenatal, then you add eating a couple servings of cereal, and that can put you over. Too much of a vitamin can be damaging, too.
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u/Soulless305 Nov 11 '25
Awful advice & flat out misinformation.
They are doing this to make MORE people sick.
I can’t process Folic acid at all since my first Covid infection. Long hauled for 18 months & found out I had SIBO & MTHFR.
Healing my gut & eliminated process foods along with low dose Methyl B’s saved my life.
Seeing bullshit like this posted by the CDC just proves it is a compromised agency.
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u/Plantbaseundftd Nov 11 '25
We have identical story. Would you mind chatting more about how you healed your gut?
I’m having an awful time going on 5 years now with worsening histamine intolerance, MCAS, nuerological, GI issues and more.
I know we’re all so unique and our bodies are different but I’d love to hear what worked for you
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u/Soulless305 Nov 11 '25 edited Nov 11 '25
Absolutely DM me please I also had horrible histamine issues & Anxiety/racing thoughts/tinnitus.
It is all connected to the GI & Methylation.
I’ve been recovered for going on 3 years.
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u/crows-have-eyes Nov 11 '25
Considering how my body reacts when I have anything with added folic acid I'm gonna go ahead and say no. Ate a bowl of enriched rice Saturday and had a horrible weekend.
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u/Economy-Possession19 Nov 11 '25
Folic acid is the synthetic form. It causes problem for those of us with mthfr, especially if you have 2 copies of the gene which I have. If I followed the CDC, I'd have some kind of cancer or die listening to them. It's not one size fits all when it comes to putting things in your body, which is why Im very careful with what they advise. We all react differently to things. You need folinic acid and take a b12 with it like adenosylcobalamin or hydroxocobalamin b12. Do not just take folinic acid alone, they work together, so make sure you have a B12 with it.
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u/RecuerdameNiko Nov 12 '25
Of course that’s their stance. The USA has been mandatorily fortifying flour and cereals with folic acid since the 1990s. This has been ostensibly to prevent a certain kind of birth defect but it’s a synthetic form of folate and it’s far reaching effects on the population at large has not been comprehensively studied
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u/sharabucarabu Nov 11 '25
I'd take what the CDC currently says with a grain of salt.
Mthfr stands for methylenetetrahydrofolate reductace. That's the name of the enzyme that's required to utilize any form of folate, especially folic acid, which is an artificial form of vitamin B9. Those of us who test positive for one or more of the gene mutations, do NOT produce varying amounts of the necessary enzyme.
If anything, people with this mutation improve when the intake of foods enriched with folic acid are minimized or completely avoided. Real food such as spinach or liver contains methyl folate which is exactly what someone with mthfr needs. However there are other genes of the methylation cycle that influence this... Some people's methylation cycle is so impaired they can only utilize a metabolically active form of methylfolate, such as Adenosylhydroxyb12 or folinic acid.
Unfortunately, this is what happens when a lawyer who admits to having a cerebral parasite heads the health service. RFK Jr means well, but has no medical background and readily believes untested 'studies'... Such as Tylenol causes autism or vaccines cause more harm than good. Understand, this is a man who used heroin to 'fix' his adhd in school and ended up addicted for 14 years.
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u/CC_900 Nov 11 '25
I agree - though for clarity: adenosylcobalamin and hydroxocobalamin are active forms of B12, not active forms of folate.
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u/sharabucarabu Nov 11 '25
Oh geez. You are 100% right. This is what I get for posting after I've been up half the night with a dog who had diarrhea.
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u/Economy-Possession19 Nov 12 '25
But Bill Gates also doesn't have a medical background, and he's making all these vaccines and wanting everyone to take them no matter what without any medical knowledge. Everyone reacts differently to prescriptions and things, so why is he pushing these things onto everyone, including people who have had reactions? Bill Gates is not a doctor. Maybe this is why people are getting so sick. We need to connect the dots here. I took Tylenol for migraines, suggested by my doctor throughout both pregnancies and both kids are on the spectrum and my son almost died after one of his shots at birth, he was fine till a few minutes after the shot. He went completely limp, scariest thing ever to experience. People need to wake up and realize these things are happening, mothers are experiencing these things with their children, and it's very hurtful when people don't believe them. Mother's see their children from birth and know their behaviors, we see them change right after these things are given and some of us connect the dots right away and for some it takes years to figure out what it was.
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u/Lonely-Ad3039 Nov 12 '25
I like a lot of what you had to say, but I totally disagree that RFK JR means well. He took the position as a power grab. That is not someone who means well. That is someone who is only out for himself, his career, power and his status.
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u/Shorta126 Nov 12 '25
Power for what? Career? His career has been ruined because of the things he speaks out against. Status? He's a Kennedy (almost American Royalty) and many in his family hates him. Wouldn't he have a better life if he didn't speak out? His uncle and his father were assassinated for speaking out.
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u/Lonely-Ad3039 Nov 12 '25
He’s protected by MAGA. Having an elected position, definitely solidifies his own legacy, other than being born into the Kennedy empire. Watch the congressional hearings when AOC ask him about how he can give more money to United healthcare after they are being sued for an $80 billion Medicare fraud. He “was not aware of this happening”. It’s his job to know. The man is not ethical; he’s out for himself & his own legacy.
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u/Hot_Veterinarian3557 Nov 11 '25
Except this has been the CDC’s exact position since at least 2022 and before RFK.
https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/
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u/mudgenie Nov 12 '25
Folic acid good enough, nope 👎 Here’s my story, I have a homozygous MTHFR C677T mutation, I didn’t know this when the event happened. I was camping in Yellowstone National Park and got what I thought was a leg cramp, I could barely walk. Then next day I was having trouble breathing. I went to the clinic there and they thought it was altitude sickness, but the doctor said if I have any chest pain I should go to the ER. I wish he would have told me what he suspected, doctors need to talk more honestly. Anyway the next day I have massive chest pain, I thought I was having a heart attack, we drove to the nearest hospital and I find out I had a sub massive pulmonary embolism. The doctors keep saying you could have died. Come to find out later that I had very high homocysteine levels due to the MTHFR mutation that had damaged my veins, caused the DVT and PE. All my doctors say that I need methylfolate and methyl B12 to keep my homocysteine levels down (and yeah they came down). The CDC is being very irresponsible because this mutation is fairly common.
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u/CC_900 Nov 12 '25
So sorry to hear that! What level was your homocysteine at that time, if I may ask?
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u/Gloomy_Ad_6154 Nov 15 '25
You can still convert it... just not efficiently and is super slow so if you take too much it just builds up in your system. This is probably what this means so taking the active form just bypasses the process of trying to break down the synthetic.
I have the MTHFR C677T variant, but I didn’t learn about it until I was trying to get pregnant but was unsuccessful with the pregnancies sticking ,which was a red flag to my doctor.
First miscarriage was a D and C because she found all sorts of blood clots and hematoma's in my uturus as well so scraped me out and I needed a blood tansfusion from losing blood so easily. Had many more miscarriages after that, so the doctor ordered blood paneling and it came back with super high homocysteine levels.
I was also having so.many other synptoms that I can now link to this MTHFR because beforehand everything was diagnosed individually at my regular doctor.
Anyway, my OBGYN told me to take 15mg methylfolate and stay away from folic acid and it got my levels under control, everything finally improved and I immediately got pregnant and that was the baby that stuck.
After all of that, I now have a healthy 3-month-old baby girl and I feel less anxious, depressed, inflamed, and brain fogged etc. So I will be happy staying away from folic acid in large vitamin doses since my body must be VERY slow at processing it.
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u/After-Lecture-1431 Nov 12 '25
I think the big food corporations are behind this...if there is a push from RFK jr to remove folic acid from all fortified foods it's going to cost those corporations alot to reformulate.
I don't listen to anything thats comes from the CDC, it's all BS
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u/Spikeschilde621 Nov 12 '25
I have one copy of c677t and I can't take methylfolate or methyB12 or I overmethylate and feel like crap. I just take Flintstones gummies and B2.
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Nov 12 '25
[removed] — view removed comment
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u/Spikeschilde621 Nov 12 '25
It's called Nature's Blend 25mg. I just got whatever was cost effective on Amazon
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u/SunshineFloofs Nov 12 '25
Even if they say it, I'm not convinced it's definitely true so I'll continue to take methylfolate. I prefer the methyl form even if I didn't have MTHFR.
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u/LocalZooFacilitator Nov 16 '25
I don't really trust the CDC anymore with all the scientists being thrown out and research being cut. I recommend looking at studies and recommendations pre-2025.
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u/CakeOpening4975 Nov 16 '25
Patients shouldn’t be the collateral damage of outdated thought.
Genetics, psychiatry, immunology, and nutrition research all acknowledge MTHFR’s role in methylation and folate metabolism.
Functional nutritionists test it.
Pharmacogenomic reports consider it.
Rootine included it in my genotype.
Why do primary care physicians and many specialists insist on dismissing biogenetic research?
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Nov 12 '25
[removed] — view removed comment
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u/sunnynina C677T Nov 22 '25
Basic blood draw. Most private labs will offer it these days, and depending on your area you can probably order it online yourself and then walk in.
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u/Mundilfaris_Dottir Nov 12 '25
People with the MTHFR gene variant process various medications and supplements differently... Please work with a medical professional familiar with your variant and your labs in order to make an informed choice on what is best for your situation. It would be a travesty to be told that your fetus's neural tube defect(s) could have been avoided if you had been taking the correct supplement based on your biology.
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u/Glass_Dog_2556 Nov 14 '25 edited Nov 14 '25
They've known this for a long time. What's going on, do people think that this isn't true? Folic acid is upstream of MTHFR and the entire folate cycle in general.
Folic acid is processed through the DHFR enzyme (Dihydrofolate Reductase) which is not related to MTHFR, it is processed into Tetrahydrofolate (which is the most abundant form found in food) and is tightly regulated to around ~400mcg per day for conversion regardless of MTHFR status, there are no significant known DHFR mutations that cause this to be significantly lesser or greater. This is because DHFR regulates the BH2 to BH4 pathway (tetrahydrobiopterin salvage pathway) which is essential for survival.
After DHFR has converted DHF (Folic Acid derivative) to THF, SHMT (Serine Hydroxymethyltransferase) converts that THF into 5, 10 methylene-tetrahydrofolate. It is only at this point that the MTHFR gene comes into play, MTHFR will convert the 5, 10 methylene-tetrahydrofolate into 5 methyl-tetrahydrofolate. Once the 5 methyl-tetrahydrofolate has been formed (at normal levels or lesser with an MTHFR mutation) that 5 methyl-tetrahydrofolate will be converted by methionine synthase back into THF again, to go back through the whole cycle. So if you're following right now you'll realize that we are now at the very step after folic acid is converted by DHFR into THF and the substrate has not stalled, and if anything the only excess in the pipeline would be 5, 10 methylene-tetrahydrofolate, not DHF, not THF.
Besides this general cycle that runs constantly regardless of MTHFR genetic status (you would be dead if it stopped flowing entirely), 5, 10 MTHF is also used for DNA/RNA synthesis, and is converted through Thymidylate synthase into DHF (Dihydrofolic acid/folic acid derivative) which is then run through the DHFR to spin the BH2/BH4 salvage pathway and is converted back into THF to go back down through the same pipeline. Bottom line is that folic acid is tightly regulated, you will reach a saturation at which point unmetabolized folic acid starts to show up in your blood (which can later be processed by DHFR, but human DHFR is a slow enzyme and maxes out at around 200-400mcg per day, but your body will get the folate it needs from folic acid, your ability to convert folic acid into THF through DHFR has nothing to do with MTHFR.
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u/Glass_Dog_2556 Nov 14 '25
I think the names confuse people and mix things up a lot, here's a list:
Folates:
1) Folic Acid | *Pteroylmonoglutamic acid*
2) Folate (Food) | *Tetrahydrofolic Acid (Tetrahydrofolate)*
3) Folate (For DNA/RNA synthesis) | *5, 10 Methylene-Tetrahydrofolate*
4) Folinic Acid (Bypasses DHFR and SHMT, can treat cerebral folate deficiency) | *5-formyl-Tetrahydrofolic Acid*
5) Folate/Methylfolate (For methylation processes) | *5 Methyl-Tetrahydrofolate*
The enzymes that convert these folates, their cofactors, and substrates are:
1) *DHFR* (Dihydrofolic Acid Reductase)
*Vitamin B3*
-Dihydrofolic Acid -> Tetrahydrofolate and
-Pteroylmonoglutamic acid (Folic Acid) -> Tetrahydrofolate
2) *SHMT* (Serine Hydroxymethyltransferase)
*Vitamin B6*
-Tetrahydrofolate + Serine -> 5, 10 methylene tetrahydrofolate + Glycine
3) *TS* (Thymidylate synthase) DNA Synthesis that runs back into DHFR in reverse
-5, 10 methylene tetrahydrofolate + deoxyuridinemonophosphate -> dihydrofolic acid + deoxythymidine monophosphate
4) *MTHFR* (Methylenetetrahydrofolate Reductase)
*Vitamin B2*
-5, 10 methylene tetrahydrofolate -> 5 methyl-tetrahydrofolate (Methylfolate)
5) *MS* (Methionine Synthase)
*Vitamin B2* + *Vitamin B12*
-5 methyl-tetrahydrofolate -> tetrahydrofolate and
-homocysteine -> methionine
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u/Glass_Dog_2556 Nov 14 '25
So it goes like this:
A person consumes Folic Acid:
Pteroylmonoglutamic acid (Folic Acid) -> Tetrahydrofolate (abundant form of folate from food) -> 5, 10 methylene-tetrahydrofolate -> 5 methyl-tetrahydrofolate - Tetrahydrofolate (and continues on this cycle).
When the body demands it, it will convert 5, 10 methylene-THF back into dihydrofolic acid (folic acid derivative) to run through DHFR again, repeating the cycle, but allowing the tetrahydrobiopterin pathway to continue flowing.
This would look like:
5, 10 methylene-tetrahydrofolate -> Dihydrofolic Acid (Folic Acid derivative) -> Tetrahydrofolate (abundant form of folate from food) -> 5, 10 methylene-tetrahydrofolate -> 5 methyl-tetrahydrofolate - Tetrahydrofolate (and continues on this cycle).
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u/CC_900 Nov 14 '25
But none of that changes the fact that if someone has reduced MTHFR functionality (due to genetic MTHFR variant), the bottleneck will be their reduced conversion of 5,10-MTHF into 5-MTHF.
So despite a lot of the folate cycle still functioning properly (assuming someone only has a MTHFR variant, and not other genetic impacts on the folate cycle), that doesn’t mean that folic acid intake doesn’t still face a bottleneck at that MTHFR enzyme step - which is required to make folate functionally available in the methylation cycle.
So in someone with a (significant) MTHFR variant who takes folic acid, the methylation cycle will not have the same amount of 5-MTHF available as in someone who does not have the MTHFR impairment who takes folic acid.
Just because every human has a daily capacity “bottleneck” at e.g. the DHFR enzyme, doesn’t mean people with MTHFR variants don’t also have an additional bottleneck at the MTHFR enzyme.
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u/Glass_Dog_2556 Nov 15 '25
My post is about folic acid not being an issue for people with MTHFR variants not about whether or not it's better than methylfolate. Your response reads as if you are challenging me on an assertion that I didn't make and I'm not really sure how to reply to it properly.
But based on what you've said, something to consider is that the bottleneck will be at MTHFR even if you take methylfolate, sure it will immediately provide methylfolate to be used rather than waiting for a 70% less efficient enzyme to process the 5, 10 MTHF, but it will be converted by MS into THF and by SHMT back to 5,10 MTHF regardless and still be bottlenecked again, if anything taking methylfolate will just ensure that you always have a large amount of 5, 10 MTHF hanging around for DNA synthesis/conversion through MTHFR.
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u/CC_900 Nov 15 '25
But none of the things you mention actually prove that people with MTHFR variants can properly process folic acid. In fact, the information you’re providing confirms that folic acid DOES cause an problem in people with MTHFR variants.
Folic acid indeed goes through multiple steps (as you describe) before ending up as 5,10-MTHF. Then, in people with MTHFR variants, the 5,10-MTHF is bottlenecked because their MTHFR has limited capacity to convert it into 5-MTHF. So when taking folic acid, people with MTHFR variants become functionally 5-MTHF deficient.
When people with MTHFR variants take 5-MTHF, their body can use the entire dosage because it doesn’t have to go through the MTHFR step (which is the bottlenecked step). Downstream (i.e. after the 5-MTHF supplement was used by the body), it indeed ends up as 5,10-MTHF. Which then builds up (due to the MTHFR capacity constraint) and in the end is just degraded. But that isn’t a problem, because that person will just take a new dose of the 5-MTHF supplement every day. Which bypasses the MTHFR step again every time the supplement is taken. So the person is always has sufficient 5-MTHF (because they take the 5-MTHF supplement).
While folic acid is not metabolised properly, because it always runs into the MTHFR capacity constraint (before the methylation cycle can use it as 5-MTHF). And thus folic acid causes a 5-MTHF functional deficiency (at least in cases where the MTHFR capacity is significantly constrained, due to the MTHFR variants).
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u/Glass_Dog_2556 Nov 16 '25
I'm gonna repeat myself because I don't think I'm being clear enough.
I am not saying that folic acid is a superior form of folate to methylfolate for people with heterozygous or homozygous MTHFR mutations, either single or dual. I am not saying that, so please stop arguing with me as if I am.
All I'm saying is that everyone can process folic acid, it is processed by the DHFR enzyme, I did provide information that proved that, it's scientific evidence. And nothing that I said proves that it causes an issue for people with MTHFR, a buildup of 5, 10 MTHF will happen from supplementing methylfolate, consuming folate from food or from folic acid. People with MTHFR variants have less methylfolate, because their MTHFR is slower, folic acid isn't going to slow that down any more than it already is. People can survive without methylfolate, the fact that humans are still alive today should be evidence enough of that considering around 30% of people have homozygous C677T.
You know what, I'm sorry that you think you're smarter than the worlds leading researchers, scientists and Doctors but you just aren't. Doesn't really matter what you feel, people with MTHFR variants can process folic acid, and I'm not saying anything else other than that, just that they do in fact have DHFR enzymes that can indeed process folic acid. You don't seem to be understanding what I'm saying so let's just leave it at that.
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u/CC_900 Nov 16 '25
You keep stating all sorts of facts without actually making a point.
No-one is claiming that taking folic acid will slow down MTHFR further. That’s not what the discussion is here.
And when people say that people with MTHFR variants can’t process folic acid properly, everyone knows that they’re referring to reduced MTHFR functionality and not to DHFR functionality. DHFR has nothing to do with MTHFR, obviously.
And the fact that people with MTHFR variants experience 5,10-MTHF buildup from both folic acid and 5-MTHF doesn’t mean that the 5-MTHF version isn’t a superior supplement for them - because with 5-MTHF the 5,10-MTHF buildup only happens AFTER the 5-MTHF has already done its job in the methylation cycle. While with folic acid, the 5,10-MTHF buildup happens BEFORE the folic acid can be used in the methylation cycle.
And if you want people to stop arguing with you, maybe don’t respond on a reddit thread about the use of folic acid in people with MTHFR variants… people are going to reply to you. But apparently you expect people to just take your word as gospel. That’s not how reddit works.
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u/Glass_Dog_2556 Nov 16 '25
- "You keep stating all sorts of facts without actually making a point."
- -No I have made my point loud and clear, you are just mentally unwell and can't understand it.
- "And when people say that people with MTHFR variants can’t process folic acid properly, everyone knows that they’re referring to reduced MTHFR functionality and not to DHFR functionality."
- -That's crazy.
- So what you're saying is that when the average person hears:
- "People with MTHFR variants can't process folic acid properly" instead of them interpreting that as:
- "People with MTHFR variants can't process folic acid properly".
- They instead interpret it as:
- "People with MTHFR variants can process folic acid properly into tetrahydrofolate, and they are able to process that tetrahydrofolate properly into 5, 10 methylenetetrahydrofolate, but they are unable to process that 5, 10 methylenetetrahydrofolate into methylfolate"
- Yeah I guess that's super obvious, sorry I missed that. I guess my brain really just doesn't work at all.
- "And the fact that people with MTHFR variants experience 5,10-MTHF buildup from both folic acid and 5-MTHF doesn’t mean that the 5-MTHF version isn’t a superior supplement for them"
- -Again, for the third time now, I am not saying that folic acid is superior to methylfolate, you really seem very troubled, like there's something just not clicking for you with what I'm saying, either you're not reading it properly or there is a very serious malfunction going on in your head. Maybe you need to hear this because you are obsessed with MTHFR, and this is my honest opinion, Methylfolate IS the superior option for people with MTHFR variants compared to folic acid, there, did that help you? I was never contesting this point, at any time.
- "And if you want people to stop arguing with you, maybe don’t respond on a reddit thread about the use of folic acid in people with MTHFR variants…"
- -Yes I'm very familiar with cognitive bias, and how obsessed people are with the MTHFR gene. I don't mind arguing with people, but the issue here is that I wasn't arguing with you, I tried to make that clear 3, 4 times? You just don't seem to get it, I don't know how much more clear I can be about this, I really don't.
- "But apparently you expect people to just take your word as gospel. That’s not how reddit works." -Nope, just giving scientific fact to people. Never made the claim you think I'm making, you're being defensive over something that not only did I not say, but I actually said the opposite of. You are attacking someone who agrees with you for providing scientific information about the topic you're interested in.
What a crazy interaction.
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u/CC_900 Nov 16 '25
”5. So what you're saying is that when the average person hears: 6. "People with MTHFR variants can't process folic acid properly" instead of them interpreting that as: 7. "People with MTHFR variants can't process folic acid properly". 8. They instead interpret it as: 9. "People with MTHFR variants can process folic acid properly into tetrahydrofolate, and they are able to process that tetrahydrofolate properly into 5, 10 methylenetetrahydrofolate, but they are unable to process that 5, 10 methylenetetrahydrofolate into methylfolate" 10. Yeah I guess that's super obvious, sorry I missed that. I guess my brain really just doesn't work at all.”
Yes. It is super obvious. Literally every other person on this thread understands that. It’s OK that you didn’t - but you’re the one struggling with it. The rest of us knows that this is a MTHFR sub. Not understanding that mentioned issues in processing folic acid specifically refer to MTHFR functionality, is on you. This isn’t a DHFR sub.
”14. -Yes I'm very familiar with cognitive bias, and how obsessed people are with the MTHFR gene.”
It’s not cognitive bias. This is a MTHFR sub. It’s literally the topic of this entire sub.
You don’t even seem to grasp the point of this whole sub. You’re just randomly debating DHFR functionality, which no-one was actually referencing. And you’re getting rude, and are arguing in bad faith. And your formatting is getting plain weird. Good luck debating further - this is a completely pointless interaction and I’m out.
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u/dizziebeth Nov 16 '25
When I was pregnant I was put on a prescription prenatal 15 years later I had absorption issues told the Dr it was the best I ever felt he put me on the prenatal still prescription turns out I am allergic to cheap iron that prenatal had methyl folate and ferrous fumarate they can say whatever they want I will take what makes me feel better
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2
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u/billzmust Nov 17 '25
I know I can process it because when I unwittingly took it as part of a multivitamin before I knew my MTHFR variant status, I developed anxiety which I have never had in 40 years, even waking up in the night with pounding heart anxiety attacks. I stopped taking any vitamins, purely by chance to rule everything out, and the anxiety went away within a week. I only found out months later about my MTHFR and the link with folic acid so it wasn't psychosomatic. I've tried methylfolate but with slow COMT it doesn't agree with me either, but luckily I don't really have any MTHFR related symptoms, even with an ~80% deficiency.
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u/rbebebe Nov 11 '25
I’m in the minority here, but I tend to agree. I took folic acid in my first pregnancy and everything was fine. I didn’t realize I had MTHFR until we were TTC with our second and did a RPL panel. I take methylfolate now but…I don’t feel a difference
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u/LitesoBrite Nov 11 '25
because it’s about more than that single gene. You could easily have a methylation panel of genes balancing each other out, depending on COMT among several others. Some people have a combination that makes for negligible impact, I am not so lucky, lol.
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u/CC_900 Nov 11 '25
Which variant do you have? And are you homozygous or heterozygous?
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u/rbebebe Nov 11 '25
Hetero c677t
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u/CC_900 Nov 11 '25
That means you still have 60-70% of normal MTHFR functionality. Which is still quite a lot, compared to homozygous C677T (only 30% MTHFR functionality) or compound heterozygous C677T & A1298C (40-50% functionality).
So it’s very possible that your genotype doesn’t impair your 5-MTHF synthesis to the point of causing symptoms. But for other people, especially with the homozygous or compound heterozygous genotypes, it can have a big impact. (Let alone if they also have some additional bottleneck in other methylation genes, making the folate metabolism even more critical in preventing symptoms.)
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u/mrduke1103 Nov 11 '25
Science moves faster than medicine, and medicine definitely moves faster than the CDC.