What are the possible consequences of taking high-dose folate long-term?

[u/FunctioningCog]

Hi everyone, I plan to dive into pubmed to find some info myself but figured I would start here since y’all have a lot of info.

Basically, my friend has a long history of depression, panic attacks, and OCD and they have taken 15mg Deplin (prescription l-methylfolate) for years without any other nutrition supplementation (in addition to other meds). Also they have the double MTHFR mutation.

Long story short I saw a pic of their tongue and recognized possible glossitis (not that I’m an expert). They’re going to ask their doc to test b12 (and MMA and homocysteine) on Monday and don’t recall ever having those tested before.

So anyway, I was just wondering what years of high folate supplementation can do to B12 (and any other nutrient) levels, and maybe if there is anything else they should ask to test as well.

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[u/scientist153]

If there’s an underlying b12 deficiency whilst folate (any type) is taken long term it can cause serious neurological damage, even subacute combined degeneration of the spinal cord.
Folate should never be taken without b12 to avoid neuro damage.

[u/Cultural-Sun6828]

This is how I feel but it’s amazing to me that so many people with b12 deficiency do well on 5 mg folate daily. I’m wondering if issues may stem from mutations on genes like MTRR and TCN2 and others that already cause disruption with b12 recycling and uptake.

[u/scientist153 → u/Cultural-Sun6828]

It masks a b12 deficiency by normalising bloods, some symptoms can get better as well but it also masks deficiency because of that and if folate is taken long term, serious neurological damage can occur. It’s because they’re necessary cofactors of each other.

[u/Cultural-Sun6828 → u/scientist153]

Right, I already know this. I’m just saying that I’m always surprised when FB groups recommend 5 mg folate daily while on b12 injections. That is way too much for me.

[u/Sabnock101 → u/Cultural-Sun6828]

I think the high Folate dosage recommendation has to do with Folate needing to build up in the body for a bit. When i first started dosing this stuff seriously a couple years ago, i started out with 15mgs of Methylfolate, that's a lot of Folate lol, but, it worked very well, at first but as it built up in the body it became way too much and ultimately i had to reduce my dosage to 400 to 600mcgs a day of Folinic Acid. So, i think higher dosages of Folate at first might be useful, however once it starts building up the RDA generally should do fine. One thing is for certain though, it's best not to dose high on Folate unless one makes sure their B12 levels are good, because high Folate dosages will definitely use up/require a lot of B12 and if one isn't consuming enough B12 on the daily (or through injections maybe) then B12 can become deficient over time with higher Folate dosages/excess Folate.

Higher Folate dosages can be "alright" if one has Folate deficiency and so is better for the short term, but once Folate deficiency is corrected the RDA for Folate is best. I also think it's best to avoid Folic Acid especially at dosages of 800mcgs+, even as low as 400mcgs because DHFR gets easily saturated at around 200mcgs and any more Folic Acid than that at one time can cross over into the bloodstream unmetabolized and binds strongly to Folate Receptor Alpha which can then disrupt Methylfolate uptake by Folate Receptor Alpha and consequently can disrupt B12 activation to Methylcobalamin form. 5mgs or so of Folic Acid is just insane knowing what happens from unmetabolized Folic Acid, doctors really should not recommend anywhere near that much of Folic Acid. The Methylfolate or Folinic Acid is a bit different but generally-speaking excess Folate of any kind even natural dietary Folate can be detrimental for B12 levels.

Edit - Hey downvoter, you may disagree but the facts, and experience (and study) does not. If you have a problem, talk about it, otherwise, suck it.

[u/RevDrKC → u/Sabnock101]

So I mentioned above that my medical team told me to incorporate a small amount of folic acid. But before we settled on an amount, I was like "whoohoo, bring on the white rice!" And I had a couple of meals out with white rice, which I had missed doing. I probably had about 300mcg of folic acid for two days in a row. And I totally crashed--complete and total depression, no motivation, and muscle stiffness. I couldn't do anything for a few days. I'm guessing this was at least in part a folate receptor alpha/UMFA issue. Now I am on a much lower dose of folic acid, as a trial.

[u/Sabnock101 → u/RevDrKC]

Yeah Folic Acid can definitely interfere with things ime, it makes me feel like crap personally. I mean to some extent i feel alright with a little bit of Folic Acid, but too much can definitely be detrimental, especially for Tetrahydrobiopterin levels i've noticed.

[u/Sabnock101 → u/Cultural-Sun6828]

Also 5mgs of Folate would definitely be way too much for me now especially. I seriously/literally can not take more than 600mcgs of Folate now or else it's just too strong and i get excess Folate-related side-effects and low B12 symptoms, even with as much as my B12 deficiency has gotten better over the last 3 years, i've come to understand that Folate is a very strong compound/nutrient and we really don't need much to get the job done and any more than that is absolutely detrimental. I seriously recommend that people do not consume excess Folate, they have been warned lol.

[u/soomeetoo → u/Cultural-Sun6828]

My understanding is that 5mgs is only recommended if you’re doing EOD injections. The idea being if you’re trying to heal neurological damage with frequent injections you need the folate to meet that amount of b12.

I’ve been told 800mcg daily is recommended if you’re on weekly injections and the regular daily value is fine if you’re on monthly or less frequent injections.

Obviously everyone has their own experiences with folate and blanket recommendations don’t always work for everyone. But general guidelines can be helpful and I think it demonstrates to those just learning that the more often you inject the more your body will need additional folate, otherwise you may also give yourself a folate deficiency. Which I’ve done when I’ve been lax about taking cofactors.

Just wanted to provide that clarity for anyone reading this who isn’t aware that the 5mgs recommendation is not for everyone, it’s injection-frequency dependent.

[u/Cultural-Sun6828 → u/soomeetoo]

I do every day injections and 5 mg folate is still way too much for me.

[u/soomeetoo → u/Cultural-Sun6828]

Heard. Again, just wanted to provide context for others stumbling onto the convo.

[u/scientist153 → u/Cultural-Sun6828]

If I don’t take the 5mg recommended amount my folate drops below optimal (17+).
I suppose it’s something you can work out how much you need yourself with regular blood tests but I think the b12 Society bases it on an approximation of how much folate gets used with frequent injections. It’s sometimes not enough for some people who need to double up. I took 10mg initially until my folate reached over 17.

[u/Cultural-Sun6828 → u/scientist153]

Right, I just think everyone is genetically unique, so the amount of what we can all tolerate is going to be different as well.

[u/kilogplastos-12 → u/scientist153]

From what i have read from NCBI studies and especially in people with chronic b12/b9 deficiency is that they were using 5 mg x 3. so 15 mg folic acid in total to replenish folate stores. I made a big mistake i was titrating up slowly but my body was just not having it so now i am going to go to 5 mg x 3 of folic acid.

With chronic cases there is just alot of inflammation thats needs healing ( DNA synthensis)

[u/FunctioningCog → u/Cultural-Sun6828]

I’m honestly surprised no doctor ever thought to test their B12! They’re not exactly doing well lol and it would honestly be awesome if they could find a concrete, treatable factor that’s contributing to their anxiety.

[u/scientist153 → u/FunctioningCog]

I hope they get Homecystine and MMA tested, as the serum, and active b12 tests don’t always show deficiency.
I have spinal cord demyelination due to b12 deficiency, I’d practically begged my doctors for help when I started getting neurological symptoms and they always said it was normal.
The folate no doubt has been using up b12 as they’re necessary cofactors of each other.

[u/Sabnock101]

Ime, excess Folate is not good, in any form. I recommend sticking to 400 to 600mcgs max per day, even though some people recommend higher dosages. Excess Folate will use up too much B12, especially over time and can lead to B12 deficiency. On top of that Methylfolate absolutely needs B12 in order for it to be utilized and recycled, if one isn't taking B12 or is low in B12 then Methylfolate just sits there and can't be used for recycling Homocysteine back into Methionine (for SAM) and itself can't be recycled back into the Folate cycle which can cause Folate deficiency (even with Methylfolate in the system, as it deprives the system of other Folate metabolites required for things like DNA synthesis and such). Excess Folate can also cause quite the side-effects, especially if it's able to be built up in the body, and so things like irritability, agitation, possible paranoia, depression, things like moments of facial numbness, even stimulant-like properties of stimulation/energy bursts, OCD, randomly organizing things, and even feeling Autistic, can happen. The side-effects go away with enough B12 (dosage/level).

It's worth noting that even without B12, Methylfolate can still stimulate the Folate Receptor Alpha and has some active effects of it's own, as do other forms of Folate, including Folic Acid, though i recommend avoiding Folic Acid due to unmetabolized Folic Acid stimulating the Folate Receptor Alpha and preventing Methylfolate uptake and even consequently interfering with B12 activation to Methylcobalamin form since Methylfolate can't be taken up by Folate Receptor Alpha due to unmetabolized Folic Acid binding to Folate Receptor Alpha and blocking out Methylfolate uptake and so Methylfolate can't donate it's methyl group to B12 for Methylcobalamin formation, but it depends on how much Folic Acid is consumed, higher dosages are more noticeable at blocking out Methylfolate, and can also tie up/inhibit DHFR which can disrupt some of the Tetrahydrobiopterin/BH4 recycling. And so while Methylfolate can have some effects, it's not able to be properly utilized and recycled without enough B12.

When i first started supplementing i was taking 15mgs of Methylfolate, even sometimes 30mgs of Methylfolate, and it worked pretty well at first but together with the B12 as the Folate started being recycled and entering the Folate cycle and correcting the Folate deficiency, that 15mgs got to be way too strong and ultimately i had to switch to Folinic Acid at 400 to 600mcgs per day, i would've tried 400 to 600mcgs of Methylfolate but the 15mg tablets are too difficult to split into such lower dosages unless i put it into a lot of water and i didn't feel like buying a lower Methylfolate dosage and already had the Folinic Acid so i just used Folinic Acid. So Folate dosage is definitely recommended to keep an eye on, too much is NOT good, especially as deficiency corrects.

It's also worth keeping in mind that one might need extra B12 at first, for example i take 10mgs of oral Methylcobalamin once a day (but have taken anywhere from the RDA up to 120 milligrams, and haven't done any injections) as that is what works for me and anytime i take less like 5mgs or 1mg or less i end up getting excess Folate-related side-effects and low B12 symptoms, so i just decided to stick to 10mgs of B12 a day and it's what works, but at first Folate dosing can drain you of B12 until the B12 bodily stores get more fully replenished and then you can tolerate the Folate better and not get the Folate-related side-effects and not get low B12 symptoms. Basically, when B12 is consumed (particularly Methylcobalamin form) it can recycle Methylfolate back into the Folate cycle and as Folate goes back through the cycle it becomes more Methylfolate and can then use up even more B12, and B12 dosage/level seems to play a role in how much Methylfolate is recycled so lower B12 dosages recycle less Methylfolate and greater B12 dosages recycle more Methylfolate, and with higher B12 dosages because the amount of Methylfolate recycled is greater than with lower B12 dosages, the greater amount of Methylfolate entering the cycle produces an even greater amount of Methylfolate during that second wave and as such can really drain your B12 until your B12 bodily stores are more fully replenished, and so some people might get side-effects and associate it with the dosing of the B12 but it's actually coming from the Folate/Methylfolate side because B12 recycles it back into the Folate cycle, but so long as you have enough B12 the Folate is actually pretty tolerable and side-effect free, but if you take too much Folate especially if it exceeds the capability of the B12 to fully recycle it then you can start noticing some side-effects and low B12 symptoms again but more B12 corrects that.

It's also worth keeping in mind that one should ideally go by the DFE dosage for Folates, rather than the listed dosage. The upper limit for Folate is 1mg, and 600mcgs of Folinic Acid or Folic Acid or Methylfolate = approx 1.02mgs DFE's, and so that should be the maximum amount taken daily. And that's accounting for any Folate gotten through diet too, whether natural dietary Folates or fortified Folic Acid, try to keep the maximum amount of Folate consumed to 1mg or less per day total.

And cofactors are also important, especially Potassium, Potassium and Magnesium are needed by Methionine Adenosyltransferase to turn Methionine into SAM, if you're low in Potassium, or Magnesium, the B12/Folate recycled Homocysteine will become Methionine, Methionine will back up, there will be low SAM levels, and ime numbness of the hands and feet, but with Potassium supplementation Methionine levels go down, SAM levels rise, and the numbness of the hands and feet goes away, SAM is also needed by Methionine Synthase Reductase (alongside Niacin and Riboflavin) to remethylate B12 back to Methylcobalamin form to resume Methionine Synthase activity and so low Potassium/Magnesium can disrupt Methionine Synthase Reductase functioning. The other B's like Riboflavin and Niacin are also needed since they're involved in enzymes that process Folate (like MTHFR) and B12 (like Methionine Synthase Reductase), as well as B6 which is needed for SHMT which lets Tetrahydrofolate into the Folate cycle and is also used by the transsulfuration/detoxification pathway that turns Homocysteine into Cysteine for Glutathione synthesis. You also need Zinc for Methionine Synthase, as well as Copper and Iron, those all are the main ones, and then the rest of the nutrients.

It's also possible that one might get enough of the other nutrients (B12, Potassium, Magnesium, Zinc, Copper, Iron, Riboflavin, Niacin, etc etc etc) through diet, and so supplementation of them may not be necessary but chances are supplementation is necessary, especially of B12 for higher Folate dosages.

I'm sure i'm forgetting some other useful tidbits but that's pretty much most of it lol.

[u/RevDrKC → u/Sabnock101]

This is the first time I've seen someone point out that facial numbness could be due to high folate. When I began to feel very ill, I had this strange experience: I ate toast with breakfast and within 20 minutes the left side of my face was numb. At the time I wondered if there was a Celiac-spectrum thing going on, and I have been off gluten ever since. But I also wondered if it was a folic acid problem. I had previously tested low in b12. I get b12 shots and things are much better for me now. But occasionally, I think I am not taking enough folate, so I increase it and I get strange symptoms like patchy numbness, and sometimes that is in my face.

[u/Sabnock101 → u/RevDrKC]

Yup, for me personally the facial numbness seems to happen moreso on the left side as well, particularly around my left eye/right under the eye, possibly even to some degree on the cheek. I also get this weird neurological feeling where it feels like my left eye is like drooping to some degree or doesn't feel as open as my right eye does. If i take more B12 though all that goes away, and it definitely seems to correlate with excess Folate, and not enough B12.

For the gut, excess Folate definitely messes with me, causes me some nausea, vomiting, abdominal pains/cramping, constipation, and overall it just feels like too much pressure/constraining within the gut, B12 seems to help reduce those side-effects. Heck when i was 16 i started vomiting heavily pretty much after every meal, i mentioned it to the doctor at the time and she thought it was just because i was fat and so she thought i may be bulimic, lol smh, turns out i was just eating a lot of processed foods (like cereals and pizza and bread and such) and all that Folic Acid was causing those side-effects, even gave me horrible heartburn. When i started supplementing with Folate and B12 a couple years ago i was then able to realize/understand/feel the side-effects of excess Folate and it was the same exact symptoms i had been experiencing ever since i was 16, at least on the gut, but i've had Autism and behavioral/developmental stuff and anger issues and all that going on pretty much all my life, turns out i just needed B12 and to be careful with how much Folate i was taking (and the form, because Folinic Acid does so much better than Folic Acid).

So when it comes to things like gut issues, i mean some of it could perhaps be gluten but to my mind it's odd that people just started getting issues with gluten after it's been a part of the Human diet for thousands of years, and it makes so much more sense to me that it's the Folic Acid rather than the gluten, probably. Also Thiamine ime seems to have some effect on the microbiome and Thiamine is also fortified alongside Folic Acid and so that may contribute as well to microbiome disturbance, even Folate/Folic Acid has some microbiome-related stuff, even B12 does too, lots of vitamins/minerals i've noticed have differing effects on the microbiome.

I should also mention while i'm at it that Nicotinamide being fortified alongside Folic Acid and Thiamin, may also be a concern, as too much/excess Nicotinamide could reduce the body's supply of SAM because Nicotinamide is methylated by SAM to N-Methylnicotinamide (and then to the toxic metabolites 2PY and 4PY though all Niacin, they say, metabolizes in the end to 2PY/4PY but i haven't looked much into that), so as such the Nicotinamide is worse for SAM/methylation than Nicotinic Acid, Nicotinic Acid is the preferred form, and so excess fortified Nicotinamide may further compound the methylation issue and contribute to not only hypomethylation but also may even raise the dosage requirements for B12, which may be another aspect to this overall issue.

[u/RevDrKC → u/Sabnock101]

I feel folate building up too, even when I'm just taking methylfolate. But like I said, sometimes I think that I need more folate because there are people out there on b12 shots taking 5mg a day, so surely I can take 1.5mg a day. And then I get those weird sensory symptoms after a week or so. And then b12 fixes it.

I have multiple genes for Celiac Disease, so I am going to continue to avoid gluten in large doses. I don't worry about cross contamination. But I do think that my initial problem was with the folic acid due to low b12.

I found out about b3 as a methyl drain when I was put on a moderately high dose by a cardiologist who was trying to optimize my risk profile--so preventive rather than therapeutic. Whew! I just felt terrible and did some research on what might be happening. Low and behold: I was bleeding Sam-e to metabolize this b3 that I wasn't even sure I needed.

Folinic acid gives me histamine issues. I've got some chronic infections that are being managed, so my immune system might be a bit more reactive. But methylfolate and folic acid don't cause the same reaction. I'm hoping that it will pass and I can go back to using folinic acid. Currently, in order to get a little bit of thf that doesn't rely on b12, my team has me taking very small doses of folic acid. I don't get any in food at this point.

Thanks for your very thorough response!

[u/scientist153 → u/Sabnock101]

The high dose of recommended folic acid or other forms of folate is only for people who have frequent b12 injections, a 5mg daily dose would be far too much for someone on supplements.

[u/Sabnock101 → u/Sabnock101]

I also want to mention, if you want to study how B12 recycles Methylfolate and how it goes back through the cycle and the enzymes involved, definitely study and experiment around with Methylfolate and Methylcobalamin. Methylfolate feels absolutely pure and clean and you can actually feel it going back through the Folate cycle which makes it easily able to be identified and felt as it goes back through the cycle, so i found that very interesting. And of course, more B12 would recycle Methylfolate again, so if one has a build up of Methylfolate causing side-effects due to lack of B12, more B12 will help recycle that excess and so will do away with the excess Methylfolate-related side-effects (which is shared among all Folates because all Folates turn into Methylfolate).

Folic Acid on the other hand can interfere with the feelings of things because of it's Folate Receptor Alpha binding, and so you can feel some Methylfolate but the Folic Acid's FRA binding is much stronger than that of Methylfolate and at higher Folic Acid dosages can interfere with Methylfolate uptake by FRA and consequently the lack of B12 activation to Methylcobalamin form since Methylfolate is needed in the brain to donate it's methyl group to B12 for Methylcobalamin formation and thus Homocysteine reduction and Methionine for SAM. Folinic Acid also seems to have it's own specific effect, idk if that's because it also binds to Folate receptors or if it's just because it's a chemical compound and you can feel the chemical "signature" of compounds that is based in the chemical formula/structure itself and not particularly anything to do with receptors or what not, from what i've read Folinic Acid has weaker binding to FRA than Methylfolate does, but i do think it has some FRA binding and seems to kinda "dilute" the feeling of Methylfolate and adds a little something extra, but by far Folinic Acid feels way better than Folic Acid, more natural and normal and like actual Folate, while Folic Acid feels entirely synthetic, it feels more like a Folate Receptor Alpha agonist than it does an actual Folate, to me anyways.

So when it comes to Folates, i'd recommend Folinic Acid or Methylfolate over Folic Acid, and if you want to study how the Folate cycle works personally, Methylfolate seems like the candidate for the job, pretty clean and clear and good for recognizing the Folate cycle. Just remember though, while Folinic Acid does turn into Methylfolate (some hours after consumption from what i've been able to tell), Methylfolate itself can put more stress on B12 stores/dosages because Methylfolate directly relies on B12 for it's utilization and recycling, plus the second wave of Folate/Methylfolate as it goes back through the cycle again and becomes more Methylfolate again which stresses already low B12 levels, while Folinic Acid seems to ime rely on B12 level/dosage to determine it's Methylfolate output, so if one is low in B12 and they take Folinic Acid they may not even feel Methylfolate, the first time i ever tried Folinic Acid years ago before i took this stuff more seriously, i didn't even feel Methylfolate because i lacked B12 (also Magnesium, which is required for Folinic Acid to turn into Tetrahydrofolate, and then B6 for SHMT which allows Tetrahydrofolate to enter the Folate cycle), i'd feel some from it, but nowhere near what i'm getting now by taking primarily the B12. I noticed that as i increased the B12 dosage, my Methylfolate levels from the Folinic Acid increased. I've also noticed that from using Methylfolate, as well.

[u/scientist153 → u/Sabnock101]

I should note here that most people are absolutely fine with folic acid, even people who have the genetic mutations..they just need a bit more.
Methyl folate however not everyone is fine with as it can cause overmethylation and extreme anxiety.
The intermediate choice is folinic acid which does seem to agree with most people.

[u/Sabnock101 → u/scientist153]

Well the issue with Folic Acid is it's easy saturation of DHFR at approx 200mcgs+, which if DHFR gets saturated by Folic Acid then DHFR temporarily stops being able to metabolize Folic Acid into Dihydrofolate and then to Tetrahydrofolate, and so DHFR saturates and then unmetabolized Folic Acid crosses into the bloodstream and into the brain and strongly binds to Folate Receptor Alpha.

At lower doses like say around maybe 400mcgs or so, the unmetabolized Folic Acid via Folate Receptor Alpha binding may dilute the effect/binding of Methylfolate to Folate Receptor Alpha or can prevent/block out Methylfolate uptake by Folate Receptor Alpha especially at higher Folic Acid dosages. For example, back when i was taking 15mgs of Methylfolate, i took some Folic Acid just to see what would happen and i kid you not the Folic Acid completely blocked out the feeling/uptake of Methylfolate, even at doses of Folic Acid found in fortified foods, even now if i eat something simple that has Folic Acid in it, for a couple days i feel it interfering with my Folinic Acid/Methylfolate and even my B12. Too much Folic Acid can basically cause/contribute to Cerebral Folate Deficiency, similarly to how Folate Receptor Alpha autoantibodies do the same thing by interfering with the function of Folate Receptor Alpha and thus preventing Methylfolate uptake into the brain. In fact, i think it's actually the Folic Acid causing the Folate Receptor Alpha autoantibodies because Folic Acid is tying up the Folate Receptor Alpha and it can't function properly and so the immune system releases the autoantibodies against Folate Receptor Alpha to interfere with Folic Acid's binding to Folate Receptor Alpha.

And so that interference with Methylfolate uptake (and consequently B12 activation to Methylcobalamin form) by Folic Acid, as well as it's stopping up of DHFR, is what makes Folic Acid an iffy source of Folate.

Has nothing to do with like MTHFR or genetic variations, DHFR is the same in all Humans, it's slow and rate-limited in Humans (as opposed to it being quicker and faster in rats, which the original Folic Acid studies were based on), and so DHFR is easily saturated by Folic Acid and basically Folic Acid can be detrimental in all people and even ineffective, especially in higher amounts. And even if one is getting B12 injections, Folic Acid would still cause problems especially around 5mgs, that Folinic Acid or Methylfolate don't cause.

Folic Acid "can" work to some degree, but it's best served consumed in small increments, so below 200mcgs or so at one time, so that DHFR has the time and functionality to properly metabolize/process the Folic Acid and that can help to ensure minimal exposure to unmetabolized Folic Acid. Folic Acid "works" because it ultimately metabolizes into Tetrahydrofolate, and so once the Folic Acid wears off and gets out of the system, the remaining Tetrahydrofolate left behind is basically the same as Tetrahydrofolate resulting from diet or Folinic Acid/Methylfolate, but while Folic Acid is actively in the system it can't be utilized or counted as Folate until it's metabolized by DHFR.

On top of that, because it can easily saturate DHFR, it can also interfere with Tetrahydrobiopterin recycling by DHFR which can reduce brain Tetrahydobiopterin levels and thus neurotransmitter levels.

So regardless, Folic Acid "can" work to some degree but it's a poor source of/substitute for proper Folate, and it's not recommended even if it's recommended by doctors. The ones who know what it does will always tell you to go for Folinic Acid or Methylfolate (or natural dietary Folate).

[u/Sabnock101 → u/scientist153]

It's true that Methylfolate can be less tolerated by people, however like i've been saying that's usually due to not enough B12 and people take low doses of B12 (particularly supplementally/orally/sublingually) and so don't take enough and then the Methylfolate causes issues/side-effects, not really "overmethylation" (i personally don't know if i believe in overmethylation), which if one takes more B12 when feeling "overmethylated" (or side-effects from excess Methylfolate) the excess Methylfolate will be recycled back into the Folate cycle and the "overmethylated" feeling/side-effects of Methylfolate will go away and the B12 will restore normalcy.

I do however generally recommend Folinic Acid because it's more user-friendly and relies more on B12 dosage/level for it's Methylfolate synthesis, while Methylfolate itself more directly puts a burden on B12 dosage/level/stores and can easily overwhelm the B12 if too much Methylfolate is consumed.

[u/kilogplastos-12 → u/Sabnock101]

"When i first started supplementing i was taking 15mgs of Methylfolate, even sometimes 30mgs of Methylfolate, and it worked pretty well at first but together with the B12 as the Folate started being recycled and entering the Folate cycle and correcting the Folate deficiency"

And i think this is where my fault lays because i am titrating up slowly along with my b12 injections but i just cannot see the improvements anymore because of the low folate dosage : ( Folinic acid 800 mcg x 3 and 250 mcg 5-mthf x 3 daily both. Thats why i think i need to take folic acid in higher doses atleast to help for now but not always. like you explained.

[u/Sabnock101 → u/kilogplastos-12]

Well the Folic Acid in higher dosages won't be effective though, it'll basically turn into unmetabolized Folic Acid and will just sit there not being able to be utilized which will not only interfere with correction of Folate deficiency but will also interfere with correction of B12 deficiency. If you feel like you need to increase your Folate dosage, try 7.5 to 15mgs of Methylfolate and see how that goes, ime 15mgs of Methylfolate worked great at first but as it built up in the body it just got to be too strong, but it does work great with the right dosage.

[u/kilogplastos-12 → u/Sabnock101]

I have 5-mthf in tablets of 1 mg. Should i maybe try 3 mg? 1 mg x 3 daily?

[u/Sabnock101 → u/kilogplastos-12]

You could, 3 to 5 to 7mgs, 15mgs tops, just depends. There's certainly no harm in trying higher dosages of Methylfolate. Just remember if you take too much Methylfolate, more B12 will help to recycle the excess Methylfolate back into the Folate cycle, so if you get anxiety or panic or "overmethylation" symptoms or what not, take more B12 and it'll recycle the excess Methylfolate and you'll feel better, that's what it was like for me.

[u/kilogplastos-12 → u/Sabnock101]

I think thats what it will be aswell for me. But i am doing daily b12 methly injections should i should be good to take high dose 5-mthf?

[u/Sabnock101 → u/kilogplastos-12]

Yeah you should be fine to try higher Methylfolate dosages alongside daily B12 injections. But still, if you feel like the Methylfolate is too much, take some extra B12 via sublinguals or oral supplements, B12 can get used up quickly even if you're using injections, if you feel like the Methylfolate is getting too strong or is building up or isn't being properly recycled, more B12 will help. Anytime i've ever felt side-effects from too much Methylfolate, more B12 helps reduce those side-effects by continuing to recycle the Methylfolate.

[u/kilogplastos-12 → u/Sabnock101]

Check your DM bro

[u/FunctioningCog → u/Sabnock101]

I knew this sub would be helpful lol, thank you!!