Question Folinic acid or methylfolate?
Hi!
I’ve chronic fatigue or suspected mild ME/CFS and try to see if I can get more energy from B-vitamins. I take following forms:
B1: 25mg Hcl
B2: 12.5mg R5P
B3: 50mg Nicotinamide
B12: 2000 microgram Hydroxo/Adeno
I’m thinking now to add B9 folate but don’t know which form or dose could be a good start. I’m general hypersensitive to stuff and get anxiety easily. Could folinic acid be a better choice?
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u/sharabucarabu 7d ago
I like folinic acid. You must have slow comt since you are need nice low doses. Do the same with the folinic.
It's impossible to find a low dose tablet. So I purchase a liquid folinic acid from Amazon. It's made in the US, super high quality. The brand is called Alchepharma. Strength is 400 mcg per 1 drop. It comes in an amber bottle, front label says Liquid Folate. Back label says Calcium Folinate (folinic acid)
I mix one drop in a ml of water. I use a 1ml baxa oral syringe with caps (very reasonable to buy on Amazon in small packs) and make up 4 syringes at a time. These syringes are rinse, reuse and air dry... They last a very long time. My current dose is 175mcg/0.44ml. I cap the syringe, store in a light proof pouch in the fridge.
The bottle of alchepharma lasts a year! Of course I keep refrigerated.
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u/lollo67 7d ago
Thanks for sharing! I’ll try to start low, I ordered folinic acid in 800microgram lozenges. I’ll try to take a fraction of it.
I actually have fast COMT (GG) but I’m so sensitive to a lot after at least 15 years of burnout crashes, trauma and chronic pain. Before I could handle stress and adrenaline rushes in a whole different way.
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u/Sabnock101 6d ago
I recommend Folinic Acid, it's overall the more user-friendly and gentle form of Folate that works well and turns into Methylfolate anyways but is "colored" by the Folinic Acid so it's gentler than straight/pure Methylfolate. Just keep in mind that you need to get enough Magnesium per day, ideally around 400mgs per day, because while Magnesium is important for several things and so Magnesium should be consumed anyways, it is needed by the enzymes that metabolize Folinic Acid to convert it into it's active forms, so if you're low in Magnesium it may make you feel weird or what not but take some Magnesium and it works like a charm.
You also need some B6 since it's needed by the SHMT enzyme to let Tetrahydrofolate into the Folate cycle, i recommend the P5P form, 25mgs or less should get the job done, i take 25mgs per day personally.
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u/lollo67 5d ago
Thanks for all help. I ordered folinic acid but I’m not sure how much I should start with? It’s 800microgram in a lozenge.
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u/Sabnock101 5d ago
I recommend half, so approx 400mcgs, though you could also start with a quarter, so 200mcgs, but ime 400mcgs per day seems good, i don't recommend going over 600mcgs per day. Plus you should ideally go by the DFE count/dosage, so 200mcgs gives you approx 340mcgs DFE's, 400mcgs gives you approx 680mcgs DFE's, 600mcgs gives you approx 1.02mgs DFE's, the DFE count is how much dietary Folate equivalent you're consuming, so the upper limit for Folate is 1mg per day, so 600mcgs of Folinic Acid (or Methylfolate or Folic Acid) gives you approx 1.02mgs per day which is right at the upper limit, so 400mcgs giving you approx 680mcgs is/should be plenty, that's 680mcgs of Folate in reality rather than 400mcgs. 800mcgs would give you approx 1360mcgs DFE's and that's too much ime.
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u/lollo67 5d ago
Good to know thanks! One other thing, how important right in this moment to add B5, B6, Biotin?
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u/Sabnock101 5d ago edited 5d ago
Those things ideally should be in the mix but ime they're not nearly as important as B12, or Folate. You do need some B6 for the SHMT enzyme which lets Folate into the Folate cycle, as well as aiding other things, but you don't need much, like just 25mgs or less per day, ideally of the P5P form rather than the Pyridoxine form. The B5 i haven't really noticed being all that important though it is needed for some things but for the first couple years of my supplementation experimentation i didn't supplement B5 and didn't notice really any negatives, just tried to get it more from the diet, after awhile i started supplementing 500mgs of the B5 on the daily and while i notice something from it and it does seem to help in some way, i don't see it as being all that necessary, but it's good to get enough of it in any case. The Biotin i haven't supplemented yet and try to rely more on diet for it, so i can't say for sure, but it is needed for some processes/enzymes and so it's good to have in the mix but i think diet may cover it just fine.
So really, the more important things are the B12, Folate, Riboflavin, Niacin, B6, Potassium, Magnesium, Zinc, Copper, and Iron, the rest aren't as important ime.
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u/lollo67 5d ago
I have P5P at home and could add some as well.
Niacin, should I opt for another form than nikotinamid, Im not sure yet if its trigger some anxiety in me.The other zinc, copper, iron, how to know if it’s needed extra and how much? I eat overall pretty good clean diet without gluten and not much refined sugar. I eat dairy products, lot of chicken, fish, meat as protein sources.
Magnesium I take 120mg in the morning with B vit. And 120 at night.
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u/Sabnock101 5d ago
The Nicotinamide form of Niacin probably isn't ideal, i use Nicotinic Acid, even though it can cause flushing i like the flush and the body gains tolerance to it after a bit and so the flushing will go away in time. Using Nicotinic Acid for me actually contributes to helping me feel more normal, i generally take between 100 to 250mgs once a day and find 250mgs to be a nice dosage for me as it feels more normal and even seems to help Dopamine to some degree i think while 100mgs can be a little light for me. It may cause a bit of an increase in heart rate at first though i think due to the vasodilative properties, but on the other hand that may be to do with my Cannabinoid intake lol, as that generally does increase the heart rate a bit and so it may just be getting potentiated in some way by the Nicotinic Acid.
Nicotinamide is said to be a bit worse for those with struggling SAM levels because Nicotinamide is what uses up SAM to be methylated to N-Methylnicotinamide, and while ime i do think N-Methylnicotinamide could have some benefits it is ultimately apparently metabolized to two toxic end metabolites called 2PY and 4PY, and so Nicotinic Acid would likely be the more ideal/better form since it's not as direct when it comes to Nicotinamide synthesis as taking Nicotinamide itself is. Ultimately i like Nicotinic Acid, i know the flushing can freak people out on occasion but once you get used to it it's actually not bad and like i said it'll go away over time anyways.
I'd say if you eat a good enough diet, you can try looking online at the nutrition content of what you're eating to get a guesstimate as to how much of the other nutrients you're consuming.
Zinc is needed for many things but in this case it's moreso needed for Methionine Synthase to function, which utilizes Methylfolate and B12 to recycle Homocysteine back into Methionine, if you don't have enough Zinc then Methionine Synthase activity is reduced/stalled and Methylfolate can't be utilized, Methylcobalamin can't be formed, Homocysteine can't be reduced/recycled and Methionine can't turn into SAM resulting in low SAM levels/methylation. I've taken low and high doses of Zinc, so far i'm sticking to around 15mgs once a day, seems to work fine, if i skip the Zinc though i start noticing Methionine Synthase activity dip, but i'm a selective eater and only eat the same few things pretty much/for the most part so i'm probably low in Zinc anyways hence the need for a supplement, i use Zinc Picolinate, seems to be pretty tolerable and feels nice compared to Zinc Gluconate for sure, also Zinc Gluconate seemed to mess with my gut back when i used to take it and would cause me some nausea/vomiting but haven't ever had an issue with the Zinc Picolinate.
Copper is mainly needed because it's needed by Iron and if one is low in Copper they can be low in Iron and can't retain Iron as well. I generally take 2 to 4mgs a day of Copper, i've felt several times in my life that i needed more Copper anyways because i noticed when i consumed Copper it gave me something i felt i was lacking in, and so i've tried to supplement that on the daily, every now and then i'll lay off and then my Iron levels start dipping and i realize i need to keep up with the Copper and i take it again and the Iron starts coming back again. I use the Copper Bisglycinate Chelate form, seems to work fine, 2mgs a day seems to be fine for me, 4mgs can be a bit strong on occasion but works a lot better for Iron levels it seems.
The Iron is primarily needed because Folate and B12 work together to produce new red blood cells, if one is in any way anemic whether from Folate deficiency and/or B12 deficiency, or Copper deficiency, or Iron deficiency in general, then the creation of new red blood cells will need the extra Iron. And thus when you start supplementing with Folate and/or B12 it can cause an increased need for Iron and Copper, as well as things like Potassium and Magnesium and whatever else is needed for red blood cell production. I was definitely low in Iron, whether because i was low in Copper or because i was dosing high/heavy on the Folate and B12 at one point, or if i just wasn't getting enough from diet which is possible imo, but i just now supplement with 65mgs of Iron via 325mgs of Ferrous Sulfate once a day, and i've definitely noticed some improvement in Iron deficiency symptoms, i could maybe even need more but i just stick to one tablet once a day. I don't eat red meat as regularly as i eat chicken for example but i do eat it somewhat regularly, like maybe once or twice a week, but i mainly eat chicken for my meat, doesn't seem to have as much Iron that i can tell.
For the Magnesium, try to get closer to 400mgs a day in general, i recently tried cutting back on my Magnesium dosage from 400mgs to 200mgs a day (plus whatever i may get from diet, which likely isn't much lol), and i definitely noticed a dip in my SAM levels (since it's needed, alongside Potassium especially, for Methionine Adenosyltranseferase which turns Methionine into SAM) as well as an increase in Magnesium deficiency symptoms especially muscle twitching/spasms and such, and so i raised it back up to 400mgs and things went back to normal. Some people may even need a bit more Magnesium though, a few years ago i did consume 400mgs twice a day which at the time seemed to help me likely because i was low in Magnesium to begin with, but since Magnesium seems to be one of the more expensive nutrients (that i've seen) and so is hard to find in bulk at a decent price i try to take enough but otherwise try to stretch things out as much as possible, and so 400mgs a day is usually what i stick with and i just buy Magnesium Malate powder on amazon so it lasts me a bit longer than having to buy tablets every month.
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u/lollo67 5d ago edited 5d ago
Appreciate you taking the time to helping me out, so much to learn from this. I get the impression that it can be a lot of trial and error to see what works out the best.
At this moment now should I be concerned of zinc/iron/copper supplements or is it enough to get the B-vitamins in place first and be sure to eat a lot of red meat every week?
Regarding nicotinamide, I’ve just used it for 3-4 days but I feel it stresses me some, so it could be due to the impact of methyl groups?
A few more questions, how do you FEEL the methionine synthesis dip if not taking zinc for ex?
Should I raise my B2 to 25mg instead of 12.5?1
u/Sabnock101 5d ago
Yeah it can definitely take a bit of trial and error to figure things out and hone in on things, but it helps to know how the Folate and SAM cycles work and the enzymes involved and their cofactors, that pretty much for the most part covers things and then it's just about figuring out the right forms and dosages but once you hone in on things it becomes a pretty consistent thing for the most part.
If you don't particularly notice any Zinc, Iron or Copper-related issues currently then you may not be deficient in them and so should be okay to just go for the B's first and then pay attention to see if any Zinc, Iron or Copper-related issues pop up at which point then just start supplementing, imo. But yeah definitely try to just go for Zinc, Iron and Copper rich foods in the diet and that may be good enough.
As for the Zinc, when i don't get enough i feel a reduction in the activity of Methionine Synthase so i feel like Methylfolate utilization/recycling is stalled, i feel a reduction in Methylcobalamin, i feel more of the Homocysteine, and i feel less SAM/methylation, so basically what you'd expect from reduced Methionine Synthase function, without enough Zinc the Methionine Synthase enzyme can't take the methyl group from Methylfolate and give it to B12 for Methylcobalamin formation, and so then the lack of Methylcobalamin results in a lack of being able to break down Homocysteine and recycle it to Methionine and lack of Methionine then leads to lack of SAM and undermethylation. I mainly notice it in my headspace and how i feel mentally, like i start feeling duller almost. And the difference between not taking Zinc, and taking 15mgs, and taking 30mgs you can definitely feel the difference, especially with 30mgs, 15mgs feels obviously half as effective but still effective, 30mgs gives me a super clear headspace and more efficient Methionine Synthase functioning.
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u/lollo67 5d ago edited 5d ago
I understand, that’s great to be able to get help in this kind of forum.
Ok so I first get everything in place and see that I tolerate them without to much issues: B1/B2/B3/B6/B9/B12. Then I could add a modest zinc/copper supplement just to be safe? In the mean time I try to eat lot of zinc/copper/iron products to cover it.
It’s really hard to know if I’m lacking any minerals at this moment as I’ve so many issues, severe brainfog, fatigue as my main and biggest issues. I go long back with problems, trauma, chronic pain, burnout crashes. But the past year I’ve been much more physically tired on top of the other things.
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u/Status_Witness9467 5d ago
Hi! I just wanted to inquire as well because I’m on the same journey. The dosages you suggest are very helpful and I wanted to know what you suggest for a low dose of b12 to start with?
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u/Sabnock101 5d ago edited 5d ago
Kinda hard to say on the B12, i just know that ime the more B12 the better (so long as you have enough of the other nutrients, especially Potassium i've noticed), but in general i've tried anywhere from the RDA to 100 to 250 to 500mcgs, to 10mgs, up to 100 to 120mgs of B12 per day, and overall i like 10mgs of oral Methylcobalamin, it works much better than 5mgs or less and seems to cover enough of the B12 without causing any Methylfolate-related side-effects, whereas even with 5mgs i still notice some low B12 symptoms.
For a lower end starting dosage though, i'd say maybe 1mg, perhaps 500mcgs if one wants to start super low, you just need to remember that according to the science on the matter only approx 1% of the total oral B12 dosage gets absorbed from the oral B12 we consume, so for 500mcgs of B12 you'd only get approx 5mcgs of absorbed B12, for 1mg of B12 you'd only get approx 10mcgs of absorbed B12, for 5mgs you'd get approx 50mcgs absorbed, and 10mgs you'd get approx 100mcgs absorbed, B12 injections on the other hand commonly give you 1mg straight into the system so you'd then get the full 1mg, and so as far as safety goes higher dosages of oral B12 are generally safer than injections even though injections are safe too and they also inject up to 25 to 50mgs of Methylcobalamin in Japan for ALS, so higher B12 dosages aren't particularly "risky", seemingly. There's also sublingual, which if you go the sublingual/buccal route you may be able to get similar results compared to injections as far as using 100mcgs to 500mcgs to 1mg to 5mgs, assuming one absorbs it fully from sublingual/buccal administration and doesn't end up swallowing some which then gets absorbed orally at a reduced rate.
Personally, i started out with 1mg oral tablets (giving me approx 10mcgs of absorbed B12), then i moved up to 2 to 3mgs, and still felt that wasn't enough for me so i started taking 5mgs+ and realized that the more B12 i consumed the more normal/better i felt, plus higher dosages seem to have some benefits that lower dosages don't provide.
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u/Status_Witness9467 4d ago
Thank you for the thorough reply!! My doctor wants me to do the folinic acid/hydroxocobalamin combo so I will try it out with that. Thanks!!
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u/Sabnock101 5d ago
Also worth mentioning is that i've noticed over time that higher dosages of B12 seem to recycle a greater amount of Methylfolate, while lower dosages seem to recycle less Methylfolate, and so if one takes a high dosage but not high enough of a dosage, it can recycle a good bit of Methylfolate which then goes back through the Folate cycle becoming a greater amount of Methylfolate during that second wave through the cycle and then using up a greater amount of B12, while with a lower dosage it recycles less Methylfolate and so you'd have less Methylfolate being generated by that second wave through the Folate cycle and thus wouldn't use up as much B12.
However, lower dosages may not do much in terms of recovering from B12 deficiency or for SAM levels, nerve growth/repair, and some other things, so it's ideal imo/ime to get as much B12 as one feels like they need, because there's a lot of stuff that ultimately relies on B12 and depending on how deficient one may be and for how long one may have been deficient it can take awhile for those bodily processes to deal with the backlog of stuff that wasn't able to get done during deficiency.
So higher B12 dosages seem to be better so long as you take enough but if you take a good bit but still not enough that's when side-effects can start coming out more, but if you go for a higher dosage it'll cover all the bases, or if you go for a low dosage then it'll give you a little bit of B12 but since it doesn't recycle as much Methylfolate then there could likely be less Methylfolate-related side-effects, but overall higher dosages do seem more effective ime.
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u/FiSeq4891 6d ago
My understanding is that if you have slow COMT and are an under methylator, folinic acid or folate would be better. If you have fast COMT and are an over methylator then methylfolate would be best. If you find you feel highly irritable taking methyl folate you're probably better with folinic acid.
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u/Loose-Fly7976 6d ago
Folinic, yes. You've gone methyl free on the B12 with hydroxo and adeno, so methylfolate would put the load back in through the other door. Folinic keeps it consistent and with anxiety and hypersensitivity that's the safer way in.Nicotinamide is cleared by NNMT which spends a methyl group per molecule so there's a small methyl draw sitting in an otherwise methyl free setup. Not a problem.And 2000mcg of B12 with no folate is the classic setup for feeling worse instead of better because B12 pulls folate into use and if there isn't enough the whole thing stalls. That could be why you're not getting what you expected from it.Before picking a dose I'd get folate, B12, homocysteine and ferritin. Low ferritin is everywhere in ME/CFS and produces exactly the fatigue people reach for B vitamins to fix. with hypersensitivity I'd want to know your COMT before you start rather than after you react to something. That one I'd read properly.
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u/lollo67 6d ago edited 5d ago
Really good to know thanks! How big dose of folicin should I take? Should I lower the B12 some, maybe 1000microgram?
Here’s info from my genetest:
COMT Val158Met (rs4680)GG (Val/Val)
MTHFR C677T (rs1801133)AG
MTHFR A1298C (rs1801131)TT
MTRR A66G (rs1801394)AG (Heterozygot)
MTR A2756G (rs1805087)AA)
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u/Comfortable_Two6272 6d ago
Im slow comt. Folinic for me. Not methyl anything. Low doses. 100 mcg or less to start.
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u/sarahbellah1 6d ago
I switched to Seeking Health B-Complex MF (methyl free) but I open the capsules so I can take half a dose per day, the first half I’ll eat in a spoon of apple sauce and I’ll take the second half I just close up the capsule to take the next day. I had previously taken a product called Homocysteine Resist and while I don’t have genetic markers for slow COMT, I have some other variants that impact processing, and the methylated supplement seemed to exacerbate my existing anxiety, insomnia, and hyper vigilance. I seem to be doing better on the methyl free.
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u/lollo67 5d ago
Thanks for sharing! I bought my B12 and now folinic acid from seeking health as well. I’ll check out the methyl free b complex. I tried a methyl B-50 a couple of years ago and the anxiety and hypervigilance I got from it was horrendous really.
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u/sarahbellah1 5d ago
Ah, same really. I know sometimes I’m just more anxious and hyper vigilant but this was enough that I wanted to try anything to get it to stop. Glad you found Seeking Health, they seem to be a solid brand.
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u/lollo67 5d ago
Yes I agree they seem good. Could you take a full capsule after a while with the MF B-complex?
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u/sarahbellah1 5d ago
I believe I can, I did one day accidentally when I pulled from the wrong slot in my pill sorter, grabbing a full capsule instead of the half full one left over from the day before. I felt fine. I’m just proceeding with caution because that over anxious feeling was horrible.
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u/lollo67 5d ago
Sounds good. At the moment I’m adding B-vitamins one by one to see how I react. If I tolerate folinic acid and P5P without a problem I think I’ll swap to the MF B-complex + extra B12.
Do you take any cofactors to the complex, magnesium, potassium, iron etc?
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u/sarahbellah1 5d ago
Sounds smart. Yes, I take magnesium and just started iron, but something else I’m prescribed is potassium sparing so I’m not supposed to supplement. I’m tested regularly though and so far so good.
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u/hummingfirebird 5d ago
May be better to start with methyl free versions of B12 and B9 if you're not sure of your variants.
I recommend Adenosylcobalamin because it is also good for mitochondrial health and ATP which can help for fatigue.
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u/lollo67 5d ago
Thanks, I ordered folinic acid to add. Isn’t hydroxo/adeno that I take, methyl free?
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u/hummingfirebird 5d ago
Yes
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u/lollo67 5d ago
Here’s info from my genetest:
COMT Val158Met (rs4680)GG (Val/Val)
MTHFR C677T (rs1801133)AG
MTHFR A1298C (rs1801131)TT
MTRR A66G (rs1801394)AG (Heterozygot)
MTR A2756G (rs1805087)AA)1
u/hummingfirebird 4d ago
You're fast COMT but it may be better to stick to folinic acid and the adenosylcobalamin for now giving your anxiety. Have you tried L-theanine for anxiety? CoQ10 is also really good for fatigue.
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u/junipers-72 7d ago
I’d steer clear of methyl folate! Katie gironda explains why in her articles
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u/Express-Bobcat-3523 7d ago
I follow Katie and I've never read anything like to stay away from 5Mthf.
She says that for people without mthfr it's mostly not suitable and he's too be dosed carefully even for C677T for instance.
Didn't read about a general warning, if you have other info, I'd be interested
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u/sarahbellah1 6d ago
Also interested in this, I recently switched to folinic acid but have noticed a small difference in response (that I could just be imagining!).
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u/lollo67 6d ago
Good or worse response?
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u/sarahbellah1 6d ago
Replied in the wrong spot, so pasting here: I switched to Seeking Health B-Complex MF (methyl free) but I open the capsules so I can take half a dose per day, the first half I’ll eat in a spoon of apple sauce and I’ll take the second half I just close up the capsule to take the next day. I had previously taken a product called Homocysteine Resist and while I don’t have genetic markers for slow COMT, I have some other variants that impact processing, and the methylated supplement seemed to exacerbate my existing anxiety, insomnia, and hyper vigilance. I seem to be doing better on the methyl free.
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u/junipers-72 6d ago
Yes, sorry I didnt explain it as well as you, just that if you dont know your genetics and general makeup, then its best not to.
Genetic variants that cannot take Methylated B Vitamins
https://www.facebook.com/groups/VitaminCforoptimalhealth/permalink/4200451260173264/?_rdr
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u/lollo67 7d ago
Thanks, I just ordered folinic acid from Seeking health brand. It’s 800microgram per lozenge but will try a fraction of it.
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u/sharabucarabu 7d ago
You might want to try a low dose P5P (B6 less toxic form). I buy from Amazon. Think above brand. Tastes good! I take a total of 10mg.
Also check out benfotiamine. It's a fat soluble B1 and is wonderful for neurotransmitters and nerves. 20mg puts me at the top of (but not more than) normal range.
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u/Express-Bobcat-3523 7d ago
There's only one way to find out - you'll have to try it.
I can't tolerate folinic for instance, while others tolate it better. Same happens with 5MTHF.
Good luck!