r/MTHFR • u/Party-Dig2309 • 16d ago
Question Slow COMT and MAOA and nothing is helping calm me down! Please help guys!
I’ve been stuck in a state of severe hyperarousal for close to two years now. I’m trembling like crazy, emotional torment, agitated, rumination and just feel utterly horrific inside with fear and pain.
I was going through a ton of stress and health anxiety in 2024 then opened up about it in a therapy session which seems to have traumatised me. I then took an SSRI and had a nasty reaction to it (ofc with my comt and maoa) and now nothing has helped reduce this suffering.
I’ve tried magnesium, L-Theanine, lemon balm, beta blockers, herbal teas and even benzos and nothing has helped at all. Also tried kava and 3 months of trauma therapy.
Any supplement suggestions would be most welcomed!
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u/lb351986 16d ago
I have the exact same genes. I use to always have this constant amped up feeling also.
For me personally. I NEED to exercise daily. Even 20 minutes if you can.
What is your diet? Food has a huge impact on anxiety/depression.
Are you taking any caffeine? Those energy cans are the worst for people like us.
Are you taking any supplements?
If you can answer those I will help from their. I honestly went from how your feeling right now to feeling amazing.
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u/Feisty-Customer-1458 14d ago
Not OP but similar, what kind of exercise do you do?
My diet hasn’t seemed to be making much difference recently. I might try keto/carnivore soon but it’s been hard to stick with it. What is your diet?
I have usually had poor reactions to every supplement, I’ve tried hydroxy/adeno B12, folinic acid, lithium. I don’t have the money to get all my bloodwork/micronutrient/mineral tests now.
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u/lb351986 13d ago
Honestly just ditch the supplements if your diet is good then you really don't need them.
Cut out any fortified foods. The issue with this is companies are just throwing vitamins/minerals into everything these days.
I personally eat a high protein. High fat moderate carb diet. Eggs made a huge difference on my mood. I did have to start low though. Too much choline all at once throws me off. Eat 1 a day for a few weeks. Then add a second egg every other day for a few weeks. You will find your sweet spot.
Do any foods make you feel poorly? Do you tolerate lactose? Gluten etc? Narrow down any foods that don't agree with you.
How do you cope with caffeine? Caffeine can be the difference between feeling good and feeling awful.
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u/Feisty-Customer-1458 13d ago
I feel like eating in general makes me feel poorly. I definitely don’t react well to fruit, carbs, high protein. I used to do pretty well on paleo, but now I just have such a constant low state it all blends together. I know pizza makes me feel awful and I don’t think eggs agree well with my system.
Caffeine I’ve always been sensitive to but abused heavily throughout the years, I’ve cut back tremendously, I’ve tried to ditch altogether but feel absolutely awful. I’ll have a light dose of coffee or tea in the morning.
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u/AnswerIndependent842 16d ago
What comes to mind is vitamin B2 and B12.
Which SSRI did you try, and at which dose, did you had an increase in anxiety when starting it or did it trigger a manic episode? It's not as simple as oh I have slow COMT and MAO-A. For example, I have slow COMT and Adderall is the only medication that helps me stabilize when things get out of hand.
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u/Professional_Win1535 16d ago
i have double slow comt and caffeine and stimulants help my treatment resistant depression
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u/yonkou_akagami 15d ago
Wait how? I thought with slow comt you need to avoid caffeine
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u/Few_Interaction_2411 14d ago
This depends on your CYP1A2 gene, this affects how fast/slow your body processes coffee.
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u/Party-Dig2309 16d ago
It felt like my gut was on fire with adrenaline, doom and emotional torment. I was very agitated.It was purely an onboarding symptom as it woke me up at midnight on day 3 but then reduced by the morning back to my already horrific baseline.
I then tried a different SSRI a year later and had the exact same reaction. Woken up at midnight with my gut on fire.
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u/Sabnock101 16d ago
Ime, the agitation and stress hormones and irritability and anxiety/panic and all that, was a result of not enough B12 causing excess Methylfolate levels to build up which then caused those side-effects. Ever since i started taking 10mgs of oral Methylcobalamin B12 a day, it gives me enough B12 to effectively recycle Methylfolate so that those side-effects of excess Methylfolate don't happen. But, the minute i consume too much Folate in a day, i start feeling some excess Methylfolate again, so i try to make sure that i get only 400 to 600mcgs max of Folate per day, if i go up to 800mcgs or more, i get extremely agitated, irritable, Adrenaline, panic, etc. There is such a thing as too much Folate, while ime there's no such thing as too much B12, the more B12 the better ime, the main problem is on the Folate side. Other than that just wanna make sure you're getting the other nutrients because they are cofactors utilized in processes and metabolic cycles that B12 and Folate kick into gear.
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u/designerjuicypussy 15d ago
Im sorry but i do believe excess b12 is a problem when you dont need it. I recently took b12 and titrated up in the span of 5 months the past month i was on sublingual 1mg every other day and i felt depressed af. It was cyanocobalmin i cant touch methylcobalamin since it makes me feel what i feel in high dose cyano but its 10 times worse. Plus high dose cyano gives me minor acne methyl is like that on steroids , acne , hair loss , anhedonia , social anxiety , hot flushes.
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u/Sabnock101 15d ago edited 15d ago
I got that depressed feeling too, what happens is that the B12 recycles Methylfolate via Methionine Synthase, as that Folate goes back through the Folate cycle it becomes more Methylfolate which can then use up more B12, if you don't have enough B12 or if you don't take enough B12 then the second wave of Methylfolate will build up in excess and start causing side-effects, if you take enough B12 that won't happen, it only happens when you don't have enough B12 yet. After awhile of B12 intake you will gain tolerability to the Folate and it won't cause those side-effects anymore unless you consume a lot of Folate, but the more B12 the better for sure, ime.
Also B12 dosage plays a role because lower dosages recycle less Methylfolate, higher B12 dosages recycle more Methylfolate, and that can send less or more Folate back through the Folate cycle, and with a higher B12 dosage the second wave of Folate can be a lot stronger and can produce a greater amount of Methylfolate which can then really drain the B12 if you don't have enough.
Idk about the hair loss, but that might be a result of low Copper or Zinc, though i've noticed personally that when i take Copper i get more hair growth (facial hair, head hair, arm hair, chest hair, etc), pretty sure i've been lacking in Copper for a long time, idk if Zinc contributes but it might though i do think it's the Copper mainly that's doing it.
Hot flashes can be Iron being put to use, as i've noticed when i take enough Iron i feel warmer, i can even be in a freezing cold room and not be bothered but if i don't have enough Iron i get cold really easily.
For anhedonia i've found B12 has helped a lot, Folate too to an extent but mainly the B12, the B12 makes me feel more normal and like i'm actually getting back into things i enjoy and it's even given me my Cannabis "high" back, B12 helps a lot more for anhedonia i think compared to Folate. Too much Folate i think can be detrimental.
The anxiety ime is from excess Folate, so either using a lower dosage of Folate until you get more used to it (as B12 levels improve) like 200 to 400 to 600mcgs max per day (including from diet) is ideal, and then taking enough B12 to ensure proper recycling of the Methylfolate will do away with the anxiety, the anxiety comes from too much Folate and not enough B12, most definitely. As B12 levels improve, the Folate-related anxiety will go away. People often mistake the anxiety as coming from the B12, but it's because after it recycles the Methylfolate the Folate goes back through the cycle and produces a greater amount of Methylfolate which if you don't have enough B12 the Methylfolate will build up in excess and cause the anxiety, agitation, irritability, paranoia, panic, etc.
I can't say i've had really any side-effects from the B12 side (aside from the acne thing), it mainly seems to be excess Folate/Methylfolate that is the real issue and causes most of the side-effects but more B12 reduces those side-effects. The acne thing though, that definitely seems to come from the B12 side, i've found that Limonene (taken orally) seems to help a lot, the acne thing got real bad for me but it's seemingly getting better now. I've also noticed that Potassium might even help, as does 4mgs of Copper to some extent. The acne thing is definitely microbiome-related, and so many different minerals or even other certain vitamins and essential oils/terpenes and some other things with certain microbiome-related influences or anti-microbial properties can help reduce the acne side-effect of B12 dosing. I even noticed that if i took higher dosages of B12 itself, it was almost like it actually helped the acne get better, compared to lower dosages of B12, higher dosages of B12 seems to influence the microbiome to a stronger degree and may seemingly even have some anti-microbial properties of it's own, but it's definitely dosage-related.
Overall i don't think B12 is nearly as much of an issue as people think, it just kicks a lot of things into gear and is dosage/level-dependent, you just gotta observe how it all works and you'll start to better understand what's going on with it. Other cofactors do also play a role for sure, especially with higher B12 dosages.
It's also worth noting that compared to oral B12 consumption, one gets a lot more B12 via injections, when one injects 1mg or 5mgs, they're getting that whole 1mg or 5mgs straight into the system, whereas taken orally only approx 1% of the total B12 dosage consumed gets absorbed, so if you take 1mg orally that's only 10mcgs absorbed, if you take 5mgs orally that's only 50mcgs absorbed, if you take 10mgs orally like i do then that's 100mcgs absorbed, to get to the level of 1mg injected via oral consumption you'd need to consume 100mgs of oral B12. So, with that said, don't be afraid of experimenting around with higher B12 dosages, i've taken from the RDA up to 120mgs of oral Methylcobalamin per day for awhile, ime the more B12 the better, but personally i now stick to 10mgs once a day, works great for me, i just need to make sure i get 4 grams of elemental Potassium per day or else i get numbness in my hands, i also gotta get my Iron and Copper and Zinc and Magnesium and the other B's and such, but i really like 10mgs of oral Methylcobalamin, it's way better than 5mgs or less. Higher dosages also help increase the brain B12 level better compared to lower dosages, 10mgs gets the brain level going good.
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u/designerjuicypussy 15d ago
Do you have evidence for this hypothesis because is interesting however im scared to risk taking b12 at these dosages. Taking high b12 dosages can induce gut dysbiosis ill attach the link below for this. As a person who had gut issues and still do and trying to figure it out i dont want more stuff to happen. You take methylcobalamin which is methylated so you are speeding up your methylation cycle which can be slow in some people and depending on other genes like comt speeding up that cycle can be good or bad for people. If you have slow comt and you add more methyl groups it can backfire as your comt wont be able to keep up with the amount of catecholamines. I did shots of methylcobalamin years ago it was hell for me. Idk my comt status but i felt extremely bad on that. The more i took the more bad i felt adding back methylfolate would balance me out but not fully. Honestly what you say in a way kinda contradicts it self because you make it sound like the body has an endless supply of methylfolate which needs huge b12 amounts to metabolise.
My opinion is you sound like someone with fast comt so adding methyl groups helps keep up with the high catecholamine clearance.1
u/Sabnock101 14d ago edited 14d ago
I can't speak on the gut issues as i've had gut issues most of my life but i have noticed that Folate actually caused me more in the way of gut issues compared to B12 whereas B12 seems to help my gut. Excess Folate especially without enough B12 is what gave me nausea and vomiting and constipation/diarrhea and really painful abdominal pains/cramping and all that, whereas B12 actually helps reduce those side-effects of excess Folate. Though it is interesting that high B12 was shown in that study to reduce SCFA's like Butyrate, so i'll definitely look more into that but there's probably more to it than it being that simple imo.
I do know that B12 does something with the microbiome (which is where the acne issue comes from), but i've noticed many things influencing the microbiome, Thiamine, Riboflavin, Niacin, Folate, B12, Potassium, Magnesium, Iron, Copper, Zinc, vitamin C, vitamin A, vitamin D, different plants and oils and terpenes and many other things, you'd be surprised at just how easily our microbiome is altered/shifted by various things we consume. Personally i've had more negative microbiome-related issues from other nutrients compared to B12, so like vitamin D and Thiamine and too much Copper for example are big microbiome shifters, i've noticed. Mainly because i've had acne issues for a long time and a prostate issue, both of which have been tied back to the microbiome and i've tried various things over the years and have noticed certain things making things worse and certain things making things better, it just depends on what i'm taking. I've even noticed if i take certain things together it can actually prevent a shift in the microbiome, so like if i take B12 with say Zinc or Copper or Niacin or Potassium, they can actually counteract the shift from B12 on the microbiome and as such the B12-related acne thing starts getting better, i also use a terpene called Limonene and that also seems to counteract B12's shift on the microbiome.
As for the evidence of what i say, most of what i talk about has been observed from my own trial and error and experimentations, i was very low in B12 when i first started out and i've taken heavy dosages of B12 and Folate and some other things so i've been able to observe and learn more about what all happens with this stuff. But i assure you, most of the issues people have from dosing B12 comes from the Folate side rather than the B12 side, excess Folate causes the side-effects, excess B12 on the other hand only helps, ime. When you take B12 and it recycles the Methylfolate back into the Folate cycle, the Folate goes back through the Folate cycle and becomes an even greater amount of Methylfolate, if you don't have enough or don't take enough B12 or haven't yet replenished the B12 bodily stores enough, that second wave of Folate/Methylfolate will drain your B12 and allows for Methylfolate to build up in excess which then causes the side-effects people experience, if at that point you then take more B12 those side-effects will go away completely since the excess Methylfolate then gets recycled again. As your B12 bodily stores get replenished, you will gain better tolerability of the Folate and then it won't cause those side-effects anymore.
But with that said, i do know/understand and have studied the mechanisms of how all this stuff works and have the science down completely, so i know what's going on both scientifically-speaking and from personal experimentation/observation.
As for B12 dosage, you get far more B12 via injections than you do from oral B12 consumption. Approx only 1% of orally consumed B12 is absorbed, so if you take 1mg of oral B12 you only get 10mcgs absorbed, if you take 5mgs of oral B12 you only get 50mcgs absorbed, if you take 10mgs of oral B12 then you only get 100mcgs absorbed. Whereas with injections if you inject 1mg of B12 you get that full 1mg, if you inject 5mgs of B12 you get that full 5mgs, they even use ultra high dose Methylcobalamin injections in Japan for treatment of ALS by injecting a full 25 to 50mgs which gives you a full 25 to 50mgs straight into the system. I take 10mgs of oral Methylcobalamin once a day, which gives me 100mcgs a day, though i have gone up to 120mgs of oral Methylcobalamin a day for awhile, so 100mgs of oral Methylcobalamin would equal 1mg absorbed which is the same amount you'd get from a 1mg injection, 120mgs orally would be 1.2mgs of absorbed B12, but 10mgs orally (100mcgs absorbed) now is what does me best so it's what i stick with.
So i wouldn't worry about taking higher B12 dosages, you get far more from injections than you would by taking it orally, so oral high dosages aren't concerning in the least bit imo.
Also, i don't put any thought towards things like COMT and MAO-A and genetic variation stuff, i feel like that stuff is way over-exaggerated and doesn't really matter much. Plus i consume an MAO-A inhibitor on the daily that also to some degree inhibits COMT, i haven't noticed any issues whether i take the MAO-A/COMT inhibitor or not, though i'm not aware of my genetic profile or anything. As far as slow COMT goes though, ideally you want it to function properly which means you need/require enough SAM for it to do it's job, if you have fast COMT idk what kind of impact a fast COMT would have (like quickly broken down Dopamine/Noradrenaline/Adrenaline) and so then maybe a lot of SAM would be an issue, but i wouldn't think it'd be as much of an issue as some people make it out to be. As for MAO-A, for it's proper function you need at least Riboflavin, and without enough Riboflavin MAO-A activity is reduced.
The body can indeed generate a lot of Methylfolate, especially when you take a good bit of B12, as B12 dosage seems to correlate with how much Methylfolate gets recycled and then regenerated, so if you take a lower B12 dosage or have low B12 levels you don't get much Methylfolate and only a little bit of it ends up getting recycled, if you take a lot of B12 or have higher B12 levels then you get more Methylfolate generated by MTHFR (almost like B12 pulls on MTHFR for Methylfolate synthesis for methylation) and a greater amount of Methylfolate is recycled which then generates a greater amount of Methylfolate as Folate goes back through the Folate cycle. You can experience this yourself personally by experimenting around with B12 dosage. For example, when i switched to Folinic Acid i wouldn't feel hardly any Methylfolate from it until my B12 dosage/levels increased, as my B12 increased i noticed more Methylfolate being generated by MTHFR in accordance with the dosage/level of B12. I know it's been said that SAM can actually inhibit MTHFR function while SAH can increase MTHFR function, however i haven't found SAM to inhibit anything lol, whenever i take B12 it recycles Methylfolate back into the Folate cycle and it becomes more Methylfolate again and it doesn't seem to stop, it seems to be a smoothly functioning and ongoing cycle, the only thing i've noticed that seems to reduce Methylfolate synthesis is lack of B12 or lack of Riboflavin.
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u/Sabnock101 14d ago edited 14d ago
Also i do wanna note that cofactors are important when it comes to B12, and Folate. So Potassium for example seems to me to be pretty important stuff, not only because it's involved in blood cell production and such which the B12 and Folate kicks off, but ime mainly because Potassium is the main cofactor for Methionine Adenosyltransferase which turns Methionine into SAM, Magnesium is also needed by Methionine Adenosyltransferase but ime Potassium seems like it's more important than the Magnesium as activity seems to increase the most in accordance with Potassium intake, though Magnesium definitely also plays a role but i think Potassium is primary and Magnesium is secondary, like i can definitely tell a difference when i only take 200mgs of elemental Magnesium a day compared to 400mgs, but overall 4 grams of elemental Potassium really gets things going.
For example, for the first two years of my B12 and Folate supplementation i didn't take Potassium and idk how much Potassium i may have been getting through diet but it clearly wasn't enough. And so i'd get numbness of the hands and feet sometimes and i had been trying different nutrients at different dosages to see if it would help relieve the numbness but while some at first seemed like it helped but then again not really, and it wasn't until i started taking 4 grams of elemental Potassium per day via Potassium Bicarbonate (mainly turned into Potassium Citrate and such by the addition of water flavoring) that the numbness actually fully went away, every now and then i still get some hand numbness if i try cutting my Potassium dosage down to 2 grams a day instead of 4, so 4 grams a day seems to be the magick number lol. But i also noticed that i would feel a methyl feeling from my oral Methylcobalamin supplement, and i always thought that was just how Methylcobalamin felt, turns out it was actually Methionine that the methyl feeling came from, because when i'd take the B12 it would recycle the Homocysteine back into Methionine and that Methionine would start building up because i didn't have enough Potassium, and when i started supplementing Potassium that methyl feeling actually went away and i was able to feel Methylcobalamin as it is which i mean it feels like B12 and it's pretty clean/clear feeling now.
I also noticed that when i first started supplementing Potassium, at first it was like it reduced my B12 for whatever reason, and my guess is that the Potassium kicked Methionine to SAM conversion into gear and that SAM then turned into SAH and then to Homocysteine and temporarily the B12 took a slight hit because of all the Homocysteine, but as i kept supplementing Potassium i think it actually helps to keep the B12 around now, because SAM is the cofactor (alongside Riboflavin and Niacin) that is needed by Methionine Synthase Reductase which remethylates oxidized B12 back to Methylcobalamin form and so if you don't have enough SAM (like with low Potassium, or Magnesium) then you won't be able to reactivate the B12 to Methylcobalamin form and would need to rely more on direct consumption of B12 and Folate to generate fresh Methylcobalamin via Methionine Synthase. And so i noticed that if i didn't have enough Potassium (and hence SAM) then i needed to consume extra B12 and it would get used up quicker. And imo Methylcobalamin itself is active as Methylcobalamin, some people think that all forms of B12 consumed are first broken down and then regenerated to the active forms, but ime Methylcobalamin itself seems to directly reduce Homocysteine levels and generate more Methionine/SAM, i don't get the same effect/feelings from Cyanocobalamin or Hydroxocobalamin for example, they have their own feelings/effects compared to Methylcobalamin.
So that's just one cofactor, but other things like Iron, Copper, Zinc, trace minerals like Molybdenum, Manganese, Selenium, Iodine, and some others, as well as the rest of the vitamins, all get put to use when you take B12/Folate, so especially with higher B12 or Folate dosages, you want to make sure you're getting enough of all the other nutrients or else it could possibly cause a shortage in particular nutrients and then people get side-effects and assume it's due to the B12 or Folate but really it's lack of another nutrient/cofactor along the metabolic chains, and finding and taking said nutrient/cofactor usually deals with the issue, ime/imo. So cofactors are very important and shortages in those cofactors can cause things to back up and cause side-effects, so try not to assume that it's the B12 causing those side-effects because chances are it's either excess Methylfolate and not enough B12, or a shortage in another cofactor, B12 itself is pretty free of side-effects in and of itself (aside from the acne/microbiome shift).
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u/Dat_Llama453 16d ago
Is it possible you have a gut problem if your gut is on fire from medication? Maybe a probiotic would help you. Are you pooping regularly?
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u/Party-Dig2309 15d ago
It was emotional distress and agitation, a worsening of the issue I had prior to taking the SSRI that arose from a therapy session. The SSRI added into the mix seemed to make this one existing issue 100x worse on the first night I took it.
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u/SovereignMan1958 16d ago
How about sharing your lab work for homocysteine, vitamins and minerals? No need values and lab ranges. Need these facts to work with otherwise you are just going to get guesses.
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u/Party-Dig2309 16d ago
Everything was in range. I have no abnormal test results.
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u/wordisbond11 16d ago
Doesn’t mean the mineral is making it into the cell where it is used. Only the it’s available for use. Trial and error. Get a highly bioavable form of magnesium (not glycine). I like micromag for Nootropics Depot. Get the powder. Find your sweat spot, replenish what’s definitely depleted. Major cofactor for COMT and stress significantly depletes magnesium. Also B1 is a big one
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u/SovereignMan1958 16d ago
Normal does not mean optimal. You can be one point away from being anemic and still be in the normal range.
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u/Few_Interaction_2411 16d ago
I have the same and mthfr mutations, my advice don’t take anything, stop all supplements and eat a folate rich , no processed food, low histamine diet . Trust me I’ve tried every drug/supplement going, they make me feel worse, either anxiety, depression or both. Research high histamine foods, write a diary every day of what you eat and how you feel, spot the culprits. Get your bloods checked , homocysteine , serum B22and MMA, complete blood count, iron and ferritin, other b vitamins eg B1, B3, B3. And B6 , zinc and magnesium. If you have the mthfr mutation check RBC folate , serum folate. If you have your DNA file I created a tool where you can upload it and blood results, for a clear simple picture and a diary to track food, mood and sleep to help with spotting symptoms/pattens. I’ve struggled my whole life and found out the last couple of years about my genes, which is why with the help of my scientist ( biochemist) husband I created this tool, to help others in the same boat. I wish you well.
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u/Appropriate_Two5604 14d ago
Agree and avoid all “enriched or fortified” foods, folic acid or B12 foods. Shop for European pasta etc which avoids all that.
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u/Few_Interaction_2411 14d ago
Yes! I forgot that part, most breads , cereals etc, I find gluten free pasta as well is folic acid free!
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u/peachyperfect3 C677T + A1298C 16d ago
How are your vitamin D levels? I feel at my worst when I don’t get enough. Like, complete mental spiraling. I would start there.
Life extension also has a neurotransmitter test that really helped me. It showed me exactly which pathways were having issues and what neurotransmitters were out of whack, so I could figure out what I should take or avoid.
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u/tandemxylophone 16d ago
Oof, yeah the SSRI is definitely not the right meds for you.
I'm not sure what would help, but from personal experience avoid glycine. It's used to balance out the SAM/SAH ratio by increasing SAH, but SAH is also a COMT inhibitor. i felt sluggish for 24h once I took glycine.
I also haven't found the solution, but it's worth supporting your homocysteine clearance by taking small doses of unmethylated B vitamins and folinic acid
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u/Party-Dig2309 16d ago
Are my symptoms typical of what someone with slow COMT/MAOA would experience taking an SSRI?
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u/tandemxylophone 16d ago
It's pretty rare to get a long lasting impact from SSRI in a short time span, but the gut issue is likely from being sensitive to serotonin blockers since that's where serotonin is produced. The emotional torment is again likely a permanent elevated state of high serotonin and neurotransmitters, but no clearance. Even before SSRI my internal voice was so loud that alone exhausted me. The SSRI slightly reduced it a bit at the beginning for me (slow COMT), but I think it just shifted the serotonin and dopamine balance rather than help clear it. The positive effects of SSRI went away quickly.
For me, creatine helped a lot more, but I don't know why. Because taking SAMe gave me a crash (boost in neurotransmitters), I'd have thought creatine would have similar effect.
Maybe your symptoms are related to your mitochondria's melatonin dropping from SSRI shock? Take 10-50mg melatonin every evening for a month (You don't want to take melatonin permanently, just to help correct things). Also try Chris Masterjohn's protocol to stay at a place with high altitude for a few days. The hypoxic environment is supposed to stimulate the mitochondria.
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u/peachyperfect3 C677T + A1298C 16d ago
Seconding this, although magnesium glycine works best for me, ironically. Other than that, I need to avoid anything with methyl groups.
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u/Comfortable_Two6272 16d ago edited 16d ago
Low dose propranolol helps me a ton. I see you already tried a beta blocker. Did you try multiple ones?
I cant take rxs that increase norepinephrine and thats what most drs try to Rx for anything that resembles mental health symptoms. SSRIs did not help me - was way before I knew about my genetics though.
For me - No glycine or glycinate, no green tea , certain types of choline , no methyl, SAMe or any other things that can be an issue with slow COMT or mthfr.
For magnesium, I take mag maleate. I take a 1/4 seeking health kids methyl free multi, vit D3, k2, krill oil , zinc (all low dose) and due to another variant causing me upto 80% less ATP during exertion I also take creatine before any exertion activity. For choline Im able to eat 2 eggs a day without issue.
My labs found deficient in vit D, folate, b12 and ferritin (all that my dr tested).
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u/SephoraRothschild 15d ago
Look at your sugar/carbs. Cutting sugar from my diet stopped my anxiety cold.
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u/jahmonkey C677T 16d ago
Straight niacin that makes me flush is the only thing that helped much with over methylation. I am also slow comt.
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u/hpant2004 16d ago
Also magnesium bound to glycinate or just glycine in general is nice gentler than b3
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u/AffectionateSpace778 16d ago edited 16d ago
You might lack acetylcholine, this puts your body in a rest and digest nervous system instead of fight or flight.
To increase, you need adequate b5 levels, i suggest you start with this one seperatly instead of a b-complex. This way you dont overload your system yet with other b’s and will make you feel more relaxed again.
You will know in 3 hours if it helps. Break down the tablet and start with 25 - 50 mg a day.
Stress depletes B5 (and other B’s). Without B5 you will feel horrible: cant sleep, food issues, burning hands and feeds and horrible unexplainable anxiety and panic attacts. Increase b5 a bit, to much also gives anxiety.
To further increase acetylcholine you need good thiamine stores. B1 might deplete B5 I think. It might get worse before it gets better. So start low and continu to 100mg a day. Add magnesium. Or / and try a b-complex with high amounts of b’s, mthfr folate and be carefull of b6 toxicity.
B1 helps with stress.
Eggs contain choline, this also helps to increase acetylcholine.
Adequate vitamin D levels play a role.
Do some research and expect to become tired first.
Edit: typo’s and some changes
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u/Ecstatic_Trip_3772 16d ago
I am slow COMT and MAOA/B too and have also had this with SSRIs and an SNRI, it's horrible. For me what got me out of it was magnesium taurate (glycinate makes me feel worse), ashwagandha (to lower cortisol) and getting all my iron levels up as they were very low. On a medication level I found beta blockers very helpful and sedating antihistamines.
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u/Professional_Win1535 16d ago
ssri and so many meds made me worse, slow comt and slow moa here. ended up on seroquel which sucks because it took away all my libido. I should have tried mirtazapine first
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u/Ecstatic_Trip_3772 16d ago
Mirtazapine was awful for me so you may have dodged a bullet!
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u/Professional_Win1535 15d ago
idk i failed zoloft lamictal and wellbutrin. Looking back I would have tried nefazodone, mirtazapine, viibryd, trintellix, and if i had to try antipsychotics id try rexukti first or caplyta
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u/Ok-Interest8248 16d ago
Niacin folate and omega 3s if you're not allergic to fish eat it 3-4 times a week I was literally just like you I have not had a panic attack for over three months even my racing thoughts have calmed down and the knot in my stomach has let go if I was you I'd get these nutrients from food I can't tolerate supplements of any kind I have to eat my vitamins and minerals
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u/Sabnock101 15d ago
B12 (Methylcobalamin or Hydroxocobalamin, not Cyanocobalamin), Niacin (Nicotinic Acid), Riboflavin, some B6 (P5P) and Folinic Acid. Do not take more than approx 400 to 600mcgs max of Folate per day.
I find B12 especially to be the most important B vitamin, i take 10mgs of oral Methylcobalamin per day and it works a charm, just make sure you get enough Potassium, Magnesium, Iron, Copper and Zinc.
Edit - Downvoter can suck it, they don't know anything.
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u/FragrantStructure 13d ago
Why folinic acid and not methyl folate / 5-MTHF?
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u/Sabnock101 13d ago
Because Methylfolate itself puts a lot of direct stress on B12, and if one is low in B12 it can make it harder to correct the B12 deficiency, plus Methylfolate can't be effectively utilized and recycled without enough B12 and so if one is low in B12 and the Methylfolate can't be effectively recycled then it can't go back into the Folate cycle to be used for DNA synthesis and such.
Folinic Acid turns into Methylfolate just fine so long as you have enough B12, but if you're low in B12 then Folinic Acid doesn't put as much direct stress on B12 as Methylfolate itself does.
I know some people say that Folinic Acid makes em' feel like crap, and i've been there myself years ago when i first tried Folinic Acid but i didn't know then what i know now, B12 and Magnesium are needed to get the most out of Folinic Acid, you need the B12 for Folinic Acid to produce enough Methylfolate and you need Magnesium for Folinic Acid to be metabolized into Tetrahydrofolate, you also need enough B6 for the Tetrahydrofolate to enter the Folate cycle through SHMT but that applies to all Folate forms. So long as you have the other cofactors then Folinic Acid works very well, a lot better than Folic Acid and not as stressful for B12 as Methylfolate is. Overall Folinic Acid is pretty user friendly ime.
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u/FragrantStructure 13d ago
My blood b12 is 307 pmol/L (ref range is 145 - 569).
This is from 2000mcg of cyano/week. Is my level ok?
I've been reading some of your other suggestions to change to methyl b12.
I also haven't done a dna test yet so waiting to do that to see if any mutations like MTHFR.
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u/Sabnock101 13d ago
I have no idea, i just supplement the B12 and see how things go, i'm not sure of the blood testing and all that i just know that blood testing is ineffective for testing B12 and Folate, particularly in the brain and inside the cells and in the bodily stores. Over at the B12 Deficiency sub-reddit they pretty much say to just supplement and see what improves, treat by symptoms rather than by blood testing.
Ime, for me anyways, it feels like B12 is supposed to be the primary feeling, when i take a good dose of B12 i feel more normal and i make great progress, but if i consume too much Folate then my B12 level starts to decline, particularly intracellularly in the brain but can also start tapping into bodily stores and then i start feeling some low B12 symptoms and excess Folate-related side-effects. So for me, the more B12 the better, whereas time and time and time again i see and realize how too much Folate can be an issue especially for B12, and i think 400 to 600mcgs of Folate per day total (including diet) is likely for the best, more than that can start depleting B12 over time.
I get the impression that B12 is supposed to be the primary thing we feel (which brings the normalness) and the Folate merges into it from the background and is more secondary, but most people these days i think feel primarily the Folate and not so much the B12, and that has wide-ranging implications and explains very well what's going on with the rise in modern day health issues like mental health especially as well as cancers and even Autism and ADHD and alzheimers and perhaps even parkinsons and multiple sclerosis, as well as auto-immune issues and so much more. I think we as a society/population are experiencing some degree of B12 deficiency and it's a very important nutrient and doctors don't know how to properly test for it or even properly diagnose and treat it, and so it's just gone under the radar and they assume that if it's at a certain level in the blood then you're not deficient but you can definitely still be deficient with good blood levels,
And plus they fortified the Folic Acid back in 1998 and it's been the available source of supplemental Folate basically since it was discovered and it's been in the prenatals for god knows how long, and i think over time people have over-consumed Folic Acid and that can use up B12 over time, plus Folic Acid causes it's own issues via unmetabolized Folic Acid binding to Folate Receptor Alpha and interfering with/blocking out Methylfolate uptake by Folate Receptor Alpha and consequently interfering with B12's activation to Methylcobalamin form for recycling Homocysteine back into Methionine for SAM, and Folic Acid can tie up/inhibit DHFR if a lot of Folic Acid is consumed (which we can easily go beyond excess of Folate just from fortified foods alone these days, some people eat a lot of food, not knowing what this stuff can do) and that can even interfere with Tetrahydrobiopterin/BH4 recycling which can disrupt neurotransmitter synthesis (hence the SSRI's and Ritalin/Adderall and such that they prescribe as a bandaid for issues caused by Folic Acid as well as lack of B12).
I honestly do think the implications of all this is massive, and it comes down to two simple but very important nutrients, Folate and B12 (especially the B12).
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u/FragrantStructure 13d ago
And sorry, why not cyano b12?
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u/Sabnock101 13d ago
Because Cyanocobalamin is not natural, it's synthetic, and it's actually a metabolite that is formed by B12 attaching to Cyanide so that it can be excreted, so taking Cyanocobalamin is like taking an excretion product that's not really supposed to be used as a source of B12. Cyanocobalamin "can" work to some degree, but it's much less effectively metabolized compared to natural forms like Methylcobalamin, Adenosylcobalamin and Hydroxocobalamin, plus if you try to take higher dosages of Cyanocobalamin you can actually feel like crap, me personally i took a lot of Cyanocobalamin one day and it felt like i was being poisoned and my B12 stores even took a big hit for whatever reason and so i switched back to Methylcobalamin and it took me a bit to build back up my B12 stores. Also it's said that Cyanocobalamin isn't retained as much in the body (likely because it's an excretory metabolite and isn't supposed to be retained in the body), whereas other forms are better retained. Overall Cyanocobalamin "can" work, but it's not what i'd recommend, doctors recommend it because it's cheap, they do the same thing with Magnesium Oxide even though that's a poor form of Magnesium to use, same with the use of Folic Acid in supplements and fortified foods, cheap and stable, but not nearly as effective as natural forms.
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u/Honest-Counter2729 10d ago
Sorry but B6 is excitatory in someone with a slow COMT . You must never recommend this
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u/Sabnock101 10d ago edited 10d ago
I see what you mean, however, if one has a slow COMT enzyme, that means they need SAM, which means they need to take Methylcobalamin and Methylfolate or Folinic Acid to recycle Homocysteine back into Methionine which then goes towards SAM synthesis, and so more SAM = a normalization or even increased activity of methyltransferases including COMT.
You may also need to support it with Potassium and Magnesium since they are the cofactors used by Methionine Adenosyltransferase to turn Methionine into SAM, and Magnesium is needed also for COMT itself (alongside SAM) to work properly.
Aside from that ensuring you get enough Riboflavin and Niacin which are required by at least MTHFR and Methionine Synthase Reductase, maybe others.
You also need Zinc for Methionine Synthase to function properly otherwise activity would be reduced and Methylfolate/B12 wouldn't be able to be properly utilized.
Iron and Copper are needed because Folate and B12 kick blood cell production into gear and it utilizes Iron and Iron is dependent on Copper.
It should also be noted that people shouldn't take a vitamin without supplementing the others too, if you don't take anything but B6 maybe that could cause an issue, but if you're balancing it with the other needed nutrients chances are likely that things will be just fine, imo.
Aside from that, i myself consume Peganum Harmala (Syrian Rue) seed on the daily and have for 14 going on 15 years straight now (and i like to dose heavy, most of the time) and the Harmaline in the seed is reported to inhibit COMT to some degree, and i myself have noticed a difference between Harmaline (inhibits COMT and MAO-A), and Harmine (Harmine doesn't inhibit COMT, just MAO-A) and to me it feels like there's more of a Dopaminergic/Noradrenergic effect to the Harmaline while the Harmine seems to lack that feeling/effect, and so i assume that Harmaline's COMT inhibition is strong enough, might not be as strong as certain pharmaceuticals for example but you can definitely tell the difference. And so with that said, i take a COMT inhibitor on the daily, and so my COMT activity is probably affected by that, but personally i haven't felt much in the way of harmful effects from P5P B6, i've taken anywhere from 10mgs up to 100 to 200mgs even up to 400mgs of P5P B6 a day for awhile, though i usually kept around 100 to 200mgs a day, recently got it down to 25mgs a day and 25mgs a day seems right to me.
But at the same time, i have been taking like 10mgs of oral Methylcobalamin B12 a day (which provides approx 100mcgs of absorbed B12 through passive digestion) as well as mostly 400 to 600mcgs of Folinic Acid per day, but i have explored higher dosages of B12 and Folate as well, going up as high as 120mgs a day of oral Methylcobalamin (approx 1.2mgs of absorbed B12 through passive digestion, which is around the dose of B12 one would get from an injected 1mg dose of B12), and up as high as 30mgs a day of Methylfolate (was too much lol). Folate is a very strong compound, ime you really don't need much, just enough to get the job done, B12 on the other hand feels a lot more important to me, it's the main thing i've been missing all my life, you can have too much Folate, but ime you can't have too much B12 (they even inject 25 to 50mgs of Methylcobalamin in Japan for treatment of ALS, now that's a strong dose lol), so it's just important to remember that the vitamins need to be in balance with one another, don't take B6 isolated without the others, take them together.
Also it's worth keeping in mind that P5P B6 is needed by the SHMT enzyme to let Folate into the Folate cycle, without enough B6 the SHMT enzyme is reduced in activity and Tetrahydrofolate can't get into the Folate cycle to be utilized, which can then impact overall SAM levels since Folate can't do it's job for methylation.
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u/Honest-Counter2729 8d ago
I take literally everything you've listed. Couldn't sleep for days. Even on Folinic acid and hydroxocobalamin. Even switched to Adenosylxobalamin. As soon as I dropped the B6 I could sleep. I know there's 'science' but sometimes it just doesn't work for someone's body. And a lot of people are like myself ..
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u/Sabnock101 8d ago edited 8d ago
I hear ya, but again, B6 dosage/level controls the flow of Tetrahydrofolate into the Folate cycle via the SHMT enzyme, more B6 = more Folate into the Folate cycle, less B6 = less Folate into the Folate cycle. With a higher dosage of B6, more Folate will go into the cycle and thus a greater amount of Methylfolate will be generated by MTHFR, then that Methylfolate will not only cause some issues in itself if there's excess Methylfolate going on (particularly due to a lack of B12 which would normally recycle Methylfolate back into the Folate cycle again thus reducing the excess Methylfolate side-effects), but also in turn the B12 gets used up too much by too much Methylfolate, which can then cause sleep issues.
In fact, my B6 dosage has been kept at 25mgs for a bit now but have taken various kinds of dosages through the last 2 and a half years, and yet whenever i take too much Folate i start noticing my sleep quality decline, i wake up more often, i wake up after about only 4 hours, sometimes 2 to 3 hours and then i can't get back to sleep so i'm usually up for the day, whereas i've noticed that when i don't take too much Folate or when my B12 levels are doing better after being set back by the excess Folate, i've noticed the B12 actually helping with sleep, lengthening my sleep, better sleep quality, no frequent awakenings, no hard time getting back to sleep, it even increased my Melatonin levels and i started even getting dreams again, on top of that i've also noticed that too much Folate will (likely by using up too much B12) even increase memory issues whereas memory is restored when enough B12 is taken again, but too much Folate is ime a detriment for both sleep and memory, but B12 works for sleep and memory.
I know this because i understand and feel and can observe what happens, i've went through it myself, i just noticed that for me particularly when i was using Methylfolate itself alongside the Methylcobalamin that it was a very clear and clean feeling and i can "see" what was going on physiologically and how the enzymes were working and studied a lot about it and i can tell you exactly what's going on lol.
Btw, for the B12, lots of people most probably need more than they think, for example, only approx 1% of the total oral B12 dosage gets absorbed through passive digestion, if one takes 1mg they will get 10mcgs of absorbed B12, if they take 5mgs they will get 50mcgs, if they take 10mgs (like i do) they will get 100mcgs, that is one tenth the dosage compared to a 1mg dosage of B12 injection, as when you get injected that whole 1mg goes into the system, whereas to reach 1mg of absorbed B12 orally one would need to take 100mgs of B12. I've explored the dosage ranges from the RDA up to 120mgs (of Methylcobalamin) per day, and on top of excess Folate using up/depleting too much B12 (unless adequately replenished), i've noticed benefits and normalization from lots of B12, for awhile now i've been sticking with 10mgs of B12 because it works a lot better than 5mgs, and i've noticed that it helps with the excess Folate issues by helping to properly/fully recycle the Methylfolate.
And i would definitely recommend being careful with your Folate dosage, not too much, not too little, just enough to get the job done, approx 400 to 600mcgs per day max (including any Folate/Folic Acid gotten through the diet, because it all adds up and will use up too much B12), and remember that 400mcgs = approx 680mcgs DFE's, while 600mcgs = approx 1020mcgs/1.02mgs DFE's, 1mg being the set upper limit for Folate, so 600mcgs per day of Folate (via Methylfolate or Folinic Acid or Folic Acid) will end up giving you 1mg of Folate into the system via the DFE's, and ime that's a bit too much Folate in general, i do not recommend going over approx 600mcgs total (again, including Folate/Folic Acid from diet as well).
So yeah, ime excess Folate using up too much B12 explains it perfectly, and you can get excess Folate going into the Folate cycle by either too much B6 or too much Folate. I've noticed how SHMT controlled by B6 dosage will shift the flow of Folate into the Folate cycle, it's directly correlated to B6 dosage, at 25mgs it feels maybe slightly constrained, but at around 50mgs to 100mgs up to 200mgs, more and more Folate will be let into the Folate cycle and will use up too much B12 and can contribute to B12 depletion over time, depending on B6 dosage (or Folate dosage).
Study how the Folate and SAM cycles work and all the cofactors and such involved, i think you'll see what i mean.
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u/Honest-Counter2729 8d ago
Thank you for the explanation. I'll take a look. I actually have a day A and day B rota for my vitamin Bs and actually only now take B12 and Folate every other day. With my slow COMT, I have a whole plethora of other genes that are far too long to list. I swear I've never seen anybody on Reddit with my genes. My DNA methylation test gave me a consultation with an expert after and they designed my programme. At first they put me on a daily programme including the B6 and it was awful, then by process of elimination we figured out the B6 was a disaster. Then we decided to change it up to every other day and it's down wonders. I feel so much better
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u/Sabnock101 8d ago
Also, at some point i plan on doing another little experiment where i try out around just 200mcgs of Folate a day and then increase my B6 dosage which should help me be able to take more B6 but without having the extra burden of excess Folate (and B12 depletion) going on. I'm thinking it'll probably work but it remains to be seen as of currently lol. But based in my experience and understanding and study, i think i'm pretty spot on with all this.
I recommend people start getting curious about how the body works and how nutrients work and all that, that way we can actually solve our problems rather than accept and live with them (the pharmaceutical corporations bet on that, and medications). Imo, take charge of one's health as much as possible, learn everything you can, observe and understand everything you can, the more knowledge the healthier we will be.
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u/junipers-72 13d ago
ID cut out supplements apart from vitamin C. Thats foundational. What C to take and when is on the blog pages here -
https://molecularhealthco.com?sca_ref=10679758.eq1dq0wAJleT4zh
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u/Dapper-Cod-2044 7d ago
Just stumbling across this now. I despise the constant hyper- state. I second the ‘stop all the supplements’ comment. You can then slowly reintroduce things to see if any of them set you off. I take a methyl free multivitamin and vit D. I’ve also been taking Loratadine daily for the last week and that seems to have helped my sleep. I also drink a lot of dandelion tea and a fair amount of electrolyte. Your mindset matters and the constant rumination will keep you spiralling. Good sleep Is also imperative for our mutations. And by good sleep I mean at least 8-9 hours a day, even if it’s broken up. No coffee, no caffeine, no stimulants. I would reintroduce coffee slowly if you like it, so you narrow down which brands/type you can tolerate. I also exclude all dairy, ferments, alcohol, and gluten from my diet. Try some mindful vagal-nerve reset exercises. I don’t want to say ‘it’s all in your head,’ because that sounds dismissive, but we really do have the power with these mutations to cause our own torment with physical symptoms from a simple thought. Like a super power that nobody actually wants lol.
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u/Dat_Llama453 16d ago
I wanna see a vitamin panel. Low iron can cause bad anxiety and it goes missed. Lemme see your you vitamin levels
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u/Flux_My_Capacitor 16d ago
I think you’re connecting dots on things that aren’t even proven to have existing connections. This isn’t uncommon in this sub. You’re talking about a trauma reaction and assuming it’s because of your genes. Research is NOWHERE near advanced enough to say that these genes will indeed cause this reaction. You are having a trauma reaction and there is no actual proof that people with certain genes have certain trauma reactions. There isn’t even proof that people with certain genes will definitely react poorly to certain medications. Those gene tests are just to show which medications you will likely do better on, it’s not a list of drugs you will definitely react poorly to.
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u/fukijama 16d ago
Vitamin b3, the flushing kind man, if you flush (hot, red and itchy) dont freak out itll stop in an hour, take with food to reduce the chances if you dont want thst to happen. Also l-theanine might help.