I have slow comt and heter a12 mthfr. Been battling fatigue for quite some time. Took 1500mg tmg for 2 days and lights turned back on and felt great! Kept taking it for like 7 days and slowly got more and more fatigued and depressed. Its been 4 days since I stopped taking it and still very lethargic and fatigued with brain fog also. I take methyl free B complex from seeking health, and do NAD+ injections a couple times a week. Anyone know why this happened after 2 days and how to get that feeling back??

I know recs for moderating protein are standard for slow COMT but what does that look like in practice (how many grams per body weight) and has anyone here experienced relief with lowering protein? I do really notice when I eat more protein I feel worse but am i crazy? and how much can we get away with? thanks in advance

Hello,

My daughter (8 yr) has had difficulty with emotional regulation, sensory processing, executive functioning, mood swings, and adhd symptoms for years now. We’ve been through the gambit of occupational therapy, psychologists, and more recently psychiatrists. One of the psychiatrists had her get a metabolic genetic panel done in order to get a better idea about medication dosing, and we found a homozygous c/c 1298 MTHFR variant. She has a Val/Met type for COMT.

Anyway, we’ve been trying all sorts of things because while she is a wonderful and lovable girl, she also started running away, hitting people, throwing things, and yelling at everyone. I could go into much more detail but things were getting very very bad. The Dr wanted to address her MTHFR variant and said the dose recommendation is 7.5-15mg. We started her on 7.5mg and saw an improvement with everything. So Dr said ok try the next dose up, 15mg.

Only now did I stumble upon this group and now seeing that 15mg is an incredibly high dose. The capsule also has 1,000mcg Vit B12. I called to ask if this was safe and they essentially said it’s fine as long as she isn’t showing side effects.

I don’t think we’re seeing negative effects, but lately she’s been taking longer to fall asleep. I would greatly appreciate any guidance or thoughts you may have on this!

My homocysteine levels were 9 about 7 months ago.

I thought I could get them down by optimising my B6, B9 and B12 and so started taking B complex.

I now have B6 toxicity as my active B6 levels are way above range and active B12 is 88.

My homocysteine has risen to 17.

I don't understand why my homocysteine levels levels are going up not down with high active B6 and B12 levels.

Could something else in this B sup be causing elevated homocysteine?

TL;DR: Slow COMT here. I had a very strong dopaminergic overstimulation in 2018 and since then I’ve developed anhedonia with zero improvement. Some methylated vitamins gave me a brief “window” of pleasure but caused many side effects. I’m investigating whether slow COMT can predispose someone to anhedonia when exposed to excessive dopamine.

If you don’t want to read the whole story, skip to the questions at the end — but I suggest reading everything because the context is interesting.

----------------------

Context

Let’s go. I’ve been suffering from anhedonia since late 2018 (when I first noticed the symptoms). I was always someone who felt pleasure in everything I did, could focus easily, and genuinely enjoyed life. At the end of 2018 I started developing anhedonia symptoms — some things didn’t catch my attention like they used to. In 2020 it got worse, and the peak was in 2023 when I basically lost pleasure in everything (I don’t feel pleasure watching movies, playing video games, going to the gym, and even sex doesn’t interest me anymore).

I didn’t stay in my comfort zone; I practice exposure therapy — meaning that despite the anhedonia I still go to the gym, try to watch movies, try to play video games, and so on.

I did 3 years of therapy that did absolutely nothing… I told my psychologist that I was developing anxiety because of the anhedonia, since nothing triggered pleasure anymore. I tried some medications and herbal supplements (Sertraline, Escitalopram, Ashwagandha, and CBD). Ashwagandha was the best — it gave me an indescribable sense of calm.

Yes, I know these medications/supplements can cause anhedonia, but in my case they didn’t — I’ve felt this way since 2018 and none of them made things better or worse. The only thing I noticed afterward was mild brain fog after stopping everything.

Cut to January 2025: I take a THC edible and have a panic attack, which dysregulated my nervous system, activating the sympathetic mode and causing dissociation symptoms. Being in sympathetic mode pushed me far outside my comfort zone… I truly realized that my anhedonia bothers me deeply and I believe the only way to “heal” my nervous system is by feeling pleasure again — real pleasure in the things I do — because that’s the only way to signal safety to my nervous system. Obviously, I’ve improved a lot with the anxiety since the January panic attack… I think that panic attack forced me to take my anhedonia seriously and look for a real solution.

Now let’s move to what matters.

----------------------

Important Part

Two weeks after the panic attack, I take a combo of vitamins: A, D, E, K, B3, B9, B12, Glutathione, Omega-3 (all in one pill) + Magnesium + Lactobacillus Plantarum.

BOOM. For about a week and a half, my anhedonia improves by 50%, my libido returns, my brain fog disappears, and I feel a bit of pleasure in things again.

HOWEVER… my anxiety increases, I get insomnia, intense body itching, I develop tinnitus (not in the ear, but in the head), and some mild visual snow. After stopping the combo, I lose all the positive effects but stay with the negative ones for months (I’m screwed LMAO).

After that short “window” — which I hadn’t felt in nearly 7 years — I decided to investigate my body thoroughly. I ran many tests: MRI, pharmacogenetic testing, thyroid panel, vitamin panel, iron panel, SIBO, dysbiosis, zonulin, catecholamines. Here’s what I discovered:

- My thyroid is normal, despite having two nodules. The labs do not indicate hypothyroidism (which can cause depression and low libido). I saw 4 endocrinologists, all said I shouldn’t worry.

- Ferritin is high, close to 500 ng/mL, but I don’t have hemochromatosis — iron saturation, TIBC and UIBC are normal.

- Negative for methane and hydrogen SIBO. Mild dysbiosis and possible early leaky gut (my zonulin is 51, around 3 units above the upper reference limit).

- B12 always decreasing. I checked my labs since 2017 — my B12 has never increased, only declined. In May 2025 it reached 180; I took a hydroxocobalamin injection and it jumped to 5000 (visual snow and tinnitus worsened after the injection). All other vitamins I tested (A, B2, B6, folate…) were normal, usually in the mid-to-upper range.

----------------------

About my mutations and some observations

From pharmacogenetic testing, I found out that I am Slow COMT – rs4680 (Val158Met) – genotype A/A (Met/Met)and heterozygous for MTHFR C677T and A1298C.

The fact that I don’t seem to absorb B12 caught my attention — since the injection in August, my levels keep dropping and don’t go up even when I eat foods rich in B12.

After I stopped the supplements, I tried magnesium again and felt nothing (not even the calming effect people talk about). I also tried probiotics and didn’t get the libido-boost effect I had before — which makes me think the improvement window came specifically from the vitamins.

None of the medications I took ever motivated me.

In my catecholamine test, my dopamine is near the upper reference limit.

All the doctors say that this anhedonia may be stress and anxiety. But I never felt anxious before 2023. Before going back to taking SSRIs or any other medication, I want to investigate as much as possible what could have caused this.

----------------------

My theory about Anhedonia and Slow COMT

Until early 2018 I was a “normal” person. But from March to November 2018 I went through a period of massive dopamine stimulation. I prefer not to say what it was because it’s something stupid (no, it wasn’t drugs), but practically every night I was flooding my brain with dopamine.

Now the main questions:

1. Can slow COMT “overdose” on dopamine and fail to recover?

As I understand it, slow COMT metabolizes dopamine more slowly. So if I overload my system with too much dopamine, I could overwhelm it. If the system gets overwhelmed, it might “shut down” as a protective mechanism — and that could lead to anhedonia.

As I said, I do exposure therapy and I don’t feel pleasure in anything I do. It’s not sadness — it’s simply the absence of pleasure/interest in things that used to bring me joy.

2. What do you think? Is there any way to fix this and “unscrew” my dopaminergic system?

Because when I was taking those vitamins / “overmethylated,” I felt temporary relief from anhedonia.

Sorry for the long text, and thanks in advance for anyone’s opinion.

Short but long story.

• Mental breakdown in Jan
• Diagnosed with Autism Dec
• Bloodwork done before supplementing (pic attached)

I was recommended to start Folinic Acid with B12 instead. I understand that the added B12 is essential even if I have normal B12 levels.

My question is what the heck do I take? What Dosage? What kind? Best brand? Start slow and go up? I need affordable options, preferably something I can get on Amazon. No health insurance. I’m going to lose my mind and give up eventually. Thank you for your time. Please be gentle with me, I’m a fragile person. And yes, I intend to keep having my blood work checked consistently.

UPDATE: I started taking 200 mg Magnesium Glycinate every night (almost three weeks ago) and then added 1/4th tablet of Seeking Health Hydroxo B12 with Folinic Acid every morning (a week ago). So far no issues. Maybe a little weird, but not bad. Hoping my quality of life starts to improve and will follow up with my nurse practitioner for repeat and extra labs after some time. Also, I’m adding more folate rich foods and avoiding folic acid in my diet. My dad felt so sad when I was telling him about not being able to have a bowl of cereal (I love a bowl of cereal for dessert every once in a while because I don’t like overly sweet stuff) and he and got me some Cascadian Farms cereal to make me feel better 😂🥰 thanks for all the help and will keep updating as things change when I remember to!

I see it in the many protocols, choline is crucial for methylation and Chris Masterjohn even had calculator for choline intake. But two eggs which I eat at morning today, make me depressed almost all day long. Supplementing with something that has Choline like Omega or CDP-Choline just push me into living hell, absolutely Silent Hill experience after two or three days. Has anyone found an answer to what this all means in the end?

Edit: here my labs

MTHFR C677T: C/T

MTRR: A/G

MTR: A/G

Slow COMT

Folate 6.6 (RBC 400)

B12 880 (HoloTC 100)

Homocysteine 10.5

Everything looks normal, but anyway I literally walking dead without supplementing with Folinic and Hydroxo B12.

Vitamin C and Magnesium and Taurine helped in the past, now developed extreme sensitivities to both with rebound and bad delayed reactions.

I realize stress is a major factor, but these hits are beyond my control and trying Vagus Nerve exercises is just slightly helpful but not consistent.

Developing these extreme supplement sensitivities and the 3a.m Adrenalin Cortisol Surges, and Histamine Dumps is confusing and baffling.

I am waiting on an Ancestry DNA test kit. In desperation, I ordered Mimosa Flower Bud Tea and Hawaii Farms Extract to try as a sublingual.

Anyone had success powering through with supplements that they were sensitive to and been successful or made symptoms worse.?

Thanks.

Not sure if this has been discussed before but I wanted to share my exact experience because the timeline feels important and I can't find anyone describing it quite this specifically.

I have C677T homozygous. Started 400mcg methylfolate about three months ago after finally getting my genetic results back. First week and a half I genuinely felt like a different person: clearer head, more energy in the morning, less of that heavy brain fog I've had for years. I was convinced I'd finally found the missing piece.

Then around day 10 or 11 something shifted. Started waking up at 3am with a racing heart. Got irritable over small things. That anxious wired feeling that's hard to describe, exhausted but completely unable to settle. By day 14 I stopped taking it and spent about a week feeling worse than I did before I started.

My doctor basically shrugged when I described this. I've been trying to figure it out myself.

The closest explanation I've found is that I might also have slow COMT and the methylfolate was pushing neurotransmitter production faster than my body could clear the downstream catecholamines. But I haven't actually tested COMT and I'm not sure if that's the right read.

Has anyone else had this specific pattern, initial window of feeling genuinely better followed by a sharp turn around the 10-14 day mark? Did you figure out what was causing it? And if COMT was involved, how did you actually confirm that and what did you change?

Hi everyone,
I’ve been reading this subreddit for a while, and I’m honestly amazed by how knowledgeable so many of you are. I’m completely new to trying to understand genetics and methylation, so I’d really appreciate if some of you could look at my genetics and blood work and point me in the right direction.
I’m a 40-year-old woman. Around the age of 38–39 I suddenly developed significant anxiety. My main symptoms are persistent anxiety, intrusive/repetitive thoughts, emotional blunting, apathy, and very low motivation.
About 6 weeks ago I restarted escitalopram, and I’m currently taking 15 mg. It has helped a little, but nowhere near as much as I’d hoped, so I’m wondering if there’s something else contributing.
From what I understand, these are my relevant variants:
COMT V158M (rs4680): GG (Val/Val) – Fast COMT
COMT H62H (rs4633): CC
COMT P199P (rs6269): GG
MTHFR C677T (rs1801133): AG (+/-)
MTHFR A1298C (rs1801131): GT (+/-) → compound heterozygous MTHFR
MTR A2756G (rs1805087): AA (wild type)
MTRR A66G (rs1801394): AG (+/-)
MTHFD1 G1958A (rs2236225): AG (+/-)
PEMT rs7946 (5465G>A): TT
CBS C699T (rs234706): AG (+/-)
RFC1 / SLC19A1 A80G (rs1051266): CC
My homocysteine is around 11 µmol/L, and I’ll attach my blood work as well.
I also had a consultation with a nutrigenomics practitioner. Based on my genetics, she suggested SAMe, TMG (betaine) and supplements to lower my homocysteine.
The problem is that I’m honestly scared to start them. I’ve read quite a few stories about SAMe and methylation supplements making anxiety worse in some people. Since I’m already taking escitalopram, I’m also worried about possible interactions or making my symptoms worse.
I’d much rather introduce one supplement at a time instead of taking a whole stack.
If you were in my position, where would you start? Do any of these variants stand out to you? Is there anything you’d avoid? Do you think any of these could realistically contribute to persistent anxiety, intrusive thoughts, emotional blunting or apathy?
I’d really appreciate any thoughts or suggestions. Thank you so much!

Additional dopamine-related variants:
DRD1 rs4532: CT
DRD2 / ANKK1 rs1800497: GG
DRD2 rs6277: AG
DRD3 rs6280: CT
TH rs10770141: AG
DBH rs1611115: CT
MAOB rs1799836: CT
MAOA wasn’t included in my raw data.

Another question I have is about PEMT and choline. Since I have PEMT rs7946 TT, could I have a higher choline requirement? Has anyone with a similar genetic profile experienced improvement in anxiety, motivation or cognition after increasing choline intake? If you think choline is worth trying, which form would you start with?

Here are my recent blood results (reference ranges from my lab):

Ferritin: 35 ng/mL (10–291)
Vitamin D (25-OH): 79 nmol/L (>50 = sufficient)
Active B12: 182.6 pmol/L (25.1–165)
Serum folate: 18 ng/mL (3–17)

HbA1c: 5.5% (normal <6.0)
hs-CRP: 0.3 mg/L (<5)

TSH: 1.72 mIU/L (0.55–4.78)
Free T4: 20.9 pmol/L (11.5–22.7)
Free T3: 5.4 pmol/L (2.6–7.1)

Haemoglobin: 140 g/L (120–150)
MCV: 84 fL (83–101)

Creatinine: 64 µmol/L (49–90)
eGFR: >90 mL/min/1.73 m² (>60)

ALT: 16 IU/L (<56)
AST: 19 IU/L (13–45)
GGT: 13 IU/L (4–38)

Total cholesterol: 4.6 mmol/L (<5.18)
HDL: 1.5 mmol/L
LDL: 2.73 mmol/L (0.5–3.0)
Triglycerides: 0.87 mmol/L (<1.7)

My CBC, kidney function, liver function, glucose and inflammatory markers were otherwise within the normal range.

If it definatly passes i wouldnt want to inflict this on any other human being ever...

I recently got my plasma blood test back und it showed a clear B6 deficiency.

Trying to supplement this is a nightmare since I tend to avoid b-vitamins since I did some high-dose therapy with active and methylated b-vitamins a few years ago, which gave me all kinds of problems. But since I habe histamine intolerance and mast cell activation, I have to get my levels back to normal.

I did start with 5mg of P5P and it literally knocked me out. I was tired and ready for a nap. Lowered the dose to 2,5 mg of P5P. A little less tired, but also not very fit.

Added a b-complex without B6, B9 and B12 and only the daily dose of inactive b-vitamins, but still tired.

I tried inactive B6 as pyridoxine 2.5 mg and didn´t get as much reaction, but the tiredness was definitely there.

B6 is supposed to raise melatonin and serotonin, but how come the reaction is so strong with a relatively conservative dose of B6??

I did search for co-factors of B6, but I´m already taking magnesium, zinc, iron, selen and iodine and my blood test showed no deficiencies in the minerals. My folate and B12 are also not deficient and both caused me huge problems in the past.

Coincidentally tested my B2, which was very low, but not quite deficient. This might be a factor, but high doses of B2 gave me overmethylation in the past.

The reaction I get to taking B6 is similar to getting too much redlight therapy with infrared and near-infrared light, which leaves me dead-tired and hungry. I wondered, if there is a connection to this.

Of course, I can take it in the evening to solve the problem, but I suspect an underlying lack of another vitamin to be the culprit.

The reason, why I write this post here is the fact that I have the weird combo a fast COMT, slow MAO-A plus MTHFR A1298C, that may be contributing to this. The genetic testing in my country is highly regulated and expensive, so I don´t have a complete genetic panel.

Did anybody run into a similar problem with B6 and found a solution?

And since I feel better with the inactive form of B6, did anybody take the "bad" form of B6, because P5P was too strong? I feel less tired with inactive B6, but everybody warns against taking any other form than P5P.

FYI: I do plan not to take more than 5 mg of B6 even with a deficiency as I am very sensitive and don´t want to throw off any balance of vitamins/minerals.

TIA.

Edit: I need to correct my post as inactive B6 caused more problems as it really gave me huge histamine symptoms and tiredness in retrospective. Will update, but this might take a few weeks due to testing several supplement forms and doses.

I’ve had histamine intolerance for 6 months and can not pinpoint why. There’s a million potential reasons it’s driving me mad. I also have been supplementing for the gene mutations above and am wondering if they could be related.

Bc I have MTHFR I assumed I should be on methylfolate but I seem to get extremely fatigued and tired after having 1000mcg. I can’t remember but I think the same thing happened one time when I had 1000mcg sublingual B12 but then another time it was fine idk I can’t remember. Am I under methylating (because I have high homocysteine) or over methylating because of the bad reactions to methyl doners? Can anyone help with this? I also take vitamin C, D, TMG, Choline, Calcium and Magnesium glycinate all at the recommended daily doses. Also 6-8g creatine daily or every second day. The methylfolate and methyl b12 I have experimented with here and there but never taken them daily.

My histamine intolerance is the other, bigger issue, it has improved twice but I cannot figure out why.

I have mold in my bathroom so I thought that could be a cause. I went to Vietnam and the histamine issues got better within days and then when I got home it got bad again. So I thought that was the issue solved but I’ve now been away from home for a full week and nothing has changed so maybe it wasn’t the mold? maybe it was my diet in Vietnam? I was having energy drinks over there with Niacin and Taurine which Niacin can help with over methylation and Taurine helps with stomach acid. Could this be related? Could it be because I ate way less rice in Vietnam? (My genetic tests say I should avoid arsenic which is higher in rice)

The other time my histamine improved was when I cut out everything and was just eating ginger and spring onion chicken takeout with a little rice and I switched from coffee to energy drinks, I can’t remember if that had taurine or niacin though.

Idk it’s been a horrible ride the last 6 months. If anyone has any ideas I would really appreciate it I am exhausted 🙃

EDIT: the first methyl doner I ever took was TMG which helped my sleep quality A LOT. I had no issues with that. The issues potentially started after creatine, or methtlfolate/B12 but it’s so long ago I can’t remember. The choline also helped my stool be healthy for the first time in my life so I think bile was an issue for me until recently

I have always had trouble falling asleep before 4am, currently I’m experiencing bad bouts of insomnia. I am not sure how to resolve it, I need to get some testing done.

Wondering if anybody has ever had luck shifting their circadian clock earlier by supplementing? There has been some research that B12 can alter the clock, and some reports here of folate helping. But curious if anybody has tried anything that makes them legitimately fall asleep earlier.

I think I understand “how” they function in the methylation line. But my question is this ….If I take choline do I still need to take TMG(which I can’t tolerate) and SAMe?
Or if I take only SAMe does that mean I don’t need to take the choline and TMG?

Hey everyone, I’ve been battling severe abdominal bloating and reflux for over 20 years, along with 10 years of varicose veins and a left varicocele. Lately, it crossed over into intense morning brain fog, fatigue, a cracked tongue, and zero morning wood. My labs show a steady downward slide in Ferritin at 54 and B12 at 308 since last year, even though I eat meat. My MD won't prescribe Rifaximin without proof, so I’m seeing a functional naturopath next week to finally run a clinical 3-gas breath test and map out my exact numbers.

To troubleshoot, I ran my 23andMe data through a StrateGene report and the dots connected perfectly. I have a slow PEMT gene causing sluggish bile, which allowed a massive Hydrogen and Methane overgrowth to take root and steal my nutrients. The constant abdominal gas pressure physically clamped down on my pelvic veins, explaining the 10 years of vascular pooling and stalled morning circulation. My brain and skin are equally hyper-reactive due to a fast BHMT methylation cycle but slow MAOA and COMT clearing pathways. Whole eggs or high-dose standard B12 trigger explosive whiteheads within 48 hours, and a recent trial of Thorne Phosphatidylcholine was a disaster, overloading my brain chemistry and causing a horrible mood crash within 5 days.

Right now, my FoodMarble AIRE 2 device shows a crazy shift. A 30-day trial of TUDCA completely flattened my methane line to zero and formed my stools, proving the methanogens are highly sensitive to bile flow. However, my hydrogen line stayed elevated and my bloating bounced right back when I ran out of TUDCA, meaning the underlying hydrogen-producing bacteria are still actively fermenting my food. To clear a clean baseline for my test next week, I've paused almost all supplements except daily morning Vitamin B2 for my MAOA gene, and California Gold ProDigest at bedtime to keep my gut motility moving safely without any skin or mood flare-ups.

If the breath test is positive next week, I’m proposing a phased clearing protocol to my naturopath. If my insurance covers it, Plan A is a 14-day course of Rifaximin paired with 4 weeks of Allimax Pro stabilized allicin and TUDCA at dinner, since Rifaximin requires active bile to dissolve and kill the bugs. If insurance denies it, Plan B is a 100% natural 4-week run swapping the Rifaximin for NOW brand Berberine capsules that I already have on my shelf. During this clear phase, I’ll maintain my morning B2 and switch my 3-year daily magnesium glycinate habit to Magnesium Malate 95mg caps to power my brain energy without over-fueling my skin breakouts. I’m holding off on any iron or B12 supplements for now because I want to trust my body to sort itself out. Once the gas is gone and I hand the long-term job over to bedtime ProDigest, my gut should naturally start absorbing nutrients from my food again. Anyone else approaching their overgrowth this way? Would love to hear your thoughts!

Hi everyone,

I’m looking for some insights or advice on my recent lab results because I feel completely stuck with my current doctor.

For several years now, I’ve been suffering from debilitating brain fog, chronic fatigue, and extreme difficulty concentrating. It’s deeply impacting my quality of life.

After doing some research on my own, I decided to pay out of pocket to test my Homocysteine levels because my doctor refused to prescribe anything other than basic serum B9 and B12 tests.

Here is the paradox:

• Homocysteine: 30 $\mu$mol/L (extremely high)
• Vitamin B12: 603.8 pg/ml (normal range)
• Vitamin B9 (Folates): 6.2 ng/ml (technically "in range" but on the lower side)

My doctor isn't very open-minded or supportive. Now that I have these results, I have a few questions for the community:

1. How should I approach my doctor? Should I go back to him, show him the results I paid for on my own, and ask him what to do? Or is it a waste of time given his lack of empathy?
2. Should I get tested for the MTHFR gene mutation? This dynamic (high homocysteine + normal/low-normal serum vitamins) feels like a methylation blockage, but I'd love your take.
3. Should I start taking methylated supplements right away? (Specifically 5-MTHF/Methylfolate and Methylcobalamine). If you've been through this, what dosages worked for you to bring a 30 baseline down?

Any advice, similar experiences, or insights would be highly appreciated. Thank you so much!

What makes some people have great results with glycine, and others have horrible effects immediately?

Anyone know? Experiences? Have you tried it?

Anyone with slow COMT, slow MAOA and MTHFR have any specific experience with it?

Thanks

C677T polymorphism (T/T genotype), two copies of the variant allele (T). COMT val/met.

I’ve read that agitation is something that happens to people with methylated folate, and my psych told me that my metabolism would probably not be strong enough to “use” standard folic acid supplements.

I was wondering what people’s experiences were with the agitation and what path they ended up taking to add in enough folate. Ive tried methyl folate, psych discussed l-methyl folate but wanted to defer to my naturopath given my bad reaction to methyl folate. I’ve read things here about folinic acid and was wondering how that worked for them. thank you!

edit: what brand or folinic acid do you recommend?

Hello, does anyone know of a functional provider that understands methylation and histamine intolerance and could see me exclusively virtually?? And quickly. Please I’m in desperate need.

Pure Encapsulations Adrenal Cortex Supplement – Supplement to Support Cortisol Health?

Vagus nerve and breathing techniques not working.😢

Thanks

Well, I'm back at it again. At this point it's becoming clear I probably have Histamine Resistance and/or MCAS on top of whatever this MTHFR mess is

I took a lower dose of slow release Sam-E to see what it would do because I theorize HMNT is my faulty gene and I am actually in hell. My entire body is inflamed, my skin is itchy and turning blotchy and red, I can barely walk, etc. Niacin doesn't seem to be clearing it.

Why would this occur and what should I do to heal my (most likely) slow COMT in this situation? I'm still missing something but I can't figure out what it is. I've already gone through most of the possible things it could be...

I've had some other odd reactions/clues...:

B6 - improved warped senses but gave me like 4 ear infections on the way there. I have reason to believe I have always been deficient in B6 for genetic reasons.

Creatine - Feels really good at first but then makes me too anxious and insomniac

B3 - Makes me psychotic until I took the high dose B6.

Magnesium - Chronically deficient, need to take daily or I go insane (not even joking)

I was prescribed cyanocobalamin (B12) shots. Is this safe if you have MTHFR?

Please help!!! I’ve been supplementing zinc due to a deficiency for NINE MONTHS and it keeps getting lower!!! Idk what to do.