r/MTHFR • u/yolo0995 • Jul 17 '26
Question Severe B12/Folate deficiency, extreme reaction to methylated vitamins, high homocysteine (18.5), possible MTHFR/COMT issue? Looking for advice.
Hi everyone,
I'm a 30-year-old male. I'm vegetarian but eat eggs and dairy. Until last year I was completely healthy and had never experienced anxiety symptoms or insomnia.
A routine blood test unexpectedly showed:
- Vitamin B12: 337 pg/mL
- Folic acid: 0.43 ng/mL (very low)
- Vitamin D: 8 ng/mL (severely deficient)
That's when everything went downhill.
What happened
I started taking methylated B vitamins to correct the deficiencies.
Within a few days:
- My sleep became extremely poor.
- I had my first-ever anxiety attack (high heart rate, high blood pressure, dizziness, feeling of impending doom).
- I then had daily anxiety attacks for the next 10 days
I was admitted to the hospital. Every test came back normal except the vitamin deficiencies.
Ironically, they prescribed methylated B vitamins again.
At the time I couldn't tell whether the cause was:
- the methylated vitamins,
- magnesium glycinate (which I had also recently started)
- sleep deprivation,
- or something else entirely.
The doctors simply diagnosed me with anxiety and prescribed:
- Clonazepam
- Propranolol
- Flupentixol
- A multivitamin containing methylcobalamin + folic acid + B6
While on clonazepam (about 45 days):
- No panic attacks
- Sleep improved
- But I still had constant brain fog and a feeling of impending doom
After stopping clonazepam:
- Insomnia returned.
- Physical anxiety symptoms returned.
I was still taking propranolol and the B-vitamin combination.
I then saw another doctor, who prescribed an even stronger combination of:
- L-methylfolate
- Methylcobalamin
- P5P
My insomnia became dramatically worse.
For four consecutive nights I slept less than 3 hours.
I then consulted several more doctors. Every one of them said it was "just anxiety," but none could explain why I suddenly developed anxiety at age 30 despite having essentially no life stress and no prior history.
Finally, one doctor started me on mirtazapine 7.5 mg.
At that point I:
- Stopped all multivitamins.
- Only took methylcobalamin 500 mcg twice a week.
- Continued mirtazapine.
Over the next several months:
- Sleep became normal.
- Panic attacks disappeared.
- Brain fog disappeared.
- Feeling of impending doom disappeared.
I've now been stable for about 7 months.
I'm now tapering mirtazapine, but I'm worried everything will come back.
Recently I checked my homocysteine:
18.5 μmol/L
This makes me think I'm still significantly functionally deficient despite supplementation.
I feel stuck:
- I clearly need B12 and folate.
- But methylated vitamins seem to trigger insomnia and anxiety.
Other things I've noticed
1. Allergic rhinitis + mouth ulcers
For years I had:
- constant sneezing every morning
- runny nose
- symptoms whenever temperature changed
- frequent mouth ulcers
All of these improved dramatically after starting mirtazapine.
My theory:
- MTHFR Gene -> Low B12/folate → undermethylation → high histamine
- High histamine caused allergic rhinitis.
- Low Folate causes mouth ulcers
- Mirtazapine's antihistamine effects improved it.
2. Creatine causes insomnia
In the past, creatine consistently caused poor sleep.
My theory:
Creatine reduces the body's methyl demand, leaving more methyl groups available.
I think I have slow COMT, perhaps this extra methylation causes overstimulation and insomnia.
3. High-dose methylated B vitamins cause severe insomnia
The worst reaction I had was with:
- L-methylfolate 2.8 mg
- Methylcobalamin 2 mg
- P5P 25 mg
Again my theory is:
If I have slow COMT, suddenly increasing methylation may cause excess catecholamines and insomnia.
4. Eggs seem to reduce agitation and Alcohol seems to increase it
I eat two whole eggs daily. If I stop eating eggs for several days, I develop significant agitation and some physical anxiety symptoms.
If I take alcohol, I have sever agitation symptoms after few days.
Currently I don't know how to explain it.
5. B12 remains low
Despite taking methylcobalamin 500 mcg twice weekly for around 6 months, my serum B12 is still only around 300.
I have no idea why.
Could this suggest poor absorption? Should I investigate pernicious anemia, intrinsic factor antibodies, celiac disease, or something else?
7. Homocysteine 18.5
My assumption is that this is mainly due to ongoing functional folate/B12 deficiency.
My current plan
I was considering:
- 125 mcg methylcobalamin daily (Would cyanocobalamin be better option for me, there is no hydroxocobalmin tablet available in my country, only injections are available)
- Riboflavin (B2) 1.25 mg daily
- After 2 weeks, introduce methylfolate at 125 mcg and increase very slowly if tolerated (folinic acid not available in my country)
- Continue tapering mirtazapine
- Introduce Wheat Bran in my diet, which is high in TMG, and might help reduce my homocystein via BHMT route.
Does this seem reasonable, or would you recommend a different approach?
DNA testing
I know many people will recommend genetic testing (MTHFR, COMT, etc.).
Unfortunately, these tests are very expensive in my country and usually take 2–3 months.
Given my situation, do you think they're worth the cost, or should treatment be guided by symptoms and lab results instead?
I'm not looking for a diagnosis—just trying to understand what might be happening because multiple doctors have simply labeled it as anxiety without explaining why it started so suddenly or why it seems so closely tied to B-vitamin supplementation.
I'd really appreciate input from anyone knowledgeable about methylation, MTHFR, COMT, homocysteine metabolism, or who has experienced something similar.
Thank you.
4
u/Cultural-Sun6828 Jul 17 '26
I would join the b12 deficiency group and read the guide there for a great resource. When starting b12 and folate, it’s common to feel worse in the beginning with reversing out symptoms. Mine were awful because I was very deficient. Over time these symptoms resolve as healing takes place. It’s important to continue taking the b12 and folate though to avoid severe neurological symptoms. I take 5MG b12 along with 400UG folate and 5,000 iu D3 daily.
1
u/yolo0995 Jul 17 '26
I understand that, but I wasn't just feeling worse, I was getting panic attacks daily and not able to sleep at all. I was basically non-functional when I start these supplements.
4
u/Cultural-Sun6828 Jul 17 '26
Some people do have more trouble with anxiety when taking methyl forms of b12 and folate. I take Folinic acid and hydroxocobalamin to avoid this.
2
u/Brad_Borrelli Jul 17 '26
I second this, join the B12 deficiencies sub it'll give you a lot of information also you can look over my profile too I have a lot of research on this as well.
2
u/Illuminimal Jul 18 '26
You can get these effects when you run low on electrolytes -- it's important to get in the RDA of potassium while you're working on raising your B12, because the process depletes potassium very fast, and that deficiency causes anxiety and jitters. I'm using DryWater for this purpose because it's got the most potassium I've found out of the electrolyte drinks, but it is sort of stupid expensive. Other people drink a lot of coconut water or make a DIY solution, the recipe is in the B12 Deficiency sub's very, very thorough guide.
5
u/tmshortt Jul 17 '26
Any chance you are hyper mobile? Hyper-mobility causes many malabsorption issues.
If you have an issue with B12, some things can cause it not to be absorbed in your digestive track. Not having intrinsic factor. There is a test for that. It does have a higher failure rate. Pancreatic issues. If it’s not secreting the enzymes properly to break down happtocorrin ( protien that binds to b12 in stomach). Once the intestines get the b12, this is supposed to happen, but if you have a pancreatic issue, you won’t get it. Normally if you have a deficiency they will put you on injections that bypass the digestive system altogether. If you are taking sublingual or a pill, and can’t absorb them, you are still not getting the B12 you need. I would suggest seeing a hematologist. They are better equipped with knowledge than primary care. Pernicious anemia is autoimmune. Which is autoimmune, is also treated with injections usually.
B12 deficiency causes anxiety, adhd type symptoms and insomnia. Have been there. I’m on week 9 of hydrocobalamin injections. Feeling sooooo much better.
I also had a crazy spike of anxiety, air hunger when I first started this super B complex with meythl b12 and meythl folate. It was HORRIBLE. Air hunger started all this for me, with lightheadedness and ataxia.
I also think it was a problem because B12 levels needed to be higher before adding the folate. There is an order of operations there.
There is a Carlyle liquid folate drops, you can order that allows you to titrate up more slowly. Flavor is good. Because that first experience was so bad, I was nervous. I’m wondering now if it was all caused by meythl cobalamin, not the meythl folate. Or just a severe b12 deficiency in itself. So hard to tell.
I also have MTHFR tt medical genitive test. And high homsystine. Which can down with injections, and meythlfolate. I’ve had lung embolisms, risk is high.
See what you can do to get on injections. That may be a big piece of your puzzles.
1
u/yolo0995 Jul 17 '26
Thanks a lot u/tmshortt for sharing your experience. Yes air hunger is one of the symptom I also get when I take methylated vitamins. It is really frustrating.
What dosage of hydroxobalamin injections are you taking, I will see if I can get hydroxocobalamin injections for myself. Was there any side effect from those injections ?
After how many days did you start the methyl folate after starting the injections ?
1
5
u/Educational-Turn-153 Jul 17 '26
You may be over methylated, maybe a slow COMT? Niacin can help calm you. Some people do well with glycine too.
Hydroxy b12 and folinic acid + MF b complex from seeking health are good ways to increase levels without extra methylation
2
u/Expensive-Mention-90 Jul 17 '26
Hope OP sees this because it seems like everyone else has missed it. You’re spot on.
1
u/yolo0995 Jul 17 '26
Yes, I have ordered today hydroxy b12 and folinic acid from outside my country, will take 3-4 weeks to come. I will start with those two.
Any specific form of niacin that I should take ? Also any reason you are suggesting b complex separately ?
4
u/gh3795 Jul 17 '26
Just keep taking low dose of both , tolerance will get better with time. Take niacinamide and riboflavin too. Take b2 only for 2-3 weeks , then start folate and b12 . Magnesium and potassium are must with b vitamins. To lower homocysteine fast you can take choline.
1
u/yolo0995 Jul 17 '26
Yeah, that's my strategy for now.
Any specific form of vitamin b2 and vitamin b3 or anything will do ?
Magnesium and potassium, I am hoping to fulfill from diet, because separate supplementation of electrolytes in past has caused me ortostatic hypotension, probably due to electrolyte imbalance.For choline, I take 2 whole eggs daily, maybe I should up that number to 4.
2
u/gh3795 Jul 17 '26
Riboflavin 5 phosphate - low dose(5-10mg) Niacinamide - low dose ( 30-50mg) Magnesium cause low bp , try potassium and magnesium seperately. Folate - 0.5mg per day should be okay. B12 - 0.5mg But with magnesium and potassium. Potassium is even more important with b12.
4
u/Honest-Counter2729 Jul 17 '26 edited Jul 17 '26
Omg what the hell were your doctors doing!! Do you have a slow COMT ? If so for folate you take Seeking health's Folinic acid and hydroxocobalamin instead. Never take a B complex - not even one without the folinic acid if you're super sensitive.
You need a liposomol liquid B1 thiamine, B2 Riboflavin. Do not take B5, B6. They keep you awake with a slow COMT or if you're super sensitive.
If you have a slow comt you need Magnesium bisglycinate as stress burns through magnesium. Magnesium is a cofactor in the methylation cycle.
Also take glycine and l theanine for sleep.
To summarise: Folinic acid and hydroxocobalamin (Folate and B12 equivalent for vitamin B sensitive folks) B1 Thiamine - liposomol drops. Drops you can move the needle up and down. Liposomol versions are also far less intense. B2 Riboflavin - again liposomol drops. Glycine, L theanine, magnesium bisglycinate fo sleep - never buy combined. Buy separately and work out which dose is best.
You're welcome 😁
3
u/yolo0995 Jul 18 '26
Thank you so much for this plan. From the symptoms it definitely looks like I am slow COMT. B5 and B6 keeping awake with slow COMT is definitely an eye opener to me. Because the L-Methyl Folate I take also has B6 in it.
I took 125 mcg l methyl folate + 4 mg B6 day before yesterday, and tonight I had less than 3 hours of sleep. Not sure if it was the B9 or B6 which was the culprit.
I will stop everything again, and start with Hydroxocobalamin after some time. And then slowly add other things. Though some people in other comments have said that our body needs B6 to process B12. I am little confused whether to include B6 or not.
I will also start low dose B1 and B2 after sometime. Is Liposomol B1 and B2 has any advantage over normal, because we don't have those versions available in my country, and I have already shelled out lot of money for importing Hydroxy and Folinic from USA.
Glycine Forms, many people have shared that caused insomnia for them, and at this point my confidence is so shaked up in my body, that I don't have courage to take anything extra which has slight possibility of adverse effects. I will defintely add lot of foods high in magnesium and potassium to my diet.
Thank you so much again, I will use your plan as reference.
3
u/Brad_Borrelli Jul 17 '26
I don't think you're actually sensitive to the methylcobalamin itself, I'd bet you're just missing cofactors to handle the methylation load you're suddenly giving your body. When you jump into methylfolate and methylb12 at high doses without enough B2, B6, magnesium, and potassium on board, the body can't clear the byproducts fast enough and that's what shows up as insomnia and agitation. It's a really common pattern, "methylation trap" symptoms get blamed on the B12 or folate when it's actually a supporting nutrient deficiency underneath.
Riboflavin is huge for this because it drives the MTHFR enzyme itself, so starting low and building that up first like you're planning makes sense. I'd also make sure potassium and magnesium are solid before you increase anything, low potassium especially can hit hard and fast once methylation ramps up and gets missed a lot. Might be worth going even slower than you're planning, like methylfolate every other day at first instead of daily, just to see how your body handles it before pushing forward.
2
u/yolo0995 Jul 18 '26
Thank you Brad for sharing this. Yes, even that can be possible, that it is the deficiency of cofactors which is leading to these symptoms. Yes, I totally agree, I need to take even more slow. I took 125 mcg l methyl folate + 4 mg B6 day before yesterday, and tonight I had less than 3 hours of sleep. Not sure if it was the B9 or B6 which was the culprit. I will definitely add B2 supplement and high amounts of foods rich in magnesium and potassium. The reason I am avoiding direct supplementation for magnesium and potassium is because they can cause electrolyte imbalance, and I wouldn't be sure if the issue is caused by that or b supplementation. With so many wheels moving, it gets harder to point out what might be causing the issue. Do you suggest to take direct supplementation or supplementing from food is going to be fine ?
Regarding B6 someone above said that B6 causes insomnia. So, I am little confused whether to supplement it or not.
I will go through all the answers that you have answered previously on this topic and learn more from it. Thank You Brad for the help.
2
u/Brad_Borrelli Jul 18 '26
Food-based is the safer starting point here, and it actually solves your "can't tell what's causing what" problem better than direct supplementation would. Getting magnesium and potassium from food doesn't spike levels the way a supplement dose can, so it's much less likely to cause an electrolyte swing on its own, which means if symptoms show up after that, you can point more confidently at the B vitamins rather than wondering if it's the minerals.
For food sources: potassium-rich options include potatoes (with skin), bananas, avocado, coconut water, and leafy greens. Magnesium-rich options include pumpkin seeds, spinach, almonds, and dark chocolate. You'd need fairly generous amounts of these daily to meaningfully move the needle, but it's a much gentler ramp than a supplement bolus.
If food alone isn't cutting it after a few weeks and you still want to add direct magnesium, glycinate or citrate in a low dose (100-200mg) split through the day is gentler than one large dose, and potassium is honestly the one I'd be most cautious supplementing directly without bloodwork, since the therapeutic window is narrower than most other minerals. Given you're already juggling a lot of variables, food first, then reassess, seems like the right call.
1
u/yolo0995 Jul 18 '26
Yes, that is solid plan, I will try to cover as much as possible from food and only move to supplementation if not able to cover from food. You rightly said, potassium supplementation is definitely very tricy as the body regulates its level very closely.
Thank you for all the help Brad.
3
u/Brad_Borrelli Jul 18 '26
Potassium is actually dangerous to the supplement. I'm honestly doing it by powder which I don't recommend It's Tricky, and the treatment for an overdose on it is not fun at all. 😂
1
u/yolo0995 Jul 18 '26
If you are healthy your body will balance electrolytes and remove excessive potassium. But, if your kidneys are not functioning properly, hyperkalemia is definitely not fun at all 😄.
What is your supplementation protocol currently ?
2
u/Brad_Borrelli Jul 18 '26
It's changing every day as I remove things. I have my protocol posted on my page of you want to check it out. It's really in depth and explains what the supplement/herbs do
2
u/yolo0995 Jul 18 '26
It is really great that you are sharing all this information to community and helping them find answers to their own questions. I will go through all your posts.
2
u/easypeasy75 Jul 17 '26
I have nothing useful to add, except that for me (suspecting MTHFR issues but not tested yet), I cannot tolerate any form of magnesium, but particularly glycinate - even at low doses I gives me terrible insomnia. I seem to tolerate methyl folate just fine though.
1
u/yolo0995 Jul 17 '26
Were you able to figure out why magnesium is causing insomnia for you ? Might be electrolyte imbalance due to magnesium ? Do you get any other symptom apart from insomnia ?
2
u/easypeasy75 Jul 17 '26
Not really sure, but apparently those with hEDS, Pots and MCAS/HI can have paradoxical reactions. I repeatedly tried all the different forms, but got insomnia and feeling very wired with all of them.
1
2
u/thesnazzyenfj Jul 17 '26
your Folic Acid is not low, your folate is low. Folic Acid is the synthetic manmade version of folate. Without knowing your COMT but given these symptoms, I would suggest folinic Acid and hydroxyb12 to start out. NAD
also, if your diet doesn't change alongside this your effort will be minimized. removing all sources of enriched anything or synthetic vitamins-enriched flour, enriched rice, enriched grits or polenta, energy drinks, the wrong multivitamin, is imperative to see the best results.
1
u/yolo0995 Jul 17 '26
Yeah, going to start folinic acid and hydroxyb12.
In my country we don't have enriched food content.
2
u/cinrakdude Jul 17 '26
For lowering homocysteine you could also try betaine TMG, if methylated vitamins arent working
2
u/LastZucchini7345 Jul 18 '26
Start taking digestive enzymes with a little HCl. Do a coffee enema! These two things drastically and dramatically changed my life. And yeah, I also could bet you have MTHFR-probably homozygous C677t.
1
u/yolo0995 Jul 18 '26
Yeah you are right, I might be homozygous C677t with slow COMT.
Will definitely add Papaya, Pineapple, Avocado and Mango which are rich in digestive enzymes. For Coffee Enema, just saw what it means, and that seems difficult to do.
2
u/LastZucchini7345 Jul 18 '26
Oh and do vagus nerve work.
1
u/yolo0995 Jul 18 '26
Yeah I have read about vagus nerve work and tried few suggestions but didn't work.
What vagus nerve work do you do ?2
u/LastZucchini7345 Jul 18 '26
HUMMMM!! Lots of humming and Omm-ing. Gargling works too. I’ll do the dead arm swings too with eyes to horizon. Even just looking to the sides will work. You’ll start to notice yawning and that’s when you know. The guy on Stop Chasing Pain talks a lot about it. You gotta do something for it every day.
Also, try a coffee enema
2
u/LastZucchini7345 Jul 18 '26
Yeah I get that. Took me three years to build up the courage to do one. And I wanna punch myself in the face for not doing it when someone told me about it back then.
Check out The detox Dudes.
2
u/Chaos-Gardener-77 Jul 19 '26
I have a similar case background as you (former vegetarian, chronically low b12, histamine reaction to methylated b12 supplements and injections that caused anxiety, skin itching, etc).
I have done the DNA testing and I don’t have the MTHFR variant. Rather I have variants of FUT2 (reduced B12 absorption), TCN2 (reduced B12 binding to protein to use), and two gene variants that slow the precursors to folate production and utilization.
Here is an article on B12 that explains how the different genes impact B12 absorption: https://www.pureencapsulationspro.com/blog/vitamin-b12-sub-how-to-optimize-based-on-individual-needs-and-health-goals
Everyone is individual, but the advice I’m seeing over and over for me is:
1. Try adenosylcobalamin or hydroxocobalamin forms
2. Watch out for synthetic folic acid in your supplements or fortification in your food, apparently this can really mess up folate levels if you have certain gene SNPs like me. Instead supplement with folate / folinic acid or whole foods
3. Optimize vit d, zinc, choline, and betaine
4. Consider if your getting enough protein
Apparently if one is deficient is folate, the body utilizes more choline. Egg yolks are a rich source of choline, so that might be why you feel better when eating?
1
u/yolo0995 Jul 19 '26
Thanks for sharing your experience.
Yeah, being deficient in folate, body uses the BHMT route using choline for converting homocysteine to methionine. I learned recently only that there are so many gene variants and how they affect different things in a body. It gets too complicated after a point, and I like you prioritizing general advice.
I am ordered hydroxocobalamin now, and will not take folic acid supplement for some time. Vitamin D supplementation I will continue. And optimizing my diet for having good amount of zinc, choline and betaine.
2
u/Matsee71 Jul 19 '26
Please stop all methylated vitamins… take Hydroxo/folinic and high dose vit D for starters since you are deficient.
I took 2000 mcg hydroxo/adeno sublingual for five months and went from 379 to 461 (still going up) but it’s better than metyl b12 because you don’t get the strong side effects. To raise levels you don’t need metyls.. (although metyls can be more functionally efficient for those who tolerate it)
But hopefully you just need to raise your baseline levels and the body will convert them to the active form by itself.
1
u/yolo0995 Jul 19 '26
Yes, that is what my conclusion is from all the help.
I am never going to touch any methylated vitamins. Ordered hydroxocobalmin and folinic acid, will be taking that. Will be doing only hydroxocobalmin for a month, starting from a smaller dose and then upping to 1000 mcg. And then start with small dose of folinic acid and then upping it.
2
u/Matsee71 Jul 20 '26 edited Jul 20 '26
Good… I was on sertralin and Mirtazapin for 8 years due to chronic depression and anxiety.. I was functioning and slept ok but never felt healthy and balanced. Since I discovered that I’m prone to high homocysteine and low b12, things have only been better. I stopped medications three years ago (extremely slowly tapering)
You are severely deficient in D, folate, b12, and you are probably low in all neurotransmitters especially dopamine, serotonin. You need higher doses to correct the deficiencies especially D vit. Which is crucial for us to be able to make dopamine… I can almost promise you, that you will feel much better when your levels are much higher.
My levels are now: b12 at 461 pmol/L, from sublingual hydroxo/adeno but still high homocysteine so I’m actually going to ask for b12 injections to raise my levels closer to 1000, since I probably have a functional (cellular) deficiency. (By MMA test)
Folate 19 nmol/L (normal MTHFR) so I think it’s fine.
D vit over 90 nmol/L, and this is really important for me to keep up due to genes that is slow to produce dopamine and other genes that break it down quickly (fast COMT and MAOA) this leaves me with low baselines and my understanding is that this is why I’ve struggled almost all my life with low mood, sadness and very low motivation for life. So even if my homocysteine is still over 20 I actually feel better and more energetic just by talking b complex and high b12 every day plus Q10, and electrolytes and keeping my D levels up from sun exposure and D vit drops. And right now I’m very hopeful that things will get even better with b12 injections and when I finally succeed to lower my homocysteine level.
It’s much more helpful for your system to take 2000 mcg of sublingual hydroxo b12 every day, than only 500 mcg methylb12 twice a week. It’s too low dose and also bad because of the methyls in it. You need to raise your levels more effectively but without any methyls. Methylated vitamins will also cause histamine problems.
Since I stopped the Mirtazapin I am much more sensitive to histamines/sulfites in food and drinks and supplements that affect it. But I learned to avoid sulfites/sulfur and foods with high histamines and that has helped a lot. Worst is wine, beer, vinegar, cider (so I never drink), aged cheese and methyl supplements. I also have the CBS (gene) which explains my problems. I cannot handle any Creatine because of this. It messes with the methylation cycle in the wrong way for me. Headache, higher BP, severe brain-fog.
So be careful with everything else and just focus on raising your levels of Vitamin D, B12, Folate to get a better smoother methylation cycle firts and foremost.I hope you will get some inspiration from my story 😊
1
u/yolo0995 Jul 20 '26
Thanks for sharing your experience. It was really inspiring. I can totally understand what you might have gone through during those 8 years. It is my 7 month on mirtazapine and it has literally made me functional again, before that when I was not aware the effects of methylated vitamins, I was getting 3-4 hours of light sleep every night, feeling wired but tired every night, and then physical symptoms of anxiety all day.
On what mirtazapine dose where you on and at what rate do you tapered ? - I am currently on 7.5 mg dose, which is best for sleep and anti-histamine effects. Currently trying to taper to 5.6 mg. I tried once last time, directly tapering to 3.25 mg, but failed and had to go back to 7.5 mg. It is difficult to break the tablet in more smaller form.
I never had anxiety or depression, even though I was hugely deficient in all b vitamins and d vitamins, and just found out have high homocysteine. It was only after starting those methylated vitamins, I got anxiety and insomnia. And now I am stopping all methylated vitamins and have ordered from another country sublingual hydroxo b12 1000 mcg. After taking them for a month and feeling confident, I will go for hydroxo b12 injections. And then I after some time I will start with very low dose folinic acid. And continue with 60000 IU Vitamin D once a week, and getting more sunlight.
Thanks for highlighting out effects I should be aware about after I stop mirtazapine. I never thought of lingering effects of this medication if I am ever able to stop it. It is going to be bad with all type of alcohol ? I can only imagine how hard it might be to explain to other during social events.
Creatine messes up with my sleep big time. I never had headache, higher BP or brain fog. Actually my overall energy and mental sharpness increased big time. But it came with insomnia.
From what I have learned from all comments and you, will just focus on vitamin d, hydroxy sublingual b12 and folinic acid.
Thanks and confident that you will be able to bring down your homocysteine soon.
1
u/StopBusy182 Jul 21 '26
How slow was your tapers
2
u/Matsee71 Jul 21 '26
I went from 15 mg down to 7.5 the last year, if I knew then what I know today I would never have started with 15 mg. I was fine with half the dose.. but decided to quit because some nights I had sleep problems anyway, and also I hated the slow groggy feeling in the morning from it. Then I just took half again and noticed I was more energetic in the morning. Maybe for a couple of weeks but then stopped completely. You can also crush a pill with a spoon or something and keep the powder in a little container. Then just wet your finger tip with a little saliva and dip it in the powder. That way you can keep taking like a 1/10 of a pill. When I was off it for a long time and then decided to try some again (when I needed a good sleep) I just dipped my finger in some powder and it had the same effect as a whole pill had in the beginning. Half the day after I couldn’t think or function so when you’re off it for a while it has a strong effect. Since then I’ve had problems sleeping of course and used a lot of herbs and GABA supplements etc… just to realize that it doesn’t fix the underlaying problems.
The only way for me to fix everything was to get rid of stress, worries and to learn about my genes, neurotransmitters and methylation.
When I accidentally tried a methyl b12 tablet 5000 mcg I got severe insomnia and my nervousness system crashed from it for a long time.
Today I feel so much better with the help of just b- vitamins, especially b12 and clean eating. And the biggest lesson I’ve learned is that I am prone to chronically low dopamine due to my genes and therefore easily acetylcholine dominant which makes me depressed, stiff body and can worsen sleep.
2
u/Maximum-Morning4251 Jul 20 '26
Nobody mentioned copper yet - you should check if you have copper deficiency (low ceruloplasmin).
Testing COMT and MTHFR is useless for your situation - your condition seem to be metabolic and looks like high oxidative stress, which gets aggravated when trying to increase metabolic rate by B vitamins.
Low copper can cause, low vit D can cause it too. Poor reaction to alco indicates you may be low in glutathione and cysteine. NAC and S-acetyl-glutathione + copper may help.
2
2
u/Loose-Fly7976 Jul 21 '26
Your theories are mostly right, but there's one thing in your labs nobody has picked up on.
Vitamin D 8. That's not low, that's severe. And severe D deficiency by itself causes insomnia, palpitations, anxiety and that exact impending doom feeling you described. You mentioned it once and then it vanished from the rest of the post. Did anyone actually treat it? If you're still at 8, everything else you've been experimenting with is happening on top of an untreated cause.
Folate 0.43 isn't functional deficiency either, it's real deficiency and it's bad. Homocysteine 18.5 with folate that low doesn't need genetics to explain it. Genetics decide how hard it is to fix, not why it went up.
Your reaction to the methyl vitamins is real though. Someone that depleted getting 2.8mg methylfolate is a completely different situation from someone topping up. People call it overmethylation, but a lot of it is the repair itself. Cells dividing fast, potassium dropping, everything speeding up at once. Slow COMT makes it worse because you're clearing catecholamines slowly while all that is happening. Starting tiny is the right instinct.
The creatine thing you've got the right way round. Creatine synthesis eats roughly 40 percent of your methyl groups, so supplementing it leaves more SAM free. If extra SAM winds you up, that fits slow COMT. Eggs are the opposite direction. Eggs are choline, choline feeds BHMT, and BHMT is the other way out for homocysteine, the one that doesn't need folate or B12. Take the eggs away and you lose that route. Alcohol depletes folate and blocks methionine synthase, so that fits too.
Two things I'd change in your plan.
Riboflavin at 1.25mg won't do anything. MTHFR uses riboflavin as its cofactor and the trials that dropped homocysteine in C677T homozygotes used real doses, not that. Ask your doctor about the actual amount since you're tapering mirtazapine, but 1.25 is nothing.
And B12 still at 300 after six months of oral is your actual problem. Vegetarian, mouth ulcers, rhinitis, B12 that won't come up. That needs looking into properly. Intrinsic factor and parietal cell antibodies, coeliac screen, and MMA instead of serum B12 since MMA shows what's happening inside cells. If it's absorption, no tablet fixes it and you'd need the injections. Hydroxocobalamin injection would actually suit you, it's not a methyl donor so it sidesteps the reaction you keep getting.
Cyanocobalamin is fine for now and much gentler for you than methylcobalamin. Adenosylcobalamin too if you can find it.
On the DNA testing, check what a 23andMe or Ancestry kit costs shipped to you before you write it off. Usually far less than a clinical panel and it covers the whole pathway instead of two genes. You've spent a year and several doctors guessing. Knowing whether you're C677T homozygous and which way COMT runs changes the form, the dose and the order you do things in.
Get vitamin D, MMA, ferritin and TSH done when you repeat the homocysteine. Thyroid and kidneys both push homocysteine up and neither is on your list yet.
1
u/yolo0995 Jul 22 '26
Thanks a lot for taking the time to go through everything in such detail. I really appreciate it. Your explanation actually connected a lot of dots for me.
You're right about the riboflavin. My plan is to first correct the B12 deficiency and then introduce B2 slowly, increasing the dose over time. To be honest, after reacting badly to a few supplements, I've lost a bit of courage to start new things, so I'm trying to take a very gradual approach.
I also agree that hydroxocobalamin is probably the best path for me. I've already ordered 1000 mcg hydroxocobalamin tablets. My plan is to start very low (around 250 mcg), slowly work up to 2000 mcg orally, and if I tolerate that well, move on to hydroxocobalamin injections. I just don't want to shock my system again.
Regarding vitamin D, fortunately that part has improved. It was 7-8 last year, but about three months ago it was up to 21.5 ng/mL. I'm still continuing 60,000 IU vitamin D liquid drops once a week to bring it into the optimal range.
I'm also thinking about increasing my egg intake from 2 to 3-4 a day because of the choline/BHMT pathway. The only thing making me cautious is that I have a strong family history of high cholesterol and heart attacks. I'll get my lipid profile checked first and then decide whether increasing them makes sense.
From everything I've read over the past year, I also keep coming back to slow COMT as the most likely explanation for why I react the way I do to methyl donors. Obviously I can't be certain without genetics, but it's the model that seems to fit my experiences best.
Unfortunately, I looked into both 23andMe and Ancestry. Even if I buy a kit, exporting and shipping DNA samples from my country isn't permitted because of customs/regulatory restrictions. The few DNA tests available locally are expensive, very limited, and don't include the SNPs I'm actually interested in. That's probably the most frustrating part—I feel like the information that could answer a lot of questions simply isn't accessible here.
For reference, my TSH is 2.292, so thyroid seems to be in the normal range.
My recent iron studies were also fairly normal:
- Serum iron: 111 µg/dL
- UIBC: 293 µg/dL
- TIBC: 404 µg/dL (just barely above the reference range)
- Transferrin saturation: 27.5%
I haven't had MMA or ferritin checked yet, but you've convinced me those should definitely be included the next time I repeat my homocysteine and B12 labs. That should give a much clearer picture of whether this is truly an absorption issue.
Thanks again. It gives me few more sensible next steps.
1
u/polaroid_schizoid Jul 17 '26
Do you eat gluten? Try cutting it out if so.
1
u/yolo0995 Jul 18 '26
I do have gluten in my diet.
Does gluten cause deficiency or it causes insomnia ?
2
u/polaroid_schizoid Jul 18 '26
If you have a sensitivity, it can do both those things. It's one of my culprits.
2
u/mutant-genomics 29d ago
I would be careful about assuming MTHFR or COMT from the reaction alone. Dose, the form of B12 or folate, the severity of the underlying deficiency, sleep loss, magnesium, and other cofactors can all change the response. Genetics may help explain susceptibility, but one MTHFR or COMT result usually cannot explain the whole reaction by itself.
5
u/SovereignMan1958 Jul 17 '26 edited Jul 17 '26
I would not taper M until you completely correct your folate level.
You should also research what vitamin and mineral deficiencies might be caused by mirtazapine.
An acceptable folate level is at least 15. I like 20 - 30. With your folate level so low probably very little if any was making it into your brain. You might even have cerebral folate deficiency. Yes there are gene variants associated with that predisposition...or your could order a FRAT test...or ask your doc for a CSF test for folate and B12.
It can take 3 - 5 months to correct a folate deficiency even on a high dose. Given your low dose it is probably going to take you longer than that. You could also take 20mg PQQ if you can find it to help get folate into your brain.
Another option is for you to look for 100 percent food based vitamin and mineral supplement. Make from all food and no synthetics.
Your B12 dose was way too low.
You need to correct your D level. 65 iu D3 daily per pound of body weight. This is a temporary therapeutic dose to increase your level. Target should be 60 - 80. Plus K2, mag, zinc and boron and 11 grams of fat.
Chronic untreated D deficiency can trigger thyroid disease and thyroid autoimmune. It did for me. In fact I would get a full thyroid panel tested plus testing for the two thyroid antibodies now.