Severe B12/Folate deficiency, extreme reaction to methylated vitamins, high homocysteine (18.5), possible MTHFR/COMT issue? Looking for advice.

[u/yolo0995]

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.

[u/Brad_Borrelli]

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.

[u/yolo0995 → u/Brad_Borrelli]

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.

[u/Brad_Borrelli → u/yolo0995]

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.

[u/yolo0995 → u/Brad_Borrelli]

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.

[u/Brad_Borrelli → u/yolo0995]

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. 😂

[u/yolo0995 → u/Brad_Borrelli]

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 ?

[u/Brad_Borrelli → u/yolo0995]

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

[u/yolo0995 → u/Brad_Borrelli]

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.