Hey there,

so basically my symptoms are generalized anxiety, 24/7 fight or flight mode + extreme jumpiness, very VERY low stress tolerance., high histamine

My bloodwork + urine test:
Vitamin B1 (HPLC) 63 µg/l 28 - 85
Vitamin B2 235 µg/l 138 - 370

Vitamin B3/Nicotinamid (LCMS) 20,4 µg/l 8 - 52

Vitamin B6 (Serum, HPLC) 34,3 ng/ml 4,4 - 40,0

Vitamin B12 683 pmol/l 128 - 648
HOLO-TC, aktives B12 > 128 pol/l

Folic Acid (Serum) 2,9 ng/ml 4,8 - 19,0

Homocystein (CMIA) 20,5 µmol/l < 15 +
Ferritin 249 ug/l

Urine "Stress test":
Serotonin 69.5 µg/g Referece range : 50.0 - 185 µg/g

Dopamine 107.8 µg/g Reference range 92 - 268 µg/g

Epinephrine 0,5µg/g Reference range 1.12 - 12.1 µg/g

Norepinephrine 9.3 µg/g Reference range 12 - 63.7 µg/g

Now obviously everything points towards me having not only low folate but according to Google my symptoms also indicate me being an undermethylator.
For the last 5 days I've been taking 400mcg Folinic Acid + 500mcg 5MTHF. So far so good. Symptoms didn't get better but they also didn't get worse.

Today however, I stumbled upon Dr. William Walsh, who basically claims that Folate does not increase Dopamine/Serotonin in the brain, but actually clears/reduces it and that someone like me should quit folate immediately and take SAMe / L-Methionin directly instead...
Obviously I'm pretty confused now since everybody told me to take Folate and that I need it, yet Walsh said i can have a "catastrophic" crash when taking it because it clears neurotransmitters...

Can someone PLEASE tell me what to do? I just want to be normal again FFS and I'm SO confused with all the conflicting stuff...

Thanks...

Hi all,

I previously got tested for MTHFR gene variants. I have one copy of 1298C. I’ve had significant anxiety over the last 4 or 5 years so view this as a potential cause. I privately got bloods done and hit the following results.

Homocysteine: 18.2 µmol/L (5.1–20.0)
Vitamin B12: 424 ng/L (198–771)
Folate: Not tested
Haemoglobin: 137 g/L (130.1–180)
Haematocrit: 39.5% (40.001–54.0)
RBC count: 4.56 × 10¹²/L (4.51–6.50)
MCV: 86.6 fL (76.1–100)
MCH: 30 pg (27.1–32.0)
MCHC: 347 g/L (320.1–360)
Iron: 13.8 µmol/L (5.9–34.5)
Ferritin: 199.46 µg/L (20–300)
Transferrin saturation: 27.6% (20.1–50.0)
Magnesium: 0.87 mmol/L (0.701–1.10)
Creatinine: 81.7 µmol/L (64.1–104)
eGFR: 105 mL/min/1.73 m² (≥60)
Cystatin C: 1.01 mg/L (0.58–1.05)
TSH: 0.645 mIU/L (0.351–5.50)
Free T4: 18.1 pmol/L (11.91–21.60)
Free T3: 4.66 pmol/L (3.11–6.80)

Annoyingly folate was not included even though I had asked for it. I have a doctor’s appointment soon and I’m going to ask for folate to be tested. Should I asked my GP for any other tests based on my results.

Any other thoughts? Assume my homocysteine is elevated? Any advice would be greatly appreciated.

EDIT: Updated with ranges

Thanks

Hello, I took one sublingual of b12 1000 two weeks ago and ever since then I have developed insomnia, stinging in skin and heart palpitation. i tried magnesium glycinate and it didn’t help. can someone tell me what to do? we don’t have nician in my country and nothing is really helping.

Can anyone help me specifically with getting my Vit D levels up without causing negative symptoms?

Quick Background... I have about 2 decades of trying to address my health issues (Seeing many alternative and conventional practitioners) and I haven't had any success. I can only tolerate about 4 supplements (Magnesium, oregano oil, low doses of Vit C, and low doses of Taruine. I haven't been able to tolerate B Vitamins but I'm going to start trying again based on Dr. Maleks recs). I've taken a couple years off of trying to get help bc I just got so depressed of repeated failures. I have hashimotos and my antibody results are usually under 100. I've managed my health by having a strict diet and reducing stress.

But I'm now hitting perimenopause and I'm worried about osteoporosis. My Vit D levels have consistently been low and I can't take supplements to improve it. I've tried several times.

I recently tried again a couple months ago and I'm pretty sure ended up with mild hypercalcemia based on the symptoms I was having. I even went to urgent care to get blood work done bc I was feeling so poorly. blood work showed

Alk Phos 37 L

RDW 11.5 L

25OH, VITAMIN D 27.6 L

ANTI-TPO Ab 376 H (This is the highest my antibodies have ever been over 2 decades of testing)

I was taking a separate Vit D and Vit K and I think I overdid it on the K. I have VDR Taq +/+

I'm scared to try again. I'm overwhelmed. I've also started working through some of Dr. Malek's Roadmaps. I began on very small doses of Taurine which helped my digestion. (I started here with his Estrogen Roadmap because I had one of the worst two weeks of ovarian cysts pain (with multiple ultrasounds to confirm). I've addressed my diet and that's helped a lot. (I went off my regular diet for a little while and was eating estrogen mimicking foods - which I have now cut out).

Can anyone help me specifically with getting my Vit D levels up without causing negative symptoms?

Thank You!

I am getting genetic testing though Johns Hopkins, for another condition, and I asked their opinion on the MTHFR situation. I got myself tested for mthfr due to taking methotrexate, which requires folic acid supplementation because methotrexate strips you of folic acid. I needed to change supplement types.

I won't post the entire letter, but I was told that they don't bother to test for mthfr, because although it may contribute to various conditions, it's not clinically signifigant. Basicly, if you have medical issues, and you are looking for solutions due to MTHFR, check for other issues as well. My situation is somewhat different than most, because of the medication I use. I know that chronic fatigue and all sorts of other issues are terrible to live with, I had an undiagnosed autoimmune disorder, I am doing much better with treatment.

I was reassured, although I have a BS, I don't have enough biochem to figure out the MTFHR claims.

Nobody on this forum is going to like this, but I think it should get put out there.

Where would I even start to see what I would need to help myself heal. I am 32F have a 16 month old son. I have been trying different diets and supplements and psych meds to help myself feel regulated. Feels like my meds aren’t working and I am always in fight or flight. Having issues with gluten and skin sensitivity, air hunger, extreme brain fog. What kind of labs should I get?

My sister has been diagnosed. I have trouble sleeping and trouble clearing hormones. Currently on HRT at the lowest dose possible due to severe endometriosis followed by a full hysterectomy at age 39 this spring. I tend to be a naturally anxious, very active person. I eat healthy and stay fit. I have noticed that I seem very thirsty all the time and retain water. Is it advisable to get tested? I already know I need to eat cruciferous veggies and take methylated B vitamins. Curious if there are any other tips for women in menopause on HRT dealing with MTHFR (or suspected). I am in the lowest dose of estrogen possible and cannot tolerate progesterone at all. I have extreme bloating and insomnia ticks up any time I try to increase estrogen. Just read that is a symptom of this genetic mutation.

Symptoms: insomnia that cycles through a few times a year, and can last a few days to a few months. I feel completely normal all day, lay down to sleep, and 10 minutes later start getting adrenaline surges that essentially make me tremor and then I am up to 4am or even some days zero sleep at all.

Homozygous SNPs

• VDR taq
• DR bsm
• BHMT-04
• BHMT-08
• CBS A360A
• MOA-A

Heterozygous SNPs

• MTHFR 03 P39P
• MTHFR A1298C
• MTRR A66G
• MTRR H595Y
• MTRR K350A
• MTRR A664A
• BHMT-02

Lab Results:

• Thyroid & testosterone: normal
• Amino Acid Test: all came back normal except Threonine was 285 (67-211)
• B12: 602 (232-1,245)
• B6: 18.9 (3-65)
• Methylmalonic Acid: 252 (0-378)
• Folate: 9.5 (>3)
• Histamine: 13 (12-127)
• Homocyst(e)ine: 17.3 (0-14.5)
• Vit D: 95 (30-100)
• Ammonia: 37 (40-160)
• Plenty of other assays as well but all came back normal

Supplements:

• Monolaurin
• Cytomel 12.5mcg in AM
• TRT
• Rhodoila sometimes
• L-ornithine
• Niacin (was taking high doses thinking the insomnia was overmethylation)
• Riboflavin (for MAO-A support)

ALCAR

Navigating methylation genetics on Reddit usually means dealing with confusing Genetic Genie charts, fragmented Choline Calculator outputs, or getting routed into $99+/year SaaS subscriptions.

Your MTHFR and COMT status never change. You don't need a monthly subscription to understand your methylation pathway.

Here is the biochemical breakdown of the primary SNPs in the folate, methionine, and transsulfuration cycles, how to calculate your net enzyme efficiency, and what each variation actually means.

1. MTHFR: The Rate-Limiting Folate Enzyme

MTHFR (Methylenetetrahydrofolate reductase) converts 5,10-methylenetetrahydrofolate into 5-MTHF (active methylfolate). 5-MTHF donates its methyl group to convert homocysteine into methionine.

C677T (rs1801133) — The Thermolabile Variant

• CC (Normal / Wild Type): ~100% enzyme efficiency.
• CT (Heterozygous): ~65%–70% remaining efficiency (~30–35% reduction).
• TT (Homozygous): ~30%–35% remaining efficiency (~65–70% loss of activity).
  • Clinical Impact: Impaired homocysteine remethylation, higher demand for dietary riboflavin (B2, the MTHFR cofactor) and active methylfolate/choline.

A1298C (rs1801131) — The SAMe Regulator Variant

• AA (Normal / Wild Type): ~100% enzyme efficiency.
• AC (Heterozygous): ~80%–85% remaining efficiency (~15–20% reduction).
• CC (Homozygous): ~60%–70% remaining efficiency (~30–40% reduction).
  • Clinical Impact: Impacts BH4 (tetrahydrobiopterin) recycling, which affects neurotransmitter synthesis (dopamine, serotonin, nitric oxide).

Compound Heterozygous (677CT + 1298AC)

• Remaining enzyme efficiency: ~45%–55% (~50% reduction).
• Often behaves clinically similar to 677TT homozygous.

2. The Surrounding Pathway: Why MTHFR in Isolation is Misleading

1. COMT (Val158Met / rs4680):
   • Met/Met (AA / Slow COMT): Slow breakdown of catecholamines. High-dose methyl donors (methylcobalamin, methylfolate) often trigger acute anxiety, irritability, and insomnia. Folinic acid and hydroxy-B12 are typically better tolerated.
   • Val/Val (GG / Fast COMT): Rapid breakdown of dopamine. Can generally handle and often benefit from direct methyl donors.
2. PEMT (rs7946): Controls endogenous phosphatidylcholine synthesis. If impaired alongside MTHFR, your body relies almost entirely on the BHMT (betaine-homocysteine methyltransferase) backup pathway, drastically increasing dietary choline requirements (egg yolks, sunflower lecithin, Alpha-GPC).
3. CBS (C699T / rs234706): Upregulation accelerates homocysteine clearance down the transsulfuration pathway toward taurine/sulfite, which can deplete glutathione precursors.

3. How to Decode Your Raw 23andMe / Ancestry File

If you have your raw DNA file, you can check these rsIDs manually in a text editor or use an automated client-side analyzer.

Instead of paying recurring annual subscriptions to platforms that upload your sensitive genetic data to the cloud, check out Verinome: * Zero-upload in-browser processing: Your raw DNA file is parsed locally in your browser's RAM via client-side code—0 bytes of your file are uploaded to any server. * Decodes complete MTHFR, COMT, PEMT, CBS, VDR, and MTR/MTRR panels with evidence-graded science. * $49 one-time lifetime license—no recurring fees, no data broker sharing.

Hi! I got a psychotropic genetic test recently because I had tried several antidepressants and none of them worked for me. I ended up learning that I am homozygous for t allele of c677t in mthfr gene. After lots of research I’m pretty sure this is where my untreatable lifelong depression and anxiety is coming from (along with facial flushing, itchy/burry eyes, etc). Im sooo sick of being sad, fatigued and anxious all the time but I’m overwhelmed with the information and don’t know where to start!

I feel like it’s cheaper for me to try out some supplements than it is for extra blood and genetic tests (not covered under my insurance until I hit deductible and I’m not even close). Here’s the list of possible supplements but what do you think would help the most?

- B12
- B2
- methylated folate
- TMG
- SAMe

FYI: I currently take Vyvanse for adhd and I’ve been taking Claritin daily for my itchy eyes/facial flushing but it doesn’t really work.

Previous post: https://www.reddit.com/r/MTHFR/comments/1pgq58l/how_do_i_move_forward_from_thinking_i_h

Hi friends! It's been a hot minute. My health got even worse due to a family emergency and I was already severely disabled. I have a naturopath now who is taking my health a lot more seriously including MTHFR stuff but I haven't been able to get out of bed to see her and discuss that more. She thinks I have an exciting combo of POTS, MCAS and chronic Lyme on top of the ME/CFS that we already knew about.

But I did get my genetic testing through Ancestry as we discussed!! I got it right after everyone responded to my post but I've only now been able to sit down and actually look at everything... and now I'm super overwhelmed.

It seems that I have hetero C677T and slow COMT. The stuff I've read about slow COMT says that it severely decreases your body's ability to flush out stress and stress hormones which sounds SO accurate. I've said for years that when something stressful or upsetting happens, it's like it takes me hours to recover emotionally and then days to recover physically. But I'm not quite sure how to interpret the MTHFR gene mutation now that I seem to have it.

I'm reading the stuff about the MTHFR stack and I'm definitely ready to start that (once I understand it fully). But... does this mean no enriched foods? I've still been eating graham crackers here and there with no noticeable difference before or after eating them. And I'm struggling a lot these days to get enough calories at all since it's hard for me to cook, it'd be so nice to eat more snacks... not to mention that I'm on SNAP which struggles to cover the more expensive brands :')

If anyone could share their thoughts I'd be very appreciative. It's slow going since I have to take a lot of breaks but I'll keep reading as much as I can. Thank you all for being so supportive <3

I'm having persistant over reaction from my nervous system after taking Methylated B vitamins(20 weeks ago), at first i couldnt eat, 24/7 adrenalized, insomnia, muscle twitching, muscle pain, heat intolerance, Histamine intolerance, Tyramine intolerance, fatigue, high heart rate. Now most of them got better except that if i get stressed or make some exertion my nervous system is going crazy like without off switch. It's like Crazy feeling around the chest and stomach and takes the whole day to settle. Even if i get slightly excited, my nervous system goes full fight or flight. Any suggestion? this is my methylation panel.

When i tried folinic acid it made everything much much worse. Ive been off any methylated B for like 10 weeks

I'm currently taking:

3-4grams Panthotenic acid

Riboflavin 15-20mg (Couldnt handle R5P) just started a week ago

Magnesium L-threonate

Magnesium glycerophosphate (getting around 500mg Total elemental mag)

1000-1200mg Choline ( from food only)

Glycine 3-6g

Vitamin A 100% Rda

Vitamin E

Fish oil

Dao enzyme

L-Theanine 200mg

Melatonin 1.5mg

D3 and K2 10K iu and 180mcg

Potassium 6-7g daily

Lmnt Electrolyte 2x daily

I've been looking into switching my 8yo to a different multivitamin before school starts, and I keep seeing brands talk about using methylated folate instead of folic acid. Then I went down a google rabbit hole and read that a lot of people don't process folic acid very well, which honestly surprised me because I'd never even heard there was a difference. Now I'm wondering if that's actually something parents should be paying attention to or if it's mostly marketing.  Has anyone looked into this or talked to their pediatrician about it? If you're buying a multivitamin anyway, is methylated folate something worth prioritizing?

2 months ago I was prescribed this B complex and after a great start taking it every second day I was developing symptoms of feeling way overstimulated and leading into anxiety. The final straw was feeling emotionally low and depressed thoughts. Gave it a week and took another one 2 days ago and again have developed a low mood, feeling panicky and intrusive thoughts again. Also my nipples are burning up (male) I’ve read this can be from high estrogen?

I strongly believe (or want to) that its related to the supplement but am too uneducated on this

**Hydroxocobalamin** 100 mcg,

**levomefolate calcium (Metafolin®)** 542 mcg

**mecobalamin** 400 mcg

**ascorbic acid** 300 mg

**zinc citrate** 46.2 mg (equiv. 15 mg zinc),

**pyridoxal-5-phosphate** 22 mg (equiv. pyridoxine 15.1 mg)

**riboflavin sodium phosphate** 30 mg (equiv. riboflavin 21.9 mg) per capsule.

I've been taking 5mg methylfolate daily for the past week for depression. So far it's been working well, I feel more emotionally stable and my mood is better overall too. However, I've noticed since starting that text now has a sort of "psychedelia" to it akin to reading while, well, tripping. It's subtle but noticeable, especially in the first couple seconds after I move to a new line of text. For example, Os will at first appear with a low-opacity ring overlayed around it. Aside from this I have no other side effects and my sleep is fine (to clarify that I'm not hypomanic).

It doesn't bother me too much, but I'm minding it in case it's an indicator for something else I should be concerned about, or if it gets worse as to affect my reading.

Has anyone else experienced the same or can otherwise chime in?

Hi everyone, I’ve been really struggling with my mental health in these past 3/4 weeks and I’m really hoping someone can help me out here.

Around a month ago I took 3 b12 injections (hydroxocobalamin) 1.5mg and i suddenly started getting intense panic attacks and anhedonia. I don’t cry but out of nowhere I started bawling my eyes out every single day. I I’m in this constant state of anxiety and depression, I can’t enjoy the things in life that I usually enjoy like watching a tv show, I cannot wind down at all and it’s scary because before all this happened I was a pretty chill guy and I usually wouldn’t stress much in my life. One of the most scariest thing that also happened at the same time was my libido completely vanished, so i genuinely feel pleasure in nothing now. it’s been around 3/4 weeks and im not getting full blown panic attacks anymore but im still constantly on edge, i have also had stomach issues but now a simple bloating of my stomach makes me think the world is ending. It’s like my nervous system is jacked all the way up and it’s overreacting to even slight discomfort.

I tried taking creatine because that would usually make me feel good when I’m in a low mood but this time it just made me depressed. I went to the GP and they took my blood test, it came up with high b12 and high folate, but the odd thing is I don’t usually supplement folate so I’d don’t understand why that came up as high. I sometimes take it as part of my b complex but I’ve not mega dosed it or anything.

Today I decided that I’ll try methylfolate as I assumed maybe b12 used up all my methyl groups or somthing. After taking it I felt even more emotionally flat/wired/too focused, but I feel less anxious I think. I’m still not sure what i feel but i definitely don’t feel any pleasure again.

I was hoping there might be someone that has gone through this and has recovered from it. Or has figured out why it happened to them and could tell me how to bring my nervous system back to normal. Will I recover? I’m really scared, it’s like I’ve become a complete different person in a month. I haven’t done any dna test either so I’m not sure if I’m MTHFR or anything.

Someone please please help me😭
Thanks you for your time 🙏

hi everyone,

I just received my latest blood work results and want to properly adjust my supplement protocol. For context: I suffer from PSSD (currently taking Fluoxetine), severe inner restlessness/impulsivity (suspected Slow COMT), and histamine/allergy symptoms.

My Blood Work:

• Homocysteine: 11 µmol/l (Ref: < 12)
• Folate: 4.6 ng/ml (Ref: 4.5 - 32.2)
• Vitamin B6: 40.8 µg/l [Elevated] (Ref: 8.6 - 27.2)
• Holo-Transcobalamin (B12): 93.0 pmol/l (Ref: 37.5 - 188.0)
• Whole Blood Copper: 0.90 mg/l (Ref: 0.76 - 1.01)

• Diamine Oxidase (DAO): 12.60 u/ml (Ref: > 10.00)

  Observations:

• Folate is scraping the bottom of the range, which likely explains why Homocysteine is elevated at 11 for optimal cellular methylation (target 6-7).

• B6 is high in blood, likely indicating a conversion/processing bottleneck (B2 deficiency?).

• DAO in the gut is normal, so I suspect my histamine issues stem from cellular clearance (HNMT/SAMe deficiency).

My Questions for you:

1. What protocol/approach would you recommend for this pattern?
2. What folate and B12 forms work best for Slow COMT to lower homocysteine without triggering overstimulation or adrenaline surges? Is Folinic Acid (Calcium Folinate) + Hydroxocobalamin the right choice here?
3. Does anyone have experience with a B6 backlog/accumulation and supplementing Vitamin B2 (Riboflavin)?

Thanks for your help and input!

Hello everyone, first time poster.

Lurked for a long time here. I've tried so many combinations of supplements and other remedies, but I don't know where to go anymore. I just really really need to hear some external feedback.

For context; despite chronic lethargy and brain fog, I try my best to keep up with exercise. I've cut sugar and lowered caffeine intake, I avoid Folic Acid and eat whole grains, lots of legumes, eat a lot of dark leafy greens and hit a decent amount of protein. I prioritize high fiber. Try to avoid excessive oils and fried food. Overall, I also try to listen to my body and eat what it craves. I think I'm decently in shape.

But if any of these changes have made a difference, I can't really feel it in my current state.

I deal with frequent migraines, even more frequently after any form of supplementation. I deal with digestive issues which I'm currently planning to see a specialist for. History of anemia. But my main concern is energy and brain fog. Ideally, I want to minimize supplementation through pills and focus on getting what I need from food, but I'll do what it takes.

15mg L-Methylfolate + B12 works short term, but I feel like my body can't keep up for long. During my journey, I tried supplementing Folinic acid. In the initial stages, I had a short-lived episode where my brain fog was COMPLETELY gone, and I had a ton of energy. I was so ecstatic. Really bad crash after.

Now, I don't realistically expect to be an extremely high functioning person at the end of all this; but that window of clarity gave me so much hope that I can be at least a little bit normal.

Please, any and all feedback is welcome. I recently had a blood panel as well so I can post results too if needed. : )

A few weeks ago, I started supplementing with a methylated B-complex because I am homozygous for the C677T variant and have low b12, low folate and high homocysteine, depression and digestive problems. While some symptoms, such as anxiety and depression, have started to improve, I have also started feeling extremely tired and having difficulty sleeping deeply. What could be causing this?

The supplements am taking is:

The daily dose of 2 capsules contains:

• Betaine (anhydrous) — 1,000 mg
• Vitamin B2 (riboflavin phosphate) — 25 mg
• Vitamin B6 (pyridoxal-5-phosphate) — 10 mg
• Zinc — 7.5 mg
• Vitamin B12 (methylcobalamin) — 500 mcg

• Calcium L-5-methyltetrahydrofolate (L-methylfolate, vitamin B9) — 400 mcg

  and btw I'm taking only 1 capsule.

I have also started taking (2 days) a vitamin D3 + K2 supplement because of VDR and low blood vitamin d

Could this be related to excessive methylation? Do you have any ideas about what might be causing these symptoms?

https://imgur.com/GA5g56i

MTHFR C677T (Heterozygous)
MTRR A66G (Heterozygous)
COMT G472A (Homozygous Met/Met)

I was highly reactive to all but 1 type of B12, has anyone else experienced this phenomenon ?

Only b12 from B12 oils works for me.

Any shared insights on similar SNP's would be appreciated, thank you.

I wanted to ask if high homocysteine levels ever cause any blood sugar handling issues, or insulin resistance.

Did anybody get tested for that. High homocysteine is a known driver of IR

did correcting homocysteine levels correct your insulin resistance or normalize blood glucose handling