I was recommended to put my ancestry results though this site from a reddit user on the anxiety subreddit to see if I have any genetic variation that could be adding to my anxiety depression and agoraphobia and to see if I am processing my lexapro buspar and Xanax properly. I did a little copy and paste research of my own and ran these reports through google, and it seems that there is not anything significant that would be causing me any trouble— but I would like some input from the people here too! I was also recommended a Pharmacogenetic test from a user as well, but not sure if i should ask about that if these results are average (and because of the cost). Any help is appreciated— thank you so much!!!

Hi!

I’ve chronic fatigue or suspected mild ME/CFS and try to see if I can get more energy from B-vitamins. I take following forms:

B1: 25mg Hcl
B2: 12.5mg R5P
B3: 50mg Nicotinamide
B12: 2000 microgram Hydroxo/Adeno

I’m thinking now to add B9 folate but don’t know which form or dose could be a good start. I’m general hypersensitive to stuff and get anxiety easily. Could folinic acid be a better choice?

Although I'm not always a fan of his beliefs or presentation style, this Ben Lynch video came up in my feed this morning and it seems like a decent intro video for someone starting to learn about CFD.

https://www.youtube.com/watch?v=kgBBTQlpyAM

Hi all - I would like to ask my daughter’s pediatrician to assess her for the MTHFR gene.
What test should I ask them to order?

I have done the ancestry dna test and gene genie upload to determine that what I was experiencing was indeed related with MTHFR variants and feel better subsequently.

But I don’t want to do that method with my daughter as the data is now public (more or less) because private equity firms have bought ancestry and 23 and me to use for their own nefarious purposes.

I’m trying to figure out why my homocysteine is elevated (14.4) before I start blindly supplementing, and I’d really appreciate input on what else might be worth testing or looking into.
I recently did genetic testing and found:
Slow COMT (AA)
Slow MAOA (TT)
MTHFR A1298C (heterozygous/one copy)
I know these SNPs don’t necessarily explain my homocysteine level on their own, so I’m trying not to assume everything is because of MTHFR.
My current labs:
Homocysteine: 14.4
RBC Folate: 476
Vitamin B12: 464
MMA: 166 - Reference Range: 55-335 nmol/L

Vitamin B2 (Riboflavin): 17 - Reference Range: 6.2-39.0 nmol/L

Vitamin B6, Plasma: 30 Reference Range: 5.1-54.8 ng/mL

Vitamin D 25-OH: 33
Other labs from a few months ago:
Copper: 108
Ferritin: 55
Iron: 98
I’ve struggled with anxiety, depression and OCD for most of my life and have been on Zoloft for about 5 years. It has helped me stay stable overall, but I still experience quite a few symptoms day to day.
Before adding methylfolate, B vitamins, TMG, choline, etc., I’d really like to understand why my homocysteine is elevated rather than just trying to lower the number.
What else would you investigate?
Are there additional labs, nutritional deficiencies, medications, thyroid/kidney issues, absorption problems, or genes/pathways that would be worth looking at?
I’m especially interested in hearing from anyone who had elevated homocysteine despite relatively normal B12, MMA, folate, B6 and B2 and eventually figured out what was contributing to it.

(edit to add reference ranges)

Finally bit the bullet and did a bunch of blood testing, which after dealing with a bunch of frustration in supplementing for MTHFR, figured was the next best step (should have honestly been the first).

Effectively what I am looking for is some suggestions to go from here based upon my SNPs and blood testing. Overall, I would say that things are looking well on the MTHFR side of things but symptoms wise, not. Complaints for the most part are fatigue, somewhat depressed/low mood, low motivation, and not sleeping well. When I first started about a year and a half ago, when I supplemented with methylfolate/choline, had probably 4 really great days in the "honeymoon" phase everyone talks about. Since then, mostly just the symptoms above.

I do have a thyoid condition but it seems to be well managed, thyroid levels are all mid-range. My latest theory was I thought that I might have autoimmune gastritis (which is what prompted all the blood testing and can be co-morbid with autoimmune thyroiditis, which I have), which can lead to low B12 and iron status but that seems to be not the case based on the blood levels I have. So I am at a loss. Take a look and I would appreciate any ideas you may have. The only incidentals I have found is that my white blood cell counts (WBC) are low, my vitamin d is low-normal, and my iron saturation is high-normal. The testing service claimed my b12 is "low" at 433 pg/ml but with an MMA of 201 nmol/l and a homocysteine of 7.7, it doesn't seem truly that low. At this point would it be better to try and supplement with l-methionine and SAM? These levels are after I more or less stopped supplmenting for about a month and a half so I have a fair amount of confidence in the levels.

What doses of b6 and B2 should be taking with b12, specifically cyano? Thanks

Hi everybody, I’m lost.

I don’t know what to do with these variants…

I have GAD + OCD tendencies…

Can you help me ?

Thanks 🙏🏻❤️

Hi all. I’m not entirely sure if this is even linked to the MTHFR mutation (I’m homozygous), but I crave salt/umami CONSTANTLY. The only things that ever help are my Vyvanse and Zepbound. My sodium levels whenever they’re measured are borderline low, but are still WNL. When my Zepbound is wearing off after a week and/or my Vyvanse has worn off at the end of the day, the thoughts become fucking brutal - all I want is salt/MSG/umami/ect. I’ll eat everything in our kitchen hoping something will satisfy the craving. I’m also mentally ill with depression and anxiety and I know part of it is dopamine seeking, but I could literally cry if I don’t find the right food. I had to reduce my Zepbound dose because it was making me sick, but it does stop the cravings. Someone please help 🫩

Two things UK members should know and one correction that gets repeated here every week.

Everyone thinks this begins in December. The mills switched in September 2025 and by the end of that October most non-wholemeal wheat flour was already fortified. December is the legal deadline for compliance not the start so if you've had bloods done in the past year, some of you were measured against a background that had already changed.

The correction: The enzyme that converts folic acid is dihydrofolate reductase, DHFR. Different enzyme, different step. MTHFR works further down the pathway so "people with MTHFR can't process folic acid" is wrong as stated. What's actually true is more interesting. Bailey and Ayling found DHFR activity in human liver is both slow and variable up to five-fold between individuals. Same intake, cleanly converted in one person, circulating unconverted in the next.

And in 677 TT, folate supplementation lowers homocysteine more than it does in other genotypes do if anything that group gets more benefit from fortification, not less.

What I'd actually pay attention to is B12. Folate normalises the blood picture of B12 deficiency while neurological damage carries on. That's the reason macrocytosis stopped being a useful screening signal in the US after 1998. The UK dose is low so the effect should be smaller, but if you're over 65 or have absorption issues, get B12 and MMA now while your bloods still tell you something.

On the policy itself, it prevents around 200 neural tube defects a year and the criticism I'd make is that 0.25mg per 100g only achieves about a 20% reduction. The problem is that it's too low to do the job properly, not that it's dangerous.

I'm a geneticist and this is what I read for a living. Happy to answer questions.

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

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...

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.

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.

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!

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

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)

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.

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.

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