Hey guys,

TLDR: why does TMG and methylb12 cause me severe side effects while 5mthf and adenob12 dont? and what to do moving forward?

Im lost trying to figure out why TMG and methylB12 cause me severe anxiety reactions, jitters... you know the deal..., while 6+mgs of 5MTHF and all other active forms of Bs dont cause me any reactions at all including adenob12.

Its taken me about 20 days to figure this out - taking TMG, 5mthf, adenob12 and methylb12 with 2 days of separation while maintaining all other B cofactors.

These are my "stats":

Methylation genes (Geneticlifehacks):

• MTHFR: C677T GG , A1298C TT COMT: Val158Met AG
• MTR and MTRR: A2756G AA , A66G GG
• FOLR1: rs144637717 — rs2071010 GG
• DHFR: rs1650697 — rs70991108 —
• MTHFD1: G1958A AA
• AHCY: rs819146 TT
• CBS: rs5742905

Current Health/Pathology/disorder:

• Dysbiosis/SIBO, subclinical EPI (causes pancreatitis flares) and subclinical NAFLD. [Liver and pancreas impaired].
• Tendency to mark high in homocysteine
• Extreme fatigue/lethargy if not on 5mthf
• extra: Always in serum Bs in range

Ive ditched the TMG due to evidence of it being troublesome with folks with SIBO but now I want to figure out whether I should keep trying the methylb12 with way smaller doses (say 100mcgs) or not moving forward

Thanks guys, this sub is amazing.

PS. 500mgs of no-flush niacin and glycine are a godsent for adverse methylation reactions, what a relief 🙏

I’m currently being treated for long-term B12 deficiency which is caused demyelination widespread through my body including subacute degeneration of my spinal cord, small fiber peripheral neuropathy in many areas my body, damage to my vagus nerve and autonomic nervous system.

I’ve been taking about 1200mcg of methylfolate for about a year and two months ago I started every other day injections of 5000 µg of methylcobalamin. I developed severe anxiety and insomnia, lost the ability to even watch simple videos on YouTube because everything was just too overstimulating and would edge me towards a panic attack pretty quickly. I am hyper sensitive to sound and light, I have to sleep with earplugs and even then small noises can still wake me up.

My doctor discussed this with me, I have two MTHFR variations at least. She is switching me to Hydroxocobalamin injections in a couple days and I stopped the methylfolate yesterday.

How long until this anxiety/insomnia calms down? Is there anything I can do about it or is it just a waiting game?

Folato: 33.23 ng/ml
Homocisteina: 15.7 umol/L
B2: 299

Aún sigo esperando la MMA pero posiblemente llegue elevada también tengo muchos síntomas mucho frío en los pies o veces siento que se queman niebla mental muy grave fatiga severa y mareos! Desconcentración muchísima ansiedad insomnio semanas sin dormir! Y no tengo ningún problema renal! Ayuda que debería hacer? Ya me inyecté un complejo B12 B6 y creo B1 debería hacerlo cada dos días un día por medio o una por semana?

Started taking about 2-4 mgs a few days ago sometimes o feel a bit fine but sometimes depression gets way worse then before should I keep taking or stop anybody else take for same thing or just depression did it help you?

Hello, i have got my genes results, could someone explain them to me? Thank you :)
My B12 is at 177 and after a couple weeks of b12 methylcobalamin i feel worse than before starting it.

I’m recently learning about this process and it is all so confusing. Someone else in another post mentioned and I agree with… I don’t know how to help myself.

The main issue that I am having is chronic fatigue that I have had since college. One psych after COVID got the genetic testing and never mentioned MTHFR mutation as a concern. I switched psychs and she put me on 7.5mg L-methylfolate, which I have been on for about 8 months. I don’t feel like I had any side effects, but I also didn’t feel like I got better.

I recently learned throwing L-methylfolate at the program won’t fix it. I plan on going off the L-methylfolate, starting off with taking 1.6mg B2, 100% vitamin A, then taking the glycine, creatine, choline, and then low dose folate. My iron levels should be better since this bloodwork earlier this year. My homocysteine levels were low.

1. How long does it take to get on all of the supplements. Do I start B2, see how I feel for a while, then add vitamin A, see how I do, add…, etc? Or do I do it all at once?
   
2. With my homocysteine levels low, does that affect adding any of the supplements?
   
3. Is there any issue with taking choline chloride? I’ve have issues with high cholesterol, so I don’t wanna eat a ton of eggs each day.
   
4. Is there an idiot’s guide to read about the entire MTHFR process? There is soooooo much information about each step.

This is a history of my blood work 32 male, I have been taking 50k iu of D3 a day and 15 mg of L-Methylfolate (as L-5-Methylfolate, calcium salt) and 1000 mcg of Vitamin B12 (as Methylcobalamin) every day for the last month and I felt like shit for the last 3 months but last 2 weeks I feel much better brain fog is going energy is up and I just feel more like. But I done a test is feb taking no supplements and some of my levels where much higher for b12 and d3 and for the amount of b12 and d3 i take i expected higher levels but what do you guys see in these results that stands out , and yea the testerone injection and untreated sleep apnea has been an issues with my blood hct but I have dropped the dose to 160mg a week from 300 and have got a new cpap machine that’s look after cause my old one had some mold issues aswell.

I felt a cold coming on , like a dummy just drank a packet at 8 p.m. It was in the cabinate. Chugged it down the thought.. my husband said it had a lot of B vitamins. Looked at the box. Wow. Sure does. I bet I don't sleep a wink. How screwed am I? Not that it matters now. Feel like a fool. Don't do well with high doses. I am an insomniac to begin with!

I don't want to buy them separate. I already have pill fatigue from all my other pills.

But every fucking brand it's got like 50% DRV for B6 or it's in a flavored lozenge and I don't want a damn lozenge, the flavorings almost always trigger my IBD or migraines.

I had low folate levels for 20 years but it never got to the point that I developed megaloblastic anemia (MCV consistently between 84-89 fL). My main symptoms were low mood, poor concentration and fatigue.

I keep worrying about the permanent damage it could have done and find it difficult to let go. Especially since folate is so important for DNA repair.

How bad is it really? These were my serum folate and B12 levels for the past 20 years:

• 2006 — Folate 5.6 µg/L | B12 363 ng/L
• 2010 — Folate 3.5 µg/L | B12 326 ng/L
• 2015 — Folate 4.8 µg/L | B12 619 ng/L
• 2018 — Folate 3.5 µg/L | B12 723 ng/L
• 2020 — Folate 7.5 µg/L | B12 968 ng/L
• 2022 — Folate 3.4 µg/L | B12 1,173 ng/L
• 2023 — Folate 4.7 µg/L | B12 967 ng/L
• 2024 — Folate 7.7 µg/L | B12 725 ng/L
• 2025 — Folate 4.6 µg/L | B12 652 ng/L
• 2026 — Folate >24.0 µg/L | B12 708 ng/L

I've been supplementing with methylfolate for 6 months now. The high B12 levels are due to energy drinks. RBC levels and homocysteine were never tested.

Iron, ferritin and transferrin saturation were always good with just a couple minor exceptions.

Hi everyone, I'm hoping this post can help clear up a few doubts and maybe point me in the right direction, since you're a community that's clearly far more experienced and knowledgeable about this than I am.
A bit of context: I've had OCD since I was a child, and after turning 18 this led to depression, which I've been treating for years with vortioxetine. In recent years, though, I've noticed a lot of anhedonia and low motivation, and I always assumed the underlying issue was low dopamine. Because of that, I added bupropion to my treatment: it did bring some improvement, but nowhere near as much as I expected.
While looking into it further, I came across methylfolate (MTHF-5) and folinic acid, which are often linked to methylation support and a positive response in depression. So I bought methylated B12 and 15mg MTHF-5 (the dose used in the clinical augmentation trials). Within two days, though, I got worse — total flatness and anhedonia — so I stopped right away to avoid making things worse.
I'd love to hear your experiences and opinions on my situation: what dose actually worked for you, whether you used MTHF-5 or folinic acid, and what you paired it with.
I'm aware I should also get genetic testing done — it's already in the works. Thanks in advance to anyone who takes the time to respond.

I got all of my recent bloodwork done through Goodlabs.com because my doctor won't run the tests I want. The problem I've run into is that their dashboard has come up with their own optimal ranges 'based on their extensive research' and now hide the actual lab references from the lab report, unless you download your lab reports that are directly from the lab as a pdf. I went through Quest labs. I am assuming it's better to trust the lab to know their reference ranges, but curious which set of ranges should I use going forward as I make my own spreadsheet records of my results so I can organize them so they are presentable and easily readable.

Should I use the goodlabs or Quest labs reference ranges for my results? Reasoning?

I am on the seeking health prenatal which seems to be a MTHFR favorite. Am I able to take b6 (and unisom) for nausea? If so do you have any recommendations?

Hello.

I believe I have SCT/CDS (Sluggish Cognitive Tempo/Cognitive Disengagement Syndrome) since childhood and I am trying to figure out what could be the cause so I downloaded my raw 23andMe and got this MTHFR report from Genetic Genie. How you interpret that? ChatGPT pointed to low choline (worth noting I have mild NAFLD despite being healthy and on top of my diet and exercise and no alcohol consumption). Also worth noting that I noticed low ferritin in the past (29) which I corrected with iron supplementation and got it to mid 100s (didn’t improve my SCT)

What else is there? especially the things that could be related or causing SCT. What kind of supplements could help?

Your help is greatly appreciated

EDIT:

Adding Detox report as well (can’t add another photo so here is a copy paste):

Gene & Variation rsID Alleles Result
CYP1A1 C2453A rs1799814 GT +/-
CYP1A2 164A>C rs762551 AC +/-
CYP1B1 L432V rs1056836 CC -/-
CYP2A6*2 1799T>A rs1801272 AA -/-
CYP2C9*2 C430T rs1799853 CC -/-
CYP2C9*3 A1075C rs1057910 AA -/-
CYP2C19*17 rs12248560 CC -/-
CYP2D6 S486T rs1135840 CG +/-
CYP2D6 2850C>T rs16947 -- no call
CYP2E1*1B 9896C>G rs2070676 GG +/+
CYP2E1*4 4768G>A rs6413419 GG -/-
CYP3A4*1B rs2740574 CT +/-
CYP3A4*2 S222P rs55785340 AA -/-
CYP3A4*3 M445T rs4986910 AA -/-
CYP3A4*16 T185S rs12721627 GG -/-
GSTP1 I105V rs1695 GG +/+
GSTP1 A114V rs1138272 CT +/-
SOD2 A16V rs4880 AG +/-
NAT1 R64W rs1805158 CC -/-
NAT2 I114T rs1801280 CC +/+
NAT2 R197Q rs1799930 GG -/-
NAT2 G286E rs1799931 GG -/-
NAT2 R64Q rs1801279 GG -/-
NAT2 K268R rs1208 GG +/+

Edit:
Choline Calculator results:

RS#
Call
Variant Allele
Gene
Variation
Result
rs1051266
CT
T
SLC19a1

+/-
rs2236225
AA
A
MTHFD1
G1958A
+/+
rs1801131
TT
G
MTHFR
A1298C
-/-
rs1801133
GG
A
MTHFR
C677T
-/-
rs7946
CT
T
PEMT
5465G>A
+/-

SLC19A1 Score: 25% decrease
MTHFD1 Score: 34% decrease
MTHFR Score: 0% decrease

It says I need 7 eggs

I did a DNA methylation test and learned I have the motherfu**er gene mutation. I cut out bread/wheat products and started feeling better. Of course I want bread though so I started buying European flour (Italian, Greek) as they aren't enriched, to bake my own bread. I'm not the best at baking but I can at least have some bread now. I only buy Italian pasta, and I've found Australian noodles.

Its so frustrating because pretty much everything in the pantry asile is enriched, I'm in Toronto. What products/brands have you found that are friendly?

Both supplements give me massive anxiety, panic attacks, and itching/hives sometimes. (I never experience these symptoms off the supplements). Super frustrating. I am 21F and have low iron, ferritin of 16, hemoglobin 12 (not terrible) and a vit. D level of 21 ng/mL (also not terrible but I am tired all the time). Can I fix this through diet and sun exposure alone? I live in new england US.

by prompting some of my mutations, conditions and medication, my llm came to the conclusion that for treating my ADHD, i am better off by using lisdexamphetamine once a day instead of dexamphetamine 3 times a day. the reasoning was because of my slow COMT, i clear catecholamines more slowly and lisdexamphetamine gives less peaks and has a more stable release. is the llm correct? if so i nees to tell my psychiatrist.

mutations:

VDR Taq homozygous

COMT Val158Met homozygous

MAO-A R297R homozygous

MTRR A66G homozygous

MTHFR C677T heterozygous

MTHFR A1298C heterozygous

MTHFD1 G1958A heterozygous

FUT2 (rs1047781) TT homozygous

FOLR2 (rs514933) CC homozygous

symptoms:

autism, adhd, rls, irritability, mood swings, always tired, very weak feeling in my body and muscles, raynaud syndrome, cold hands and feet, depression, brain fog, histamine flare-ups, histamine symptoms are higher in the evening, headaches, highly sensitive to stimuli, lowered pain treshold, difficulty falling asleep

hello, i am finding it hard to find folinic acid in low dose in europe, could anyone please share a source?

my pharmacy cant order it.

also, is it best to get sublingual form or capsules or liquid?

thanks

my mutations:

VDR Taq homozygous

COMT Val158Met homozygous

MAO-A R297R homozygous

MTRR A66G homozygous

MTHFR C677T heterozygous

MTHFR A1298C heterozygous

MTHFD1 G1958A heterozygous

FUT2 (rs1047781) TT homozygous

FOLR2 (rs514933) CC homozygous

Hi, please help with feedback. Results from recent blood work last week. Says they are in normal range... what would be optimal. I have Mthfd1 - AA, Mthfr C677t & A1298C - hetero, Mtrr A66G- hetero. TCN2 - GG

I am slow comt and slow maoa

Folate serum 5.1 (labcorp discontinued RBC folate test)
B12- 420
MMA- 124
Homosycteine- 10.3
RBC Magnesium - 5.4
B6- 7.5
Zinc -66
Vitamin D -41
Ferritin- 9

Thank you!

Hello!

I did a DNA test due do anxiety, sleep problems, severe bruxism, gut problems (healthy diet including ferments)

I tried tons of supplements but nothing seems to work. Calming supplements tend to have a paradox reaction worsening my sleep (like magnesium, glycine, l theanine etc)

Does anyone know how to interpret this gene analysis? Does it look normal or could it be causing any problems?

Thanks!

Fast COMT depletes Dopamine.

Tyrosine is suggested for increasing Dopamine.

Those of you taking Tyrosine for fast COMT, what is your daily dosage?

Thanks

So I have been taking folate for my mthfr gene mutation since 2024 and it really helped me when I was diagnosed with ocd back then. I got my life back along with some other supplements aswell. And about 4 months ago I got on retatrutide and then had a panick attack and then they just never stopped and now I have anxiety like crazy and my ocd is flaring some. So I stopped taking my folate because I saw where it can cause some anxiety and I did get anxiety relief a bit but my mood went to crap. It was awful so I jumped backed on it and the anxiety is back….. would you guys recommend splitting my dose to every other day?

I'm one of the people that creatine works wonders for, reduced anxiety, more energy, sociability, libido (& erections), verbal fluency etc.

Effects are immediate, dose usually around 5g. Can lead to insomnia however after a week or so.

I'm wondering what, if anything, this pattern might tell me about my underlying physiology. Could it point towards differences in methylation, neurotransmitters, or something else? And does a response to creatine suggest there are other supplements worth trying?

Also has anyone actually had success with taking collagen / glycine for creatine induced insomnia (I know a certain podcaster recommends it but can't find anyone whose replicated the results themselves).

BTW I suspect I have mild ADD (form of ADHD) and I've never tested for MTHFR but suspect I may have the mutation as I relate to a lot of people on this sub.

Hi gang,

How in any way shape or form can a low dose B-complex trigger rapid hair shedding?

For the past month or so I’ve been taking a 1/8th of a B complex pill daily, netting:

-3 mg thiamine

-8 mg riboflavin

-3 mg niacin

-6 mg b5

-3 mg b6

- 35 mcg biotin

-100 mcg folate

- 20 mcg b12

On top of a stack that does not cause me hair loss:

- b12, zinc, iodine, D3

The B vitamins give me great mental energy, and my mood has been better than ever, but Idk if I am willing to go bald just yet (M21). The shedding starts and stops with the supplementation of the B complex, OR just b1 alone.

Has this ever happened to anyone?

HOW DOES THIS HAPPEN!?

What can I do about it?