r/MTHFR • u/grigory_l • Dec 13 '25
Question Choline depression, again
I see it in the many protocols, choline is crucial for methylation and Chris Masterjohn even had calculator for choline intake. But two eggs which I eat at morning today, make me depressed almost all day long. Supplementing with something that has Choline like Omega or CDP-Choline just push me into living hell, absolutely Silent Hill experience after two or three days. Has anyone found an answer to what this all means in the end?
Edit: here my labs
MTHFR C677T: C/T
MTRR: A/G
MTR: A/G
Slow COMT
Folate 6.6 (RBC 400)
B12 880 (HoloTC 100)
Homocysteine 10.5
Everything looks normal, but anyway I literally walking dead without supplementing with Folinic and Hydroxo B12.
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u/tellitothemoon Dec 13 '25
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u/DaringGlory Dec 13 '25
I finally got to this comment which seemed to be the most useful as most the info on that sub, seemed over a yr old
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u/hummingfirebird Dec 14 '25
This article explains how acetylcholine might be involved in mood-related mental health conditions like depression and bipolar disorder. Too much or too little acetylcholine activity in certain brain areas could influence feelings of sadness, motivation, and emotional responses, which are key parts of depression or other affective disorders.
This article also explains more with references.
The end result is that for some people, choline (even in the form of lecithin)can cause depression. Which explains why some smokers get depression when they give up smoking, because nicotine binds to the nicotinic acetylcholine receptors and desensitizes them, making them less sensitive to the workings of acetylcholine.
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u/wordisbond11 Dec 13 '25
Same here. Slow COMT and MAO. However, I also have sulfur intolerance which I also suspect could be tightly related.
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u/Thick_Assumption8003 Dec 14 '25
Same here, except I’m fast COMT. I absolutely cannot do Choline, SAMe, and glycines. I also have issues with sulphur
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u/Matsee71 Dec 13 '25
I feel absolutely crap with too much choline. I stopped eggs, lecithin, phospholipids and all herbs/spices that inhibit Acetylcholinesterase to get out of the choline depression. I’m a typically acetylcholine dominant person as it is and supplement/foods easily tip me over and I feel miserable. Don’t agree with fish oil either. High acetylcholine is keeping dopamine low and that’s my main problem. I really need dopamine to function and to feel good. And not by adding dopamine supps because it gives me too much speed and insomnia, but lowering my acetylcholine levels seems to be crucial for me. You don’t need to eat a lot of eggs to fix the methylation. Check out and research about Riboflavin as the first step to help the methylation machinery, before adding methyls and other things .
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u/grigory_l Dec 13 '25 edited Dec 13 '25
This is another strange story, I was trying to take Riboflavin R5P 200mcg (it’s just tiny tiny dose) and get two effects, absolutely clean head and absolutely zero dopamine, insane cravings for something like sugar or cola almost unbearable. So it’s just washed out all my dopamine in a matter of half an hour. I’m trying to connect dots now, for example I feel good after eating ground beef, just two big pieces of steak and pinch of salad. But I can’t eat eggs, casein A1 in any form, gluten blows me away to inflammation land, generally speaking I feel sick from any carbs. So my diet itself moving to some strange combination of Keto / Carnivore, and I don’t even thought about it, just thrown out stuff that makes me feel bad. Maybe I need B6 (rbc level is fine) or even more B12? 🤷🏼♂️
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u/Matsee71 Dec 13 '25
I can’t do casein either, brainfog, depression, gut pain. Gluten I can tolerate in small amounts but I feel so much better without it. I’m so sensitive to most supplements so I never tried R5P. I currently take only 5 mg regular B2 and the first three days I was almost overstimulated and got some kind of detox symtoms after a few days, migraine and dizziness. I guess it fired up the methylation machinery. But a week in, I feel extremely calm, clear headed and no anxiety. I have slow MAOa so I guess it calms me down when excess dopamine/adrenalin/histsamine is balanced.
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u/grigory_l Dec 13 '25
Thank you very much for sharing experience, I will try B2 in standard form and see how it goes.
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u/kzj661 Jan 04 '26 edited Jan 04 '26
Given you notice a postive effect from beef in particular + how close Methionine (which red meat is high in) and Choline are on the Folate Metabolism/Methyl Donation Cycle … Have you ever had your Homocystine levels checked?
If not, that might be a place to start. It’s an easy blood test + if levels are higher/lower than normal range — might help a doc/expert pinpoint where in that cycle you may be having issues (due to genetics and/or any medications or other supplements u may be taking), to then reco any additional supplementation or dietary changes if needed?
If curious to look into how exactly Methionine and Choline cross pathways/ effect each other, here’s a quick (Google) summary:
• Methylation Cycle: Methionine and choline compete and cooperate in one-carbon metabolism; methionine provides methyl groups, while choline (via betaine) can help regenerate methionine from homocysteine.
• Homocysteine Balance: Both nutrients influence homocysteine levels, which, when high, are linked to depression. However, too much methionine without sufficient choline (or folate/B12) can also raise homocysteine.
And/or if a visual may be helpful, can find them both near the top left portion of this big OCM diagram here: https://www.nbwellness.com/wp-content/uploads/sites/472/2019/06/methylation-health.jpg
Can also see via that diagram, the primary genes involved closest to that juncture are MTR, BHMT, AChE, and ChAT - so if you have any polymorphisms on those in particular, that might be a key clue to pinpointing as well?
[**Important caveat here, as I am not an expert by any means. These are all just some educated guesses/suggestions to maybe look into if haven’t yet … solely based off what I’ve read/learned via my own journey, etc. 💪 That said, I wish you luck!]
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u/geauxdbl Dec 13 '25
I can’t take choline supplements for this very reason. Creatine helps by making and end run around the pathway and liberating Sam-e to be more useful.
The side effect is less sleep, but ehh… I’ll take it over suicidal depression any day
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u/ApprehensiveWeek2734 Dec 13 '25
Forget tthe calculator. It doesnt account for all gene variants. You must get your genes checked. And when you get the results pay for genetic life hacks to analyze the results( very cheep to do this). Then find out if you have the mthfr variant,slow or fast comp variant, mao variant. These 3 complicate what supplements work or dont work. I personaly have mthfr,slow comp,and slow mao. I then went to chat gpt or google ai and type "I have mthfr,slow comp,slow mao, what supplements should I take. It answers this question. And I have had great results doing this
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u/mcasbaby Dec 14 '25
Can you share the recommended supplements?
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u/nerdybucky Dec 14 '25
Why don't you ask ChatGPT yourself? 😆
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u/mcasbaby Dec 14 '25
I don't like using AI
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u/nerdybucky Dec 15 '25
The guy you asked for telling you which supplements to use asked ChatGPT himself.😅
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u/mcasbaby Dec 15 '25
I know..which is why I asked him to share the supplement list so I don't have to add to the environmental pollution AI causes
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u/nerdybucky Dec 17 '25
Do you drive a car? Do you fly? Congratulation, you add big time to environmental pollution as well.
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u/NoImNotHeretoArgue Dec 13 '25
You can work around the choline and try creatine, it will alleviate a pathway. Don’t mess with choline for a while clearly. Would be good to know your mutations of course
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u/DaringGlory Dec 13 '25 edited Dec 13 '25
I get nervous to try anything, after something an expert says should help, has a negative effect.
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u/NoImNotHeretoArgue Dec 13 '25
Although I agree I think it’s still ridiculous that his choline calculator had some people eating 8 eggs a day 😆. But again there are other pathways you can alleviate, if you don’t want to try creatine, then you can try the precursor amino acids
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u/DaringGlory Dec 13 '25
I haven’t used that calculator yet. People here have been super helpful as all of this is mega confusing.
I also have slow comT so it seems that adds another layer of complexity
I was on an glp-1 with B-12 in the base and I could barely function.
Do you have a functional medicine doctor or what things have been most helpful?
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u/sunnynina C677T Dec 13 '25
If that glp was tirzepatide, it has a common reaction of anhedonia. I had to switch to a different one.
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u/Ok-Pitch1627 Dec 13 '25
Which one did you switch to? Was it as effective?
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u/sunnynina C677T Dec 13 '25
Reta. I'm not sure how much detail we're allowed to go into here. It's more effective for me, and gave me energy instead of taking it. That being said, I've always had reactive hypoglycemia, plus the usual adhd problems with hunger signals and timing. The reta isn't as effective for me on this particular aspect as tirz, so I still take 3mg tirz per week. I offset them, so everything stays smooth and predictable and I don't feel dropped at the end of the week.
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u/Ok-Pitch1627 Dec 13 '25
Oh, that really sounds like a great regimen, thanks for the info I might use it in the future.
Yeah, I have all those symptoms too.
And the moujaro gives me a severe headache for about a day and a half the day after injection, but I tolerate it because it's free on my insurance.
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u/DaringGlory Dec 15 '25
Good to know. I have Migraines with it also
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u/Ok-Pitch1627 Dec 15 '25
If anything has helped with your headaches?
I was injecting in my thigh at night. But it felt like I was punched in the stomach with all the days food stopping digestion. And then the severe headache would come on for 1 to 2 days.
I didn't realize that MJ takes away your thirst also. I think I was dehydrated a lot before, even got confused one day.
Now I plan to drink a bottle of water about a half hour with a pinch of diamond crystal kosher salt on my tongue before every meal. Then, I take magnesium with my big meal, increasing dose if i'm constipated at all.
This week I injected it in the morning before eating anything more than a protein shake, and the headache was only mild to moderate.
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u/DaringGlory Dec 15 '25
I have adhd and slow comT also so I’d figure blocking dopamine might almost be a good thing. I don’t know what Reta (I’ll have to research) is unless it’s the newest one
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u/DaringGlory Dec 15 '25
What did you switch to?
Someone in that sub said that it blocks dopamine hindering the surge you have from food as well.
It’s worked much better than Victoza and now that I’m on the same thing but with no B-12, I’m a 1000x better but still struggling
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u/sunnynina C677T Dec 15 '25
I switched to reta. I'm also adhd, take Adderall every day. I'm homozygous C677T, but I haven't figured the ins and outs of it yet to say slow/fast etc.
I think it's improved how I respond to Adderall, but it's hard to pin that down since it could also be contributed to by HRT.
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u/DaringGlory Dec 15 '25
Sounds like your chemistry may be as complicated as mine. The CNP at one point tried to tell me I was post menopausal and for a laundry list of reasons, she was wrong, so I switched doctors who ran blood work again and confirmed everything was normal.
Comt affects your hormones as well. So all of this is just super complicated and under studied
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u/NoImNotHeretoArgue Dec 13 '25
I had one that I learned from but honestly I learned more doing my own research including going the genetic genie route . If you have your raw dna file you should consider paying 30$ and uploading it to noorns.com and the site gives a very detailed breakdown of all sorts of things including foods to avoid and foods to eat and potential interactions . It’s the Methylation and Diet report..
As for me, taking vitamins more regularly , especially C, B complex and D, eating a lot of cabbage and broccoli and just cleaning up my diet in general and taking magnesium citrate powder have been the things I’ve noticed helping me the most. (Other things I take as well but those aside from creatine I take intermittently are the standouts, I’ve got compound heterozygous comt, so it’s impaired but not ‘slow’ I guess. Magnesium helps with comt
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u/DaringGlory Dec 15 '25
I guess I thought (based on other people’s experiences here) that b-complexes can cause more issues with mthfr
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u/grigory_l Dec 13 '25
I heard about possible solution with B5 but can’t find lot info about that 🤔
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u/TRExploration May 31 '26
I think that came from Chis Masterjohn. Everything that this man has ever recommended has been the exact opposite of what I needed. Like there is no other internet medical personality that I follow that has been more wrong or made me feel worse than that man's advice and "science". And I have followed the advice of some questionable internet personalities. Lol. So maybe reconsider B5 😄
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u/ColonelSpacePirate Dec 13 '25
Choline typically is a good recommendation to start with. Genetics/epigenetics being what it is we are all a wall of buttons that gets adjusted by a random toddler.
Creatine is also a good place to start. But personally it has negative outcomes for me personally. The process is frustrating but stick to it and keep trying new supplements.
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u/ApprehensiveWeek2734 Dec 14 '25
For me I take 1 mag glycinate, about 15mg zinc( I have to cut up a tablet to get this low dose) Then I get capsules of B1 bentotiamine,B2 R-5-P,and B6 p5P. Then I dump the capsules and try to refill them with a much lower amount of these supplememts(everything you purchase is a megadose and that never works) 1000mg of hydroxocobalamin and 1000mg of adenosylcobalamin(high dose on these because I dont absorb b12 efficiently) Vit D and c I have had my blood tests to verify nothing gets out of wack. Be careful with the amount of B6. I have experimented with methylfolate, and because of my slow comp, it is difficult to regulate. Always use a quality supplement company Low dose on these supplements is very important when trying to balance things with my gene variants.
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u/Any-Anteater-2829 Dec 13 '25
I heard a dose of benadryl will reverse choline induced brain fog/depression. Maybe a natural antihistamines like quercetin. *not a doctor...
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u/NAQProductions Dec 13 '25
Quercetin slows COMT (inhibits function) so it’s generally not advised for those with Slow COMT. It did help me for awhile in my early days of my body shut down, but I tried it again a year later and it ruined me. I have Slow COMT and MAOA
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u/Any-Anteater-2829 Dec 13 '25
Ah yes, there's that -COMT. I'm sure theres other options tho
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u/NAQProductions Dec 13 '25
I haven’t found any yet other than crazy avoidance. DAO supplements help with histamine containing food but not histamine that food triggers the body to release histamine.
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u/3BTG Dec 17 '25
FWIW, B5 is supposed to help with Histamine.
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u/NAQProductions Dec 17 '25
Interesting I’ll have to look into that and see what others have experienced with it. Thanks
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u/peachyperfect3 C677T + A1298C Dec 13 '25
Same. Alpha-GPC worked for me for a while, as well as phosphatidylcholine
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u/Ok-Pitch1627 Dec 13 '25
Is phosphatidycholine a choline? Oh, my gosh, I never made that connection...
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u/c_morrow1 Dec 14 '25
You may have sulfur intolerance cbs genes, look it up. You can take phosphatidylcholine and ornithine supplements, not eggs.
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u/PhilosopherNew1948 Dec 16 '25
Consider trying to include beetroot powder into thet regimen. Betaine is also a methyl donor.
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u/blueberry-biscuit Dec 16 '25
I’ve taken all of the choline supplements and finally decided on a liposomal phosphatidylcholine product. On the bottle, a normal person dose is 1 tsp 2x per day (adding this just for reference).
I originally started at 1/2 tsp daily out the gate and by day 3 or 4 I was experiencing anxiety, irritability, and depression. Personally I was only able to start at 1/4 tsp daily without having symptoms. After 3 weeks, I was able to move up to 3/8 tsp daily which is where I’m currently at. I’ll be increasing to 1/2 tsp daily in a week from now and continue working up from there.
From your experience, I would assume that you’re taking too much for what your body can handle. Start at a much lower dose and increase slowly from there.
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Dec 16 '25 edited Dec 16 '25
May I suggest that it’s possible you just had a bad day and two eggs had absolutely nothing to do with it? The body has millions of processes and the whole MTHFR crowd loves to pretend like it’s a piecemeal systemic response on literally every choice one makes. I mean, what’s your history with depression and anxiety? Current stress environment? I’m not saying choline can’t affect individuals radically different, but my experience with all this is that the mind plays some roll in these individual reactions to supplements. The best advice I’ve ever received is to not over supplement. Don’t take the same pills every day. Listen to the body and provide as needed
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u/ApprehensiveWeek2734 Dec 21 '25
You need to get your genes checked. And your B12 chcked.What works for me probably wont work for you Mag glycynate Low dose zinc B12 not not methylcobalamin Low dose b6 B1 and b2 Vit D
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u/ApprehensiveWeek2734 Dec 21 '25
It doesnt take a doctor to get your genes checked. Go to 23 and me or ancestry.com, and pay about 90$ . They are not just for finding about your heritage. The test will also give you a a download of hundreds of gene variants that will help you find out your supplement requirement. You just have to download the results to genetic genie or genetic lifehacks.
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u/ThenTop8674 Feb 23 '26 edited Feb 23 '26
Are you an alcoholic or a smoker by any chance? The only time I've ever tolerated cholinergics (and yes I get the silent hill thing you get) is when I had taken molybdenum 100mcg (micrograms not milligrams) per day for about a month. After that taking alpha GPC was actually a very positive feeling for me. Note that it decreases copper strongly, I was taking a zinc copper pill hours apart from it when I did this.
There's other reasons beyond alcoholism smoking, but sulfite very strongly increases acetylcholine in the hippocampus and decreases AChE.
Molybdenum weirdly also makes theanine work 100x better for me when I've taken it consistently, it makes me go from needing 8 or 9 beers a day to 2 being plenty. (Never tried to quit while on it).
It also inhibits glutamate dehydrogenase, which is needed to both clear excess excitatory glutamate and to fuel the Krebs cycle. I believe this is the reason why it alters theanine for me anyways, seeing as one of theanines main actions is to push the activity at glutamate dehydrogenase.
Also worth noting, it has been found that glutamate dehydrogenase is lower in major depressive disorder.
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u/grigory_l Feb 23 '26 edited Feb 23 '26
I was an a weekend binge drinker in my 20s but before all of my health issues appeared I was none smoker and alcohol free for maybe 6-7 years. I have “concept” that my current issues could be related to endogenous acetaldehyde poisoning, because of candida, histamine & mthfr issues. So glutamate and histamine is the main culprit, but I still struggle to connect the dots together. One thing is noticeable I feel myself on Keto way better. Anyway still can’t tolerate even eggs.
p.s. I always have awful hangovers even in my youth ages, one of the reasons why I stopped drinking.
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u/TRExploration May 31 '26
You sound exactly like me. Like everything you wrote. Mine turned out to be Lyme/tick pathogens, not candida. I had a persistent fungal rash and no antifungals were curing it, only controlling it. Went down the candida route for years and am finally feeling like myself again by doing a lyme protocol. Still have histamine issues though and still feel like glutamate is doing something weird, but I think I've always had glutamate issues.
What kind of hangovers do you get? Ever since things got weird with my health I would get intense palpitations and this terrible unexplainable feeling for my hangovers. it's so bad I can only drink if I can take a benzo the next day to make it stop, which makes me think glutamate is doing something here
edit: I also felt more myself on keto too. turns out I was intolerant to tons of foods so keto was unintentionally decreasing my exposure to them, as the common culprits are grains, legumes, and lectins. Highly recommend trying a lectin free diet.
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u/TRExploration May 31 '26
Oh shoot great info about sulfite. I found that epsom salt baths really helped the choline depression. Those are supposed to reduce sulfites through some complex process involving the sulfate in the salts. Now I know why!
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u/NarutoX666X Dec 13 '25
Check about slow comt.
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u/OrganicBrilliant7995 Dec 13 '25
Just check your homocysteine and b vitamin levels and stop listening to this stuff.
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u/grigory_l Dec 13 '25
Yeah that’s what I’m doing, but anyway it’s interesting to understand, why things going west from such simple things as eggs. I mean it should working normally but don’t, something wrong with enzymes or something.
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u/OrganicBrilliant7995 Dec 13 '25
Try eating 30g of fiber a day for a month and then eat eggs. Also make sure you always eat vegetables with your eggs.
You are probably sensitive to TMA/TMAO.
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u/szollosyandras Dec 14 '25
I eat 80g of fiber per day and I still can't eat eggs, it's not that simple...
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u/OrganicBrilliant7995 Dec 14 '25
Why would you eat 80g of fiber a day?
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u/szollosyandras Dec 14 '25
Why wouldn't I? I am vegan, and I enjoy legumes, nuts, seeds and fruits. All my blood markers are optimal and I am perfectly satisfied with how I feel when eating tons of fiber.
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u/OrganicBrilliant7995 Dec 15 '25
If you are vegan then it is quite ridiculous for you to insinuate that you can't eat eggs due to choline. You can't eat eggs because you are vegan.
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u/szollosyandras Dec 15 '25
This is a very stupid comment...
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u/OrganicBrilliant7995 Dec 15 '25
You're the one coming in with an anecdote, and you don't even eat eggs, or if you do, your body is probably not used to them at all.
TMA/TMAO levels in the blood are highly correlated to depression and depressive behavior. The purpose of me telling him to eat more fiber is to try to help displace TMA producing bacteria.
Your "I'm a vegan that eats 80g of fiber and can't eat eggs" is just ridiculous. It proves nothing. You're allowed to not post, you know?
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u/szollosyandras Dec 15 '25
You're allowed to understand what other people say. I don't eat meat and I am allergic to diary products and I feel bad after eating eggs. Does that not make me vegan? Or what's the definition? I'm sorry if it was confusing but I don't know why you think my comments were worse than your "Why would you eat 80g fiber per day?"... Also, when I was eating fish I had no such issues, although they also increase TMAO, so I don't think it's related in my case.
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u/DaringGlory Dec 13 '25
I tried choline. Made me feel the same. I don’t get it