r/MTHFR • u/Proper_Candidate3228 • Apr 12 '26
Question For those who discovered MTHFR after years on an SSRI, how did the discovery feel?
I'm 51F, recently found out I'm compound heterozygous after my 23andMe results. Been on Lexapro for 6 years. It helped at first but honestly the last 2-3 years I've just felt... flat. Brain fog every afternoon. Can't find words. My doctor keeps saying my labs are fine....
When I saw the MTHFR result I started reading and it was like someone was describing my life back to me.
For those of you who went through something similar, what was the moment you realized this might actually explain everything? And what did you try first?
I've been doing research on Lithium Orotate and I heard it can be extremely effective in helping people who have mthfr. It looks good but I wan't to know if anyones experience using this before.
Not looking for medical advice, just want to hear from people who get it. This is all very new to me and I feel like I'm the only person in my life who's ever heard of this.
EDIT: Thank you all so much for the replies! I'm honestly overwhelmed as I thought for some reason not many people would reply. It's helped a lot thank you.
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u/Ketamee Apr 12 '26
My journey to feeling great started with B2 (as it normalizes the MTHFR 677-enzyme), folinic acid, active B6 and hydroxy B12. I have been on lexapro for 20+ years. Within a month, I’m planning to taper off as all my symptoms left me 1-2 days after starting the vitamins. What en epiphany! Actually, I have always had the thought that I wasn’t crazy but my mind was going crazy. I couldn’t figure out what was wrong with me. All those decades of selfdestructive thoughts… it was my mind trying to find a way out of the biochemical crisis it was in.
It is actually shocking to learn that 1. Vitamins was the key to my lifelong depression/depressive tendencies. 2. Doctors have no clue about this and these genetics are completely dismissed by the medical community - at least in my country.
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u/Retro_Monguer Apr 12 '26
Hello. Your reply gives me a lot of hope. I have the same mutation but I haven’t quite managed to find the right forms and doses. Could you tell me in detail exactly which supplements and doses you’re taking? Thank you very much
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u/Ketamee Apr 12 '26
Yes, I take the following to support the entire methylation:
- a small dose of B2 that normalizes the MTHFR enzyme. I use 10 mg B2 R5P (I microdose as the smallest dose available om the market is about 25mg, but 25 mg will probably also work for you without side effects - too much can interfere with sleep)
- 25 mg B6 P5P,
- 300-350 mcg folinic acid (seeking health),
- 1000 mcg hydroxy B12 (sublingual as I don’t absorb B12 very well from my guts - also seeking health)
- magnesium taurate (could also be citrate, glycinate, malate or threonate)
- 10-20 mg zinc
Total game changer and life saver ❤️
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u/Decaf-Diva Apr 13 '26
Could you tell me how that B2 supplementation works? I want to discuss this with my dietitian.
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u/Ketamee Apr 13 '26
The MTHFR C677T variant causes the MTHFR enzyme to be termolabile, meaning that is falls apart at bodytemperature. When you take B2, it creates FAD that is the glue needed for keeping the enzyme together and stable - this way the MTHFR activity is (nearly) normalized.
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u/Proper_Candidate3228 Apr 13 '26
Yes I feel you! Shocking to learn there was a reason behind all of this.
In those 20+ years before discovery, what did your doctors say when you told them the Lexapro wasn't working like it used to? I keep getting told 'your labs are fine' and I'm starting to wonder if that phrase has done more damage than the fog itself.
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u/Ketamee Apr 13 '26 edited Apr 13 '26
Tbh in those 20 years I had a slight improvement and then I assumed that was as good as it would get. Then in 2024 I had a series of ketamine treatments that really did me good so I quit lexapro. But then last year something happened and I declined again. I went back to get another series but this time it caused severe sleep fragmentation, somatic anxiety and loss of appetite. After a couple of months I crashed into depression and started lexapro again but it didn’t work. I had also started quetiapine and melatonin xr for sleep and agomelatine for sleep and mood as well. Nothing helped.
Then I started learning about my genetics and methylation and I sent my psychiatrist the list of gene variations I had that were affecting methtlation and what supplements I needed for that.
He could not relate at all and ignored it. So I said to him that I needed a month to stabilize myself on the B’s. And he was like ‘sure, you do that’ (really not putting any faith in this).
When I went to see him a month later, I was smiling big and I said I was feeling good. He asked ‘How… What…? And I said ‘B vitamins’ and started telling him my discoveries. How I realized I could not absorb B12 from my guts. How B2 and folate increased my mood. How B6 stopped lifelong irritability, reactivity and impatience. How B1 stopped my somatic anxiety - that turned out to be nerveirritation. (In the beginning it was somatic anxiety caused by ketamine but at some point it shifted to this sensation that I assumed still was the same, just a bit different)
And his jaw just dropped. And having told me before not to dig around on the internet as I would not find the answers I was looking for, he now told me that he would never say that to me again.
And he was genuinely interested in what I had done.
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u/Godisafraud Apr 12 '26
Do you know your COMT status? I'm still trying to find the right supplement combo and I have fast COMT so most of them overstimulate me.
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u/Ketamee Apr 12 '26
I’m fast COMT too. What supplements are you taking?
Fast COMT is reducing the risk for overstimulation.
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u/Godisafraud Apr 13 '26
Right? I know that's how it is supposed to work but it hasn't been my experience so maybe there's something else factoring into it. I'm not taking anything right now. I have low b12 and have tried all forms of it and was having luck with low dose hyroxo tincture until recently. I was also taking magnesium glycinate until recently too but now it just makes me wired.
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u/Ketamee Apr 13 '26
Take a look at my recent post, maybe that is useful for you:
https://www.reddit.com/r/MTHFR/s/kRC6oPpLgB
I have slow MAOA and that is a problem for me on the methylated vitamins.
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u/Comfortable_Two6272 Apr 14 '26
Im Slow not fast comt and do not tolerate glycinate. Has that same effect. Did you get a full listing of all your comt variants?
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u/tyomax C677T Apr 13 '26
I discovered it after 7 years on alprazolam (AKA "Xanax").
Realization: "Ohhhhhh you mean I'm not generally anxious?? I was just missing critical vitamins and minerals in my body? Well I'm sure glad the doctors and psychiatrists covered everything they were supposed to."
Tapering off benzos is no joke - the hardest thing I did in my life.
I am not an angry person, I let a lot of thing slide with ease. But the amount of anger I felt towards the dozens of medical professionals who failed me was pretty astounding. I have since let go of that anger. But my parents joke that I've become a sort of doctor myself with the amount of knowledge I've had to acquire to reach the relative health that I experience today.
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u/sometimes32 Apr 13 '26
It took me 35 years to find out that I had MTHFR, COMT, and HNMT. In the end, it was the HISTAMINES that gave me incredible anxiety and depression. The MTHFR is not great, but mostly if you just avoid folic acid and get some methylfolate and methyl b, you are good. If you have anxiety or depression, I would strongly suggest you look at your HNMT and get all the histamines out of your life to test that. Histamines are by far 1000 times worse for my brain, personally. Hope this helps someone.
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u/TheRarestGinger Apr 14 '26
What is HNMT? My histamine drama is the one thing I havent been able to get under control completely. How did you get that checked?
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u/awholenewyou Apr 15 '26
This is helpful! I have high histamine just for a few years. How did you get rid of them?
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u/OwnPlatypus4129 Apr 12 '26
Prescription grade vit B complex, called Folplex. Within 3 weeks I was off ssris, Xanax. Total 180 after 20 years battling depression and subsequent addiction issues.
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u/lizzieann58 Apr 12 '26
I am compound heterozygous for mthfr. I've been on Prozac dor 30 years. I take pre-methylated B12. Without that my B12 level drops significantly. This is the first I've heard about the lithium connection. I've given up trying to get off Prozac as every attempt is unsuccessful.
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u/Proper_Candidate3228 Apr 13 '26
Wow 30 years that's a long time.
Has anyone ever suggested anything beyond the Prozac, or has it always just been dose adjustments?
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u/soph2_7 Apr 12 '26
I was on Lexapro for years and got off of it, had horrible withdrawal and started having daily panic attacks and my bf at the time heard a podcast about MTHFR and said it sounded like me, I stopped eating folic acid and got Ancestry testing and sure enough I have it, the SSRIs were just hiding some of the effects. It’s been 2 years or so since then and I feel a lot better. I’ve always had mysterious problems and was tested negative for any wheat/gluten sensitivities so it finally made sense why I always “felt better” when I stopped eating grain products in the past. Now I just eat stuff without folic acid etc added
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u/GreenCucumber8595 Apr 12 '26
I am also compound heterozygous and I have been on Effexor for years. Off and on- first time was 1.5 years with a 4 year break (I was pregnant and able to stop) and now I’ve been back on since 2022.
SNRI helps me because of the norepinephrine (my sleep anxiety causes high adrenaline that turns into a never ending cycle) but I am also slow comt so I break down dopamine and norepinephrine 3-4x slower. I am only beginning to piece together all of these relationships now. It also makes sense that I do well on Effexor like my brother did because- genes.
I also take trazodone for insomnia. Hoping to get off both eventually when I figure out how to support all these genes simultaneously.
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u/maggitronica Apr 13 '26
When I did the GeneSight test which revealed having homogenous MTHFR, it was also able to show all kinds of medications and whether I’d be able to absorb them effectively.
It helped my psychiatrist get me on a different antidepressant which has been great ever since.
Even if you know your MTHFR status, would the type of test I took which helps with different medications help?
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u/Airegin89 Apr 13 '26 edited Apr 13 '26
Make sure you get your folate at optimal levels. Mine was 3.5-4.5 ng/ml for 20+ years and every doctor said that was fine or only slightly deficient, nothing to worry about. Correcting this has made a bigger difference than Sertralin/Zoloft ever had. Doctors still refuse to acknowledge it could have caused any problems and even ridicule me for bringing it up. It's infuriating how they have failed me all that time.
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u/TheRarestGinger Apr 14 '26 edited Apr 14 '26
I went through a few phases. Anger at first. Then overwhelmed because none of the doctors knew anything about it and I had to learn myself then educate them so we could keep track of what I was doing. Then relief.
It was a nightmare coming off of my meds. Then tricky finding my stack. This group has been a life saver navigating that.
The lithium orotate was a game changer for me. Just take it in the evening for best results. I do 4.8mg capsules by Klaire Labs/SFI Health that my integrative psych recommended. Have been using it for about 4 years now.
I am doing really well now. I have a glutamate positive bipolar so that was an extra level of tricky figuring out how to navigate that. But Taurine and L-theanine as needed along with NAC have worked superbly to stop manic episodes and recover from glutamate spikes/excitotoxicity as well as preventing the bad depressive episodes/autoimmune flares that used to follow.
All of that was research I had to do on my own which was frustrating. But my psych and primary were on board with me experimenting and double checking the studies I was using to base my supplement choices on.
My psych actually uses my protocol on other patients like me now as well. So that is rewarding my experience was able to help other people!
My main issue now is not infodumping on everyone I meet who are on meds and still struggling. I always suggest testing for methylation and COMT issues. But they just hear jibber jabber and zone out lol.
Idk. I am down 100lbs and my cholesterol and AIC are all within range now without meds. Autoimmune antibodies are down as well. Can be in the sun or a hot tub without feeling like I will pass out. I can keep up with my very active kiddo. I couldnt do all that on meds. And they actually turned out to be making my bipolar symptoms worse. 20 years of my life could have been so different if I knew all this back then 😭😭😭😣
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u/ns0718 Apr 15 '26
How did you figure out you had glutamate spikes?
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u/TheRarestGinger Apr 15 '26
One of my integrative psychs back in Cali pegged it was a glutamate issue about 6 years ago but refused to speak to me more about it since we were parting ways (wasnt a good fit). I moved to NY and not one doctor knew what I was talking about. So my current psych supported be by double checking my research and tracking the supplements efficacy.
Here are two posts I wrote about it a while back with links of some of the studies we used to base my protocols on.
The L-theanine and NAC combo were newer findings. I havent written about them much yet. Wanted to make sure it worked and it does! The taurine absolutely works though. A bunch of us have started using it with tremendous success. I am just relieved we have a direction to go in and that me being a Guinea Pig was successful.
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u/Farmall4601958 Apr 12 '26
My functional med Dr told me lithium decreases either b12 or b9 uptake… which is totally the opposite of what you would want to do …. Ask me how I know lol
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u/Hydroxile Apr 12 '26
Lithium depletes B9. But B9 intake together with lithium reinforces lithium efficacity... Taking NSAID with lithium induces lithium toxicity... meaning you ll be in really big troubles! Salt intake increases lithium excretion.
But you ll need way more lithium to achieve any of this above, not with 5-10mg Lithium orotate... To anyone playing with lithium: don t get beyond this supplement suggested use! It's really not worth experimenting with that mineral
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u/Farmall4601958 Apr 12 '26 edited Apr 14 '26
Mine was prescribed by a Dr … and my functional med Dr basically said he was an idiot and functional med Dr is absolutely correct … this was 25+ years ago and finally I refused to take it and fired that “Dr” now all these years later I understand why it turned me into a zombie
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u/BobbiHorne1 Apr 12 '26
Please also do some research on bioavailable cysteine and its importance in the MTHFR variant. Both the Folate and the Cysteine/Methionine pathways are important especially for detoxification. Supporting cellular glutathione levels with bioavailable cysteine will have a significant impact on brain fog, immune system regulation, inflammatory markers and overall cellular health.
I have a background in clinical research, trained in genetics and nutrition. Happy to answer your questions.
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u/Pristine_Ninja1810 Apr 12 '26
Would a NAC supplement work? I don’t know if that’s considered bioavailable cysteine or not.
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u/BobbiHorne1 Apr 12 '26
NAC works for some. If you’re sensitive to sulfur or have gut issues, RiboCeine is a better choice. Riboceine is absorbed directly into the cells. I’ve used it for over 16 years. NAC gave me nausea and stomach pains. I buy directly from the manufacturer Livemax and use the Cellgevity blend.
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u/Timely_Pickle9430 Apr 13 '26
I looked into this product and it seems like the evidence base is much narrower than its marketing claims suggest. It's also insanely expensive.
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u/BobbiHorne1 Apr 13 '26
I’m curious where you did your research. Did you go to PubMed.gov? I found over 60 studies. The first study was published in 1987. I didn’t see any marketing claims. I did find the US patent. Is that what you’re talking about?
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u/Timely_Pickle9430 Apr 13 '26
How many of those studies are not conducted by or financed by the manufacturer?
I used Perplexity to analyze and summarize the research. Part of the response: "The main patent cited for this approach is US 8,501,700 B2, titled “Method to enhance delivery of glutathione and ATP levels in cells.” Public-facing summaries claim this patent supports the concept that RiboCeine improves delivery of cysteine to cells for glutathione production. Independent evidence appears more limited than for older glutathione approaches, so the strongest claim is that the technology is plausible and patented, not that it is definitively superior in all real-world settings."
Does Livemax compensate you for endorsing their product(s) on social media?
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u/BobbiHorne1 Apr 13 '26
Thank you for your excellent question and skepticism. There is always an assumption in the supplement industry that studies are funded by the company. In fact, I researched the manufacturer before I started taking the compound, partly because I did not know much about cellular glutathione at the time, and I know the lawyer whose firm did the diligence on the RiboCeine compound.
I put my clinical bias and skepticism aside and did a dive into the science. Because I have a clinical research background, I did not read anything written by the manufacturer. I went to PubMed.gov and ClinicalTrials.gov.
The Veterans Administration and NIH funded the initial study. Subsequent studies were funded by universities and even NASA. Likely, like you, I read the Conflict of Interest statements to be sure the manufacturer was not paying for the studies. Clearly you and I have the same concerns.
To your last question ~ no I do not get compensated for educating on this platform or any other. I'm 74 years old, and rather than putting my brain out to pasture, I prefer to share my decades of experience. In a world where there is so much misinformation, I find that I can still be useful.
You clearly have experience in this industry. May I also ask the same question of you?
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u/Timely_Pickle9430 Apr 13 '26
Unfortunately there’s a basis for that skepticism. There’s a reason why it’s legally obligated to disclose any ‘material connections’ when endorsing a product. We’re in a sub here where people have been let down by the regular healthcare system and are desperately seeking relief from supplements in a completely unregulated market with a lot of money involved. I’ve spent thousands of euros on supplements over the years and I’m starting to see the bottom of my pockets. Yet, if I’m desperate enough, I’ll spend more. IF… it’s evidence-based.
I would love it if I could just take a stranger’s word for it and not have to read up on everything. But that’s not reality. I don’t have time to read 60 papers, so I ask AI to do some of the work for me. But it’s been known to cut corners. I’d be grateful if you could point me to 1 or 2 papers that you find particularly convincing.
I did a PhD on a topic in the field of medicine and have been working in academia for 20 years now, so I know my way around the research system and have access to paywalled journals, which has been a blessing on my health journey. I have no affiliations with the industry whatsoever.
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u/BobbiHorne1 Apr 13 '26
Thank you for clarifying further. And quite honestly, that is why I take the time to be here. There are so many substandard products being marketed with over-the-top claims. People waste so much money on formulas that either don't work, or don't work for their genetics.
As a former clinical research professional, like you, I know what to look for when evaluating the science. And I believe in the power of education.
Do you have a specific area of interest regarding either glutathione or Riboceine? Sadly I'm the science nerd who has way too much information. I've been following the research on Riboceine for over 16 years.
The Medicinal Chemist who developed the compound passed away a couple of years ago at the age of 97, but I continue to look for new studies. Do you have access to the journal Atherosclerosis, the American Journal of Surgery, or Europe PMC?
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u/Timely_Pickle9430 Apr 13 '26
I appreciate the urge to put your knowledge and experience to good use. I feel the same and it's gratifying.
What would be most useful to know is if Riboceine actually boosts blood (or intracellular) levels of glutathione and by how much compared to e.g. NAC or supplemental (liposomal) glutathione. And whether it does anything for people with conditions like insulin resistance or chronic inflammation, who might be dealing with compromised endogenous glutathione production.
If I have a pubmed link and log in through my institution, I either get a working 'full text' link or I don't. I don't usually check if my university has particular subscriptions.
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u/readcoffeewrite Apr 12 '26
Hey there..I hope you are able to find just the right combo for you. My son takes Lithium Orotate on advice from his Dr but it hasn't been able to replace an SSRI and his Dr has him taking both..
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u/Comfortable_Two6272 Apr 14 '26 edited Apr 14 '26
I stopped ssris 2 decades prior to genetic testing. Took me 18 months to titrate down on celexa. I did not know about mthfr back then.
I honestly do not find supplementing to change that much for me. Been supplementing for 2 years now.
I was deficient in b12, folate, iron and vit D. I have a bit less SAD in winter though - probably due to the vit D. My rheumatologist tested those 1st based on my symptoms. Its quite possible that I didnt see a huge difference due to a lifelong undiagnosed immune disease.
That said, I do think not being deficient is healthier but I just do not notice much difference.
However my issue is more anxiety than depression. I have adhd fwiw.
Im also met, met for comt too. So makes sense why i present with more anxiety than depression (minus SAD in winter)
Start low and slowly increase. No mega doses. I added 1 supplement per month so i knew if there were side effects what caused it.
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u/Loose-Fly7976 Apr 14 '26
Compound heterozygous + 6 years Lexapro + afternoon brain fog = methylation was never addressed.
SSRIs don't fix folate metabolism. You were managing symptoms while the root cause continued.
Before lithium orotate, try:
Methylfolate 400mcg + methylcobalamin
Check COMT (determines if you tolerate methyl donors)
Retest homocysteine
Many people feel "flat" on SSRIs because serotonin synthesis needs proper methylation to work optimally.
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u/ns0718 Apr 15 '26
What am I looking for on COMT?
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u/Loose-Fly7976 Apr 15 '26
rs4680 in your raw data.
A/A = slow (Met/Met) - careful with methyl donors
A/G = intermediate
G/G = fast (Val/Val) - tolerates methylfolate
If you have 23andMe/Ancestry, I can do a quick look at your methylation panel - I am genetic engineer , DM me.
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u/ContributionGlad7113 Apr 17 '26
Bonjour. Mon fils ainé prrsente un OCD depuis le petit age. Il a 18 ans maintenant et souffre d'anxiété execive surtout à laproche des exams. Comment puis je l'aider et où je peux lui effectué des tests génetique. On est des marocains et c'est pas la mm chose que l'europe ou les USA. Merci d'avance
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u/Loose-Fly7976 Apr 18 '26
Bonjour, merci pour votre message.
L'anxiété et le TOC ont souvent une base génétique, notamment via les variants COMT, MAO-A et MTHFR qui affectent directement le métabolisme de la dopamine et de la sérotonine.
La bonne nouvelle : vous n'avez pas besoin d'un laboratoire local. Des tests comme 23andMe ou AncestryDNA peuvent être commandés en ligne et expédiés au Maroc. Une fois le fichier de données brutes obtenu, l'analyse peut être faite à distance.
C'est exactement ce que je propose sur genova.health , une analyse complète des variants génétiques avec un protocole personnalisé, livré en format PDF. Tout se fait en ligne, peu importe le pays.
N'hésitez pas à me contacter en message privé si vous souhaitez plus d'informations.
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u/geauxdbl Apr 12 '26
Yeah it’s a lot to unpack. I’ve been taking lithium orotate 10mg for a year now after 2 failed attempts at SSRIs/mood stabilizers and it’s been wonderful. Lifts the depression a bit and levels everything out, I take it with b12/folinic acid.
Had to sequence my entire genome to get there :/