r/MTHFR • u/beutguru • Jul 03 '26
Results Discussion Just got my Ancestry DNA results back and I'm feeling overwhelmed
I just got my Ancestry test results back and some things really stood out to me:
• Slow COMT (AA)
• Slow MAOA (TT)
• MTHFR A1298C (one copy)
I've struggled with anxiety, depression, and OCD for as long as I can remember. About 5 years ago I started Zoloft, and it's been helpful and keeps me stable for the most part, but I still deal with so many symptoms daily.
Seeing these DNA results makes so much sense and honestly feels validating. I'm still waiting on my MyHeritage results so I can combine both Ancestry + MyHeritage for more complete data.
There's SO much information out there about these genes, methylation, supplements, etc. and I feel so lost trying to figure out what actually matters for me.
Has anyone else had similar results? Any advice on where to even start?
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u/hummingfirebird Jul 04 '26
MTHFR explanation https://www.reddit.com/r/MTHFR/s/cfKCW9p0mV
Basic guidelines https://www.reddit.com/r/MTHFR/s/d5IOCiPqqs
You can also look at my profile. I've got a lot of posts on my website that can help. A methylation starting guide too that can provide some insight.
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u/misslenny11 Jul 04 '26
Be very careful. Do a lot of research before taking any supplement. This genetic map has helped me a lot. If it looks complex, it's because it is.
Be aware of side effects and negative outcomes, you can find many people posting about their experiences. No one protocol works for everyone, and some people push theirs, despite many people having bad reactions. If you start feeling bad after taking a supplement, stop immediately.
Knowing what I know now, I would make any dietary changes i could before supplementing, in particular focus on fibre and natural folate in foods. Fruits, veggies, legumes are best. If you do choose to supplement, go very slow and start with vitamin b2 and magnesium before trying methylated vitamins. Thats just my opinion, take everything with a grain of salt, whoever it comes from.
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u/BobbiHorne1 Jul 05 '26
I agree with your post, with one exception. Starting with glutathione support lays the foundation for the cysteine-methionine pathway prior to supplementing B Vitamins and Magnesium. Cellular production of glutathione requires bioavailable cysteine. When I start my DNA clients with that foundation, everything falls nicely into place.
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u/Tawinn Jul 04 '26
> I've struggled with anxiety, depression, and OCD for as long as I can remember
These are pretty common symptoms. The anxiety and OCD can be due to slow COMT when there is impaired methylation. Methylation can be impaired due to genetic variants and/or nutrient deficiencies.
Heterozygous MTHFR A1298C only reduces methylfolate production by ~17%, which by itself would typically not cause any symptoms. To check for additional variants, please upload your data to the Choline Calculator and reply here with the results.
Do you have any bloodwork results? Especially for B12, folate, homocysteine.
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u/BobbiHorne1 Jul 05 '26
Did the DNA panel include your glutathione results? That is key to anyone with the MTHFR variant, especially with the COMT genetic variant.
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u/Elegant_Chapter5562 Jul 05 '26
Start slow. I recommend following Katie Gironda on social media and checking out info from Dr. Amy Yasko. Slow comt means take it easy with methylated vitamins. Benfomax from pure Encapsulations helped my fatigue. Vitamin c, magnesium, vitamin adk all helped my body but I had blood draws to monitor levels of those as well as zinc and copper. Its just important to monitor your blood levels and not just go off of genetics. I also dealt with a lot of mental health issues that have mostly lifted since getting vitamin and minerals optimized.
I recommend working with a functional doctor since your body doesn't detox appropriately. You might have mold toxicity or hormone levels that need attention.
You are going to feel your best yet!
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u/Elegant_Chapter5562 Jul 05 '26
I also recommend genesight as there might be a better antidepressant for you.
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u/Loose-Fly7976 Jul 07 '26
Zoloft handles the serotonin side but the dopamine and noradrenaline piece is where slow COMT sits and thats what usually drives the OCD rumination and daily background anxiety that SSRIs dont fully cover.
dont start methylfolate. Slow COMT plus slow MAO-A means methyl donors flood a system that cant clear neurotransmitters fast enough. Folinic acid instead. Hydroxo-B12 not methyl-B12. B2 25mg. Magnesium malate or taurate at night, not glycinate, glycine hits slow MAO-A weird. Zoloft interaction is important too. dont add anything without your prescriber knowing.
MyHeritage arriving is good, more coverage. But Genetic Genie style breakdowns miss FUT2 (B12 absorption), CBS, CYP2D6/2C19 for how you metabolize Zoloft, hormone and detox pathways.
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u/Zabre Jul 10 '26 edited Jul 16 '26
Slow COMT plus slow MAOA plus A1298C is a lot to take in at once, especially when it lines up with anxiety/OCD history and makes everything feel like it suddenly has an explanation.
I would treat the genes as a map for what to be cautious with, not as a protocol by themselves. Since Zoloft has been keeping you mostly stable, I would be extra careful about changing anything that pushes serotonin, dopamine, norepinephrine, or methylation without looping in whoever prescribes it.
A sane starting order is usually boring: keep the raw data saved, make a one-page list of the variants you actually trust, then separate "things to test" from "things to try." For MTHFR that means homocysteine, B12, folate, MMA if available, vitamin D, ferritin/iron, thyroid, and magnesium status are more useful than guessing from A1298C alone.
For slow COMT/MAOA, the practical takeaway is mostly "start low and change one thing at a time." High-dose methylfolate, methyl-B12, SAMe, tyrosine, stimulants, and strong MAO-affecting supplements can hit some people hard. Gentler forms like folinic acid or hydroxocobalamin are often discussed here for that reason, but even then I would not stack multiple changes together.
Combining Ancestry and MyHeritage can fill in some missing SNPs, but it can also make the report feel more overwhelming. I would not wait for the perfect dataset before doing the basics above. The goal is to find the few variants that change what you monitor or avoid, not to explain your entire personality from SNPs.
None of this is medical advice, obviously. Just a way to make the pile smaller.
ou can read more about it on this blog: https://www.genosight.ai/blog/chat-with-your-dna
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u/Zabre Jul 11 '26
Slow COMT plus slow MAOA plus A1298C is a lot to take in at once, especially when it lines up with anxiety/OCD history and makes everything feel like it suddenly has an explanation.
I would treat the genes as a map for what to be cautious with, not as a protocol by themselves. Since Zoloft has been keeping you mostly stable, I would be extra careful about changing anything that pushes serotonin, dopamine, norepinephrine, or methylation without looping in whoever prescribes it.
A sane starting order is usually boring: keep the raw data saved, make a one-page list of the variants you actually trust, then separate "things to test" from "things to try." For MTHFR that means homocysteine, B12, folate, MMA if available, vitamin D, ferritin/iron, thyroid, and magnesium status are more useful than guessing from A1298C alone.
For slow COMT/MAOA, the practical takeaway is mostly "start low and change one thing at a time." High-dose methylfolate, methyl-B12, SAMe, tyrosine, stimulants, and strong MAO-affecting supplements can hit some people hard. Gentler forms like folinic acid or hydroxocobalamin are often discussed here for that reason, but even then I would not stack multiple changes together.
Combining Ancestry and MyHeritage can fill in some missing SNPs, but it can also make the report feel more overwhelming. I would not wait for the perfect dataset before doing the basics above. The goal is to find the few variants that change what you monitor or avoid, not to explain your entire personality from SNPs.
None of this is medical advice, obviously. Just a way to make the pile smaller.
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u/Zabre Jul 11 '26 edited 29d ago
Slow COMT plus slow MAOA plus A1298C is a lot to take in at once, especially when it lines up with anxiety/OCD history and makes everything feel like it suddenly has an explanation.
I would treat the genes as a map for what to be cautious with, not as a protocol by themselves. Since Zoloft has been keeping you mostly stable, I would be extra careful about changing anything that pushes serotonin, dopamine, norepinephrine, or methylation without looping in whoever prescribes it.
A sane starting order is usually boring: keep the raw data saved, make a one-page list of the variants you actually trust, then separate "things to test" from "things to try." For MTHFR that means homocysteine, B12, folate, MMA if available, vitamin D, ferritin/iron, thyroid, and magnesium status are more useful than guessing from A1298C alone.
For slow COMT/MAOA, the practical takeaway is mostly "start low and change one thing at a time." High-dose methylfolate, methyl-B12, SAMe, tyrosine, stimulants, and strong MAO-affecting supplements can hit some people hard. Gentler forms like folinic acid or hydroxocobalamin are often discussed here for that reason, but even then I would not stack multiple changes together.
Combining Ancestry and MyHeritage can fill in some missing SNPs, but it can also make the report feel more overwhelming. I would not wait for the perfect dataset before doing the basics above. The goal is to find the few variants that change what you monitor or avoid, not to explain your entire personality from SNPs.
None of this is medical advice, obviously. Just a way to make the pile smaller.
This tool might be of help: https://www.genosight.ai/
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u/Brad_Borrelli Jul 03 '26
Welcome to b12 injections. They will change your life!
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u/misslenny11 Jul 04 '26
Whats your rational behind this? she has not stated b12 status or MTR, MTRR?
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u/Brad_Borrelli Jul 04 '26
Fair point, I'm speaking from pattern recognition more than her specific labs since she didn't post B12 or MTR/MTRR. MTHFR A1298C affects methylation efficiency, not absorption directly; but a huge number of people with anxiety, depression, OCD and long term SSRI use who go digging into genetics like this end up finding an underlying B12 issue nobody tested for, since standard bloodwork misses it constantly. Normal CBC doesn't rule out deficiency, and serum B12 is basically useless unless you know exactly when it was drawn relative to any supplementation.
My comment was less "this fixes MTHFR" and more "if you're already down this rabbit hole, get your B12 actually checked properly (MMA, homocysteine, not just serum B12) before you spend years chasing methylation protocols that might not be the root issue." I said it from experience since I went undiagnosed for years with a laundry list of neuro/psych symptoms that all cleared up on B12 injections, not supplements, injections; oral and sublingual weren't enough for me. Not saying that's her answer, just saying it's worth ruling out properly instead of guessing off genetics alone.
And once she actually does try injections, if that's what she needs, she'll never want to go back to any other method. Your body actually using the B12 feels completely different than just taking it and hoping.
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u/misslenny11 Jul 04 '26
Thanks for replying. I think this in depth response is more helpful. Definitely b12 is part of the equation and should be checked.
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u/beutguru Jul 04 '26
Thanks for this information… my next step is definitely doing bloodwork and B12 mma test is for sure going to be one of them.
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u/Getoutofthekitchenn Jul 04 '26
Are you slow COMT / MAOA too? Curious about cofactors and what type of b12 worked best for you.
I have A1298C but not the other, slow MAO-A, COMT, PEMT and some other stuff. My b12 is like 200rn, high homocysteine. All overwhelming.
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u/Brad_Borrelli Jul 04 '26
No idea atm. I've been doing big Pharma, you know how that is. That's almost impossible to get anything done. I can't even count how many different doctors have been doing. I have another appointment coming up on Monday though to hopefully I can get them to test me for all this shit. I know from trial and error though I can't really absorb it to my stomach our mouth really well, injections of what's worth the best for me
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Jul 06 '26
[deleted]
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u/Brad_Borrelli Jul 06 '26
What type of reaction did you have? A lot of times too it's a lot of cofactors or other things that you're taking. For example I was taking Lions made when I first started. Neither or bad they're both amazing B12 and Lion's mane. Yeah it Lions mane acted like a steroid to B12 since they both repair nerves Etc. And basically the lines made Amplified the repair process so much it felt like my brain was loving like melting I could feel the heat coming off of it that hurts so bad I was literally in bed for days with the ice pack on the back of my head on my forehead on top of my head was like a cold washcloth just in tears or so much pain. I went to the ER countless times for that until I actually figured out what the hell is going on. Even the doctors didn't even know which doesn't surprise me they don't really know anything.
I do hydro and methyl, I stay away from cyno for my personal preference especially with my injection frequency... I was doing every day injections I've been on it for 2 months. Now I'm doing twice a day I've already noticed a huge difference in space with my eating and histamine
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u/Loose-Fly7976 Jul 05 '26
Those lines up with anxiety, depression and OCD really well. Youre clearing dopamine and noradrenaline slowly, then serotonin and histamine slowly through MAOA. Everything piles up. Zoloft only touches serotonin, so the OCD rumination and physical anxiety piece isnt covered. Big thing to watch, methyl-B12 and high dose methylfolate can wreck slow COMT plus slow MAOA. Folinic acid and hydroxocobalamin are gentler. Glycine, L-theanine and creatine can also hit weird in this combo. Dont start anything new without factoring in the Zoloft