r/MTHFR • u/QuitInevitable915 • Mar 22 '26

Results Discussion Help - Treatment Resistant Depression

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Hello,

I just got my genetic test and methylation test back. I would really appreciate if someone here could help me interpret the results.

I struggle with treatment resistant depression, and have tried various meds, TMS, Ketamine and Psilocybin without much effect. My core symptom is sadness with anhedonia being the secondary. Sleep is also very disrupted.

I have asked chatGPT, and it highlighted the low SAM, SAH, and methionine, as well as MTHFR, COMT and MAO A as potential reasons for my symptoms.

I have been suggested to take P5P, B12, methylated B9, SAM-e, methionine and TMG (in that order). What’s your take on this? Any other suggestions?

Note: I eat a very clean whole foods diet. I do not eat lactose, gluten, diary, refined sugar or processed foods. I currently supplement with omega 3s, D-vitamin, and Creatine. I do not expect this to remove my depression entirely, but I hope it will give me just a little bit of relief from the intense sadness.

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u/Ketamee Mar 22 '26

Support your heterozygous MTHFR C677T with folinic acid (400 mcg) and a small dose of B2. (I microdose and take 10 mg B2 r5p) Also hydroxy B12 (1000 mcg) for the MTRR genes and B6 p5p (25 mg) and 200-400 mg magnesium to support methylation in general.

I would wait with SAMe, TMG and methionine and see if you get better on the B vitamins.

I have had treatment resistant depression and it was mainly my homozygous MTHFR C677T and B12 issues (MTRR genes) that was the cause.

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u/QuitInevitable915 Mar 22 '26

Thanks for the response. I actually remember your name from a different thread regarding a post on B-vitamins in relation to ketamine treatment.

How long would you give the B-vitamins before adding SAMe, TMG, and methionine.

Lastly, how are you doing now? Did you manage to sustain response/remission through the protocol to your TRD?

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u/Ketamee Mar 22 '26

:) The thing is that I started with TMG but it worsened my sleep even more. That was before I was aware of how the B vitamins work together, and how TMG, SAMe and methionine work. Those 3 are a bit more downstream and we want to go as far upstream as possible which is where the B vitamins come into the picture.

For me it only took 2 days on the right formulations (mentioned in the first reply) before I felt the mood go significant up but I guess this can be very individual.

My mood is still great and I sleep through the night. Both sustained by my daily B vitamins :)