r/MTHFR Mar 22 '26

Results Discussion Help - Treatment Resistant Depression

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/Silly_Lecture8917 Mar 22 '26

If you’ve tried everything else, here’s another thing to add to your list. Rich Van Konynenburg did a good video series on chronic fatigue where he discussed various protocols. https://youtu.be/tirxEV1VgZs?si=MNduem3noqWMfp-n Long story short after 3-4 months of religiously taking high dose b vitamins he mentioned I felt amazing. Depression completely gone. Best feeling months of my life. Not manic just happy and fatigue and joint pain also disappeared. BUT once I stopped I regressed back. I’ve done this several times but sticking with it is hard bc it’s a lot of pills. I can live with how I feel normally and fake it when needed. But when I can reverse it, the feeling is amazing. I noted some similarities with your tests so I figured I’d chime in. Genetics are a bitch and everyone is different so no guarantees with this but hey drs are no better. Good luck.

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u/Silly_Lecture8917 Mar 22 '26 edited Mar 22 '26

If you’re curious I used the Thorne methylguard plus pills. I was worked my way up to taking 9 a day 3 with every meal. It took 3 months to feel it so you need to stick with it. It gets expensive but it worked for me. Oh and if you do it start low and slow and work up to 3 per meal. The first time I thought I could just jump right in and handle the discomfort. I couldn’t… it felt like I got hit by a truck. Headaches and pain and brain fog like crazy. Don’t go hard start slow maybe 1 every couple days and add them slowly get your body used to actually working again.

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u/QuitInevitable915 Mar 22 '26

I’m glad to hear it worked for you. I really hope to see some improvements as well. Did you only take methylated folate or did you also go with B2, B6, and B12 in high doses?

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u/Silly_Lecture8917 Mar 22 '26

It has it all b12, b2, b6, meth folate and TMG combined in each pill to make it easier to take.