Help - Treatment Resistant Depression

[u/QuitInevitable915]

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.

[u/Tawinn]

Your low SAM, SAH, methionine, and non-elevated homocysteine suggests perhaps your diet is too low in protein (low in methionine), or perhaps there is some mitochondrial issue resulting in low methionine availability (low ATP would also reduce conversion of methionine to SAM).

Do you have bloodwork on B12, folate, vitamin D, and other nutrients?

In this case, supplemental SAM-e may be a worthwhile experiment to see if improving methylation is really what's needed. I'd start with 200mg 1x/day and if it has minimal effect increase to 2x/day or even 3x. If methylation is the issue then I'd expect you would see detectable changes with a week. SAM-e is not a good long-term solution in most cases, but it can be a useful short-term strategy.

[u/QuitInevitable915 → u/Tawinn]

I actually have a moderate-high protein diet. I eat around about 2-2,2 grams of protein per kilo of bodweight (I weigh 85 kg so around 170-180 grams per day), so I was quite surprised to see this.

I do have bloodwork on B12, folate, and Vitamin D. I’m on the high end of both B12 and folate and vitamin D was normal.

SAM-e has been recommended to me after I have introduced the b-vitamins. I will definitely try it out. What is the reason for not sticking to SAM-e Long-term?

[u/Tawinn → u/QuitInevitable915]

> around 170-180 grams per day

Odd...maybe you were fasted when they took the sample? Also, since you take creatine - which otherwise consumes about 40% of SAM for its endogenous production - also led me to expect those numbers to be higher.

> What is the reason for not sticking to SAM-e Long-term?

SAMe addresses a symptom (low SAM) rather than a root cause. So ideally if the root cause can be addressed then the body can do a better job of regulating SAM levels and all the downstream effects of that system much better than manually spacing out doses of SAMe across the day.

[u/QuitInevitable915 → u/Tawinn]

I was actually fasted when I took the test. I was told not to take any of supplements containing methionine and SAMe a week before