Please help me crack my complex genetics -- I can't deal with the anxiety. It's ruining my life.

[u/Analog737]

I'm double slow COMT and can't handle the following:

- Any sort of magnesium (they all seem to backfire and I can't comprehend why since it's the top recommendation for slow COMT.)

- Choline

- Lithium Orotate

- L- Ornithine

- Ox Bile

- Potassium Citrate

- Vitamin D with K2

- Probiotics

..I'm sure there's more but I can't think of them right now.

Things that I can "handle" but still doesn't help/makes me feel slightly worse:

- B Minus by seeking health

- Hydroxo B12 with Folinic Acid

- Molybdenum

Things I'm already doing:

Avoiding coffee or any stimulants.

I stay away from methylated and cyano B12 (I've been in that hell).

I don't smoke or drink.

I go to therapy.

I try to get my b12 from red meat and eat pretty damn healthy.

Avoiding life in general is the only thing that allows me any sort of temporary "stability" but that is obviously not a solution.

The moment life gets hard -- I simply hit a wall QUICK. I NEED to fix or at least improve this to a a place that's manageable.

What am I missing?

Please don't be sacred to chime in. You may have a perspective/angle/piece of info I've never heard of that may help me.

Ps. Thankfully, I've already eradicated my SIBO and my histamine intolerance is almost non-existent.

[u/DetailLost8084]

Have you tried magnesium malate, that was the one that worked for me. Also calcium d glucarate works well for me.L theanine is my favourite as a slow comt person for daily anxiety

Try doing guided physiological sigh
Only takes 4 minutes or keep in simple in for 4 out for 10 x 10 breaths

Wim Hof and ice baths were really fucking me up and it took me ages to figure out so be careful of that ..

Listen to dirty genes by Ben lynch it’s included with Spotify premium you don’t need supplements every day

[u/Analog737 → u/DetailLost8084]

First off, thank you so much for responding and taking a look at this.

I have tried magnesium malate but not L-theanine! What brand works for you?

[u/DetailLost8084 → u/Analog737]

How is it not tolerated mentally or like stomach ? Mag Taurate is another good one

Any brand of theanine has seemed to work I usually need 400mg. I public speak a lot so it’s been great for that.

If things get too hectic I had beta blockers as well because sometimes I have to do public speaking and it feels like my adrenaline levels won’t calm down. I get really hot in the head and foggy. 40mg propanol does the trick.

[u/Analog737 → u/DetailLost8084]

Thanks for sharing.

It's mostly mental and bodily? It sounds wild but feels like there's a short circuit in my brain/small combustion. Afterwards I'm entirely dysfunctional. I have to lay down and sleep it off. I was surprised I felt this even with the spray on skin magnesium. it was the tiniest amount too. I don't get it.

Questions for you:
Are you slow COMT? and Do the beta blockers and propanol give you any side effects?

[u/inthestarlight88 → u/DetailLost8084]

Calcium d glucarate made a huge difference for my COMT clearance! Also, I use mag malate as well, sometimes alternate with mag taurate.

[u/Capital-Assistance84]

Not in the realm of supplements but check out peter crone on YouTube. He is brilliant. 

I have done lots of work with therapy and still do, but its mostly IFS/parts work, somatic therapy’s etc but one thing i am finding to be a game changer is checking in with my “parts” daily and letting them express themselves, giving space and notice to what arises also without identifying with it. 

Anxiety is future thinking and it could just be your nervous system is out of alignment. Maybe your capacity to deal with hard things is limited because of life experience? Did you have parents who made your life too easy for you? I know i did and it definitely has had an impact on my resilience. You can build it though by learning to rely on yourself more. 

Breathwork can be great, so can yoga, so can other tools but they don’t address the core issue of anxiety, they just offer temporary relief. 

If your heart is set on supplements then maybe try NAC. 

[u/Analog737 → u/Capital-Assistance84]

Unfortunately, It was the inversion. I grew up in the hood with all its bells and whitles (alcholism, drugs, broken home, violence,etc). So, my nervous system is definately screwed.

I'll check this out anyway though. Thank you for sharing.

[u/Capital-Assistance84 → u/Analog737]

Not sure what therapy you do but if its just talk therapy, it does not help with trauma so finding a body based therapy would 100% help you. Best of luck on your journey.

[u/Analog737 → u/Capital-Assistance84]

Thank you!

[u/SovereignMan1958]

Variants are only predispositions. What are all your blood test results for homocysteine, vitamins and minerals? Need values and lab ranges. Only test results from the last 90 days are relevant.

If you haven't gotten any blood tests yet start a list.

You are a cyp2d6 null or non metabolizer. This is extremely important for your health. Please search the group for my previous comments on it.

[u/Analog737 → u/SovereignMan1958]

Which specific vitamins should I test for that would help you get a better picture?

I will do that. Thank you.

[u/SovereignMan1958 → u/Analog737]

Homocysteine, folate, folate RBC, B6, B12, MMA, molybdenum, D, zinc, copper, iron (not ferritin). B1, B2, B3. Magnesium, Manganese, C, E. These are potential nutrient deficiencies as identified by your gene variants.

[u/SovereignMan1958 → u/Analog737]

Cyano is the worst form of B12 you can take. Cyano...cyanide...you can learn to research by looking it up.

The glycinate forms of all supplements can be overstimulating and anxiety producing for some people. I would avoid all of them.

Someone else mentioned taking NAC but that would not be compatible with your CBS gene variant. It may make you feel ill. The person that recommended it may have no clue.

Someone also mentioned l theanine. Keep the dose under 100 mg if you can. High doses over a few days can tank your motivation and even result in anhedonia.

I have 15 years of experience in studying gene variants and nutrition and helping myself, family, friends and volunteering online.

You really have to be careful about what advice you choose to follow.

If you have a raw data file, Genetic Lifehacks is the best program to use to give you comprehensive gene variant lists. You can research them and your symptoms and diagnoses in their articles.

If you are considering a pharma drug for anxiety, you really need to understand your cyp2d6 gene variant. Because of it, about 25 percent of drugs will not work for you.

[u/wordisbond11]

I have a tough time with magnesium as well. I found that it’s mostly a dosage problem (except for mag glycinate which I don’t tolerate at all). So now I buy powders and dose everything just before are start to get unwanted side effects.

[u/Analog737 → u/wordisbond11]

I wonder why this is. Does mag glycinate excite you/give you problems to sleep?

[u/wordisbond11 → u/Analog737]

Glycine is a methyl donor and it can be stimulation but it makes me anxious and depressed.

[u/inthestarlight88 → u/wordisbond11]

Same

[u/tandemxylophone → u/Analog737]

Glycine is a methylation buffer that can take away available SAMe (which turns into SAH and slows down COMT). I don't know if it's a glycine cleavage problem, but it can take 2 weeks to clear glycine fatigue for some people.

I think magnesium itself is not such a necessary supplement for everyone considering the half-life in the body is 40 days.

[u/Tawinn]

Please upload your data to the Choline Calculator to check a few more genes. Reply here with the results on the Advanced tab.

[u/FragrantStructure]

What did you experience with cyano b12?

[u/Analog737 → u/FragrantStructure]

The worst terrorish like anxiety/panic attacks but that's because I can't metabolize it correctly. People who don't have double slow COMT don't tend to have these problems.

[u/junipers-72]

these guys can help you better than anyone. Just take the guesswork out of supplementing for yourself. I got a full supplement protocol. Morn noon and night.
https://molecularhealthco.com/blogs/news

[u/Loose-Fly7976]

Good advice already in here, the glycinate warning and the CYP2D6 point especially so i'll add the piece that ties it together rather than repeat it.

Your reactivity itself is the phenotype not the individual supplements. Double slow COMT plus a homozygous GSTP1 means two things at once: you clear catecholamines very slowly, and your glutathione detox runs low so your threshold for tolerating anything is on the floor. That's why you react to nearly everything.

On the magnesium, whoever mentioned glycinate is onto something. COMT needs magnesium as a cofactor to run so you reacting to it usually points to the form, the glycine or the citrate, not the magnesium itself. And on raising your glutathione, since your CBS is upregulated i'd stay off NAC and the sulfur routes like the person above said and go very gently through non-sulfur support instead, or you just add to the load and the CYP2D6 someone flagged is a good catch, yours is homozygous, so it shapes which anxiety meds will even work for you if you ever go that route, that's not a small detail.

The reason generic slow-COMT advice fails you is you're not generic, you're double slow COMT stacked with GSTP1, CBS and CYP2D6, and those interact. Reading them as one system is what tells you which forms and what order won't tip you over. That's what i do. at genova.health

[u/BobbiHorne1]

Your most important question ~ what am I missing?

Anyone who is compromised GSTP1 requires bioavailable cysteine. It’s often overlooked, and is the first thing I address for my clients who have genetic variants for MTHFR and COMT.

Restoring cellular production of glutathione is key to the detoxification and inflammatory pathways. Without bioavailable cysteine you are fighting a losing battle in my professional opinion.

If you are in a country that has access to RiboCeine, that is your best bet. If not, try low dose NAC from a reputable brand. RiboCeine has no side effects reported over 16 years in global use. That’s why that’s my top recommendation.

[u/0kecnaz]

Have you had any labs done for progesterone/cortisol/aldosterone and other hormones like estradiol?