methylation paradox help

Need some help.

I have ALL the symptoms of slow COMT. Laser focus, anxiousness, inability to calm, sensitivity to catecholemaines, cant handle stress. In addition, SSRIs made me sleep all day. I.e. i couldnt methylate the serotonin. Anything that increases methyldonors (methylfolate, phosphyditylcholine, p5p, etc) gives me agitation and insomnia, indicating an inability to handle neurotransmitters.

After having severe inability to switch off yesterday after some coffee, I decided to pull up my genetic genie report and look into this. I had assumed I had very slow COMT w/ inabilty to methylate neurotransmitters, and high levels of epinepherine/norepinepherine causing this autonomic stress I always feel.

What I found surprised me. My rs4633/rs4680 SNPs both indicate I have FAST comt. In addition, both of the OAT tests and the Dutch test I did all said the same thing. I do not have high levels of neurotransmitters, they're all actually extremely low. Dopamine/ epinepherine/ serotonin, all of them. So these tests are all telling the same story. I'm MTHFRR homozygous, so i naturally dont create neurotransmitters. I'm also fast comt, so i methylate neurotransmitters very quickly. So it would naturally make sense that my neurotransmitter levels would be on the mat. So all the tests tell the same story as each other, even if its not what I expected.

But if this is the case, why do I experience all of the symptoms of high neurotransmitter levels and slow COMT?

I'm very senitive to coffee. I'm also the most sensitive person I've ever met to methyl donors, cant even handle 1 mcg of methylfolate (this is so low a dr didnt even believe my claim). Anything that increases neurotransmitter levels gives me extreme anxiety and insomnia, and sometimes headache. Yet my neurotrasnmitter levels are very low, and supposedly I'm fast COMT so can remove them extremely quickly.

In addition, I have one other question as an aside. When i read about slow comt, chris masterjohn and most other websites advocate for things which either increase methyldonors or spare them (creatine, SAMe,etc). Isn't this counter-intuitive, since even though it will increase methylate and help COMT, youre creating neurotransmitters so net net it will have the effect of increasing symptoms, which seems to corroborate with what people report anecdotally.

Bluelyme thanks for the thoughts. This is along the lines of what i was thinking. The markers say one thing, but all you can go on are symptoms and how you react to things. And my body seems to be telling me that it cant handle neurotransmitters or really anything that gets methylation going. I'm prob too full on toxins.

I do use tudca and a binder at night. I'm on very few supplements but these are two i continue to use. Maybe my methylation ability gets better the longer i stay in ketosis and the more toxins i shed.

I've considered coffee enemas and liver flushes to push the process along, but i'm also not sure its necessary and feelin decent in ketosis so may just keep the status quo for now.

If you aren't making neurotransmitters, you need to focus on the ingredients required to make them. The two most important amino acids are tryptophan and tyrosine. Make sure you have adequate supplies of each and that may mean supplementing niacin as it can raise tryptophan levels.

Try to get rid of things that block the neurotransmitter pathway. Aluminum and lead are the two biggest culprits so detoxifying those can help the pathway function better. I prefer Pectasol-C powder but there are other binders that can do it.

Eat a lot of polyphenols in raw plants because IMO, the pterin moiety is prone to availability problems. Copper can be deficient and it helps in the pathway as well. Lithium does the same. You have to have the right ingredients to make a good cake and the same applies to our biological pathways. If you want them to work, you have to have the right ingredients. It's much more complicated than that, but this is the first step.

Fishingforlighr, thanks this is very insightful and helpful! I’ve actuality started using activated charcoal at night because I’m in ketosis, which can cause detox symptoms in the beginning. I hadn’t considered it from the mold angle wrt to methylation, but that makes sense and I believe it.

Which binder do you use and at what time I’d say? I was using QuickSilver ultra binder but I wasn’t sure if it was causing joint pain. I’d found mixed reviews on silica so moved to just charcoal for now, but would be open to another product

One last thing - different mycotoxins/toxins in general are absorbed at different rates by different binders. A small amount of a wide variety of binders is generally better than a large amount of one. Activated charcoal, bentonite clay, and chlorella are all good places to start.

Again, if you feel herx-like symptoms from binders, its a sign you are processing more toxins than your body can handle! I made the mistake of trying to push through early on, and regretted it. The improvements I have seen have come with babying my body, so to speak.

From my understanding, mycotoxins (and all toxins in a quantity too large for the body to immediately release) are stored in fat cells (which are present in the brain). Your liver/many detox pathways are constantly working to detox the body, and regular bile flushes that occur after eating (especially fatty foods) carry these toxins out of the liver, and through the digestive tract. Unfortunately, 95% of that toxin-laden bile is re-absorbed and re-used, so only ~5% actually escapes.

I was concerned with the problem you mention. If your detox pathways are compromised, will those toxins ever reach the end stage at which they can be carried out by the bile? I've done quite a bit of research, and discussed the idea w/my LLMD, and come up with the following...

While your detox capabilities may be simultaneously under-performing and over-whelmed, they are still functioning. If your detox capabilities completely ceased, you would soon die. Your body is constantly detoxing anything from your own hormones/neurotransmitters to the thousands of tiny chemicals you inadvertently absorb through cleaning products, processed food, the air itself, etc... So no matter what, there will always be toxins present in your bile.

You might have a severely under-performing detox system, hence your sensitivities, but there will always be toxins flowing in and out of your liver via bile. The more binders you take, the less those toxins re-circulate.

It's also important to note that progress in detoxification is exponential! (Well, maybe not literally exponential, but definitely increasing in magnitude). The more you alleviate the load on your body, the better your detox system will function, and the cycle continues. You might only clear 10% of your bodies toxic load in the first month of taking tiny doses of different binders, but in that process you body becomes a little less inflamed and reactive, and a little more efficient in its own detox capabilities. All of the sudden you clear 15% in the next month, and the improvements snowball. This is a very sketchy/half-assed description, but I hope you get the point!

P.S. From what I understand, there is no way for toxins to exit your body other than via bile/the digestive tract (aside from sweating, but its effectiveness on many mycotoxins hasn't been researched much). There are things you can take that help push toxins out of fat cells (phosphatidylcholine, for example), but they'll still be processed through your liver.

Good synopsis Fishing, this has been very helpful, and your thinking makes sense.

Another great way to release toxins is through ketosis. I have looked into this since I've been in ketosis a while.
As you mentioned, toxins are by definition fat soluble (if they were water soluble they'd be peed out). In ketosis you will burn a lot of fat, and release a lot of toxins. Binders are a must. My first 2 months in ketosis every time, I can feel the toxic load on my body. This time I was happy to have learned I must use binders.