Methylation issues / COMT Met/Met and poor acetylator

[awl29]

Hi Triff,

many thanks for your reply!

Freddd has not been in I see. I just want to say that he would tell you that NAC can completely destroy methylation in many people, including himself and it can take moths (like 6 months) to restore it. Fredd will have to tell you detail this is only ballpark. I would never take it.

The bad thing is that it seems to have not only destroyed methylation (if at all the cycle was running...), but also it and primarily the Glutathione seem to have relocated critical amounts of mercury which seemingly used to be stored "safely" somewhere in my belly and brought it into my head and the CNS...

I still have strong symptoms of CNS irritability: mostly nerve pain in my back and head (ears, teeth), headache/tinnitus, slight tremors, and muscle twitching at almost any location in regular intervals.

After having done some more lab work ordered by my doc, I will therefore start the Cutler protocol using 25 mg of DMSA (due to my body weight - 240 lbs) every 4 hours on Thursday and truly hope that this will help about these symptoms...

I have Two COMT +/+ genetic mutations and I never get hypermethylation. This may be because I have genetic difficulty making BH4 to begin with, no idea. However I will tell you that I would have anxiety 24/7 and be unable to function if I did not take DHEA, which banishes it in under 15 minutes. I take 75mg DHEA in a divided dose to be right with the world and 30mg pregnenolone. I do not suggest you do the same as this is a very individual doe that works for me. Freddd used to take 100mg pregnenolone and 25mg DHEA, which is more normal. As we all fine tune our protocols, I dunno if he still takes it in that amount. This is hormone replacement, however, and I would read all they have to say about hormone replacement at www.lef.org and come up with a cancer avoidance stratgey (as I did) before I embarked on any such supplementation regime.

Does the need for a "cancer avoidance strategy" also apply to DHEA?

I am also taking 50mg every morning, but I cannot really say that they help regarding my COMT Met/Met related anxiety/agitation...!?

If I had an episode like yours, I would be taking P5P and TMG to try to clear the log jam. In my own personal case it does not seem that taking 200-300mg P5P is any more effective in lowering homocysteine than 100mg P5P so I think that pathway (at least in me) can only go so fast (but I would take the 100mg P5P) and then I would take 2g TMG to clear the backup. I would tend to take extra TMG if symptoms persisted. I know it sounds crazy because TMG helps you make SAMe. But listen to this...lyme uses up your MB12 and when you replace the mB12 with hydroxycobalamin you simply may not have the methyls to convert hydroxy to mB12 (the only form your body can use) and you may just be accumulating homocysteine with nowhere to get rid of it, which is a feedback to the methyl cycle affecting methylation btw. I would want to clear it out and the only way to do that is to make sure you are getting as much P5P as your body can use (I have several CBS +/+ mutations so I can't use P5P any faster than 100mg/day apparently but maybe you can), and TMG to supply methyls to turn hydroxyB12 to mB12 and also to get rid of the backup of homocysteine through the BHMT pathway. *I* think if you clear up the log jam, it will help you feel better. That is what I always do when I have a problem and it works for me.

I am also already taking 50mg of P5P (evenly divided between morning and evening), but can definitely try to go to 100mg. Regarding Trimethylglycine, I did not know that this exists until now. My doc had prescribed ordinary Glycine, but I left this out recently due to the fact that I did not feel any difference from taking it. Should TMG work better? If it is a methyl group donator, it might make me even more anxious and agitated like SAMe does (probably also due to CBS and/or SUOX issues which have not yet been looked at)...

Of course to get the protocol to work you do need mfolate. But your question was how to clear up the "all hell breaks lose" and I think you have to clear up the log jam to do that. I do not know how cysteine plays into that, I mean how you can neutralize taking NAC (maybe not possible). But I do have experience with my own very broken genes, clearing methyl cycle log jams. It may help you as it does me. At worse it will clear homocysteine but not clear your symptoms (in other words it can only help even if you can't tell it's helping).

My doc and I decided to stay away from 5-MTHF for now at least, as we just got the lab news back that I only seem to have a neglectable MTHFR issue (MTHFR A1298 = AC), and wait and see how my body will be able to cope with the Cutler protocol (while still continuing with Levaquin)...

Thanks again for your kind help & BR,
awl29

 

[triffid113]

I also have two CBS +/+ genetic defects. I actually think the DHEA is what helps (and maybe the only thing that helps) with that (as testosterone helps with that and that is one of the things made with CBS). When my test results showed the dreaded CBS mutations I was terribly depressed until I realised that I had priorly had a homocysteine test and it showed elevated homocysteine (despite what my genetic mutations were SUPPOSED to cause). So that cleared up my depression right away as I realised that LABS TRUMP GENETIC TESTS. I have 18 out of 30 genetic defects and was able to get my homocysteine perfect. However to do so it is NOT just a small amount of pills. I posted my protocol here once under Rydra Wong...it is very extensive. The core of it is Freddd's protocol, but Freddd's protocol is often misrepresented as his support nutrients are neglected. If you should neglect zinc, for instance, or have it be used up by allergies as happened to me, your "core methylation protocol" will no longer do the job. So the support nutrients are needed! For me, this is the core protocol that works:

1 Jarrow mB12 sublingual (I have proved I only need this during allergy season due to compromised absorption then)
2g TMG
50mg P5P (but I take 100mg if I am having any trouble)
1 Solgar metafolin
2 Thorne Basic B, divided dose
I do not need adenosylcobalamin

ut the other supplements I take are too many to list (again...I did it once). DHEA, pregnenolone are hormone replacement and could potentially lead to cancer. I take Life Extension's cruciferous vegetable extract (with DIM and I3C) as an anti-cancer supplement - it contains cysteine, fyi, but it works for me). I also take 7000 units of D3/day (I have the VDR genetic defect) and he Thorne multi which has active B's but also has selenium. I had read that breast cancer is linked to insufficient D, selenium, and/or iodine. I cannot take iodine or it drives me hyperthyroid (that is a worry bead for me). The broccoli supplement I take is due to Meridian Valley labs who wrote on my hormone test that broccoli is one of the things that prompts your body to make hormones that don;t lead to cancer.

Anyway, anyone trying to follow a methylation protocol w/o a good multi probably will not achieve proper methylation. There are many support nutrients needed.

My method is simple and cheap...gt your homocysteine reading ($60) and try your supplements until you get it to 6.3...then your methylation will be perfect. Since testosterone helps get around the CBS defects, it will help shuttle away methyls and that is what works for me. The dose of DHEA required for dealing with depression is - well you google it - but there were studies done on depression vs DHEA and the dose was 100mg for men. I am female and 75mg does it for me (but what it does for me is pretty prompt in regards to anxiety).

 

[Vegas]

Let me add one more question, please:



As I still seem to react badly to sulfa supplements, would you still recommend to try an epsom salt bath at this time? I tend to think I should be rather cautious - especially after having read this page:

http://www.healthyawareness.com/articles/about-mercury/epsom-salt-baths.aspx

Thanks again & BR,
awl29

As I understand it, the sulfa antibiotic reaction is indicative of an acetylation problem so we are really talking about different forms of sulfur and different problems. Although, acetylation is pretty closely linked to the methylation problems discussed in detail on this site. Acetyl-Co-A is formed as part of the Kreb's Cycle from pyruvic acid, and this ties back into the use of B12, folate, & direct methyl donors.

I do think you would be wise to use caution with the epsom salts in case you can't handle the sulfate. RVK has hypothesized that they may be problematic for those with large numbers of sulfate reducing bacteria. Interestingly, Taurine, can also be reduced to Sulfate in humans... I'm not sure to what degree. Theoretically, someone with problems with sulfate may also experience similar problems with taurine. .

 

[Vegas]

Hi Vegas,



I don't think that I have any issues with neither thiol foods nor supplements. I perfectly tolerate Chlorella, acetylcysteine, garlic/allicin, dairy products, asparagus (living in a region which is famous for its asparagus!), cauliflower, sauerkraut and basically anything on these lists. I haven't tried Silymarine yet - will ask my doc about it...

>>Some with low cysteine seem to tolerate if not crave these high thiol foods. If they are not causing any obvious symptoms, I wouldn't worry about it. The only way to tell for sure is to stop eating them for 4-5 days and see if you feel better or worse. I actually started becoming more reactive to these as I got better, which I think corresponded to the fact that my plasma cysteine values were improved, yet I still had a great big load of Hg left to chelate.

Unfortunately, it seems (just tried it again today...) that I still don't tolerate Taurine - it again caused very similar anxiety/agitation/tremor symptoms like SAMe and oral glutathione did (pointing to sulfa issues like with Bactrim?) when I tried them earlier this year.

>>Didn't you also have a problem with NAC? Well if you have what sounds like poor sulfation, adverse reaction to taurine, problem with methionine, and assuming the oral GSH is just getting broken down to more cysteine, it sounds like a big bottleneck at the beginning of the transulfuration pathway. Cysteine can be quite toxic. Yeah, you probably do have a CBS problem, just don't get hyperfocused on this.

Am I assuming correctly that these are also detox issues and point to my impaired ability to detox due to a partial methylation cycle block? And might this be related to genetic issues with CBS and/or SUOX (which have not yet been looked for)?

>>It does appear you have detox issues, and the glutathione metabolism certainly appears to be involved. I have no idea what influence your genetics may have contributed to your current situation. I don't have any genetic data to rely upon for guidance, but I have observed similar reactions with my children. Most notably from those substances that are hot topics here: MB12, MTHF, & Riboflavin + Mn, and to a lesser extent some of the downstream products like sulfate.

 

[Vegas]

Hi Triff,

many thanks for your reply!



After having done some more lab work ordered by my doc, I will therefore start the Cutler protocol using 25 mg of DMSA (due to my body weight - 240 lbs) every 4 hours on Thursday and truly hope that this will help about these symptoms...

awl29

If this proves to be difficult, you might want to consider oral DMPS, which is available in DE. It offers the benefits of having a much longer half-life; therefore, it needs to be dosed less often. Additionally, it is less likely to cause a yeast flare up. Good luck.

 

[awl29]

Hi Triff, hi Vegas,

sorry for my much delayed response - I fell really ill with antibiotics-induced diarrhea during the last two weeks, but as I am now treated with tinidazole (it is still neither proven nor disproven that Clostridium difficile is involved, but other Clostridia spp. definitely are), things seem to slowly improve...

As I understand it, the sulfa antibiotic reaction is indicative of an acetylation problem so we are really talking about different forms of sulfur and different problems. Although, acetylation is pretty closely linked to the methylation problems discussed in detail on this site. Acetyl-Co-A is formed as part of the Kreb's Cycle from pyruvic acid, and this ties back into the use of B12, folate, & direct methyl donors.

I already know that I have two NAT2 issues making me a real "slow acetylator" causing the reation to sulfa antibiotics like Bactrim, but thankfully it looks like I neither have issues with thiol-containing foods nor with sulfate such as in Epsom baths: I have taken two Epsom salt baths in the meantime, and I am able to tolerate a typical dose of one cup per bathtub quite fine...

So the bacteria in my gut that have gotten out of control seem to be the Clostridium species , not sulfate-reducing ones...

If this proves to be difficult, you might want to consider oral DMPS, which is available in DE. It offers the benefits of having a much longer half-life; therefore, it needs to be dosed less often. Additionally, it is less likely to cause a yeast flare up. Good luck.

Even through the period of diarrhea, I have made it through my first two rounds on the Cutler protocol - I noticed some increase in agitation and anxiety, but also very noticeable improvements related to tremors, involuntary muscle twitching, tinnitus and brain fog. Unfortunately, headaches and my special variant of a pulsating ear noise that is synchronous with my blood stream did not improve so far.

So I think that the initial theory of the i.v. Glutathione having caused Mercury redistribution (the "all hell broke loose" effect I suffered from) can be confirmed from this.

I am still hesitant to add ALA that early into my chelation rounds, as I assume that I currently still carry much more toxic mercury/heavy metals in my belly fat (weighing ~ 240 lbs) than in my head/brain.

Does anybody have some advice as of when to add ALA (I am also thinking about 25mg initially, as this is the lowest dose capsule I can get hold of) starting from a similar situation like mine?

Thanks again & best regards,
awl29

 

[awl29]

If this proves to be difficult, you might want to consider oral DMPS, which is available in DE. It offers the benefits of having a much longer half-life; therefore, it needs to be dosed less often. Additionally, it is less likely to cause a yeast flare up. Good luck.

Just noticed that I forgot to add that DMPS is available in Germany, but only as a prescription drug.

Also, from what I read about the Cutler protocol, DMPS might be more difficult to tolerate for people with chronic infections like myself than DMSA.

Yes, the seemingly inevitable yeast also is/will become an issue, but this one is currently my least severe, I think/hope...

BR,
awl29