Methylation issues / COMT Met/Met and poor acetylator

[awl29]

Hi all,

(Sorry for the lengthy first post - I will try to make it shorter in the future... )

I am new to this fantastic forum and would like to introduce myself and the issues I am currently facing:

I am living in Germany (Europe's #1 Lyme country... ) and suffering from stage 3 Lyme disease and chronic Bartonella infection - likely caused by a tick bite in 2002 - since late 2008 (only finally diagnosed in 2010), and due to prolonged antibiotics therapy, I now also am affected by CFS/mitochondriopathy.

Due to the Bartonella infection (which is currently treated with Levaquin with yet unknown outcome) and the fact that I have the COMT Met/Met variant (causing decreased deactivation of stress hormones), a hyperactive nervous system, and a permanent feeling of subtle anxiety for no known reason are my current main issues (against which I am taking "some" Clonidine and 3 mg of Bromazepame per day).

In addition, I already know that my phase 2 detox system is negatively affected by reduced GSTP1 activity, a "null" GSTM1 and two NAT2 variants making me a slow acetylator - which caused several issues with my tolerance of antibiotics in the past...


I am also undergoing treatment for CFS/mitochondriopathy, which included - in addition to several other vitamins, minerals etc. - the following i.v. injections twice a week:

• 5mg of Methylcobalamin
• 10mg of Adenosylcobalamin
• 2 amps of Glutathion 600mg
• 3 amps of NAC (300 mg acetylcysteine)
• 3 amps of Vitamin C (1000mg).

I did not have any issues with tolerating these injections so far, but also hardly noticed any effect (ok, maybe a slightly increased activily level for some few hours) besides my urine turning red/orange even a few minutes after injection.

Due to the fact that the above treatment didn't seem too successful, my doc and I changed this on Thursday last week to become

• 3mg of Hydroxycobalamin
• 2 amps of Glutathion 600mg
• 3 amps of NAC (300 mg acetylcysteine)
• 3 amps of Vitamin C (1000mg)

and - quite unexpectedly - all hell broke loose:

It started on Thursday afternoon with severe headache, tiredness and feeling completely powerless (and I first thought: well, finally, there is something going on!), but then throughout Thursday night, I got severe symptoms of anxiety and agitation:

• complete sleeplessness even though increased doses of Bromazepame and Clonidine
• psychiatric symtoms (severe depression even up to temporarily feeling suicidal)
• really severe panic attacks with coughing and crying for several hours
• tremor of arms and hands when trying to do fine motor activities
• strange thoughts and dreams, a feeling like continuous brain fog
• hugely reduced ability to concentrate
• transient numbness of fingers, feet (especially heels while lying in bed).

Even today, four days later, my level of agitation and anxiousness is still far away from what used to be "normal" throughout the last months although I still take considerably more Clonidine and Lexotanile than usually.

I did some thorough resarch of the posts in this forum and developed some theories that could possibly explain what happened to me:


1) I might have been experiencing immediate conversion of active MB12 and AB12 to Glutathionyl-B12 as described by Freddd for my first series of injections:

The mechanism is pretty simple. Glutathione, whether infused or precursors like NAC/l-glutamine, combines with (...) specifically mb12 and adb12, the two active forms. It combines with these two forms at least, virtually immediately, and without limit. It would appear that 1mg of glutathione can combine with 4mg of cobalamin. As the body's entire load of cobalamin is said to be 2.5 to 5 mg, 1.25mg of glutathione is enough to destroy 100% of the body's entie load of active and inactive cobalamins. When it combines with cobalamin forming glutathionylcobalamin for some reason it becomes a preferred excretion form being excreted even more rapidly than cyanocbl, the preferred speed champion for kidney excretion. This can be easily seen by anybody who takes b12 of a large enough dose. Suddenly the urine becomes MUCH redder very suddenly providing very visual evidence of the rapid excretion of far more than can be accounted for by the most recent dose.

2) Changing the MB12 and AB12 combo to HB12 as for my most recent injection might have produced more stable active forms of B12 and (re)started the methylation cycle for the very first time, thereby causing all my symptoms perceived.


3) I am completely unsure how to classify the reactions my body developed to that most recent injection: Would/could this be

• real "detox" symptoms (due to Lyme or Bartonella toxins or amalgame)?
• the paradoxical folate deficiency symptoms that have been described by both Rich and Freddd as the consequence of some break up in the methylation cycle - again quoting Freddd:

  Then when the methylfolate enters the cell for a DNA transaction and finds no cofactor in the form of mb12 the methylfolate is flushed out of the cell. This was identified by Rich as the "methyl trap", sometimes also called the "methylfolate trap", which was first hypothesized perhaps 50 years ago. This gives a high serum level of methylfolate yet induces severe folate deficiency symptoms so may look paradoxical but isn't caused by taking folic acid or folinic acid.

So I'd like to ask the experienced people here (would be particularly amazing to get an opinion from Rich and/or Freddd):

Do you think my assumptions in 1) to 3) about what happened to me might be valid?

Regarding 3) specifically:
I will have my MTHFR being analyzed within next few weeks, but from my description, are you able to discern (or maybe at least provide an assumption) which one is more likely?

For now, I have stopped any B12 intake until the symptoms will be down to the level I am used to.
Would you recommend that I start with 5-MTHF even before I know the results of my genetic testing (note that I never took any 5-MTHF so far, only folic acid which always tended to cause issues)?

And would it be more advisable to stay with the i.v. a combo of HB12 and Glutathione/ACC (which I now know I am responsive to...) or remove the Glutathione and ACC from the injection and continue with MB12 and AB12?

(Note that I wouldn't be surprised to receive different advice here due to the different points of view of Freddd's and Rich's protocols.)


Thanks a million in advance for any help!

Best regards from Germany,

awl29

 

[place]

My hope is both will take a look at this case as it looks complicated. Two things I see that are missing are the Methylfolate and potassium. Both Rich and Fred support adding both of these to your protocol. I am homo for MTHFR gene and I really respond well to the methylfolate.

Best of luck.

 

[awl29]

My hope is both will take a look at this case as it looks complicated. Two things I see that are missing are the Methylfolate and potassium. Both Rich and Fred support adding both of these to your protocol. I am homo for MTHFR gene and I really respond well to the methylfolate.

Best of luck.

Thanks very much, place!

Note that potassium citrate (2 x 400mg per day) has already been part of my oral "vitamins, minerals etc." - but maybe that's too few for a 110kg/240lbs person. On the other hand, serum potassium values have always been within normal range so far (two weeks ago, exactly Freddd's "target" value of 4.50 mmol/l).

Methylfolate/5-MTHF indeed is the main thing I'd be interested in, because I never ever have tried it so far...

BR,
awl29

 

[minkeygirl]

I don't understand much of the science behind this but I noticed yesterday that I am waking earlier feeling antsy and jittery and my brain is really going bonkers today racing and all over the place. I am also feeling unstable, like I'm on the verge of crying (this just hit me)

After taking some NuSalt potassium yesterday since I had nothing else I was foggy, had a headache and my guts were twisted in knots like they were cramping. I should get 99 mg potassium today.

Since taking the dibencozide this morning my gut is knotting up again.

I'm taking 5 mg B12 Jarrow, 3000 mcg dibencozide (has folate because the list I saw was not updated) and 800 mcg methylfolate. 4000 C, tons of other stuff on the protocal which I take anyway.

Help please.

Thanks

 

[Vegas]

Hi all,

(Sorry for the lengthy first post - I will try to make it shorter in the future... )

I am new to this fantastic forum and would like to introduce myself and the issues I am currently facing:

I am living in Germany (Europe's #1 Lyme country... ) and suffering from stage 3 Lyme disease and chronic Bartonella infection - likely caused by a tick bite in 2002 - since late 2008 (only finally diagnosed in 2010), and due to prolonged antibiotics therapy, I now also am affected by CFS/mitochondriopathy.

Due to the Bartonella infection (which is currently treated with Levaquin with yet unknown outcome) and the fact that I have the COMT Met/Met variant (causing decreased deactivation of stress hormones), a hyperactive nervous system, and a permanent feeling of subtle anxiety for no known reason are my current main issues (against which I am taking "some" Clonidine and 3 mg of Bromazepame per day).

In addition, I already know that my phase 2 detox system is negatively affected by reduced GSTP1 activity, a "null" GSTM1 and two NAT2 variants making me a slow acetylator - which caused several issues with my tolerance of antibiotics in the past...


I am also undergoing treatment for CFS/mitochondriopathy, which included - in addition to several other vitamins, minerals etc. - the following i.v. injections twice a week:

• 5mg of Methylcobalamin
• 10mg of Adenosylcobalamin
• 2 amps of Glutathion 600mg
• 3 amps of NAC (300 mg acetylcysteine)
• 3 amps of Vitamin C (1000mg).

I did not have any issues with tolerating these injections so far, but also hardly noticed any effect (ok, maybe a slightly increased activily level for some few hours) besides my urine turning red/orange even a few minutes after injection.

Due to the fact that the above treatment didn't seem too successful, my doc and I changed this on Thursday last week to become

• 3mg of Hydroxycobalamin
• 2 amps of Glutathion 600mg
• 3 amps of NAC (300 mg acetylcysteine)
• 3 amps of Vitamin C (1000mg)

and - quite unexpectedly - all hell broke loose:

It started on Thursday afternoon with severe headache, tiredness and feeling completely powerless (and I first thought: well, finally, there is something going on!), but then throughout Thursday night, I got severe symptoms of anxiety and agitation:

• complete sleeplessness even though increased doses of Bromazepame and Clonidine
• psychiatric symtoms (severe depression even up to temporarily feeling suicidal)
• really severe panic attacks with coughing and crying for several hours
• tremor of arms and hands when trying to do fine motor activities
• strange thoughts and dreams, a feeling like continuous brain fog
• hugely reduced ability to concentrate
• transient numbness of fingers, feet (especially heels while lying in bed).

Even today, four days later, my level of agitation and anxiousness is still far away from what used to be "normal" throughout the last months although I still take considerably more Clonidine and Lexotanile than usually.

I did some thorough resarch of the posts in this forum and developed some theories that could possibly explain what happened to me:


1) I might have been experiencing immediate conversion of active MB12 and AB12 to Glutathionyl-B12 as described by Freddd for my first series of injections:


2) Changing the MB12 and AB12 combo to HB12 as for my most recent injection might have produced more stable active forms of B12 and (re)started the methylation cycle for the very first time, thereby causing all my symptoms perceived.


3) I am completely unsure how to classify the reactions my body developed to that most recent injection: Would/could this be

• real "detox" symptoms (due to Lyme or Bartonella toxins or amalgame)?
• the paradoxical folate deficiency symptoms that have been described by both Rich and Freddd as the consequence of some break up in the methylation cycle - again quoting Freddd:

So I'd like to ask the experienced people here (would be particularly amazing to get an opinion from Rich and/or Freddd):

Do you think my assumptions in 1) to 3) about what happened to me might be valid?

Regarding 3) specifically:
I will have my MTHFR being analyzed within next few weeks, but from my description, are you able to discern (or maybe at least provide an assumption) which one is more likely?

For now, I have stopped any B12 intake until the symptoms will be down to the level I am used to.
Would you recommend that I start with 5-MTHF even before I know the results of my genetic testing (note that I never took any 5-MTHF so far, only folic acid which always tended to cause issues)?

And would it be more advisable to stay with the i.v. a combo of HB12 and Glutathione/ACC (which I now know I am responsive to...) or remove the Glutathione and ACC from the injection and continue with MB12 and AB12?

(Note that I wouldn't be surprised to receive different advice here due to the different points of view of Freddd's and Rich's protocols.)


Thanks a million in advance for any help!

Best regards from Germany,

awl29

Large doses of the cobalamins can certainly cause a few of those adverse symptoms, but I think you are looking in the wrong direction. If you spend enough time on this forum you will learn about those who suffered major setbacks from using intravenous glutathione. Consider discontinuing this and the I/V cysteine. Your GSTM SNP has been implicated as a highly significant risk factor for heavy metal toxicity. Similarly, the acetylation problem would have a similar effect because co-a, which is used in many of these reactions, is a thiol. Your symptoms, especially the tremors, depression/suicidal ideation, suggest Hg redistribution to the brain, something that supraphyisological doses of GSH and cysteine can do. Your symptoms are VERY familiar to me dating back to my acute mercury exposure. Most with Lyme have HM problems, and I have noticed that the Lyme Conferences have increasingly focused on heavy metals in recent years. COMT doesn't help either...Hg makes this so much worse because the catecholamines just hang around causing other problems including brain fog, sweating, difficulty sleeping, etc.. Please take the psych symptoms very seriously. One can very quickly go from stable to suicidal. Brain Hg can radically alter neurotransmitters. I had one stunning experience that I will never forget.

 

[awl29]

Hi Vegas,

many thanks for your reply!

Please take the psych symptoms very seriously. One can very quickly go from stable to suicidal.

No immediate danger as long as my intellect can still control my brain and there is some hope left to be able to sort out this puzzle...

I will definitely stop any i.v. substances, i.e. B12 as well as Glutathione and acetylcysteine until this current episode has been sorted out and there is at least some kind of explanation why it happened...

If you spend enough time on this forum you will learn about those who suffered major setbacks from using intravenous glutathione. Consider discontinuing this and the I/V cysteine. Your GSTM SNP has been implicated as a highly significant risk factor for heavy metal toxicity. Similarly, the acetylation problem would have a similar effect because co-a, which is used in many of these reactions, is a thiol. Your symptoms, especially the tremors, depression/suicidal ideation, suggest Hg redistribution to the brain, something that supraphyisological doses of GSH and cysteine can do. Your symptoms are VERY familiar to me dating back to my acute mercury exposure.

I only learned about my COMT and phase 2 detox issues recently, and heavy metals definitely are an issue for me - I had the last remaining 4 amalgame fillings removed (with proper protection) in March/April, but was quite stable afterwards. So far, my doc did not want to start a chelation therapy yet due to my Lyme background, because he would like to fill up B12 and Glutathione levels first in order not to cause any severe reactions...!? Is he completely wrong?

And what approach to chelation - especially using which chelation agents - would you recommend in my case?


But the main question I'd have regarding your theory is: Why did my severe adverse reactions only start after replacing MB12 and AB12 by HB12 for the very last of my i.v. shots (keeping Glutathione, ACC and Vit C at the exact same levels)? Please note that I received more than 20 i.v. shots using the initial combo (5mg MB12, 10mg AB12, 600mg Glutathione, 300 mg ACC, 3g VitC) throughout the last 10+ weeks without any such adverse reaction...!?

How would you explain the fact that all this suddenly started only now (i.e. after the 20+th injection including Glutathione and ACC)? Is there anything different with HB12 (as opposed to MB12 and AB12) that could have caused this?

After one more night with palpitations, high BP/heart rate, anxiety and sleeplessness (needed another 6mg of Lexotanile to finally find some sleep...) I would also be most interested in any suggestions how to slow this current process down as fast as possible...

I took an additional 800mg of potassium citrate in the early morning, and my feeling was that it helped at least somewhat - so could potassium deficiency still be part of the issue, and what is a safe max. daily dose of potassium citrate?


Thanks a million for any advice!

BR,
awl29

 

[Vegas]

"Why did my severe adverse reactions only start after replacing MB12 and AB12 by HB12 for the very last of my i.v. shots (keeping Glutathione, ACC and Vit C at the exact same levels)? Please note that I received more than 20 i.v. shots using the initial combo (5mg MB12, 10mg AB12, 600mg Glutathione, 300 mg ACC, 3g VitC) throughout the last 10+ weeks without any such adverse reaction...!?
How would you explain the fact that all this suddenly started only now (i.e. after the 20+th injection including Glutathione and ACC)? Is there anything different with HB12 (as opposed to MB12 and AB12) that could have caused this?"

I believe the addition of the Hydroxo and the subsequent adverse symptoms was purely coincidental. You are right to question the temporal relationship of this event, but the side effects you experienced are extremely concerning for Hg redistribution. The delayed effect is not entirely clear, but it seems to involve both a cumulative concentration of Hg in the brain, and the involvement of some particularly sensitive tissues. Some of the hormone receptors, for example, have 4,6, or more thiol groups, so they grab hold of Hg and the bonds are don't let go. Some people who do IV GSH get adverse effects from the beginning, but with others the effects are delayed. Often times those who experience adverse effects have no forewarning when it happens. The same thing has been reported by many after inappropriately using Lipoic Acid. The trend that I have always observed on this site is that those who suffer major setbacks do so after either inappropriate use of chelating agents or via intravenous glutathione...this strongly suggests a Hg burden. These really can cause major harm in certain people.

Getting B12 levels up may be helpful, but the real changes in many happen when you add Methylfolate (as many have found some of these are not so pleasant, but it can dramatically improve your metabolism of catecholamines as can the addition of sulfate and molybdenum). Increasing GSH with large bolus doses of GSH is not going to achieve lasting improvement of plasma GSH. You might conjugate some other toxins and enhance their excretion, but you are not going to materially improve your HM toxicity, and you may worsen your situation considerably. If you do have significant Hg toxicity, then this is oxidizing your GSH. Getting the Hg out makes the biggest difference. To do so you will need to use ALA taken every three hours around the clock, without interruption...although the recommendation from Andy Cutler is to do so only after 90 days post-amalgam has elapsed.

I would suggest you "Google" low-thiol foods and try to adhere to eating only these for a week to see if this helps your symptoms. Avoid all the high thiol foods and high-thiol supplements. A low-thiol diet is essentially a low-sulphur diet, but most meats are o.k. Zinc, Selenium (no selenite), Magnesium, C, E, B2, B1, & small doses of Methyfolate might be a good place to start. Possibly silymarin, after a thiol exclusion diet. Lots of Taurine and Magnesium may be helpful...assuming you tolerate these. As noted above, sulfate & possibly moly, along with a combination of B12 + 5MTHF can help with the stress hormones.

 

[awl29]

Hi Vegas,

many thanks one more time for your help!

I believe the addition of the Hydroxo and the subsequent adverse symptoms was purely coincidental. You are right to question the temporal relationship of this event, but the side effects you experienced are extremely concerning for Hg redistribution. The delayed effect is not entirely clear (...)

I still am not completely convinced that all of this reaction can be blamed only on mercury/amalgame...

I rather tend to think it might be a combination of Hg (or maybe even Bartonella) toxins and potassium deficiency when my methylation cycle seems to have started at least intermittently through the i.v. HB12 combined with Glutathione - my argument for this thesis would be: Throughout today, I have increased my intake of potassium from its previous 800mg to 2400mg, and felt really very much better than before - heart palpitations did completely vanish, and anxiety/agitation is at least improved and can once again be controlled with Clonidine/Lexotanile (as before this nightmare started).

I will also take 800 more mgs of potassium citrate immediately before I go to bed now (together with my usual 3mg of Lexotanile and 400 mg of Clonidine as before all this started) and keep you updated tomorrow morning about its effects...

Indeed, it seems that I have to get hold of 5-MTHF and try this out as soon as possible, but starting slowly (not that easy to get hold of it in Germany, I might need to order from the UK or convince my doc to prescribe it - which might only work after MTHFR mutation has been confirmed...).

Finally, I assume you had a pretty good experience with the Cutler protocol for Hg chelation? Did you use DMPS or DMSA before and in parallel to ALA? I will try to convince my doc to use this once I will be 90 days post my last filling by mid of July...

Thanks again & BR,
awl29

 

[awl29]

One more addition - I am also very grateful for your advice about thiols:

The need to avoid thiols due to my phase 2 detox issues perfectly explains why I was completely unable to tolerate Bactrim (which I found out to be a thiol drug only now!) against my Bartonella infection: After about 2 days of taking Bactrim, I had about the same neuropsychiatric side effects as in this current episode, but in a somewhat reduced strength...

I now start to understand what these phase 2 deficiencies really mean...

BR,
awl29

 

[Vegas]

One more addition - I am also very grateful for your advice about thiols:

The need to avoid thiols due to my phase 2 detox issues perfectly explains why I was completely unable to tolerate Bactrim (which I found out to be a thiol drug only now!) against my Bartonella infection: After about 2 days of taking Bactrim, I had about the same neuropsychiatric side effects as in this current episode, but in a somewhat reduced strength...

I now start to understand what these phase 2 deficiencies really mean...

BR,
awl29

Bactrim and other sulfa antibiotics have in the past made me quite ill as well. This is actually caused by your poor acetylation. This class of antibiotics is primarily detoxed via acetylation. The target molecule is bound to an acetyl group. While there is great genetic variance with respect to how well acetylation works in a particular person, this situation can apparently be compounded by environmental exposures throughout the course of one's life. By the way, B5 can have some impact on acetylation, but I have found the conenzymated form of B5, pantethine, vastly more effective.

 

[Vegas]

Hi Vegas,

many thanks one more time for your help!



I still am not completely convinced that all of this reaction can be blamed only on mercury/amalgame...

I rather tend to think it might be a combination of Hg (or maybe even Bartonella) toxins and potassium deficiency when my methylation cycle seems to have started at least intermittently through the i.v. HB12 combined with Glutathione - my argument for this thesis would be: Throughout today, I have increased my intake of potassium from its previous 800mg to 2400mg, and felt really very much better than before - heart palpitations did completely vanish, and anxiety/agitation is at least improved and can once again be controlled with Clonidine/Lexotanile (as before this nightmare started).

I will also take 800 more mgs of potassium citrate immediately before I go to bed now (together with my usual 3mg of Lexotanile and 400 mg of Clonidine as before all this started) and keep you updated tomorrow morning about its effects...

Indeed, it seems that I have to get hold of 5-MTHF and try this out as soon as possible, but starting slowly (not that easy to get hold of it in Germany, I might need to order from the UK or convince my doc to prescribe it - which might only work after MTHFR mutation has been confirmed...).

Finally, I assume you had a pretty good experience with the Cutler protocol for Hg chelation? Did you use DMPS or DMSA before and in parallel to ALA? I will try to convince my doc to use this once I will be 90 days post my last filling by mid of July...

Thanks again & BR,
awl29

You are probably right--that it is multifactorial. That is certainly good news that the Potassium proved to be of such benefit for the heart palps. I suppose if it is purely an acute potassium deficiency, this will resolve over time. Also it is worth mentioning that enormous doses of cobalamins have been known to cause their own problems, including extreme agitation. I still think the tremors and psych symptoms are very suspicious for Hg as they are classic symptoms.

I have had a very positive experience with what has essentially Dr. Cutler's protocol, with a few minor adaptations. I used DMSA exclusively for 5-6 months before starting ALA. You may fare better with oral DMPS if you can get it. This is just speculation based upon your Lyme diagnosis.

 

[awl29]

Hi Vegas,

good news!

Indeed, I caught some desperately needed 7.5 hours of sleep last night and only woke up once with a slightly increased BP/heart rate, but no heart issues/palpitations and no more feelings of anxiety more intense than before this episode started. So it indeed looks that I am on the mend again - but it will still be challenging to make the right decisions on how to proceed with my therapy starting from next week...

Base line: I think I need to be happy that the level of my Hg intoxication seems not as high as initially feared, but there still is some real work to do to figure out how to make my methylation work "properly" again due to the detox issues.

One more question, if I am allowed to: When you talked about MTHF, you added

it can dramatically improve your metabolism of catecholamines as can the addition of sulfate and molybdenum

I couldn't find some general advice about potential advised dosages of molybdenum, and regarding "sulfate", my question would even be: what kind of sulfate do you mean in particular? Or doesn't it matter which particuar metal's sulfate we are talking about? Also, at which dosages?

My doc never talked to me about either of those two so far, so I assume I'll have to tell him here what I learned from you...

Thanks a million & BR,
awl29

 

[Vegas]

COMT and MAOA are involved in catecholamine degradation at an "upstream location" in the metabolism. The byproducts of these enzymatic processes are eventually conjugated to sulfate and to a lesser extent glucuronide. The molybdenum comes into play because it can catalyze the SUOX reaction to produce more sulfate. We don't know if you have a SUOX inefficiency, but given all the B12 you are taking, it wouldn't be a bad idea to add some support for this enzyma. If you want to add exogenous sulfate, then I think magnesium sulfate baths are the superior alternative because you can get great absorption of both magnesium, which can further calm he autonomic nervous system, and sulfate. Together, these will both help with your stress hormones. I used about a kilo in a bath, but you may have to work up to this...and you can read about problems some have with this, which Rich speculates is caused by SRB in the gut. Alternatively, you can take glucosamine sulfate, but don't take this at the same time as a calcium supplement because these can bond in the gi tract. As for Moly, 500 mcg/day is a good dosage. Both sulfate and moly can cause problems in some, so work up to these, if you choose to take them. For glucuronidation, you can use artichoke extract and kombucha, again not tolerated by everyone, but these things really work. Still it all starts with COMT and MAO, so slowly add in some MTHF and perhaps some B2 as I believe the MAOA reaction requires riboflavin. B2 seems to be coming up more and more on this forum.

Excessive stress hormones can linger and make you feel quite ill when they are poorly metabolized. I would get brain fog for hours after an adrenaline surge. Any stressor would cause the stomach cramping that people here call "buterflies," I couldn't tolerate any stressful situation without a strong physiological response. These measures + chelation totally eliminated this. I don't know if these things will help with your situation, but they may be things to consider.

 

[awl29]

Thanks Vegas,

I didn't know that epsom salt is magnesium sulfate... Will most likely use this, as I am already doing basic baths, but was using baking soda so far. Also, additional magnesium is always good to counter the bad side effects of Levaquin on the tendons...

Today was slightly more agitated in some parts and much too sleepy in the afternoon - I still have to figure out the optimal dosage of potassium citrate - and finally the day ended with an unexpected bitter defeat for the German team at the Euro against Italy...

BR,
awl29

 

[Vegas]

Levaquin is indeed some nasty stuff, only to be outdone by another fluoroquinolone antibiotic, Cipro. I've had experience with both, and in each instance the infection worsened. I always assumed the infection was simply not sensitive to that particular class of anti-microbials, but the fluoroquinolone antibiotics have a very bad track record from anecdotal reports. I knew they put great demands on gluathione, but recent studies have shown just how bad this class of AB can be. Very significant decreases in glutathione, huge increase in reactive oxygen species, and associated lipid peroxidation...factors, which the authors believes causes the tendon and cartilage pathology. There are better antibiotics out there for sure. I could see how long-term fluroquinolone use would contribute to perpetuation of someone's illness. Of course, many people feel better on this class of antibiotics, so perhaps, as the authors indicated, Gatifloxacin, is a better option. Still, some pretty scary stuff if they say talk about SOD enzyme depletion, and recommend that patients use antioxidants with these antibiotics.


"There was a considerable increase in lipid peroxide levels indicating an enormous oxidative stress. Caution to be taken for patients especially on Ciprofloxacin and Levofloxacin therapy. These studies necessarily warranty the use of exogenous antioxidants as adjuvant in combination with fluoroquinolones, and their benefits should be carefully examined in a controlled clinical setup."

"The efforts of the endogenous antioxidant enzymes like SOD to remove the continuously generated free radicals initially increase due to an induction but later enzyme depletion occurs by 73.3% and 32.2% for ciprofloxacin and levofloxacin respectively, resulting in oxidative cell damage. Hence when the generation of reactive free radicals overwhelms the antioxidant defence, lipid peroxidation of the cell membrane occurs. This causes disturbances in cell integrity leading to cell damage/death. In the present study the repeated administration of CFX (recommended dosage regimen of CFX for UTI) resulted in increase free radical adduct generation by CYP450 mediated metabolism that cumulate and may result in increased ROS[26] and substantial reduction in antioxidant defence. Perhaps this could be the reason for the adverse effect in particular tendinitis attributed to free radical generation. The present investigations support the pathogenesis of chondrotoxicity explained by the magnesium-chelating properties of these drugs, leading to radical formation and finally to irreversible cartilage lesions. Animal toxicological studies have been published confirming that the quinolone-induced tendopathy is a drug-induced, dose-dependent effect of these agents and profoundly seen with CFX and LVX.[31]
In vitro studies on tendon cells also report low toxicity after 24 hr for all fluoroquinolones, but a high-significant tenotoxicity after 48-72 hr. Free radical overproduction was observed for all fluoroquinolones, but significant anion superoxide increased only with pefloxacin and ciprofloxacin. Studies separate two models of fluoroquinolones tenotoxicity: Pefloxacin or ciprofloxacin induced a higher intrinsic tenotoxicity than ofloxacin or levofloxacin.[32] A reported hypothesis indicates that, up on administration of fluoroquinolones the glutathione content falls rapidly so the intracellular antioxidant enzymes lose their ability to modulate the overproduction of ROS[33] which was also observed in the present study. Gatifloxacin produced lesser oxidative stress and can be consider safe relative to ciprofloxacin and levofloxacin."


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249743/?tool=pubmed

 

[awl29]

Hi Vegas,

regarding Levaquin, I currently don't have any other choice than to continue taking it.

I know that this is like driving a car, trying to put the gas pedal to the metal (trying to improve methylation, recover from CFS/mitochondriopathy, detox and improve metabolism) while also hitting the brake quite hard at the same time (trying to keep Lyme and Bartonella under control, which is hard because they had nearly 10 years to disseminate through my body)... Squaring the circle...

The Bartonella (or "Bartonella Like Organism", as Burrascano named them) strain that I am suffering from does not at all react to neither Macrolides nor Rifampin, which means that the Chinolones remain as the only therapeutic option as far as antibiotics are concerned, and - as also stated by Burrascano (see e.g. here) - Levaquin works best of them.

When leaving "my" Bartonella untreated for about a month, I get severe anxiety, agitation, attacks of nearly uncontrollable rage and later depression, horrible IBS, complete insomnia, tinnitus and/or acute hearing loss, blurred view, crunching sounds in all my joints and suffer from general pain throughout my whole body, which indeed in combination feels even worse than the effects of the HB12 last week.

All these symptoms nearly completely vanish again within one to two weeks of taking Levaquin - but fatigue and CFS like symptoms do not (as expected)...

Fortunately, with the help of transdermal magnesium and an oral magnesium intake of 1600 to 2000mg per day, I can at least tolerate long-term Levaquin without tendon issues getting out of control...

Gatifloxacin is not available throughout the whole of Europe: it was unsolicitedly revoked by its manufacturer due to severe issues with hypoglycaemia in 2004. I have already tried imported Factive (which is also not available in the EU, but can be imported from Russia, India or the U.S. at a very high cost of about EUR 10 / US-$12.50 per single tablet), but it didn't help any better than Levaquin...

I am really looking forward to try Byron White's A-BART after resolving issues with getting it through German customs, because I read some impressive success stories...

BTW: Feeling about the same today as yesterday, but I still need > 2000 µg of potassium in order to control heart symptoms and additional agitation... Any idea about how long this might last even though I am not going to add neither new B12 nor Glutathione?

Thanks anyway for the warning about the Chinolones - I am perfectly aware of their dangers...

BR & have a great weekend,
awl29

 

[awl29]

Hi Vegas,

I would suggest you "Google" low-thiol foods and try to adhere to eating only these for a week to see if this helps your symptoms. Avoid all the high thiol foods and high-thiol supplements. A low-thiol diet is essentially a low-sulphur diet, but most meats are o.k. Zinc, Selenium (no selenite), Magnesium, C, E, B2, B1, & small doses of Methyfolate might be a good place to start. Possibly silymarin, after a thiol exclusion diet.

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...

Lots of Taurine and Magnesium may be helpful...assuming you tolerate these. As noted above, sulfate & possibly moly, along with a combination of B12 + 5MTHF can help with the stress hormones.

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.

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)?

Thanks heaps one more time for your kind help!

BR,
awl29

 

[awl29]

Let me add one more question, please:

The molybdenum comes into play because it can catalyze the SUOX reaction to produce more sulfate. We don't know if you have a SUOX inefficiency, but given all the B12 you are taking, it wouldn't be a bad idea to add some support for this enzyma. If you want to add exogenous sulfate, then I think magnesium sulfate baths are the superior alternative because you can get great absorption of both magnesium, which can further calm he autonomic nervous system, and sulfate. Together, these will both help with your stress hormones. I used about a kilo in a bath, but you may have to work up to this...and you can read about problems some have with this, which Rich speculates is caused by SRB in the gut.

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

 

[awl29]

All,

can anybody give an estimate on how long it will take for my body to slow down the methylation process that have been started much too violently exactly two weeks ago (see my initial post in this thread) to its previous (broken) level for me to become stable again?

I have completely stopped any B12 as well as folic acid intake (except from food) since June 22nd, but still seem to feel both

• the "start" effects of methylation that was broken for a long time: I am taking up to 4-4.5g of potassium every day (body weight: 113kg/250lbs) which still helps to calm down down headache, muscle twitching, agitation and nausea (also getting severe IBS/diarrhea from so much potassium and magnesium...)
• the effects of too much mercury detox having being kicked off/relocated by this unfortunate last injection: headache, tinnitus, tremor, mind fog?

After that experience, I would like to properly re-start methylation very slowly and carefully, but for now I fear that the current state might continue for much too long without any change...!?

Thanks a million for your kind help & best regards,
awl29

 

[triffid113]

Hi all,

• 5mg of Methylcobalamin
• 10mg of Adenosylcobalamin
• 2 amps of Glutathion 600mg
• 3 amps of NAC (300 mg acetylcysteine)
• 3 amps of Vitamin C (1000mg).

I did not have any issues with tolerating these injections so far, but also hardly noticed any effect (ok, maybe a slightly increased activily level for some few hours) besides my urine turning red/orange even a few minutes after injection.


Due to the fact that the above treatment didn't seem too successful, my doc and I changed this on Thursday last week to become

• 3mg of Hydroxycobalamin
• 2 amps of Glutathion 600mg
• 3 amps of NAC (300 mg acetylcysteine)
• 3 amps of Vitamin C (1000mg)

and - quite unexpectedly - all hell broke loose:


It started on Thursday afternoon with severe headache, tiredness and feeling completely powerless (and I first thought: well, finally, there is something going on!), but then throughout Thursday night, I got severe symptoms of anxiety and agitation:

• complete sleeplessness even though increased doses of Bromazepame and Clonidine
• psychiatric symtoms (severe depression even up to temporarily feeling suicidal)
• really severe panic attacks with coughing and crying for several hours
• tremor of arms and hands when trying to do fine motor activities
• strange thoughts and dreams, a feeling like continuous brain fog
• hugely reduced ability to concentrate
• transient numbness of fingers, feet (especially heels while lying in bed).

...

Best regards from Germany,

awl29

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. However I do take a cysteine supplement...I take the cruciferous vegetable extract supplement by Life Extension www.lef.org which contains broccoli, DIM, I3C...and raises my cysteine. I'm afraid I do not know what form of cysteine this comes in but it does a very good job of modulating my hormones since I take bioidentical hormone replacement and I have had perfect homocysteine (and thus SAMe) on it. Anyway, after Freddd's experience, I would NEVER take NAC.

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.

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 P%P 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 th 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.

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).

Triff