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Need for massive amount of B12 and MTR A2756G polymorphism

Lotus97

Senior Member
Messages
2,041
Location
United States
So while you say " I don't see how any of what you say is possible" it might be a good idea for you to do some more reading sufficient to make your own models from the research info and let's discuss that. I trust the journals on mercury more than I trust the many belief systems on mercury that ignore all the scientific evidence. Show why the scientific evidence and all those journal articles are wrong. Are you going to after the chemistry? The pharmacodynamics? Or what?
I trust Rich. He was very knowledgeable in the areas of both methylation and mercury toxicity. He worked with people dealing with both issues in addition to consulting with various doctors. He has said that toxins, including metals can and most likely will be released during the process of methylation. This is different than the issue of methylcobalamin methylating mercury although there has been a study to suggest that this too is possible.
Hi Sushi,

I think the whole things, the entire result set of the model is somewhere on this very methylation menu in a thread on a discussion of mercury. In 1978 I told the director of an HMO that we could get a lot of answers from the medical histories if we included some additional things. I was using the known need for the 3 vitamins to prevent neural tube defects. I was sure plenty of other things could also be found including different treatments that work.better with whatever side effects taken into account. They got bought in the rush to cash in on HMOs and hence destroy them. As soon as they were bought the health management part went down the drain and it was cash management.
I don't see how this answers her question. You've said a lot of things that sound convincing to the average reader, but you haven't really provided any actual evidence. Sushi is very busy now and has asked you this question twice already. There are many people here who suspect mercury toxicity and are looking for answers. If you don't know then just say so.
 

Helen

Senior Member
Messages
2,243
Hi kday,
I am really sorry for your situation. I have similar problems, and I am very happy to have found this forum with all knowledge and experiences that people shares. Sorry for my English..
kday
So my questions are, what more can I do about this them supplementing massive amounts of methyl-B12. I have added folate, P5P, etc, but it’s been pretty clear the last couple years that the biggest need is methyl-B12.

If you have had the GST-genes (GSTM1, GSTP1 and GSTT1) sequenced in the 23andme test that could give an idea of your glutathione conjugating ability. Maybe your methylation is working with supplements, but you can´t make use of the glutathione. I have seen this in five out of five gene tested people diagnosed with mercury intoxication and ME/CFS (including myself). Rich got all these test results and after that he wrote about this situation as an explanation to why some don´t get better on a methylation protocol. Sorry, I can´t find this input from him.

I also wanted to know how heavy metals would be implicated. On the diagram below, it looks like MTRR recycles B12. I also see with word “lead” there, and was wondering if the diagram is talking about lead as in the heavy metal. I am heterozygous for MTRR A66G, but I don’t know how much weight that has. But my question is, is this implying that I could have bioaccumulated lead my entire life if there wasn’t much methyl-B12 to be recirculated by MTRR.

As far as I have understood, all heavy metals (mercury/amalgam fillings probably the worst) and toxins might be triggers to ME/CFS as they put demand on the glutathione (Rich).

From PubMed:
(one-carbon metabolism= methylation)

Mutat Res. 2009 Jul 10;667(1-2):4-14. doi: 10.1016/j.mrfmmm.2008.07.003. Epub 2008 Jul 17.
Arsenic metabolism is influenced by polymorphisms in genes involved in one-carbon metabolism and reduction reactions.

http://www.ncbi.nlm.nih.gov/pubmed/?term=18682255

But my question is, is this implying that I could have bioaccumulated lead my entire life if there wasn’t much methyl-B12 to be recirculated by MTRR.

Yes, unfortunately according to Rich and Amy Yasko.

People with many GST polymorphisms and a toxic overload are very sensitive to detoxification, according to a professor in genetics. Any supplement that increases methylation and detoxification could be harmful/dangerous he said, so this is a difficult situation. So far there seems to be no safe advice for this group.

Helen
 

Lotus97

Senior Member
Messages
2,041
Location
United States
As far as I have understood, all heavy metals (mercury/amalgam fillings probably the worst) and toxins might be triggers to ME/CFS as they put demand on the glutathione (Rich).
One thing Rich suggested in one of his papers is that it might not necessarily be the heavy metals that cause CFS (although some cases it might be), but rather that people with ME/CFS have a hypersensitivity to metals and other toxins. And exposure to toxins can then worsen the condition.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
I trust Rich. He was very knowledgeable in the areas of both methylation and mercury toxicity. He worked with people dealing with both issues in addition to consulting with various doctors. He has said that toxins, including metals can and most likely will be released during the process of methylation. This is different than the issue of methylcobalamin methylating mercury although there has been a study to suggest that this too is possible.

I don't see how this answers her question. You've said a lot of things that sound convincing to the average reader, but you haven't really provided any actual evidence. Sushi is very busy now and has asked you this question twice already. There are many people here who suspect mercury toxicity and are looking for answers. If you don't know then just say so.

Hi Lotus,

You know, if everything were "proven" and correctly so, none of us would be sick as we are or have been. So you are saying that we should not consider the science that is available on these issues, to collect information across many different studies and apply it if it conflicts with somebody's belief systems? The claims being made concerning MeCbl don't mesh with all sorts of studies. I've been writing serum haflife simulations, using pharmacodymamic data for dozens of medications for 20+ years.

Mercury in our bodies is a very widespread phenomina. I had a bunch of amalgams. I played with metallic mercury. Lots of people may have varying degrees of problems becasue of mercury. WHat I am syaing is that WHATEVER EFFECT MECBL HAS ON MECURY MUST FIT INTO KNOWN CONSTRAINTS concerning MeCbl and monomethylmercury. Becasue of sufficient surviving monomethylmercury poisoning events (Japan for instance) we have numerous excellent serum half life measurements studies. During the just about every study dione for a long time throuw in the serum halflfe measusrements on whatever forms they were working with. Establishing daily oral equivalence to injections included all ranges of time periods with serum measurements. In addition the unchanged nature of the cobalamin being excreted in urine for 24 hour accumulations was measured as well. Within those constraints, we are talking about some small number of micrograms, for HyCbl, MeCbl, AdoCbl, CyCbl that is retained in the body. And if you prefer 98% excretion to 99% excretion UNCHANGED in 24 hours or 48 hours you may prefer, a case could be made for any of the them. However, on 1000mcg absorbed by injection only leaves 10 or 20 or maybe even 30 mcg behind, lets be generous. All the entire effects in the body, all the detoxing, all of everything is done by the 10 or 20 or 30mcg left behind. The same is true with AdoCbl, all the effects it has, anti-inflammatory, mitochhondria, etc are due to the 10 or 20 or 30 mcg left behind. The differences by larger dose appears to be mostly a deth of penetration effect. What affects that is cyanide poisoning, glutathione, nitrous oxide, arsenic and probably a few more things that combine with it until one or the other are no longer available. Mercury does not act like that, clearly. With so much of the population carrying some mercury load that is bound to be reflected in the urine excretion resuts. So anything assuming that some huge bulk of MeCbl is acting as massive methyl donors just isn't a good explanation. It has to be excreted unchanged, regardless of types. There are a few toxins that change that. And those produce a cobalamin product that comes out the kidneys generally.

And you might be interested to know that NAC and glutathione cause mercury to be deposited in the brain at least according to one source.

I'm not disputing people have all sorts of heavy metals and other toxins. That complicates matters. However, there are constraints. As much as I fault CyCbl and HyCbl research, I agree that for things like serum levels and halflife and so on they probablay can do that quite well. The serum halflife of all involved substances, toxic effects, toxic levels (hypersensitivity can occur to mercury). If you want to make a case that mercury is reacting at a very fast rate with MeCbl, there needs to be evidence. Dr Cutler has stated that as far as he is concerned IF MeCbl and Hg react in vivo tyhen they dp so very slowly and at very low levels. That is what the evidence suggests. An interesting study would to be start somebody on MeCbl who has a lot of mercury, take a series of fecal Hg for basline and then daily for 4 months and derive the rate of reaction for that. Further it would build by the day for about 700 days until it has leveled out with that 71 day serum halflife. These are some predicitons that can be made based on known scientific evidence. The amount so deposited would allow us to calculate the number of mcgs of mercury and MeCbl reacted daily. Now that would be evidence. As no pharmaceutical company is going to make billions off of that it will come from a university. It probably isn't sexy enough to garner much desire to do such a study. Until somebody runs that study. If somebody has done that I would like to read it
 

kday

Senior Member
Messages
369
Hi kday,
I am really sorry for your situation. I have similar problems, and I am very happy to have found this forum with all knowledge and experiences that people shares. Sorry for my English..


If you have had the GST-genes (GSTM1, GSTP1 and GSTT1) sequenced in the 23andme test that could give an idea of your glutathione conjugating ability. Maybe your methylation is working with supplements, but you can´t make use of the glutathione. I have seen this in five out of five gene tested people diagnosed with mercury intoxication and ME/CFS (including myself). Rich got all these test results and after that he wrote about this situation as an explanation to why some don´t get better on a methylation protocol. Sorry, I can´t find this input from him.



As far as I have understood, all heavy metals (mercury/amalgam fillings probably the worst) and toxins might be triggers to ME/CFS as they put demand on the glutathione (Rich).

From PubMed:
(one-carbon metabolism= methylation)

Mutat Res. 2009 Jul 10;667(1-2):4-14. doi: 10.1016/j.mrfmmm.2008.07.003. Epub 2008 Jul 17.
Arsenic metabolism is influenced by polymorphisms in genes involved in one-carbon metabolism and reduction reactions.

http://www.ncbi.nlm.nih.gov/pubmed/?term=18682255



Yes, unfortunately according to Rich and Amy Yasko.

People with many GST polymorphisms and a toxic overload are very sensitive to detoxification, according to a professor in genetics. Any supplement that increases methylation and detoxification could be harmful/dangerous he said, so this is a difficult situation. So far there seems to be no safe advice for this group.

Helen
Late reply. But I seem to have a probable GSTT1 deletion (null data for all SNPs). GSTM1 and GSTP1 are ok I think. I'm going to see where my glutathione is within a week or so. I'm not sensitive to the supplements, but at times I feel poisoned with all sorts of symptoms. I think it's mercury because removing an amalgam last week reproduced all of these symptoms. I discussed these results with my physician (along with my high urine sulfate levels) and his reply was he thinks these issues are big and thinks I am not producing glutathione like I should.

I tolerate IV glutathione fine. Would combining IV glutathione with methylating nutrients help detox. I guess I'll see where my levels are first. But if they are low (which my doctor expects), it looks like we might have to take a unique approach?

And would giving glutathione directly to cells via S-Acetly-Glutathione be of help? I've taken it before but I used way to much and felt both sick and toxic like my body was trying to fight something. Lowering the dose I didn't feel much, but only had a little left in the bottle.

My genetics suck, but I'm not going to throw my hands in the air and believe there is no way around them. In the mean time I'm trying to get my sulfate less than the maximum (1200) and hopefully closer to the 400 mark. I'm doing diet changes and molybdenum, and even though the strips are pretty much maxed out, I think I'm starting to notice a positive difference.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Late reply. But I seem to have a probable GSTT1 deletion (null data for all SNPs). GSTM1 and GSTP1 are ok I think. I'm going to see where my glutathione is within a week or so. I'm not sensitive to the supplements, but at times I feel poisoned with all sorts of symptoms. I think it's mercury because removing an amalgam last week reproduced all of these symptoms. I discussed these results with my physician (along with my high urine sulfate levels) and his reply was he thinks these issues are big and thinks I am not producing glutathione like I should.

I tolerate IV glutathione fine. Would combining IV glutathione with methylating nutrients help detox. I guess I'll see where my levels are first. But if they are low (which my doctor expects), it looks like we might have to take a unique approach?

And would giving glutathione directly to cells via S-Acetly-Glutathione be of help? I've taken it before but I used way to much and felt both sick and toxic like my body was trying to fight something. Lowering the dose I didn't feel much, but only had a little left in the bottle.

My genetics suck, but I'm not going to throw my hands in the air and believe there is no way around them. In the mean time I'm trying to get my sulfate less than the maximum (1200) and hopefully closer to the 400 mark. I'm doing diet changes and molybdenum, and even though the strips are pretty much maxed out, I think I'm starting to notice a positive difference.

HI Kday,

Arsenic does very strongly what mercury does very weakly at most, and that is strip the methyl groups (CH4, one-carbon) from MeCbl. In old houses with Paris Green wallpaper or arsenic treated lumber, molds that generate MeCbl also cause poison gas to be formed. The multi-methyl arsenates are extremely volitle gasses. A person with a bunch of arseninc in their body will start exhaling "garlic" odor for no apparant reason. Ventilate the room well. That is a very toxic gas. The person exhaling it should have lots of fresh air. The limit on the formation on arsenate gases is basically the avaialble methyl groups. It would appear that it doesn't take much arsenic to induce partial methylation block or maybe methyltrap. The glutathione destroys the MeCbl also. Each arsenic atom takes 4 methyl groups at least comparted to the one CH4 that mercury ties up.
 

Helen

Senior Member
Messages
2,243
Hi kday,
I can´t tell if supplementing glutathione would be good or not for you. But as you have had (and maybe still have) mercury fillings they could harm you a lot in many, many ways . And will probably do for a long time depending on your genetic detox ability. But you will surely feel much better after the last amalgam filling has been removed. Take your time, it is not good to go too fast.
With a GSTT1 deletion you unfortunately have less enzymes to conjugate glutathione with, but hopefully your methylation is supported with your supplements as much as possible. Though mercury demands glutathione more than most toxins according to researchers.
Selenium is important as a mercury binder . 3-500 mcg is recommended by experts now and for the future to bind stored Hg. Drinking lots of clean water, and sweating if possible are safe ways to help eliminating mercury.
Vitamin C, 2-3 gr per day are important among other antioxidants.
I think you can find good information here www.IAOMT.org.
I hope you soon will feel better.
 

Sea

Senior Member
Messages
1,286
Location
NSW Australia
If you have had the GST-genes (GSTM1, GSTP1 and GSTT1) sequenced in the 23andme test that could give an idea of your glutathione conjugating ability. Maybe your methylation is working with supplements, but you can´t make use of the glutathione. I have seen this in five out of five gene tested people diagnosed with mercury intoxication and ME/CFS (including myself). Rich got all these test results and after that he wrote about this situation as an explanation to why some don´t get better on a methylation protocol. Sorry, I can´t find this input from him...


Yes, unfortunately according to Rich and Amy Yasko.

People with many GST polymorphisms and a toxic overload are very sensitive to detoxification, according to a professor in genetics. Any supplement that increases methylation and detoxification could be harmful/dangerous he said, so this is a difficult situation. So far there seems to be no safe advice for this group.

Helen

Curiouser and curiouser... I have no call for 12 out of the 14 SNPs listed for GSTT1. I had 4 years of remission following removal of amalgams, so surely it has to be part of the puzzle for me.
 

kday

Senior Member
Messages
369
Post-amalgam removal - I feel the need for B12. I know "it just worked" in the past to calm symptoms. It's only been like 9 days or so. I tried to take it today and felt toxic with severe chest pain all day. Luckily I was able to sleep half the day. I know you aren't supposed to take this stuff until a month or two after removal at least. It's just the only tool I know that works for autonomic neuropathy type symptoms. And all it does right now is amplify the pain and misery to the point that I feel I could die any second. Not a new feeling, but a truly torturous one that I can ever get used to.

Speaking of Selenium and C - been doing that. I actually took way too much selenium at the beginning (each dose seemed to help, so I took 100 mcg many times a day). I know Selenium can be toxic, but I tend to listen to my body wants in the moment and not what literature says. Not always the smartest thing to do. I stopped for a couple days and then cut back to about 300 mcg a day.

Freddd - I am confused about where you are going with arsenic. Where I used to live had very high levels of inorganic arsenic in the water to the point that they replaced all the wells, pipes, and entire infrastructure. I was tested a few years back through LabCorp and while no where near their acute poisoning cutoffs, I was in the lower end of range that is considered to be chronic poisoning according to medical literature. But so was everyone else that drank the water there probably.

I can't tolerate log cabins (staying in one was a disaster), mold, burning, and many other things. I don't live in an old house, but the house I used to live in seemed to have negative health impacts after revisiting a couple times.

When I feel very ill with nervous system all keyed up and very stressed and slightly sweaty, I do have a very offensive sulfuric odor that is much more pungent than garlic - whatever that means. But this comes and goes.

If you gave me one word to describe how I feel it would be poisoned.
 
Messages
41
Location
California
Thank you all for interesting inputs.

I got this answer from Dr. Neil Nathan (who made a study together with Rich)

"mercury is a specific toxin for the methyl synthase enzyme that is critical in methylation. Even tiny amounts of mercury have been shown, by Dr. Richard Deth who is the dean of methylation chemistry, to poison the methylation cycle. While everyone is different, I suspect that everyone with mercury toxicity will have trouble to a greater or lesser degree with methylation."
Neil

It is also an experience among people in Sweden that have got sick from mercury that amalgam visible on X-ray has to be removed totally. That use to be a big step towards health, but some get into the CFS-club. Maybe because of genetic defects that increases the ability to make use of glutathione (GST-genes).

Do you know if in this study, they had the entire tooth removed or just the amalgam filling? It remember reading about a study where they it was found that even after amalgams were removed from teeth, the teeth them selves contained mercury that had leeched out them from the amalgams. So, even after the filings gone, they still had mercury in their teeth. A very unpleasant thought!
 
Messages
41
Location
California
...
If you have had the GST-genes (GSTM1, GSTP1 and GSTT1) sequenced in the 23andme test that could give an idea of your glutathione conjugating ability. Maybe your methylation is working with supplements, but you can´t make use of the glutathione. I have seen this in five out of five gene tested people diagnosed with mercury intoxication and ME/CFS (including myself). Rich got all these test results and after that he wrote about this situation as an explanation to why some don´t get better on a methylation protocol. Sorry, I can´t find this input from him.
...

Does anyone know to get the exact snp's for the GST genes? I looked at snpedia and some other sites but can't find them.

Thanks
 

Helen

Senior Member
Messages
2,243
Curiouser and curiouser... I have no call for 12 out of the 14 SNPs listed for GSTT1. I had 4 years of remission following removal of amalgams, so surely it has to be part of the puzzle for me.

Yes, it probably has. GSTT1 has to do with the stomach. Maybe this could be a clue. A friend of mine with a GSTT1 mutation is very sensitive for getting diverticulitis (correct?).
 

Helen

Senior Member
Messages
2,243
Post-amalgam removal - I feel the need for B12. I know "it just worked" in the past to calm symptoms. It's only been like 9 days or so. I tried to take it today and felt toxic with severe chest pain all day. Luckily I was able to sleep half the day. I know you aren't supposed to take this stuff until a month or two after removal at least. It's just the only tool I know that works for autonomic neuropathy type symptoms. And all it does right now is amplify the pain and misery to the point that I feel I could die any second. Not a new feeling, but a truly torturous one that I can ever get used to.

Speaking of Selenium and C - been doing that. I actually took way too much selenium at the beginning (each dose seemed to help, so I took 100 mcg many times a day). I know Selenium can be toxic, but I tend to listen to my body wants in the moment and not what literature says. Not always the smartest thing to do. I stopped for a couple days and then cut back to about 300 mcg a day.


When I feel very ill with nervous system all keyed up and very stressed and slightly sweaty, I do have a very offensive sulfuric odor that is much more pungent than garlic - whatever that means. But this comes and goes.

If you gave me one word to describe how I feel it would be poisoned.

Hi kday,
I am really sorry for your situation. I was surprised to read the sentence about B12 that I have marked. It is an experience among many I have talked to that thanks to B12 during, and afterwords the amalgam removal, they didn´t get too bad. They seem to feel better after the removal, than people without support from B12.

Overdosing selenium is said to give you an odour of garlic (more than 500 mcg - but we are all different).

It is not possible to have amalgam removed without being poisoned to a smaller or greater degree. Unfortunately. I hope your dentist was using of all kinds of protections for you.

All the best!
Helen
 

Helen

Senior Member
Messages
2,243
Do you know if in this study, they had the entire tooth removed or just the amalgam filling? It remember reading about a study where they it was found that even after amalgams were removed from teeth, the teeth them selves contained mercury that had leeched out them from the amalgams. So, even after the filings gone, they still had mercury in their teeth. A very unpleasant thought!

Hi Ktrd,

In the study that Dr. Nathan and Rich were responsible for, they didn´t control for amalgam at all. I miss that.

Yes, experienced dentists have shown that there may still be mercury in the teeth and also in the cheekbone. But the main source are the fillings and many people recover after removal -but all of the fillings must be removed. Most people get at least better from that.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Hi Ktrd,

In the study that Dr. Nathan and Rich were responsible for, they didn´t control for amalgam at all. I miss that.

Yes, experienced dentists have shown that there may still be mercury in the teeth and also in the cheekbone. But the main source are the fillings and many people recover after removal -but all of the fillings must be removed. Most people get at least better from that.


Hi Helen,

Unfortunately Rich did not have design control. There are a lot of things I would have rathered see done differently in the study including a broader and more specific symptoms gathering info. There are cloudy areas about how data other than first interview was collected concerning symptoms. It just wasn't designed to milk the most info possible. As these people were already in treatment, the whole group of them, they then defined the group of 21 out of 30, by seeing who fit the strict definition of the disorder they were using. For the final report some symptoms were changed around from the ones in the SMP assessment at 6 months and treatments customized for the last 3 months.
 

Sea

Senior Member
Messages
1,286
Location
NSW Australia
Yes, it probably has. GSTT1 has to do with the stomach. Maybe this could be a clue. A friend of mine with a GSTT1 mutation is very sensitive for getting diverticulitis (correct?).

My mother has suffered with diverticulitis since her early 40s. So far I have escaped that although IBS is a problem for me
 

Helen

Senior Member
Messages
2,243
My mother has suffered with diverticulitis since her early 40s. So far I have escaped that although IBS is a problem for me
Sea, this is sad but I think it is better to have an explanation to symptoms than not. Maybe one day there will be a treatment too.

Unfortunately Rich did not have design control.
Freddd, agree. At least the clinical study gave us some valuable information to go on with. I like the story about the 80+ woman and participant in the trial, who went to Paris for a holiday after having recovered from her ME/CFS thanks to the treatment she got.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
My mother has suffered with diverticulitis since her early 40s. So far I have escaped that although IBS is a problem for me

Hi Sea,

And folate insufficiency symptoms point right at IBS however one got there. For me IBS turns on and off with my other intial folate insufficiency symptoms.
 

Sea

Senior Member
Messages
1,286
Location
NSW Australia
Hi Sea,

And folate insufficiency symptoms point right at IBS however one got there. For me IBS turns on and off with my other intial folate insufficiency symptoms.

Yep, I am currently trying to get my head around what I should do now that I've got my 23andme results. I was hoping it would be simple (silly me). You can see from the results in my signature that there are complications to just jumping in with mB12 and folate