Lyme disease, CFS, autism and glutathione

January 13, 2006

Hi all.

At the risk of giving Tony a stroke (:-) (sorry, Tony!), here is

something I just posted on the Experimental list, in response to

some prodding by some folks that are known over here, too, I think:

Hi, Nelly, Sue, Sheila and the group.

Thanks very much for posting this. It has really stimulated my

thinking about why Lyme disease is symptomatologically so similar to

CFS.

First, some review. As we all know, it has been terribly difficult

to do the differential diagnosis between Lyme disease and CFS. The

symptoms overlap considerably and even the best of the lab tests do

not have the sensitivity and selectivity we would all like to see.

Symptoms are manifestations of the pathophysiology of a disease,

i.e. how the functioning of the body of the sick person is abnormal

as a result of the disease. Therefore, if we see that the symptoms

of two diseases are very similar, we should suspect that they must

have some aspects of pathophysiology in common.

Pathophysiology is intimately involved with abnnormal gene

expression in the cells of the sick person, because gene expression

is a reflection of how the cell is conducting its business, and the

misconduct of the business of the cell is pathophysiology.

Because of this, I was quite struck some time ago when Sheila

reported that Dr. Gow said in a recent talk that he had found that

the gene expression pattern in peripheral blood mononuclear cells

(monocytes and lymphocytes) is " identical " in CFS and Lyme disease.

This implies that the pathophysiology of these two disorders in

these cell types is the same. (Note that we can't say anything

about what's going on in other cell types in the body in these two

disorders from this work. There are no doubt different things that

happen in other cell types between Lyme and CFS, and so this is not

saying that the two are identical in every way. But in these

mononuclear cells, this is saying that the pathophysiology of the

two is the same.)

As you know, I am of the firm view that in at least a large subset

of CFS there is glutathione depletion. In another subset, it looks

as though there are genetic variations in the enzymes that make use

of glutathione (glutathione transferases and glutathione

peroxidases), and the results in terms of pathophysiology are much

the same, even though the first group has low glutathione, and the

second group may have elevated glutathione. In either subset, the

people do not have normal glutathione function.

As you also know, based on the work by the DAN! project in autism, I

now believe that the basic abnormalities in the biochemistry in

autism and CFS are the same or similar. The glutathione depletion

brings down the methylation cycle, and a vicious circle develops

that produces a host of problems because of the depletion of SAMe

(the main methylator in the body), cysteine, glutathione, taurine

and sulfate.

So, if the pathophysiology of CFS involves the inability to use

glutathione effectively, whether because glutathione itself is

depleted or because the enzymes that use it have below-normal

activity, and if the pathophysiology of CFS and Lyme are indeed

identical, then it follows that there must be a problem with the

glutathione system in Lyme disease as well.

With that introduction, let me now review some things I found in the

literature, including the paper to which you (Nelly) drew my

attention. I will give the PubMed ID numbers for the references

that support these statements.

(PMID 1477785) First, in in vitro experiments it has been found

that the growth of Borrelia burgdorferi (Bb), the bacterium that

causes Lyme disease, in the culture medium is decreased by 80% if

cysteine is not present in the culture medium.

(PMID 147785) It has been found that cysteine diffuses passively

into Bb, i.e. there is no active transporter protein that pumps it

into the bacterium.

(PMID 1477785) It has been found that Bb incorporates cysteine in

three of its proteins. One has a mass of 22 kilodaltons. The

others have been identified as outer surface protein A (Osp A), with

a mass of 30 kilodaltons, and outer surface protein B (Osp , with

a mass of 34 kilodaltons.

(PMID 1639493) Bb produces a water-soluble hemolysin. This is a

substance that is able to break down red blood cells and release

their hemoglobin. It is likely that this substance incorporates a

cyteine residue, and this cysteine must be in its reduced state in

order for the hemolysin to break down red blood cells.

(PMID 16390443) Bb does not produce glutathione, which is the

principle non-protein thiol (substance containing an S-H or

sulfhydryl group) in human cells. Instead, Bb cells have a high

concentration (about 1 millimolar) of reduced coenzyme A (CoASH).

Bb also produces a CoA disulfide reductase enzyme that has the

responsibility to keep CoASH in its chemically reduced form, so it

can function. This enzyme is in turn reduced by NADH (reduced

nicotinic acid diethylamide), which is reduced by metabolism of Bb's

fuel. (This is analogous to glutathione reductase in human cells,

which requires NADPH, which in turn is reduced by the pentose

phosphate shunt on glycolysis, which metabolizes glucose as fuel.)

In Bb, CoASH is able to reduce hydrogen peroxide, as glutathione

peroxidase, together with glutathione, do in human cells.

(PMID 11687735) It has been found that when people were infected

with Bb and had the characteristic erythema migrans (bulls-eye

rash), the total thiol and glutathione in blood analysis were found

to be significantly decreased. The activity of glutathione

peroxidase was also significantly decreased. Malondialdehyde, a

marker for lipid peroxidation, was significantly elevated. After

antibiotic treatment with amoxycillin, which eliminated the acute

symptoms of Lyme disease, both the total thiol and the glutathione

levels recovered to normal. However, the glutathione peroxidase

activity was still significantly below normal, and the

malondialdehyde remained significantly elevated. This suggested

that Bb lowers the thiol and glutathione levels in its host, and

inhibits the activity of glutathione peroxidase.

I think this also suggests that while antibiotic therapy eliminates

acute Lyme symptoms and brings recovery of glutathione levels, the

Bb infection may still be suppressing the activity of glutathione

peroxidase, and this may be a mechanism involved in long-term (or

chronic or post-) Lyme disease.

One way in which a pathogen can inhibit its host's glutathione

peroxidase activity is to hoard selenium, because this is a cofactor

for that enzyme. You may recall that that is the mechanism that

Prof. Harry has hypothesized for HIV and AIDS

(http://www.hdfoster.com). I could not find any reference in the

literature connecting Bb and selenium, and I don't know whether

anyone has looked at that. Have any of you who are positive for

Lyme had your selenium level measured?

It seems pretty clear that Bb uses cysteine and that it depletes

glutathione and total thiol (which includes cysteine and protein

thiols as well as glutathione) in its host, at least in the acute

phase. It also suppresses the activity of glutathione peroxidase,

but I'm not sure whether it does it by lowering the host's selenium

level, or by some other means. This suppression appears as though

it could be chronic. I think there is a good chance that this

lowering of glutathione and/or suppressing of the activity of

glutathione peroxidase could very well be the explanation for the

similarities in symptomatology and the " identical " gene expression

in the peripheral blood mononuclear cells in CFS and Lyme disease.

It may also be that a host whose glutathione has been depleted by

other factors may be more vulnerable to developing Lyme disease,

once inoculated with Bb. I am speculating a little here, but this

is exciting!

If this is true, what are the consequences for treatment of long-

term Lyme disease, the subject that Sue raised? I think this

remains to be seen, but it does suggest that the DAN! autism

treatments may have a contribution to make in the treatment of long-

term Lyme disease as I've suggested that they also do in the

treatment of CFS. Before we can reach such a conclusion, though, I

think it behooves us to get more data on glutathione levels,

selenium levels, and glutathione peroxidase activity in people with

positive tests for long-term Lyme disease, as well as some

experience trying these treatments as part of the treatment of long-

term Lyme disease. I'm not suggesting that they would replace other

treatments for Lyme disase, such as antibiotic therapy, detoxing of

neurotoxins, or other approaches to deal with the bacteria

themselves or do deal with particular characteristics of Lyme

disease that are not found in autism or CFS. Nevertheless, these

treatments might make a significant impact. Time will tell. Thanks

for rattling my cage about this, Sheila, Sue and Nelly.

Rich

January 13, 2006

Sorry, a little error: NADH is actually reduced nicotinamide

adenine dinucleotide. Sorry about that.

Rich

>

> Hi all.

>

> At the risk of giving Tony a stroke (:-) (sorry, Tony!), here is

> something I just posted on the Experimental list, in response to

> some prodding by some folks that are known over here, too, I think:

>

> Hi, Nelly, Sue, Sheila and the group.

>

> Thanks very much for posting this. It has really stimulated my

> thinking about why Lyme disease is symptomatologically so similar

to

> CFS.

>

> First, some review. As we all know, it has been terribly

difficult

> to do the differential diagnosis between Lyme disease and CFS.

The

> symptoms overlap considerably and even the best of the lab tests

do

> not have the sensitivity and selectivity we would all like to see.

>

> Symptoms are manifestations of the pathophysiology of a disease,

> i.e. how the functioning of the body of the sick person is

abnormal

> as a result of the disease. Therefore, if we see that the

symptoms

> of two diseases are very similar, we should suspect that they must

> have some aspects of pathophysiology in common.

>

> Pathophysiology is intimately involved with abnnormal gene

> expression in the cells of the sick person, because gene

expression

> is a reflection of how the cell is conducting its business, and

the

> misconduct of the business of the cell is pathophysiology.

>

> Because of this, I was quite struck some time ago when Sheila

> reported that Dr. Gow said in a recent talk that he had found that

> the gene expression pattern in peripheral blood mononuclear cells

> (monocytes and lymphocytes) is " identical " in CFS and Lyme

disease.

> This implies that the pathophysiology of these two disorders in

> these cell types is the same. (Note that we can't say anything

> about what's going on in other cell types in the body in these two

> disorders from this work. There are no doubt different things

that

> happen in other cell types between Lyme and CFS, and so this is

not

> saying that the two are identical in every way. But in these

> mononuclear cells, this is saying that the pathophysiology of the

> two is the same.)

>

> As you know, I am of the firm view that in at least a large subset

> of CFS there is glutathione depletion. In another subset, it

looks

> as though there are genetic variations in the enzymes that make

use

> of glutathione (glutathione transferases and glutathione

> peroxidases), and the results in terms of pathophysiology are much

> the same, even though the first group has low glutathione, and the

> second group may have elevated glutathione. In either subset, the

> people do not have normal glutathione function.

>

> As you also know, based on the work by the DAN! project in autism,

I

> now believe that the basic abnormalities in the biochemistry in

> autism and CFS are the same or similar. The glutathione depletion

> brings down the methylation cycle, and a vicious circle develops

> that produces a host of problems because of the depletion of SAMe

> (the main methylator in the body), cysteine, glutathione, taurine

> and sulfate.

>

> So, if the pathophysiology of CFS involves the inability to use

> glutathione effectively, whether because glutathione itself is

> depleted or because the enzymes that use it have below-normal

> activity, and if the pathophysiology of CFS and Lyme are indeed

> identical, then it follows that there must be a problem with the

> glutathione system in Lyme disease as well.

>

> With that introduction, let me now review some things I found in

the

> literature, including the paper to which you (Nelly) drew my

> attention. I will give the PubMed ID numbers for the references

> that support these statements.

>

> (PMID 1477785) First, in in vitro experiments it has been found

> that the growth of Borrelia burgdorferi (Bb), the bacterium that

> causes Lyme disease, in the culture medium is decreased by 80% if

> cysteine is not present in the culture medium.

>

> (PMID 147785) It has been found that cysteine diffuses passively

> into Bb, i.e. there is no active transporter protein that pumps it

> into the bacterium.

>

> (PMID 1477785) It has been found that Bb incorporates cysteine in

> three of its proteins. One has a mass of 22 kilodaltons. The

> others have been identified as outer surface protein A (Osp A),

with

> a mass of 30 kilodaltons, and outer surface protein B (Osp ,

with

> a mass of 34 kilodaltons.

>

> (PMID 1639493) Bb produces a water-soluble hemolysin. This is a

> substance that is able to break down red blood cells and release

> their hemoglobin. It is likely that this substance incorporates a

> cyteine residue, and this cysteine must be in its reduced state in

> order for the hemolysin to break down red blood cells.

>

> (PMID 16390443) Bb does not produce glutathione, which is the

> principle non-protein thiol (substance containing an S-H or

> sulfhydryl group) in human cells. Instead, Bb cells have a high

> concentration (about 1 millimolar) of reduced coenzyme A (CoASH).

> Bb also produces a CoA disulfide reductase enzyme that has the

> responsibility to keep CoASH in its chemically reduced form, so it

> can function. This enzyme is in turn reduced by NADH (reduced

> nicotinic acid diethylamide), which is reduced by metabolism of

Bb's

> fuel. (This is analogous to glutathione reductase in human cells,

> which requires NADPH, which in turn is reduced by the pentose

> phosphate shunt on glycolysis, which metabolizes glucose as

fuel.)

> In Bb, CoASH is able to reduce hydrogen peroxide, as glutathione

> peroxidase, together with glutathione, do in human cells.

>

> (PMID 11687735) It has been found that when people were infected

> with Bb and had the characteristic erythema migrans (bulls-eye

> rash), the total thiol and glutathione in blood analysis were

found

> to be significantly decreased. The activity of glutathione

> peroxidase was also significantly decreased. Malondialdehyde, a

> marker for lipid peroxidation, was significantly elevated. After

> antibiotic treatment with amoxycillin, which eliminated the acute

> symptoms of Lyme disease, both the total thiol and the glutathione

> levels recovered to normal. However, the glutathione peroxidase

> activity was still significantly below normal, and the

> malondialdehyde remained significantly elevated. This suggested

> that Bb lowers the thiol and glutathione levels in its host, and

> inhibits the activity of glutathione peroxidase.

>

> I think this also suggests that while antibiotic therapy

eliminates

> acute Lyme symptoms and brings recovery of glutathione levels, the

> Bb infection may still be suppressing the activity of glutathione

> peroxidase, and this may be a mechanism involved in long-term (or

> chronic or post-) Lyme disease.

>

> One way in which a pathogen can inhibit its host's glutathione

> peroxidase activity is to hoard selenium, because this is a

cofactor

> for that enzyme. You may recall that that is the mechanism that

> Prof. Harry has hypothesized for HIV and AIDS

> (http://www.hdfoster.com). I could not find any reference in the

> literature connecting Bb and selenium, and I don't know whether

> anyone has looked at that. Have any of you who are positive for

> Lyme had your selenium level measured?

>

> It seems pretty clear that Bb uses cysteine and that it depletes

> glutathione and total thiol (which includes cysteine and protein

> thiols as well as glutathione) in its host, at least in the acute

> phase. It also suppresses the activity of glutathione peroxidase,

> but I'm not sure whether it does it by lowering the host's

selenium

> level, or by some other means. This suppression appears as though

> it could be chronic. I think there is a good chance that this

> lowering of glutathione and/or suppressing of the activity of

> glutathione peroxidase could very well be the explanation for the

> similarities in symptomatology and the " identical " gene expression

> in the peripheral blood mononuclear cells in CFS and Lyme

disease.

> It may also be that a host whose glutathione has been depleted by

> other factors may be more vulnerable to developing Lyme disease,

> once inoculated with Bb. I am speculating a little here, but this

> is exciting!

>

> If this is true, what are the consequences for treatment of long-

> term Lyme disease, the subject that Sue raised? I think this

> remains to be seen, but it does suggest that the DAN! autism

> treatments may have a contribution to make in the treatment of

long-

> term Lyme disease as I've suggested that they also do in the

> treatment of CFS. Before we can reach such a conclusion, though,

I

> think it behooves us to get more data on glutathione levels,

> selenium levels, and glutathione peroxidase activity in people

with

> positive tests for long-term Lyme disease, as well as some

> experience trying these treatments as part of the treatment of

long-

> term Lyme disease. I'm not suggesting that they would replace

other

> treatments for Lyme disase, such as antibiotic therapy, detoxing

of

> neurotoxins, or other approaches to deal with the bacteria

> themselves or do deal with particular characteristics of Lyme

> disease that are not found in autism or CFS. Nevertheless, these

> treatments might make a significant impact. Time will tell.

Thanks

> for rattling my cage about this, Sheila, Sue and Nelly.

>

> Rich

>

January 14, 2006

Rich

Your wise beyond words.If I gave you constant IV's of toxic

substances I would expect your genes to unwind improper strands of

DNA.I think anyone that has done any type of investigation on there

spine or feet will tell you they suffer bone spurs or a myriad of

other problems that are starting to become clearer-which could

pretty much determine SOMETHING IS mutating in your DNA.But the

first step is to take away the toxic source not go out and blame the

DNA. If you sat back and started looking at the simple facts of cfs

in just basic block form, everything makes more sense, YOU RELY ON -

DOCTORS GAVE HIM AN EVERYTHING'S NORMAL AND THEN YOU STEP UP TO THE

PLATE FROM THERE AND GIVE US THIS DRIBBLE THAT IS 100% THE WRONG WAY

OF GOING ABOUT THINGS IMO.

My other gripe is that many HEALTHY people are having 10.000 dna

processes occuring anyminute of the day to there body- we as toxic

non healers probably run millions of constant dna repair processes

any minute of the day and we just don't get repairs completed

BECAUSE WE ARE NOT RECOVERING.The foolish researcher will ignore

the obvious mess that's been caused in the blood stream and got to

step 3 (glutathione and methylation) for me this is the huge rich V

MISTAKE.I think step 1 make your blood like normal people's and make

sure that you have the volume to repair all your injury sites. I

actually thought dialysis may be the real deal, it's also hard to

have a diseased heart muscle (low blood pressure) to WORK WITH.

AGAIN GET YOUR ASS DOWN AND AROUND THE ACTUAL PEOPLE, LOOK CAREFULLY

AT THERE HIGH INFLAMMATION LEVELS(REDNESS),THERE STRANGE RASHES

RAISED RED BUMPS, NON DISCRIPT BODY RASHES, UNUSUAL ACNE PIMPLES,

OBSERVE THERE WOUNDS AND HOW EASY THERE TOXIC SKIN BREAKS. JUST GET

YOURSELF OFF THIS CRAP SHOOT FROM RESEARCH ARTICLES AND THINKING YOU

KNOW US. YOU CAN'T FIX ANYTHING IN MY OPINION BY THEORISING WITHOUT

ESTABLISHING IN YOUR OWN MIND WHAT THE CFS/FIBRO PERSON REALLY

IS...I THINK YOU MAY ALSO FIND THE ENCEPHALITIS MAY COME FROM A

LEAKING SPINAL FLUID THAT NEEDS MORE THAN CHELATION OF MERCURY FROM

THE BRAIN, ESPECIALLY WHEN THE BRAIN IS EXPOSED TO THE ENVRONMENT SO

EASILY FROM SUCH DEFECTS IN THE SINUSES(WORMHOLES INTO THE BRAIN).