Re: CBS, insulin, glutathione, and cysteine.

[Guest guest]

Hi Mark, my impression was CBS upregulation increased ammonia and

decreased creatinine. Ammonia has toxic effects. I may have missed

statements that CBS upregulation decreased glutathione, in any case, I

don't remember reading or hearing that anywhere. It was the

CBS-ammonia connection that was important.

Also, from my talk with Deth, it seems possible, I'm not sure

if likely, but in any case possible that without the insult of a

toxic/heavy metal environment, excess hcy could lead to increased

glutathione and decreased oxidation. Where is the hcy going to go? In

ideal circumstances it will recycle to glutathione, when not needed

for methylation. In less than ideal circumstances of chronic

infection, inflammation and oxidative stress, it will not.

I am having trouble following the rest of your detailed post, but I

hope Rich can read and address it.

>

>

> FWIW, here is yet more information about the CBS upregulating SNPs from

> the medical literature. I've also added some information about cysteine

> and glutathione that I've read, that may be important, which no one else

> here has yet mentioned.

>

> To summarize my previous post: CBS upregulation via certain

> polymorphisms has been theorized by some people here to be detrimental.

> However, only one study from 2000 has shown any evidence that these

> polymorphisms upregulate CBS. C699T (+/+) and to a somewhat lesser

> degree C699T (+/-), were shown to produce lower levels of homocysteine

> levels, in response to the Post Methionine Loading test, compared to

> C699T (-/-). About 50% of the population have (-/-), and the rest have

> (+/+) and (+/-).

>

> However, basal levels of homocysteine were not significantly affected by

> these polymorphisms. This is in contrast to conditions where CBS

> upregulation is definitely known to occur, such as in Down's syndrome.

> Upregulation occurs in that condition, because the CBS gene is on the

> same mutated chromosone that causes Down's Syndrome. In Down's, basal

> homocysteine levels are significantly reduced by 25%. The fact that the

> CBS polymorphisms don't significantly decrease basal homocysteine

> levels, seems to imply that the polymorphisms have a mild or different

> effect on CBS activity.

>

> Indeed, a 2003 study on these same polymoprhisms showed no changes in

> CBS activity, as shown by the response to the PML test. Additionally, a

> study on pregnant women, actually showed an increase in basal

> homocysteine levels due to these polymorphisms. See:

>

>

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dop\

> t=AbstractPlus & list_uids=15866085 & query_hl=12 & itool=pubmed_docsum

>

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & do\

> pt=AbstractPlus & list_uids=15866085 & query_hl=12 & itool=pubmed_docsum>

>

> The explanation for these different results, might be explained by the

> following study:

>

>

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dop\

> t=AbstractPlus & list_uids=10833331 & query_hl=10 & itool=pubmed_docsum

>

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & do\

> pt=AbstractPlus & list_uids=10833331 & query_hl=10 & itool=pubmed_docsum>

>

> In that study, it was found that these CBS polymorphisms increased the

> ability of folic acid to lower basal homocysteine levels. This seems to

> imply that in people with these polymorphisms, that folic acid increases

> the rate of usage of homocysteine by the transsulphuration pathway,

> which contains CBS. But folic acid is not known to directly affect this

> path. Instead, folic acid increases the methylation path, which

> competes with transsulphuration. Therefore, the question is how would

> folic acid affect CBS activity? The study had no definitive answer.

>

> There are only a couple of substances that can increase CBS activity.

> The vitamin B6 derivative PLP is one of them. The other significant one

> is AdoMet (SAM). This is produced by methylation. It is theorized that

> this property of AdoMet, allows it to balance the use of homocysteine

> between the methylation and transsulphuration paths. I.e. too much

> methylation would produce AdoMet, and this would then stimulate

> transsulphuration. However, AdoMet is not known to be increased by

> folic acid supplementation.

>

> On the other hand, insulin significantly decreases CBS. I believe this

> might be the reason why folic acid affects CBS, as folic acid can reduce

> insulin resistance and decrease insulin levels. See the following

> studies:

>

>

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dop\

> t=AbstractPlus & list_uids=12198128 & query_hl=71 & itool=pubmed_docsum

>

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & do\

> pt=AbstractPlus & list_uids=12198128 & query_hl=71 & itool=pubmed_docsum>

>

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dop\

> t=AbstractPlus & list_uids=15899950 & query_hl=70 & itool=pubmed_DocSum

>

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & do\

> pt=AbstractPlus & list_uids=15899950 & query_hl=70 & itool=pubmed_DocSum>

>

> In the latter study, folic acid not only lowered homocysteine levels,

> but it also caused a decrease in insulin levels (due to increased

> insulin sensitivity). Additionally, it also caused an increase in Post

> Methionine Load levels of Cysteine-Glycine. Cys-Glyc is a direct

> metabolite of glutathione. Increased Cys-Glyc implies that folic acid

> upregulates the transsulphuration pathway. This effect could be due to

> the decreased insulin levels, which would increase CBS activity.

>

> And since the effects from folic acid are influenced by the CBS

> polymorphisms, perhaps these polymorphisms modify the sensitivity of CBS

> to insulin. Such a theory would explain why different studies showed

> different effects from these polymorphisms. Different patient groups

> would have different insulin profiles. People with low insulin level,

> might exhibit much different effects from these polymorphisms, than

> those with high levels.

>

> Regardless of whether this theory is true, the increased activity of CBS

> has not been shown to decrease glutathione. I wonder if this

> misconception is due to the fact that glutathione levels are decreased

> in Down's syndrome. However, increased oxidation is known to be present

> in that condition, due to several reasons, and researchers believe that

> this is the cause of the reduced glutathione levels.

>

> Additionally, in autism, glutathione levels are also low:

>

>

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dop\

> t=AbstractPlus & list_uids=16825783 & query_hl=111 & itool=pubmed_docsum

>

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & do\

> pt=AbstractPlus & list_uids=16825783 & query_hl=111 & itool=pubmed_docsum>

>

> However, these low levels could be explained by the decreased conversion

> of B6 to PLP in autism:

>

>

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dop\

> t=AbstractPlus & list_uids=16494569 & query_hl=123 & itool=pubmed_docsum

>

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & do\

> pt=AbstractPlus & list_uids=16494569 & query_hl=123 & itool=pubmed_docsum>

>

> In the first study, cystathione levels were found to be elevated.

> Cystathionine is the metbolite that is formed by CBS, and which is then

> converted to cysteine, and finally to glutathione. However, the

> conversion to cysteine is dependent on PLP, and lack of PLP would reduce

> cysteine levels. Indeed, lack of cysteine is also present in autism,

> unlike Down's where it's elevated. Studies have shown that B6

> supplementation is able to reduce cystathionine levels. And a B6

> deficiency would also increase oxidative stress, which would increase

> the conversion of glutathione to GSSG. GSSG is also elevated in autism,

> and this would also decrease glutathione levels. Thus, it's curious

> that the first study makes no mention of B6. B6 deficiency is more

> likely to be the significant reason for low glutathione in that

> condition, and not CBS upregulation.

>

> It's been suggested by people here that supplements such betaine, that

> increase methylation, would help to increase glutathione levels and

> decrease cysteine levels. Increasing methylation has not been proven to

> increase glutathione levels. Nor does it necessarily decrease cysteine

> levels. For example, see the following lab study on the use of betaine:

>

>

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dop\

> t=AbstractPlus & list_uids=15885362 & query_hl=31 & itool=pubmed_docsum

>

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & do\

> pt=AbstractPlus & list_uids=15885362 & query_hl=31 & itool=pubmed_docsum>

>

> In this study, betaine greatly increased the methylation path, which led

> to a reduction of cysteine production via the transsulphuration. path.

> However, cysteine levels stayed the same. This is because the decrease

> in cysteine levels, led to a reduction of CDO, the enzyme which degrades

> cysteine, thereby restoring the original cysteine levels. Both cysteine

> and glutathione levels remained the same, despite the increase in

> methylation.

>

> Cysteine is mainly controlled by CDO, and CDO is mainly dependent on

> cysteine levels. The higher the cysteine, the higher the CDO. CDO can

> increase many magnitudes to offset dietary cysteine, in order to

> stabilize cysteine levels.

>

> However, life style can affect serum cysteine levels. Studies have

> shown that body mass index is a strong determinant of cysteine.

> Cysteine is also positively associated with age, total cholesterol

> concentration, diastolic blood pressure, and coffee consumption. And

> one study indicates that exercise can reduce cysteine levels. Life

> style changes may make more of a difference on cysteine levels, than

> supplementation.

>

> Additionally, one study has shown that CDO is inhibited by cytokines

> such as TNF-alpha and TGF-beta. If this is true, then this could be the

> reason why some of the above factors influence cysteine levels, i.e. due

> to increased inflammation.

>

> As for glutathione, there are many factors that affect glutathione

> levels. Here's a good review article on glutathione metabolism:

>

>

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dop\

> t=AbstractPlus & list_uids=14988435 & query_hl=109 & itool=pubmed_docsum

>

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & do\

> pt=AbstractPlus & list_uids=14988435 & query_hl=109 & itool=pubmed_docsum>

>

> In particular, the following paragraph from that article explains

> factors which regulates the amount of glutathione in cells:

>

> " Gamma-Glutamylcysteine synthetase (GCS) is the rate-controlling enzyme

> in de novo synthesis of GSH. " Oxidant stress, nitrosative stress,

> inflammatory cytokines, cancer, cancer chemotherapy, ionizing radiation,

> heat shock, inhibition of GCS activity, GSH depletion, GSH conjugation,

> prostaglandin A2, heavy metals, antioxidants, and insulin increase GCS

> transcription or activity in a variety of cells. In contrast, dietary

> protein deficiency, dexamethasone, erythropoietin, tumor growth factor

> ß, hyperglycemia, and GCS phosphorylation decrease GCS transcription

> or activity. Nuclear factor {kappa}B mediates the upregulation of GCS

> expression in response to oxidant stress, inflammatory cytokines, and

> buthionine sulfoximine-induced GSH depletion. S-nitrosation of GCS

> protein by NO donors (e.g., S-nitroso-L-cysteine and

> S-nitroso-L-cysteinylglycine) reduces enzyme activity, suggesting a link

> between NO (a metabolite of L-arginine) and GSH metabolism. Indeed, an

> increase in NO production by inducible NO synthase causes GCS inhibition

> and GSH depletion in cytokine-activated macrophages and neurons. In this

> regard, glucosamine, taurine, n-3 PUFAs, phytoestrogens, polyphenols,

> carotenoids, and zinc, which inhibit the expression of inducible NO

> synthase and NO production, may prevent or attenuate GSH depletion in

> cells. Conversely, high-fat diet, saturated long-chain fatty acids,

> low-density lipoproteins, linoleic acid, and iron, which enhance the

> expression of inducible NO synthase and NO production, may exacerbate

> the loss of GSH from cells. "

>

> Unless you definitely have low serum glutathione levels, perhaps

> controlling the factors that cause a loss of GSH from cells, is just as

> important, or more so, than making sure you have adequate glutathione

> levels.

>

> The supplements which are used in Dr. Yasko's protocol have lots of good

> effects that can help people. However, based on what I've read in the

> medical literature, there is doubt as to whether they are helping in the

> ways that people here are theorizing.

>

> - Mark

>

>

>

>

>

>

>

>

[Guest guest]

Sorry to ask to a really silly question, but what is CBS ?Thanks

> >

> >

> > FWIW, here is yet more information about the CBS upregulating

SNPs from

> > the medical literature. I've also added some information about

cysteine

> > and glutathione that I've read, that may be important, which no

one else

> > here has yet mentioned.

> >

> > To summarize my previous post: CBS upregulation via certain

> > polymorphisms has been theorized by some people here to be

detrimental.

> > However, only one study from 2000 has shown any evidence that

these

> > polymorphisms upregulate CBS. C699T (+/+) and to a somewhat

lesser

> > degree C699T (+/-), were shown to produce lower levels of

homocysteine

> > levels, in response to the Post Methionine Loading test,

compared to

> > C699T (-/-). About 50% of the population have (-/-), and the

rest have

> > (+/+) and (+/-).

> >

> > However, basal levels of homocysteine were not significantly

affected by

> > these polymorphisms. This is in contrast to conditions where CBS

> > upregulation is definitely known to occur, such as in Down's

syndrome.

> > Upregulation occurs in that condition, because the CBS gene is

on the

> > same mutated chromosone that causes Down's Syndrome. In Down's,

basal

> > homocysteine levels are significantly reduced by 25%. The fact

that the

> > CBS polymorphisms don't significantly decrease basal homocysteine

> > levels, seems to imply that the polymorphisms have a mild or

different

> > effect on CBS activity.

> >

> > Indeed, a 2003 study on these same polymoprhisms showed no

changes in

> > CBS activity, as shown by the response to the PML test.

Additionally, a

> > study on pregnant women, actually showed an increase in basal

> > homocysteine levels due to these polymorphisms. See:

> >

> >

> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & dop\

> > t=AbstractPlus & list_uids=15866085 & query_hl=12 & itool=pubmed_docsum

> >

> <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & do\

> >

pt=AbstractPlus & list_uids=15866085 & query_hl=12 & itool=pubmed_docsum>

> >

> > The explanation for these different results, might be explained

by the

> > following study:

> >

> >

> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & dop\

> > t=AbstractPlus & list_uids=10833331 & query_hl=10 & itool=pubmed_docsum

> >

> <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & do\

> >

pt=AbstractPlus & list_uids=10833331 & query_hl=10 & itool=pubmed_docsum>

> >

> > In that study, it was found that these CBS polymorphisms

increased the

> > ability of folic acid to lower basal homocysteine levels. This

seems to

> > imply that in people with these polymorphisms, that folic acid

increases

> > the rate of usage of homocysteine by the transsulphuration

pathway,

> > which contains CBS. But folic acid is not known to directly

affect this

> > path. Instead, folic acid increases the methylation path, which

> > competes with transsulphuration. Therefore, the question is how

would

> > folic acid affect CBS activity? The study had no definitive

answer.

> >

> > There are only a couple of substances that can increase CBS

activity.

> > The vitamin B6 derivative PLP is one of them. The other

significant one

> > is AdoMet (SAM). This is produced by methylation. It is

theorized that

> > this property of AdoMet, allows it to balance the use of

homocysteine

> > between the methylation and transsulphuration paths. I.e. too

much

> > methylation would produce AdoMet, and this would then stimulate

> > transsulphuration. However, AdoMet is not known to be increased

by

> > folic acid supplementation.

> >

> > On the other hand, insulin significantly decreases CBS. I

believe this

> > might be the reason why folic acid affects CBS, as folic acid

can reduce

> > insulin resistance and decrease insulin levels. See the

following

> > studies:

> >

> >

> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & dop\

> > t=AbstractPlus & list_uids=12198128 & query_hl=71 & itool=pubmed_docsum

> >

> <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & do\

> >

pt=AbstractPlus & list_uids=12198128 & query_hl=71 & itool=pubmed_docsum>

> >

> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & dop\

> > t=AbstractPlus & list_uids=15899950 & query_hl=70 & itool=pubmed_DocSum

> >

> <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & do\

> >

pt=AbstractPlus & list_uids=15899950 & query_hl=70 & itool=pubmed_DocSum>

> >

> > In the latter study, folic acid not only lowered homocysteine

levels,

> > but it also caused a decrease in insulin levels (due to increased

> > insulin sensitivity). Additionally, it also caused an increase

in Post

> > Methionine Load levels of Cysteine-Glycine. Cys-Glyc is a direct

> > metabolite of glutathione. Increased Cys-Glyc implies that

folic acid

> > upregulates the transsulphuration pathway. This effect could be

due to

> > the decreased insulin levels, which would increase CBS activity.

> >

> > And since the effects from folic acid are influenced by the CBS

> > polymorphisms, perhaps these polymorphisms modify the

sensitivity of CBS

> > to insulin. Such a theory would explain why different studies

showed

> > different effects from these polymorphisms. Different patient

groups

> > would have different insulin profiles. People with low insulin

level,

> > might exhibit much different effects from these polymorphisms,

than

> > those with high levels.

> >

> > Regardless of whether this theory is true, the increased

activity of CBS

> > has not been shown to decrease glutathione. I wonder if this

> > misconception is due to the fact that glutathione levels are

decreased

> > in Down's syndrome. However, increased oxidation is known to be

present

> > in that condition, due to several reasons, and researchers

believe that

> > this is the cause of the reduced glutathione levels.

> >

> > Additionally, in autism, glutathione levels are also low:

> >

> >

> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & dop\

> >

t=AbstractPlus & list_uids=16825783 & query_hl=111 & itool=pubmed_docsum

> >

> <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & do\

> >

pt=AbstractPlus & list_uids=16825783 & query_hl=111 & itool=pubmed_docsum>

> >

> > However, these low levels could be explained by the decreased

conversion

> > of B6 to PLP in autism:

> >

> >

> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & dop\

> >

t=AbstractPlus & list_uids=16494569 & query_hl=123 & itool=pubmed_docsum

> >

> <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & do\

> >

pt=AbstractPlus & list_uids=16494569 & query_hl=123 & itool=pubmed_docsum>

> >

> > In the first study, cystathione levels were found to be

elevated.

> > Cystathionine is the metbolite that is formed by CBS, and which

is then

> > converted to cysteine, and finally to glutathione. However, the

> > conversion to cysteine is dependent on PLP, and lack of PLP

would reduce

> > cysteine levels. Indeed, lack of cysteine is also present in

autism,

> > unlike Down's where it's elevated. Studies have shown that B6

> > supplementation is able to reduce cystathionine levels. And a B6

> > deficiency would also increase oxidative stress, which would

increase

> > the conversion of glutathione to GSSG. GSSG is also elevated in

autism,

> > and this would also decrease glutathione levels. Thus, it's

curious

> > that the first study makes no mention of B6. B6 deficiency is

more

> > likely to be the significant reason for low glutathione in that

> > condition, and not CBS upregulation.

> >

> > It's been suggested by people here that supplements such

betaine, that

> > increase methylation, would help to increase glutathione levels

and

> > decrease cysteine levels. Increasing methylation has not been

proven to

> > increase glutathione levels. Nor does it necessarily decrease

cysteine

> > levels. For example, see the following lab study on the use of

betaine:

> >

> >

> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & dop\

> > t=AbstractPlus & list_uids=15885362 & query_hl=31 & itool=pubmed_docsum

> >

> <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & do\

> >

pt=AbstractPlus & list_uids=15885362 & query_hl=31 & itool=pubmed_docsum>

> >

> > In this study, betaine greatly increased the methylation path,

which led

> > to a reduction of cysteine production via the transsulphuration.

path.

> > However, cysteine levels stayed the same. This is because the

decrease

> > in cysteine levels, led to a reduction of CDO, the enzyme which

degrades

> > cysteine, thereby restoring the original cysteine levels. Both

cysteine

> > and glutathione levels remained the same, despite the increase in

> > methylation.

> >

> > Cysteine is mainly controlled by CDO, and CDO is mainly

dependent on

> > cysteine levels. The higher the cysteine, the higher the CDO.

CDO can

> > increase many magnitudes to offset dietary cysteine, in order to

> > stabilize cysteine levels.

> >

> > However, life style can affect serum cysteine levels. Studies

have

> > shown that body mass index is a strong determinant of cysteine.

> > Cysteine is also positively associated with age, total

cholesterol

> > concentration, diastolic blood pressure, and coffee

consumption. And

> > one study indicates that exercise can reduce cysteine levels.

Life

> > style changes may make more of a difference on cysteine levels,

than

> > supplementation.

> >

> > Additionally, one study has shown that CDO is inhibited by

cytokines

> > such as TNF-alpha and TGF-beta. If this is true, then this

could be the

> > reason why some of the above factors influence cysteine levels,

i.e. due

> > to increased inflammation.

> >

> > As for glutathione, there are many factors that affect

glutathione

> > levels. Here's a good review article on glutathione metabolism:

> >

> >

> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & dop\

> >

t=AbstractPlus & list_uids=14988435 & query_hl=109 & itool=pubmed_docsum

> >

> <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

db=pubmed & cmd=Retrieve & do\

> >

pt=AbstractPlus & list_uids=14988435 & query_hl=109 & itool=pubmed_docsum>

> >

> > In particular, the following paragraph from that article explains

> > factors which regulates the amount of glutathione in cells:

> >

> > " Gamma-Glutamylcysteine synthetase (GCS) is the rate-controlling

enzyme

> > in de novo synthesis of GSH. " Oxidant stress, nitrosative stress,

> > inflammatory cytokines, cancer, cancer chemotherapy, ionizing

radiation,

> > heat shock, inhibition of GCS activity, GSH depletion, GSH

conjugation,

> > prostaglandin A2, heavy metals, antioxidants, and insulin

increase GCS

> > transcription or activity in a variety of cells. In contrast,

dietary

> > protein deficiency, dexamethasone, erythropoietin, tumor growth

factor

> > ß, hyperglycemia, and GCS phosphorylation decrease GCS

transcription

> > or activity. Nuclear factor {kappa}B mediates the upregulation

of GCS

> > expression in response to oxidant stress, inflammatory

cytokines, and

> > buthionine sulfoximine-induced GSH depletion. S-nitrosation of

GCS

> > protein by NO donors (e.g., S-nitroso-L-cysteine and

> > S-nitroso-L-cysteinylglycine) reduces enzyme activity,

suggesting a link

> > between NO (a metabolite of L-arginine) and GSH metabolism.

Indeed, an

> > increase in NO production by inducible NO synthase causes GCS

inhibition

> > and GSH depletion in cytokine-activated macrophages and neurons.

In this

> > regard, glucosamine, taurine, n-3 PUFAs, phytoestrogens,

polyphenols,

> > carotenoids, and zinc, which inhibit the expression of inducible

NO

> > synthase and NO production, may prevent or attenuate GSH

depletion in

> > cells. Conversely, high-fat diet, saturated long-chain fatty

acids,

> > low-density lipoproteins, linoleic acid, and iron, which enhance

the

> > expression of inducible NO synthase and NO production, may

exacerbate

> > the loss of GSH from cells. "

> >

> > Unless you definitely have low serum glutathione levels, perhaps

> > controlling the factors that cause a loss of GSH from cells, is

just as

> > important, or more so, than making sure you have adequate

glutathione

> > levels.

> >

> > The supplements which are used in Dr. Yasko's protocol have lots

of good

> > effects that can help people. However, based on what I've read

in the

> > medical literature, there is doubt as to whether they are

helping in the

> > ways that people here are theorizing.

> >

> > - Mark

> >

> >

> >

> >

> >

> >

> >

> >