Re: Re: GSH causing pain in 2yo? - candidate for SJS or TENS?

[Guest guest]

Sulfur is part of the GSH molecule. If your son reacts to epsom salt

baths and to GSH, he may indeed be a candidate for caution when

contemplating sulfur-containing whatevers.

The search

glutathione[ti] AND (sulfur OR sulphur)

generated a number of citations, from which a smattering is presented

hereinbelow. Cites 2, 4, 5 may be the most relevant for CSB folks. No

profound lessons therein, but certainly informative tidbits about GSH.

noahparthasmom wrote:

and Dr. McCandless,

Thank you so much for answering my question. We plan on starting B-12

injections at our next DAN visit (May 30) so we'll probably put the

GSH on hold until after the salts. It figures that my son would be in

the 20% that can't handle GSH.

, your email got me thinking - does GSH contain sulfur? I'm

really naive about all of this, but my son has a similar reaction to

epsom salt baths. There's no pain, but he becomes a live wire and is

unable to sleep after an epsom salt bath. He gets so hyper with even

1/4 cup and stays up all night tossing and turning. I don't know if

there's a connection or not.

The info you sent looks really interesting. Thank you so much for

sending it.

glutathione[ti] AND (sulfur OR sulphur)

1: Biochem Biophys Res Commun. 2004 Apr 9;316(3):749-52.

Polymorphisms of glutathione S-transferase M1 and T1 modulate blood pressure of

individuals chronically exposed to natural sour gas containing sulfur compounds.

Saadat M, Bahaoddini A, Mohabatkar H.

Department of Biology, College of Sciences, Shiraz University, Shiraz 71454,

Iran. saadat@...

In order to find the effect of genetic polymorphisms of GSTM1 and GSTT1 on blood

pressure of individuals chronically exposed to sulfur compounds, the present

study was done. Study subjects (38 males, 38 females) were residents of

contaminated areas of Masjid-i-Sulaiman (southwest of Iran). The GSTM1 and GSTT1

genotypes were determined using a polymerase chain reaction (PCR)-based method.

The non-parametric Sign test was applied in order to detect differences between

the GSTs genotypes of study subjects and the normal mean values according to the

sex and age of subjects. From four combination of genotypes, systolic blood

pressure significantly decreased in combination of null-GSTM1 and present-GSTT1

(Z=-2.41; P=0.016), and diastolic blood pressure significantly increased in

combination of present-GSTM1 and null-GSTT1 (Z=+2.14; P=0.032). It is speculated

about polymorphisms of GSTs in individuals chronically exposed to natural sour

gas, which contains H2S, fulfilling a physiological role(s) in regulating blood

pressure.

PMID: 15033463 [PubMed - in process]

2: Int J Vitam Nutr Res. 2003 Nov;73(6):468-77.

The effect of graded levels of dietary casein, with or without methionine

supplementation, on glutathione concentration in unstressed and

endotoxin-treated rats.

Alhamdan AA, Grimble RF.

Institute of Human Nutrition, University of Southampton, Southampton SO16 7PX,

UK. dr_Alhamdan@...

Glutathione (GSH) concentration was measured in rats fed either graded levels of

dietary casein (experiment 1; 180 g, 120 g, 80 g, or 60 g protein/kg diet) or

graded levels of dietary casein, supplemented with methionine to equalize

dietary sulfur amino acid content to that seen in an 180 g/kg casein diet

supplemented with 0.3 g L-methionine/kg diet (experiment 2; 180 g protein +0.3 g

L-methionine, 80 g protein +6.70 g L-methionine, or 60 g protein +7.45 g

L-methionine/kg diet). Rats were given an inflammatory challenge by

intraperitoneal injection of endotoxin (lipopolysaccharide from Escherichia

coli), and were compared with ad libitum and pair-fed controls. Glutathione

concentration in various organs (liver, lung, spleen, and thymus) decreased in

animals fed the low-protein diets (80 g or 60 g/kg diet). Addition of the sulfur

amino acid, methionine, to the low-protein diets restored glutathione

concentrations in animals fed ad libitum and prevented the fall in GSH

concentration, which occurred in lung, spleen, and thymus in response to the

endotoxin. Despite the similarity in the amount of sulfur amino acid consumed

between the groups fed the 180 g protein +0.3 g L-methionine and the 60 g

protein +7.45 g L-methionine/kg diet, in experiment 2, hepatic GSH concentration

significantly increased in the latter group, in animals fed ad libitum and in

the endotoxin-treated animals, but not in the pair-fed controls.

PMID: 14743552 [PubMed - in process]

3: Biochemistry. 2004 Jan 20;43(2):352-61.

Parallel evolutionary pathways for glutathione transferases: structure and

mechanism of the mitochondrial class kappa enzyme rGSTK1-1.

Ladner JE, Parsons JF, Rife CL, Gilliland GL, Armstrong RN.

The Center for Advanced Research in Biotechnology of the land Biotechnology

Institute and the National Institutes of Standards and Technology, Gudelsky

Drive, Rockville, land 20850, USA.

The class kappa glutathione (GSH) transferase is an enzyme that resides in the

mitochondrial matrix. Its relationship to members of the canonical GSH

transferase superfamily has remained an enigma. The three-dimensional structure

of the class kappa enzyme from rat (rGSTK1-1) in complex with GSH has been

solved by single isomorphous replacement with anomalous scattering at a

resolution of 2.5 A. The structure reveals that the enzyme is more closely

related to the protein disulfide bond isomerase, dsbA, from Escherichia coli

than it is to members of the canonical superfamily. The structures of rGSTK1-1

and the canonical superfamily members indicate that the proteins folds have

diverged from a common thioredoxin/glutaredoxin progenitor but did so by

different mechanisms. The mitochondrial enzyme, therefore, represents a fourth

protein superfamily that supports GSH transferase activity. The thioredoxin

domain functions in a manner that is similar to that seen in the canonical

enzymes by providing key structural elements for the recognition of GSH. The

hydroxyl group of S16 is within hydrogen-bonding distance of the sulfur of bound

GSH and is, in part, responsible for the ionization of the thiol in the E*GSH

complex (pKa = 6.4 +/- 0.1). Preequilibrium kinetic experiments indicate that

the k(on) for GSH is 1 x 10(5) M(-1) s(-1) and k(off) for GS- is approximately 8

s(-1) and relatively slow with respect to turnover with 1-chloro-2,

4-dinitrobenzene (CDNB). As a result, the KM(GSH) (11 mM) is much larger than

the apparent Kd(GSH) (90 microM). The active site has a relatively open access

channel that is flanked by disordered loops that may explain the relatively high

turnover number (280 s(-1) at pH 7.0) toward CDNB. The disordered loops form an

extensive contiguous patch on one face of the dimeric enzyme, a fact that

suggests that the protein surface may interact with a membrane or other protein

partner.

PMID: 14717589 [PubMed - in process]

4: Carcinogenesis. 2004 Mar;25(3):359-67. Epub 2003 Nov 21.

Selective expression of glutathione S-transferase genes in the murine

gastrointestinal tract in response to dietary organosulfur compounds.

Andorfer JH, Tchaikovskaya T, Listowsky I.

Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New

York, NY 10461, USA.

A short-term feeding regimen was designed to analyze the effects of compounds

such as diallyl disulfide (DADS), diallylthiosulfinate (allicin) from garlic and

butylated hydroxyanisole (BHA) on glutathione S-transferase (GST) expression in

the gastrointestinal tract and liver of male mice. After animals were force-fed

these compounds, tissue GSTs were purified and individual subunits resolved by

HPLC and identified on the basis of mass spectrometry (ESI MS) and

immunoreactivity data. The effects of DADS and allicin on GST expression were

especially prominent in stomach and small intestine, where there were major

coordinate changes in GST subunit profiles. In particular, the transcripts of

the mGSTM1 and mGSTM4 genes, which share large segments of common 5'-flanking

sequences, and their corresponding subunits were selectively induced. Levels of

alpha class subunits also increased, whereas mGSTM3 and mGSTP1 were not

affected. The inducible mGSTA5 and non-responsive mGSTM3 subunits had not been

identified previously. Liver and colon GSTs were also affected to a lesser

extent, but this short-term feeding regimen had no effect on GST subunit

patterns from other organs, including heart, brain and testis. Real-time PCR

(TaqMan) methods were used for quantitative estimations of relative amounts of

the mRNAs encoding the GSTs. Effects on the transcripts generally paralleled

changes at the protein level, for the most part, however, the greatest relative

increases were observed for those mRNAs that were expressed at low abundance

constituitively. Mechanisms by which the organosulfur compounds operate to

affect GST transcription could involve reversible modification of certain

protein sulfhydryl groups, shifts in reduced glutathione/oxidized glutathione

ratios and resultant changes in cellular redox status.

PMID: 14633659 [PubMed - indexed for MEDLINE]

5: Nutr Cancer. 2001;40(2):205-10.

Relative activities of organosulfur compounds derived from onions and garlic in

increasing tissue activities of quinone reductase and glutathione transferase in

rat tissues.

Munday R, Munday CM.

Ruakura Agricultural Research Centre, Hamilton, New Zealand.

rex.munday@...

There is evidence that onions and garlic protect against cancer in humans. It

has been suggested that this effect is due to the organosulfur compounds in

these vegetables and that these substances act through induction of phase II

detoxification enzymes. In the present studies, we have compared the ability of

diallyl sulfide, dially disulfide, and diallyl trisulfide, compounds that are

derived from garlic, to increase the activity of the phase II enzymes quinone

reductase and glutathione transferase in a variety of rat tissues. We have also

examined the onion-derived substances, dipropyl sulfide, dipropyl disulfide,

dipropenyl sulfide, and dipropenyl disulfide, under identical conditions.

Diallyl trisulfide and diallyl disulfide were potent inducers of the phase II

enzymes. Dipropenyl disulfide was much less active, while little effect on

enzyme activity was seen in animals dosed with dipropyl disulfide. Diallyl

sulfide and dipropyl sulfide were weak inducers of quinone reductase and

glutathione transferase, but dipropenyl sulfide was very active, with an effect

similar to that of diallyl disulfide. It is possible that diallyl disulfide and

diallyl trisulfide are important in the anticancer action of garlic, while

dipropenyl sulfide could be involved in the beneficial action of onions.

PMID: 11962257 [PubMed - indexed for MEDLINE]

6: Nutr Neurosci. 2001;4(3):213-22.

Sulfur amino acid deficiency depresses brain glutathione concentration.

Paterson PG, Lyon AW, Kamencic H, Andersen LB, Juurlink BH.

College of Pharmacy and Nutrition, Cameco Multiple Sclerosis and Neuroscience

Research Center, University of Saskatchewan, Saskatoon, Canada.

phyllis.paterson@...

Dietary sulfur amino acid content is a major determinant of glutathione

concentration in some tissues. We examined whether brain glutathione (GSH), a

key component of antioxidant defense important for minimizing ischemic injury,

was also responsive to short-term sulfur amino acid deficiency. Female

Long- adult rats were fed a sulfur-deficient L-amino acid defined diet for

five days; the control diet was supplemented with L-cystine and L-methionine (n

= 6). Sulfur amino acid deficiency was confirmed by a reduction in liver

cysteine and GSH concentrations, marked decreases in food intake, and weight

loss. GSH concentration analyzed by reverse-phase high performance liquid

chromatography was significantly depressed in the neocortex and thalamus of

deficient rats. Brain cysteine was not decreased in a parallel manner. Classical

glutathione peroxidase activity was increased in the liver and brain of sulfur

amino acid deficient rats. This suggests an upregulation of antioxidant defense

but these findings may be complicated by alterations in tissue composition. The

depletion of brain GSH by a reduced supply of dietary precursors may be

important during brain ischemia when the rate of GSH utilization and the need

for synthesis are increased.

PMID: 11842890 [PubMed - indexed for MEDLINE]

7: Curr Opin Clin Nutr Metab Care. 2002 Jan;5(1):85-92.

Comment in:

Curr Opin Clin Nutr Metab Care. 2002 Jan;5(1):43-5.

Redox control of the transsulfuration and glutathione biosynthesis pathways.

Deplancke B, Gaskins HR.

Division of Nutritional Sciences, Department of Animal Sciences, University of

Illinois at Urbana-Champaign, 1207 W. Drive, Urbana, IL 61801, USA.

Intracellular reduction-oxidation status is increasingly recognized as a primary

regulator of cellular growth and development. The relative reduction-oxidation

state of the cell depends primarily on the precise balance between

concentrations of reactive oxygen species and the cysteine-dependent antioxidant

thiol buffers glutathione and thioredoxin, which by preferentially reacting with

reactive oxygen species, protect other intracellular molecules from oxidative

damage. The transsulfuration pathway constitutes the major route of cysteine

biosynthesis, and may thus be central in controlling the intracellular

reduction-oxidation state and the balance between self-renewal and

differentiation programs. This review discusses new findings on reciprocal

reduction-oxidation modulation of enzymes involved in the transsulfuration and

glutathione biosynthesis pathways, as well as studies elucidating the impact of

sulfur amino acid availability on these pathways.

Publication Types:

Review

Review, Tutorial

PMID: 11790955 [PubMed - indexed for MEDLINE]

>

>

>

[Guest guest]

,

Wow, another sulfur kid. We may be on to a small sub-type here. Test #2

indicates the importance of the amino acid interaction with GSH. I think

I finally understand this after hearing Jill . I look forward to

finally getting the amino acid test at the end of May. Maybe there will

be some clues there. One puzzling thing is that test #2 added methione,

a sulfur amino acid, to raise GSH. I would bet money our son needs that,

but I would think the sulfur part of it could be a problem. Am I

confusing Sulfur with Sulfa again??? Also, could you please state the

conclusion of this test in terms I might understand. Thank you for

sticking with this issue.

L

2: Int J Vitam Nutr Res. 2003 Nov;73(6):468-77.

The effect of graded levels of dietary casein, with or without

methionine

supplementation, on glutathione concentration in unstressed and

endotoxin-treated rats.

Alhamdan AA, Grimble RF.

Institute of Human Nutrition, University of Southampton, Southampton

SO16 7PX,

UK. dr_Alhamdan@...

Glutathione (GSH) concentration was measured in rats fed either graded

levels of

dietary casein (experiment 1; 180 g, 120 g, 80 g, or 60 g protein/kg

diet) or

graded levels of dietary casein, supplemented with methionine to

equalize

dietary sulfur amino acid content to that seen in an 180 g/kg casein

diet

supplemented with 0.3 g L-methionine/kg diet (experiment 2; 180 g

protein +0.3 g

L-methionine, 80 g protein +6.70 g L-methionine, or 60 g protein +7.45 g

L-methionine/kg diet). Rats were given an inflammatory challenge by

intraperitoneal injection of endotoxin (lipopolysaccharide from

Escherichia

coli), and were compared with ad libitum and pair-fed controls.

Glutathione

concentration in various organs (liver, lung, spleen, and thymus)

decreased in

animals fed the low-protein diets (80 g or 60 g/kg diet). Addition of

the sulfur

amino acid, methionine, to the low-protein diets restored glutathione

concentrations in animals fed ad libitum and prevented the fall in GSH

concentration, which occurred in lung, spleen, and thymus in response to

the

endotoxin. Despite the similarity in the amount of sulfur amino acid

consumed

between the groups fed the 180 g protein +0.3 g L-methionine and the 60

g

protein +7.45 g L-methionine/kg diet, in experiment 2, hepatic GSH

concentration

significantly increased in the latter group, in animals fed ad libitum

and in

the endotoxin-treated animals, but not in the pair-fed controls.

PMID: 14743552 [PubMed - in process]

3: Biochemistry. 2004 Jan 20;43(2):352-61.

Parallel evolutionary pathways for glutathione transferases: structure

and

mechanism of the mitochondrial class kappa enzyme rGSTK1-1.

Ladner JE, Parsons JF, Rife CL, Gilliland GL, Armstrong RN.

The Center for Advanced Research in Biotechnology of the land

Biotechnology

Institute and the National Institutes of Standards and Technology,

Gudelsky

Drive, Rockville, land 20850, USA.

The class kappa glutathione (GSH) transferase is an enzyme that resides

in the

mitochondrial matrix. Its relationship to members of the canonical GSH

transferase superfamily has remained an enigma. The three-dimensional

structure

of the class kappa enzyme from rat (rGSTK1-1) in complex with GSH has

been

solved by single isomorphous replacement with anomalous scattering at a

resolution of 2.5 A. The structure reveals that the enzyme is more

closely

related to the protein disulfide bond isomerase, dsbA, from Escherichia

coli

than it is to members of the canonical superfamily. The structures of

rGSTK1-1

and the canonical superfamily members indicate that the proteins folds

have

diverged from a common thioredoxin/glutaredoxin progenitor but did so by

different mechanisms. The mitochondrial enzyme, therefore, represents a

fourth

protein superfamily that supports GSH transferase activity. The

thioredoxin

domain functions in a manner that is similar to that seen in the

canonical

enzymes by providing key structural elements for the recognition of GSH.

The

hydroxyl group of S16 is within hydrogen-bonding distance of the sulfur

of bound

GSH and is, in part, responsible for the ionization of the thiol in the

E*GSH

complex (pKa = 6.4 +/- 0.1). Preequilibrium kinetic experiments indicate

that

the k(on) for GSH is 1 x 10(5) M(-1) s(-1) and k(off) for GS- is

approximately 8

s(-1) and relatively slow with respect to turnover with 1-chloro-2,

4-dinitrobenzene (CDNB). As a result, the KM(GSH) (11 mM) is much larger

than

the apparent Kd(GSH) (90 microM). The active site has a relatively open

access

channel that is flanked by disordered loops that may explain the

relatively high

turnover number (280 s(-1) at pH 7.0) toward CDNB. The disordered loops

form an

extensive contiguous patch on one face of the dimeric enzyme, a fact

that

suggests that the protein surface may interact with a membrane or other

protein

partner.

PMID: 14717589 [PubMed - in process]

4: Carcinogenesis. 2004 Mar;25(3):359-67. Epub 2003 Nov 21.

Selective expression of glutathione S-transferase genes in the murine

gastrointestinal tract in response to dietary organosulfur compounds.

Andorfer JH, Tchaikovskaya T, Listowsky I.

Department of Biochemistry, Albert Einstein College of Medicine, Bronx,

New

York, NY 10461, USA.

A short-term feeding regimen was designed to analyze the effects of

compounds

such as diallyl disulfide (DADS), diallylthiosulfinate (allicin) from

garlic and

butylated hydroxyanisole (BHA) on glutathione S-transferase (GST)

expression in

the gastrointestinal tract and liver of male mice. After animals were

force-fed

these compounds, tissue GSTs were purified and individual subunits

resolved by

HPLC and identified on the basis of mass spectrometry (ESI MS) and

immunoreactivity data. The effects of DADS and allicin on GST expression

were

especially prominent in stomach and small intestine, where there were

major

coordinate changes in GST subunit profiles. In particular, the

transcripts of

the mGSTM1 and mGSTM4 genes, which share large segments of common

5'-flanking

sequences, and their corresponding subunits were selectively induced.

Levels of

alpha class subunits also increased, whereas mGSTM3 and mGSTP1 were not

affected. The inducible mGSTA5 and non-responsive mGSTM3 subunits had

not been

identified previously. Liver and colon GSTs were also affected to a

lesser

extent, but this short-term feeding regimen had no effect on GST subunit

patterns from other organs, including heart, brain and testis. Real-time

PCR

(TaqMan) methods were used for quantitative estimations of relative

amounts of

the mRNAs encoding the GSTs. Effects on the transcripts generally

paralleled

changes at the protein level, for the most part, however, the greatest

relative

increases were observed for those mRNAs that were expressed at low

abundance

constituitively. Mechanisms by which the organosulfur compounds operate

to

affect GST transcription could involve reversible modification of

certain

protein sulfhydryl groups, shifts in reduced glutathione/oxidized

glutathione

ratios and resultant changes in cellular redox status.

PMID: 14633659 [PubMed - indexed for MEDLINE]

5: Nutr Cancer. 2001;40(2):205-10.

Relative activities of organosulfur compounds derived from onions and

garlic in

increasing tissue activities of quinone reductase and glutathione

transferase in

rat tissues.

Munday R, Munday CM.

Ruakura Agricultural Research Centre, Hamilton, New Zealand.

rex.munday@...

There is evidence that onions and garlic protect against cancer in

humans. It

has been suggested that this effect is due to the organosulfur compounds

in

these vegetables and that these substances act through induction of

phase II

detoxification enzymes. In the present studies, we have compared the

ability of

diallyl sulfide, dially disulfide, and diallyl trisulfide, compounds

that are

derived from garlic, to increase the activity of the phase II enzymes

quinone

reductase and glutathione transferase in a variety of rat tissues. We

have also

examined the onion-derived substances, dipropyl sulfide, dipropyl

disulfide,

dipropenyl sulfide, and dipropenyl disulfide, under identical

conditions.

Diallyl trisulfide and diallyl disulfide were potent inducers of the

phase II

enzymes. Dipropenyl disulfide was much less active, while little effect

on

enzyme activity was seen in animals dosed with dipropyl disulfide.

Diallyl

sulfide and dipropyl sulfide were weak inducers of quinone reductase and

glutathione transferase, but dipropenyl sulfide was very active, with an

effect

similar to that of diallyl disulfide. It is possible that diallyl

disulfide and

diallyl trisulfide are important in the anticancer action of garlic,

while

dipropenyl sulfide could be involved in the beneficial action of onions.

PMID: 11962257 [PubMed - indexed for MEDLINE]

6: Nutr Neurosci. 2001;4(3):213-22.

Sulfur amino acid deficiency depresses brain glutathione concentration.

Paterson PG, Lyon AW, Kamencic H, Andersen LB, Juurlink BH.

College of Pharmacy and Nutrition, Cameco Multiple Sclerosis and

Neuroscience

Research Center, University of Saskatchewan, Saskatoon, Canada.

phyllis.paterson@...

Dietary sulfur amino acid content is a major determinant of glutathione

concentration in some tissues. We examined whether brain glutathione

(GSH), a

key component of antioxidant defense important for minimizing ischemic

injury,

was also responsive to short-term sulfur amino acid deficiency. Female

Long- adult rats were fed a sulfur-deficient L-amino acid defined

diet for

five days; the control diet was supplemented with L-cystine and

L-methionine (n

= 6). Sulfur amino acid deficiency was confirmed by a reduction in liver

cysteine and GSH concentrations, marked decreases in food intake, and

weight

loss. GSH concentration analyzed by reverse-phase high performance

liquid

chromatography was significantly depressed in the neocortex and thalamus

of

deficient rats. Brain cysteine was not decreased in a parallel manner.

Classical

glutathione peroxidase activity was increased in the liver and brain of

sulfur

amino acid deficient rats. This suggests an upregulation of antioxidant

defense

but these findings may be complicated by alterations in tissue

composition. The

depletion of brain GSH by a reduced supply of dietary precursors may be

important during brain ischemia when the rate of GSH utilization and the

need

for synthesis are increased.

PMID: 11842890 [PubMed - indexed for MEDLINE]

7: Curr Opin Clin Nutr Metab Care. 2002 Jan;5(1):85-92.

Comment in:

Curr Opin Clin Nutr Metab Care. 2002 Jan;5(1):43-5.

Redox control of the transsulfuration and glutathione biosynthesis

pathways.

Deplancke B, Gaskins HR.

Division of Nutritional Sciences, Department of Animal Sciences,

University of

Illinois at Urbana-Champaign, 1207 W. Drive, Urbana, IL 61801,

USA.

Intracellular reduction-oxidation status is increasingly recognized as a

primary

regulator of cellular growth and development. The relative

reduction-oxidation

state of the cell depends primarily on the precise balance between

concentrations of reactive oxygen species and the cysteine-dependent

antioxidant

thiol buffers glutathione and thioredoxin, which by preferentially

reacting with

reactive oxygen species, protect other intracellular molecules from

oxidative

damage. The transsulfuration pathway constitutes the major route of

cysteine

biosynthesis, and may thus be central in controlling the intracellular

reduction-oxidation state and the balance between self-renewal and

differentiation programs. This review discusses new findings on

reciprocal

reduction-oxidation modulation of enzymes involved in the

transsulfuration and

glutathione biosynthesis pathways, as well as studies elucidating the

impact of

sulfur amino acid availability on these pathways.

Publication Types:

Review

Review, Tutorial

PMID: 11790955 [PubMed - indexed for MEDLINE]

>

>

>

[Guest guest]

,

How much epsom salts did you use in that first bath? The average man or

woman on the street will not have a bad reaction to epsom salts, so it

means something unusual is happening. I'm going to repost below something

I wrote two years ago to another list, and it may help explain your son's

reaction.

===========================

At 12:42 PM 6/19/2002 +0000, you wrote:

>I tried Epsom salts in the bath based on some posts I saw on this

>board. Both of my kids were extremely emotional afterwards,

>coincidence?? I don't know enough about this yet to understand what

>it is supposed to do, or what the side effects are.

I think the trick here, which is important to know about, is that you need

to start slowly when introducing a supplement of something for which you

have been deficient a long time, and then slowly work up to more. This is

because, unlike drugs, where the quantity of a dose is set by the doctor

trying to obtain a blood level of something FOREIGN to the body,

introducing a supplement of something the body uses every day works in a

whole different way, and this can be generalized to lots of things. I'll

explain why.

Most chemical reactions happen inside cells after substances have crossed

over the cell's outer membrane. For things cells use everyday, they have

specific transporters and receptors that are expressed on the cell surface

in the quantity that is appropriate to assure an appropriate supply to that

cell type. Not all cells like the same quantity. When everything works

right, the inside of the cell gets the appropriate quantity of what it

needs of that substance. The cell wants not too much and not too little and

it knows how to adjust the availability of that substance to the inside of

the cell when the supply outside the cell changes.

If the supply of something the body uses up every day has been low for

awhile, the cell will upregulate the transporter or receptor that is

specific for that substance. Upregulation means it will put more of these

working molecules on the cell surface in order to increase the odds that

the substance will find its receptor or transporter.

When the supply has been high for a long time, the cell will also cut back

the quantity of the receptor or transporter on the cell surface. Cells are

very fluid like that: changing and adjusting constantly: not like a machine

at all! Your car doesn't increase the gas caps when its fuel supply is

low, but it doesn't have to get its gas from the passing parade by chance

and kinetics...

So, if you have been deficient in sulfate for a long time, your cells would

have upregulated the transporters to make much of little. All over the

body, receptors that need sulfated ligands might have been upregulated as

well, trying to increase their signal or supply.

If you suddenly increase the quantity of sulfate that approaches the cell

by several fold, you can get too intense a signal, and that can be

overwhelming. That is why you should start slowly. This gives your body's

cells a chance to readjust to the new level they will be seeing. We're not

trying to overdo that level, but just to return it to something normal.

Remember that cells are accustomed to biological rhythms that change the

quantities of nutrients that cells see. This includes feeding schedules

and sleep. Cells don't make these adjustments on whim or very quickly, for

they know there will be long periods of time when the supply gets lower

just because it has been a long time since you ate something. I would

guess, for that reason, that cells tend to adjust to conditions that may

continue for at least a day or two.

The way this biology works gives me the suspicion that the children who get

the most hyper after their first epsom salts bath or baths may be the

children who have been the most deficient of this substance, and have

receptors and transporters dialed WAY up.

If you are deficient in supply, even when you have receptors or

transporters expressed at extremely high quantity, you still might be low

in quantity for the function you need. The increase of receptors or

transporters will help, but it isn't much of a solution long term.

If you get exposed to something that requires a lot of sulfate for your

body to detoxify (like phenols in fumes or foods or drugs), the level of

sulfate available for NORMAL functions will be hurting temporarily as your

body tries to recover from this demand. The loss of the function of other

molecules that use sulfate for normal function is likely what is producing

symptoms: not your body feeling toxic as if it had just been " burned " by

the substance your body was trying to detoxify. That sort of injury might

take longer and it would probably be more subtle, anyway. If you are

having neurological reactions, you are probably seeing an adjustment in the

neurological chemistry which is feeling shorted and may be overwhelmed with

sudden change.

Of course, you really need an appropriate supply of sulfate, but the story

of HOW the supply got low in the first place can be very different from

child to child, and involve organs like the kidneys, the liver and the GI

tract and systems like the immune system.

Anyway, as an example of this sort of mechanism with an entirely different

substance, I'll tell you a little about the secretin story. This sort of

receptor-quantity issue was suspected to be happening in the children with

autism who were given IV secretin. In response to the same dose that had a

predictable response in normal people, those with autism instead put out

huge quantities of pancreatic fluid. Their response was intense on the

very same dose that other patients were getting without experiencing this

overexuberant response.

Why? The sudden increase in secretin was more of a surprise for the bodies

of autistic children than it was for the other children with GI problems

being tested. The pancreas was OVER responsive to secretin probably

because this was the first good supply of secretin that it had gotten in a

long time. Scientists suspected that the amount of secretin these children

had been producing on their own had been low for a long time.

I hope all this makes sense. Your body makes secretin, but it also makes

sulfate from the amino acids cysteine and methionine. There may be a

reason this isn't happening appropriately.

I've heard of parents starting with as little as a teaspoon in the

bathwater and working up. You can also apply the solution topically, and

can control the quantity by how much surface of the skin you cover. The

half-life of sulfate in the blood is 4-9 hours.

At any rate, , and any other listmates who saw something similar

happen, please do not interpret this to mean the epsom salts were the wrong

thing...it may mean exactly the opposite! Normal people do not have any

response to epsom salts baths except maybe to feel relaxed later! They

don't get hyper or emotional...

If you have already tried reducing the quantity of epsom salts drastically

and slowly increasing the quantity, and it doesn't work to reduce this

hyper or emotional response, I'd be glad to talk to you offlist about what

else it might mean.

Anyway, I hope this helps. You've just got to think like a cell thinks!

At 03:15 AM 5/2/2004 +0000, you wrote:

> > , your email got me thinking - does GSH contain sulfur? I'm

> > really naive about all of this, but my son has a similar reaction

>to

> > epsom salt baths. There's no pain, but he becomes a live wire and

>is

> > unable to sleep after an epsom salt bath

>

>HUM... My 2 year old son Slater also went nuts after our one and

>only epson salt bath.. he was hyper in the tub and for hours

>afterwards-much worse than how he was when I put him in the bath. I

>guess I need to learn more about this too. He is showing more signs

>of aggression but not sure if it is body awareness/sensory issues,

>being a typical 2 year old or something else. Another puzzle to

>figure out..I read Dr. McCandless' response to someone about

>aggressiveness and Glutathione yesterday and wondered about our

>situation.

>

[Guest guest]

,

Would the cell explanation apply to any medicine? Our daughter started

Strattera in March. We were told to start with 25mg. for three days then

increase to 40mg. She broke out in cold sweats with cold, clammy hands on

the 40mg. I decreased it to 20mg. and she still had the same symptoms. I

decreased it to 10mg. and the symptoms stopped. Three doctors told me that

Strattera would not cause these symptoms. Our daughter's pediatrician

suggested that I keep her on 40mg and check her blood for hypoglycemia for a

week and give her the results. I started that on Friday. Her blood levels

seem within normal range, but she still has cold sweats. Last night I cut

back to 10mg. and she didn't have any symptoms today. So, I didn't check her

blood levels. She is so much more focused on the Strattera, but I'm scared

of it at this point.

Shari

Re: Re: GSH causing pain in 2yo? - candidate for

SJS or TENS?

> ,

>

> How much epsom salts did you use in that first bath? The average man or

> woman on the street will not have a bad reaction to epsom salts, so it

> means something unusual is happening. I'm going to repost below something

> I wrote two years ago to another list, and it may help explain your son's

> reaction.

>

>

>

> ===========================

> At 12:42 PM 6/19/2002 +0000, you wrote:

> >I tried Epsom salts in the bath based on some posts I saw on this

> >board. Both of my kids were extremely emotional afterwards,

> >coincidence?? I don't know enough about this yet to understand what

> >it is supposed to do, or what the side effects are.

>

> I think the trick here, which is important to know about, is that you need

> to start slowly when introducing a supplement of something for which you

> have been deficient a long time, and then slowly work up to more. This is

> because, unlike drugs, where the quantity of a dose is set by the doctor

> trying to obtain a blood level of something FOREIGN to the body,

> introducing a supplement of something the body uses every day works in a

> whole different way, and this can be generalized to lots of things. I'll

> explain why.

>

> Most chemical reactions happen inside cells after substances have crossed

> over the cell's outer membrane. For things cells use everyday, they have

> specific transporters and receptors that are expressed on the cell surface

> in the quantity that is appropriate to assure an appropriate supply to

that

> cell type. Not all cells like the same quantity. When everything works

> right, the inside of the cell gets the appropriate quantity of what it

> needs of that substance. The cell wants not too much and not too little

and

> it knows how to adjust the availability of that substance to the inside of

> the cell when the supply outside the cell changes.

>

> If the supply of something the body uses up every day has been low for

> awhile, the cell will upregulate the transporter or receptor that is

> specific for that substance. Upregulation means it will put more of these

> working molecules on the cell surface in order to increase the odds that

> the substance will find its receptor or transporter.

>

> When the supply has been high for a long time, the cell will also cut back

> the quantity of the receptor or transporter on the cell surface. Cells

are

> very fluid like that: changing and adjusting constantly: not like a

machine

> at all! Your car doesn't increase the gas caps when its fuel supply is

> low, but it doesn't have to get its gas from the passing parade by chance

> and kinetics...

>

> So, if you have been deficient in sulfate for a long time, your cells

would

> have upregulated the transporters to make much of little. All over the

> body, receptors that need sulfated ligands might have been upregulated as

> well, trying to increase their signal or supply.

>

> If you suddenly increase the quantity of sulfate that approaches the cell

> by several fold, you can get too intense a signal, and that can be

> overwhelming. That is why you should start slowly. This gives your

body's

> cells a chance to readjust to the new level they will be seeing. We're

not

> trying to overdo that level, but just to return it to something normal.

>

> Remember that cells are accustomed to biological rhythms that change the

> quantities of nutrients that cells see. This includes feeding schedules

> and sleep. Cells don't make these adjustments on whim or very quickly,

for

> they know there will be long periods of time when the supply gets lower

> just because it has been a long time since you ate something. I would

> guess, for that reason, that cells tend to adjust to conditions that may

> continue for at least a day or two.

>

> The way this biology works gives me the suspicion that the children who

get

> the most hyper after their first epsom salts bath or baths may be the

> children who have been the most deficient of this substance, and have

> receptors and transporters dialed WAY up.

>

> If you are deficient in supply, even when you have receptors or

> transporters expressed at extremely high quantity, you still might be low

> in quantity for the function you need. The increase of receptors or

> transporters will help, but it isn't much of a solution long term.

>

> If you get exposed to something that requires a lot of sulfate for your

> body to detoxify (like phenols in fumes or foods or drugs), the level of

> sulfate available for NORMAL functions will be hurting temporarily as your

> body tries to recover from this demand. The loss of the function of other

> molecules that use sulfate for normal function is likely what is producing

> symptoms: not your body feeling toxic as if it had just been " burned " by

> the substance your body was trying to detoxify. That sort of injury might

> take longer and it would probably be more subtle, anyway. If you are

> having neurological reactions, you are probably seeing an adjustment in

the

> neurological chemistry which is feeling shorted and may be overwhelmed

with

> sudden change.

>

> Of course, you really need an appropriate supply of sulfate, but the story

> of HOW the supply got low in the first place can be very different from

> child to child, and involve organs like the kidneys, the liver and the GI

> tract and systems like the immune system.

>

> Anyway, as an example of this sort of mechanism with an entirely different

> substance, I'll tell you a little about the secretin story. This sort of

> receptor-quantity issue was suspected to be happening in the children with

> autism who were given IV secretin. In response to the same dose that had

a

> predictable response in normal people, those with autism instead put out

> huge quantities of pancreatic fluid. Their response was intense on the

> very same dose that other patients were getting without experiencing this

> overexuberant response.

>

> Why? The sudden increase in secretin was more of a surprise for the

bodies

> of autistic children than it was for the other children with GI problems

> being tested. The pancreas was OVER responsive to secretin probably

> because this was the first good supply of secretin that it had gotten in a

> long time. Scientists suspected that the amount of secretin these

children

> had been producing on their own had been low for a long time.

>

> I hope all this makes sense. Your body makes secretin, but it also makes

> sulfate from the amino acids cysteine and methionine. There may be a

> reason this isn't happening appropriately.

>

> I've heard of parents starting with as little as a teaspoon in the

> bathwater and working up. You can also apply the solution topically, and

> can control the quantity by how much surface of the skin you cover. The

> half-life of sulfate in the blood is 4-9 hours.

>

> At any rate, , and any other listmates who saw something similar

> happen, please do not interpret this to mean the epsom salts were the

wrong

> thing...it may mean exactly the opposite! Normal people do not have any

> response to epsom salts baths except maybe to feel relaxed later! They

> don't get hyper or emotional...

>

> If you have already tried reducing the quantity of epsom salts drastically

> and slowly increasing the quantity, and it doesn't work to reduce this

> hyper or emotional response, I'd be glad to talk to you offlist about what

> else it might mean.

>

> Anyway, I hope this helps. You've just got to think like a cell thinks!

>

>

>

> At 03:15 AM 5/2/2004 +0000, you wrote:

> > > , your email got me thinking - does GSH contain sulfur? I'm

> > > really naive about all of this, but my son has a similar reaction

> >to

> > > epsom salt baths. There's no pain, but he becomes a live wire and

> >is

> > > unable to sleep after an epsom salt bath

> >

> >HUM... My 2 year old son Slater also went nuts after our one and

> >only epson salt bath.. he was hyper in the tub and for hours

> >afterwards-much worse than how he was when I put him in the bath. I

> >guess I need to learn more about this too. He is showing more signs

> >of aggression but not sure if it is body awareness/sensory issues,

> >being a typical 2 year old or something else. Another puzzle to

> >figure out..I read Dr. McCandless' response to someone about

> >aggressiveness and Glutathione yesterday and wondered about our

> >situation.

> >

>

>

>

>

> Many frequently asked questions and answers can be found at

<http://www.autism-rxguidebook.com/forums>

>

[Guest guest]

Shari,

We might expect that all drugs imitate something normal to the body a

little bit, for if they didn't, they would pass through our bodies and not

change things. What I wrote would apply primarily to something normal to

the body, but to whatever extent a drug like Strattera acts like something

normal, it might effect the regulation of its closest

lookalikes. Certainly, by watching the nature of the adverse responses, we

may learn more about the drug's mechanism.

I tried to find someone, via the web last night, who might have experienced

the same thing but I was not successful. You might see if there is a

Straterra discussion group somewhere and you might find someone else who

also experienced the cold sweats.

It always amazes me when someone goes to the doctor with a clear story that

I had reaction A to drug B, and the doctor says, " This drug will not cause

that reaction. " That's happened to me before, but I have also been the one

in 40,000 who had a rare reaction to taking an antibiotic. Exposure to

that drug gave me a blood disease that could have been fatal, and

eventually, there were enough of us that this happened to that it persuaded

the powers to be to severely curb the use of that drug. What is the

terrific shame is that rather than figuring out what was special about us

who had that reaction, they simply curbed the drug's use. What a

waste! Anyway, you can tell that I think it is much more useful to think

of adverse reactions as clues to important differences in our biochemical

makeup.

Shari, if you do find someone else who had cold sweats post Strattera, I

would love it if you both would consider joining

sulfurstories and there we could do a lot of comparing

notes to try to figure out what the reason was for this unusual

response. This " cold sweat " reaction could be the clue that will help you

find a more (for her) direct approach for addressing her issues. In the

meantime, I wouldn't mind at all taking a look at her labwork to see if

there are any other clues, so please feel free to write me offlist!

Also, keep our list here posted, please, if you find anyone else who had

the same reaction.

Best wishes,

At 10:28 PM 5/2/2004 -0500, you wrote:

>,

>Would the cell explanation apply to any medicine? Our daughter started

>Strattera in March. We were told to start with 25mg. for three days then

>increase to 40mg. She broke out in cold sweats with cold, clammy hands on

>the 40mg. I decreased it to 20mg. and she still had the same symptoms. I

>decreased it to 10mg. and the symptoms stopped. Three doctors told me that

>Strattera would not cause these symptoms. Our daughter's pediatrician

>suggested that I keep her on 40mg and check her blood for hypoglycemia for a

>week and give her the results. I started that on Friday. Her blood levels

>seem within normal range, but she still has cold sweats. Last night I cut

>back to 10mg. and she didn't have any symptoms today. So, I didn't check her

>blood levels. She is so much more focused on the Strattera, but I'm scared

>of it at this point.

>Shari