RE: Re: Are high B12 levels a good thing?

[Guest guest]

Thanks .Please correct me if I am wrong in the following:The take home message seems to be that we must give B12 shots even if its serum level is high, because the methyl-cobal is needed for detoxifying the cyanide. And we should avoid cyanide foods. Even if the blood level of B12 is high, its low inside the cells as in there its being used up.Ratan.To: mb12valtrex From: karenhammes@...Date: Sat, 16 Jun 2012 08:31:17 -0700Subject: Fwd: Re: Are high B12 levels a good thing?

Here you go RatanSent from my iPhoneBegin forwarded message:Date: April 28, 2012 2:26:42 PM EDTTo: mb12valtrex Subject: Re: Are high B12 levels a good thing?Reply-To: mb12valtrex

,

Hopefully, this old post of mine on the TLO listserve will be helpful in assessing the B12 issues. Also, when people are in oxidative stress (which oxalate can cause), it is not unusual for the cells to get shifted to preferring transsulfuration to remethylation, and the evidence is a lowering of plasma homocysteine.

When cyanocobalamin gets high in blood, it can mean that intracellularly, methyl and hydroxycobalamin can be quite low. Blood levels are tricky if you don't know the rules about their interpretation.

susan

Listmates,

Ten years ago Rosemary Waring found that in autism that there was very

strong evidence of rhodanese dysfunction. Rhodanese is the mitochondrial

enzyme that detoxifies cyanide by forming thiocyanate from thiosulfate.

Here is some data from her paper, "Sulphur metabolism in Autism" from the

Journal of Nutritional and Environmental Medicine (2000) 10, 25-32:

Autism(n=232) Controls (n=68)

Protein 103.2 64.5

Sulphite 106.9 7.1

Thiosulphate 130.8 18.6

Thiocyanate 6.4 44.0

Sulphate 6819.0 3030.8

In the paper, she discusses the role of rhodanese and why it could be

important.

Rhodanese converts thiosulphate to thiocyanate, so the ratio of these two

compounds helps to assess the function of rhodanese. In autism, that ratio

is 20.4. In her control population, the ratio was 0.42. That means the

ratio was 49 times normal in autism....a strong indication that this enzyme

was inhibited in this very large sample population.

When this enzyme isn't working, the burden is put upon methyl or

hydroxycobalamin to detoxify the cyanide by forming cyanocobalamin. This

conversion that becomes necessary with depressed rhodanese activity might

raise serum cyanocobalamin levels, but it would also deplete

methylcobalamin. Those relationships are nicely illustrated in the first

study I've put below which you can read for free

at: http://ndt.oxfordjournals.org/content/12/8/1622.long.

This mechanism could furnish a very good reason to explain how methylB12

shots have done so much good in autism. By using up methylcobalamin, large

amounts of cyanide could depress methionine synthase activity because of

shunting its cofactor instead to the formation of cyanocobalamin. An

evidence that this has happened would be elevated blood cyanocobalamin

levels, or changed ratios of the various cobalamins in serum, as they found

in the study I already referenced, looking at this issue in hemodialysis

patients.

Knowing this vulnerability in autism provides a good reason for avoiding

high cyanide foods and to keep children or others with these issues away

from smoking (which is a huge source of cyanide).

The CDC's agency on toxic compounds has the following limited information:

>Certain bacteria, fungi, and algae can produce cyanide, and cyanide is

>found in a number of foods and plants. In certain plant foods, including

>almonds, millet sprouts, lima beans, soy, spinach, bamboo shoots, and

>cassava roots (which are a major source of food in tropical countries),

>cyanides occur naturally as part of sugars or other naturally-occurring

>compounds.

I am in the process of finding if anyone has made a more comprehensive list

of the cyanide content of foods but so far, the information is limited

except to suspect that nuts and seeds tend to be high in cyanide. The

biggest dietary source that has caused obvious problems in large

populations is cassava, from which tapioca is made. Our oxalate project at

ARI will try and get tapioca starch flour tested as soon as possible to see

if the process of extracting the starch is as effective in removing cyanide

as it is effective in removing most of the oxalate.

People should also be aware that this depression of rhodanese could be

brought on by exposures to high levels of oxalate. How is that?

The second article below found that rhodanese messenger RNA levels and

proteins levels were depressed in hemodialysis patients at the same time

that cell reactive oxygen species were increased and superoxide levels were

increased, and this was associated with mortality in these patients.

Reactive oxygen species and elevated superoxide levels both can be CAUSED

by elevated oxalate levels (59 articles in pubmed looking at this!) which

makes sense as being relevant because oxalate levels increase over time in

hemodialysis patients because the dialysis is so inferior to healthy

kidneys in removing oxalate. That is why oxalate is considered to be a

major toxin in uremic patients, as is discussed in the third article below.

What are the symptoms of cyanide poisoning?

Look here:

http://www.bt.cdc.gov/agent/cyanide/basics/facts.asp

Basically, what it says is that cyanide impairs the use of oxygen, so that

the parts of the body most affected are those that use lots of oxygen, like

the heart and brain.

Also, cyanide can cause visual field changes:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1291478/pdf/jrsocmed00165-0053.pdf

The visual field changes in patients with tobacco

amblyopia are characteristic. They consist of a

centrocaecal scotoma, usually bilateral though not

necessarily equal on the two sides. The scotoma is

horizontally oval with a sloping edge and is most

easily detected by a reduced stimulus such as a red

or small white object. The defect for colour exceeds

that for white and there are usually two definite

nuclei within the scotoma on the horizontal meridian.

An impairment of the temporal colour fields exists

within the 300 circle and in more advanced cases a

similar defect is also seen to a small white test

object2.

It does concern me that some children with autism are eating large amounts

of products made of almonds, and some are also eating spinach (both whose

high oxalate content might further impair rhodanese furnishing a double

whammy). It equally concerns me that if millet sprouts are high, then

possibly the act of sprouting seeds may increase cyanide when people were

hoping it would decrease oxalate. So far, we haven't been finding that

sprouting is making the oxalate go down, and it might be making the oxalate

level higher, but we still need to test a lot more seeds that way.

I hope this information is of interest and helpful.

Nephrol Dial Transplant. 1997 Aug;12(8):1622-8.

Abnormal cyanide metabolism in uraemic patients.

Koyama K, Yoshida A, Takeda A, Morozumi K, Fujinami T, Tanaka N.

Division of Nephrology, Nagoya Daini Red Cross Hospital, Japan.

Erratum in:

Nephrol Dial Transplant 1998 Mar;13(3):819.

Abstract

BACKGROUND: We previously investigated the factors involved in uraemic

neuropathy in patients undergoing regular haemodialysis and found a

significant relationship between the severity of vibration sensation

impairment and the patients' smoking habits. The administration of

methylcobalamin markedly improved the severity of uraemic neuropathy in

terms of vibration perception thresholds. We presumed that abnormal cyanide

metabolism is involved in the development of uraemic neuropathy.

METHODS: Serum levels of thiocyanate (SCN-), the detoxication product of

cyanide, were determined in 12 patients with preterminal chronic renal

failure (PCRF), 30 patients undergoing regular haemodialysis (HD patients),

and 13 healthy volunteers as a control group. Nine of the 30 HD patients

were smokers. In addition, in 10 HD patients without smoking habits and 10

non-smoking healthy volunteers, the proportion of each vitamin B12 analogue

in total vitamin B12 was estimated.

RESULTS: The mean serum SCN- level of the 12 PCRF patients (5.1 +/- 1.5

micrograms/ml) was significantly higher than that of the control (2.8 +/-

0.9 micrograms/ml) (P < 0.01). The mean SCN- level before haemodialysis in

the 21 non-smoking HD patients was identical to that in the PCRF group,

whereas the level in the nine smoking HD patients (7.2 +/- 1.8

micrograms/ml) significantly higher than that in the non-smoking subgroup

(P < 0.01). In 16 HD patients with methylcobalamin treatment, serum SCN-

levels were lower than in those without methylcobalamin treatment (4.5 +/-

0.5 micrograms/ml in non-smoking subgroup, P < 0.05). And in the

methylcobalamin-treated subgroup (n = 5), the proportion of each vitamin

B12 analogue in total vitamin B12 was normal. In the untreated subgroup (n

= 5), the proportion of cyanocobalamin fraction (10.5 +/- 2.6%) was as high

as the level in Leber's disease patients, while the proportion of

methylcobalamin fraction was low. And the serum cyanocobalamin level was

higher in the treated subgroup.

CONCLUSION: In uraemic patients, cyanide detoxication capability is

impaired because of a reduced SCN- clearance, and increased cyanocobalamin

synthesis indicates elevation of cyanide pool, which would be related to

the development of uraemic neuropathy. Methylcobalamin was considered to be

utilized in cyanide detoxication process via cyanocobalamin synthesis.

PMID: 9269639

Clin Biochem. 2010 Jan;43(1-2):95-101. Epub 2009 Aug 18.

Low expression of thiosulfate sulfurtransferase (rhodanese) predicts

mortality in hemodialysis patients.

Krueger K, Koch K, Jühling A, Tepel M, Scholze A.

Medizinische Klinik, Nephrologie, Charité Campus lin,

Hindenburgdamm 30, 12200 Berlin, Germany.

Abstract

OBJECTIVES: To test the hypothesis that impaired expression of the

thiosulfate sulfurtransferase rhodanese is associated with oxidative stress

and may predict mortality in hemodialysis patients.

DESIGN AND METHODS: Sixty-two hemodialysis patients were investigated to

determine protein and mRNA expression of rhodanese in monocytes. Whole cell

reactive oxygen species and mitochondrial superoxide production were

measured by fluorescence spectrophotometry.

RESULTS: Compared to healthy subjects, hemodialysis patients showed

significantly lower rhodanese mRNA and protein expression and significantly

increased reactive oxygen species. Lower rhodanese protein expression was

significantly associated with higher mitochondrial superoxide production.

The hazard ratio for mortality in hemodialysis patients with rhodanese mRNA

below compared to patients above the median was 2.22. Survival was shorter

with rhodanese mRNA below compared to patients above the median.

CONCLUSION: Impaired rhodanese expression is associated with increased

whole cell reactive oxygen species as well as higher mitochondrial

superoxide production and predicts mortality in hemodialysis patients.

Copyright 2009

Vnitr Lek. 2010 Jul;56(7):695-701.

[Oxalic acid--important uremic toxin]

[Article in Czech]

Mydlík M, Derzsiová K.

IV. interná klinika Lekárskej fakulty UPJS a FN L, Pasteura, Kosice,

Slovenská republika.

Abstract

INTRODUCTION: Oxalic acid is thought to be a significant uremic toxin that

participates in the pathogenesis of uremic syndrome. AIM OF THE STUDY was

to summarise results which we obtained during the study ofoxalic acid in

biological fluids (plasma, saliva, urine and dialysate) in patients

suffering from chronic kidney diseases (CKD), stage 3-5 and after renal

transplantation.

PATIENTS AND METHODS: In the retrospective study were investigated 28

healthy subjects, 112 CKD stage 1-4 patients, 39 haemodialysis patients and

27 CAPD patients. Besides 21 patients were investigated after renal

transplantation. We used the following therapeutic methods: maximal water

diuresis, diet with low (2g/day) and high (15g/day) sodium chloride intake,

administration intravenous furosemide (20mg) and renal replacement therapy

[CAPD, haemodialysis (HD), haemofiltration (HF) and postdilution

haemodiafiltration (HDF)] and renal transplantation. Oxalic acid was

determined by spectrophotometric method using oxalate oxidase which is free

from vitamin C interference. Vitamin C was determined by spectrophotometric

method.

RESULTS: In CKD patients and those after renal transplantation direct

relationships between plasma oxalic acid and serum creatinine were found (r

= 0.904 and 0.943, respectively, P < 0.001). Despite of high plasma oxalic

acid in uremic patients (23.1 +/- 10 micromol/l), there was no significant

difference in salivary oxalic acid between control subjects (126.5 +/- 18

micromol/l) and CKD stage 3-4 patients (133.9 +/- 23.7 micromol/I). The

urinary excretion of oxalic acid during maximal water diuresis in healthy

subjects (n = 15) (from 37.5 +/- 17.4 to 110.2 +/- 49.3 micromol/4 hours)

and after intravenous furosemide (CKD stage 3-4, n = 15) (from 34.5 +/- 5.5

to 66.7 +/- 8.1 micromol/3 hours) increased significantly, but was not

affected by high intake of NaCI in diet (CKD stage 3-4, n = 12). One tablet

of Sorbifer Durules containing 100 mg Fe2+ and 60 mg vitamin C did not lead

to further increase of uremic hyperoxalemia in haemodialysis patients.

Four-hour HD, H F and HDF led to the significant decrease of plasma oxalic

acid, but the most significant decrease was observed during HDF (63.3%).

CONCLUSION: The results of this study indicate, that renal replacement

therapy is not effective for permanent reduction of elevated plasma levels

of oxalic acid--important uremic toxin.

PMID: 20842915

Biosens Bioelectron. 2010 Mar 15;25(7):1729-34. Epub 2009 Dec 22.

Effect of calcium oxalate on renal cells as revealed by real-time

measurement of extracellular oxidative burst.

Gáspár S, Niculi e C, Cucu D, Marcu I.

International Centre of Biodynamics, 1B Intrarea Portocalelor Street,

060101 Bucharest, Romania. sgaspar@...

Abstract

Calcium oxalate is one of the main constituents of kidney stones and has a

proved deleterious effect on renal cells that is mediated by oxidative

stress. However, the subcellular source of this oxidative stress, and

whether it is extending to the extracellular space or not, is still

disputed. Therefore, an electrochemical superoxide biosensor was

constructed, positioned above A6 renal cells, and used to measure in

real-time the extracellular oxidative burst following addition of calcium

oxalate crystals. It was observed that A6 cells do secrete superoxide into

their extracellular space in few minutes after encountering calcium oxalate

crystals. The amount of released superoxide peaks at about 20 min.

Superoxide is cleared away from the extracellular space after approximately

3h. Superoxide secretion depends on the presence of superoxide-scavenging

enzyme superoxide dismutase, the age of the cells, the amount of calcium

oxalate crystals, and the temperature. Moreover, the effect of calcium

oxalate crystals was mimicked by phorbol 12-myristate 13-acetate. The

developed sensing system can be a useful tool for biologists investigating

nephrolithiasis at cellular level.

© 2009 Elsevier B.V. All rights reserved.

PMID: 20047824

>

> Hi all!

> Looking over my son's lab work that was done and am curious about his B-12 levels. The range is 211-946 pg/mL. His were 1018. The doc was not concerned and said it just show that they are working correctly. So it seems like he is an autistic child who does not have trouble with B-12. Yes? No?

>

> Is there anyone out there who has had their child's homcysteine levels checked? His were 6 and our doc said his was normal. According to Dr. Kendal http://charlottemetrohyperbarics.com/treatment-news/dr-kendal-stewart-seminar (part 3 @ 8:56) "7 is abnormal...5 is pathetic".

>

> We are going to follow up with our doc in two weeks to talk more about biomedical therapies, and I wanted to bring up what we have been reading, to her.

>

> Any insight from experienced veterans would be great!

>

> Cristine

>

[Guest guest]

I think that is much of the message. Our son rarely does B12 shots anymore but at the onset of our biomed journey they were life changing. He understood cause & effect in about 2 weeks and it improved many things. After about a year we stopped but gains stuck. I have not had cyanide levels checked but all people produce cyanide endegenously. We avoid the foods and he gets B12 (methyl) in his B complex twice weekly. The B 12 never seems to go down no matter what I do. We steer clear of almonds, spinach and cigarettes Sent from my iPhoneOn Jun 18, 2012, at 6:41 AM, Ratan Sharma

wrote:

Thanks .Please correct me if I am wrong in the following:The take home message seems to be that we must give B12 shots even if its serum level is high, because the methyl-cobal is needed for detoxifying the cyanide. And we should avoid cyanide foods. Even if the blood level of B12 is high, its low inside the cells as in there its being used up.Ratan.To: mb12valtrex From: karenhammes@...Date: Sat, 16 Jun 2012 08:31:17 -0700Subject: Fwd: Re: Are high B12 levels a good thing?

Here you go RatanSent from my iPhoneBegin forwarded message:Date: April 28, 2012 2:26:42 PM EDTTo: mb12valtrex Subject: Re: Are high B12 levels a good thing?Reply-To: mb12valtrex

,

Hopefully, this old post of mine on the TLO listserve will be helpful in assessing the B12 issues. Also, when people are in oxidative stress (which oxalate can cause), it is not unusual for the cells to get shifted to preferring transsulfuration to remethylation, and the evidence is a lowering of plasma homocysteine.

When cyanocobalamin gets high in blood, it can mean that intracellularly, methyl and hydroxycobalamin can be quite low. Blood levels are tricky if you don't know the rules about their interpretation.

susan

Listmates,

Ten years ago Rosemary Waring found that in autism that there was very

strong evidence of rhodanese dysfunction. Rhodanese is the mitochondrial

enzyme that detoxifies cyanide by forming thiocyanate from thiosulfate.

Here is some data from her paper, "Sulphur metabolism in Autism" from the

Journal of Nutritional and Environmental Medicine (2000) 10, 25-32:

Autism(n=232) Controls (n=68)

Protein 103.2 64.5

Sulphite 106.9 7.1

Thiosulphate 130.8 18.6

Thiocyanate 6.4 44.0

Sulphate 6819.0 3030.8

In the paper, she discusses the role of rhodanese and why it could be

important.

Rhodanese converts thiosulphate to thiocyanate, so the ratio of these two

compounds helps to assess the function of rhodanese. In autism, that ratio

is 20.4. In her control population, the ratio was 0.42. That means the

ratio was 49 times normal in autism....a strong indication that this enzyme

was inhibited in this very large sample population.

When this enzyme isn't working, the burden is put upon methyl or

hydroxycobalamin to detoxify the cyanide by forming cyanocobalamin. This

conversion that becomes necessary with depressed rhodanese activity might

raise serum cyanocobalamin levels, but it would also deplete

methylcobalamin. Those relationships are nicely illustrated in the first

study I've put below which you can read for free

at: http://ndt.oxfordjournals.org/content/12/8/1622.long.

This mechanism could furnish a very good reason to explain how methylB12

shots have done so much good in autism. By using up methylcobalamin, large

amounts of cyanide could depress methionine synthase activity because of

shunting its cofactor instead to the formation of cyanocobalamin. An

evidence that this has happened would be elevated blood cyanocobalamin

levels, or changed ratios of the various cobalamins in serum, as they found

in the study I already referenced, looking at this issue in hemodialysis

patients.

Knowing this vulnerability in autism provides a good reason for avoiding

high cyanide foods and to keep children or others with these issues away

from smoking (which is a huge source of cyanide).

The CDC's agency on toxic compounds has the following limited information:

>Certain bacteria, fungi, and algae can produce cyanide, and cyanide is

>found in a number of foods and plants. In certain plant foods, including

>almonds, millet sprouts, lima beans, soy, spinach, bamboo shoots, and

>cassava roots (which are a major source of food in tropical countries),

>cyanides occur naturally as part of sugars or other naturally-occurring

>compounds.

I am in the process of finding if anyone has made a more comprehensive list

of the cyanide content of foods but so far, the information is limited

except to suspect that nuts and seeds tend to be high in cyanide. The

biggest dietary source that has caused obvious problems in large

populations is cassava, from which tapioca is made. Our oxalate project at

ARI will try and get tapioca starch flour tested as soon as possible to see

if the process of extracting the starch is as effective in removing cyanide

as it is effective in removing most of the oxalate.

People should also be aware that this depression of rhodanese could be

brought on by exposures to high levels of oxalate. How is that?

The second article below found that rhodanese messenger RNA levels and

proteins levels were depressed in hemodialysis patients at the same time

that cell reactive oxygen species were increased and superoxide levels were

increased, and this was associated with mortality in these patients.

Reactive oxygen species and elevated superoxide levels both can be CAUSED

by elevated oxalate levels (59 articles in pubmed looking at this!) which

makes sense as being relevant because oxalate levels increase over time in

hemodialysis patients because the dialysis is so inferior to healthy

kidneys in removing oxalate. That is why oxalate is considered to be a

major toxin in uremic patients, as is discussed in the third article below.

What are the symptoms of cyanide poisoning?

Look here:

http://www.bt.cdc.gov/agent/cyanide/basics/facts.asp

Basically, what it says is that cyanide impairs the use of oxygen, so that

the parts of the body most affected are those that use lots of oxygen, like

the heart and brain.

Also, cyanide can cause visual field changes:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1291478/pdf/jrsocmed00165-0053.pdf

The visual field changes in patients with tobacco

amblyopia are characteristic. They consist of a

centrocaecal scotoma, usually bilateral though not

necessarily equal on the two sides. The scotoma is

horizontally oval with a sloping edge and is most

easily detected by a reduced stimulus such as a red

or small white object. The defect for colour exceeds

that for white and there are usually two definite

nuclei within the scotoma on the horizontal meridian.

An impairment of the temporal colour fields exists

within the 300 circle and in more advanced cases a

similar defect is also seen to a small white test

object2.

It does concern me that some children with autism are eating large amounts

of products made of almonds, and some are also eating spinach (both whose

high oxalate content might further impair rhodanese furnishing a double

whammy). It equally concerns me that if millet sprouts are high, then

possibly the act of sprouting seeds may increase cyanide when people were

hoping it would decrease oxalate. So far, we haven't been finding that

sprouting is making the oxalate go down, and it might be making the oxalate

level higher, but we still need to test a lot more seeds that way.

I hope this information is of interest and helpful.

Nephrol Dial Transplant. 1997 Aug;12(8):1622-8.

Abnormal cyanide metabolism in uraemic patients.

Koyama K, Yoshida A, Takeda A, Morozumi K, Fujinami T, Tanaka N.

Division of Nephrology, Nagoya Daini Red Cross Hospital, Japan.

Erratum in:

Nephrol Dial Transplant 1998 Mar;13(3):819.

Abstract

BACKGROUND: We previously investigated the factors involved in uraemic

neuropathy in patients undergoing regular haemodialysis and found a

significant relationship between the severity of vibration sensation

impairment and the patients' smoking habits. The administration of

methylcobalamin markedly improved the severity of uraemic neuropathy in

terms of vibration perception thresholds. We presumed that abnormal cyanide

metabolism is involved in the development of uraemic neuropathy.

METHODS: Serum levels of thiocyanate (SCN-), the detoxication product of

cyanide, were determined in 12 patients with preterminal chronic renal

failure (PCRF), 30 patients undergoing regular haemodialysis (HD patients),

and 13 healthy volunteers as a control group. Nine of the 30 HD patients

were smokers. In addition, in 10 HD patients without smoking habits and 10

non-smoking healthy volunteers, the proportion of each vitamin B12 analogue

in total vitamin B12 was estimated.

RESULTS: The mean serum SCN- level of the 12 PCRF patients (5.1 +/- 1.5

micrograms/ml) was significantly higher than that of the control (2.8 +/-

0.9 micrograms/ml) (P < 0.01). The mean SCN- level before haemodialysis in

the 21 non-smoking HD patients was identical to that in the PCRF group,

whereas the level in the nine smoking HD patients (7.2 +/- 1.8

micrograms/ml) significantly higher than that in the non-smoking subgroup

(P < 0.01). In 16 HD patients with methylcobalamin treatment, serum SCN-

levels were lower than in those without methylcobalamin treatment (4.5 +/-

0.5 micrograms/ml in non-smoking subgroup, P < 0.05). And in the

methylcobalamin-treated subgroup (n = 5), the proportion of each vitamin

B12 analogue in total vitamin B12 was normal. In the untreated subgroup (n

= 5), the proportion of cyanocobalamin fraction (10.5 +/- 2.6%) was as high

as the level in Leber's disease patients, while the proportion of

methylcobalamin fraction was low. And the serum cyanocobalamin level was

higher in the treated subgroup.

CONCLUSION: In uraemic patients, cyanide detoxication capability is

impaired because of a reduced SCN- clearance, and increased cyanocobalamin

synthesis indicates elevation of cyanide pool, which would be related to

the development of uraemic neuropathy. Methylcobalamin was considered to be

utilized in cyanide detoxication process via cyanocobalamin synthesis.

PMID: 9269639

Clin Biochem. 2010 Jan;43(1-2):95-101. Epub 2009 Aug 18.

Low expression of thiosulfate sulfurtransferase (rhodanese) predicts

mortality in hemodialysis patients.

Krueger K, Koch K, Jühling A, Tepel M, Scholze A.

Medizinische Klinik, Nephrologie, Charité Campus lin,

Hindenburgdamm 30, 12200 Berlin, Germany.

Abstract

OBJECTIVES: To test the hypothesis that impaired expression of the

thiosulfate sulfurtransferase rhodanese is associated with oxidative stress

and may predict mortality in hemodialysis patients.

DESIGN AND METHODS: Sixty-two hemodialysis patients were investigated to

determine protein and mRNA expression of rhodanese in monocytes. Whole cell

reactive oxygen species and mitochondrial superoxide production were

measured by fluorescence spectrophotometry.

RESULTS: Compared to healthy subjects, hemodialysis patients showed

significantly lower rhodanese mRNA and protein expression and significantly

increased reactive oxygen species. Lower rhodanese protein expression was

significantly associated with higher mitochondrial superoxide production.

The hazard ratio for mortality in hemodialysis patients with rhodanese mRNA

below compared to patients above the median was 2.22. Survival was shorter

with rhodanese mRNA below compared to patients above the median.

CONCLUSION: Impaired rhodanese expression is associated with increased

whole cell reactive oxygen species as well as higher mitochondrial

superoxide production and predicts mortality in hemodialysis patients.

Copyright 2009

Vnitr Lek. 2010 Jul;56(7):695-701.

[Oxalic acid--important uremic toxin]

[Article in Czech]

Mydlík M, Derzsiová K.

IV. interná klinika Lekárskej fakulty UPJS a FN L, Pasteura, Kosice,

Slovenská republika.

Abstract

INTRODUCTION: Oxalic acid is thought to be a significant uremic toxin that

participates in the pathogenesis of uremic syndrome. AIM OF THE STUDY was

to summarise results which we obtained during the study ofoxalic acid in

biological fluids (plasma, saliva, urine and dialysate) in patients

suffering from chronic kidney diseases (CKD), stage 3-5 and after renal

transplantation.

PATIENTS AND METHODS: In the retrospective study were investigated 28

healthy subjects, 112 CKD stage 1-4 patients, 39 haemodialysis patients and

27 CAPD patients. Besides 21 patients were investigated after renal

transplantation. We used the following therapeutic methods: maximal water

diuresis, diet with low (2g/day) and high (15g/day) sodium chloride intake,

administration intravenous furosemide (20mg) and renal replacement therapy

[CAPD, haemodialysis (HD), haemofiltration (HF) and postdilution

haemodiafiltration (HDF)] and renal transplantation. Oxalic acid was

determined by spectrophotometric method using oxalate oxidase which is free

from vitamin C interference. Vitamin C was determined by spectrophotometric

method.

RESULTS: In CKD patients and those after renal transplantation direct

relationships between plasma oxalic acid and serum creatinine were found (r

= 0.904 and 0.943, respectively, P < 0.001). Despite of high plasma oxalic

acid in uremic patients (23.1 +/- 10 micromol/l), there was no significant

difference in salivary oxalic acid between control subjects (126.5 +/- 18

micromol/l) and CKD stage 3-4 patients (133.9 +/- 23.7 micromol/I). The

urinary excretion of oxalic acid during maximal water diuresis in healthy

subjects (n = 15) (from 37.5 +/- 17.4 to 110.2 +/- 49.3 micromol/4 hours)

and after intravenous furosemide (CKD stage 3-4, n = 15) (from 34.5 +/- 5.5

to 66.7 +/- 8.1 micromol/3 hours) increased significantly, but was not

affected by high intake of NaCI in diet (CKD stage 3-4, n = 12). One tablet

of Sorbifer Durules containing 100 mg Fe2+ and 60 mg vitamin C did not lead

to further increase of uremic hyperoxalemia in haemodialysis patients.

Four-hour HD, H F and HDF led to the significant decrease of plasma oxalic

acid, but the most significant decrease was observed during HDF (63.3%).

CONCLUSION: The results of this study indicate, that renal replacement

therapy is not effective for permanent reduction of elevated plasma levels

of oxalic acid--important uremic toxin.

PMID: 20842915

Biosens Bioelectron. 2010 Mar 15;25(7):1729-34. Epub 2009 Dec 22.

Effect of calcium oxalate on renal cells as revealed by real-time

measurement of extracellular oxidative burst.

Gáspár S, Niculi e C, Cucu D, Marcu I.

International Centre of Biodynamics, 1B Intrarea Portocalelor Street,

060101 Bucharest, Romania. sgaspar@...

Abstract

Calcium oxalate is one of the main constituents of kidney stones and has a

proved deleterious effect on renal cells that is mediated by oxidative

stress. However, the subcellular source of this oxidative stress, and

whether it is extending to the extracellular space or not, is still

disputed. Therefore, an electrochemical superoxide biosensor was

constructed, positioned above A6 renal cells, and used to measure in

real-time the extracellular oxidative burst following addition of calcium

oxalate crystals. It was observed that A6 cells do secrete superoxide into

their extracellular space in few minutes after encountering calcium oxalate

crystals. The amount of released superoxide peaks at about 20 min.

Superoxide is cleared away from the extracellular space after approximately

3h. Superoxide secretion depends on the presence of superoxide-scavenging

enzyme superoxide dismutase, the age of the cells, the amount of calcium

oxalate crystals, and the temperature. Moreover, the effect of calcium

oxalate crystals was mimicked by phorbol 12-myristate 13-acetate. The

developed sensing system can be a useful tool for biologists investigating

nephrolithiasis at cellular level.

© 2009 Elsevier B.V. All rights reserved.

PMID: 20047824

>

> Hi all!

> Looking over my son's lab work that was done and am curious about his B-12 levels. The range is 211-946 pg/mL. His were 1018. The doc was not concerned and said it just show that they are working correctly. So it seems like he is an autistic child who does not have trouble with B-12. Yes? No?

>

> Is there anyone out there who has had their child's homcysteine levels checked? His were 6 and our doc said his was normal. According to Dr. Kendal http://charlottemetrohyperbarics.com/treatment-news/dr-kendal-stewart-seminar (part 3 @ 8:56) "7 is abnormal...5 is pathetic".

>

> We are going to follow up with our doc in two weeks to talk more about biomedical therapies, and I wanted to bring up what we have been reading, to her.

>

> Any insight from experienced veterans would be great!

>

> Cristine

>

[Guest guest]

I think that is much of the message. Our son rarely does B12 shots anymore but at the onset of our biomed journey they were life changing. He understood cause & effect in about 2 weeks and it improved many things. After about a year we stopped but gains stuck. I have not had cyanide levels checked but all people produce cyanide endegenously. We avoid the foods and he gets B12 (methyl) in his B complex twice weekly. The B 12 never seems to go down no matter what I do. We steer clear of almonds, spinach and cigarettes Sent from my iPhoneOn Jun 18, 2012, at 6:41 AM, Ratan Sharma

wrote:

Thanks .Please correct me if I am wrong in the following:The take home message seems to be that we must give B12 shots even if its serum level is high, because the methyl-cobal is needed for detoxifying the cyanide. And we should avoid cyanide foods. Even if the blood level of B12 is high, its low inside the cells as in there its being used up.Ratan.To: mb12valtrex From: karenhammes@...Date: Sat, 16 Jun 2012 08:31:17 -0700Subject: Fwd: Re: Are high B12 levels a good thing?

Here you go RatanSent from my iPhoneBegin forwarded message:Date: April 28, 2012 2:26:42 PM EDTTo: mb12valtrex Subject: Re: Are high B12 levels a good thing?Reply-To: mb12valtrex

,

Hopefully, this old post of mine on the TLO listserve will be helpful in assessing the B12 issues. Also, when people are in oxidative stress (which oxalate can cause), it is not unusual for the cells to get shifted to preferring transsulfuration to remethylation, and the evidence is a lowering of plasma homocysteine.

When cyanocobalamin gets high in blood, it can mean that intracellularly, methyl and hydroxycobalamin can be quite low. Blood levels are tricky if you don't know the rules about their interpretation.

susan

Listmates,

Ten years ago Rosemary Waring found that in autism that there was very

strong evidence of rhodanese dysfunction. Rhodanese is the mitochondrial

enzyme that detoxifies cyanide by forming thiocyanate from thiosulfate.

Here is some data from her paper, "Sulphur metabolism in Autism" from the

Journal of Nutritional and Environmental Medicine (2000) 10, 25-32:

Autism(n=232) Controls (n=68)

Protein 103.2 64.5

Sulphite 106.9 7.1

Thiosulphate 130.8 18.6

Thiocyanate 6.4 44.0

Sulphate 6819.0 3030.8

In the paper, she discusses the role of rhodanese and why it could be

important.

Rhodanese converts thiosulphate to thiocyanate, so the ratio of these two

compounds helps to assess the function of rhodanese. In autism, that ratio

is 20.4. In her control population, the ratio was 0.42. That means the

ratio was 49 times normal in autism....a strong indication that this enzyme

was inhibited in this very large sample population.

When this enzyme isn't working, the burden is put upon methyl or

hydroxycobalamin to detoxify the cyanide by forming cyanocobalamin. This

conversion that becomes necessary with depressed rhodanese activity might

raise serum cyanocobalamin levels, but it would also deplete

methylcobalamin. Those relationships are nicely illustrated in the first

study I've put below which you can read for free

at: http://ndt.oxfordjournals.org/content/12/8/1622.long.

This mechanism could furnish a very good reason to explain how methylB12

shots have done so much good in autism. By using up methylcobalamin, large

amounts of cyanide could depress methionine synthase activity because of

shunting its cofactor instead to the formation of cyanocobalamin. An

evidence that this has happened would be elevated blood cyanocobalamin

levels, or changed ratios of the various cobalamins in serum, as they found

in the study I already referenced, looking at this issue in hemodialysis

patients.

Knowing this vulnerability in autism provides a good reason for avoiding

high cyanide foods and to keep children or others with these issues away

from smoking (which is a huge source of cyanide).

The CDC's agency on toxic compounds has the following limited information:

>Certain bacteria, fungi, and algae can produce cyanide, and cyanide is

>found in a number of foods and plants. In certain plant foods, including

>almonds, millet sprouts, lima beans, soy, spinach, bamboo shoots, and

>cassava roots (which are a major source of food in tropical countries),

>cyanides occur naturally as part of sugars or other naturally-occurring

>compounds.

I am in the process of finding if anyone has made a more comprehensive list

of the cyanide content of foods but so far, the information is limited

except to suspect that nuts and seeds tend to be high in cyanide. The

biggest dietary source that has caused obvious problems in large

populations is cassava, from which tapioca is made. Our oxalate project at

ARI will try and get tapioca starch flour tested as soon as possible to see

if the process of extracting the starch is as effective in removing cyanide

as it is effective in removing most of the oxalate.

People should also be aware that this depression of rhodanese could be

brought on by exposures to high levels of oxalate. How is that?

The second article below found that rhodanese messenger RNA levels and

proteins levels were depressed in hemodialysis patients at the same time

that cell reactive oxygen species were increased and superoxide levels were

increased, and this was associated with mortality in these patients.

Reactive oxygen species and elevated superoxide levels both can be CAUSED

by elevated oxalate levels (59 articles in pubmed looking at this!) which

makes sense as being relevant because oxalate levels increase over time in

hemodialysis patients because the dialysis is so inferior to healthy

kidneys in removing oxalate. That is why oxalate is considered to be a

major toxin in uremic patients, as is discussed in the third article below.

What are the symptoms of cyanide poisoning?

Look here:

http://www.bt.cdc.gov/agent/cyanide/basics/facts.asp

Basically, what it says is that cyanide impairs the use of oxygen, so that

the parts of the body most affected are those that use lots of oxygen, like

the heart and brain.

Also, cyanide can cause visual field changes:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1291478/pdf/jrsocmed00165-0053.pdf

The visual field changes in patients with tobacco

amblyopia are characteristic. They consist of a

centrocaecal scotoma, usually bilateral though not

necessarily equal on the two sides. The scotoma is

horizontally oval with a sloping edge and is most

easily detected by a reduced stimulus such as a red

or small white object. The defect for colour exceeds

that for white and there are usually two definite

nuclei within the scotoma on the horizontal meridian.

An impairment of the temporal colour fields exists

within the 300 circle and in more advanced cases a

similar defect is also seen to a small white test

object2.

It does concern me that some children with autism are eating large amounts

of products made of almonds, and some are also eating spinach (both whose

high oxalate content might further impair rhodanese furnishing a double

whammy). It equally concerns me that if millet sprouts are high, then

possibly the act of sprouting seeds may increase cyanide when people were

hoping it would decrease oxalate. So far, we haven't been finding that

sprouting is making the oxalate go down, and it might be making the oxalate

level higher, but we still need to test a lot more seeds that way.

I hope this information is of interest and helpful.

Nephrol Dial Transplant. 1997 Aug;12(8):1622-8.

Abnormal cyanide metabolism in uraemic patients.

Koyama K, Yoshida A, Takeda A, Morozumi K, Fujinami T, Tanaka N.

Division of Nephrology, Nagoya Daini Red Cross Hospital, Japan.

Erratum in:

Nephrol Dial Transplant 1998 Mar;13(3):819.

Abstract

BACKGROUND: We previously investigated the factors involved in uraemic

neuropathy in patients undergoing regular haemodialysis and found a

significant relationship between the severity of vibration sensation

impairment and the patients' smoking habits. The administration of

methylcobalamin markedly improved the severity of uraemic neuropathy in

terms of vibration perception thresholds. We presumed that abnormal cyanide

metabolism is involved in the development of uraemic neuropathy.

METHODS: Serum levels of thiocyanate (SCN-), the detoxication product of

cyanide, were determined in 12 patients with preterminal chronic renal

failure (PCRF), 30 patients undergoing regular haemodialysis (HD patients),

and 13 healthy volunteers as a control group. Nine of the 30 HD patients

were smokers. In addition, in 10 HD patients without smoking habits and 10

non-smoking healthy volunteers, the proportion of each vitamin B12 analogue

in total vitamin B12 was estimated.

RESULTS: The mean serum SCN- level of the 12 PCRF patients (5.1 +/- 1.5

micrograms/ml) was significantly higher than that of the control (2.8 +/-

0.9 micrograms/ml) (P < 0.01). The mean SCN- level before haemodialysis in

the 21 non-smoking HD patients was identical to that in the PCRF group,

whereas the level in the nine smoking HD patients (7.2 +/- 1.8

micrograms/ml) significantly higher than that in the non-smoking subgroup

(P < 0.01). In 16 HD patients with methylcobalamin treatment, serum SCN-

levels were lower than in those without methylcobalamin treatment (4.5 +/-

0.5 micrograms/ml in non-smoking subgroup, P < 0.05). And in the

methylcobalamin-treated subgroup (n = 5), the proportion of each vitamin

B12 analogue in total vitamin B12 was normal. In the untreated subgroup (n

= 5), the proportion of cyanocobalamin fraction (10.5 +/- 2.6%) was as high

as the level in Leber's disease patients, while the proportion of

methylcobalamin fraction was low. And the serum cyanocobalamin level was

higher in the treated subgroup.

CONCLUSION: In uraemic patients, cyanide detoxication capability is

impaired because of a reduced SCN- clearance, and increased cyanocobalamin

synthesis indicates elevation of cyanide pool, which would be related to

the development of uraemic neuropathy. Methylcobalamin was considered to be

utilized in cyanide detoxication process via cyanocobalamin synthesis.

PMID: 9269639

Clin Biochem. 2010 Jan;43(1-2):95-101. Epub 2009 Aug 18.

Low expression of thiosulfate sulfurtransferase (rhodanese) predicts

mortality in hemodialysis patients.

Krueger K, Koch K, Jühling A, Tepel M, Scholze A.

Medizinische Klinik, Nephrologie, Charité Campus lin,

Hindenburgdamm 30, 12200 Berlin, Germany.

Abstract

OBJECTIVES: To test the hypothesis that impaired expression of the

thiosulfate sulfurtransferase rhodanese is associated with oxidative stress

and may predict mortality in hemodialysis patients.

DESIGN AND METHODS: Sixty-two hemodialysis patients were investigated to

determine protein and mRNA expression of rhodanese in monocytes. Whole cell

reactive oxygen species and mitochondrial superoxide production were

measured by fluorescence spectrophotometry.

RESULTS: Compared to healthy subjects, hemodialysis patients showed

significantly lower rhodanese mRNA and protein expression and significantly

increased reactive oxygen species. Lower rhodanese protein expression was

significantly associated with higher mitochondrial superoxide production.

The hazard ratio for mortality in hemodialysis patients with rhodanese mRNA

below compared to patients above the median was 2.22. Survival was shorter

with rhodanese mRNA below compared to patients above the median.

CONCLUSION: Impaired rhodanese expression is associated with increased

whole cell reactive oxygen species as well as higher mitochondrial

superoxide production and predicts mortality in hemodialysis patients.

Copyright 2009

Vnitr Lek. 2010 Jul;56(7):695-701.

[Oxalic acid--important uremic toxin]

[Article in Czech]

Mydlík M, Derzsiová K.

IV. interná klinika Lekárskej fakulty UPJS a FN L, Pasteura, Kosice,

Slovenská republika.

Abstract

INTRODUCTION: Oxalic acid is thought to be a significant uremic toxin that

participates in the pathogenesis of uremic syndrome. AIM OF THE STUDY was

to summarise results which we obtained during the study ofoxalic acid in

biological fluids (plasma, saliva, urine and dialysate) in patients

suffering from chronic kidney diseases (CKD), stage 3-5 and after renal

transplantation.

PATIENTS AND METHODS: In the retrospective study were investigated 28

healthy subjects, 112 CKD stage 1-4 patients, 39 haemodialysis patients and

27 CAPD patients. Besides 21 patients were investigated after renal

transplantation. We used the following therapeutic methods: maximal water

diuresis, diet with low (2g/day) and high (15g/day) sodium chloride intake,

administration intravenous furosemide (20mg) and renal replacement therapy

[CAPD, haemodialysis (HD), haemofiltration (HF) and postdilution

haemodiafiltration (HDF)] and renal transplantation. Oxalic acid was

determined by spectrophotometric method using oxalate oxidase which is free

from vitamin C interference. Vitamin C was determined by spectrophotometric

method.

RESULTS: In CKD patients and those after renal transplantation direct

relationships between plasma oxalic acid and serum creatinine were found (r

= 0.904 and 0.943, respectively, P < 0.001). Despite of high plasma oxalic

acid in uremic patients (23.1 +/- 10 micromol/l), there was no significant

difference in salivary oxalic acid between control subjects (126.5 +/- 18

micromol/l) and CKD stage 3-4 patients (133.9 +/- 23.7 micromol/I). The

urinary excretion of oxalic acid during maximal water diuresis in healthy

subjects (n = 15) (from 37.5 +/- 17.4 to 110.2 +/- 49.3 micromol/4 hours)

and after intravenous furosemide (CKD stage 3-4, n = 15) (from 34.5 +/- 5.5

to 66.7 +/- 8.1 micromol/3 hours) increased significantly, but was not

affected by high intake of NaCI in diet (CKD stage 3-4, n = 12). One tablet

of Sorbifer Durules containing 100 mg Fe2+ and 60 mg vitamin C did not lead

to further increase of uremic hyperoxalemia in haemodialysis patients.

Four-hour HD, H F and HDF led to the significant decrease of plasma oxalic

acid, but the most significant decrease was observed during HDF (63.3%).

CONCLUSION: The results of this study indicate, that renal replacement

therapy is not effective for permanent reduction of elevated plasma levels

of oxalic acid--important uremic toxin.

PMID: 20842915

Biosens Bioelectron. 2010 Mar 15;25(7):1729-34. Epub 2009 Dec 22.

Effect of calcium oxalate on renal cells as revealed by real-time

measurement of extracellular oxidative burst.

Gáspár S, Niculi e C, Cucu D, Marcu I.

International Centre of Biodynamics, 1B Intrarea Portocalelor Street,

060101 Bucharest, Romania. sgaspar@...

Abstract

Calcium oxalate is one of the main constituents of kidney stones and has a

proved deleterious effect on renal cells that is mediated by oxidative

stress. However, the subcellular source of this oxidative stress, and

whether it is extending to the extracellular space or not, is still

disputed. Therefore, an electrochemical superoxide biosensor was

constructed, positioned above A6 renal cells, and used to measure in

real-time the extracellular oxidative burst following addition of calcium

oxalate crystals. It was observed that A6 cells do secrete superoxide into

their extracellular space in few minutes after encountering calcium oxalate

crystals. The amount of released superoxide peaks at about 20 min.

Superoxide is cleared away from the extracellular space after approximately

3h. Superoxide secretion depends on the presence of superoxide-scavenging

enzyme superoxide dismutase, the age of the cells, the amount of calcium

oxalate crystals, and the temperature. Moreover, the effect of calcium

oxalate crystals was mimicked by phorbol 12-myristate 13-acetate. The

developed sensing system can be a useful tool for biologists investigating

nephrolithiasis at cellular level.

© 2009 Elsevier B.V. All rights reserved.

PMID: 20047824

>

> Hi all!

> Looking over my son's lab work that was done and am curious about his B-12 levels. The range is 211-946 pg/mL. His were 1018. The doc was not concerned and said it just show that they are working correctly. So it seems like he is an autistic child who does not have trouble with B-12. Yes? No?

>

> Is there anyone out there who has had their child's homcysteine levels checked? His were 6 and our doc said his was normal. According to Dr. Kendal http://charlottemetrohyperbarics.com/treatment-news/dr-kendal-stewart-seminar (part 3 @ 8:56) "7 is abnormal...5 is pathetic".

>

> We are going to follow up with our doc in two weeks to talk more about biomedical therapies, and I wanted to bring up what we have been reading, to her.

>

> Any insight from experienced veterans would be great!

>

> Cristine

>