CFS,mitochondrial diease, autism

richvank

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Carnitine depletion in HIV

Hi Rich Thank you so much for sharing this information,

I'm trying to understand how HIV depletes carnitine ?

you said quote "The glutathione depletin, in my hypothesis, also leads to a partial block in the methylation cycle, and two of the consequences of the low resulting methylation capacity are low production of carnitine and coenzyme Q-10, both of which require methylation, and both of which are needed by the mitochondria."

Glutathione is a common deficiency with HIV therefore could the partial methylation cycle block/low methylation also explain how HIV depletes carnitine ?

Many Thanks
Rosemary
Hi, Rosemary.

Yes, I think that is very likely. A few years ago I gave a talk about this hypothesis to a group in which Dr. Ray Stricker was present. Dr. Stricker has considerable experience in treating both Lyme disease and HIV, practicing in San Francisco. Dr. Stricker asked me if this mechanism occurs in HIV infection, and I said that I think it probably does, but probably has not been studied.

I think it still hasn't been studied very much, but please see the abstracts below with regard to the glutathione and methylation aspects in HIV. I don't know if anyone has made the connection between this and the observed low carnitine in HIV infected patients, but it is well known biochemically that carnitine is synthesized in the body by a methylation reaction on the amino acid lysine. Some carnitine also comes in with meat in the diet.

Best regards,

Rich


Neurology. 1995 Sep;45(9):1678-83.
Cerebrospinal fluid S-adenosylmethionine (SAMe) and glutathione concentrations in HIV infection: effect of parenteral treatment with SAMe.

Castagna A, Le Grazie C, Accordini A, Giulidori P, Cavalli G, Bottiglieri T, Lazzarin A.

Department of Infectious Diseases, S. Raffaele Hospital, Milan, Italy.
Abstract

The methylation and transsulfuration pathways are intimately linked and have been implicated in the progression of neurologic damage and immune cell depletion caused by human immunodeficiency virus (HIV) infection. We studied the following metabolites related to these pathways: S-adenosylmethionine (SAMe), homocysteine, cysteine, cysteinyl-glycine, and glutathione (GSH) in blood and CSF of 16 HIV-infected patients with neurologic complications and 20 HIV-negative control patients undergoing lumbar punctures for other medical reasons. We confirmed recent studies of decreased CSF SAMe concentrations in HIV infection and demonstrated that diastereomers of SAMe are present in CSF but not in plasma or erythrocytes from both HIV-infected and HIV-negative patients. In HIV-infected patients, CSF GSH and cysteinyl-glycine, but not homocysteine or cysteine, were significantly reduced. This is the first report of decreased CSF GSH induced by HIV infection. GSH has a regulatory effect on the synthesis of SAMe in hepatic tissue, and the same mechanism may also apply in the CNS. Administration of SAMe-butanedisulphonate, 800 mg/d intravenously for 14 days, was associated with significant increases in CSF SAMe and GSH. These findings have potentially important therapeutic implications for the use of SAMe in protecting against SAMe and GSH deficiency in the CNS of HIV-infected patients.

PMID: 7675226 [PubMed - indexed for MEDLINE]


Neurology. 2002 Mar 12;58(5):730-5.
Abnormal cobalamin-dependent transmethylation in AIDS-associated myelopathy.

Di Rocco A, Bottiglieri T, Werner P, Geraci A, Simpson D, Godbold J, Morgello S.

Department of Neurology, Albert Einstein College of Medicine and Beth Israel Medical Center, New York, NY 10003, USA. adirocco@aecom.yu.edu
Abstract

BACKGROUND: White matter vacuolization of the spinal cord is common in patients with AIDS and may lead to clinical manifestations of myelopathy. The pathogenesis of AIDS-associated myelopathy (AM) is unknown and may be related to metabolic abnormalities rather than to direct HIV infection. The striking pathologic similarity between AM and the vacuolar myelopathy associated with vitamin B(12) deficiency suggests that abnormal metabolism of the B(12)-dependent transmethylation pathway may be important in the pathogenesis of AM. METHODS: The authors compared S-adenosyl-methionine (SAM), methionine, homocysteine, and glutathione in serum and CSF of 15 patients with AM vs. 13 HIV-infected controls without myelopathy (HWM). They also compared the results with a non-HIV--infected reference population (NC). All patients had normal B(12), folate, and methylmalonic acid levels. RESULTS: There was a decrease in CSF SAM in the AM group compared with the HWM group (p < 0.0001) and the NC group (p < 0.0001). CSF SAM in the HWM group was also lower than that in the NC group (p = 0.015). Serum methionine was also reduced in serum of the myelopathic group compared with the NC group (p = 0.006). CONCLUSIONS: AM is associated with an abnormality of the vitamin B(12)-dependent transmethylation pathway.

PMID: 11889235 [PubMed - indexed for MEDLINE]
 

richvank

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Hi, Tania.

sorry I just remembered something.. it appears i did have it when a baby... I forgot what my mum had told me that i was unusual as a baby. She said i was amazingly good baby as she could just sit me in front of the tv and unlike all my 3 siblings (born after me) i just then wouldnt move all day, i'd be completely fixated on the TV!!. (this was before i was able to walk.. when a baby). So it appears by that, i must of had Asperger's even when a baby.

***O.K., so you developed Asperger's pretty early. I'm still going to guess that your brain was able to develop quite a bit before you got it, based on your mental capacity. I still think that the cases of severe autism result from very early interruption of the development of the brain, while cases of Asperger's result from later interference with brain development. It's too bad that being a "good" baby from the standpoint of not needing as much attention as normal doesn't always result in the most normally developed human being.

True.. i guess you understand completely how MTHFR polymorphism plays into glutathionine depletion. (my CFS specialist has sent me some great diagrams of the biochemisty of all that .. how the remethylation pathway runs into the transulphuration pathway all the way down to glutathione and where my polymorphism fits on all this, I tried to cut and paste it all here but it wont do that from my email).

***I'm familiar with those diagrams. In fact, if you look in my PowerPoints called "Methylation and Glutathione, Keys to CFS" at the website www.cfsresearch.org you will probably recognize the diagrams there.
MTHFR polymorphism is an important one, and there are several others involving other enyzmes in the methylation cycle and related pathways that can work together to cause a tendency toward developing dysfunction in this part of the metabolism. Dr. Amy Yasko offers a Nutrigenomic panel that characterizes quite a few of these possible polymorphisms.

It must of have had so severely depleted my folate levels that i had a child who was born with severe birth defects, caudal regression syndrome (similar to spina bifida) (i didnt have diabetes in pregnancy so her case was caused by the lack of folate due to the polymorphism). I had her when i was 19 yrs old. ...............

***I'm very sorry that this happened.

i only wonder why my methylation blocks if that is what it is.. are going on and off on and off.

***I think that actually happens in quite a few people who have CFS. I think it's caused by the glutathione level sort of teetering on the boundary between being adequate and being deficient, and various factors in a person's life can push it one way or the other, producing relapses and remissions. In many cases it gets lower over time, so that remissions don't occur, and the person remains chronically ill unless this problem is treated.

One would think the mono would of triggered off CFS seeing i had a block. i so wonder why not (if anything was going to trigger, one would think it would be mono).

***Yes, that is puzzling to me, too. Mono often does cause glutathione depletion and a partial methylation cycle block. I think that about 10% of all mono cases result in chronic illness (post-viral fatigue syndrome), and I think this is the mechanism.


Does stress and lack of sleep deplete glutathionine enough that it would make CFS come right back?

***Yes, I've received histories from many people who have CFS, and stress and lack of sleep appear to be very common causative triggers.

When ive got it again after remission as well as when i very first got it... it was both severe stress related as the very first initial trigger (after that anything esp physical doing things would trigger).
***This is very consistent with stories I've heard from many people who have CFS.

***Best regards,

***Rich
 

Rosemary

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Hi Rich,

Many Thanks for your response and I appreciate the abstracts..please let me know if you ever plan to do any talks in the UK !

The most common genetic mutation in my son's neurodegenerative condition is linked to HIV infection and the children are given carnitine supplementation, which slows down disease progression.

I found your comment very helpful ...about it being well known biochemically that carnitine is synthesized in the body by a methylation reaction on the amino acid lysine

I assume that lysine levels would also be low as a result of infection ? ...since carnitine is converted from lysine and methionine perhaps this explains why amino acid supplementation would be needed, in this case supplementing higher levels of lysine and methionine ?

of course this is providing that a genetic mutation/HIV infection isn't causing the inability to convert lysine and methionine to carnitine then I would assume that carnitine would be regarded as an essential nutrient ?

Any suggestions you may have would be kindly appreciated
Many Thanks again...Rosemary

Hi, Rosemary.

Yes, I think that is very likely. A few years ago I gave a talk about this hypothesis to a group in which Dr. Ray Stricker was present. Dr. Stricker has considerable experience in treating both Lyme disease and HIV, practicing in San Francisco. Dr. Stricker asked me if this mechanism occurs in HIV infection, and I said that I think it probably does, but probably has not been studied.

I think it still hasn't been studied very much, but please see the abstracts below with regard to the glutathione and methylation aspects in HIV. I don't know if anyone has made the connection between this and the observed low carnitine in HIV infected patients, but it is well known biochemically that carnitine is synthesized in the body by a methylation reaction on the amino acid lysine. Some carnitine also comes in with meat in the diet.

Best regards,

Rich


Neurology. 1995 Sep;45(9):1678-83.
Cerebrospinal fluid S-adenosylmethionine (SAMe) and glutathione concentrations in HIV infection: effect of parenteral treatment with SAMe.

Castagna A, Le Grazie C, Accordini A, Giulidori P, Cavalli G, Bottiglieri T, Lazzarin A.

Department of Infectious Diseases, S. Raffaele Hospital, Milan, Italy.
Abstract

The methylation and transsulfuration pathways are intimately linked and have been implicated in the progression of neurologic damage and immune cell depletion caused by human immunodeficiency virus (HIV) infection. We studied the following metabolites related to these pathways: S-adenosylmethionine (SAMe), homocysteine, cysteine, cysteinyl-glycine, and glutathione (GSH) in blood and CSF of 16 HIV-infected patients with neurologic complications and 20 HIV-negative control patients undergoing lumbar punctures for other medical reasons. We confirmed recent studies of decreased CSF SAMe concentrations in HIV infection and demonstrated that diastereomers of SAMe are present in CSF but not in plasma or erythrocytes from both HIV-infected and HIV-negative patients. In HIV-infected patients, CSF GSH and cysteinyl-glycine, but not homocysteine or cysteine, were significantly reduced. This is the first report of decreased CSF GSH induced by HIV infection. GSH has a regulatory effect on the synthesis of SAMe in hepatic tissue, and the same mechanism may also apply in the CNS. Administration of SAMe-butanedisulphonate, 800 mg/d intravenously for 14 days, was associated with significant increases in CSF SAMe and GSH. These findings have potentially important therapeutic implications for the use of SAMe in protecting against SAMe and GSH deficiency in the CNS of HIV-infected patients.

PMID: 7675226 [PubMed - indexed for MEDLINE]


Neurology. 2002 Mar 12;58(5):730-5.
Abnormal cobalamin-dependent transmethylation in AIDS-associated myelopathy.

Di Rocco A, Bottiglieri T, Werner P, Geraci A, Simpson D, Godbold J, Morgello S.

Department of Neurology, Albert Einstein College of Medicine and Beth Israel Medical Center, New York, NY 10003, USA. adirocco@aecom.yu.edu
Abstract

BACKGROUND: White matter vacuolization of the spinal cord is common in patients with AIDS and may lead to clinical manifestations of myelopathy. The pathogenesis of AIDS-associated myelopathy (AM) is unknown and may be related to metabolic abnormalities rather than to direct HIV infection. The striking pathologic similarity between AM and the vacuolar myelopathy associated with vitamin B(12) deficiency suggests that abnormal metabolism of the B(12)-dependent transmethylation pathway may be important in the pathogenesis of AM. METHODS: The authors compared S-adenosyl-methionine (SAM), methionine, homocysteine, and glutathione in serum and CSF of 15 patients with AM vs. 13 HIV-infected controls without myelopathy (HWM). They also compared the results with a non-HIV--infected reference population (NC). All patients had normal B(12), folate, and methylmalonic acid levels. RESULTS: There was a decrease in CSF SAM in the AM group compared with the HWM group (p < 0.0001) and the NC group (p < 0.0001). CSF SAM in the HWM group was also lower than that in the NC group (p = 0.015). Serum methionine was also reduced in serum of the myelopathic group compared with the NC group (p = 0.006). CONCLUSIONS: AM is associated with an abnormality of the vitamin B(12)-dependent transmethylation pathway.

PMID: 11889235 [PubMed - indexed for MEDLINE]
 

IntuneJune

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Fascinating thread. Mitochondrial disease

Fascinating thread. I have not been on much lately, not because my situation has imrpoved, to the contrary, I have developed a "primary immune dificiency" and have been on support boards for that.

I have been very suspicious of mitochrondial disease and came to and did a search and discovered this thread. Anyone ready to update their thoughts, progress??

June
 

Jenny

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Fascinating thread. I have not been on much lately, not because my situation has imrpoved, to the contrary, I have developed a "primary immune dificiency" and have been on support boards for that.

I have been very suspicious of mitochrondial disease and came to and did a search and discovered this thread. Anyone ready to update their thoughts, progress??

June
Hi June

Can I ask what kind of primary immune deficiency you have? Some of us on this board have Mannose Binding Lectin deficiency. Do you know if there's a message board for this?

Jenny
 
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I am very positive that this will be the right path to embark on. In fact, I think a lot of cases are classic EBV induced post-viral fatigue and glutathione depletion/methylation cycle block (with some co-infections), when I read the symptoms on the mito-disease website it's a very close match. If Doctor's routinely would test you for all the possible pathogens at play as well as all the deficiencies/mutations mentioned on the mito-disease website I believe they could help each patient much faster by tailoring therapy to those results instead of us having often to go by trial and error to find out which drugs/supps/immunmodulators help and stick. IMO the ignorance of patients metabolic and immune-system pathways by the current healthcare system comes close to criminal negligence - the research is there..
 
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Markmc said:

I think it is great frickly. What I great find!. Finally we know what it is? fantastic! I got a mitochrondrial disease probably. I have had this feeling everybody but me knew what the heck was going on anyways.....well that is stil the case, but at least it provides some idea they know what the heck is going on.

Can the people switch diagonosis, or how does that work? problematic I guess.

Seems like it is broken and can't be fixed though? Kind of strange why nobody is talking about it here though.

I posted a llink to the mitochondrial disease in the general news, we'll see what happens. I don't know if I gave you credit though. I'll edit that in.

--------------------------------------------------------------------------------

Woah! Back up a step! Mitochondrial dysfunction CAN be fixed! There is a new substance out you can buy called PQQ. You would
have to fix whatever caused the mitochondrial degeneration in the first place (this whole forum is about protocols for doing that) otherwise when you regen mitochondia they would be brought low also, but science is emerging in this area. EVERYONE GETS MITOCHONDRIAL DYSFUNCTION IF THEY LIVE LONG ENOUGH. So when it affects everyone, money is spent and answers are found. I think the difference between CFS and mitochondrial dysfunction
is -- age of onset!
 

IntuneJune

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Jenny, is it too late to reply???

I have common variable immune deficiency diagnosed by blood work, total IgG, IgG IgA, IgM, subclasses 1,2,3,4. I see an immunologist in Boston. I am on Hizentra, a subq infusion, that I can do myself at home. Cannot say my symptoms are any better, the fibro symptoms that is. I am getting fewer, less serious infections.

June
 

Jenny

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Jenny, is it too late to reply???

I have common variable immune deficiency diagnosed by blood work, total IgG, IgG IgA, IgM, subclasses 1,2,3,4. I see an immunologist in Boston. I am on Hizentra, a subq infusion, that I can do myself at home. Cannot say my symptoms are any better, the fibro symptoms that is. I am getting fewer, less serious infections.

June
Thanks June.