Re: Rich - Mitochondrial hypothesis

[Guest guest]

Hi Rich,

Regarding your mito. and CFS hypothesis, as well as the majority of the cfs

hypotheses I have read, I have one question that has troubled me for years.

Why is it that I can take one of Dr. Jay Goldstein's drugs and be symptom

free within 30 minutes. I built up a tolerance over weeks or a few months

to each of the drugs that worked but am puzzled as to how in minutes,

sometimes seconds, all physical symptoms can dissappear. My arms would

suddenly feel light as a feather (normal but when you've had this illness a

long time you forget how it really feels to be back to normal), my thinking

crystal clear, leg strength and muscle endurance back to normal, etc. If a

drug that supposedly works only on the brain can reverse all physical CFS

symptoms, then it seems to me that there is nothing physically wrong with my

muscles and that the problem is in the brain? What are your thoughts on

this? Regards, Steve B.

Re: Mitochondrial hypothesis

>

>

> Thanks for all the helpful information about mitochondrial disease.

>

> I would just like to say that I'm convinced that PWCs have

> mitochondrial dysfunction, but that in most cases, at the beginning

> at least, I don't believe it's due to problems in the mitochondrial

> or nuclear DNA. The reason is that many if not most PWCs were to

> all intents and purposes healthy at one time. They were not ill

> from birth. (I realize that some have been ill from birth, and I

> think these are the ones who should particularly check into the

> possibility that they have genetically based mitochondrial disease.)

>

> For those who were not ill from birth, I think the mitochondrial

> dysfunction arose because of partial blockades in the Krebs cycle

> or in the respiratory chain. These partial blockades may have a

> variety of sources. For the main subset, I suspect that

> glutathione depletion allowed a rise in the concentration of

> peroxynitrite, which is known to interact with several enzymes,

> including aconitase in the Krebs cycle. For some other PWCs, it

> could be that toxins from pathogens have reacted with enzymes to

> produce the partial blockades. For others, there may be an oxygen

> shortage, as Jim has hypothesized. For others, it could be that

> carbon monoxide is blocking the cytochrome oxidase enzymes. And so

> on. In all these cases, the mitochondria have all the appropriate

> hardware, as coded correctly by the genes, but the hardware is

> blocked by some monkey wrench.

>

> Another possibility is that even though the genes have the proper

> coding, the production of enough of the appropriate enzymes is

> blocked by the RNAse-L, which indiscriminately tears up the RNA

> that is carrying the code to the ribosomes so they can make the

> enzymes, in its effort to slow down the viruses. Again, the code

> could be correct, but just not able to be implemented at a

> sufficiently high rate, so there isn't enough of the mitochondrial

> enzymes to carry on metabolism at a normal rate.

>

> Beyond this, as a PWC remains ill for a long time, there is the

> possibility that the depletion of glutathione allows the buildup of

> oxidizing free radicals, which over time do damage to the

> mitochondrial DNA, as well as the nuclear DNA. If this happens,

> then the person would have a true genetically based mitochondrial

> disease.

>

> It could be that all these cases occur within the PWC population.

> Any thoughts on this?

>

> Rich

>

>

> > Jim and Jerry;

> >

> > While I have no quarrel with your NADH theory as it relates to

> > mitochondrial supplementation, I do have a problem with the

> following

> > hypothesis:

> >

> > " My own thinking is that the breakdown of the mitochondrial

> > processes is a result of lack of oxygen at the cell and/or an acidic

> pH

> > within the cell or mitochondria which interferes with the production

> of

> > ATP. "

> >

> > While in some cases, this hypothesis may well be true, it doesn't

> allow

> > for the fact that the " factory " itself (the mitochondria) may be

> > flawed. If there is an endemic flaw, then both the quantity and

> quality

> > of the citric acid cycle and the ATP cycle will be compromised!

> >

> > What I am trying to say here is that there can be damage to the

> > mitochondrion itself, damage caused either by the Mitochondria DNA

> > replication or the Nuclear DNA which affects the " control " of the

> > Mitochondrial function .... and directly affects the function of

> Complex

> > II of the mitochondrial process " factory " or " train " .

> >

> > The reason I came back to this list, at Christie's request, was to

> alert

> > everyone to the possibility of mitochondrial dysfunction as being

> the

> > " source " of the problem. Some may have viral source, or other

> sources,

> > but do not discount the possibility that the " factory " itself may be

> the

> > problem! I am including, below, " Criteria for Mito and Guidelines

> for

> > when to suspect Mito "

> >

> > Jean

> >

> > **********

> >

> > Criteria for Mitochondrial Disease

> >

> >

> > Think mitochondrial disease when:

> >

> > 1. A " common disease " has atypical features that set it apart from

> the

> > pack.

> > 2. Three or more organ systems are involved.

> > 3. Recurrent setbacks or flares in a chronic disease occur with

> > infections.

> >

> >

> > Diagnostic testing for mitochondrial disease:

> >

> > 1. Blood for mtDNA (PCR and Southern)

> > 2. Blood and CSF for Lactate and Pyruvate, or Brain MR

> > Spectroscopy.

> > 3. Urine Organic Acids (by GC/MS).

> > 4. Plasma and Urine Amino Acids.

> > 5. Blood and Urine Carnitine.

> > 6. Brain MRI.

> > 7. Muscle biopsy and skin biopsy:

> > * Neuropathology and Electron Microscopy

> > * Mitochondrial Electron Transport Studies

> > * Fresh (coupled) Mitochondrial Polargraphy

> > * Muscle mtDNA (PCR and Southern)

> >

> > ( Naviaux M.D., Ph.D.)

> >

> > As far as diagnostic tests go, they suggest you have the first 5

> before

> > going on, as these are relatively cheap and non-invasive and can

> give

> > you a good idea of whether you are going in the right direction.

> >

> >

> >

[Guest guest]

Rich,

I think #3 sounds like the most logical of the 3 possibilities. I believe

Goldstein thinks it has something to do with nitric oxide. One of the drugs

that temporarily eliminated my symptoms was Viagra which I believe works

through some nitric oxide process (this drug only eliminates symptoms for a

few hours and is not very useful for CFS). Other drugs that eliminated my

symptoms were Nimodipine (eliminated symptoms for 3-4 months), the calcium

channel blocker, dopamine nasal spray, and talwin (latter two worked about a

month each). I fall into a subset that rarely has flu-like symptoms (have

one cold maybe every 3 years on average) and I have no pain. I was told

that about 30% of PWC's fall into my subset. It's puzzling. I've seen so

many patients walk into Goldstein's office half dead and come out half an

hour later symptom-free. I even saw one go in there in a wheel chair and

later pushed the wheel chair out herself. Unfortunately, this type of

therapy is only effective on a temporary basis for the vast majority of

patients. I am currently 90% back to normal after being on Cheney's

protocol for more than a year and while his regimen takes much longer to

realize benefits, it appears to work on a long term basis. I am also just

over 3 months into his 6-month bovine growth factor / HGH protocol and am

hopeful this therapy may provide a permanent cure. I also had the ISAC test

done recently and it indicates I have an active infection (I suspect HHV6,

EB, or CMV). After I find out the type of infection I'll attack this

illness from another direction, either antivirals or antibiotics. Thanks

for your insightful input. Regards, Steve B.

Re: Rich - Mitochondrial hypothesis

>

> > Hi Rich,

> >

> > Regarding your mito. and CFS hypothesis, as well as the majority of

> the cfs

> > hypotheses I have read, I have one question that has troubled me for

> years.

> > Why is it that I can take one of Dr. Jay Goldstein's drugs and be

> symptom

> > free within 30 minutes. I built up a tolerance over weeks or a few

> months

> > to each of the drugs that worked but am puzzled as to how in

> minutes,

> > sometimes seconds, all physical symptoms can dissappear. My arms

> would

> > suddenly feel light as a feather (normal but when you've had this

> illness a

> > long time you forget how it really feels to be back to normal), my

> thinking

> > crystal clear, leg strength and muscle endurance back to normal,

> etc. If a

> > drug that supposedly works only on the brain can reverse all

> physical CFS

> > symptoms, then it seems to me that there is nothing physically wrong

> with my

> > muscles and that the problem is in the brain? What are your

> thoughts on

> > this? Regards, Steve B.

>

>

> Steve,

>

> That's an excellent question. I don't have an excellent answer for

> it, but that's never stopped me before!(:-)

>

> What I can do is toss out some possibilities for consideration:

>

> 1. Perhaps you are in a subset for which the problem does indeed

> originate in the brain. I'm convinced that there are at least several

> subsets, and I've also heard from people who were given a large number

> of different drugs by Dr. Goldstein, and none of them seemed to help,

> so they may have been in different subsets than you are. One problem

> with this explanation is that now you seem to be helped by other

> treatments that presumably operate on tissues beside the brain.

>

> 2. Perhaps the drug affected your perception, and didn't really

> correct the underlying causes, which were in other tissues. This one

> also seems to have a few problems. For example, if your muscles were

> weak before, and were not weak after the drug, this doesn't seem like

> something you could change simply by perception. How about immune

> dysfunction symptoms? Did you have those, and did they go away also?

> How about pain? Pain is one that I can imagine a brain-active drug

> could get rid of. But some of the others don't seem so easy.

>

> 3. Perhaps the drug really acted on other tissues in addition to the

> brain, even indirectly. If, for example, the drug acted upon the

> hypothalamus and induced some hormone secretion that speeded up the

> metabolism, say from the thyroid or the adrenals or both, then maybe

> the partial blockades were overcome for a while in all the tissues,

> and the ATP production speeded up, getting rid of a whole variety of

> symptoms. However, since the basic problems out in the tissues

> weren't corrected, eventually the hormonal surge either gave out or

> was no longer effective, and the ATP production dropped back down,

> bringing the symptoms back again. I guess I like this one the best.

>

> There may be other possibilities also. These are the only ones that

> occur to me right now. What do you think?

>

> Rich

>

>

>

>

>

>

>

> This list is intended for patients to share personal experiences with each

other, not to give medical advice. If you are interested in any treatment

discussed here, please consult your doctor.

>

[Guest guest]

> Hi Rich,

>

> Regarding your mito. and CFS hypothesis, as well as the majority of

the cfs

> hypotheses I have read, I have one question that has troubled me for

years.

> Why is it that I can take one of Dr. Jay Goldstein's drugs and be

symptom

> free within 30 minutes. I built up a tolerance over weeks or a few

months

> to each of the drugs that worked but am puzzled as to how in

minutes,

> sometimes seconds, all physical symptoms can dissappear. My arms

would

> suddenly feel light as a feather (normal but when you've had this

illness a

> long time you forget how it really feels to be back to normal), my

thinking

> crystal clear, leg strength and muscle endurance back to normal,

etc. If a

> drug that supposedly works only on the brain can reverse all

physical CFS

> symptoms, then it seems to me that there is nothing physically wrong

with my

> muscles and that the problem is in the brain? What are your

thoughts on

> this? Regards, Steve B.

Steve,

That's an excellent question. I don't have an excellent answer for

it, but that's never stopped me before!(:-)

What I can do is toss out some possibilities for consideration:

1. Perhaps you are in a subset for which the problem does indeed

originate in the brain. I'm convinced that there are at least several

subsets, and I've also heard from people who were given a large number

of different drugs by Dr. Goldstein, and none of them seemed to help,

so they may have been in different subsets than you are. One problem

with this explanation is that now you seem to be helped by other

treatments that presumably operate on tissues beside the brain.

2. Perhaps the drug affected your perception, and didn't really

correct the underlying causes, which were in other tissues. This one

also seems to have a few problems. For example, if your muscles were

weak before, and were not weak after the drug, this doesn't seem like

something you could change simply by perception. How about immune

dysfunction symptoms? Did you have those, and did they go away also?

How about pain? Pain is one that I can imagine a brain-active drug

could get rid of. But some of the others don't seem so easy.

3. Perhaps the drug really acted on other tissues in addition to the

brain, even indirectly. If, for example, the drug acted upon the

hypothalamus and induced some hormone secretion that speeded up the

metabolism, say from the thyroid or the adrenals or both, then maybe

the partial blockades were overcome for a while in all the tissues,

and the ATP production speeded up, getting rid of a whole variety of

symptoms. However, since the basic problems out in the tissues

weren't corrected, eventually the hormonal surge either gave out or

was no longer effective, and the ATP production dropped back down,

bringing the symptoms back again. I guess I like this one the best.

There may be other possibilities also. These are the only ones that

occur to me right now. What do you think?

Rich

[Guest guest]

Hi ,

What is the drug that you were prescribed that provided the

immediate relief (within 30 min.) Have many other PWCFS responded as

favorably to this drug? Also, how long lasting is the results?

All the best,

Jim

clements@...

> > > Jim and Jerry;

> > >

> > > While I have no quarrel with your NADH theory as it relates to

> > > mitochondrial supplementation, I do have a problem with the

> > following

> > > hypothesis:

> > >

> > > " My own thinking is that the breakdown of the mitochondrial

> > > processes is a result of lack of oxygen at the cell and/or an

acidic

> > pH

> > > within the cell or mitochondria which interferes with the

production

> > of

> > > ATP. "

> > >

> > > While in some cases, this hypothesis may well be true, it

doesn't

> > allow

> > > for the fact that the " factory " itself (the mitochondria) may be

> > > flawed. If there is an endemic flaw, then both the quantity and

> > quality

> > > of the citric acid cycle and the ATP cycle will be compromised!

> > >

> > > What I am trying to say here is that there can be damage to the

> > > mitochondrion itself, damage caused either by the Mitochondria

DNA

> > > replication or the Nuclear DNA which affects the " control " of

the

> > > Mitochondrial function .... and directly affects the function of

> > Complex

> > > II of the mitochondrial process " factory " or " train " .

> > >

> > > The reason I came back to this list, at Christie's request, was

to

> > alert

> > > everyone to the possibility of mitochondrial dysfunction as

being

> > the

> > > " source " of the problem. Some may have viral source, or other

> > sources,

> > > but do not discount the possibility that the " factory " itself

may be

> > the

> > > problem! I am including, below, " Criteria for Mito and

Guidelines

> > for

> > > when to suspect Mito "

> > >

> > > Jean

> > >

> > > **********

> > >

> > > Criteria for Mitochondrial Disease

> > >

> > >

> > > Think mitochondrial disease when:

> > >

> > > 1. A " common disease " has atypical features that set it apart

from

> > the

> > > pack.

> > > 2. Three or more organ systems are involved.

> > > 3. Recurrent setbacks or flares in a chronic disease occur with

> > > infections.

> > >

> > >

> > > Diagnostic testing for mitochondrial disease:

> > >

> > > 1. Blood for mtDNA (PCR and Southern)

> > > 2. Blood and CSF for Lactate and Pyruvate, or Brain MR

> > > Spectroscopy.

> > > 3. Urine Organic Acids (by GC/MS).

> > > 4. Plasma and Urine Amino Acids.

> > > 5. Blood and Urine Carnitine.

> > > 6. Brain MRI.

> > > 7. Muscle biopsy and skin biopsy:

> > > * Neuropathology and Electron Microscopy

> > > * Mitochondrial Electron Transport Studies

> > > * Fresh (coupled) Mitochondrial Polargraphy

> > > * Muscle mtDNA (PCR and Southern)

> > >

> > > ( Naviaux M.D., Ph.D.)

> > >

> > > As far as diagnostic tests go, they suggest you have the first 5

> > before

> > > going on, as these are relatively cheap and non-invasive and can

> > give

> > > you a good idea of whether you are going in the right direction.

> > >

> > >

> > >