Konynenburg comenta sobre la Q-10,
Publicado: 23 Dic 2009, 00:54
Konynenburg comenta hoy mismo sobre la coenzima Q-10 y menciona los tratamientos de Myhill, Cheney y Martin Pall en relación al suyo.
Hi, all.
Coenzyme Q-10 normally plays a couple of important roles in the cells. In the mitochondria, it serves as a receiver and transmitter of energetic electrons that are obtained from processing foods in the Krebs cycle and are given to the respiratory chain, so that the energy can be used to convert ADP back to ATP, which then supplies the energy to power a large number of biochemical reactions in the cells, including those involved in use of the muscles and those involved in sending nerve impulses. Heart muscle is particularly dependent on Co Q-10 because of its high demand for ATP. Co Q-10 is also part of the basic antioxidant network in the cells.
In CFS, coenzyme Q-10 was found to be low in the recent Maes et al. study, as well as in a study by Langsjoen et al. in 1993. I've also seen low values in quite a few test results that PWCs have sent to me. Based on my hypothesis (the GD--MCB hypothesis) and review of many lab test results that people have sent me, I believe that the direct reason Co Q-10 is low in CFS is that there is a partial block in the methylation cycle, so that the capacity to carry out methylation reactions is deficient. Methylation reactions are necessary to produce coenzyme Q-10 in the body.
The question of whether to supplement Co Q-10 in CFS is somewhat difficult to answer. Dr. Sarah Myhill recommends doing so, in combination with several other supplements to support the mitochondrial function (based primarily on the the book by Dr. Sinatra, a cardiologist), in those who test positively for mito dysfunction in the Acumen Lab tests. Other CFS specialists have also recommended Co Q-10 supplementation over the past few years, including Dr. Cheney.
Some PWCS report benefit from Co Q-10 supplementation, while others find that they cannot tolerate it. Some have tried Idebenone, instead, and found that they tolerated it better and benefited from it.
Dr. Cheney's views have changed since he started using the echocardiograph to decide what is beneficial and what is not in CFS. This new approach has caused him to switch his position on Co Q-10 supplementation in CFS, and he now opposes it. I have expressed my disagreement with Dr. Cheney's interpretation of his IVRT measurements on the echocardiograph a few times in the past, both to him and on internet boards. I don't believe that a measurement made a minute or a few minutes after administering a substance is a good indicator of how it will affect the biochemistry over the longer term.
Nevertheless, I share some of Dr. Cheney's thinking about the types of treatment that are beneficial. Both he and I are concerned that it's important to treat at the level of the root issues in CFS, rather than to focus on the downstream issues. He and I both believe that the body is set up to compensate for root issues by making downstream changes. If the body's compensations or adaptations are countered while the root issues are not dealt with, the treatment can actually do more harm than good. An example that Dr. Cheney has emphasized to me in our discussions is something he learned while he was in training. If a person has heart failure (i.e. inability of the heart to pump out blood fast enough) and low thyroid function, it is very unwise to supplement thyroid hormones, because this will raise the metabolic acitivity of the cells, which will place more demands on the heart to carry oxygen to the cells via hemoglobin in the red blood cells. Having a low metabolic rate is actually a big advantage for prolonging life if the heart is not able to put out blood fast enough to supply normal metabolism in the body. So in this case, helping the heart's ability to function is the first thing to do, and then if that is successful, one can then raise the thyroid hormone level.
As some of you know, I believe that the root biochemical issue in CFS is a chronic partial block in the methylation cycle, which is coupled to glutathione depletion and a draining of folate metabolites from the cells. I think that this is one of the first things that must be dealt with in treatment. In some cases, other things must be dealt with even before this, such as certain nutritional deficiencies, which may stem from dysfunction of the gastrointestinal system, mold illness, or certain infectious diseases.
Dr. Cheney does not agree that the partial methylation cycle block is the root issue. His views have been changing about what the root issue actually is, but I think he is now focusing quite a lot on the XMRV retrovirus. I think he suspects that the virus inhibits the activity of some of the antioxidant enzymes, and that this in turn produces the observed oxidative stress. I think he believes that the combination of low ATP production and elevated oxidative stress together is what produces the diastolic dysfunction of the heart, which he focuses upon these days.
My view at this point is that in CFS it's best first to run the Vitamin Diagnostics methylation pathways panel (which won't be available again until about late January, because the lab is being moved). If this panel comes out positive for a partial methylation cycle block, which appears to be the case in nearly all CFS cases, then the person, together with their physician, should consider the Simplified Treatment Approach for lifting this partial block and restoring glutathione and the folate metabolism. This will automatically raise the body's production of Co Q-10. I believe it will also correct the mitochondrial dysfunction and will correct the diastolic dysfunction of the heart as well, which I believe is due to the mito dysfunction that results from glutathione depletion.
If this does not produce the benefits I've described, then I suggest that further testing is needed to see what is interfering with these improvements.
In cases in which Co Q-10 supplementation is not helpful, I suspect that it is because the root cause of mito dysfunction (i.e. glutathione depletion) is still present. Trying to speed up the transfer of electrons to the respiratory chain before correcting the partial block in the Krebs cycle may be producing additional oxidative stress in these cases.
I might add that Dr. Myhill does include methylation treatment in her overall protocol, based on my work, and she has also pioneered treatment of the mito dysfunction, but so far I don't think she has agreed to a connection between glutathione depletion, which is associated with the partial methylation cycle block, and the mito dysfunction. I note, though, that Dr. Howard of Acumen Lab, with whom she works closely, includes glutathione measurement in his CFS testing, so I'm hopeful that they will eventually agree on this connection.
Dr. Cheney at this point does not believe that glutathione is depleted in CFS, though he was the one who initially convinced me of that in 1999, and though I have shared a considerable amount of lab test data with him that verifies it.
Prof. Martin Pall does not buy into my hypothesis either. He continues to hold that the nitric oxide--peroxynitrite cycle is the basis of CFS. He does include both B12 and folate in his protocol, together with many antioxidants, but he gives a different rationale for them than the one I believe is primary. He believes that the main role of hydroxocobalamin is to bind nitric oxide, and the main role of 5-methyl THF is to scavenge peroxynitrite in the treatment of CFS. The form of folate he includes is folic acid. For a while, it appeared that he was going to change to 5-methyl tetrahydrofolate, but apparently he has heard that some do not tolerate it well, so I think he is now considering folinic acid. Folinic acid will likely support the methylation cycle pretty well for most PWCs, unless their cells cannot do the conversion from folinic to 5-methyl THF very well. It is a definite improvement over folic acid, though, because the conversion from folic acid to tetrahydrofolate is slow in many people. I believe that the reported difficulties in tolerating 5-methyl THF result from the fact that it is working to stimulate the methylation cycle, which also causes the detox system to work faster and mobilizes toxins into the blood more rapidly. I believe that removing the stored toxins is necessary to restore the person to health, so I think that this "intolerance" is a necessary and temporary evil.
As you can see, there are still many disagreements among the researchers and clinicians involved in CFS about what are actually the root issues. Hopefully we will be able to narrow these differences as we learn more.
Best regards,
Hi, all.
Coenzyme Q-10 normally plays a couple of important roles in the cells. In the mitochondria, it serves as a receiver and transmitter of energetic electrons that are obtained from processing foods in the Krebs cycle and are given to the respiratory chain, so that the energy can be used to convert ADP back to ATP, which then supplies the energy to power a large number of biochemical reactions in the cells, including those involved in use of the muscles and those involved in sending nerve impulses. Heart muscle is particularly dependent on Co Q-10 because of its high demand for ATP. Co Q-10 is also part of the basic antioxidant network in the cells.
In CFS, coenzyme Q-10 was found to be low in the recent Maes et al. study, as well as in a study by Langsjoen et al. in 1993. I've also seen low values in quite a few test results that PWCs have sent to me. Based on my hypothesis (the GD--MCB hypothesis) and review of many lab test results that people have sent me, I believe that the direct reason Co Q-10 is low in CFS is that there is a partial block in the methylation cycle, so that the capacity to carry out methylation reactions is deficient. Methylation reactions are necessary to produce coenzyme Q-10 in the body.
The question of whether to supplement Co Q-10 in CFS is somewhat difficult to answer. Dr. Sarah Myhill recommends doing so, in combination with several other supplements to support the mitochondrial function (based primarily on the the book by Dr. Sinatra, a cardiologist), in those who test positively for mito dysfunction in the Acumen Lab tests. Other CFS specialists have also recommended Co Q-10 supplementation over the past few years, including Dr. Cheney.
Some PWCS report benefit from Co Q-10 supplementation, while others find that they cannot tolerate it. Some have tried Idebenone, instead, and found that they tolerated it better and benefited from it.
Dr. Cheney's views have changed since he started using the echocardiograph to decide what is beneficial and what is not in CFS. This new approach has caused him to switch his position on Co Q-10 supplementation in CFS, and he now opposes it. I have expressed my disagreement with Dr. Cheney's interpretation of his IVRT measurements on the echocardiograph a few times in the past, both to him and on internet boards. I don't believe that a measurement made a minute or a few minutes after administering a substance is a good indicator of how it will affect the biochemistry over the longer term.
Nevertheless, I share some of Dr. Cheney's thinking about the types of treatment that are beneficial. Both he and I are concerned that it's important to treat at the level of the root issues in CFS, rather than to focus on the downstream issues. He and I both believe that the body is set up to compensate for root issues by making downstream changes. If the body's compensations or adaptations are countered while the root issues are not dealt with, the treatment can actually do more harm than good. An example that Dr. Cheney has emphasized to me in our discussions is something he learned while he was in training. If a person has heart failure (i.e. inability of the heart to pump out blood fast enough) and low thyroid function, it is very unwise to supplement thyroid hormones, because this will raise the metabolic acitivity of the cells, which will place more demands on the heart to carry oxygen to the cells via hemoglobin in the red blood cells. Having a low metabolic rate is actually a big advantage for prolonging life if the heart is not able to put out blood fast enough to supply normal metabolism in the body. So in this case, helping the heart's ability to function is the first thing to do, and then if that is successful, one can then raise the thyroid hormone level.
As some of you know, I believe that the root biochemical issue in CFS is a chronic partial block in the methylation cycle, which is coupled to glutathione depletion and a draining of folate metabolites from the cells. I think that this is one of the first things that must be dealt with in treatment. In some cases, other things must be dealt with even before this, such as certain nutritional deficiencies, which may stem from dysfunction of the gastrointestinal system, mold illness, or certain infectious diseases.
Dr. Cheney does not agree that the partial methylation cycle block is the root issue. His views have been changing about what the root issue actually is, but I think he is now focusing quite a lot on the XMRV retrovirus. I think he suspects that the virus inhibits the activity of some of the antioxidant enzymes, and that this in turn produces the observed oxidative stress. I think he believes that the combination of low ATP production and elevated oxidative stress together is what produces the diastolic dysfunction of the heart, which he focuses upon these days.
My view at this point is that in CFS it's best first to run the Vitamin Diagnostics methylation pathways panel (which won't be available again until about late January, because the lab is being moved). If this panel comes out positive for a partial methylation cycle block, which appears to be the case in nearly all CFS cases, then the person, together with their physician, should consider the Simplified Treatment Approach for lifting this partial block and restoring glutathione and the folate metabolism. This will automatically raise the body's production of Co Q-10. I believe it will also correct the mitochondrial dysfunction and will correct the diastolic dysfunction of the heart as well, which I believe is due to the mito dysfunction that results from glutathione depletion.
If this does not produce the benefits I've described, then I suggest that further testing is needed to see what is interfering with these improvements.
In cases in which Co Q-10 supplementation is not helpful, I suspect that it is because the root cause of mito dysfunction (i.e. glutathione depletion) is still present. Trying to speed up the transfer of electrons to the respiratory chain before correcting the partial block in the Krebs cycle may be producing additional oxidative stress in these cases.
I might add that Dr. Myhill does include methylation treatment in her overall protocol, based on my work, and she has also pioneered treatment of the mito dysfunction, but so far I don't think she has agreed to a connection between glutathione depletion, which is associated with the partial methylation cycle block, and the mito dysfunction. I note, though, that Dr. Howard of Acumen Lab, with whom she works closely, includes glutathione measurement in his CFS testing, so I'm hopeful that they will eventually agree on this connection.
Dr. Cheney at this point does not believe that glutathione is depleted in CFS, though he was the one who initially convinced me of that in 1999, and though I have shared a considerable amount of lab test data with him that verifies it.
Prof. Martin Pall does not buy into my hypothesis either. He continues to hold that the nitric oxide--peroxynitrite cycle is the basis of CFS. He does include both B12 and folate in his protocol, together with many antioxidants, but he gives a different rationale for them than the one I believe is primary. He believes that the main role of hydroxocobalamin is to bind nitric oxide, and the main role of 5-methyl THF is to scavenge peroxynitrite in the treatment of CFS. The form of folate he includes is folic acid. For a while, it appeared that he was going to change to 5-methyl tetrahydrofolate, but apparently he has heard that some do not tolerate it well, so I think he is now considering folinic acid. Folinic acid will likely support the methylation cycle pretty well for most PWCs, unless their cells cannot do the conversion from folinic to 5-methyl THF very well. It is a definite improvement over folic acid, though, because the conversion from folic acid to tetrahydrofolate is slow in many people. I believe that the reported difficulties in tolerating 5-methyl THF result from the fact that it is working to stimulate the methylation cycle, which also causes the detox system to work faster and mobilizes toxins into the blood more rapidly. I believe that removing the stored toxins is necessary to restore the person to health, so I think that this "intolerance" is a necessary and temporary evil.
As you can see, there are still many disagreements among the researchers and clinicians involved in CFS about what are actually the root issues. Hopefully we will be able to narrow these differences as we learn more.
Best regards,
(es broma). A pesar de que es caro, si te va bien, el "coctel" te permite llevar una vida casi normal, yo lo he hecho durante un año y medio. Aunque a veces da la impresión que sólo trabajas para poder pagarte los suplementos, pero bueno... si funcionan, sentirte medio-medio es mejor que sentirte mal del todo, no? Espero que te funcionen, de verdad.