Hi, all.
As I think you know, I believe that the core biochemical issue in CFS is a partial methylation cycle block, coupled with draining of the folate metabolites out of the cells by the "methyl trap" mechanism, and also coupled with depletion of glutathione. The glutathione depletion results in chronic oxidative stress. I believe that essentially all the symptoms of CFS can be related to this fundamental core issue, which is a vicious circle mechanism that keeps the person chronically ill.
It has been known for several years now that a significant fraction of women who become pregnant while having CFS experience absence of their CFS symptoms while pregnant, only to have them return after the birth of their child. This is not true in all cases, but it is true in a lot of them. The study by Schacterle and Komaroff (PMID: 14980991) found it to be true in 30% of the cases they studied. Dr. Charles Lapp has reported a higher fraction in his practice, and Dr. Teitelbaum has also found it to be common. I have wondered for several years what the explanation of this intriguing phenomenon might be. I joined the CFIDSorFMSpregnant group nearly ten years ago because I wanted to track down these reports to see if they were true. I was, and still am, the only male member of the group! Among the women in the group, some did report that their symptoms were lessened during their pregnancies.
Various hypotheses have been suggested to explain this, including increased blood volume during pregnancy, an effect on the immune system associated with the necessity for the mother's immune system not to reject the fetus, or an effect resulting from the hormonal changes during pregnancy.
If the glutathione depletion--methylation cycle block hypothesis for CFS is valid, it must be able to explain this phenomenon, or at least to mesh with it. Somehow, the biochemical issues that result from this vicious circle mechanism must be either corrected or counteracted during the pregnancy for these women.
The fact that the symptoms usually come back after the birth of the child suggests to me that this mechanism is not completely corrected during the pregnancy, but rather that the body compensatea for the effects of it during the pregnancy. So how would this compensation happen?
There has been some additional research published in the past few years directed toward developing a better understanding of toxemia (pre-eclampsia), which a small percentage of otherwise healthy women have during pregnancy. This research indicates that oxidative stress is involved in toxemia, so that has received quite a lot of study. This research fortunately is useful in understanding what goes on in normal pregnancies as well, when the woman does not have toxemia.
The research shows that during a normal pregnancy in a normal, healthy woman, there is increased production of reactive oxygen species, and these are dealt with both in the placenta and by the mother's red blood cells. There is a greater antioxidant capacity established during pregnancy to handle this oxidative stress. Also, it appears that the other aspects I mentioned, that is the problem with methylation and the problem with the folates, are also compensated during pregnancy.
It appears that the oxidative stress is taken care of by higher activity of the enzyme catalase in the red blood cells and the placenta, which eliminates hydrogen peroxide, just as glutathione together with glutathione peroxidase does. So perhaps the additional catalase could compensate for the depletion of glutathione in a pregnant woman with CFS.
In addition, there is evidence that more choline is made available during pregnancy to produce betaine, and that is used in the BHMT pathway in the liver and kidneys, which can compensate for the problem with methylation. Furthermore, the DMG that results from this reaction can support the folate metabolism. I don't know how the additional choline would be made available in women with CFS, since synthesizing it requires methylation, which is partially blocked according to the GD--MCB hypothesis. Perhaps it is taken from the woman's inventory of phosphatidylcholine. This is the biggest remaining question with this part of my hypothesis.
But if this hypothesis is true, it looks as though there are mechanisms during pregnancy that can compensate for all three of the main biochemical aspects that are included in the vicious circle that exists in the body of a woman who has CFS.
After the birth of the child, of course the placenta is expelled, and the new red blood cells that are made after the birth revert back to the way they were before the pregnancy (this can take at least several weeks, because the average life of a red blood cell is four months, and they are replaced on a continuous basis at about 1% per day). Also, the choline metabolism presumably reverts back also. Therefore, the original vicious circle mechanism remains, and is no longer compensated, so the symptoms return.
That's what I suggest goes on. I don't doubt that the increase in blood volume during pregnancy also helps. And not having to break down and get rid of estrogen every month would also be a big help, because, as I suggested in a 2007 IACFS poster paper, I think this is what causes CFS to be more prevalent in women than in men. Those who inherit certain polymorphisms experience redox cycling when their bodies are disposing of estrogen, and this biases them toward oxidative stress and glutathione depletion, which I've suggested is what leads to the onset of CFS in people who are genetically predisposed.
Of course, many women with CFS do not experience improvement of their symptoms during pregnancy, and in those cases my guess is that these compensating mechanisms are not as effective, perhaps because of genetic differences or nutritional factors that limit them in some women, just as some women develop toxemia or gestational diabetes, while most do not.
Anyway, it's something to think about. It's pretty amazing how a woman's body can "rise to the occasion" and overcome even something as debilitating as CFS during pregnancy.
Best regards,
Rich
As I think you know, I believe that the core biochemical issue in CFS is a partial methylation cycle block, coupled with draining of the folate metabolites out of the cells by the "methyl trap" mechanism, and also coupled with depletion of glutathione. The glutathione depletion results in chronic oxidative stress. I believe that essentially all the symptoms of CFS can be related to this fundamental core issue, which is a vicious circle mechanism that keeps the person chronically ill.
It has been known for several years now that a significant fraction of women who become pregnant while having CFS experience absence of their CFS symptoms while pregnant, only to have them return after the birth of their child. This is not true in all cases, but it is true in a lot of them. The study by Schacterle and Komaroff (PMID: 14980991) found it to be true in 30% of the cases they studied. Dr. Charles Lapp has reported a higher fraction in his practice, and Dr. Teitelbaum has also found it to be common. I have wondered for several years what the explanation of this intriguing phenomenon might be. I joined the CFIDSorFMSpregnant group nearly ten years ago because I wanted to track down these reports to see if they were true. I was, and still am, the only male member of the group! Among the women in the group, some did report that their symptoms were lessened during their pregnancies.
Various hypotheses have been suggested to explain this, including increased blood volume during pregnancy, an effect on the immune system associated with the necessity for the mother's immune system not to reject the fetus, or an effect resulting from the hormonal changes during pregnancy.
If the glutathione depletion--methylation cycle block hypothesis for CFS is valid, it must be able to explain this phenomenon, or at least to mesh with it. Somehow, the biochemical issues that result from this vicious circle mechanism must be either corrected or counteracted during the pregnancy for these women.
The fact that the symptoms usually come back after the birth of the child suggests to me that this mechanism is not completely corrected during the pregnancy, but rather that the body compensatea for the effects of it during the pregnancy. So how would this compensation happen?
There has been some additional research published in the past few years directed toward developing a better understanding of toxemia (pre-eclampsia), which a small percentage of otherwise healthy women have during pregnancy. This research indicates that oxidative stress is involved in toxemia, so that has received quite a lot of study. This research fortunately is useful in understanding what goes on in normal pregnancies as well, when the woman does not have toxemia.
The research shows that during a normal pregnancy in a normal, healthy woman, there is increased production of reactive oxygen species, and these are dealt with both in the placenta and by the mother's red blood cells. There is a greater antioxidant capacity established during pregnancy to handle this oxidative stress. Also, it appears that the other aspects I mentioned, that is the problem with methylation and the problem with the folates, are also compensated during pregnancy.
It appears that the oxidative stress is taken care of by higher activity of the enzyme catalase in the red blood cells and the placenta, which eliminates hydrogen peroxide, just as glutathione together with glutathione peroxidase does. So perhaps the additional catalase could compensate for the depletion of glutathione in a pregnant woman with CFS.
In addition, there is evidence that more choline is made available during pregnancy to produce betaine, and that is used in the BHMT pathway in the liver and kidneys, which can compensate for the problem with methylation. Furthermore, the DMG that results from this reaction can support the folate metabolism. I don't know how the additional choline would be made available in women with CFS, since synthesizing it requires methylation, which is partially blocked according to the GD--MCB hypothesis. Perhaps it is taken from the woman's inventory of phosphatidylcholine. This is the biggest remaining question with this part of my hypothesis.
But if this hypothesis is true, it looks as though there are mechanisms during pregnancy that can compensate for all three of the main biochemical aspects that are included in the vicious circle that exists in the body of a woman who has CFS.
After the birth of the child, of course the placenta is expelled, and the new red blood cells that are made after the birth revert back to the way they were before the pregnancy (this can take at least several weeks, because the average life of a red blood cell is four months, and they are replaced on a continuous basis at about 1% per day). Also, the choline metabolism presumably reverts back also. Therefore, the original vicious circle mechanism remains, and is no longer compensated, so the symptoms return.
That's what I suggest goes on. I don't doubt that the increase in blood volume during pregnancy also helps. And not having to break down and get rid of estrogen every month would also be a big help, because, as I suggested in a 2007 IACFS poster paper, I think this is what causes CFS to be more prevalent in women than in men. Those who inherit certain polymorphisms experience redox cycling when their bodies are disposing of estrogen, and this biases them toward oxidative stress and glutathione depletion, which I've suggested is what leads to the onset of CFS in people who are genetically predisposed.
Of course, many women with CFS do not experience improvement of their symptoms during pregnancy, and in those cases my guess is that these compensating mechanisms are not as effective, perhaps because of genetic differences or nutritional factors that limit them in some women, just as some women develop toxemia or gestational diabetes, while most do not.
Anyway, it's something to think about. It's pretty amazing how a woman's body can "rise to the occasion" and overcome even something as debilitating as CFS during pregnancy.
Best regards,
Rich