alex3619
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In short, yes. I probably have fibro, and probably have small fiber polyneuropathy, but I have never been formally diagnosed.
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Uric acid
- Thread starter Kimsie
- Start date
Hanna
Senior Member
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- 717
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- Jerusalem, Israel
@Kimsie,
I have put in attachment one page of results from Acumen Labs about ATP study (ordered by Dr Myhill).
Along with comments from Dr Myhill : (tried to keep short)
1. levels of ATP :
With excess Mg added :1.49 (range : 16-2.9) ==> very low, Dr Myhill recommended D-ribose
With endogenous Mg : 0.77 (range 0.9-2.7) ==>very low ATP-related magnesium status. Magnesium injections recommended
2. oxydative phosphorylation :
- ADP to ATP conversion efficiency : 50.7%.
Dr Myhill's comment that it is running slow (normal range >60%). But the rate of 8.7% signifies that there is no significant blockage of the active sites (up to 14% = normal).
- vitamin B3 (red cell NAD) : 10.6 (range 14.0-30.0) fairly marked deficiency
comments : reflects function of Krebs citric acid cycle. therefore to see normal levels of NAD needs not only an adequate supply of B3 but also a functionning Kreb's citric acid cycle. So a low NAD (amongst other things) also imply a poor acetyl L carnitine level. ==> supplementation
-serum L carnitine : 30.5 umol(34-48) poor result.==> suplementation
- co-enzymeQ10 (sample haemolized)
{...}
This result simply shows how well oxidative phosphorylation is working at the time the test was taken. Does not predict what will happen if the patient increases exercice levels. So it is important to continue pacing carefully.
3. Movement of ATP and AFP accross mitochondrial membranes :
This is dependant on translocator proteines (TR).
- TR 'out' is poor 22.8% (normal range >35%).
TR can be blocked in many different ways -the commonest toxic stress.==> detox (FIR sauna etc)
- TR 'in' slightly abnormal result 80.5% (normal range 55-75%). This indicates rapid depletion of mitochondrial ATP on energy demand, which is again probably due to substrate deficiency.
ATP to start off with is rather low (302). ie there is not much reserve there when energy demands are made on the cell.
However when the energy demands is made, ATP is rapidly used-up and whisked back into the mitochondria in order to be regenerated.
==> D-ribose should be helpful.
Another possible reason for TL protein blockage is intracellular acidosis.
-cell-free DNA : 16.2 ug/l (normal range up to 9.5). good measure of cellular damage.
(poor antioxidant status, toxic strss, immune activation,poor mito function, patient not pacing well).
- Superoxide Dismutase :
- SODase result is poor 39% (normal >40%, but very narrow range. small deviation significant clinically)
-Enzyme Zn/Cu form is 221 (240-410 norme), Mn form 148 (125-208) and extra cellular Zn/Cu 43 (28-70).
This shows a deficiency in Zinc and copper.
Super oxide dismutase is the most important super oxide scavenger in muscles.
- gene study normal (for Zn/Cu SODase) with low enzyme activity.
both genes for Mn-SODase and EC-SODase are normal.
==> doubltly important to tackle antioxidant status.
-Red cell glutathione peroxidase (GSH-PX) : 53U/gHb (67-90) very poor result.
red cell glutathione (GSH) : 1.83 mmol/l (1.7-2.6) - low normal result.
==>glut supplement recommended + high protein diet (amino acids for endogenous synthesis of glut.) + supplementation in Selenium.
I have put in attachment one page of results from Acumen Labs about ATP study (ordered by Dr Myhill).
Along with comments from Dr Myhill : (tried to keep short)
1. levels of ATP :
With excess Mg added :1.49 (range : 16-2.9) ==> very low, Dr Myhill recommended D-ribose
With endogenous Mg : 0.77 (range 0.9-2.7) ==>very low ATP-related magnesium status. Magnesium injections recommended
2. oxydative phosphorylation :
- ADP to ATP conversion efficiency : 50.7%.
Dr Myhill's comment that it is running slow (normal range >60%). But the rate of 8.7% signifies that there is no significant blockage of the active sites (up to 14% = normal).
- vitamin B3 (red cell NAD) : 10.6 (range 14.0-30.0) fairly marked deficiency
comments : reflects function of Krebs citric acid cycle. therefore to see normal levels of NAD needs not only an adequate supply of B3 but also a functionning Kreb's citric acid cycle. So a low NAD (amongst other things) also imply a poor acetyl L carnitine level. ==> supplementation
-serum L carnitine : 30.5 umol(34-48) poor result.==> suplementation
- co-enzymeQ10 (sample haemolized)
{...}
This result simply shows how well oxidative phosphorylation is working at the time the test was taken. Does not predict what will happen if the patient increases exercice levels. So it is important to continue pacing carefully.
3. Movement of ATP and AFP accross mitochondrial membranes :
This is dependant on translocator proteines (TR).
- TR 'out' is poor 22.8% (normal range >35%).
TR can be blocked in many different ways -the commonest toxic stress.==> detox (FIR sauna etc)
- TR 'in' slightly abnormal result 80.5% (normal range 55-75%). This indicates rapid depletion of mitochondrial ATP on energy demand, which is again probably due to substrate deficiency.
ATP to start off with is rather low (302). ie there is not much reserve there when energy demands are made on the cell.
However when the energy demands is made, ATP is rapidly used-up and whisked back into the mitochondria in order to be regenerated.
==> D-ribose should be helpful.
Another possible reason for TL protein blockage is intracellular acidosis.
-cell-free DNA : 16.2 ug/l (normal range up to 9.5). good measure of cellular damage.
(poor antioxidant status, toxic strss, immune activation,poor mito function, patient not pacing well).
- Superoxide Dismutase :
- SODase result is poor 39% (normal >40%, but very narrow range. small deviation significant clinically)
-Enzyme Zn/Cu form is 221 (240-410 norme), Mn form 148 (125-208) and extra cellular Zn/Cu 43 (28-70).
This shows a deficiency in Zinc and copper.
Super oxide dismutase is the most important super oxide scavenger in muscles.
- gene study normal (for Zn/Cu SODase) with low enzyme activity.
both genes for Mn-SODase and EC-SODase are normal.
==> doubltly important to tackle antioxidant status.
-Red cell glutathione peroxidase (GSH-PX) : 53U/gHb (67-90) very poor result.
red cell glutathione (GSH) : 1.83 mmol/l (1.7-2.6) - low normal result.
==>glut supplement recommended + high protein diet (amino acids for endogenous synthesis of glut.) + supplementation in Selenium.
Attachments
I have found another interesting tidbit. I am bringing other illnesses into this because I think using data from other Mitochondrial illnesses can help us understand the whole.
Bipolar, schizoaffective and schizophrenia have a direct relationship between serum uric acid levels and BH4 levels. This is what I would expect because of the role of uric acid as a peroxynitrite scavenger, and BH4 as both a victim and preventer of peroxynitrite. Bipolar has high uric acid, schizoaffective is lowish and schizophrenia is low.
It appears that high uric acid may be associated with fibro, and people who have ME/CFS who have high uric acid may also have fibro symptoms. Question: Can those of you who have had both uric acid and BH4 levels checked report your results? And do you have any fibro symptoms?
Uric acid was found to be low in the CSF of Alzheimer's patients. Other studies have found it to be normal in the serum.
I don't exactly know where all this fits in. This seems to have some relationship with which kinds of symptoms a person gets. The uric acid levels aren't the underlying cause of the illness, but I think that it might be helpful for those who's levels are low to raise them. The more people report their data, the more we can move towards understanding what is happening in these illnesses.
Bipolar, schizoaffective and schizophrenia have a direct relationship between serum uric acid levels and BH4 levels. This is what I would expect because of the role of uric acid as a peroxynitrite scavenger, and BH4 as both a victim and preventer of peroxynitrite. Bipolar has high uric acid, schizoaffective is lowish and schizophrenia is low.
It appears that high uric acid may be associated with fibro, and people who have ME/CFS who have high uric acid may also have fibro symptoms. Question: Can those of you who have had both uric acid and BH4 levels checked report your results? And do you have any fibro symptoms?
Uric acid was found to be low in the CSF of Alzheimer's patients. Other studies have found it to be normal in the serum.
I don't exactly know where all this fits in. This seems to have some relationship with which kinds of symptoms a person gets. The uric acid levels aren't the underlying cause of the illness, but I think that it might be helpful for those who's levels are low to raise them. The more people report their data, the more we can move towards understanding what is happening in these illnesses.
I will look at this today. One thing I need to know is if you were having PEM episodes at the time the test was taken. How was your condition at that time?
Thanks!
Hanna
Senior Member
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- 717
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- Jerusalem, Israel
@Kimsie : I forgot to link the lab results with the clinical picture you wanted :
At that time :I had been housebound for 2 years (CFS began with EBV 12 years before this test), about 3 on Karnovsky scale.
Did some work at home (painter), once- twice a week for a couple of hours, in addition to the strict minimum (food-hygiene). Got outside with wheelchair for medical purpose only. Could sustain some gentle walk inside the house, and tried to push myself in order to totalise 30 mn a day = big mistake!
I experimented PEMs, with worsening of my condition in the evening of the same day I "exercised", but the worst was 24-48 hours after. PEMs lasted generally one or two days.
I tried to follow Dr Myhill's protocole for 1.5 year with 3 deviations :
1. I havn't paced myself enough
2. I took all the nutrients (vitamins, with a fair load of B3, acethyl- l carnitine, CoQ10, minerals etc) but omitted the Magnesium daily injections (and took a minimum orally)
3. I took sublingual B-12 instead of the injections
With no result, in fact I continued my way down... and quickly was impossible to work at all.
This year, after 16 years, I have experimented my first amelioration (though I am in a middle of a big crash now) - following a ABX protocole for Lyme (ELISA was found + in 02/2014). So it seems there is also an immune activation from borrelia going on, and it may also affect the mitochondria...(I say also because PEM doesn't belong to the classical symptoms of Lyme, and I was diagnosed CFS in 1998).
I don't know if this may give you some additionnal information about your hypothesis.
At that time :I had been housebound for 2 years (CFS began with EBV 12 years before this test), about 3 on Karnovsky scale.
Did some work at home (painter), once- twice a week for a couple of hours, in addition to the strict minimum (food-hygiene). Got outside with wheelchair for medical purpose only. Could sustain some gentle walk inside the house, and tried to push myself in order to totalise 30 mn a day = big mistake!
I experimented PEMs, with worsening of my condition in the evening of the same day I "exercised", but the worst was 24-48 hours after. PEMs lasted generally one or two days.
I tried to follow Dr Myhill's protocole for 1.5 year with 3 deviations :
1. I havn't paced myself enough
2. I took all the nutrients (vitamins, with a fair load of B3, acethyl- l carnitine, CoQ10, minerals etc) but omitted the Magnesium daily injections (and took a minimum orally)
3. I took sublingual B-12 instead of the injections
With no result, in fact I continued my way down... and quickly was impossible to work at all.
This year, after 16 years, I have experimented my first amelioration (though I am in a middle of a big crash now) - following a ABX protocole for Lyme (ELISA was found + in 02/2014). So it seems there is also an immune activation from borrelia going on, and it may also affect the mitochondria...(I say also because PEM doesn't belong to the classical symptoms of Lyme, and I was diagnosed CFS in 1998).
I don't know if this may give you some additionnal information about your hypothesis.
Thank you , Hanna, for giving me this information.
My comments might be of interest to everyone.
It is important to note that the value of % ATP inhibited is also the percentage of ATP generated by oxidative phosphorylation in the ETC and this can be as low as about 20 % for both cohorts. We are forced to conclude that, for patients with low values of % ATP inhibited, the ETC is already partially inhibited
They also conclude that people who do not have low values of % ATP inhibited do not have a block in oxidative phosphorylation, this is the part I don't agree with. They don't take into account the possibility of the folate cycle using NADPH generated by oxidative phosphorylation to produce ATP in the pathway illustrated below:
I think it is possible to have what she considers a value that indicates no inhibition of the ETC on her test and still have an inhibition in the ETC. I think it is also possible that the group with low inhibition is actually able to use the glycolysis pathway for a large amount of their ATP production.
I thought it was curious that in the article they say that ATP production through glycolysis was not inhibited by Azide and that the average of 7.5% not inhibited in the controls represents ATP production through glycolysis, but in the patients who have a much larger percentage such as 60% not inhibited for example, it meant that they used some other method of ATP production, and suggests that it might be the adenylate kinase which takes 2 ADP and makes 1 ATP and one AMP. Maybe it could be that, but they draw what seems to me to be an arbitrary line at a little above the control group to delineate how much ATP can be made by glycolysis, and they don't give any reason for why they draw the line there that I can see beyond saying that there are limits to how much ATP can be made by glycolysis.
That said, I think it is quite possible that the adenylate kinase pathway is being used by these people.
From the test results I have so far, I am doubting my idea that PEM is caused by using the glycolysis pathway so I might have to drop that idea.
My comments might be of interest to everyone.
I have spent quite a bit of time looking at this article to understand the way she does this test and how she interprets it, and I think there is a problem with her interpretation. Here is a quote from the text:
It is important to note that the value of % ATP inhibited is also the percentage of ATP generated by oxidative phosphorylation in the ETC and this can be as low as about 20 % for both cohorts. We are forced to conclude that, for patients with low values of % ATP inhibited, the ETC is already partially inhibited
They also conclude that people who do not have low values of % ATP inhibited do not have a block in oxidative phosphorylation, this is the part I don't agree with. They don't take into account the possibility of the folate cycle using NADPH generated by oxidative phosphorylation to produce ATP in the pathway illustrated below:
I think it is possible to have what she considers a value that indicates no inhibition of the ETC on her test and still have an inhibition in the ETC. I think it is also possible that the group with low inhibition is actually able to use the glycolysis pathway for a large amount of their ATP production.
I thought it was curious that in the article they say that ATP production through glycolysis was not inhibited by Azide and that the average of 7.5% not inhibited in the controls represents ATP production through glycolysis, but in the patients who have a much larger percentage such as 60% not inhibited for example, it meant that they used some other method of ATP production, and suggests that it might be the adenylate kinase which takes 2 ADP and makes 1 ATP and one AMP. Maybe it could be that, but they draw what seems to me to be an arbitrary line at a little above the control group to delineate how much ATP can be made by glycolysis, and they don't give any reason for why they draw the line there that I can see beyond saying that there are limits to how much ATP can be made by glycolysis.
That said, I think it is quite possible that the adenylate kinase pathway is being used by these people.
From the test results I have so far, I am doubting my idea that PEM is caused by using the glycolysis pathway so I might have to drop that idea.
So here is another place I disagree with her interpretation about the ETC not being inhibited in your case. I think the low RBC NAD reflects the fact that your body is trying to raise NAD levels in the mitochondria to raise the NAD/NADH ratio to overcome the high NADH levels caused by the block of the ETC. Since the RBC's don't have mitochondria, they don't get very much of the NAD your body is able to produce. Her assumption is that the TCA cycle is not functioning because of a lack of substrate or supplies or ingredients, not by a block. There could be some substrates that are low, because various enzymes are inhibited, but I think the ETC inhibition is the heart of the problem.
There must be some significance about these translocator protein measurments, but I haven't figured it out yet. I think it might be related to which alternative ATP producing pathway the person uses the most, in which case it is more of a result than a cause of anything.
They didn't do a GSH/GSSG ratio, but with your lowish GSH I bet your ratio is low and your GSSG is on the high side of normal because of low NADPH for recycling the GSH.
I've had my uric acid levels checked a couple of times by my UK GP as I was taking Imunovir (Inosine Pranobex). My uric acid level was originally low and although it did go up it never reached the medium or high level.
I didn't have FM at that time. Shortly after the testing stopped (my GP stopped prescribing it) I developed FM pain and stiffness right after a serious road traffic accident.
Although I have taken Imunovir since the accident I have not had my uric acid levels tested again. I've never had a BH4 test.
Thank you @Kimsie for doing all of this brainstorming!
I didn't have FM at that time. Shortly after the testing stopped (my GP stopped prescribing it) I developed FM pain and stiffness right after a serious road traffic accident.
Although I have taken Imunovir since the accident I have not had my uric acid levels tested again. I've never had a BH4 test.
Thank you @Kimsie for doing all of this brainstorming!
Hanna
Senior Member
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- 717
- Location
- Jerusalem, Israel
@ Kimsie thank you for all the efforts.
Unfortunately, my understanding is rather impaired for the moment, and in general also. ..So it seems to you that the way Dr Myhill is drawing conclusion about the absence of inhibition of the ETC is questionnable.
Thanks also for posting the reference of the Myhill/Mc Laren article. Hope I will have the energy to read it.
Unfortunately, my understanding is rather impaired for the moment, and in general also. ..So it seems to you that the way Dr Myhill is drawing conclusion about the absence of inhibition of the ETC is questionnable.
Thanks also for posting the reference of the Myhill/Mc Laren article. Hope I will have the energy to read it.
You're welcome. If I can help other people it makes me feel somewhat better about my sons' illnesses. Besides that you people here really help me both by giving me data and by your other types of comments.
It even takes a lot of energy for me to understand articles like that one, but at least I have the energy. This is one area where I have an advantage over most of the people who post here - I can do research for many hours a day and not fall too far behind in the other things I need to do. (Besides having two guinea pigs to experiment on, we joke with D about his being a guinea pig.)
I really believe that everyone who has CFS has an inhibited ETC, and I feel that her conclusion that some of her subjects do not have an inhibition in the ETC is wrong, because she has not considered that there might be alternative energy pathways that depend to some extent on oxidative phosphorylation besides ATP synthase.
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I was just thinking today about how ribose is required to salvage purines and I thought about your high uric acid levels. In one post you said that you had not tried ribose, but I don't know if that was just in relationship to something else or if you haven't ever taken it, which doesn't seem likely to me.
Have you ever tried ribose along with some amount of niacinamide?
alex3619
Senior Member
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I have never taken ribose as a supplement.
Gondwanaland
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What does that mean? I don't want to raise my uric acid.
If a purine isn't salvaged (recycled) it will become uric acid, so if you salvage more purines, you will make less uric acid, at least in theory. You will also save some ATP because de novo synthesis of purines takes quite a lot of ATP. So taking ribose might lower uric acid in people who have high uric acid, particularly if they are taking niacinamide so that they can use the purines to increase the NAD pool.
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@Kimsie
Acumen 2012
ATP whole cells:
ADT to ATP conversion efficiency:
With excess Mg added: 1.38 nmol/10 (6) cells 1.6-2.9
Endogenous Mg only 0.86 nmol/10 (6) 0.9-2.7
Ratio ATP/ATP Mg 0.62
ADP to ATP conversion efficiency (whole cells)
ATP Mg (from above) 1.38 nmol/10 (6) (1*) 1.6-2.9
ATP Mg (inhibitor present) 0.43 nmol?10(6) (2*) <0.3
ATP Mg (inhibitor removed) 0.89 nmol/10(6) (3*) >1.4
ADP to ATP efficiency [(3* - 2*) /(1* -2*)] X 100 = 48.4 % >60
Blockage of active sites (2*/1*) X 100 = 31.2 % up to 14
ADP - ATP Translocator [TL]
Start 216 (290-7-00)
[TL] 'out' 275 (410-950) change 27.3 0ver 35% (In crease)
[TL} 'in' 190 (140-330) change 12 55% to 75% (Decrease)
Comments
Very low whole cell ATP. 31.2% block of active sites leading to:
very low mt-ATP and poor provision of ATP. Marked blocking of translocator function. Rather low ATP related Mg. Very poor ADP to ATP re-conversion.
Yes I have fibromyalgia.
Uric acid 374 umol/L (NR 175-363)
Brenda
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Hi Brenda, thank you for sharing your data. I still haven't figured out what the significance of the translocator protein changes are, so I can't comment about that, except that it probably means that you have pretty heavy use of an alternative ATP pathway outside the mitochondria.
Since ribose is required for purine salvage (recycling) taking D-ribose might help and lower the uric acid somewhat. Do you already take ribose, or have you taken it in the past? Do you take any niacinamide? That might help along with the ribose to increase the NAD pool. (Did the test show a low NAD level?) They should both be taken 2-3 times a day if possible to keep the blood levels more even. If you have a particular amount of niacinamide that you tolerate, then you can just divide it up into smaller doses. If you don't take any niacinamide it is best to start at a low dose, splitting the capsules, and build up from there, if you want to try it.
Have you ever had your B6 levels tested? Do you take B6?
Also, I imagine that you experience PEM or PER (crashing). Is that right? How large of a window of activity do you have each day? These things help me to sort out the significance of the data from the tests.
@Kimsie
Thanks. I have taken D-ribose but stopped and can't remember why. Will try again. I take 250 mg niacinamide at night if I cannot sleep but it does not seem to do much. Will try again 3 X day. No b6 tested. have tried it a few times. Will try again. No NAD levels on results sheet.
Yes for PEM. I have an activity level of 15 - 20 mins then need short rest and can do some more but can sit at computer for hours. Can manage shopping.
Thanks. I have taken D-ribose but stopped and can't remember why. Will try again. I take 250 mg niacinamide at night if I cannot sleep but it does not seem to do much. Will try again 3 X day. No b6 tested. have tried it a few times. Will try again. No NAD levels on results sheet.
Yes for PEM. I have an activity level of 15 - 20 mins then need short rest and can do some more but can sit at computer for hours. Can manage shopping.
Ok just found a few Max One that a friend sent but have not tried them yet ;
http://159326.max.com/max4u/pages/?wicket:bookmarkablePage=:com.max.web.page.MaxOnePage
with D-ribose and L-Cysteine. I will try them tomorrow. Have just taken some b6 amd 250 mg niacinamide
http://159326.max.com/max4u/pages/?wicket:bookmarkablePage=:com.max.web.page.MaxOnePage
with D-ribose and L-Cysteine. I will try them tomorrow. Have just taken some b6 amd 250 mg niacinamide
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That's good to hear. It will be interesting to see how you do with the ribose. One thing I should mention, though, is that if you don't tolerate the supplement you have you should try ribose alone, because it might be possible for the cysteine to increase glutathione and cause a detox type reaction, and I wouldn't want you to think it was from the ribose.