Acetyl L- Glutathione, ATP, Baking Soda, Sam-e & Catalase = No PEM after exercise

[MeSci]

I used to be very much a night owl in the hours I kept before getting sick. I also have overactive mast cells, so histamine (the wakefulness chemical) is a big problem - once I awake because of the bladder, it is very hard to get back to sleep.

My bladder wakes me at ~200ml. Or with less volume, if there is a lot of acidity. (Or with strong spices before bed - but that one's easy to correct.) Or with much less bladder volume, for reasons I haven't identified yet. awry (NSAIDS or flavonoids like tart cherry) usually help - now thanks to you I understand why. Potassium citrate usually helps me delay the bladder wake-up-call. Exercise usually helps me sleep longer.

Melatonin 30g does nothing. The typical talk of sleep hygiene is to me like attacking a Sherman tank with a styrofoam cup.

My question: what else besides K citrate and anti-inflammatories could you recommend to reduce urine output - within the backdrop of pH or anything else? (I'm excluding prescription meds like desmopressin.)

Okay, a quick followup question if you don't mind: from what you know of polyuria in CFS, would it be wrong to try and reduce urine output? In other words, is the system getting rid of excess bad molecules and so that shouldn't be impeded? Or is the system just gone awry a la` D Insipidus and not making enough Anti-Diuretic Hormone, so in that case the excess urination should be impeded?

Thanks again.

I'm not Steve, but I've never heard of histamine being called the wakefulness chemical before. There is lots of info here about histamine.

Re polyuria/DI and ME/CFS, there are some abstracts here.

I have posted links to some of them in at least one other thread, so maybe if you do a search for key words in the abstract(s) of interest and my name as author of the post you will find them, or just do a simple internet search - that usually finds things.

 

[Sidereal]

Aldehydes as a class are problematic. They are cross-linking agents and biochemically reactive. So they could definitely be part of the post-exertion experience. However, I suspect that lactic acidosis from use of anaerobic energy pathways is probably the greater influence. It makes sense that exercise itself can ameliorate that, if it is mild enough to cause only minor lactic acid loading of tissues, and is increased slowly enough to induce constructive adaptation. But I am not convinced that this is likely to work in everybody because of different bottlenecks in aerobic metabolism that can cause a low aerobic threshold and reliance on anaerobic metabolism. Would exercise reverse loss of control of mercury? Would exercise reverse the T4-to-rT3 pathway? Would exercise improve redox control so that inflammation would be gradually lessened? And if there is metabolic entrainment, would exercise break it?

Fascinating discussion. Thank you for taking the time to post here on PR. Do you have any thoughts on what might be causing the aerobic metabolism to break and the pH problem or how we might deal with these issues, apart from exercise? Psychiatry has argued for some decades that we are deconditioned and require a gradual programme of aerobic exercise. However, in practice these make us worse and the deconditioning theories cannot explain the overnight drastic loss of aerobic capacity some of us experienced at disease onset or onset of acute relapses, going from normal to disabled essentially from one day to the next, or the marked fluctuation/variability in symptoms some of us experience where aerobic capacity can differ from one day or even hour to the next.

Some recent work by Julia Newton's group in Newcastle has suggested problems with acid buildup in and/or disposal from the muscle in ME/CFS. Work that has been done over the last decade by Snell's group has suggested pathologically low anaerobic threshold in ME/CFS, especially on repeated cardiopulmonary exercise test taking place 24 hours after the initial test. This presentation by Prof Van Ness may be of interest. He argues that lactic acid is not the acid responsible for these symptoms:

Essentially we have a broken aerobic metabolism and cannot benefit from exercise like normal humans do; in fact, the cardinal feature of this disease seems to be this unusual phenomenon of post-exertional malaise (PEM) which means that exertion makes us worse and causes all our symptoms to actually amplify/flare 24-48 hours after exertion. In some cases, severe or prolonged exertion seems to cause a permanent worsening of the underlying condition or even set us up on a progressive course.

Although there is a spectrum of clinical severity, for some of us who are very severely affected, exertion can mean rolling over in bed or attempting to swallow food. Some of us afflicted with the symptom of postural tachycardia syndrome (POTS) can see our heart rates shoot up to 150 or more simply by trying to stand. Do you think it's possible that those who are bedridden and sometimes tube fed or paralysed with ME/CFS are actually in anaerobic metabolism all the time, simply from the "effort" of staying alive?

Tagging @alex3619 in case he would like to chime in.

 

[alex3619]

Do you think it's possible that those who are bedridden and sometimes tube fed or paralysed with ME/CFS are actually in anaerobic metabolism all the time, simply from the "effort" of staying alive?

Actually, that is one of my suspicions. I would love to see some blood work looking for this in patients. Its not a sure thing though.

Lactic acidosis takes time to develop. Julia Newton's work suggests we are highly acidic during and after exercise, but excessively alkaline at rest (one of our adaptations?). Lactic acidosis increases oxygen dumping in the short term as acidic conditions increase oxygen release from red blood cells.

However if prolonged it suppresses an enzyme called 2,3 bisphosphoglycerate which is needed for oxygen dumping. So you can get less oxygen dumped, which can drive increased lactic acid production, which makes things more acidic ... and suddenly you can wind up in the positive feedback loop called lactic acidosis. The loop is lactate derived, but the trigger can be anything that impedes aerobic metabolism, even a heart condition.

Short term lactic acid is good unless oxygen dumping is not what you want for some reason. Prolonged muscle acidity from any cause can drive the lactic acidosis spiral though. Usually this takes days to manifest, but the exact duration will depend a lot on patient chemistry.

Now staying more alkaline will improve 2,3 bpg and increase oxygen dumping during exercise induced carbonic acidity. I wonder if this might be useful by increasing oxygen availability to muscle.

I have never heard of a case of acidosis or alkalosis in ME though. I am not sure it ever happens. Lactic acidosis is not something to be unconcerned about ... its frequently fatal. I have never heard of a patient dying from this. I suspect Julia Newton is right and once we stop then we shift to alkalinity.

However someone who pushes themselves, and keeps pushing, might risk acidosis. The danger is that the change in the pH shifts lots of critical metabolic and regulatory enzymes. Every enzyme has an optimal pH range.

 

[Sherlock]

I'm not Steve, but I've never heard of histamine being called the wakefulness chemical before.

Histamine in the regulation of wakefulness.
Abstract

The histaminergic system is exclusively localized within the posterior hypothalamus with projection to almost all the major regions of the central nervous system. Strong and consistent evidence exist to suggest that histamine, acting via H₁ and/or H₃ receptor has a pivotal role in the regulation of sleep-wakefulness. Administration of histamine or H₁ receptor agonists induces wakefulness, whereas administration of H₁ receptor antagonists promotes sleep. The H₃ receptor functions as an auto-receptor and regulates the synthesis and release of histamine. Activation of H₃ receptor reduces histamine release and promotes sleep. Conversely, blockade of H₃ receptor promotes wakefulness. Histamine release in the hypothalamus and other target regions is highest during wakefulness. The histaminergic neurons display maximal activity during the state of high vigilance, and cease their activity during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The cerebrospinal levels of histamine are reduced in diseased states where hypersomnolence is a major symptom. The histamine deficient L-histidine decarboxylase knockout (HDC KO) mice display sleep fragmentation and increased REM sleep during the light period along with profound wakefulness deficit at dark onset, and in novel environment. Similar results have been obtained when histamine neurons are lesioned. These studies strongly implicate the histaminergic neurons of the TMN to play a critical role in the maintenance of high vigilance state during wakefulness.

...and Sominex is simply the antihistamine diphenhydramine.

I am figuring that when the bladder is full, the body's means to wake the person is by increasing histamine - which IIRC also goes high in the morning. With me being probable MTHFR 677, I don't break down that increased histamine so can't get back to sleep.

 

[Sherlock]

IME reversing excess acidity with oral magnesium oxide and sodium bicarbonate baths helped me to erradicate my polyuria. In addition, Saccharomyces boulardii helped in reducing histamine and vitamin A helped in solubilizing calcium.
My urine pH was 4.5 in the evening when I took my 1st bicarb bath. If I only knew it was that simple!

Congratulations! Do you mean you can sleep 7-8 hours now?

Having sugar and stirring up candida also promotes lots of urine production for me - not sure why yet. That was also very true (but not such high volume) pre-CFS. What's your idea on that?

[edit: though it's probably from something irritating the bladder lining -- maybe acetaldehyde, or methyhistamine? or something from leaky gut caused by the candida... ]

 

[Sherlock]

Fascinating discussion.

Yes, very much so. I was instantly happy to see Steve posting here. From the little I know of him from long ago, he is interested in a wide variety of conditions and so has the vantage point to correlate across conditions. As a sort of outsider, he brings a fresh perspective, too, which I welcome very much.

It turns out his old article on acetaldehyde countered by cysteine is still there http://ceri.com/alcohol.htm

Maybe that relates to MTHFR & homocysteone re CFS.

 

[Gondwanaland]

Congratulations! Do you mean you can sleep 7-8 hours now?

Could do it continuously for several weeks after my 5th dose of 10,000iu of vit A (I was taking it 1x weekly). Now I can sleep well at least 3x weekly. My current issues with insomnia are probably related to my +/+ MAO-A:

to go from stage 3/Deep Sleep into stage 4/REM your brain chemistry has to change modus. You need a little bit of noradrenalin to rise from Deep Sleep and stop the no-REM neurons from firing. (I suspect that people who lay widely awake after just a few hours of sleep get too much noradrenaline and rocket straight out of (deep) sleep. Since MAO A enzymes govern the break down of noradrenaline, people with that mutation might be more suspectable to having this kind of insomnia)

Perhaps there are some enzymes needed for transitioning from stage 2 into stage 3 sleep also...?

So I tend to wake up around 4:30, sit at the computer, exercise my OCD (reinforced by COMT?) and fall asleep again 2 hours later.

Having sugar and stirring up candida also promotes lots of urine production for me - not sure why yet. That was also very true (but not such high volume) pre-CFS. What's your idea on that?

First thing that comes to mind is histamine. Did you have any sucess with S. boulardii? Or increasing calcium solubility?

 

[Sherlock]

However, I suspect that lactic acidosis from use of anaerobic energy pathways is probably the greater influence. It makes sense that exercise itself can ameliorate that, if it is mild enough to cause only minor lactic acid loading of tissues, and is increased slowly enough to induce constructive adaptation.

Exactly right in my case. Here is what I did at my lowest point of staying in bed for days, sitting my way downstairs only for food/bathroom.

I decided one day to sit my way down the steps to get some exercise - for enjoyment plus I've always said that exercise makes the body run right. I instinctively knew what to do. It took a while to set up a dumbbell to do dumbbell rows - choosing that exercise because the muscle mass involved was not too much (like legs would be) or too little (like arms would be). Even setting up the dumbbell with the right amount of weight made me breathe hard. After I caught my breath, I proceeded to do one set with the right hand, 8 or so reps. Then I immediately teetered and gasped my way to the couch and collapsed on it for 5-10 minutes.

After that, I got up and did the other side, then collapsed again until I could crawl up the steps on all fours. Ahh. good times, good times Two days later, I'd repeat. I got better every time.

So now when I see people ask how long they should exercise, thinking in terms of 5 versus 20 minutes or so, in my mind the correct answer is 20 seconds for each side, then stop.

Btw, I didn't know about using bicarb back then.

 

[Sherlock]

Did you have any sucess with S. boulardii? Or increasing calcium solubility?

Various anticandida strategies help me - like using clove powder or even brewing live saccaromyces.

What is the purpose of using vit A with calcium? anti-acid buffering?

 

[Sidereal]

Histamine in the regulation of wakefulness.
Abstract
...and Sominex is simply the antihistamine diphenhydramine.

I am figuring that when the bladder is full, the body's means to wake the person is by increasing histamine - which IIRC also goes high in the morning. With me being probable MTHFR 677, I don't break down that increased histamine so can't get back to sleep.

Diphenhydramine helps me a lot. Before I started taking it I was mostly bedridden.

 

[Gondwanaland]

What is the purpose of using vit A with calcium? anti-acid buffering?

I must confess that I found it out by accident, but I guess this is the mechanism
After a while, taking magnesium wouldn't help with sleep anymore, on the contrary: I was getting night sweats.
So I took vit A with the intent to counter the excess magnesium w/o taking calcium orally.
I actually had to stop taking vit A due to the fact it's an immune booster and this isn't good for my autoimmune condition.

 

[Sherlock]

Diphenhydramine helps me a lot. Before I started taking it I was mostly bedridden.

Before CFS, if I took a benadryl in the evening I'd be wiped out for most of the next day. After CFS, that didn't happen anymore. I'm assuming that my baseline of circulating histamine went up [edit: which is for me the element that makes this a self-sustaining condition]. Plus, when I get sick these days (such as with a virus cold) my eyes burn and I can hardly read because of blurring - thinking again that histamine is the culprit, maybe with interferons. I suppose I should try the MC stabilizer for the eyes some day - or else stop thinking I can get away with having sugar -- except sometimes I do get away with it remarkably well.

 

[Gondwanaland]

my eyes burn and I can hardly read because of blurring

I associate this symptom with high ammonia (intuitively).

 

[Sherlock]

After a while, taking magnesium wouldn't help with sleep anymore, on the contrary: I was getting night sweats.

Hmmm... I've been getting mild sweating at night lately, thinking it was from the tart cherry. But I'd also been taking Mg citrate again lately, so maybe that was the cause. Since night sweats are a symptom of lymphoma, (as well as infection) maybe the Mg is activating B-cells to secrete cytokines.

 

[Sherlock]

intuitively

I will say that I think intuition/instinct combined with a large amount of self-perception is invaluable - more so than studies or expert opinions. The science per se does not currently have an answer - and besides, all the heterogeneity (between and even within individuals) makes that unlikely for large numbers of sufferers anyway. Studies certainly have a place, but can only take us so far until it only becomes a situation of spinning our wheels.

I used to love studying pathways, not so much anymore. Now I prefer anecdotes and serendipity.

 

[MeSci]

I have never heard of a case of acidosis or alkalosis in ME though. I am not sure it ever happens. Lactic acidosis is not something to be unconcerned about ... its frequently fatal. I have never heard of a patient dying from this. I suspect Julia Newton is right and once we stop then we shift to alkalinity.

However someone who pushes themselves, and keeps pushing, might risk acidosis. The danger is that the change in the pH shifts lots of critical metabolic and regulatory enzymes. Every enzyme has an optimal pH range.

I had serum bicarbonate 17 mmol per litre (ref range 22-29) when in hospital with severe hyponatraemia, which seems to have been a consequence of ME + overexertion + taking an ACE inhibitor.

According to this page,

Metabolic acidosis is defined as an arterial blood pH <7.35 with plasma bicarbonate <22 mmol/L.

Unfortunately, blood pH is one of the many useful tests the doctors did not do.

 

[Gondwanaland]

@Sherlock well, my intuition comes from studying pathways and making inferences from my blood results
I never found a dr who wanted to ask for an ammonia blood test

EDITED TO ADD: or for a blood pH not even at the ER!

 

[MeSci]

Histamine in the regulation of wakefulness.
Abstract
...and Sominex is simply the antihistamine diphenhydramine.

I am figuring that when the bladder is full, the body's means to wake the person is by increasing histamine - which IIRC also goes high in the morning. With me being probable MTHFR 677, I don't break down that increased histamine so can't get back to sleep.

I did a quick search for your paper and it is here. There's a lot of reference to animal studies, which I would advise ignoring - they are as likely to be irrelevant to humans as they are to be relevant.

I find sedating antihistamines helpful for sleep, and use them as part of my sleep drug rotation scheme. But it's important to note that the sedating ones don't just antagonise histamine - they also have anticholinergic properties. Although your cited paper relates this to histamine, I am fairly sure that the drugs also antagonise cholinergic activity via other (maybe direct?) pathways. This is presumably why the sedating antihistamines are sedating, and the non-sedating ones not, or at least less so.

I have found anticholinergic antihistamines helpful for a number of other ME-related symptoms: muscle tension and cramps, nausea (headache?), anxiety, etc.

I think that MTHFR 677 is a common SNP. Are you heterozygous or homozygous?

 

[MeSci]

Congratulations! Do you mean you can sleep 7-8 hours now?

Having sugar and stirring up candida also promotes lots of urine production for me - not sure why yet. That was also very true (but not such high volume) pre-CFS. What's your idea on that?

[edit: though it's probably from something irritating the bladder lining -- maybe acetaldehyde, or methyhistamine? or something from leaky gut caused by the candida... ]

This paper on sugar and lactic acid may interest you. There are threads on d-lactic acidosis that may be relevant.

I have been puzzling over the polyuria for ages, as have a number of us, and there are threads on that too.

 

[Sherlock]

This paper on sugar and lactic acid may interest you.

Thanks, that might be the most likely possibility (though wherever they said glucose I mentally ubstituted sucrose). Bread etc never ever bothered me. As they write: things are "depending on the specific bacterial population".

I have been wondering of late whether some of the symptoms I ascribe to candida might really be due to some sucrose-loving bacteria. E.g., if I take 2 iodine tablets as an antimicrobial, I don't get the most noticeable sucrose-candida effects, but do get the acidic urine anyway.

They suggest a strategy:

While limiting the supply of dietary sugars to intestinal
bacteria may lessen the degree of acidosis, organic acids may be
removed more rapidly by oxidation if the availability of the compet-
ing fuels such as fatty acids is decreased.

Sounds like a case for intermittent fasting. Or going back to flooding the intestine with baking soda. Or using potassium bicarbonate - if that is non-laxative.