Measured high endogenous acetaldehyde blood levels, discovered something.

[Issie]

I still have the box of taurine. I hope it'll be of help once I can decrease my need for stress hormones enough. I'm slowly getting there .

Not thinking......that was NOT so good of an experiment for you! The depression it caused and low energy, lack of even energy to talk or interact...not thinking. Maybe, pass that one on. (My friends love me, they have gotten to try so many of my discards and failed experiments, for free.)

There will be another way to tweak, when one thing fails. Keep looking......... and it may be the combination. I couldn't use beta alanine, but could L-Carnosine and it is what makes it up along with histidine.

L-Carnosine also takes down aldehydes and ups histamine. Histamine also helps take down acetaldehyde. This is a whole new approach for me with MCAS. Increasing histamine to tweak the histamine receptors to moderate histamine and make it work correctly. There is a thread on this too. I'm NO LONGER using antihistamines, but adding histamine to correct an over response to histamine. Complex and a bit complicated. But I've about got that one figured out.

Here's article on L-Carnosine and aldehydes.

Detoxification of aldehydes by histidine-containing dipeptides: from chemistry to clinical implications - PMC

Aldehydes are generated by oxidized lipids and carbohydrates at increased levels under conditions of metabolic imbalance and oxidative stress during atherosclerosis, myocardial and cerebral ischemia, diabetes, neurodegenerative diseases and trauma. ...

www.ncbi.nlm.nih.gov

 

[dejurgen]

Another aid with bile, that I use when I'm having gallbladder and liver issues, is Ox Bile. When I feel soreness on the upper right side and feel there are issues, using this will help take down this inflammation, help bile move better and provides relief.

Issie had some success with ox bile but was surprised as it is high in taurine. She did really poor on taurine supplements.

Looking back at it, taurine might have worked in the bile because of bile releasing it slower. Consuming a single dose of pure taurine can create quite some osmotic pressure upsetting parts of the body.

If so, that would also point to likely malabsorption problems. Human bile is secreted somewhere at the start of the small bowel to aid digestion. Much of the taurine in it is reabsorbed. When having malabsorption, one hence risks to be low on taurine. When having one malabsorption problem, one can suspect more of them.

 

[dejurgen]

Taurine is a strong osmolite. That can be of help but can IMO be quite tricky to supplement for people with our kind of diseasses. An alternative *MIGHT* be L-cysteine.

L-cysteine is a precursor to taurine. It has however AFAIK way less "osmolitic strength", meaning that it is way less strong at pulling water quickly out of tissues or dehydrating tissues.

The body then can convert L-cysteine to taurine at a slower pace, reducing the size of the potentially damaging "osmolitic shock" by spreading its conversion to taurine and slowing the increase in taurine levels. The body can also decide to shift the L-cysteine to other chemicals if desired or considered safer.

When having CBS mutations, having https://en.wikipedia.org/wiki/Homocystinuria is a real possibility as Meirav said. One of the listed treatment options is:
"occasionally adding cysteine to the diet can be helpful, as glutathione is synthesized from cysteine (so adding cysteine can be important to reduce oxidative stress). "
Of coarse, wikipedia is no medical site...

Cysteine, just as taurine, can reduce oxidative stress.

L-cysteine, just like L-carnosine can directly "catch" acetaldehyde by chemically reacting with it, removing one molecule of L-cysteine and one molecule of acetaldehyde in the proces. The end product of that reaction is a hopefully less toxic product that can hopefully be safely removed by the body. We have read several research papers on that.

Histamine, just like diamines putrescine and spermidine, can also react chemically with acetaldehyde and aid in its removal.

Putrescine and spermidine are build from ornithine and often seen in increased amounts in inflammatory conditions. This correlation is often explained as putrescine and spermidine causing inflammation, but some researchers suggest it could have some beneficial effects in inflammation too. This could be reducing toxic amounts of acetaldehyde for one.

L-cysteine and N-Acetyl-L-Cysteine (NAC) are not the same. It is likely that taking the NAC variant is less good at catching acetaldehyde as, while not being the same, an acetyl group already has been added to L-Cysteine.

Issie however says she had once more bad to very bad experiences with taking NAC. She also adds "NAC is more usable form and is metabolized better." Having less of it (L-cysteine) absorbed may make "microdosing" a bit easier I'd say. As some say: every disadvantage has its advantage. I do have L-cysteine waiting for some time in my cabinet.

I each time try and stabilize my health first, try and have a good view on my health before changing a single thing, try a supplement I have good hopes for at very low dose, watch out for frequent nasty surprises even at such low doses and then evaluate after about a month. At that rate I can't test that much a year so it'll take some time till I get to test L-cysteine myself. Issie has keener senses then me so she can decide at shorter time intervals.

Taurine, given the information Meirav posted, seems to reduce acetaldehyde by influencing the ALDH enzymes. That has the benefit of not being a "single use" acetaldehyde scavenger but ALDH is a reduction enzyme indirectly needing oxygen. When the acetaldehyde is formed by too high oxidative stress inside
cells, chances are that that is cause by... hypoxia. Then the ALDH enzymes will be a bit less helpfull too. So Taurine and L-cysteine have different roles (and locations / circumstances) they work best to scavenge acetaldehyde.

When trying, consult your doctor and still ask him to slash dosing. As Issie often says: when taking a pure product, it often becomes as potent as a real drug. We both sure experienced that!

I expect the main difference between L-carnosine and L-cysteine in regard with catching acetaldehyde to be that L-carnosine does it's job mainly inside (brain and heart cells) (maybe gut cells too, I don't remember for sure) and L-cysteine may work more in the bloodstream. Remember that cysteine has sulphur in it too for if you have problems with sulpur metabolism.

 

[dejurgen]

Seeing you are really helped with taurine, having low K+ AND Na+ (as you wrote on the https://www.healthrising.org/blog/2...ndrome-pots-renin-aldosterone/#comment-988961 blog) makes sense to me. Just as having modest Mg and Ca while trying to up them.

Also the sentence "I can drink so much, but the water doesn't get into my cells" that Issie said so many times makes much more sense now. And now you say it too ;-).

Taurine is a main osmolite *inside* human cells. Being low on it makes the cells less osmolitic meaning they'll draw in less water. In other words: the water doesn't get into your cells.

Then the inner pressure in the cells decreases, and your cells become shrimpled. They'll risk even crushing in or imploding. Compare it to a WWO I submarine diving too deep. The water pressure will crush the submarine like if it were made from paper.

Something similar can happen if the inner osmolitic pressure in the cells is too low. Not a nice mental picture is it? Such "crumbled cells" risk quite a bit to be attacked by the immune system.

So the immune system has to be turned down as it sort of is the explicite task of the immune system to clean up "crumbled (own) body cells". Still, the many partly crumbled cells will have an increased chance at being attacked by the immune system. That's auto-immune problems.

At the same time: the immune system has to be turned down in order to not cause *massive* auto-immune problems. That's having the need for a weakened immune system.

And so we end up with another sort of paradox in ME and similar diseases: we seem to have both too strong AND too weak an immune system. See above ;-).

This "crumbling of cells" may be an essential part of POTS too. When standing up, the fluid / blood pressure on the lowest cells increases quite a bit. That means "crumbling those cells even more". It's a bit like getting that WWO I submarine in a lot deeper water. Its metal will start to make plenty of scary and loud sounds.

If so, the heart CAN'T increase it's pressure a lot to get the blood to the head quickly enough because that would further increase the pressure on those cells under siege in the lower legs. Adaptations must be done first. Slow increase of pressure to supply the head with blood sounds like POTS to me.

There do exist several potential options here, for example:
* Releasing (plenty of) histamine (in the *returning* or venous part of the blood flow). That increase the diameter of the veins returning to the heart. That reduces the pressure needed (on top of the pressure need to counter gravity) to push the blood back to the heart. Remember: having the same flow in wider tubes requires less pressure. So the local tissue doesn't have to press that hard to get the blood returning (to the heart) or it can reduce pressure.
* The histamine will also increase the permeability of local cells around the blood vessels. That means that water will easier get in and out of the blood vessels. When done around the returning blood vessels, it will increase the ease of collecting pooling blood / fluid for return to the heart. When done more at the capilaries in between the arterial and vein side, it will let leak plenty of fluid in the surrounding tissues. That does sound bad, but "organised fluid leak" is comparable to a safety valve in a heating installation or many other hydraulic installations. What happens if you have got a leak? Pressure drops! When done right, this again drops the dangerously high pressure (increase from standing up quickly) on the "crumbling" limb cells when quickly standing up.

One can say that the latter is increasing blood pooling in the legs. It is. It does however have the ability to (temporarily, until adaptions are complete) help reduce the mechanical (pressure induced) stress on the lower limb cells. There is no free lunch. Mast cells do have pressure sensitive receptors by the way. Those might help to decide to dump plenty of histamine.

This "dumping" of water in the intercellular space and connective tissue surrounding the capilaries will cause for some amounts of seconds less blood to return to the heart. A normal reaction of the heart then is to pump quicker but with smaller displacements (per pumping action / heart beat). That IMO helps protecting the wall of the heart chambers from damage (from dangerous underpressure and risk for rupture) when too few blood returns to the heart. I wrote on that one before. It will however cause very high heart rate while few blood reaches the head, feeling floaty headed or fainting.

When acummulating too long, it will increase pressure again a bit as "a full bag" exerts more pressure then "a less full bag". Compare it with the tension on the plastic of a kids baloon when filled to the brink with water or filled only with a bit of water. So the body can't allow this accumulation of fluids to exist for too long or it'll cause troubles too. Moving the legs by walking or fiddling a bit will help to remove both pooled fluids and pumping blood better back to the heart.

Too much of all of the above may weaken the tissues strength over (years of) time however... ...making preventing bad edema more and more challenging. In either case, having lower total blood volume, a common thing in our disease, helps to prevent too bad lower limb edema and reduces excess pressure when standing up quickly a bit too.

That may be another reason for the body to try and lower blood volumes. It may even be another partly reason for creating other osmolite imbalances (ratios between Na+ / K+ / Mg / Ca /...) in order to trigger a secondary drop in total blood volume...

The above is very very close to describing POTS plus POTS initiated MCAS in action.

I'm (very) far from an EDS specialist but I can imagine that having crumbled cells too isn't really helping "structural integrity". "Crumbling cells" do not necessarily need to mean a reduction of the size of the cells in all directions.

For example, when having a perfectly round and well inflated soccer ball and then releasing much of its air, it's total volume will decrease a lot. But it could turn more into a sort of a dish like shape when standing on it, up to the point that the (soccer) football has a *bigger* maximum diameter but a far lower height (then the fully inflated round ball).

When instead pulling at the only partly inflated soccer ball, it could become longer but less wide, resembling an American football that looks more like a bean.

Combine those visuals and you may end up with something like EDS when puling on limbs. It might be interesting to watch out for how EDS evolves with Meirav (and Issie) when they feel being able to hydrate better.

 

[Issie]

Carnosine works in the brain the blood, muscles etc.

Carnosine - an overview | ScienceDirect Topics

www.sciencedirect.com

Use of Carnosine for Oxidative Stress Reduction in Different Pathologies

The main properties and biological effects of the antioxidant carnosine, the natural dipeptide <i>β</i>-alanyl-L-histidine, are considered. Data on the effective use of carnosine in different pathologies are presented. Special attention is paid to issues of use of carnosine in neurologic and...

www.hindawi.com

It is synthesized and contained in human muscle and nervous tissues, is easily absorbed in the digestive tract, penetrates through blood-brain barrier, and has high bioavailability and membrane-stabilizing action. Carnosine is a low molecular weight hydrophilic antioxidant of direct action, though it can also have an impact on the antiradical protection system of the organism [13]. Results of experiments on rats showed that carnosine accelerates the metabolizing of cortisol and noradrenaline released into blood of animals under stress, showing the mediation effect of carnosine [14]. Decrease in level of stress hormones in blood leads to a decrease in the severity of OS.

It has also been reported that carnosine prevents toxic effects of hyperhomocysteinemia in rats [30]. It is known that homocysteine is a potent initiator of oxidative stress in many tissues. However, the molecular mechanism of such protection is not clear. Perhaps carnosine modulates affinity of glutamate receptors to homocysteine, prevents accumulation of ROS, or has other protective mechanisms.

 

[Issie]

As for L-carnosine affect on aldehydes and therefore acetaldehyde

Detoxification of aldehydes by histidine-containing dipeptides: from chemistry to clinical implications - PMC

Aldehydes are generated by oxidized lipids and carbohydrates at increased levels under conditions of metabolic imbalance and oxidative stress during atherosclerosis, myocardial and cerebral ischemia, diabetes, neurodegenerative diseases and trauma. ...

www.ncbi.nlm.nih.gov

Histidine dipeptides such as carnosine form Michael adducts with lipid-derived unsaturated aldehydes, and react with carbohydrate-derived oxo- and hydroxy- aldehydes forming products of unknown structure. Although these peptides react with electrophilic molecules at lower rate than glutathione, they can protect glutathione from modification by oxidant and they may be important for aldehyde quenching in glutathione-depleted cells or extracellular space where glutathione is scarce. Consistent with in vitro findings, treatment with carnosine has been shown to diminish ischemic injury, improve glucose control, ameliorate the development of complications in animal models of diabetes and obesity, promote wound healing and decrease atherosclerosis. The protective effects of carnosine have been linked to its anti-oxidant properties, it ability to promote glycolysis, detoxify reactive aldehydes and enhance histamine levels. Thus, treatment with carnosine and related histidine dipeptides may be a promising strategy for the prevention and treatment of diseases associated with high carbonyl load.

 

[Issie]

I will make a note of other things I'm doing to tweak this.

DHM with Yucca and a Liver Cleanse/support Chinese formula at night. And during day a combination pill of Bee propolis/pollen/royal jelly. This helps take ammonia down, as does Yucca. This is also connected to CBS methylation issues and problems with ammonia.

I'm still not great, but better. I still need to pace and not get under too much stress or have to much drama or I crash. As most ME patients with a grocery cart full of other things, I'm super sensitive and have a keen awareness. But I do feel I'm finding some nice bandaids ?.

 

[AcH influenced]

Holy cow I don't look for a couple of days on Health Rising and I suddenly see a whole new page of all your ideas. Where do you people get the energy from, are you absolute sure you have ME / CFS ;-) ?

Interesting, I might actually try the Taurine just for fun. Over the years I drank a few of these Red Cow alternatives here and there and at least it did not seem to make things much worse immediately but I can try the pure stuff carefully since it is not that expensive. I'll heed the warnings, thanks. Can't go to a doctor for tests but I don't mind experimenting I actually like it sometimes but I got tired of trying expensive supplements very quickly...

Fisetin is also a very interesting substance as a nootropic.... I once made the mistake in the beginning of trying that stuff out with an extra pill in the evening but stupidly combined that with a lot of coffee too ! Oh dear that was like how a bad "trip" experience must be for a whole evening it made me extremely anxious but with high energy and tiredness at the same time but I could not concentrate at all anymore and did not know where to look for comfort ! Happy when it finally subsided, never again !

>@dejurgen it is very fitting what you said about coffee and energy paradox. People always complain that coffee stops them from falling asleep but I can take 2 big coffee 2 hours before sleeping and it makes no difference to me at all in sleep quality and sometimes it seems even to work better overall. It is a double edged sword though this coffee thing I want to try to live without coffee once again but I always seem to be drawn to it as a drug addict. Isn't it weird how this disease seems to turn everything upside down and how weird we react to certain medicine and supplements ?

I do have some interesting news though I actually got hold of some Metadoxine the naughty way and tried that. It was one of these things I had secretly very high hopes of because it is a prescription medication specifically related to acetaldehyde and such but it did not work out. I am very happy I only took half a pill at first because it made me feel very weird... and not in a good way. The second half the next day and I did not feel like continuing. Can't really describe how exactly it made me feel but definitely not like anything I have experienced before. Completely different / bad / strange. I might try again once again in the future just for evaluating what it was like again but not good overall. So no, another experiment that did not work, I give up "scavenging" or try making the acetaldehyde less in that kind of way for good I think.

It might be wrong but I actually think it says something about what is going on because this drug is usually very well tolerated even by alcoholics in a very sorry state. So why do I react so really weird / bad then ? What is going on in a biological manner ? I said it before but this whole endogenous acetaldehyde thing, although we can of course learn a lot from the alcohol research, might just work a bit different than is currently known. There is just no / hardly any information available to us.

I have discovered something new and very important that I am sure you all will find very interesting I am working at it and will take some time, more later.