Dengue Fever/shock May Be Simply An Endotoxin-driven Symptom

haidut

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I have been studying endotoxin and its mechanisms lately, so I will post more on that soon. For now, I will just say that endotoxin seems to mediate most of its effects through the so-called TLR4 "receptor". In agreement with Peat's writings about flu and its connection to endotoxin, this study shows that the Dengue virus triggers the fever/shock through a protein that is an agonist/activator of the TLR4 "receptor". In other words, the Dengue fever is very much like the fever or shock that endotoxin itself causes. Blocking the TLR4 "receptor" completely stopped the Dengue fever. I wonder how many other viral "diseases", in addition to flu and Dengue, are simply an endotoxin "receptor" activation.
Niacinamide, cyproheptadine, mianserin, and methylene blue are some of the substances that can stop the endotoxin process and the associated fever and shock.

Viral Protein That Triggers Dengue Shock Identified
"...The team found that NS1 binds to Toll-like receptor 4 (TLR4), a molecule on the surface of immune cells known for recognizing and activating inflammatory responses against bacterial lipopolysaccharide (LPS), a component of bacterial cell membranes. When the researchers blocked TLR4 signaling with either a TLR4 antagonist or an anti-TLR4 antibody, the effect of NS1 on immune and endothelial cells was lost. Further experiments also showed that treatment with a TLR4 antagonist alleviated vascular leakage in a mouse model of dengue infection. This suggests that NS1 may act in manner similar to bacterial toxins such as LPS—by binding TLR4 and activating the production of inflammatory cytokines that then triggers vascular leakage. Indeed, the hallmarks of LPS-induced bacterial sepsis—increased production of inflammatory cytokines, increased vascular permeability, and subsequent septic shock—are uncannily similar to dengue-induced shock. Scientists are now interested in developing anti-dengue vaccines and drugs that target the NS1/TLR4 interaction. In a separate study published in the same issue of Science Translational Medicine, researchers led by Professor Eva Harris at the University of California, Berkeley found that immunizing mice with small amounts of NS1 protected them against subsequent lethal dengue infection. Such a vaccine, if developed, could prevent at-risk patients from progressing to severe dengue."
 

Parsifal

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I have been studying endotoxin and its mechanisms lately, so I will post more on that soon. For now, I will just say that endotoxin seems to mediate most of its effects through the so-called TLR4 "receptor". In agreement with Peat's writings about flu and its connection to endotoxin, this study shows that the Dengue virus triggers the fever/shock through a protein that is an agonist/activator of the TLR4 "receptor". In other words, the Dengue fever is very much like the fever or shock that endotoxin itself causes. Blocking the TLR4 "receptor" completely stopped the Dengue fever. I wonder how many other viral "diseases", in addition to flu and Dengue, are simply an endotoxin "receptor" activation.
Niacinamide, cyproheptadine, mianserin, and methylene blue are some of the substances that can stop the endotoxin process and the associated fever and shock.

Viral Protein That Triggers Dengue Shock Identified
"...The team found that NS1 binds to Toll-like receptor 4 (TLR4), a molecule on the surface of immune cells known for recognizing and activating inflammatory responses against bacterial lipopolysaccharide (LPS), a component of bacterial cell membranes. When the researchers blocked TLR4 signaling with either a TLR4 antagonist or an anti-TLR4 antibody, the effect of NS1 on immune and endothelial cells was lost. Further experiments also showed that treatment with a TLR4 antagonist alleviated vascular leakage in a mouse model of dengue infection. This suggests that NS1 may act in manner similar to bacterial toxins such as LPS—by binding TLR4 and activating the production of inflammatory cytokines that then triggers vascular leakage. Indeed, the hallmarks of LPS-induced bacterial sepsis—increased production of inflammatory cytokines, increased vascular permeability, and subsequent septic shock—are uncannily similar to dengue-induced shock. Scientists are now interested in developing anti-dengue vaccines and drugs that target the NS1/TLR4 interaction. In a separate study published in the same issue of Science Translational Medicine, researchers led by Professor Eva Harris at the University of California, Berkeley found that immunizing mice with small amounts of NS1 protected them against subsequent lethal dengue infection. Such a vaccine, if developed, could prevent at-risk patients from progressing to severe dengue."

Very interesting, thanks! In my experience, the flu and colds are just endotoxins.

So with the dengue, the mosquitoes give you bacterias and endotoxins from these bacteria in your blood give you the symptoms?
 
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haidut

haidut

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Very interesting, thanks! In my experience, the flu and colds are just endotoxins.

So with the dengue, the mosquitoes give you bacterias and endotoxins from these bacteria in your blood give you the symptoms?

Pretty much, yes. I guess the finding is that if you managed to antagonize the endotoxin "receptors" most of these pathogens would be benign.
 

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@haidut - aside from starches, I would love to hear a list of foods/substances that you may have found to trigger endotoxin, since you have been studying it. While I know it seems it's different for everyone, hard-boiled eggs are a huge trigger for me. I'm still suffering from over-boiling my eggs the other day. I can eat them raw no problem, which I find strange.

Also, is there some sort of thyroid withdrawal that could lead to a serotonin surge/endotoxin symptoms? This seems to be a huge issue for me when I stop thyroid, which is why I was happy to switch to topical usage. But when it's gone from the system, it kind of feels like a bomb has gone off. Fortunately, my MB is on the way.....
 

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But in general how do you know whether the fever is good or bad? You can always kill the fever or reduce it by intervention such as taking aspirin, but will you heal faster and does it help to get rid of the infection or does it tamper with the mechanism the body has to get rid of it (and that could certainly include inflammation)? This study suggests that in the case of Dengue, the fever seems to promote an inflammation that is not helpful. But what about flu... If I get a flu, although I intervene to make sure I get sleep or keep nourished, I am very hesitant as to whether directly control and lower the temperature. (Actually even the nourishment is not that simple -- there could a reason why you are nauseous and should not eat for a while.)
 
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Parsifal

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@haidut - aside from starches, I would love to hear a list of foods/substances that you may have found to trigger endotoxin, since you have been studying it. While I know it seems it's different for everyone, hard-boiled eggs are a huge trigger for me. I'm still suffering from over-boiling my eggs the other day. I can eat them raw no problem, which I find strange.

Also, is there some sort of thyroid withdrawal that could lead to a serotonin surge/endotoxin symptoms? This seems to be a huge issue for me when I stop thyroid, which is why I was happy to switch to topical usage. But when it's gone from the system, it kind of feels like a bomb has gone off. Fortunately, my MB is on the way.....

Maybe eggs are a problem because they increase the flow of bile from the gallblader and haidut said in a podcast (on digestion) with Danny Roddy that bile is as much serotoninergic than endotoxins? I wonder if too much taurine/glycine or caffeine could have the same effects? @haidut
 

lindsay

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Maybe eggs are a problem because they increase the flow of bile from the gallblader and haidut said in a podcast (on digestion) with Danny Roddy that bile is as much serotoninergic than endotoxins? I wonder if too much taurine/glycine or caffeine could have the same effects?

I don't have a gallbladder any longer. Had it removed about ten years ago. That being said, I do take Ox Bile because it's the only thing that allows me to consume proteins and digest them easily - especially eggs. However, I did begin taking a taurine supplement on Thursday (the day the stomach went sour). I stopped taking it on Friday. Symptoms just subsided today. That could explain my problem because last week I was eating a lot of gelatin too. I just can't win. I guess I don't need all these supplements. But I've not had a problem with the Ox Bile in the past. This is the first real bad episode I've had in a LONG time.
 
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haidut

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@haidut - aside from starches, I would love to hear a list of foods/substances that you may have found to trigger endotoxin, since you have been studying it. While I know it seems it's different for everyone, hard-boiled eggs are a huge trigger for me. I'm still suffering from over-boiling my eggs the other day. I can eat them raw no problem, which I find strange.

Also, is there some sort of thyroid withdrawal that could lead to a serotonin surge/endotoxin symptoms? This seems to be a huge issue for me when I stop thyroid, which is why I was happy to switch to topical usage. But when it's gone from the system, it kind of feels like a bomb has gone off. Fortunately, my MB is on the way.....

If you search the forum you will find many threads on foods increasing serotonin. Basically, anything high in tryptophan and low in BCAA, and anything that irritates the gut will increase serotonin synthesis. Also, anything estrogenic or increasing cortisol will also eventually lead to serotonin increase.
 
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haidut

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Maybe eggs are a problem because they increase the flow of bile from the gallblader and haidut said in a podcast (on digestion) with Danny Roddy that bile is as much serotoninergic than endotoxins? I wonder if too much taurine/glycine or caffeine could have the same effects? @haidut

Depending on how much bile acid you produce, yes, it can be serotonergic. But bile acids are needed for proper fat digestion, so you do need some. Bile acid also activates the bile acid receptor, just like allopregnanolone and progesterone, and that increases synthesis of T3 thus raising metabolism. Still, that is one of the reasons high fat diets are not healthy (IMHO) - i.e. through bile acid release and PUFA interacting directly with the colonic cells, high fat diet increases gut serotonin.
 

lindsay

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If you search the forum you will find many threads on foods increasing serotonin. Basically, anything high in tryptophan and low in BCAA, and anything that irritates the gut will increase serotonin synthesis. Also, anything estrogenic or increasing cortisol will also eventually lead to serotonin increase.

Thank you for your answer. This would explain why cheese is my favorite protein. Although it's higher in tryptophan, it's also higher in the BCAA's, and far more satisfying than milk - IMO. But as for "irritating" foods, well than I think that's where it gets confusing. There are many foods which are powerful antibiotic foods and which lower endotoxin and estrogen which could cause "irritation" - such as oranges, orange peel, carrot, etc. Antibiotics can also be incredibly gut "irritating." But also with positive effects. Also, I recall RP mentioning Tomato skin as being serotonergic in his article on serotonin, but tomato skins also contain naringenen. I know this study is speaking of the extract of tomato skin, but it's interesting nonetheless:

Anti-allergic activity of naringenin chalcone from a tomato skin extract. - PubMed - NCBI

Anyhow, this is where I get very confused by serotonin because on the one hand, the bad effects are well known and I've experienced them long term from my use of Zelnorm in college - horrible terrible drug. On the other hand, if a food is slightly "irritating" but also well known to lower endotoxin, is it really serotonergic? Also, any thoughts on the Taurine which was mentioned? I began taking that supplement on Thursday, which coincided with my 3 day bout of Nausea & accompanying headache (I have never been a migrainer unless I eat something that bothers my stomach). I thought it was the eggs I ate at first, but I'm beginning to think it was the Taurine supplement - I got one of the ones with no excipients. I took it on Thursday and Friday and my symptoms didn't subside until yesterday - I came to my senses on Saturday and stopped all internal supplements. I suspected the supplement, but was too excited to try this Taurine stuff. That being said, I wasn't able to enjoy any positive effects from it whatsoever.
 
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I had no benefit from taurine either. At first. Now I feel it is highly supportive. I think there is an adaptation phase and you have to start very slow and low.
 

lindsay

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I had no benefit from taurine either. At first. Now I feel it is highly supportive. I think there is an adaptation phase and you have to start very slow and low.

That is good to know :) What was your beginning dose (if you recall) and how often did you take it? I cannot risk another "episode" - if it was the taurine - so it will have to wait until a period of time when I do not have to work for a couple of days. But I'm not opposed to giving it another go - even if it's just drinking some Red Bull.
 
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That is good to know :) What was your beginning dose (if you recall) and how often did you take it? I cannot risk another "episode" - if it was the taurine - so it will have to wait until a period of time when I do not have to work for a couple of days. But I'm not opposed to giving it another go - even if it's just drinking some Red Bull.

I would start with just a tiny amount, like perhaps 200mg. That's what I do. And then increase it.

I had some heartburn from it at first. And felt weird mentally. That's long gone, after a week or two.
 

Parsifal

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Depending on how much bile acid you produce, yes, it can be serotonergic. But bile acids are needed for proper fat digestion, so you do need some. Bile acid also activates the bile acid receptor, just like allopregnanolone and progesterone, and that increases synthesis of T3 thus raising metabolism. Still, that is one of the reasons high fat diets are not healthy (IMHO) - i.e. through bile acid release and PUFA interacting directly with the colonic cells, high fat diet increases gut serotonin.

Interesting. At first coffee made me release a lot of bile and I felt awful, same with glycine and taurine and now I'm taking the 3 of them and don't feel like it increases the bile too much and my liver seems healthier.
 

lindsay

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I would start with just a tiny amount, like perhaps 200mg. That's what I do. And then increase it.

I had some heartburn from it at first. And felt weird mentally. That's long gone, after a week or two.

Head face-first into palm..... Boy was I dumb - that must have been what caused the nausea and headache for sure! I saw the serving size was 1/4 tsp (or 1 gram) and thought, "Sounds like a starting point!" No wonder I felt horrid for two days. In fact, the headache was so bad, I ordered Riboflavin powder, thinking for sure I was becoming a migrainer. When I got the Riboflavin powder, I was VERY cautious and only took a tiny bit - no side effects there. Whew! Well, at least that means I can probably eat eggs again without issue :)
 

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Effect of Tryptophan and Selected Analogues on Body Temperature of Endotoxin-poisoned Mice

It's conflicting: on some occasions endotoxin is associated with an increase in temperature, while other cases a decrease. Is it based on how well-prepared the organism is to defend from a threat? If already exhausted, endotoxin only depleting it even more, forcing the temperature down as conservation; or if able to deal with it, mounting a reaction such as fever by upping the temperature, consuming things faster with the intent of getting rid of the problem as soon as possible.
 
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haidut

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Effect of Tryptophan and Selected Analogues on Body Temperature of Endotoxin-poisoned Mice

It's conflicting: on some occasions endotoxin is associated with an increase in temperature, while other cases a decrease. Is it based on how well-prepared the organism is to defend from a threat? If already exhausted, endotoxin only depleting it even more, forcing the temperature down as conservation; or if able to deal with it, mounting a reaction such as fever by upping the temperature, consuming things faster with the intent of getting rid of the problem as soon as possible.

Yes, I have seen endotoxic response in both young and old people. In young people and children it can cause high fever and even vomiting/nausea. In older people it most often causes profound hypothermia and hypotension (pre-shock state), which is due to the excessive amount of NO the endotoxin triggers, and which is why methylene blue is used as an antidote for those people or people getting the same symptoms during surgery.
 

triple

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Pretty much, yes. I guess the finding is that if you managed to antagonize the endotoxin "receptors" most of these pathogens would be benign.


How would one antagonize the endotoxins receptors ?
I am travelling to SE Asia and considering retiring there but Dengue seems to be quite prevalent
 

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