The Benefits Of Fasting Are Due To Lowering Endotoxin (LPS), Not Less Calories

baccheion

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When vitamin D sufficient, the body releases antimicrobial peptides as-needed to balance intestinal flora.
 
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haidut

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I was surprised to hear this RP clip last night. Without caveat, he says that a healthy person can go not eating for 12-15 hours without a stress response.


I think for most people, it is no more than 3-4 hours and for some very hypo/sick ones it could be as little as an hour.
 

Wagner83

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I already posted a study showing that benefits of fasting are due to lower endotoxin. There is nothing special to fasting beyound lower endotoxin and lower PUFA (initially). After a few days of chronic fasting stress hormones become chronically elevated and all hell breaks loose. The increased lipolysis alone is pretty bad. That's probably why cancer patients see great response from fasting for up to a week and then their tumor becomes really aggressive.
The Benefits Of Fasting Are Due To Lowering Endotoxin (LPS), Not Less Calories
Courtesy of Amazoniac : NYAS Publications
 

Alpha

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I think for most people, it is no more than 3-4 hours and for some very hypo/sick ones it could be as little as an hour.

I don't think humans need to eat every 3-4 hours. It's all dependent on calories. Timing is largely irrelevant.
 

CLASH

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Easiest ways to lower endotoxin in the gut while also protecting the body from it:

1) eat alot of beef tallow, coconut oil, cocoa butter

2) avoid refined carbohydrate sources and starches; yes that includes table sugar, especially if you have gut issues

3) limit your carb/ fiber sources solely to tolerated fruits/ juice and vegetables that have little to no starch

4) get adequate vitamins; I think at this point most of us on the forum know what these are

5) avoid/ limit PUFA as much as possible

6) eat enough protein with the fat to help the liver

7) bring awareness to the tension in your body periodically and conciously relax it utilizing the breath. This will help to restore blood flow to the gut.

8) BONUS: carrot salad enema...
 
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haidut

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I don't think humans need to eat every 3-4 hours. It's all dependent on calories. Timing is largely irrelevant.

I meant it as an example of how unhealthy most people are these days, not as a prescription.
 

SB4

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Perhaps this has been answered elsewhere on the forum but I can't seem to find anything.

What are the down sides to blocking TLR4? It has to have some useful function to have been preserved so long. If you have lots of endotoxin and that endotoxin gets transported into the blood stream by chylomicrons, wouldn't you need TLR4 to warn your body it is coming and to mount a proper response?

Does TLR4 facilitate transfer of LPS to the bloodstream?
 

lvysaur

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Perhaps this has been answered elsewhere on the forum but I can't seem to find anything.

What are the down sides to blocking TLR4? It has to have some useful function to have been preserved so long.

Can't give a technical answer, but this is logically specious. Many traits that could have been useful in ancient contexts are no longer so. For example, low metabolism, smaller body size, etc.
 

SB4

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Can't give a technical answer, but this is logically specious. Many traits that could have been useful in ancient contexts are no longer so. For example, low metabolism, smaller body size, etc.
That is a good point but even so, we don't know that it is no longer useful. Does anyone know what it could have been useful for even if it is now obsolete.
 

rei

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Rest assured most that we have preserved carries a function. As long as it is there evolution has not finished replacing it. This is almost admitted even in the medical field with for instance the reversal of opinion of the appendix. The ability to regulate metabolism is crucial even if at a glance modern way of living would seem to prefer to constantly burn all the calories you can. But in reality this is essentially what is happening. If your metabolism goes down it is only because it was impossible to continue on with higher metabolism using the nutrition and environment you existed in. Same goes with body size, you grow as big as the environment allows.
 

rei

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I was surprised to hear this RP clip last night. Without caveat, he says that a healthy person can go not eating for 12-15 hours without a stress response.

In the latest jodelle interview he said a healthy person can go 24 hours. I believe "exercising" the glycogen stores might be similarly healthy as exercising the muscles.
 

SB4

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I recently came across this article. It basically shows that TLR4 is important in killing a specific CNS virus in mice.

They saw mice with healthy gut biomes responded better to hepatitis virus than ones who made received antibiotics etc. When they administered TLR4 to the mice with bad biomes their symptoms improved.

Those mice with the disrupted microbiomes displayed significantly weakened immune responses to the hepatitis virus, and ultimately showed worse signs of neurodegeneration, including paralysis. Interestingly, those mice with disrupted microbiomes also showed less active brain immune cells, called microglia, than the healthy mice.
Taking the research one step further, the team homed in on what mechanism the gut bacteria could be using to enhance the activity of microglia in the CNS and brain. Experiments revealed one particular immune signaling protein, called TLR4, seemed to be the key to this process. To confirm the hypothesis that microglia activity can be enhanced through TLR4 signaling from the microbiome, the researchers administered TLR4 to virally infected mice with disrupted microbiomes. And, amazingly, the animals indeed showed reduced neurological damage from the virus.

To me this makes sense as TLR4 is probably conserved for a reason. Perhaps if you eat some bad food then TLR4 provokes an immune response to kill anything dangerous that might get it.
I suspect that in some situations this response isn't need / is excessive so in those cases blocking would be good however in other cases you could do harm.
Maybe TLR4 is needed to prevent certain bacteria / viruses that are destroyed in cooking so most dodgy food will activate TLR4 but it wouldn't be needed.

@haidut
 
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haidut

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Perhaps this has been answered elsewhere on the forum but I can't seem to find anything.

What are the down sides to blocking TLR4? It has to have some useful function to have been preserved so long. If you have lots of endotoxin and that endotoxin gets transported into the blood stream by chylomicrons, wouldn't you need TLR4 to warn your body it is coming and to mount a proper response?

Does TLR4 facilitate transfer of LPS to the bloodstream?

The TLR family of receptors mostly sense pathogen presence.
Toll-like receptor - Wikipedia
"...Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes"

So, without any TLR4 you'd probably be more vulnerable to bacterial infections. But unless you were born with a mutation so that you lack TLR4 entirely, I don't think you'd need to worry about blocking TLR4 too much. Even the most potent antagonists would not completely shut it off and even the most potent ones tend to have relatively short half life and receptor-association timeframes. Unlike an enzyme like aromatase that can be "suicidally" blocked and as such have estrogen driven to very low levels, I don't think a similar situation is possible with TLR4. In the vast majority of cases, it is overactivation of TLR4 (sepsis) that causes issues, not underactivation.
 

yerrag

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Conversely, administering endotoxin (LPS) to the fasted mice quickly reversed the benefits of CR and restored the mice to their previous levels of "health". Perhaps even more importantly, the study found that mice with higher levels of endotoxin (LPS) did NOT benefit from caloric restriction! This could explain why dieting/fasting does not benefit so many people that attempt it. To further confirm that the benefits of CR were due to lower endotoxin (LPS) levels, the authors did an experiment with a group of mice that had regular daily caloric intake but was given a TLR4 antagonist. Those regular, unfasted mice given a TLR4 antagonist enjoyed the same reduction/prevention of obesity, insulin resistance, and chronic inflammation as the mice subjected to CR. In fact, as the study mentions itself, administering TLR4 antagonist may one day become an effective method to treat obesity and other metabolic conditions.

I've not had a belly this large, ever. Even without having to walk a lot or work out a lot. I began to wonder where it came from. I lately blamed high-fructose intake and would blame this part of the peaty diet. But reading this thread again made me reconsider. I realize that my belly grew just lately and it was resisting my attempts to go back to my normal. In the past, I could essentially will myself to a flat stomach with a snap whenever I saw it getting bigger, but not this time. I was resigned to accepting this as part of aging, but I laugh now as we know in this forum not to be like the lab coats in hospitals, so I'm glad this thread has lead me to consider LPS as the cause. And I really think this is the case with me.

On the subject still on getting fat, I noticed also that I had been wondering why I was getting sleepy and being on a low-energy state during the day. I would now ascribe that to being low on sugar during the day, and I think I can point it to the effect of endotoxins. Perhaps the endotoxins are interfering with sugar intake in the tissues. If endotoxin impeded sugar intake, it would cause blood sugar to increase, and this would lead to an insulin response where insulin would cause the liver to convert sugar to fat, in the process lowering blood sugar to where it would be low and low blood sugar would lead to my feeling of low energy.

Ever since using proteolytic enzymes to lyse atherosclerotic plaque that led to activating dormant bacteria from disrupted biofilms, and the nuking of bacteria (thru immune system response as well as antibacterials - doxycycline and topical turpentine), I've been seeing my belly grow. I realized now that I've not taken consideration the die-off from nuking bacteria - LPS. This may be what's causing my belly to grow.
Endotoxin (LPS) May Be A Causative Factor In Alzheimer Disease (AD)

I experienced this myself. with my attempt to lyse plaque as mentioned above, I've noticed that it's been harder for me to recall words and terms - many just remain at the tip of my tongue. Maybe the endotoxins are forming amyloid plaque in my brain who knows?

And something new I observed: I had a lot of hairloss during this episode. Could LPS be the cause as well?
 
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salvio

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Because I found this:


Effect of caloric restriction on gut permeability, inflammation markers, and fecal microbiota in obese women.​


Abstract​

Recent findings suggest an association between obesity, loss of gut barrier function and changes in microbiota profiles. Our primary objective was to examine the effect of caloric restriction and subsequent weight reduction on gut permeability in obese women. The impact on inflammatory markers and fecal microbiota was also investigated. The 4-week very-low calorie diet (VLCD, 800 kcal/day) induced a mean weight loss of 6.9 ± 1.9 kg accompanied by a reduction in HOMA-IR (Homeostasis model assessment-insulin resistance), fasting plasma glucose and insulin, plasma leptin, and leptin gene expression in subcutaneous adipose tissue. Plasma high-molecular weight adiponectin (HMW adiponectin) was significantly increased after VLCD. Plasma levels of high-sensitivity C-reactive protein (hsCRP) and lipopolysaccharide-binding protein (LBP) were significantly decreased after 28 days of VLCD. Using three different methods, gut paracellular permeability was decreased after VLCD. These changes in clinical parameters were not associated with major consistent changes in dominant bacterial communities in feces. In summary, a 4-week caloric restriction resulted in significant weight loss, improved gut barrier integrity and reduced systemic inflammation in obese women.

 

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Hello @haidut very much sorry for asking the same question but could you please tell me the maximum dose of kuinone, cardenosine, lisuride, metergoline, lanosterol, diamant, androsterone and pansterone combination in 1:1 ratio, 6- keto-progesteron, defibron and energin, which would, in principle, be tolerated by humans. I really apologize for this question, I just really need to know the maximum dosages of your wonderful products! BEST WISHES!
 

Dr. B

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As many of you know, the argument for/against fasting has been raging on the forum for several years at this point. While Ray has spoken several times favorably about potentially skipping a meal or two, he has repeatedly said that chronic fasting is not something he recommends due to its negative effects on metabolism. When asked to elaborate on any possible benefits of caloric restriction (CR), he said that any real benefit is likely due to the lower endotoxin (LPS) levels and reduced PUFA stores, and not the actual reduction in calories. He also said that some additional benefits may be due to reduced intake of tryptophan, methionine and cysteine.
Well, this new study sides with Peat on the topic of fasting. The study found that reducing calories by about 40% led to changes in the microbiome that resulted in less endotoxin (LPS) synthesis and release in the bloodstream. As a result, the fasted animals had less fat mass while preserved lean mass and at the same time improved insulin sensitivity. Doing a fecal transplant from the fasted mice to naive mice provided the same benefits as CR while keeping their food intake unchanged. Conversely, administering endotoxin (LPS) to the fasted mice quickly reversed the benefits of CR and restored the mice to their previous levels of "health". Perhaps even more importantly, the study found that mice with higher levels of endotoxin (LPS) did NOT benefit from caloric restriction! This could explain why dieting/fasting does not benefit so many people that attempt it. To further confirm that the benefits of CR were due to lower endotoxin (LPS) levels, the authors did an experiment with a group of mice that had regular daily caloric intake but was given a TLR4 antagonist. Those regular, unfasted mice given a TLR4 antagonist enjoyed the same reduction/prevention of obesity, insulin resistance and chronic inflammation as the mice subjected to CR. In fact, as the study mentions itself, administering TLR4 antagonist may one day become an effective method to treat obesity and other metabolic conditions. I posted a few other studies showing that endotoxin (LPS) overload is probably involved in many (most) chronic conditions, so an effective blocker of endoxotin (LPS) signalling may become quite successful as a true cure for many diseases.
Endotoxin And Iron Finally Recognized As Potential Causes Of Many Diseases
Endotoxin (LPS) May Be A Causative Factor In Alzheimer Disease (AD)
Endotoxin (LPS) Theory Of Atherosclerosis (CVD)
Gut Bacteria May Cause ALL Autoimmune Conditions; Antibiotics Can Cure

The TLR4 antagonist used in the study was the rather obscure chemical CLI-095. It has not been approved for human use and even in animal studies it is relatively unknown. However, there are already quite a few other TLR4 antagonists with much longer track record of usage in humans and likely better side effect profile.
TLR4 - Wikipedia

Among those antagonists, the most widely used ones that Peat has spoken about include cyproheptadine, ketotifen, naltrexone and the caffeine derivative propentofylline. Ketotifen is already being tested in human trials for other conditions associated with TLR4 overactivation including systemic sclerosis (scleroderma), Lupus, RA, and even IBD conditions like Crohn's.
Emodin, progesterone, niacinamide, vitamin D, vitamin A and vitamin B3 would probably be the most applicable OTC ones.

Functional Gut Microbiota Remodeling Contributes to the Caloric Restriction-Induced Metabolic Improvements - ScienceDirect
How gut bacteria may help you diet and stay healthy

"...In order to see what role gut bacteria might play in the process of becoming healthier following a calorie-restricted diet, the scientists transferred some of these bacteria from the dieting mice to a group of mice bred not to have gut microbiota...The researchers found that simply performing this microbiota transfer allowed the mice to become leaner and produce more beige fat, despite staying on their regular diets. After analyzing the composition and behavior of these microbiota, Prof. Trajkovski and team observed that they produced fewer toxic molecules known as lipopolysaccharides (LPS). However, when the researchers tried to boost LPS levels so that they would reach their usual levels, they noticed that the mice with higher LPS saw fewer health benefits, despite dieting."

"...The researchers point out that LPS actually trigger an immune response as they activate a protein known as toll-like receptor 4 (TLR4). In the recent study, they noticed that mice that had been genetically engineered not to express TLR4 actually enjoyed similar health benefits to the ones seen by the rodents on the calorie-restricted diet. "Clearly the immune system not only combats infections, it also plays a key role in regulating metabolism," notes Prof. Trajkovski. Without activated TLR4, the mice not only produced more beige fat and thus saw more weight loss, but they also reacted better to insulin. These rodents' livers were also more effective at processing sugar and fat, and the mice became better at adjusting to colder temperatures. "This is turning into an entirely new field of research," Prof. Trajkovski says. After identifying these mechanisms, the team decided to test the effectiveness of two different compounds: one aimed at reducing LPS production, and the other aiming to block TLR4. Both of these drugs were effective in mice and induced a similar health outcome as that produced by calorie-restricted dieting."

"It may one day become possible to treat obese people with a drug that simulates caloric restriction. We are currently investigating the precise changes in bacterial communities, and we are also testing other compounds that reduce LPS production and signaling." -- Prof. Mirko Trajkovski
what do you think about palmitic acid being tlr4 agonist. isnt it present in beef and dairy fat. what should be done
 

Dr. B

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Perhaps this has been answered elsewhere on the forum but I can't seem to find anything.

What are the down sides to blocking TLR4? It has to have some useful function to have been preserved so long. If you have lots of endotoxin and that endotoxin gets transported into the blood stream by chylomicrons, wouldn't you need TLR4 to warn your body it is coming and to mount a proper response?

Does TLR4 facilitate transfer of LPS to the bloodstream?
Can't give a technical answer, but this is logically specious. Many traits that could have been useful in ancient contexts are no longer so. For example, low metabolism, smaller body size, etc.

Doesnt the metabolism have to have limits otherwise the body would just consume itself? And even fat oxidation to some extent is needed otherwise the body would also consume itself? If you drive metabolism up too high, cortisol starts going up, which then starts burning up your organs and hair and muscles and skin to use as energy? Although its odd why it does that instead of just burning up more fat stores? This is why T3 for instance doesnt cause fat loss the more you take it, and it can easily start burning up muscle tissue… in my case I put on weight from using 48mcg T3 daily, and burnt up muscle tissue too. By the end of the 6 weeks of using it, I had gained 20 pounds, lost muscle, lost hair, and was worse off than before I started it, with a slower metabolism.
 

Dr. B

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It should also be mentioned for people who don't like/aren't able to take drugs to get TLR4 antagonist effects, that some vitamins also act as TLR4 antagonists. Haidut has posted studies in the past discussing Vitamins A,D, B2, and B3 as having TLR4 antagonist effects.
Yes in the OP these were mentioned alongside progesterone and emodin.
I havent used emodin i have to look into that more. However, as a guy, which of those substances can you really use regularly year round? Progesterone can cause the sex organ shrinkage, and i think Peat said its a temporary effect but im still wary of using that. IMO the only one of those you could use daily and do fine would be a low dose vitamin D3 like 1000 to 2000 IU orally. That should keep side effects minimal and hopefully provide some endotoxin benefit? Vitamin A as a supplement can cause hair loss, oily hair and skin and acne… B3 can have a potential catabolic effect and can affect other B vitamins status. A and D3 could affect other fat solubles or vitamins too which is why i was thinking the lower dose of D3 would be better.


Do you still get all the anti endotoxin effects of vitamins A, D3 and B3 if you get them from food sources? In that case it means liver or whole milk or even cod liver oil, should have excellent anti endotoxin effects since all of them have good amounts of vitamin A or D or both? So you can stick to liver/milk and maybe supplement a small amount vitamin D orally and that should be good to cover endotoxin?
 

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