Lowering LPS in the context of leaky gut

[cristi_b]

Recently I've become interested in lowering the level of LPS in my organism as I now believe it is the major factor in a lot of my symptoms(including my vitamin D intolerance as it activates the mast cells and leads to Histamine release). From research papers I've read there seems to be a link to leaky gut: LPS can cross more easily into the blood stream in case of leaky gut, but also that it contributes to inflammation in the intestines and can actually lead to leaky gut(this is why I'm interested in both subjects).

I do not know for sure which bacteria in my gut causes the LPS, so it's difficult to treat. It is also dangerous for me to attack the infection/dysbiosis before solving the leaky gut because the huge amounts of LPS released during killing of the bacteria will further affect my neurons and I have lots of cognitive problems as it is. This is why I'm interested in both subjects: protection from LPS and solving the leaky gut.

I'm trying to make a supplement stack to tackle both problems at the same time and I would like your input/help to improve it or even correct it if I understood something wrong from the research.

Here is my list so far:

1) For Leaky gut
- Sodium Butyrate
- Retinol/Retinyl Palmitate: vitamin A is said to have a role in the gut lining and I'm forced to use active vitamin A as I have some genetic modifications that make me a poor converter to active form
- Collagen Type I: involved in repairing cells in colon
- Glutamine: this one is a maybe for me, as I have glutamine near the maximum limit(checked by blood test) and I also have high ammonia and more glutamine is dangerous in case of high ammonia

2) Protecting brain from LPS
- Curcumin(+Piperine)
- EGCG
- Fisetin
- Honokiol
- Trans-ferulic acid: single study said good not only for neuro-damage by LPS, but also protects gut from LPS and helps DAO activity

 

[Carl]

The LPS is a big problem in ME/Fibro because it promotes inflammation and is used for that purpose in research. You cannot treat "Leaky Gut" in the way you propose, I can guarantee that it will not work because it is a pathogenic infection which causes it and this is all linked to the cause of ME/Fibro. Therefore none of that will provide benefit and Glutamine is a downright lie propagated by supporters of the drugs industry IMO. I can guarantee 100% that it will not fix it.

FYI Most of the LPS enters the bloodstream in the transverse colon which is where the colon permeability is compromised. The cause does not lie there despite Hip sticking Glutamine up his rear end because it is a consequence of an attack by pathogens in another location courtesy of attack against the vagus nerve. This is not known by science and medicine who are far behind.

If I remember correctly, you should check this out to confirm what I believe, boswellia serrata (frankincense) is meant to have some effect against LPS in the bloodstream. I remember that it is meant to bind to it and promote it's excretion if I remember correctly.

Alkaline Phosphatase (ALP) is meant to counter LPS from bacteria.
Lactoferrin binds to LPS on bacteria and makes them more susceptible to destruction by the immune system or antibiotics. Additionally, lactoferrin binds to free-floating LPS and prevents it from causing inflammation.
In a cell study, lactoferrin prevented the production of the pro-inflammatory cytokine IL-8 caused by Escherichia coli LPS.
LipoPolySaccharides (LPS) is a potent activator of macrophages, which produce a variety of pro-inflammatory mediators such as NO, PGE-2 and interleukins.

 

[cristi_b]

Thank you, you gave me a lot of information I did not have:

1) Alkaline Phosphatase (ALP) degrades LPS: I actually had pain in area around my liver for more than 10 years and I suspected it was dealing with something, only recently I realized it was the LPS but I did not know about ALP

2) Lactoferrin binds to LPS: I will put it on my list of supplements to buy

3) Escherichia coli LPS raises IL-8: I actually tested my level of IL-6 and was thinking about testing TNF-alpha, I will add IL-8 to my future tests. Also E. Coli was on my watch list of probable bugs in my body as it is urease positive(I have high ammonia) and ODC positive(I have low Ornithine) plus I got some good things from supplements that tackle this bug. My stool test was negative for E. Coli though and so was my urine sample. Maybe I need to check my lungs, but I don't know if that's possible.

4) LPS enters the bloodstream in the transverse colon: Woww did not know that, do you have a specific research paper that explains more?

5) vagus nerve being involved: I long suspected the vagus nerve to be involved, some of my symptoms appear when I am relaxed, in the ventral vagal state. My body seems to be dealing with a larger quantity of something toxic while relaxed. My initial guess was that the level of Nitric Oxide increases too much, but I did not understand why until I found in a research paper saying that LPS can lead to higher N.O.

6) LPS leads to pro-inflammatory mediators such as NO, PGE-2 and interleukins: some of those inflammatory markers are making my veins pop out and cause urinary urgency; I'm sure of it, but so far I can only guess about the mechanism.

7) Boswellia serata: I actually tryed at the start of this year, I wrote in my log some good effects about it(some interesting 3D visual effects, lower heart rate, time seemed to be dilated/slowed down) but unfortunatly I had to stop because of its negative effects on me(diarrhea, feeling of fainting, irritability). I did not know it had something to do with LPS, I pressumed it changed some inflammation markers.

You cannot treat "Leaky Gut" in the way you propose, I can guarantee that it will not work because it is a pathogenic infection which causes it and this is all linked to the cause of ME/Fibro. Therefore none of that will provide benefit and Glutamine is a downright lie propagated by supporters of the drugs industry IMO. I can guarantee 100% that it will not fix it.

I cannot stop testing various theories because it is all I can do for myself, doctors have given up long time ago. Besides I have a few victories that give me hope, stuff I've stumbled upon(probably by chance more than anything):
- solving pain in the liver area with ZINC
- keeping diarrhea at bay with CHITOSAN
- solving/stopping the heart palpitations(extrasystoles) with DAOSiN
- controlling my chemical allergies
- managed to make my body accept vitamin D so I can get outside in the sun
- lately my eyesight seems to be getting better(as I'm trying to lower LPS levels)

There are more stuff to solve, but I simply cannot give up. So any other information you can share please do. I will also post here whatever I stumble upon.

 

[katabasis]

Have you considered low-dose naltrexone? Naltrexone blocks TLR4 receptors, which is one of the pathways your immune system uses to detect pathogens. LPS is one of the primary ligands for TLR4 receptors, so if you suspect LPS is triggering a lot of symptoms for you, low-dose naltrexone should theoretically reduce immune activation/inflammation. A lot of people with ME/CFS and related conditions have benefited from taking low-dose naltrexone, and you should be able to easily find a lot more info on the specifics of this treatment if you are interested.

 

[cristi_b]

Have you considered low-dose naltrexone? Naltrexone blocks TLR4 receptors, which is one of the pathways your immune system uses to detect pathogens.

Thanks, I did not know about naltrexone. Last week I also found some information about dextromethorphan that helped the brain cope with LPS induced problems, too bad both are based on prescription in my country. You can not normally get them until a doctor agrees to prescribe them.

Later Edit: Just discovered this thread with a lot of ideas for leaky gut.

 

[cristi_b]

I found that Hesperidin has some beneficial effects on me:

- I recall names of people/celebrities/singers easier(I call this "name memory"): when I see a singer on TV and his/her name does not occur to me automatically(like it should), I try to think about it and name just appears out of the blue

- I notice more details in fast moving objects(I call this "visual time dilation" as I've seen it in some supplements): time seems to be dilated so I can see more each second, motion seems more fluid because of this, both in real life and also on TV / computer monitors

From research papers I find that there are several benefits to Hesperidin and I'm not sure yet which ones cause better cognition for me, but at least some of them are related to LPS:
- lowers TNF-alpha and InterLeukin 1-Betha, both of which are linked to LPS induced neuroinflammation
- enhances antioxidant defenses (via Nrf2 and HO-1)
- promotes neuronal survival by regulating Bcl-2/Bax and Caspase-3 levels
- lowers nitrate/nitrite and increases BNDF levels in hippocampus
- blocks inflammatory process by inhibiting NF-κB, COX-2 and iNOS(consequently leading to lower Nitric Oxide)
- lowers IL-6
- decreases CRP

 

[WinterWren]

I found that Hesperidin has some beneficial effects on me:

- I recall names of people/celebrities/singers easier(I call this "name memory"): when I see a singer on TV and his/her name does not occur to me automatically(like it should), I try to think about it and name just appears out of the blue

- I notice more details in fast moving objects(I call this "visual time dilation" as I've seen it in some supplements): time seems to be dilated so I can see more each second, motion seems more fluid because of this, both in real life and also on TV / computer monitors

From research papers I find that there are several benefits to Hesperidin and I'm not sure yet which ones cause better cognition for me, but at least some of them are related to LPS:
- lowers TNF-alpha and InterLeukin 1-Betha, both of which are linked to LPS induced neuroinflammation
- enhances antioxidant defenses (via Nrf2 and HO-1)
- promotes neuronal survival by regulating Bcl-2/Bax and Caspase-3 levels
- lowers nitrate/nitrite and increases BNDF levels in hippocampus
- blocks inflammatory process by inhibiting NF-κB, COX-2 and iNOS(consequently leading to lower Nitric Oxide)
- lowers IL-6
- decreases CRP

That’s interesting about Hesperidin, it’s high in grapefruit seed extract which is one of the only things that helps my cognitive dysfunction these days. I take it at night and feel clearer in the morning. Not every night though. It’s anti microbial and also high in quercetin but I’ve tried a bunch of quercetin on it’s own with no effect.

The other thing that helped for maybe a year was taking apo-lactoferrin at night. Unfortunately I started reacting badly to it. It also cleared up cognitive dysfunction and I felt better overall.

My thinking lately has been around dealing with LPS, leaky gut, and the possible high IL10 in our digestive system that stops our immune system from dealing with exercise induced leaky gut (from this health rising article https://www.healthrising.org/blog/2...-exertional-malaise-chronic-fatigue-syndrome/) which is just a theory.

Lactoferrin is supposed to decrease IL10 in digestive system and I wish I could find a replacement to test out. L-theanine is also supposed to help with exercise induced leaky gut but I have no idea how or where I read that…

 

[Dysfunkion]

I'm gonna try it myself and see if it does anything for me, ordered the nootropics depot one.I dug around and apparently there is some other form of it too but I want to see how I react to this first. I am also focusing on LPS now myself after a very puzzling reaction to wheatgrass which I had to stop because it began giving me dizzy spells, driving my immune system nuts, and increasing my physical fatigue (not surprised, the way 99 percent of things go with me). But I do consistently get a burst of a certain kind of cognitive energy with it even though it overall made me weaker and wasn't good for me. Now that my reaction to it is dying down I'm left with more sensory clarity though. EGCG has also been a miracle for me lately no surprise in this context, in fact I'm drinking some green tea as I type this.

 

[Dysfunkion]

I got to try it, took 500 mg while I was in a PEM crash at 12 PM. Very strange results that I don't really know what to think of right now. I got an intense mental energy and a lot of what I perceive to be neuro-inflammation relief. My senses became so sharp and clear like they haven't in literally years. But there was a downside it seems to really irritate my immune system as I felt all face burny on and off throughout the day and it did increase my tinnitus with face sensations it peaking around 5 PM as expected by how I observe my circadian immune rhythm acts but nowhere else on my body. The initial immune system reaction (keep in mind here I also had PFS before from saw palmetto) as caused temporary sexual dysfunction followed as the day went on by an increase in it and improved sensitivity which I found very odd. This is probably one of the more confusing reactions I had to a supplement. Cistus tea in my usual rotation seems to calm this down a bit and later my coffee seemed to be more stimulating and satisfying.

I'm going to have to see how I feel in the morning and take things from there. I think this can be useful for me if I can tame this immune response by possibly playing with lower doses. There is also the methyl chalcone form but I know that the biological effects of that will be somewhat different. It may avoid this reaction while giving me the same benefits of this form though and I'm probably going to put an order in to find out. This reaction began to occur within the first 10 minutes of taking it so as usual it seems to be centered around an immediate gut reaction.

Update 6/27 - I slep extremely well last night and laying down was very comfortable but my immune system is still feeling very revved up and I woke up with red stingy eyes and a hangover-ish headachy feeling with some irritability. My senses are still far clearer in every way though as of posting this. Having my morning coffee helped with the irritability somewhat. I'm gonna ride this out over the next few days without taking any of this stuff again and give updates on where this goes. There is many things this stuff does so it can be a pool of things going on here.

Some of mental hangover type symptoms and a decrease in burning eyes as well as lessening the evening facial burning hesperidin re-induced were resolved save for a little bit of the burning eyes and a warm feeling in my head by a small amount of a capsule of Osha Root which I remembered is what initially made me get to a new level of progress with my saw palmetto PFS situation which I'm not thinking innate gut infections viral or otherwise played a role in based on this. I think I'm going to take another capsule of it in the morning and even though it can at a full capsule tend to make me more tired I have no work or anywhere to go but the store so that's fine. I'll have some activated charcoal before bed too to help clean up the hesperidin mast cell implosion some more.

Next I'm going to give andrographis a try here, it's one of the last Lyme anti-virals I have yet to try. I'm trying to narrow specifically what this immune reaction that is so problematic is. IT appears to be repeatable with repeatable routines that are able to bring it down. Hesperidin seems to have helped something as noted by the sensory clarity but also ramped it up. I remember early on in my PFS journey which may actually have been a viral overload journey with a side of hormone and androgen receptor problems that this specific immune response got so bad that eventually everything would make it worse so it's an immune chain reaction that wasn't present before in my life. Got first progress with MK7 K2 and bombing it with activated charcoal, then propolis, then cistus, and then osha root. Increasing my coffee intake and then adding another 1000 mcg to the methyl-b12 reintegration K2 allowed is what allowed me to tolerate 2000 mcg again consistently which has been fine since. If the reaction pops back up osha root is able to beat it back and drinking it right now Cistus appears to be fine too with it. I'm gonna keep on track with this and see what the andrographis dose next, probably going to start at a fraction of a capsule to avoid any annoying disasters.

 

[bad1080]

LPS = lipopolysaccharides?

 

[Carl]

LPS = lipopolysaccharides?

yes

 

[cristi_b]

The information about TLR4 receptors and it's connection to LPS is very interesting, now I'm rechecking all supplements if they have an effect on TLR4.

In the meantime I have tested several supplements:

1) Fisetin And Trans-Ferulic Acid. I can feel the effects of both of them on a cognitive level(usually I try to solve webSudoku puzzles in order to see the effects) but unfortunately they are cleared from bloodstream quite fast and effects do not last very long: 1-1.5h. Basically both supplements are not worth it, as they are expensive and I would need to take a pill/tablet every 1.5h in order to protect my brain from LPS. This is not feasible. I have read that there is a Fisetin variant, called Bio-Fisetin, based on fenugreek(galactomannans) which has a more lasting effect, but it comes in smaller doses which complicates the cost of it(as I would need to take several pills in order to get the same effect).

2) Collagen: haven't felt anything cognitively, it probably needs more time to work on repairing the colon lining and stopping the permeability, but one thing that caught my attention is that I seem to be more allergic on it. Same thing happens when I take vitamin C(which leads to collagen production) my chemical allergies/sensitivity start to surface. I'm not exactly sure why this happens: less permeability should mean less LPS(and so less allergic manifestations) but the opposite happens. Maybe it "bothers" some pathogens in my colon and they produce even more LPS or maybe because collagen Type I stimulates IL-1β production(source). The mechanism is not clear to me at the moment.

3) DHA 700mg in triglyceride form: this has a good and lasting(more than 12h) effect on me. My time on websudoku, on hard level, drops from 9-12min to 7-9min. This feels great cognitively: I think more clearly, my working memory and concentration is improved. DHA does not directly downregulate TLR4 receptors(so doesn't directly protect against LPS) but it reduces TNFα and IL-6 secretion(source) and, at the same time, protects the neurons(as it is part of the cell membrane).

4) Curcumin 500mg + Piperine twice daily: somewhat effective as I seem to not be so absent minded, also my eyesight has improved since using this supplement. Curcumin is proven to have antagonist activity on TLR4 receptors(source). It's possible I need to take more than 2x500mg daily, but I haven't tryed that as the Piperine would cause more Iron to be absorbed and I have already too much Iron in my blood.

 

[cristi_b]

Update 6/27 - I slep extremely well last night and laying down was very comfortable but my immune system is still feeling very revved up and I woke up with red stingy eyes and a hangover-ish headachy feeling with some irritability. My senses are still far clearer in every way though as of posting this. Having my morning coffee helped with the irritability somewhat. I'm gonna ride this out over the next few days without taking any of this stuff again and give updates on where this goes. There is many things this stuff does so it can be a pool of things going on here.

Have you ever tried Resveratrol? I have had good results in the past with it and I did not understand why, it seemed anti-inflammatory to me and it also made me more motivated with my thinking more focused. Now, since I'm checking everything through the lense of LPS and TLR4 activation, I found a study that says it down-regulates TLR4 signaling(source). Might be worth checking how you respond to it.

Lately I've been thinking that keeping these cytokines IL-1β, IL-6, IL-8 and TNF-α at a low level is not really beneficial in the long run: basically it is the body's response to an infection, this activation of TLR4 by LPS is a defense mechanism that existed for a long, long time and shouldn't be stopped permanently. I think that suppressing these cytokines should only be done for a short time and only while treating the underlying infection. Otherwise the infection would take advantage of the lack of inflammation(cytokines) and proliferate. In my case, because I don't know where the infection(source) is, or even if it's a single source or multiple ones, I need it to stop causing damage to my neurons. But my end goal is finding the infection and resolving it.

 

[cristi_b]

While asking perplexity to find information for me, I came across a possible link between "leaky gut" and "peroxynitrite":

Let me see if I understood correctly: there is a link between leaky gut and higher peroxynitrite levels?

Answer
Yes, that's correct. The search results indicate there is a link between leaky gut (increased intestinal permeability) and higher peroxynitrite levels.The key points are:

Gut Dysbiosis and Oxidative Stress​

• Gut dysbiosis, an imbalance in the gut microbiome, can lead to increased oxidative stress and inflammation in the gut.
• This oxidative stress can stimulate the production of reactive oxygen and nitrogen species, including peroxynitrite.

Peroxynitrite and Gut Inflammation​

• Elevated peroxynitrite levels have been observed in inflammatory bowel diseases like ulcerative colitis, where gut dysbiosis is a key factor.
• Peroxynitrite can further exacerbate gut inflammation by increasing epithelial permeability, contributing to a "leaky gut".

Nitric Oxide Metabolism and Dysbiosis​

• Dysregulation of nitric oxide (NO) metabolism has been linked to gut dysbiosis and conditions like ulcerative colitis.
• Increased inducible nitric oxide synthase (iNOS) activity in the inflamed gut can lead to excessive peroxynitrite formation when combined with superoxide.

So in summary, the evidence suggests that gut dysbiosis and the resulting oxidative stress and inflammation can drive increased peroxynitrite production, which in turn can contribute to leaky gut by further damaging the intestinal epithelium. This creates a self-perpetuating cycle of gut dysfunction.

So, not only that bacteria can release LPS that causes increased inflammation and permeability of the gut, but there is also a second mechanism involving peroxynitrite. There's not one, but 2 vicious cycles:

Maybe this is the reason for "leaky gut" being so hard to solve, it is reinforced by 2 mechanisms. I will order an S.O.D. supplement, which is said to lower peroxynitrite, in order to test this theory.

 

[cristi_b]

That’s interesting about Hesperidin, it’s high in grapefruit seed extract which is one of the only things that helps my cognitive dysfunction these days. I take it at night and feel clearer in the morning.

The Hesperidin capsules I used are extracted from Citrus Aurantium skin. This plant also has Nobiletin, so now I'm not so sure it was Hesperidin alone that was helping me, because Nobiletin is a NF-kB inhibitor.

Some updates for the supplements I tested:

1) Honokiol
My sense of touch is better when taking taking this supplement and also I dream more during the night. I've seen this effect before in supplements like Magnesium, which are known to affect the NMDA Receptors. This supplement has proven to me I have problems with the NMDA Receptors. There are 2 explanations for my NMDAR issues: tests last year revealed I have high Ammonia levels and NMDA Receptors are affected by inflammation from LPS(source).

2) EGCG
I seem to be in a better mood when I take EGCG, people seem more friendly, music seems more melodical and I seem to be less stressed. I have seen this effect before with Methylated B9 supplement. I'm not sure yet why this happens or what mediates this effect on me.

3) SOD
1st time I've tried SOD I've had a bad reaction: it put my body in sympathetic activation, my heart was beating fast and I've had insomnia. I was feeling better cognitively but that might have been just the effect of the sympathetic activation which can improve thinking abilities. I will try again to see if I have a similar reaction, but I did not like the effect and If I get the same reaction I will not use SOD anymore. In that case I will have to look for a different solution for high peroxynitrite...

 

[Carl]

14 Factors that May Reduce Lipopolysaccharides (LPS)
Resveratrol can help lower the inflammation produced by LPS. Resveratrol upregulates SOD2 (Mitochodria) and Catalase production which can help lower free radicals and help prevent grey hair.
That article lists Peanuts for it's high oleic acid content which is also in olive oil however Red Peanuts also combines fairly high Resveratrol & Oleic acid. I love Red Peanuts, I am drawn to them probably because of their anti LPS functions.

BTW Many types of Red Peanuts were grown to maximize oleic acid content and many contain fairly high amounts of it. You just have to be careful with the fat content and weight gain.
Resveratrol inhibits LPS-induced inflammation through suppressing the signalling cascades of TLR4-NF-κB/MAPKs/IRF3
Resveratrol treatment modulates several antioxidant and anti-inflammatory genes expression and ameliorated oxidative stress mediated fibrosis in the kidneys of high-fat diet-fed rats

BTW if you take SOD, then you should also take Catalase so that the hydrogen peroxide gets converted to water. Otherwise you will have problems with it. Resveratrol upregulates both.
Resveratrol attenuates oxidative stress in mitochondrial Complex I deficiency: Involvement of SIRT3
That might show some potential benefit to ME sufferers.

 

[Carl]

A quote from that first link of the most noteworthy points:

Takeaway​

Lipopolysaccharides (LPS) are bacterial toxins that may enter the blood if you have an infection or “leaky gut.”
Limited research has associated LPS with many chronic health problems–from heart disease to diabetes to IBS to sleep issues.
These small particles are thought to trigger systemic inflammation and other nonspecific symptoms. For example, scientists can use LPS to experimentally induce fatigue, poor memory, anxiety, and social disconnection.
However, more research is needed to understand if LPS plays a significant role in causing any disease.
Potential healthy ways to reduce LPS include cooking with olive oil and eating foods high in pre- and probiotics, polyphenols, and omega-3 fatty acids. Meditation and vagus nerve stimulation might also help, according to limited research data.

 

[cristi_b]

BTW if you take SOD, then you should also take Catalase so that the hydrogen peroxide gets converted to water. Otherwise you will have problems with it. Resveratrol upregulates both.
Resveratrol attenuates oxidative stress in mitochondrial Complex I deficiency: Involvement of SIRT3
That might show some potential benefit to ME sufferers.

The SOD supplement I took was Solaray SOD Plus, which has SOD and CAT(Catalase) and some additional ingredients. I am also starting to get a similar with Buffered Vitamin C: higher heart rate and insomnia(sympathetic activation). I am beginning to wonder if I have too much anti-oxidants as I read this can happen when you have too much inflammation in the organism and that it leads to a pro-oxidant state(source).

For Resveratrol, as I mentioned previously, I get good effects from it: more motivated, my thinking more focused but it also causes me to sleep less. That might be from excessive amounts of SOD and CAT, but I'm not sure.

Other updates:

- Chelated Copper supplement: I got extreme bout of diarrhea with urgency; Copper was proven to activate TLR4 and NF-kB(see source1 and source2), this would be an indication that supplementation with this mineral would be detrimental in case of inflammation to the gut from LPS

- came accross several studies that says Astanxanthin is beneficial in case of LPS and high Peroxynitrite(for example see this research paper and this one). I have ordered an Astanxanthin supplement, the trouble is I would need a very high dose to reach the concentrations presented in the research, it's not clear if it's feasible or not, I will have to try and see.

 

[godlovesatrier]

The only thing backed up by trials is larozotide acetate. Phase I and ii both have good results.

Apart from that you're probably looking at ways to crowd out inflammatory bacteria in the gut by maximising your firmicute bacteria. But that's often easier said than done.

 

[cristi_b]

The only thing backed up by trials is larozotide acetate. Phase I and ii both have good results.

Interesting, I did not know about it, too bad it is not available commercially.

Other Updates:

1) Had to stop Sodium Butyrate: it was starting to give me head aches

2) Tried NAC to attack biofilm in gut, don't know exactly how helpful it is for that yet, but one thing I noticed is better smell sensations. It comes and goes: every now and then I catch a whiff of something from the open window in my room and it's triggering memories, it's quite a pleasant experience. I've asked perplexity about it and is seems NAC also helps olfactory neurons(source) and has neuroprotective effects including against LPS(see source) . This was a happy accident as I was not looking for something to improve my smell.