Endotoxin Inflammation Stack

LucH

@wrl said in Endotoxin Inflammation Stack:

@LucH
Wouldn't it mainly be about promoting good digestion(rapide!)/stomach HCL/bile/enzymes, which would help minimise bacteria.

yes of course, but not at first time. The liver is overloaded with residues of endotoxines.
First relieve (and help to get rid of), then assist digestion, and afterwards optimize metabolism to find energy back.
That's how I would phase out.

Ismail

@herayclitus assuming you were/are taking this every day?

What’s your diet like?

wrl

@LucH
Ah ouah, I forgot about the liver burden aspect

@herayclitus said in Endotoxin Inflammation Stack:

(obviously not medical advice)

I've been dealing with some chronic inflammatory symptoms recently that seem to be endotoxin-related (anhedonia, loss of appetite, nausea, low-grade fever, difficulty sleeping, diarrhea, migraines, etc.) I found not getting enough protein and fat to be the main triggers.

This stack worked for me almost as well as antibiotics:

Zinc, 120mg

Quercetin, 1g

Methylene blue, 2mg

Aspirin, 1g

T3, 12μg (split into 2 doses)

Cyproheptadine, 3mg (in the evening)

The dosing for everything is pretty modest, except for the zinc (I think the high-dose zinc is essential though)
I was curious if anyone else had a similar experience, and what worked for you

I think that intestinal permeability is the main problem re. endotoxin. If the endotoxin (LPS) stays inside the intestine and does not get into the bloodstream then the systemic inflammation doesn't happen and the allergies/sensitivities to partially digested food molecules don't happen either.

Ray Peat told me in an email exchange (sorry, don't have it now to share) that thiamine and magnesium are needed to heal the gut. High dose thiamine hcl + magnesium glycinate worked for me. I also supplemented with other b vitamins during that time, but I only high dosed the thiamine. I used thiamine hcl.

link:
https://www.eonutrition.co.uk/post/thiamine-deficiency-a-major-cause-of-sibo
also:
https://www.hormonesmatter.com/sibo-ibs-constipation-thiamine-deficiency/
and
https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/dietary-supplementation-of-thiamine-enhances-colonic-integrity-and-modulates-mucosal-inflammation-injury-in-goats-challenged-by-lipopolysaccharide-and-low-ph/8B5E668F2BD04E289AA015E7A77680B3

There is discussion online that thiamine deficiency contributes to leaky blood/brain barrier too. It is mentioned as the cause of brain damage in alcoholism; the alcohol depletes the thiamine, the bbb is compromised, then heavy metals (notably iron) leak into the brain causing damage. Something about thiamine being needed for tight junctures regarding the epithelial cells. Can't find it now....

herayclitus

@LucH I think zinc and methylene blue were the most impactful supplements for me. As far as diet, getting at least 1g/kg protein per day, adequate saturated fat, and easily digestible carbs helps. The carrot salad is also helpful

herayclitus

@Ismail I took it for 2-3 days until symptoms subsided. I think increasing fat and protein helped, I might have dropped those too low before. For carbs, I tend to tolerate well-cooked starches better than whole fruit, but I still get a fair amount of carbs from juices

herayclitus

@mostlylurking Thanks for sharing this--I think it's definitely a leaky gut issue, as alcohol aggravates it worse than anything else. I have been taking thiamine HCl and gelatin as well. Magnesium tends to irritate my gut but I might try it again in a lower dose

LucH

Some target points to deal with

B1 is needed for communication between the brain and the stomach (vagal innervation).
High dose B1 is needed for passive assimilation, with staples. I’d take Mg bisglycinate every day (300 mg x 2 or x3, according to stress); and B2 50 mg (every other day, thrice a week). B2 is needed when taking B1.
B1 for gut motility
Dr Costantini and bacterial overgrowth
SIBO, IBS, and Constipation: Unrecognized Thiamine Deficiency? – June 2020
https://www.hormonesmatter.com/sibo-ibs-constipation-thiamine-deficiency/
To understand how thiamine impacts gut function we have to understand the GI tract. The GI tract possesses its own individual enteric nervous system (ENS), often referred to as the second brain. (vagal innervation). Enteric neurons also use acetylcholine to initiate peristaltic contractions necessary for proper gut motility. Thiamine is necessary for the synthesis of acetylcholine and low levels produce an acetylcholine deficit, which leads to reduced vagal tone and impaired motility in the stomach and small intestine.
=> choline or glycine needed.
For Dr. Constantini, a chronic thiamine deficiency can indirectly produce an inability to digest and absorb foods, and therefore produce a deficiency in most of the other vitamins and minerals. In fact, this is indeed something I see frequently. And sadly, as thiamine is notoriously difficult to identify through ordinary testing methods, it is mostly missed by doctors and nutritionists. To summarize, B1 is necessary in the gut for:
 Stomach acid secretion and gastric emptying
 Pancreatic digestive enzyme secretion
 Intestinal brush border enzymes
 Intestinal contractions and motility
 Vagal nerve function
If I have problem to digest protein, Betaine HCL, at the evening meal. Digestion is optimal at midday.
If I have problem to digest fats: Enzymedica Lypo Gold for fat digestion.
Note: you’re not going to solve this kind of problem with 100 mg B1. Passive assimilation is needed when targeting High dose B1, in several staples, not only with B1 HCl. I can give a link for the protocol of Dr. Allil Overton, on my forum, if wanted (“mirzoune et ciboulette”)
Dr. Overton says, when talking about Thiamine (nod need to listen to):
https://www.hormonesmatter.com/talking-about-thiamine/
“Thiamine (vitamin B1) is critical for the metabolism of food into cellular energy or ATP. Without sufficient thiamine, cellular energy wanes, and with it, the capacity to maintain the energy to function declines. Chronic, unrelenting fatigue is a common characteristic of insufficient thiamine. At its root, fatigue is the physical manifestation of poor energy metabolism.
Why is this nutrient such a problem? Two reasons. First, B1 is the gatekeeper to energy metabolism and so if it is low, everything downstream gums up and does not work well. Second, modern diets, medicines, and other chemical exposures contain numerous anti-thiamine factors that derail thiamine absorption and metabolism. This pushes many people into states of chronic deficiency, one that is simple to correct if identified. Unfortunately, however, patients can go years before the deficiency is recognized.”
Additional info
Thiamine Deficiency - A Potential Cause of SIBO and other Gut Dysfunction?
Elliot Overton – Nutrition and Functional Medicine – 2019
https://www.eonutrition.co.uk/post/thiamine-deficiency-a-major-cause-of-sibo
Thiamine deficiency - A consequence or cause of SIBO?
How can thiamine deficiency cause gut dysfunction?
Key points:
Thiamine's key role in energy metabolism of the brain regions responsible for controlling autonomic balance, coupled with its role in acetylcholine synthesis, indicate that a deficiency could easily cause the symptoms which we associate with SIBO.
The autonomic nervous system is involved in:
 Secretion of stomach acid, pancreatic enzymes, and brush border enzymes
 Release of bile from the liver
 Maintaining regular intestinal peristalsis (motility)
 Reducing intestinal permeability (leaky gut)
 Reducing inflammation

LucH

Targeting Dysbiosis (and leaky gut)
Two things:

avoid fermentation and bacterial overgrowth
Tight junctions are no longer operational. Low-grade inflammation and lack of glutamine (1/4 tsp glutamine 2x/d in a shake). Some B6 PLP would be helpful. Mind overdose. I’d take only 20-25 mg B6 PLP if brain sensitive.
If bacterial overgrowth is suspected, I’d follow a strict protocol if you want to avoid a hide and seek game. It is illusory to want to kill all bacteria. We will strengthen the presence of certain resistant bacteria. Some bacteria will take refuge behind a biofilm.
Tactic: we weaken, we ration, we estourbit / hammer and then we kill. Then we occupy the place. Nature hates an empty place.

Mind stagnation in the second part of the intestines when eating starches. Get informed on MMC (migrating Motor Complex):

The migrating motor complex (MMC) is an electrical and contractile activity of digestive motility which takes place in the inter-digestive periods (between two meals), and interrupted by food intake. Each MMC is accompanied by an increase in gastric, pancreatic and duodenal secretions. They are thought to serve to evacuate contents in the small intestine between meals, and also to transport bacteria from the small intestine into the colon. An alteration of this phase notably favors the development of chronic bacterial colonization of the small intestine, a source in particular of bloating, diarrhea, or even steatorrhea, of the majority of food intolerances. When contractile activity is low, we then speak of lazy intestines. Support and rehabilitation is often necessary, with a prokinetic (I took Resolor 0.5 mg), initially.
Mostlylurking thinks B1 could help too, in this case. Indeed.

Ismail

@herayclitus I’m in a very similar situation to you, ie endotoxin and inflammation etc.

I’m on the fence about “fat” a little bit though, I definitely feel better having more fat (ofc saturated and very little to no PUFA), however from my limited research I was under the impression that fat is what helps endotoxin to proliferate (as well as certain fibres).

Have you tried the carrot salad, consistently, on an empty stomach by any chance?

Ismail

@mostlylurking I wish I could get back the feeling I had when I used Elliot Overton’s Thiamega B1 supplement. I split the capsule into 4, and took after each meal I had, I felt such a sudden energy boost, like I could achieve anything.
I tried the next day, however it didn’t give me the same energy.
I can only surmise I may have “depleted” something whilst high dosing the B1, so I took it with a b-complex as well as magnesium. Still didn’t give the same energy boost.
Any idea what I may be missing? In terms of possible co-factors that help the uptake of B1? Thanks

herayclitus

@Ismail Yes, I eat a fairly low fat diet normally, mostly saturated. Going below 15% of calories from fat seems to cause gut irritation for me, though, so I try to stay between 15-25% ideally. I know even with saturated fat there's a concern of activating TLR4. I do use the carrot salad pretty frequently (and mushroom soup works well too). Using olive oil instead of coconut oil on the carrot salad seems to help somewhat, as Danny and Ray suggested in one of the Generative Energy podcasts. Maybe the olive oil polyphenols have an anti-inflammatory effect, or there could be some benefit to balancing out saturated fat with MUFA. Regarding high-dose thiamine: I've noticed substantial cognitive benefits from 1800mg thiamine daily on memory, but it doesn't seem to improve mood at all

@Ismail said in Endotoxin Inflammation Stack:

@mostlylurking I wish I could get back the feeling I had when I used Elliot Overton’s Thiamega B1 supplement. I split the capsule into 4, and took after each meal I had, I felt such a sudden energy boost, like I could achieve anything.
I tried the next day, however it didn’t give me the same energy.
I can only surmise I may have “depleted” something whilst high dosing the B1, so I took it with a b-complex as well as magnesium. Still didn’t give the same energy boost.
Any idea what I may be missing? In terms of possible co-factors that help the uptake of B1? Thanks

Elliot Overton's Thiamax B1 is a TTFD product. I was unable to tolerate it because my glutathione level was very low due to my high oxidative stress level (caused by my mercury toxicity). TTFD uses glutathione to work so if you are deficient, it can make the situation worse. I learned from Elliot Overton that taking thiamine hcl does not lower glutathione and it can actually improve glutathione status. So I stuck with thiamine hcl and follow Dr. Costantini's protocol. My glutathione status normalized in about 4 months (blood testing). I still high dose thiamine hcl; I've still got the mercury problem, but I'm pretty much without negative symptoms now; actually, I'm fine. High dose thiamine hcl (+magnesium glycinate and other b vitamins) normalized my entire digestive tract. Even though my gut bacteria was severely damaged by the Bactrim antibiotic, things got sorted out pretty quickly once I attained my optimum dose of thiamine hcl per Dr. Costantini's Therapy info (based on body weight).

@herayclitus said in Endotoxin Inflammation Stack:

@mostlylurking Thanks for sharing this--I think it's definitely a leaky gut issue, as alcohol aggravates it worse than anything else. I have been taking thiamine HCl and gelatin as well. Magnesium tends to irritate my gut but I might try it again in a lower dose

Are you drinking alcohol? As long as you do that, you will have problems.

Wernicke Encephalopathy "Thiamine deficiency is characteristically associated with severe alcohol use disorder. Although Wernicke encephalopathy mostly affects people who have a thiamine deficiency due to chronic alcoholism, various other causes include severe malnutrition, hyperemesis gravidarum, prolonged parenteral nutrition, malignancies, immunodeficiency syndromes, liver disease, hyperthyroidism, and severe anorexia nervosa. Chronic alcohol consumption may cause thiamine deficiency due to impaired absorption of thiamine from the intestine...."

"A common inciting event that precipitates WE is an acute infection. Other triggers include prolonged carbohydrate or glucose loading in the presence of thiamine deficiency. In general, patients who receive glucose should also be administered thiamine at the same time."
-end paste-

I've had Wernicke's encephalopathy (fall 2020). I was borderline thiamine deficient even though I was taking 100mgs of thiamine hcl daily and I don't drink alcohol. But my intake of orange juice and fruit was pretty high. And my oxidative stress level was high because of heavy metal toxins (mercury mainly) - high oxidative stress gobbles up thiamine. And then I took Bactrim antibiotic for a UTI. That's all it took; I nearly died. But then I read up about thiamine, found Dr. Costantini's website, implemented what I learned, and managed to pull myself back from the brink.

I found the information on Dr. Costantini's website most helpful. He treated Parkinson's Disease patients with high dose thiamine hcl. There is a connection between gut disbiosis and acquiring Parkinson's Disease. I had suffered with multiple gut disbiosis issues for many years: poor esophageal peristalsis, very low stomach acid, SIBO, leaky gut, constipation/diarrhea, almost universally reactive to foods and environmental toxins. I did not understand that there is a connection between gut disbiosis and Parkinson's Disease until I studied it online.

I'd like to suggest that you spend some time at Dr. Costantini's website; read the Therapy page, the FAQs, the About Dr. Costantini, and watch the patient videos.

GreekDemiGod

@mostlylurking why such high doses of zinc and for how long?

@GreekDemiGod said in Endotoxin Inflammation Stack:

@mostlylurking why such high doses of zinc and for how long?

Are you asking me why I'm taking zinc and the dose? Please help me find what you are referring to. Thanks.

I'm taking 15mgs of zinc daily for a while because I tested deficient on a blood test last spring. I'll get retested in a few weeks. I got my zinc level tested because it is one of the things that is known to watch for deficiency in when high dosing thiamine.

zorba990

@herayclitus That much Zinc will deplete copper and manganese which can lead to things like tendon and ligament weakness among others - so watch out for that.

@zorba990 I'm getting tested again in a couple of weeks. I'm aware of the copper issue; I wasn't aware of of the manganese issue though, thanks. My manganese was alarmingly high about 2 years ago; haven't had it tested recently. I wonder if high manganese would cause zinc deficiency?

LucH

@zorba990 said in Endotoxin Inflammation Stack:

That much Zinc will deplete copper

10 ou 15 mg zinc supplement in not going to deplete copper. Up to 30 mg OK.
The transporters are the same ones.
I take zinc (10 or 15 mg) when I don't eat red meat.
30 mg when there is inflammation or a flu but not when the flu is over-infected (not in infectious bronchitis).
If you eat some pecan nuts or macadamia nuts 2x/wk (5 or 6, no more useful) you won't lack manganese.
The concentration of zinc in blood plasma stays relatively constant regardless of zinc intake.

I've got scientific links to explain why, provided you take into account 3 points:

Many of the studies demonstrate that the copper to zinc ratio was more important as a marker of insufficiency, deficiency, or imbalance than the serum levels of the individual minerals.
Not above 2/0 for Zn / Cu.
No more than 30 mg zinc supplement. 10 - 15 mg is optimal.
If you take a supplement, mind interference. Namely with iron and Ca. I don't take zinc when I eat cheese since the limit of Ca could be very low (< 40 mg).

Part of the sources:
Zn metabolism
Copper and Zinc, Biological Role and Significance of Copper/Zinc Imbalance - Journal of Clinical Toxicology
https://www.omicsonline.org/copper-and-zinc-biological-role-and-significance-of-copper-zincimbalance-2161-0495.S3-001.php?aid=3055
In blood plasma, Zn is bound to and transported by albumin (60%, low-affinity) and transferrin (10%) [27]. Since transferrin also transports iron, excessive iron can reduce zinc absorption, and vice-versa [28]. The concentration of zinc in blood plasma stays relatively constant regardless of zinc intake [29]. Zinc may be held in metallothionein reserves and also transferred in metal transporters of ZIP and ZnT family transporter proteins [30]. Metallothioneins in intestinal cells are capable of adjusting absorption of zinc by 15-40% [31]. Excess zinc particularly impairs copper absorption because metallothioneins absorb both metals [32].

https://lpi.oregonstate.edu/mic/minerals/zinc#safety
Long-term consumption of zinc in excess of the tolerable upper intake level (UL; 40 mg/day for adults) can result in copper deficiency.

Copper and zinc compete for binding sites and are antagonists
There is competition between zinc and other minerals for carriers or uptake sites.

Effect of dietary zinc and protein levels on the utilization of zinc and copper by adult females.
https://www.ncbi.nlm.nih.gov/pubmed/6875690?dopt=Abstract
J Nutr. 1983
=>

No influence on copper retention or excretion with food intake, up to 2 mg Cu,

with low, moderate or high zinc diet, fed either with a moderate protein, or a high protein intake, during a 24-day study, with a balanced diet in twenty-three young adult female.
2. The effect of dietary zinc on intestinal copper absorption.
https://www.ncbi.nlm.nih.gov/pubmed/7282591
Am J Clin Nutr. 1981 Sep.
=> The mucosal cells from animals fed low amounts of zinc retained less copper than the cells from animals fed high amounts of the element.
=> Zinc exerts its antagonistic effect by inducing the synthesis of a copper-binding ligand, probably a thionein, in the mucosal cells which sequesters copper from the nutrient medium, making it unavailable for serosal transfer. This may be a possible mechanism by which dietary zinc decreases copper absorption and leads to a decreased copper status.
=> Zinc modulates copper absorption.

zorba990

@mostlylurking Yes they all compete with each other that way so such an induced deficiency is possible. 120mg is way too much in my opinion to use for any length of time. I personally gave myself tendonitis a few times before realizing what 50mg zinc was doing to me over time. A friend at work did the same thing with overdosing a supplement called ZMA - gave himself numerous tendon and ligament issues and eventually had to have surgery.

@zorba990 said in Endotoxin Inflammation Stack:

@mostlylurking Yes they all compete with each other that way so such an induced deficiency is possible. 120mg is way too much in my opinion to use for any length of time. I personally gave myself tendonitis a few times before realizing what 50mg zinc was doing to me over time. A friend at work did the same thing with overdosing a supplement called ZMA - gave himself numerous tendon and ligament issues and eventually had to have surgery.

I've just been taking 15mgs of zinc, not 120mgs. The blood tests showed a deficiency, both doctors thought I should supplement with a little zinc, so I chose the 15mg one instead of the 30mg one. I take high dose thiamine hcl; it helps with the high oxidative stress I have due to my mercury toxicity. Zinc deficiency is one of the things to watch out for when high dosing thiamine for any length of time; I've been doing it for almost 4 years.

My copper tested fine at the time.