Game-Changing "Leaky Gut" Treatment (Larazotide Acetate) will soon be available

[mitoMAN]

https://www.news-medical.net/news/2...related-MIS-C-in-children-suggests-study.aspx
"Finally, one patient with MIS-C was treated with a zonulin antagonist called larazotide to visualize the effects on SARS-CoV-2 antigens in the blood and the overall clinical response. The child treated with larazotide had multiple medical problems and had a history of severe COVID-19 with respiratory failure and cardiac arrest. One month later, the patient developed signs of MIS-C, failing to show improvement with steroids nor intravenous immunoglobulins (IVIG). High viral RNA titers were present in the stool, as well as spike antigens in plasma even two weeks after these agents were started.
Treatment with larazotide led to a dramatic reduction in viral antigens, inflammatory markers and clinical parameters, compared to the ineffectiveness of either steroids or IVIG."

"It also serves as a 'proof of concept that zonulin antagonism directly reduces SARS-CoV-2 antigenemia with abatement of the cytokine storm and subsequent clinical improvement in a single patient.'

Larazotide has a high safety margin and is undergoing phase 3 trials for the treatment of resistant celiac disease, an inflammatory bowel condition. Its use led to a 90% fall in spike antigen levels in the blood, with significant improvement in inflammation, fever and general illness."

 

[Hoosierfans]

This is an amazing story and great news! I am on week 3 of 3 x day Lorazatide .25 mg. No major symptom improvement yet. Based on this study and others in Celiac disease, I am going to increase my dose to .5 mg 3 x day next month.

 

[jepps]

I should also say that I am chronically iron deficient. I get IV infusions every 2-3 months as, for some reason, I don’t absorb oral iron. Interestingly I recently came up copper deficient but I *have* been able to raise my copper levels through oral supplementation. It will be interesting to see if Larazotide helps me absorb and hold on to iron.

A very effective treatment for iron deficiency for me was the natural peptide bonomarlot (bone marrow peptide). Iron supplements or iron infusions were not very effective. Before taking bonomarlot I had ferritine levels of 10 - 15. Since taking bonomarlot (one capsule every second day since two years) I have persistent ferritine levels of 100 - 110. Also haemoglobin is 14 - 15 (instead of 11 - 12).

 

[Henrik]

I'm keen on giving larazotide a shot as well. Does anyone know a reputable source? I'd be happy to pitch in for testing if needed.

 

[sometexan84]

This is an amazing story and great news! I am on week 3 of 3 x day Lorazatide .25 mg. No major symptom improvement yet. Based on this study and others in Celiac disease, I am going to increase my dose to .5 mg 3 x day next month.

Any Larazotide updates?

 

[op2pig]

I assess my zonulin levels and determined that my zonulin levels were normal. So I am not proceeding with larazotide now as a treatment for my autoimmune disease. So I cannot provide any other updates.

 

[Hip]

NOTE: people experimenting with larazotide as an ME/CFS treatment may be administering this peptide in the wrong way, meaning it may not actually help stop bacterial toxins from leaking into the blood.

Both the small intestine and the colon can be leaky. You can have a leaky small intestine, a leaky colon, or both. (The lactulose/mannitol test incidentally only detects leakiness in the small intestine; it cannot detect a leaky colon).

Here is a leaky gut study on IBS which found that in IBS-D, it is the colon which is leaky, and the worse the colonic leak, the more frequently the patient passes stools. Whereas they found in IBS, the small intestine is not leaky. So location is important.

When we use larazotide as an experimental ME/CFS treatment, presumably the objective is to heal leaky gut, in order to stop bacterial toxins like LPS secreted by bacteria in the intestines from entering into the bloodstream, where these toxins are highly pernicous.

But the vast majority of intestinal bacteria live in the colon; very few bacteria live in the small intestine (unless you have SIBO). In fact the small intestine is normally considered quasi-sterile.

In this paper, table 1 shows the population of bacteria per ml of volume in various parts of the gastrointestinal tract: the colon has 10^11 bacteria per ml, whereas the upper small intestine as only 10^4 per ml, and the lower small intestine has 10^8 per ml.

Many ME/CFS patients do have SIBO, according to this study. But levels of bacteria in SIBO are not that great, up to around 10^5 per ml in the small intestine, according to this paper.

So the main source of bacterial toxins will be the colon. If we want to stop these bacterial toxins from entering the blood, we might therefore want to target colon leakiness with larazotide. Targeting just small intestine leakiness is unlikely to help much, because few bacteria live in the small intestine.

Unfortunately oral larazotide is broken down in the small intestine, and so does not reach the colon:

the peptide is broken down in the small intestine and there is no systemic absorption of LA or the fragments

Source: here

So oral larazotide will not help heal a leaky colon. Thus taking larazotide orally may achieve very little in terms of stopping bacteria toxins in the colon from entering the blood.

To address this issue, my speculative idea would be to take larazotide (as well as possibly other leaky gut supplements) as an colonic enema, or introduce larazotide in solution to the colon via a colon tube. This may then fix colon leakiness, and thus help prevent bacterial toxins from the colon entering the blood.



The same problem applies to other leaky gut supplements, like zinc-carnosine and glutamine: when taken orally, these may be absorbed or broken down in the small intestine, so that they do not actually reach the colon. Thus the colon may receive no benefit from these supplements, yet the colon would seem to be the most crucial area of the intestines to heal.

So again, administering these leakly gut supplements directly into the colon by means of a colon tube may be for more effective for treating the LPS leak from the intestines presumed to be driving ME/CFS.

I am plannning to administer a cocktail of leaky gut supplements into my colon by means of a colon tube, to see if that improves ME/CFS symptoms.

You can buy colon tubes cheaply on Amazon.

 

[Hip]

One issue with using a colon tube however is that these tubes are only about 50 cm long, whereas the colon itself is about 150 cm in length.

So that means you will only be able to target the latter part of the colon.



An alternative approach I was looking at a few years ago was to use capsules that deliver their contents to the colon. Then you could fill those capsules with leaky gut supplements and drugs in order to target the colon.

This is similar in concept to enteric capsules, which are designed to resist stomach acid and deliver their contents to the small intestines; but in this case the capsule remains intact until it reaches the colon, and then opens up and delivers its content directly to the colon.

Unfortunately I could not find any commercially-available colon capsules, but I did find a capsule coating compound called Eudragit S 100 which you can paint onto a regular capsule to turn it into a colon targeted capsule.

So using Eudragit S 100, you could make up some capsules containing leaky gut repair supplements and drugs, then paint them with this Eudragit S 100 coating, so that the capsule only releases its contents when it arrives in the colon.



I detail making your own colon-targeted capsules using this Eudragit S 100 product in this thread here: Encapsulating leaky gut repair supplements in capsules to target the colon.

I've yet to get around to buying some Eudragit and making these colon capsules, but after hearing about the Markov CBIS theory of ME/CFS, where Dr Markov posits ME/CFS is due to bacteria toxins leaking into the blood, and have a renewed interest in trying to fix a leaky colon.



Note that if you have IBS-D, then a study found this involves colonic permeability (leaky colon).

 

[junkcrap50]

Here is a leaky gut study on IBS which found that in IBS-D, it is the colon which is leaky, and the worse the colonic leak, the more frequently the patient passes stools. Whereas they found in IBS, the small intestine is not leaky. So location is important.

Do you know what they found with IBS-C ? Or what type of gut permeability IBS-C patients have? The abstract doesn't mention it in the results.

Unfortunately oral larazotide is broken down in the small intestine, and so does not reach the colon: the peptide is broken down in the small intestine and there is no systemic absorption of LA or the fragments
Source: here

I'm not seeing where they say this nor how that conclusion is reached. (Didn't read whole paper but searched it to find relevant parts.) They measured only in the proximal jejunum as the farthest point along the GI track. And it showed they had roughly the same larazotide acetate concentrations there as was present when leaving the stomach. They also don't mention anything about LA metabolism. Other than in other studies, LA was detected at certain levels within plasma. So, why is it thought that LA doesn't pass through to the colon or that it is broken down before then?

Not discounting your idea. I think colonic administration of LA would be worth trying.

Interesting that there isn't much that I could find about large intestinal permeability. None of the permeability tests are run while the testing solution passes through the colon. EDIT: Though I see you do mention it in this post:

By the way, if you want to get tested for leaky gut, note that the lactulose/mannitol leaky gut test only checks the small intestine; it cannot detect any colon leakiness you may have. The polyethylene glycol (PEG) test checks your intestines as a whole for leakiness (the small intestine and the colon). The sucralose test specifically checks just the colon for leakiness (but I am not sure if this test is commercially available). Ref: 1

 

[mitoMAN]

I can say that taking Larazotide in delayed release capsules reduced my gluten interolance, bloating, pain, normalized stool and cut my serum Zonulin in half.

It seems to still have an effect taken that way. However I agree that Enamas might be superior. But well, you dont want to do that daily trust me. I have done that with other peptides before.

 

[Hip]

Do you know what they found with IBS-C

All they say about IBS-C in the paper is that they found reduced intestinal permeability in these patients.

I'm not seeing where they say this nor how that conclusion is reached.

They say in the paper:

the peptide [larazotide] is broken down in the small intestine and there is no systemic absorption of LA [larazotide] or the fragments [of broken down peptide]

So firstly larazotide is not absorbed into the bloodstream; it remains in the digestive tract. Secondly, as larazotide travels along the small intestine, it is broken down; so by the time it reaches the colon, there is going to be little or no larazotide left to work on the colon.

I can say that taking Larazotide in delayed release capsules reduced my gluten interolance, bloating, pain, normalized stool and cut my serum Zonulin in half.

That's very interesting. Do you know where along the digestive tract your delayed release capsules are designed deliver their contents? There are capsule technologies these days that can deliver their contents at quite precise locations along the digestive tract.

However I agree that Enamas might be superior. But well, you dont want to do that daily trust me. I have done that with other peptides before.

I have not used enema equipment, but have tried a colon tube connected to a large syringe. Inserting the 50 cm tube is very quick, and then to the end of the tube you just attach a 50 ml syringe containing you medication dissolved in 50 ml of distilled water, and plunge down the syringe to push that 50 ml of water into the colon. The whole procedure takes about 5 or 10 minutes to complete, I find.

Just noticed you tagged me at the beginning of this thread some time ago, @mitoMAN, but I did not see that. (If you edit a post to add a tag, incidentally, it does not work).

 

[junkcrap50]

Wow. I can't seem to read today. Thanks @Hip for pointing the obvious out to me. I needed it. (Not sarcasm, even though it reads that way. )

 

[markus.bagelmann]

Current Study is testing 0.25mg instead of 0.5mg

https://clinicaltrials.gov/ct2/show/NCT03569007


I will be taking 0.25mg as well the coming weeks/months.

Is it possible that the first doses give a worsening of symptoms?
Can this dosage (0.25) help in this sense?

Hi @mitoMAN, do you have a source for buying larazotide acetate?
.

Current Study is testing 0.25mg instead of 0.5mg

https://clinicaltrials.gov/ct2/show/NCT03569007

I will be taking 0.25mg as well the coming weeks/months.

 

[joshualevy]

That clinical trial has failed.
It is now marked "Terminated by Sponsor" which you can see here:
https://clinicaltrials.gov/ct2/show/NCT03569007

And the company involved issued a press release two months ago saying it had failed (in corporate pharma speak, of course, they never used the word "failed", but it clearly did fail):
https://feeds.issuerdirect.com/news-release.html?newsid=4598003219390084

 

[markus.bagelmann]

You mean that 0,25 instead of 0,50 is not enough or that in general larazotide acetate has no efficacy for the relief of persistent symptoms in adult patients with celiac disease on a gluten free diet?

 

[joshualevy]

The study tested both doses, and the company canceled it, so I think it is fair to say that both doses failed. If even one looked like it might possibly succeed in the future, they surely would have continued with the trial.

 

[Hip]

That clinical trial has failed.

It failed to help in the clinical trial for "patients with celiac disease who continue to experience gastrointestinal symptoms while adhering to a gluten-free diet".

However, some ME/CFS patients have found larazotide acetate helpful for their gut issues.

 

[ForumMember]

Does anyone know of a source for larazotide acetate that ships to the UK?

 

[markus.bagelmann]

Try with Frazer Pharm in China.

 

[ForumMember]

Try with Frazer Pharm in China.

Thank you