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Larazotide - zonulin inhibitor for leaky gut GROUP BUY

larazotide zonulin zonulin inhibitor leaky gut intestinal permeability celiac inflammatory bowel disease ibd

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#1 gintrux

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Posted 20 November 2019 - 11:47 AM


There is an experimental drug called Larazotide, which works as as zonulin inhibitor and should restore intestinal permeability (leaky gut) to a normal state. Zonulin is the hormone increasing intestinal permeability.

There are significant amount of studies done on it (with humans!):

 

Larazotide acetate promotes tight junction assembly in epithelial cells.
Tight junctions (TJ) control paracellular permeability and apical-basolateral polarity of epithelial cells. Dysregulated permeability is associated with pathological conditions, such as celiac disease and inflammatory bowel disease. TJ formation is dependent on E-cadherin-mediated cell-cell adhesion and actin rearrangement, and is regulated by the Rho family GTPase and aPKC signaling pathways. Larazotide acetate, an 8-mer peptide and TJ modulator, inhibits TJ disassembly and dysfunction caused by endogenous and exogenous stimuli in intestinal epithelial cells. Here, we examined the effect of larazotide acetate on de novo TJ assembly using 2 different model systems. In MDCK cells, larazotide acetate promoted TJ assembly in a calcium switch assay. Larazotide acetate also promoted actin rearrangement, and junctional distribution of zonula occludens-1 (ZO-1), occludin, claudins, and E-cadherin. Larazotide acetate promoted TJ maturation and decreased paracellular permeability in "leaky" Caco-2 cells. Taken together, our data indicate that larazotide acetate enhances TJ assembly and barrier function by promoting actin rearrangement and redistribution of TJ and AJ proteins.

https://www.ncbi.nlm...pubmed/22401910

 

A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. METHODS:

In this dose-ranging, placebo-controlled study, 86 patients with celiac disease controlled through diet were randomly assigned to larazotide acetate (0.25, 1, 4, or 8 mg) or placebo three times per day with or without gluten challenge (2.4 g/day) for 14 days. The primary efficacy outcome was the urinary lactulose/mannitol (LAMA) fractional excretion ratio. Secondary endpoints included gastrointestinal symptom severity, quality-of-life measures, and antibodies to tTG.

RESULTS:

LAMA measurements were highly variable in the outpatient setting. The increase in LAMA ratio associated with the gluten challenge was not statistically significantly greater than the increase in the gluten-free control. Among patients receiving the gluten challenge, the difference in the LAMA ratios for the larazotide acetate and placebo groups was not statistically significant. However, larazotide acetate appeared to limit gluten-induced worsening of gastrointestinal symptom severity as measured by the Gastrointestinal Symptom Rating Scale at some lower doses but not at the higher dose. Symptoms worsened significantly in the gluten challenge-placebo arm compared with the placebo-placebo arm, suggesting that 2.4 g of gluten per day is sufficient to induce reproducible gluten toxicity. Larazotide acetate was generally well tolerated. No serious adverse events were observed. The most common adverse events were headache and urinary tract infection.

https://www.ncbi.nlm...pubmed/22825365

 

Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study. METHODS:

This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels.

CONCLUSIONS:

Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.

https://www.ncbi.nlm...pubmed/23163616

 

Larazotide Acetate for Persistent Symptoms of Celiac Disease Despite a Gluten-Free Diet: A Randomized Controlled Trial

 

Results

The primary endpoint was met at the 0.5 mg dose of larazotide acetate with fewer symptoms compared with placebo by Modified Intention to Treat (n=340) (ANCOVA p=0.022, MMRM p=0.005). The 0.5mg dose showed effect on exploratory endpoints including, 26% decrease in Celiac Disease Patient Reported Outcome Symptomatic Days (p=0.017); 31% increase in Improved Symptom Days (p=0.034); ≥50% reduction from baseline of weekly average Abdominal Pain Score for ≥6 out of 12 weeks of treatment (p=0.022); and a decrease in Non-GI symptoms of headache and tiredness (p=0.010). The 1 and 2 mg doses were no different than placebo for any endpoint. Safety was comparable to placebo.

Conclusions

Larazotide acetate 0.5 mg reduced signs and symptoms in CeD patients on a GFD better than a GFD alone. While results were mixed, this study represents the first successful trial of a novel therapeutic agent targeting Tight Junction regulation in patients with CeD who are symptomatic despite a GFD. Clinicaltrials.gov, NCT01396213

https://www.ncbi.nlm...les/PMC4446229/

 

 

 

The fact that the drug did not change Lactulose-Mannitol ratio does raise some eybrows on its efficiency, but I'd still be interested in experimenting.

I know my account is fresh and there have been legitimacy issues with group buys, so if anyone experienced in organizing group buys would like to take this over, that would be ok.

 

Any interest?



#2 StevesPetMacaque

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Posted 22 November 2019 - 11:07 PM

I'd try a gram or 2.



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Also tagged with one or more of these keywords: larazotide, zonulin, zonulin inhibitor, leaky gut, intestinal permeability, celiac, inflammatory bowel disease, ibd

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