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Larazotide research
Healing

Larazotide

Also known as: Larazotide acetate, AT-1001, INN-202

Larazotide is a research compound. It has been studied in human clinical trials for celiac disease but is not currently FDA-approved. For informational purposes only.

📚 Content aggregated from:3 peer-reviewed sources·r/Peptides community·PubMed / NCBI

Overview

Larazotide (AT-1001) is a synthetic octapeptide that acts as a tight junction regulator — it competitively blocks zonulin, the primary physiological driver of intestinal permeability ('leaky gut'). It is one of the few compounds studied in human clinical trials specifically for tight junction dysfunction, with Phase 2 data in celiac disease demonstrating reduced intestinal permeability and symptom improvement even in the presence of ongoing gluten exposure.

Research Summary

Zonulin upregulation disrupts the tight junction proteins occludin and claudin, allowing paracellular passage of antigens, LPS, and inflammatory triggers into systemic circulation. Larazotide acts as a tight junction agonist by competitively displacing zonulin from its receptor and directly stabilizing tight junction complexes. The Phase 2b CeD trial (N=342) showed larazotide reduced the ratio of lactulose/mannitol (L/M ratio, standard intestinal permeability marker) and improved GI symptom scores versus placebo in actively-challenged celiac patients.

Dosing Range

low

0.25mg

moderate

0.5mg

high

1mg

Units: mg · Frequency: 3x daily (before meals)

Dosing ranges are aggregated from preclinical research and community protocols. Not medical dosing guidance.

Administration Routes

Oral (capsule)Subcutaneous injection (research use)

Reconstitution Notes

Primarily oral — capsule or powder dissolved in water taken before meals. For injectable research use: reconstitute with bacteriostatic water to 0.5mg/mL. Stable 28 days refrigerated.
Step-by-step reconstitution guide →

Supplies you'll need

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Reported Side Effects

  • Headache (most commonly reported adverse event in trials)
  • Nausea (mild)
  • Generally well-tolerated — adverse event rate similar to placebo in clinical trials

Research Papers

3 peer-reviewed sources

Community Experiences

Aggregated from public forums. Anecdotal — not clinical evidence.

r/Peptides

Community reports on larazotide for leaky gut, celiac-adjacent symptoms, autoimmune conditions, and gut dysbiosis.

View original thread
r/CeliacDisease

Celiac community discussing AT-1001 trial results and research access options.

View original thread

Overview

Intestinal permeability — the loosening of tight junctions between intestinal epithelial cells — underlies or contributes to an enormous range of conditions: celiac disease, Crohn's, IBS, food sensitivities, autoimmune diseases, and chronic systemic inflammation. Larazotide is one of the only compounds with Phase 2 human trial data specifically targeting this mechanism.

The Zonulin System

Tight junctions are the "gatekeepers" between intestinal cells. Zonulin — discovered by Alessio Fasano's lab — is the primary physiological regulator of these junctions. When zonulin is elevated (triggered by gliadin/gluten, dysbiosis, or stress), tight junctions open, allowing paracellular passage of:

  • Undigested food antigens
  • Bacterial LPS (endotoxin)
  • Microbial fragments
  • Inflammatory cytokines

This "leakage" into systemic circulation drives immune activation, contributing to autoimmune flares, food intolerances, and neuroinflammation.

How Larazotide Works

Larazotide does NOT block zonulin from being produced — it competitively occupies the zonulin receptor on tight junction complexes, preventing zonulin from binding and triggering junction opening. Additionally, it directly stabilizes occludin and ZO-1 (tight junction scaffold proteins) at the cell membrane.

The result: tighter junctions, reduced antigen translocation, lower systemic inflammatory load.

Clinical Trial Data

The most important data comes from CeD (Phase 2b) in celiac patients challenged with gluten:

  • Larazotide 0.5mg 3x/day reduced L/M ratio (intestinal permeability marker) vs placebo
  • Improved GI symptom response rate
  • Well-tolerated — no significant safety signals

Phase 3 trials have been initiated and have stalled — ImmunGene (formerly Innovate Biopharmaceuticals) has not completed full Phase 3 enrollment, making this still a research compound.

Stacking Context

In research protocols, larazotide is often combined with:

  • BPC-157 — systemic gut healing and angiogenesis
  • KPV — mucosal anti-inflammatory
  • Glutamine — tight junction substrate provision
  • Probiotics — zonulin-modulating microbiome support

The combination targets gut permeability from multiple angles: structural (larazotide), anti-inflammatory (KPV), and regenerative (BPC-157).

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