Larazotide is an octapeptide zonulin antagonist that restores gut barrier integrity by tightening intestinal junctions, reducing permeability and associated inflammation (e.g., celiac disease, “leaky gut”).
Larazotide
Also known as: AT-1001; Zonulin Antagonist
Overview
Benefits
- Enhanced gut health
- Celiac support
- Reduced inflammation
- Symptom relief
Consider This Peptide If You Want To
- Support gut health by reducing intestinal permeability
- Decrease inflammation and improve digestive function
Dosage & Administration
Dosage Guidelines
Recommended Dosage
• Amount:500 mcg
• Frequency:daily
• Duration:12 weeks
• Rest Period:12 weeks
• Time of Day:morning
• Ingestion:oral
Administration Routes:Oral
Oral Administration:
• Standard Dosage: 500 mcg three times daily (TID)
• Timing:
• Duration: 12-week cycles, with evaluations for ongoing treatment
Research Findings on Dosage:
• Commonly Reported Dosage:
◦ Oral: 500 mcg three times daily (TID).
• Duration: 12-week cycles, with evaluations for ongoing treatment.
Mechanism of Action
Mechanism of Action
How this peptide works in the body
Tight Junction Regulation:
Larazotide functions as a zonulin antagonist, preventing the activation of zonulin receptors on intestinal epithelial cells. By inhibiting zonulin-mediated signaling, Larazotide stabilizes the tight junctions between epithelial cells, reducing paracellular permeability. It promotes the redistribution and assembly of tight junction proteins, including occludin, claudins, and zonula occludens-1 (ZO-1), strengthening the gut barrier and preventing the entry of harmful antigens, toxins, and pathogens into the bloodstream.
Actin Cytoskeleton Stabilization:
Larazotide modulates the activity of myosin light chain kinase (MLCK), a key enzyme responsible for regulating the contractility of actin-myosin filaments. By inhibiting MLCK activation, it prevents the phosphorylation of myosin light chain (MLC), reducing tension on actin filaments and maintaining the structural integrity of tight junctions. This stabilization prevents actin polymerization-induced junctional disassembly, preserving the gut barrier function under inflammatory and pathological conditions.
Inflammatory Pathway Modulation:
By reducing paracellular antigen penetration, Larazotide limits the activation of gut-associated lymphoid tissue (GALT), preventing excessive immune responses. This suppression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interferon-gamma (IFN-γ), alleviates gut inflammation and systemic immune activation. Additionally, it mitigates T-helper 1 (Th1) and Th17 immune responses, which are associated with autoimmune conditions like Celiac disease and Crohn's disease.
Consider Stacking With
- Probiotics
- Glutamine
Side Effects & Cautions
Common Side Effects
- Occasional nausea or abdominal discomfort
Research & References
Research Highlights
Celiac Disease Trials:
Phase III clinical trials demonstrated significant reduction in symptoms when used as an adjunct to a gluten-free diet.
Achieved 26% fewer symptoms and a 31% increase in symptom-free days in patients with persistent gluten exposure.
Leaky Gut Studies:
Shown to reduce intestinal permeability and associated systemic inflammation in animal models.
Tight Junction Restoration:
Promotes the redistribution of tight junction proteins and reduces actin polymerization-induced barrier disruption.
References
Fasano, A., et al. "Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer." Physiological Reviews, 2011
Wang, W., et al. "Larazotide Acetate for the Treatment of Celiac Disease: A Phase 2 Clinical Trial." Gastroenterology, 2015
Tripathi, A., et al. "Mechanisms of Zonulin Modulation on Tight Junctions and Its Role in Celiac Disease." PLOS ONE, 2009
Kelly, C. P., et al. "Larazotide Acetate in the Treatment of Celiac Disease: A Randomized Controlled Trial." American Journal of Gastroenterology, 2013