The Sunlight Experiment

Supplement Monograph

Larazotide

PeptideGut

Larazotide (larazotide acetate) is an eight-amino-acid tight-junction-regulating peptide trialled in celiac disease; investigational, not an approved supplement or drug.

Work in progress Updated July 2026

What Is Larazotide?

Larazotide (larazotide acetate) is an eight-amino-acid, orally administered peptide that regulates intestinal tight junctions, developed as a zonulin antagonist to reduce “leaky” gut permeability. It has been studied mainly as an adjunct to the gluten-free diet in celiac disease. Of the peptides in this batch it has the most human trial data, but it is an investigational drug that has not been approved, and it is not a dietary supplement.

Evidence

In a randomised, double-blind, placebo-controlled gluten-challenge study, larazotide acetate limited gluten-induced increases in intestinal permeability and symptoms in celiac patients 1Reference 1Kelly CP et al et al. · 2013RCTLarazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study — randomised/RCTView study →. A larger phase-2b randomised trial in patients with persistent symptoms despite a gluten-free diet found the 0.5 mg dose reduced symptoms versus placebo 2Reference 2Leffler DA et al et al. · 2015RCTLarazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial — randomised/RCTView study →. Its tight-junction / zonulin-antagonist mechanism is reviewed in 3Reference 3Slifer ZM et al et al. · 2021ReviewLarazotide acetate: a pharmacological peptide approach to tight junction regulation — reviewView study →. Importantly, a subsequent phase-3 celiac trial was discontinued after an interim analysis, so larazotide has not demonstrated confirmatory efficacy or reached approval; broader “leaky gut” uses beyond celiac are not established.

Dosage & Safety

Trial doses were in the range of ~0.5 mg taken orally before meals; this is trial context, not a personal recommendation. Larazotide was generally well tolerated in celiac trials, and because it is minimally absorbed it acts locally in the gut. However, it is an investigational drug, not an approved dietary supplement, and its interactions, pregnancy safety and long-term effects are not established / not assessed in this pass. Informational only.

References

  1. Kelly CP et al. (2013). Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study — randomised/RCT. Aliment Pharmacol Ther. https://pubmed.ncbi.nlm.nih.gov/23163616/
  2. Leffler DA et al. (2015). Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial — randomised/RCT. Gastroenterology. https://pubmed.ncbi.nlm.nih.gov/25683116/
  3. Slifer ZM et al. (2021). Larazotide acetate: a pharmacological peptide approach to tight junction regulation — review. Am J Physiol Gastrointest Liver Physiol. https://pubmed.ncbi.nlm.nih.gov/33881350/