P4042 - Dose-Related Effects of Ricinoleic Acid (Castor Oil) on Gut Permeability in Healthy Participants: Provocative Test for Treatments Aimed at Restoring Barrier Function

David Y.. Yang, MD¹, Camille Lupianez-Merly, MD², Kara Jencks, MD², Saam Dilmaghani, MD, MPH², Irene A. Busciglio, BS², Deborah Eckert, RN², Michael D. Ryks, ², Roy Dyer, PhD², Brady A. Vizenor, ², Yuxi Zhao, PhD³, Anna Sapone, MD, PhD³, Michelle Rooks, PhD³, Jeremy Gale, PhD³, Michael Camilleri, MD, MACG^2
1University of Alberta, Edmonton, AB, Canada; ²Mayo Clinic, Rochester, MN; ³Pfizer Research and Development, Cambridge, MA

Introduction: Intestinal barrier dysfunction is implicated in multiple conditions. Tools to disrupt gut permeability in healthy participants are needed to facilitate research into agents that restore intestinal barrier integrity. Nonsteroidal anti-inflammatory drugs (NSAIDs) disrupt predominantly gastric and small intestinal permeability. Ricinoleic acid, the active component of castor oil (CO), increased colon permeability in rabbits (PMID 863205). The aim of this study was to determine the dose-related effects of CO on gut permeability in healthy human adults.

Methods: A single-center, double blinded, randomized controlled trial of healthy participants 18-70 y/o randomized (1:1:1:1) to placebo (PBO), or 750 mg, 1500 mg, 3000 mg CO administered orally daily for 5 days. On day 5, gut permeability was tested by quantifying urinary excretion of probe molecules after oral ingestion of 100 mg ¹³C-mannitol (¹³C-M) and 1 g lactulose (PMID 33865841). Three urine collections were acquired: 0-2, 2-8, and 8-24 hours. Bowel functions were appraised using a standard daily diary (stool consistency [BSFS], and bowel movement frequency). The primary endpoints were 2-8 h ¹³C-M and lactulose excretion, reflecting small intestinal and colonic permeability. Statistical analyses were completed in Sigmaplot using Kruskal-Wallis (KW) test for detecting differences among treatments and t-test for comparing 3000 mg CO to PBO.

Results: 24 participants (12F) were recruited and 21 completed the trial (1 dropout, 2 incomplete data). Data from 1 participant were excluded due to recent suspected infectious gastroenteritis. Overall gut permeability assessed by 0-24 h excretion of the sugar probes (analyzed using KW test) showed significant differences among treatments for ¹³C-M (p=0.008), and borderline significant difference for lactulose (p=0.056) (table). For comparison of 3000 mg CO vs PBO by t-test, ¹³C-M (p=0.087) and lactulose (p=0.044) for 2-8 h urine were higher for 3000 mg CO group. 0-24 h urinary excretions in 3000 mg CO group were significantly greater than PBO group for both probes (table). In addition, 3000 mg CO was associated with looser stool consistency and slightly increased bowel frequency. Adverse events were generally mild with 1 drop-out due to abdominal pain.

Discussion: A 5-day course of 3,000 mg castor oil increases gut permeability in healthy participants, suggesting that castor oil can be an alternative to nonsteroidal anti-inflammatory drugs for studies requiring the perturbation of gut permeability.



Disclosures:


David Y.. Yang, MD¹, Camille Lupianez-Merly, MD², Kara Jencks, MD², Saam Dilmaghani, MD, MPH², Irene A. Busciglio, BS², Deborah Eckert, RN², Michael D. Ryks, ², Roy Dyer, PhD², Brady A. Vizenor, ², Yuxi Zhao, PhD³, Anna Sapone, MD, PhD³, Michelle Rooks, PhD³, Jeremy Gale, PhD³, Michael Camilleri, MD, MACG². P4042 - Dose-Related Effects of Ricinoleic Acid (Castor Oil) on Gut Permeability in Healthy Participants: Provocative Test for Treatments Aimed at Restoring Barrier Function, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.