S801 Dose-Related Effects of Ricinoleic Acid (Castor Oil) on Gut Permeability in Healthy Participants: Provocative Test for Treatments Aimed at Restoring Barrier Function
Bibliographic record
Abstract
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 (Figure 1). 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 1). 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 1). 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. Conclusion: 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.Figure 1.: Urine excretion of sugar probes 0-24 hr on day 5 of Castor Oil treatment: Dose-related effects. Table 1. - mg, median (Q1,Q3) Placebo (PBO) Castor Oil (CO) 750mg CO 1500mg CO 3000mg P-Value (KW test) P-value of 3000mg CO vs PBO (t-test) 2-8h 13C-mannitol 3.82 (1.75, 4.44) 3.06 (2.11, 3.99) 2.82 (2.01, 3.86) 5.23 (3.82, 6.20) 0.091 0.087 2-8h lactulose 0.42 (0.29, 0.90) 0.49 (0.28, 0.54) 0.60 (0.40, 0.79) 1.21 (0.75, 1.54) 0.060 0.044 0-24h 13C-mannitol 7.78 (3.67, 8.73) 7.99 (7.32, 10.0) 6.31 (4.81, 7.02) 11.87 (10.02, 17.25) 0.008 0.024 0-24h lactulose 0.92 (0.81, 1.70) 1.20 (1.02, 1.54) 1.22 (0.94, 1.55) 2.06 (1.77, 2.66) 0.056 0.019 BSFS (mean ± SD) 3.61 ± 0.66 4.38 ± 0.84 4.66 ± 1.11 5.01 ± 0.88 BM/day (mean ± SD) 1.37 ± 0.39 1.67 ± 0.82 1.90 ± 1.82 1.54 ± 0.59
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".