The Effect of Capsaicin and Cinnamaldehyde on Intestinal Permeability

The Effect of Capsaicin and Cinnamaldehyde on Intestinal Permeability, Gallbladder Motility and Satiety

An altered permeability has been proposed to play an important role in the pathogenesis of several gastrointestinal disorders, such as irritable bowel syndrome and inflammatory bowel disease. Nutrients derived from food are able to influence the permeability of the intestine and can therefore also affect gastrointestinal symptoms. In this study, the investigators will investigate the effects of capsaicine and cinnamaldehyde, which can be found in hot peppers and cinnamon, respectively, on gastrointestinal physiology.

Objective:

To obtain more information about the effects of capsaicin and cinnamaldehyde on the intestine, these substances will be infused directly in the duodenum. Hereafter, the permeability of the intestine, gallbladder motility and the effects on satiety will be assessed.

Hypothesis:

Duodenal capsaicin and cinnamaldehyde infusion induces changes in the intestinal epithelial barrier function by selectively acting on TRPV1 and TRPA1 receptors and releasing serotonin from enterochromaffin cells as determined by the multi sugar permeability test

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: Capsaicin; Dietary supplement: Cinnamaldehyde; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6202 AZ
      • Maastricht University Medical Center+

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Based on medical history and previous examination, no gastrointestinal complaints can be defined.
2. Age between 18 and 65 years. This study will include healthy adult subjects. Subjects over 65 years have an increased risk for comorbidities, therefore, subjects over 65 years will not be included. Furthermore, age has an influence on the homeostasis of the intestinal mucosa [21], which can potentially influence outcome parameters of the study.
3. BMI between 20 and 30 kg/m2

Exclusion Criteria:

1. History of severe cardiovascular, respiratory, urogenital, gastrointestinal/ hepatic, hematological/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological/psychiatric diseases, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol. The severity of the disease (major interference with the execution of the experiment or potential influence on the study outcomes) will be decided by the principal investigator.
2. Use of medication, including vitamin supplementation, except oral contraceptives, within 14 days prior to testing
3. Administration of investigational drugs or participation in any scientific intervention study which may interfere with this study (to be decided by the principle investigator), in the 180 days prior to the study
4. Major abdominal surgery interfering with gastrointestinal function (uncomplicated appendectomy, cholecystectomy and hysterectomy allowed, and other surgery upon judgement of the principle investigator)
5. Dieting (medically prescribed, vegetarian, diabetic, macrobiological, biological dynamic), pregnancy, lactation
6. Excessive alcohol consumption (>20 alcoholic consumptions per week)
7. Smoking
8. Blood donation within 3 months before the study period
9. Self-admitted HIV-positive state

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Capsaicin	Dietary supplement: Capsaicin; 1.5 mg capsaicin administered intraduodenally
EXPERIMENTAL: Cinnamaldehyde	Dietary supplement: Cinnamaldehyde; 70 mg per intervention administered intraduodenally
PLACEBO_COMPARATOR: Placebo; Physiological saline	Dietary supplement: Placebo; Physiological saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the effect of capsaicin and cinnamaldehyde (CA) infusion on intestinal permeability	Measurements performed in plasma	Measured at start and end of infusion (30 min), on each of the 3 test days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the effect of capsaicin and CA infusion on the activation of the TRP receptors as defined by the mucosal concentrations of the neuropeptides SP, CGRP and NKA	Measurements will be performed in mucosal biopsy samples	1 day
To assess the effect capsaicin and CA on parameters that are known to be associated with satiety, measured by satiety hormones in blood plasma and mucosal tissue (CCK) as well as satiety scoring on a visual analogue scale	Visual analogue scores will be collected from the start of the infusion until 90 minutes thereafter.	1 day
To assess the effect of capsaicin and CA on serotonergic function in duodenal biopsy specimens by measuring serotonin and its metabolites by HPLC	Measurements will be performed on biopsy specimens	1 day
To assess the effect of capsaicin and CA on gallbladder motility by ultrasound		Measurements will be performed during the testday starting from 08.00 AM to 11.00AM
To assess the effect of capsaicin and CA on the expression of tight junction proteins measured by immunohistochemistry and by quantitative PCR	Measurements will be performed in biopsy specimens of the duodenal mucosa	1 day

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: Top Institute Food and Nutrition
• Investigators: Principal Investigator: Ad Masclee, MD PhD, Maastricht University Medical Center

Publications and helpful links

General Publications

• van Avesaat M, Troost FJ, Westerterp-Plantenga MS, Helyes Z, Le Roux CW, Dekker J, Masclee AA, Keszthelyi D. Capsaicin-induced satiety is associated with gastrointestinal distress but not with the release of satiety hormones. Am J Clin Nutr. 2016 Feb;103(2):305-13. doi: 10.3945/ajcn.115.123414. Epub 2015 Dec 30.

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (ACTUAL): June 1, 2011
• Study Completion (ACTUAL): December 1, 2011

Study Registration Dates

• First Submitted: April 12, 2011
• First Submitted That Met QC Criteria: August 16, 2012
• First Posted (ESTIMATE): August 17, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): August 17, 2012
• Last Update Submitted That Met QC Criteria: August 16, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: capsaicin; cinnamaldehyde
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Antineoplastic Agents; Protective Agents; Antineoplastic Agents, Phytogenic; Dermatologic Agents; Antipruritics; Antimutagenic Agents; Capsaicin; Cinnamaldehyde
• Other Study ID Numbers: MEC 10-3-058