CYP2C19 Variants and Limonene Metabolism

Functional Consequences of CYP2C19 Variants on Limonene Metabolism in Humans

The investigators will examine whether a non-invasive screening tool for CYP2C19 genetic variants can be developed by measuring limonene metabolism.

Study Overview

• Status: Recruiting
• Conditions: CYP2C19 Genetic Variants
• Intervention / Treatment: Dietary supplement: Limonene

Detailed Description

Cytochrome P450 2C19 is an important enzyme that metabolizes many drugs. However, individuals with genetic variants of CYP2C19, such as CYP2C19*2 and CYP2C19*3, are poor metabolizers of these drugs. Therefore, it is of interest to determine whether the investigators can develop a non-invasive assay to identify genetic variants of CYP2C19 by using a substrate for CYP2C19 found in citrus fruit, limonene. The purpose of the study is to examine changes in limonene levels in human breath after drinking orange peel extract for people with CYP2C19*2 and CYP2C19*3 genetic variants versus those that do not.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eric Gross, MD/PhD; Phone Number: (650)721-4521; Email: ergross@stanford.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford School of Medicine
      • Contact: Eric Gross, MD/PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age range: Greater than 18 years and less than 45 years.
• Gender: Male or Female
• Ethnicities: East Asian

Exclusion Criteria:

• Pregnant and/or Breastfeeding
• previous allergic reaction to limonene, citrus fruits, bovine gelatin, glycerin
• past medical history of cerebrovascular or cardiovascular disease
• veganism
• history of chest pain or shortness of breath in the past month
• certain medications that are CYP2C19 substrates or CYP2C19 inhibitors
• Non-East Asian descent
• age less than 18 y.o or age greater than 45 y.o

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CYP2C19*2 and CYP2C19*3 Variants; The group of participants has been genotyped to have the CYP2C19*2 and/or CYP2C19*3 variant during the first part of the study. The participants will consume 1 oz water mixed with 500mg limonene (Jarrow Formula orange peel extract) and be asked to swish 5 times and swallow. All participants will then provide breath samples over the course of 2 hours. The breath sample outcomes will be compared to those of the wild-type CYP2C19 study subjects.	Dietary supplement: Limonene; The investigators will ask the participants to swish 5 times and swallow 1 oz water mixed with 500mg limonene (Jarrow Formula orange peel extract). The participant will be monitored for a total of 2 hours. Breath samples will be acquired at a total of 11 time points throughout the study. Measurements include 2 baseline measurements followed by the orange peel extract consumption.
Experimental: Wildtype CYP2C19; The group of participants has been genotyped to have wild-type CYP2C19. The participants will consume 1 oz water mixed with 500mg limonene (Jarrow Formula orange peel extract) and be asked to swish 5 times and swallow. All participants will then provide breath samples over the course of 2 hours. The breath sample outcomes will be compared to those of the CYP2C19*2 and/or CYP2C19*3 study subjects.	Dietary supplement: Limonene; The investigators will ask the participants to swish 5 times and swallow 1 oz water mixed with 500mg limonene (Jarrow Formula orange peel extract). The participant will be monitored for a total of 2 hours. Breath samples will be acquired at a total of 11 time points throughout the study. Measurements include 2 baseline measurements followed by the orange peel extract consumption.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breath limonene value in parts per billion	The amount of limonene in the breath will be measured by mass spectrometry for each participant.	2 hours

Collaborators and Investigators

• Sponsor: Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2021
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 1, 2021
• First Submitted That Met QC Criteria: October 12, 2021
• First Posted (Actual): October 14, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 59978

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes