CYP2C19 Variants and Limonene Metabolism

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

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.

Official Title
-----------------
Functional Consequences of CYP2C19 Variants on Limonene Metabolism in Humans

Conditions
-----------------
CYP2C19 Genetic Variants

Intervention / Treatment
-----------------
* Dietary Supplement: Limonene


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Human volunteers participating in this study will be given an over the counter orange peel extract and limonene levels will be measured.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CYP2C19*2 and CYP2C19*3 Variants<br>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<br>* 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.<br>|
| Experimental: Wildtype CYP2C19<br>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<br>* 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.<br>|

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 |