Effect of Kale Consumption on Human Xenobiotic Metabolizing Enzymes

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to determine how daily consumption of kale changes the activity of human xenobiotic metabolizing enzymes. Secondary objectives are to measure absorption and metabolism of kale phytonutrients, and to determine how kale consumption affects gene expression related to metabolism and lipid measures associated with cardiovascular health.

Detailed Description
-----------------
Consumption of Brassica vegetables (which include broccoli, cabbage, and kale) is inversely associated with the incidence of several cancers, including cancers of the lung, stomach, liver, colon, rectum, breast, endometrium, and ovaries. Brassica vegetables are a good source of many nutrients, but the unique characteristic of Brassicas is their rich content of glucosinolates. Glucosinolates are sulfur-containing compounds that are converted to bioactive metabolites by a plant enzyme called myrosinase, which is released when the vesicles containing myrosinase are ruptured by chewing or cutting. These bioactive compounds are considered to be the active agent for cancer prevention. Their ability to reduce risk of cancer may derive in part from their ability to modulate foreign-substance metabolizing enzymes, which include enzymes called Phase I cytochrome P450s and Phase II enzymes. The primary aim of this study is to investigate how daily consumption of kale influences foreign-substance metabolizing enzymes, which in turn may reduce cancer risk. Secondary aims of this study include measuring metabolism of kale nutrients, effect of kale consumption on fecal microbiota, and how kale consumption influences risk factors for cardiovascular disease.

Official Title
-----------------
Effect of Kale Consumption on Human Xenobiotic Metabolizing Enzymes

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Other: Base Diet
* Other: Kale Treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 5 years cancer free Not a tobacco product user Blood glucose less than 126 mg/dL Able to voluntarily agree to participate and sign an informed consent document Exclusion Criteria: Brassica vegetable allergy or intolerance use of oral contraceptives Women who have given birth in the previous 12 months Type 2 diabetes requiring the use of diabetes pills, insulin, or non-insulin shots Use of blood-thinning medications such as Coumadin (warfarin), Dicumarol, or Miradon (anisindione) History of bariatric surgery or nutrient malabsorption disease Pregnant, lactating, or intending to become pregnant during the study period Crohn's disease or diverticulitis Suspected or known strictures, fistulas or physiological/mechanical GI obstruction Self-report of alcohol or substance abuse within the past 12 months and/or current acute treatment or rehabilitation program for these problems (long-term participation in Alcoholics Anonymous is not an exclusion)

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 75 Years

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

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

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

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Base diet<br>Subjects will consume a base diet prepared using traditional American foods with a macronutrient composition representative of a typical American diet. | Other: Base Diet<br>* Base Diet<br>|
| Other: Kale Treatment<br>Subjects will consume 500 g of kale per 2000 kcal of food, split between breakfast and dinner, as a supplement to the base diet. | Other: Kale Treatment<br>* Base Diet plus Kale<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CYP1A2 activity will be analyzed | Plasma will be analyzed for caffeine metabolite ratios | Day 7 | 
| CYP1A2 activity will be analyzed | Plasma will be analyzed for caffeine metabolite ratios | Day 14 | 
| CYP1A2 activity will be analyzed | Plasma will be analyzed for caffeine metabolite ratios | Day 42 | 
| CYP1A2 activity will be analyzed | Plasma will be analyzed for caffeine metabolite ratios. | Day 49 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The ability of fecal microbiota to metabolize glucosinolates will be determined | Fecal samples will be presented with glucosinolates to determine the change in the ability of fecal microbes to metabolize the glucosinolates. | Days 14 and 49. | 
| Metabolites of Kale | Metabolites of Kale will be measured in plasma and urine. | On days 35 and 36 | 
| Fecal microbiota will be analyzed for microbial DNA | Fecal microbial communities will be determined using DNA extracted from fecal samples. | Days 0, 14, 35, and 49 | 
| UGT1A1 activity will be analyzed | Serum will be analyzed for bilirubin concentration to assess UGT1A1 activity | On days 7, 14, 42, and 49 | 
| Glutathione S-transferase alpha concentration | Glutathione S-transferase alpha concentration will be measured in serum | On days 7, 14, 42, and 49 | 
| Total cholesterol | Total cholesterol will be measured in serum | On days 0, 7, 14, 35, 42, and 49 | 
| LDL cholesterol | LDL cholesterol will be measured in serum | On days 0, 7, 14, 35, 42, and 49 | 
| HDL cholesterol | HDL cholesterol will be measured in serum | On days 0, 7, 14, 35, 42, and 49 | 
| Triacylglycerides | Triacylglycerides will be measured in serum | On days 0, 7, 14, 35, 42, and 49 | 
| Apolipoprotein A1 | Apolipoprotein A1 will be measured in serum | On days 0, 7, 14, 35, 42, and 49 | 
| Apolipoprotein A2 | Apolipoprotein A2 will be measured in serum | On days 0, 7, 14, 35, 42, and 49 | 
| Apolipoprotein B | Apolipoprotein B will be measured in serum | On days 0, 7, 14, 35, 42, and 49 | 
| Changes in gene expression | messenger RNA concentrations in whole blood will be measured | On days 0, 14, 35, and 49 |