Daily Consumption of Well-Cooked Broccoli May Affect Glucosinolate Metabolites and Inflammatory Biomarkers

Study Overview
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Brief Summary
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The objectives of the study are 1) to determine the influence of daily consumption of well-cooked broccoli on plasma and urinary glucosinolate metabolites, and 2) to determine inflammatory marker changes consistent with decreased cancer risk.

Detailed Description
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Consumption of Brassica vegetables is inversely associated with incidence of several cancers, including cancer 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 (Broccoli in particular) is their rich content of glucosinolates. Glucosinolates are sulfur-containing compounds that are converted to isothiocyanates (ITC) by an enzyme in the plant called myrosinase, which is released when the vesicles containing myrosinase are ruptured by chewing or cutting. The isothiocyanates are considered to be the active agent for cancer prevention. Some of the mechanisms by which isothiocyanates likely inhibit cancer include modulation of cytochrome P450 enzymes, induction of phase II enzymes, and apoptosis. The aim of this study is to investigate how daily consumption of broccoli with myrosinase inactivated by cooking influences glucosinolate metabolism and absorption, and consequent regulation of inflammatory markers.

Official Title
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Daily Consumption of Well-Cooked Broccoli May Affect Glucosinolate Metabolites and Inflammatory Biomarkers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Other: Control Diet
* Other: Base Diet with Broccoli


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non tobacco user Cancer Free Not currently taking glucosinolate/isothiocyanate containing supplements Exclusion Criteria: 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 (anisinidione) 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
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control Diet<br>Participants will receive a controlled diet (base diet), typical of an American diet, with 0 g/day of broccoli (control). | Other: Control Diet<br>* Participants will receive a controlled diet with 0 g/d of broccoli. Meals will be prepared using traditional American foods with a macronutrient composition representative of a typical American diet.<br>* Other names: Base Diet;|
| Active Comparator: Brassica Diet<br>Participants will receive a controlled diet with 100 g of broccoli at both breakfast and dinner daily. | Other: Base Diet with Broccoli<br>* Participants will receive a controlled diet with 100 g of broccoli at both breakfast and dinner daily. Meals will be prepared using traditional American foods with a macronutrient composition representative of a typical American diet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in glucosinolate metabolites will be measured in blood plasma and urine | To track the change of endogenous broccoli isothiocyanates in this crossover study, glucosinolate metabolites will be measured in both blood plasma and urine | At end of diet period 1 (week 3) and at the end of diet period 2 (week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition will be determined by dual energy x-ray absorptiometry (DEXA) | Determine fat, lean, and bone mineral mass, and visceral fat deposition in our subjects | Day 0, just prior to beginning the controlled diet | 
| The ability of fecal microbiota to metabolize glucosinolates will be determined | Fecal samples will be presented with glucoraphanin to determine the ability of fecal microbes to metabolize it | once per week during diet periods 1 and 2 (weeks 1, 2, 3, 10, 11, and 12) | 
| Fecal microbiota will be analyzed for microbial DNA | Fecal microbial communities will be determined using DNA extracted from fecal samples | once at the beginning and end of diet periods 1 and 2 (weeks 1, 3, 10, and 12) | 
| Markers of gut health will be analyzed in blood | Zonulin in blood serum will be measured by ELISA | once in the third week of diet periods 1 and 2 (weeks 3 and 12) | 
| Markers of inflammation will be measured in blood | Cytokines and acute phase proteins will be measured in blood | at end of diet period 1 (week 3) and at end of diet period 2 (week 12) |