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The Pennsylvania State University the Graduate School Department of Food Science the BIOAVAILABILITY of ERGOTHIONEINE from MUSHR

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The Pennsylvania State University the Graduate School Department of Food Science the BIOAVAILABILITY of ERGOTHIONEINE from MUSHR The Pennsylvania State University The Graduate School Department of Food Science THE BIOAVAILABILITY OF ERGOTHIONEINE FROM MUSHROOMS AND THE ACUTE EFFECTS ON ANTIOXIDANT CAPACITY AND BIOMARKERS OF INFLAMMATION IN HUMAN PARTICIPANTS A Thesis in Food Science by AuBrei Jayne Weigand Submitted in Partial Fulfillment of the Requirements for the degree of Master of Science December 2009 The thesis of AuBrei Jayne Weigand was reviewed and approved* by the following: Robert B. Beelman Professor of Food Science Thesis Advisor Penny M. Kris-Etherton Distinguished Professor of Nutrition Devin G. Peterson Associate Professor of Food Science John D. Floros Professor of Food Science Head of Department of Food Science *Signatures are on file in the Graduate School. ii ABSTRACT The growing demand of functional foods in the market is leading research on bioactive components found in food. Recently mushrooms have been discovered to contain ergothioneine, a known antioxidant. Ergothioneine was discovered in 1909 and although it has been widely studied, its bioavailability from mushrooms in humans is still unknown. The overall goal of this research was to assess the bioavailability of ergothioneine from mushrooms and evaluate its bioactive effect as part of a small pilot study. An HPLC method for the separation and quantification of ergothioneine from red blood cells and plasma was developed. Healthy men (n=10) ages 23-50 years were recruited to assess the bioavailability of ergothioneine through a dose-response time-course study. A randomized crossover design was employed in which each subject consumed a test meal containing 0g, 8g, and 16g of brown button mushroom powder. At baseline (t=0) and at the subsequent time points (0.5, 1, 2, 4, 6 hours) ergothioneine concentrations were measured. In addition, plasma Cu, plasma Se, glucose, triglycerides, HDL, LDL, total cholesterol, ORACtotal and C-reactive protein were also monitored. No statistically significant differences were observed among the various end points (p<0.05). An ergothioneine response was observed in 90% of the subjects. Of those that responded 67% had an ergothioneine response after the 8 g dose and 100% had a response after the 16 g dose. The postprandial triglyceride response was blunted after the mushroom treatments when compared to the control meal of 0 g. A negative correlation (R2=0.9957) was found for the peak ergothioneine concentration and the percent increase in postprandial triglycerides. ORACtotal values decreased with the 8 g and 16 g doses compared to the control meal. iii TABLE OF CONTENTS LIST OF FIGURES ........................................................................................................................... vii LIST OF TABLES ............................................................................................................................ viii ACKNOWLEDGEMENTS ............................................................................................................... ix CHAPTER 1 INTRODUCTION ........................................................................................................ 1 Problem Statement ............................................................................................................................. 1 Hypothesis .......................................................................................................................................... 1 Objective ............................................................................................................................................ 1 CHAPTER 2 LITERATURE REVIEW ............................................................................................ 3 Functional Foods and Phytochemicals ............................................................................................... 3 Inflammation ...................................................................................................................................... 4 Measuring Inflammation .................................................................................................................... 5 Free Radicals and Antioxidants .......................................................................................................... 6 Measuring Antioxidants ..................................................................................................................... 7 Discovery and Properties of Ergothioneine ....................................................................................... 8 Dietary Sources of Ergothioneine ...................................................................................................... 9 Antioxidant Properties of Ergothioneine ............................................................................................ 9 Uptake and Metabolism of Ergothioneine ....................................................................................... 14 Measuring Ergothioneine in Erythrocytes ........................................................................................ 17 Mushroom Consumption and the Benefits ....................................................................................... 17 CHAPTER 3 SEPARATION AND QUANTIFICATION OF ERGOTHIONEINE IN HUMAN PLASMA AND ERYTHROCYTES BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY .................................................................................................................... 19 ABSTRACT ..................................................................................................................................... 19 Introduction ...................................................................................................................................... 20 Materials and Methods ..................................................................................................................... 21 Chemicals ................................................................................................................................ 21 Standard Solution and Standard Curve .................................................................................... 21 Preparation of Samples ............................................................................................................ 21 Quantification of Ergothioneine by HPLC .............................................................................. 23 LC-MS ..................................................................................................................................... 23 Statistical Analysis .................................................................................................................. 24 Results and Discussion ..................................................................................................................... 24 Conclusion ........................................................................................................................................ 26 iv CHAPTER 4 DETERMINING THE BIOAVAILABILITY OF ERGOTHIONEINE IN HUMANS ............................................................................................................................................ 30 ABSTRACT ..................................................................................................................................... 30 Introduction ...................................................................................................................................... 31 Materials and Methods ..................................................................................................................... 32 Experimental Design ............................................................................................................... 32 Mushroom Powder Preparation and Micronutrient Analysis .................................................. 33 Ergothioneine Analysis of Mushroom Powder ....................................................................... 35 Subject Recruitment ................................................................................................................ 35 Mushroom Feeding Test Day .................................................................................................. 37 Ergothioneine Analysis ........................................................................................................... 38 C-reactive Protein (CRP), Glucose, and Lipid Analysis ......................................................... 39 ORACtotal ................................................................................................................................. 39 IL-6 and TNF-α Analysis ........................................................................................................ 40 Copper and Selenium Analysis ............................................................................................... 40 Lymphocyte Cell Isolation for Future Studies ........................................................................ 41 Statistical Analysis and Calculation ........................................................................................ 41 Results and Discussion ..................................................................................................................... 41 Baseline Characteristics, Compliance, and Adverse Effects ................................................... 41 Glucose ...................................................................................................................................
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