Health Benefits of Plant-based Diets: Effects of Dietary Phytochelatins on Toxic Metal Absorption Public
Dennis, Kristine (Fall 2020)
Abstract
Plant-based dietary patterns reduce risks of chronic disease, including cardiovascular disease, type 2 diabetes, and chronic kidney disease. The mechanisms through which plant-based diets protect health are not fully understood. Phytochelatins (PyCs), metal-binding compounds produced by plants, may be beneficial through reducing absorption of toxic dietary metals, such as cadmium (Cd). Cd accumulates in the body and can lead to increased chronic disease risk at current dietary levels. The interaction of PyCs with Cd may be one mechanism through which plant-based diets confer health benefits. However, dietary PyC types and concentrations are unknown, and the functional effects of these compounds are minimally understood. The purpose of this dissertation was to establish foundational understanding of dietary PyCs and how these compounds may protect from Cd exposures.
The present body of work examines the role of PyCs in human health using molecular and population-based approaches. In Aim 1, we created a database of over 46,000 exact masses of PyC and PyC-metal complexes, establishing a tool to facilitate PyC research in biological systems using high-resolution mass spectrometry. The second aim examined PyC concentrations in twenty commonly consumed plant foods. PyCs were quantified in all food types with PyC2-Gly the most common. In Aim 3, PyC2-Gly absorption and function was investigated in an intestinal epithelial cell model by co-treating cells with PyC2-Gly and Cd at expected dietary concentrations. We discovered PyC2-Gly is absorbed into and through the intestinal cell monolayer and may reduce Cd absorption. The fourth aim investigated if intake of metal-binding plant compounds, as measured via plant food score (PFS), was associated with lower Cd body burden. In a cross-sectional study in the REGARDS cohort, higher PFS was associated with lower Cd body burdens in middle-aged but not older adults. In the closing chapter, I provide my perspective on the potential implications of this research and explore remaining open questions and future directions.
This dissertation demonstrates PyCs are widely distributed in the human diet and may protect from toxic metal exposures, adding to our understanding of the potential mechanisms through which plant-based diets promote health.
Table of Contents
CHAPTER 1: Introduction.................................................................... 1
Plant-based dietary patterns and chronic disease prevention............... 1
Dietary exposome – impact of interacting dietary exposures.............. 2
Overall goals and specific aims............................................................ 4
Chapter 1 References ........................................................................... 8
CHAPTER 2: Phytochelatin database (PyCDB): A resource for phytochelatin
complexes of nutritional and environmental metals.......................... 14
Abstract............................................................................................... 15
Introduction........................................................................................ 17
Materials and Methods....................................................................... 19
Results and application....................................................................... 24
Conclusions........................................................................................ 28
Chapter 2 References.......................................................................... 29
Supplementary Information ............................................................... 38
References for Supplementary Information....................................... 51
CHAPTER 3: Distribution of phytochelatins, metal-binding compounds, in plant
foods: a survey of commonly consumed fruits, vegetables, grains, and legumes.... 52
Abstract............................................................................................... 53
Introduction........................................................................................ 54
Material and Methods......................................................................... 57
Results and Discussion....................................................................... 62
Conclusion.......................................................................................... 72
Chapter 3 References.......................................................................... 73
CHAPTER 4: Transport and function of a common dietary phytochelatin,
PyC2-Gly, in intestinal epithelial cells.................................................. 89
Abstract............................................................................................... 90
Introduction........................................................................................ 91
Materials and Methods....................................................................... 94
Results................................................................................................ 96
Discussion........................................................................................... 99
Chapter 4 References........................................................................ 104
CHAPTER 5: Plant food intake is associated with lower cadmium body burden
in middle-aged adults.......................................................................... 117
Abstract............................................................................................. 118
Introduction...................................................................................... 119
Methods............................................................................................ 121
Results.............................................................................................. 126
Discussion......................................................................................... 128
Chapter 5 References........................................................................ 134
CHAPTER 6: A perspective on phytochelatins as beneficial components of
plant-based diets.................................................................................. 148
Future directions............................................................................... 151
Conclusions...................................................................................... 153
Chapter 6 References........................................................................ 154
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