NUTR333-23-Flavonoids-6

1 Flavonoids The Stars of the Phytochemicals Flavonoids The Stars of the Phytochemicals NUTR*3330 Fall 2023 1 Phytochemicals; What are they? Phytochemicals; What are they?  “phyto” is Greek for plant  chemicals found in plants  generally non-nutritive substances…..  physiologically active components  proposed to contribute toward disease- prevention  Plant chemists have long known that the biological activity associated with phytochemicals serve an important function in plant survival  more than 900 classes have been identified and many more continue to be discovered 2 Phytochemicals Examples Phytochemicals Examples  Flavonoids  Phytoestrogens  Catechins  Lycopene  Glucosinolates  Phytochemicals often have sub-types as well 3 Plant Polyphenols Plant Polyphenols  Plant metabolites  Ubiquitous in all plant organs  Largest category of phytochemicals  Range from simple phenolic molecules (e.g. simple phenols) to highly polymerized compounds (e.g. tannins) 4 Plant Polyphenols Plant Polyphenols  Essential to plant physiology  Contribute to plant morphology  Pigmentation  Contribute to growth and reproduction of the plant  Provide plants with resistance to pathogens and predators  Protect crops from plague and pre-harvest seed germination  Several industrial applications 5 Plant Polyphenols Plant Polyphenols  Naturally occurring compounds found in plants (fruits, vegetables, grains)  >8000 phenolic structures identified  Common structural feature:  Aromatic ring with at least one hydroxyl group  Derived from a common intermediate, phenylalanine, or a close precursor, shikimic acid 6

2 Plant Polyphenols Plant Polyphenols  Generally divided into 4 classes  Phenolic acids  Flavonoids  Stilbenes  Lignans  Based on the number of phenol rings and on the structural elements that bind these rings to one another. 7 Plant Polyphenols Plant Polyphenols  What influences the amount of polyphenols in plants?  Light • highest amounts in leaves and outer parts of plant • only trace amounts in subterranean parts  Genetic factors  Environmental conditions  Degree of ripeness  Variety  Processing  Storage  Levels can vary greatly even within a plant species  What is the impact of all of these variables? 8 Polyphenols in Food Polyphenols in Food  Contribute toward the sensory qualities  Bitterness  Astringency  Colour  Flavour  Odor  Oxidative stability 9 Polyphenols were traditionally considered “anti-nutrients” Polyphenols were traditionally considered “anti-nutrients”  Interfere with bioavailability  Macronutrients :  Bind protein to reduce absorption….increased fecal nitrogen • However, polyphenol must be highly polymerized and most low molecular weight polyphenols do not do this  Micronutrients  Form complexes with minerals and reduce absorption 10 Polyphenols Evolution Polyphenols Evolution  Historically understood as compounds that could interfere with bioavailability of nutrients  However, renewed interest due:  antioxidant capacities  potential beneficial human health effects 11 Plant Polyphenols: Repeat Slide Plant Polyphenols: Repeat Slide  Generally divided into 4 classes  Phenolic acids  Flavonoids  Stilbenes  Lignans  Based on the number of phenol rings and on the structural elements that bind these rings to one another. 12

4 Flavonoids in Foods Flavonoids in Foods  Widely distributed in foods and beverages of plant origin  Fruits, vegetables, tea, cocoa, wine  However, key note is that the amount of flavonoids in foods can vary a lot  Why is this?  What is the source of this variation?  Key phytochemical concept to understand this variation 19 Flavonoid Intake Flavonoid Intake  Challenges in determining dietary intake related to determination of flavonoid content in plant  Content variation factors  Variety  Crop year  Location  Genetic variation  Light amount  Environmental conditions  Degree of ripeness  Processing and storage  Amount of skin surface area • cherry tomatoes contain 6 times more quercitin per gram fresh weight than normal size varieties 20 Flavonoid Intake Flavonoid Intake  Challenges in determining dietary intake related to Analytical Methodology • Lack of standardization in methodology • Information in the literature is inconsistent  What other more general challenge is there regarding quantification of dietary intake of flavonoids?  What are the implications of all of these factors with respect to the relation of flavonoids to human health and disease?  Why do we need to know flavonoid intake levels? 21 Flavonoid Database Flavonoid Database  Inventory of the flavonoid content of foods  Translate dietary assessment data that we collect INTO flavonoid intake levels  USDA Database for the Flavonoid Content of Selected Foods  500 foods  28 different flavonoids  5 of the 6 subclasses (does not include ISOFLAVONES) 22  Inventory on the flavonoid content of 506 foods (not isoflavones)  Translate dietary data that into flavonoid intake levels  Why is this important?  https://www.ars.usda.gov/ARSUserFiles/804 00525/Data/Flav/Flav_R03-1.pdf 23 Studies can use the Flavonoid database to relate intake to health outcomes Studies can use the Flavonoid database to relate intake to health outcomes 24

5  N=1063 women in Western Australia  USDA database and Phenol-Explorer database  low (<547mg)  moderate (547-<813mg)  high (>813) flavonoid intake  RR=0.37 (0.22, 0.58) 25 Activity Break Activity Break  Access the USDA flavonoid database:  https://www.ars.usda.gov/ARSUserFiles/804005 25/Data/Flav/Flav_R03-1.pdf  Choose a fruit or vegetable and search for it.  Notice details like:  The flavonoid sub-classes that are quantified  The range of levels across different types of the fruit or vegetable, for example Gala apples vs Golden Delicious apples  Notice the larger standard error and broader range (min and max) of some of the flavonoids 26  This study was designed to quantify dietary intake of polyphenols in US adults over time  Assessed diet then analyzed for polyphenol content with a database (a different one than the USDA one)  http://phenol-explorer.eu/  I will lead us to peruse this study together and I will point some things out, things that relate to what we have already covered.  You do not need to know the details of this study, we are perusing it to reinforce core ideas we already covered in the slides before this . 27  This study related intake of flavonoids to mortality  Dietary assessment then analysis for flavonoids  I will lead us to peruse this study together and I will point some things out, things that relate to what we have already covered.  You do not need to know the details of this study, we are perusing it to reinforce core ideas we already covered in the slides before this. 28  Different databases  Introduces yet another variability factor in phytochemical intake quantification  QUOTE: “Mainly, it has been found that the USDA estimates were greater than the PE estimates for flavanol and anthocyanin subclasses, but the opposite was observed for flavonol, flavanone, and flavone subclasses.”  Main idea is that databases are needed and with advance of multiple databases comes another source of variation 29 Flavonoid Intake Notes Flavonoid Intake Notes  Flavonoid intake has been related to many aspects of health  Studies involve a dietary assessment and an analysis of the foods and beverages consumed for flavonoid content using a datebase  There are many factors that cause variation in these numbers  These studies do not consider if the flavonoids are absorbed. 30

7 Flavonoid Biologic Effects Flavonoid Biologic Effects  (2) Hormonal/Anti-Hormonal Effects  Primarily estrogenic and anti-estrogenic  Relation to hormone-dependent cancers  Isoflavones main flavonoid in this area  Will discuss more when we discuss phytoestrogens, of which isoflavones are a major class 37 Flavonoid Biologic Effects Flavonoid Biologic Effects  (3) Anti-proliferative Effects  Inhibition of cellular transformation and proliferation  Relevant for existing cancer cells  Inhibit growth of cancer cells in vitro  Interact with enzymes associated with DNA • Inhibit DNA topoisomerase II – Reduce stability of cancer cells – Facilitates apoptosis (death of cancer cells) 38 Flavonoid Biologic Effects Flavonoid Biologic Effects  Other biologic effects:  anti-bacterial  anti-viral  anti-fungal  anti-inflammatory  anti-allergic  anti-mutagenic  All intuitive based on their role in the plant itself  All of these biologic effects have potential relevance to human health and disease…. 39 Flavonoid Health Effects Flavonoid Health Effects  research evaluating the role of various flavonoids in reducing the risk of several diseases or conditions including:  Major one: Cancer • Antioxidant • Anti-estrogenic • Anti-proliferative  Major one: Cardiovascular disease • Antioxidant • Estrogenic • Anti-inflammatory  Other possibilities • any condition associated with oxidative stress 40 Linking Flavonoids and Health: Key Issues Linking Flavonoids and Health: Key Issues  Flavonoid content in plants  Flavonoid content of foods  Content variation…….Analytical methods variation  Flavonoid Intake:  Dietary assessment…….Food composition databases  Intake biomarker availability  Flavonoid Metabolism:  Pharmacokinetics: ADME (absorption, distribution, metabolism, excretion)  Key metabolites not yet identified  Bioavailability Influencers (intake amount and absorption) • All of the above plus food matrix….food processing • Contribution of gut microflora 41 AJCN 2015 42

8  Bioavailability emphasized: “ Bioavailability studies have to consider intestinal metabolism, intestinal absorption, liver metabolism, tissue uptake and metabolism, biological effect in tissue, urinary and fecal excretion,” …….“Therefore, to measure polyphenols bioavailability, it is important to be able to have a perfect characterization of ingested polyphenols, to be able to analyze their metabolites in blood circulation, to be able to measure a biological effect with relevant biomarkers, to be able to measure urinary and fecal excretion; then after you will be able to report the bioavailability of a specific polyphenol” 43 Universal Concept Review Universal Concept Review  Learned about some KEY phytochemical concepts so far…  Role of polyphenols and flavonoids in the plant  Influencers on amount in the plant  Role of polyphenols and flavonoids in food  Influencers on amount in the food  Challenges in quantifying accurate intake amounts  Glycoside/algycone concept  Relevance of bioavailability  Importance of metabolites 44