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ARS Home » Northeast Area » Beltsville, Maryland (BHNRC) » Beltsville Human Nutrition Research Center » Food Components and Health Laboratory » Research » Research Project #426315

Research Project: Absorption, Metabolism, and Health Impacts of Bioactive Food Components

Location: Food Components and Health Laboratory

2018 Annual Report


Objectives
Diet is a lifestyle factor that is fairly easy to change and can have a significant impact on health. The human diet contains thousands of bioactive food components which have a multitude of physiologic actions, some of which can interrupt processes in the development of a host of chronic diseases. The goal of this project plan is to enhance the understanding of biological actions of food-based bioactive compounds to improve their efficacy in promoting health and preventing disease. We have organized the research team to broadly address the main factors affecting health benefits of dietary bioactive compounds: how much is in the food (content), how much we absorb from the food and how well we retain it (bioavailability/metabolism/elimination), and how the bioactive compounds work in the body (mechanisms of action). With respect to content, we intend to address agricultural practices that impact the amount of bioactive compounds present in crops and how to extend the shelf life of agricultural products. With respect to bioavailability, metabolism, and elimination, we intend to study both phenotypic and genotypic characteristics of individuals that impact the body’s nutrient handling. With respect to mechanisms of action, we will address reduction of risk for cancer, as well as other obesity related diseases. Bioactive compounds will include polyphenols, carotenoids, and sulfur compounds, because all demonstrate promising health benefits, and work with these compounds capitalizes on previous progress in our laboratory. Objective 1. Delineate bioavailability, pathways of metabolism, and rates of elimination of bioactive substances from common foods (e.g., polyphenols, sulfur compounds, and other compounds as appropriate), and identify characteristics of humans that influence the body’s utilization of those bioactive substances. Objective 2. Determine the impact of bioactive substances from common foods (e.g., polyphenols, sulfur compounds, and other compounds as appropriate) on markers of cancer risk in human and cell models. Objective 3. Elucidate efficacy of bioactive substances from common foods (e.g. polyphenols, sulfur compounds, and other compounds as appropriate) on risk factors for diseases related to obesity. Objective 4. Determine the impact of food composition heterogeneity (as influenced by genetics, environment, and agricultural production) on the variability in response of biomarkers of chronic disease to consumption of specific bioactive substances and its interaction with an individual’s nutrigenomic profile. Objective 5. Determine the impact of agriculture, food production, and post-harvest practices on bioactive component content and variability, nutrient-nutrient interactions, and shelf life, with emphasis on fruits and vegetables.


Approach
Epidemiological studies have shown that diets high in fruits and vegetables are associated with decreased risk of chronic diseases. However, the scientific foundation necessary to translate these epidemiological findings into dietary recommendations is weak. Studies will be conducted to determine the effect of postharvest processing on phytonutrient content. The initial focus of the postharvest studies will be leaf lettuce and tomatoes, and these studies will be expanded to include kale, spinach, swiss chard, and/or strawberries. Several studies will be conducted on phytonutrient (anthocyanins) bioavailability and metabolism. Methods will be developed to isotopically label quercetin in lettuce and isoflavones in soy. The influence of phytonutrients on biomarkers of chronic disease will be investigated, with an initial focus on phytonutrients found in garlic due to possible roles in cancer prevention. Genotyping will be included in clinical studies whenever sufficient scientific justification exists. This research will be conducted through plant growth and postharvest studies, human feeding trials, quantitative and qualitative chemistry, molecular biology, and kinetic mathematical modeling techniques. Information generated from this project can be used to develop recommendations for dietary intakes of phytonutrients that will improve health and reduce risk of chronic disease.


Progress Report
Progress was made for objectives of this National Program 107 plan, which focuses on Component 3 to provide a Scientific Basis for Dietary Guidance. Progress has been made addressing Problem Statement 1A (Determine Agricultural Practices that Influence the Nutritional Status of Americans), 3A (Improve the Scientific Basis for Updating National Dietary Standards and Guidelines), 3B (Identify Roles of Food, Food Components and Physical Activity in Promoting Health and Preventing Disease), and 4A (Understand the Causes and Effects of Obesity and Obesity-Related Disorders) through studies on glucosinolates and polyphenol availability and metabolism. Two studies of Brassica vegetables were completed – one with kale and one with broccoli. There is an inverse association of consumption of Brassica vegetables with cancer risk, and results from these studies will help determine the most efficacious Brassica vegetables and the mechanisms by which they reduce cancer risk. Nearly 40% of men and women will be diagnosed with cancer at some point in their lifetimes and national expenditures for cancer care could reach $156 billion in 2020. Given the high social and financial impacts of cancer, it is important to understand how dietary modifications may contribute to reduced cancer risk. The first study of Brassica vegetables was designed to identify and quantify the plasma and urinary metabolites of indole glucosinolates from broccoli and to identify novel metabolites that may have roles in reducing cancer risk. Historically, broccoli research has focused on isothiocyanates derived from aliphatic glucosinolates. The focus of the recent study was on the indole glucosinolates (originating from glucobrassicin), which also show promise for reducing the risk of cancer but have received comparatively less research attention. In this completed study, pharmacokinetic tests were performed after consumption of broccoli. Sample analyses are ongoing. The second study conducted with Brassica vegetables was designed to determine how daily consumption of kale changes the activity of human xenobiotic metabolizing enzymes, to measure the absorption and metabolism of kale phytonutrients, and to determine how kale consumption affects gene expression related to metabolism. Kale is becoming an increasingly popular Brassica vegetable with per capita consumption of kale increased by 50% from 1997 to 2015 yet far less research has been conducted with kale compared to other Brassica vegetables, especially broccoli. The dietary intervention of this study was completed and analyses are ongoing. Following up on previous research conducted with blackberries, a new study was initiated and the dietary intervention was completed that focused on mixed berries (raspberries, strawberries, cranberries, blueberries and blackberries). The primary objective of this study was to determine which components of berries (fiber or anthocyanins) improve glucose metabolism in humans using meal tolerance tests. Additionally, a study of adipocytes in cell culture was conducted to determine if cyanidin 3-glucoside (an anthocyanin) or berry extracts leads to increases in insulin sensitivity, reductions in lipid droplet formation, and a white-to-brown (beige) phenotypic switch of the tissue. This study helped us understand the metabolic mechanisms observed in the human studies. We found that administration of a purified anthocyanin or a berry extract caused differences in mitochondrial respiration states in the cultured adipocytes. These observations support the phenotypic switches caused by anthocyanins noted in the human studies, and investigations into molecular pathways of metabolic regulation are underway.


Accomplishments
1. Blueberry juice consumption increases blood concentration of nitrates and nitrites. These compounds are involved in blood pressure regulation, and high blood pressure is a major risk factor for heart attacks and strokes. ARS researchers at the Beltsville Human Nutrition Research Center, Beltsville, Maryland, participated in a study of men and women and demonstrated that consumption of blueberry juice, rich in anthocyanins, tended to reduce systolic blood pressure and significantly increased the concentration of circulating nitrates. Blueberry juice may improve systolic blood pressure by increasing nitric oxide production in blood vessels, resulting in a lower risk for cardiovascular disease.


Review Publications
Novotny, J., Chen, T., Terekhov, A., Gebauer, S.K., Baer, D.J., Ho, L., Pasinetti, G., Ferruzzi, M.G. 2017. The effect of obesity and repeated exposure on pharmacokinetic response to grape polyphenols in humans. Molecular Nutrition and Food Research. 61. https://doi.org/10.1002/mnfr.201700043.
Stote, K.S., Sweeney, M.I., Kean, T., Baer, D.J., Novotny, J., Shakerley, N.L., Chandrasekaran, A., Carrico, P., Melendez, J.A., Gottschall-Pass, K.T. 2017. The effects of 100% wild blueberry (Vaccinium angustifolium) juice consumption on cardiometablic biomarkers: a randomized, placebo-controlled, crossover trial in adults with increased risk for type 2 diabetes. Biomed Central (BMC) Nutrition. 3. https://doi.org/10.1186/s40795-017-0164-0.
Roseland, J.M., Nguyen, Q.V., Douglass, L.W., Patterson, K.Y., Howe, J.C., Williams, J.R., Thompson, L.D., Brooks, J., Woerner, D.R., Engle, T.E., Savell, J.W., Gehring, K.B., Cifelli, A.M., Mcneill, S.H. 2017. Fatty acid, cholesterol, vitamin, and mineral content of cooked beef cuts from a national study. Journal of Food Composition and Analysis. https://doi.org/10.1016/j.jfca.2017.12.003.