Location: Food Components and Health Laboratory
2015 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 polyphenol availability in lean and obese individuals.
With the continuing rise in obesity come increases in many chronic diseases. Consumption of dietary bioactives, such as polyphenols, provides protection against multiple chronic diseases associated with obesity. However, polyphenol bioavailability appears to differ dramatically in at-risk obese compared to healthy individuals, and long term exposure appears to further influence bioavailability, a difference likely in part related to gut health.
A study was conducted to determine differences in adaptive bioavailability of polyphenols in lean and obese individuals, and association of bioavailability with biomarkers of gut health. This research was completed to fulfill objectives 1 and 3 (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, and 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). Lean (n=14) and obese (n=14) adults recently completed an intervention in which they consumed polyphenol-rich blueberries, apples, and green tea for 10 weeks. To test adaptation, a bolus dose of a polyphenol-rich smoothie beverage was provided on 3 occasions in the morning (at the beginning of the intervention period, after 2 weeks, and after 10 weeks of intervention) followed by serial blood and urine collections. The clinical intervention has been completed. Polyphenol metabolites are being measured in blood and urine by LC-MS/MS for pharmacokinetic modeling. Gut permeability is being assessed by the lactulose-mannitol ratio test, and gut inflammation will be assessed by fecal calprotectin. Microbiota will be assessed in fecal samples. Findings from this study will expand understanding of how risk factors and repeated polyphenol intake influence polyphenol bioavailability and gut health. This will facilitate our ability to develop recommendations for improving physiological impact of polyphenols from fruit and vegetables.
We have previously demonstrated that consumption of low calorie cranberry juice improves markers of cardiometabolic health. This research has been expanded to identify additional biochemical changes associated with consumption of low calorie cranberry juice using biochemical profiling. This study, and these new data, contribute to Objective 3 and 4 (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; and 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). Research volunteers participated in a double blind, placebo controlled randomized clinical trial, and consumed low calorie cranberry juice or a color/flavor/calorie-matched placebo beverage (PB) as part of a controlled diet for 8 weeks. Urine and plasma were collected and measurements made using several mass spectrophotometric platforms. Biochemical differences in plasma and urine attributed to consumption of low calorie cranberry juice were detected. These biochemicals were linked to alterations in gut microflora metabolism, redox balance, fatty acid degradation, and glycerolipid metabolism; all processes linked to cardiovascular health. Additional changes in gut microflora metabolites were seen such as those in the families of amino acids (phenylalanine, tyrosine, tryptophan), bile acids, and benzoate-containing molecules. Low calorie cranberry juice consumption increased levels/maintenance of plasma cysteine, an essential amino acid required for synthesis of glutathione, which would be beneficial for synthesizing glutathione when demand required. A specific compound not found in cranberry juice or plasma but found in urine could be a potential biomarker of consumption for cranberry juice. These changes may be linked to potential beneficial actions of cranberry juice consumption, as shown in the improved clinical cardiometabolic parameters reported previously.
Wild blueberries have a high content of polyphenols, but there are limited data evaluating their health benefits in people at risk for type 2 diabetes. A study was conducted to investigate whether 100% wild blueberry juice consumption causes biomarker changes in glucoregulatory control or in those that reflect protection against oxidative stress, inflammation or vascular status, all of which are associated with diabetes risk. This research is consistent with objective 3 (to 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). A single-blind randomized cross-over design study was conducted in which women at-risk for type 2 diabetes consumed wild blueberry juice or a control beverage as part of their free-living diet for 7 days. Outcome variables included biomarkers of glucose regulation, oxidative stress, inflammation, vascular status, and blood pressure. There were no differences detected between wild blueberry juice and placebo consumption on biomarkers of glucose regulation and surrogate markers of insulin resistance, oxidative stress, inflammation, and vascular status. However, consumption of wild blueberry juice consumption showed a trend for lowering systolic blood pressure when compared to the control beverage.
Consumption of Brassica vegetables is inversely associated with incidence of several cancers, including cancer of the lung, stomach, colon, rectum, prostate, breast, endometrium, and ovaries. Whereas many studies support the inverse association between Brassica vegetables and cancer incidence, in a few studies, these associations were not observed. One of the reasons for the conflicting results may be related to genetic polymorphisms, particularly for glutathione S-transferase. Since isothiocyanates are metabolized by glutathione S-transferase, it has been hypothesized that deletions in genes for GST isoforms will result in longer and higher circulating levels of isothiocyanates, thus influencing chemoprotective effects. A second possible reason for apparently conflicting results may be related to pattern of intake. A study was conducted to investigate the influence of dietary intake and genotype on absorption of Brassica isothiocyanates. Genotype for glutathione S-transferase also seems to influence the potential protective role of dietary Brassicas. Epidemiological studies that include glutathione S-transferase genotyping suggest that genotype may influence ability for Brassica intake to alter cancer risk. This variability no doubt influences chemoprotective effects, and may be related to genotype and dietary pattern. This research supports Objective 1, 2 and 4 (to 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; to 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; and to 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). To investigate the influence of dietary pattern and genotype on isothiocyanates plasma and urinary response, a controlled feeding intervention was conducted with two treatment periods administered in a cross-over design: 1) control diet 2) Brassica diet. During the Brassica period, subjects consumed the same base diet as that during the control period plus glucosinolate/isothiocyanate treatment foods at breakfast and dinner. At the end of each treatment period, a pharmacokinetic test with a broccoli challenge was conducted. Measurement of isothiocyanates in blood and urine is currently underway. By measuring isothiocyanates in both blood and urine, we will be able to determine if the adaptation is occurring in absorption or elimination.
Accomplishments
1. Brassica vegetables affect DNA integrity. The probability of developing cancer sometime during one’s lifetime is 1 in 2 for men and 1 in 3 for women. Broccoli, a member of the Brassica family, has been among the most promising foods for cancer prevention, though the potential for other Brassicas to impact cancer risk has been much less studied. ARS researchers in the Beltsville Human Nutrition Research Center, Beltsville, Maryland,We found that Brassicas cabbage and mustard, as well as a phytonutrient called allyl isothiocyanate found in processed cabbage and mustard, caused DNA strand breaks shortly after consumption, but those DNA strand breaks disappeared quickly, suggesting DNA repair mechanisms were in play. These results demonstrate to health professionals that Brassicas may play a role in cancer risk through effects on DNA integrity and repair. These results will be useful to scientists who study the role of diet in cancer prevention.
