W2002: Nutrient Bioavailability--Phytonutrients and Beyond
Statement of Issues and Justification
Statement of Issue(s) and JustificationDiet, including specific nutrients and bioactive food components, plays a vital role in improving health and reducing risk for developmental and chronic disease. This collaborative research project brings together scientists with broad nutrition science expertise and experience to test hypotheses that ultimately will enhance the well-being of the population through reduced risk and incidence of several chronic diseases including cancer, obesity and osteoporosis. We plan to advance the understanding of the requirements for nutrients and bioactive food components in maintaining optimal health and to translate our findings to public health practice. There are numerous chronic diseases and developmental disorders for which risk may be modified in relation to exposure to bioactive dietary constituents. However, for the purpose of this collaborative research project the investigators are targeting cancer, bone health, obesity, birth defects and cognitive function and neurological disease. These diseases, and the associated interactions with nutrients and bioactive food components, are complex and require diverse approaches to advance knowledge that will lead to effective preventive and therapeutic strategies.
The numbers are staggering when one reviews disease incidence for these chronic diseases in the United States. Cancer is the second leading cause of death in the U.S. with 1 in 2 Americans receiving a cancer diagnosis in their lifetime and over 550,000 cases diagnosed annually. Specific to our efforts, breast cancer accounts for over 180,000 cancer cases annually and prostate cancer accounts for 9% of all cancer diagnosed in males. Numerous nutrients and bioactive food components have been shown to increase or decrease cancer risk. Currently, our investigative research team is collaborating on several dietary constituents including, but not limited to, folate, zinc, vitamin E, isothiocyanates, polyphenols, soy isoflavones, lycopene and citrus monoterpenes. All of which have important roles in human health and protection against chronic disease.
Osteoporosis, another leading chronic illness in older Americans, has a prevalence rate in people over age 50 years of over 12,000,000 cases (2002) is expected to increase to an estimated 14 million cases by 2020. Consequences of osteoporosis are severe with a mortality rate of 24% in the 12 months following newly diagnosed hip fracture. We will continue to expand research on calcium, and isoflavones and will expand into other nutrients and bioactive food components (BAFC) including iron, vitamin D and non-digestible carbohydrates (i.e., fructooligosaccahrides). Application of new and novel techniques and approaches to assess the impact of dietary interventions on bone outcomes, through the collaborative and complementary expertise within the research group will afford an unprecedented opportunity for research in this area.
Perhaps no chronic illness is of greater concern to the American public than obesity. Over 66% of Americans are overweight or obese (Ogden et.al., 2006) and nearly 40 million have some form of non-alcoholic liver disease (Angulo, 2002), a clinical condition which is strongly and significantly associated with the rising incidence of obesity. Efforts to reduce the clinical consequences of obesity through dietary interventions are not only warranted, but provide significant promise. Novel approaches including green tea polyphenols and/or vitamin E supplementation may help to control the undesirable biological changes including inflammation and oxidative stress responses that further impair the health status of obese individuals.
Neural tube defects (NTD), including spina bifida and anencephalus, are diagnosed in nearly 30 per 100,000 live births in the U.S. It is well established that increased folate during early pregnancy will reduce birth defects by over 70%; however, the mechanism for protection, which is believed to be genetic, is not fully understood. Because of this dramatic effect of folate the U.S. food supply was fortified for folic acid in 1998. Concerns have been raised about potential adverse effects of excess folic acid intake in U.S. population as well as other concerns about the level of fortification being insufficient to maximize the reduction in birth defects. Current work on the genetic basis for the folate effect on NTDs will be a primary effort of our investigators and is expected to result in the identification of at-risk individuals.
One concern expressed in relation to high folic acid intake is the masking of anemia in the elderly with the consequent development of neurological disease in B12-deficient individuals. Impaired status of various vitamins including B vitamins and antioxidants as well as antioxidant bioactive food components have been implicated in impaired cognitive function. Our efforts to elucidate the optimal intake and/or exposure levels of select dietary constituents (vitamins and BAFC) will play a critical role in advancing knowledge resulting in the maintenance of optimal cognitive function in the elderly.
Thus, there is significant need to further understand the role of bioactive dietary constituents in reducing the risk of chronic disease. The opportunity for our experts to share knowledge, techniques and resources is central to advancing our understanding in a timely, resource-efficient and strategic manner. For example, while researchers in bone health focus on vitamin D as a nutrient of relevance to bone formation, others in cancer research are able to appreciate the role of vitamin D and to rapidly advance our understanding of its functional potential in cancer prevention through collaborations only possible through this project. Other examples of this rich cross-fertilzation is the dual preventive potential of folate in cognitive disease and cancer risk reduction, or iron as a modifier of disease risk in both cancer and bone-related disease.
Technical Feasibility of Studying Bioavailability and Bioactivity of Food Components: This W1002 multistate group is an extremely diverse group with unique expertise that is ideally poised to identify the mechanisms and bioavailability of nutrients and other bioactive food components on chronic disease prevention. All of the proposed involves ongoing methodologies in the respective investigators laboratories and through this collaborative effort, are extremely feasible (see related and previous work). W1002 researchers have established an international reputation in studying the mechanisms and bioavailability of nutrients and other bioactive food components important in chronic disease prevention. We have extensive experience in kinetic modeling of nutrients, bioavailability studies in rodents and humans, epigenetic and genetic polymorphism studies, as well as significant expertise in the study of osteoporosis, cancer and inflammatory disorders in both model systems and in the human population. Many of the proposed methodologies were pioneered by W1002 members, and have been recognized.
Advantages of a Multi-state effort for the study of bioavailability and bioactivity of food components: Through this multi-state effort we are able to examine mechanisms at the molecular cellular level and directly translate these effects to the population at large. This type of effort and scope would not be possible without the collaborative expertise of each multistate station. Defining the bioavailability and function of bioactive dietary chemicals in chronic disease is a complex and requires multifactorial approach. No single station has the capacity, resources, or equipment to undertake the proposed work in isolation. Through this multistate effort, we are able to combine efforts and share resources that are unique to each individual station. The issues to be addressed and benefits to be achieved are common to the nation as a whole, not a single state. Since several of the issues are being addressed in different ways among researchers in several states, information exchange and collaborations will facilitate goal achievement, limit duplication of effort among member's respective units, and potentially produce new and innovative methodologies for understanding the metabolism and roles for these bioactive food compounds.in human health. The diversity of expertise (from basic science to human population studies to outreach/extension) in faculty at major land-grant universities facilitate translational studies that data arising from W1002 collaborative activities will be disseminated to the greatest extent possible among stakeholders and will thus provide maximum benefits to the U.S. public. W1002 efforts and focus are not duplicated in any other regional project.
Impact of Research/Endpoints: We expect the multidisciplinary , translational research supported by the W1002 investigators to have significant impact on health, which will be identifiable as measurable endpoints. In a general sense, we expect select aspects of this research to result in the identification of new nutrition based prevention strategies for cancer, obesity, osteoporosis and other significant chronic diseases. More specifically, we expect this work help establish more effective biomarkers for nutrient status and new dietary requirements in the population. For example, W1002 researchers have been conducting research in folate and/or vitamin D metabolism and requirements which are expected to re-define requirements (DRIs) for these nutrients in the context of chronic disease risk reduction in the future. Further, collaborations in the area of cancer are expected to result in the development and testing of new chemoprevention agents and dietary recommendations that will impact oncology patient care in the future. If this work is not completed, this would markedly hamper our understanding of the metabolism and mechanistic role of each nutrient in maintaining optimal health. Without the research proposed by this multistate, optimal requirements for the nation cannot be adequatly assessed and could impact the prevalence of many chronic diseases, such as cancer, obesity and osteoporosis. Other endpoints for the W1002 group include more tangible items such as collaborative research grants, publications as well as outreach endpoints such as support of local extension staff and faculty in developing important patient/public-oriented educational materials integrating our research findings.
Because of the interactions and collaborations of W-1002 scientists, agriculture and health related entities have been provided with considerable information for use in the prevention of nutrition-related chronic diseases, consistent with regional and federal priorities. This group has published over 290 articles in the last 5 years. Data related to previous priorities addressed in W-1002 research has served, in part, as the basis for: * the fortification of cereal grains with folate to decrease the risk of neural tube defects; * the inclusion of health statements about calcium and osteoporosis, and hyperhomocystinemia and heart disease on food labels; and * the increased DRIs for calcium for young adults.
This research is innovative and novel in that it utilizes a translational approach to understand the role of nutrients, especially those consumed as a whole food on optimal health. The collaboration among basic, clinical, epidemiological and extension faculty from diverse academic institutions across the U.S. affords the opportunity to advance scientific understanding of the role of, and requirements for, nutrients and bioactive food components in maintaining optimal health. Further our robust scientific interactions, which are possible through this collaborative agreement, afford an opportunity to translate research findings to public health practice in a time and cost-efficient manner.
CRIS Search: A CRIS search with key words bioavailability & nutrients and phytochemical or phytonutrient revealed 30 active projects. The committee is familiar with all projects. There are no similar regional projects. A recent review of active multi-state projects suggests only one project has the potential for overlap with our efforts, W2122, beneficial and adverse effects of natural, bioactive dietary chemicals on human health and food safety . However, there are several important distinctions between the projects. First, this project focuses on cancer, obesity, osteoporosis, neural tube defects and cognitive function while W2122 addresses issue related to cancer, foodborne toxins, immunity and antimicrobials. Food safety is the central theme of their research and is not included in our focus in any definitive way. In fact, the one area of potential overlap (cancer) is approached very differently in the two applications. Our proposed project contuation uses a collaborative translational model to identify and implement effective dietary strategies involving select BAFC to reduce risk while the W2112 investigative team employs basic science techniques alone to more clearly characterize the role of select bioactive food compounds (BAFC) in promoting cancer risk or modulating risk associated with exposure to food-based toxins such as aflatoxin or heterocyclic amines. Another potential overlap is in the area of neural tube defects (NTD); however, here we are addressing the role of B vitamins in prevention and the W2112 group is identifying potential neurotoxins in crop feeds that contribute to risk. Further, a search of related research within the USDA CRIS database suggests there are individual investigators completing related research, including work on BAFC in cruciferae (UCBerkeley), chlorophyll (UHawaii), bitter melon (UHawaii), soy (UIllinois), bioidentification methods for BAFC (UCDavis), and several projects related to quantification of BAFC in select crops/foods (Beltsville). The vast majority are basic science related with few indicating the translational approach to BAFC research proposed here.
Without question, the information derived from the proposed research is innovative and unique, and the proposed dissemination of information to both the scientific community and lay public will provide part of the framework on which future nutrient recommendations can be based. Table 1 outlines a list of proposed nutrients and phytochemicals for initial analysis, their biomarkers & endpoints/clinical outcomes.
Back to Top