Goal: To advance dietary supplement science and catalyze innovative, collaborative research to close critical knowledge gaps of public health interest
ODS research is rooted in its core competencies in biological, population, and analytical sciences and the knowledge gained from historical and current ODS activities. ODS' goal is to coordinate the development and support of broad research opportunities that leverage the expertise of NIH and its partners across the federal government and dietary supplement research community.
Research Objective 1
Advance the study of the biological effects of dietary supplements on resilience and health across the lifespan
Currently, about one-half of adults and one-third of children and adolescents in the United States consume dietary supplements. Some use them to address known nutrient deficiencies while others consume them to improve their health or to prevent future health problems. ODS' focus on biological sciences reflects the importance of understanding how dietary supplements affect health and the intrinsic and extrinsic factors that may modulate those effects.
For decades, ODS has supported NIH ICO efforts to advance the understanding of how dietary supplements affect health. For example, ODS has collaborated with researchers from the National Eye Institute (NEI) to provide ongoing support for The Age-Related Eye Disease Studies (AREDS and AREDS2). These clinical trials tested whether taking a mix of dietary supplements could prevent the onset of age-related macular degeneration (AMD) in older adults or slow the progression of AMD in people who have it. Although the supplement formulations (which contain the antioxidants vitamin C, vitamin E, and beta-carotene, plus zinc and copper) did not prevent AMD onset, they did reduce the risk of developing advanced AMD by about 25 percent in those already diagnosed with the degenerative condition. Because high doses of beta-carotene supplements can increase the risk of lung cancer in people who smoke, a second study (AREDS2) examined the effectiveness of the same supplement with lutein and zeaxanthin in place of beta-carotene. The AREDS2 supplement reduced the risk of AMD progression even more than the original AREDS supplement. A 10-year follow-up assessment of the AREDS2 study confirmed the benefits of replacing beta-carotene with lutein and zeaxanthin. The results of new analyses indicate that, in addition to slowing the progression from intermediate to advanced AMD, the AREDS2 supplement may help preserve central vision in people with late-stage dry AMD.
In another example of collaboration on biomedical science with other federal agencies, ODS works with the Department of Defense (DoD) Consortium for Health and Military Performance (CHAMP) on systematic reviews that explore dietary supplements, immune health, and resilience outcomes. The reviews include expert panel recommendations that provide evidence-based insight into strategic decisions for future research. The collaboration also created an interagency agreement (IAA) to explore mechanisms and effectiveness of dietary supplement ingredients and their potential to minimize environmental heat injury. These preliminary studies suggest that astaxanthin and curcumin can provide synergistic benefits to protect mitochondrial integrity and enhance resilience outcomes in mice models of heat-induced skeletal muscle injury. The study is ongoing and seeks to further understand the pathways and mechanisms that drive these outcomes and inform the design of future studies in humans. ODS will continue its partnership with the DoD, finding new opportunities that strengthen the value of the collaboration.
The above-mentioned examples demonstrate how ODS leverages its mission as a coordinating office to drive innovation across NIH and the federal government. Going forward, ODS will emphasize biological sciences by reengaging existing strategic partnerships and developing new ones across NIH ICOs. The goal of these partnerships will be to enhance the knowledge of how dietary supplements may affect resilience and health across the lifespan by identifying the mechanisms through which they work. Knowledge gaps to explore include:
- Underlying biological states and mechanisms that influence a system's cellular, molecular, physiologic, and behavioral/psychological response to stress or disease
- Protective pathways, disease prevention, and health promotion
- Interactions among diet, dietary supplement use, individual health behaviors, medications, and exposomes (environmental and lifestyle exposures) that impact health
Research Objective 2
Advance the study of population-based dietary supplement use, related nutrient intake, and their effects on resilience and health across the lifespan
Adequate nutritional intake is critical for optimal health and development throughout the lifespan. Developing a complete profile of nutrient intake (from food as well as dietary supplements), along with a profile of the nutritional and health status of all Americans, is vital for the development of effective nutrition policy. Because much of the data in this area are based on self-report, ODS will increase the rigor and reproducibility of population research by identifying improved participant recruitment and data collection strategies, continuing to augment dietary assessment data with objective measures (such as well-validated biomarkers and metabolomic studies), and employing new technologies such as wearable devices.
ODS' collaborations with the Centers for Disease Control and Prevention (CDC) and National Center for Health Statistics' (NCHS) Division of Health and Nutrition Examination Surveys (DHANES) have advanced the ability to describe total nutrient intakes that include both dietary supplements and food as well as biochemical markers of nutrient status of public health concern for the U.S. population. ODS has supported the development of population-based data collection methods and tools for investigating dietary supplement usage patterns in segments of the population. These collaborations resulted in new methods to collect data from the National Health and Nutrition Examination Survey (NHANES) on the use and composition of infant formula; improved dietary supplement questionnaires (including validation studies of questionnaires); and input on dietary assessment in the Dietary Guidelines for Americans planning guide.
Population sciences will remain key to identifying nutrient and other bioactive deficiencies or excesses that might impact the health of the whole U.S. population or subgroups and for generating hypotheses to inform new biological and analytical sciences research. For example, to help inform future supplement recommendations, population data from epidemiological surveys that include dietary supplement data programs (such as NHANES, the NIH All of Us Research Program, and the Environmental influences on Child Health Outcomes [ECHO] program) might be combined with findings from biological and analytical research. When possible, biomarkers that provide independent assessment of intake and nutrient status will be used to validate self-reported intake data. Currently the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the U.S. Department of Agriculture's (USDA) National Institute of Food and Agriculture (NIFA) are working together to establish dietary biomarkers development centers to explore, develop, and validate metabolomics-based dietary intake biomarkers. ODS' biological, population, and analytical researchers will seek to develop partnerships with NIDDK, USDA NIFA, and other NIH ICOs involved in the development of these biomarkers of nutritional status and intake.
To better advance the health of all Americans, future work will investigate differences that might exist between various segments of the population (e.g., by rural/urban, chronically ill/not chronically ill, military/civilian, or family status). Population-based nutrition and health outcome research will seek to address knowledge gaps in:
- Diet and dietary supplement use patterns and their interactions and implications for nutrient deficiencies and excesses, health outcomes, lifestyle behaviors (i.e., physical activity and sleep), and dose-related effects of dietary supplements
- Nutrient requirements and dietary reference intake gaps
- Nutrient intake, food security, and nutritional and health status
Research Objective 3
Advance the study of the composition, quality, safety, and efficacy of dietary supplements
Dietary supplements commonly contain mixtures of vitamins, minerals, and/or other natural products, such as botanicals. Even supplements marketed as having a single active ingredient—such as an extract from the leaf of a plant—may in fact contain numerous unique phytochemicals in a milieu of hundreds or even thousands of other chemical compounds. Relatively simple single-chemical entities may occur in marketed products as different chemical isomers (e.g., cis- or trans-resveratrol, vitamin E as a mixture of tocopherols and tocotrienols) or as a unique formulation marketed for its purportedly enhanced bioavailability (e.g., chemical modifications of curcumin). In addition to this complexity, tens of thousands of supplement products are available on the U.S. market that combine anywhere from two to dozens of purported active dietary ingredients. To understand exactly what is being studied, dietary supplements used in biomedical investigations must be rigorously identified and characterized, including details of dissolution and disintegration to ensure bioefficacy. This characterization helps ensure product integrity and enhances researchers' ability to understand and learn from any variability in outcomes associated with changes in product composition.
ODS Analytical Methods and Reference Materials (AMRM) staff have developed and expanded the availability of reliable, scientifically valid analytical methods for quantitative and qualitative characterization of dietary supplements and their ingredients. In partnership with the National Center for Complementary and Integrative Health (NCCIH), ODS also supports the Consortium for Advancing Research on Botanical and Other Natural Products (CARBON) Program to promote collaborative, transdisciplinary research on the safety, effectiveness, and mechanisms of action of botanical dietary supplements that have a high potential to benefit human health and to support the development of methods and resources that will enhance the progress of this research.
The knowledge gained and resources developed through AMRM and CARBON will propel ODS analytical sciences work forward to identify product integrity research gaps and develop new research opportunities that address:
- Dietary supplement ingredients, composition, quality, and integrity
- Dietary supplement safety, bioavailability, bioconvertibility, and bioefficacy
- Biomarkers of nutritional status and dietary supplement intake