The Office of Dietary Supplements (ODS) initiated the Consortium for Advancing Research on Botanical and Other Natural Products (CARBON) Program in partnership with the National Center for Complementary and Integrative Health (NCCIH)
in 1999, in response to a Congressional mandate.
The purpose of the CARBON Program is 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 CARBON Program includes Botanical Dietary Supplements Research Centers (BDSRC), two Centers focused on enhancing methods and resources for research on the health effects of complex natural products, and pilot projects collaborating with the Centers. All the Centers are jointly funded by ODS and NCCIH, with additional funding from the National Institute on Aging (NIA) for the 2020-2025 project period. The BDSRCs focus on foundational research is expected to increase the value of future clinical trials, while providing a rich environment for training and career development. A Natural Product Technology, Methodology, and Productivity Optimization Center will focus on developing methods to accelerate research on complex natural products such as botanicals for human health and on collaborations to develop applications of these methods. A Natural Products Nuclear Magnetic Resonance (NMR) Open Data Exchange will facilitate the accessibility and utility of natural product chemical structure data (NMR raw data). The ODS-supported pilot projects, to be awarded in response to PAR 20-228, will collaborate with these Centers, to extend understanding of products studied in the Botanical Dietary Supplements Research Centers, or to leverage methods in use in the CARBON Program for early phase research relevant to natural product dietary supplements.
Botanical Dietary Supplements Research Centers awards for 2020-2025:
Natural Product Technology, Methodology, and Productivity Optimization Center award for 2020-2025:
Natural Products Nuclear Magnetic Resonance Open Data Exchange award for 2020-2025:
- Natural Products Magnetic Resonance Database (NP-MRD), Pacific Northwest National Laboratory, Richland, WA; Simon Fraser University, Burnaby, British Columbia, Canada; University of Alberta, Edmonton, Alberta, Canada; University of Missouri, Columbia, MO
Prior years (1999-2020) CARBON program awards
Botanicals Enhancing Neurological and Functional Resilience in Aging (BENFRA)
Principal Investigator: Amala Soumyanath, Ph.D.
Institution: Oregon Health and Science University, Portland, OR
Website: https://www.ohsu.edu/benfra
Partners: Oregon State University, Corvallis, OR; Oregon’s Wild Harvest, Inc., Redmond, OR; University of Mississippi, Oxford, MS
This new Center will establish a pipeline of experimental approaches and techniques required to optimize the design and interpretation of future clinical trials of botanicals traditionally used for resilience to age-related changes in sleep, mood and cognition. In vivo and in vitro activities and biomarkers of activity will be studied for two such botanicals, Centella asiatica (gotu kola), and Withania somnifera (ashwagandha), in preclinical models including fruit flies, mouse primary neuron cultures, mouse brain slices and intact mice. This work will help to identify the most appropriate clinical outcomes to be assessed in a clinical trial. Biological testing and chemical profiling will optimize conditions for cultivating the source plants, and guide the composition and doses to be used in future clinical trials.
Influence of Dietary Botanical Supplements on Biological and Behavioral Resilience
Principal Investigators: Giulio M. Pasinetti, M.D., Ph.D., and James W. Murrough, M.D., Ph.D.
Institution: Icahn School of Medicine at Mount Sinai, New York, NY
Website: https://icahn.mssm.edu/research/molecular-neuroresilience/research
Partner: Rutgers, The State University of New Jersey, New Brunswick, NJ
This new Center will acquire data needed to optimize future clinical trials of a polyphenol-containing dietary supplement derived from grapes for resilience to stress-induced psychological impairment. Clinical studies of bioavailability and pharmacokinetics of the product will be combined with preliminary assessments of the clinical effects. Preclinical and clinical studies will assess and validate biomarkers of activity.
Spirulina Oral Supplement for Enhancing Host Resilience to Virus Infection
Principal Investigators: Ikhlas Khan, Ph.D. and Nirmal Pugh, Ph.D.
Institution: University of Mississippi, University, MS
Website: https://umbdsrc.org/
Partner: University of Mississippi Medical Center, Jackson, MS
Extracts of Arthrospira platensis, or spirulina, have been reported to enhance resilience to and recovery from respiratory viral infections. Looking at resilience to influenza viruses in preclinical models and in biomarker-based clinical studies, this new Center will determine the best formulation, timing, and dose of a bioassay-standardized spirulina extract, optimize the methods used to standardize the extract, and identify the optimal immune outcomes to use in a future clinical trial.
Center for High-throughput Functional Annotation of Natural Products
Principal Investigators: John B. MacMillan, Ph.D., Nadja B. Cech, Ph.D., Roger G. Linington, Ph.D.
Institution: University of California, Santa Cruz, CA
Website: https://hifan2.sites.ucsc.edu/
Partners: University of North Carolina, Greensboro, NC; Simon Fraser University, Burnaby, British Columbia, Canada
While it is hypothesized that additive or synergistic activities of individual chemical constituents contribute to the biological effects of botanical extracts and other chemically complex natural products, this has been clearly demonstrated in only a few cases. Bottlenecks that contribute to slowing this research include the challenges of accurately defining the chemical composition of complex mixtures, and of elucidating the contributions of individual constituents and sets of constituents to the biological activity. This Center proposes to address these challenges through the integration of orthogonal assay systems using sophisticated informatics approaches, an approach that has been demonstrated to work with complex mixtures as well as with pure compounds.
Project 1 will employ innovative, cell-based, high content phenotypic screening in primary macrophages, epithelial cells, and primary neurons, providing agnostic and extensive coverage of critical biological pathways that are believed to be relevant to the health effects of botanicals. Project 2 will take advantage of developments in untargeted metabolomics,and feature reduction to develop a robust pipeline to accurately, replicably, and efficiently define the chemical composition of complex mixtures. The third project specifically addresses the question of synergy and additivity through the development of informatics approaches that use the comprehensive biological and chemical signatures generated in the other projects. This project will develop universal tools that will allow the community to probe their own biological and chemical assay results to generate compound-activity maps. The Center as a synergistic whole will deliver critical technology platforms for the in-depth study of botanicals and other natural products, and tools based on these platforms that can be used by the research community.
Natural Products Magnetic Resonance Database (NP-MRD)
Principal Investigator: John R. Cort, Ph.D.
Institution: Pacific Northwest National Laboratory, Richland, WA
Website: http://www.np-mrd.org/
Partners: Simon Fraser University, Burnaby, British Columbia, Canada; University of Alberta, Edmonton, Alberta, Canada; University of Missouri, Columbia, MO.
This Center will develop the Natural Products Magnetic Resonance Database (NP-MRD), a central, user-friendly repository for NMR data generated by the natural products community, with powerful associated tools. The core of the NP-MRD will be an open-access, web-enabled, community-focused, FAIR (findable, accessible, interoperable, reusable)-compliant database containing NMR data and structures for an estimated 350,000 natural products. The database will contain (1) legacy NMR data derived from the literature, existing public databases, and “private” data archives, (2) new NMR data submitted by depositors for novel NPs, and (3) calculated NMR data for all NPs. Data deposition will be both rapid (less than five minutes) and simple. The NP-MRD will be closely integrated with “sister” databases containing mass spectrometry, biosynthetic gene cluster, and bioactivity data. It will provide rigorous validation and data checking, and powerful database search, filtering, and querying tools. In addition to data storage, retrieval, and curation, the NP-MRD will host an extensive suite of software tools for natural products research.