Strengthening Dietary Supplement Research: An Expanded Priority for the NIH Office of Dietary Supplements

New Developments from Federal Colleagues

The National Institutes of Health (NIH) Office of Dietary Supplements (ODS) has developed and long-supported programmatic activities to promote high-quality experimental designs and data analyses in dietary supplement research since its creation in 1995 [1,2]. These programmatic activities are vital considering that the translation of dietary supplement research to inform consumer use and health care practices and improve public health requires a robust and trustworthy evidence base. This evidence must be built upon investigations that are rigorous, reproducible, and transparently reported in the peer-reviewed literature. To date, the overarching goal of ODS’ work has been to ensure dietary supplements are rigorously studied by providing researchers with reliable, scientifically valid tools and material resources necessary to accurately capture dietary supplement intake and study their biological effects on human health.

The Analytical Methods and Reference Materials (AMRM) Program, Dietary Supplement Ingredient Database (DSID), and Consortium for Advancing for Advancing Research on Botanical and Other Natural Products (CARBON) Program are ongoing ODS activities advancing rigor in dietary supplement research. The AMRM Program develops, validates, and disseminates analytical methods and reference materials for dietary supplement ingredients, products, and their metabolites in principal partnership with the National Institute of Standards and Technology [3,4]. DSID is a multiagency effort led by ODS and the USDA, Agricultural Research Service, Methods and Application of Food Composition Laboratory that provides researchers with chemically analyzed and statistically derived estimates of ingredient levels found in representative samples of select dietary supplements sold in the United States [5]. Data from DSID are meant to improve research precision when relying solely on label-reported ingredient content and estimating population-level nutrient intake. Finally, the CARBON Program, a long-standing partnership with the NIH National Center for Complementary and Integrative Health, promotes translational research and supports the development of methods and resources to enhance the chemical characterization of botanicals and other natural products with potential to affect human health [6]. Collectively, these programs, and other prior coordinated efforts like the Vitamin D Initiative [7], have strengthened the science behind dietary supplements and our ability to learn from the variations in health outcomes that have been observed when studying the myriad supplement ingredient and product formulations available to consumers.

The importance of ODS and its programmatic activities to promote high-quality research are amplified when considering the scope of the NIH investment in dietary supplements. Between fiscal years 2019 and 2023, NIH funding for research categorized as relevant to understanding the health effects of dietary supplements or individual nutrients averaged ∼$276 million per year [8]. ODS further estimates that 46% of that total NIH investment from 2019 to 2023 supported research with hypotheses and research aims directly testing dietary supplement interventions and health effects, when compared with more indirectly relevant research that investigated broader nutrition topic areas such as nutrient metabolism or dietary patterns [8]. Recent research on dietary supplements, supported in part by NIH, has yielded significant findings that improve our understanding of how dietary supplement ingredients may [[9], [10], [11]] or may not [[11], [12], [13]] benefit human health. Even so, along with these long-standing ODS activities and many scientific advances, the current state of dietary supplement research, like nutrition science in general [14,15], can still be fraught with inconsistent measures, heterogeneity, or equivocation across studies, even among the most well-studied dietary supplements [[16], [17], [18]]. Thus, the totality of the existing evidence base is often too weak to generate the scientific consensus needed for clear guidance for the effective use of many dietary supplements.

New ODS Strategic Plan Calls for Bold Action to Strengthen Dietary Supplement Research

In November 2024, ODS published its Strategic Plan for 2025–2029, A Blueprint for A Coordinated Dietary Supplement Research Agenda at NIH [19], which reimagines ODS with new goals, objectives, and priorities. Its revitalized mission is to coordinate collaborative, innovative, and cutting-edge dietary supplement research across NIH and other federal agencies to optimize health across the lifespan. One objective of its strategic plan calls for ODS to strengthen and harmonize methodologic approaches and promote scientific best practices in the design, conduct, and reporting of dietary supplement research. To meet this objective, ODS has initiated new activities that collectively advance Reproducibility and Integrity Guidance to Optimize Research (RIGOR) for dietary supplements. RIGOR is designed to address the heterogeneity and equivalency that challenge the development of a translatable evidence base and often precludes scientific consensus on the health effects of dietary supplements. Driving questions for RIGOR are “how can ODS promote a more comparable and reproducible evidence base of mechanistic (i.e., structure/function) and clinical dietary supplement research?” and “where can ODS resources best support advances in dietary supplement analytical sciences and methodology?”

RIGOR Activities and Anticipated Outcomes

RIGOR activities will consist of complementary and synergistic NIH portfolio analyses, state-of-the science workshops, and the development of resources and guidance. RIGOR will initiate projects that 1) improve ODS tools needed to routinely assess the landscape of dietary supplement-related research topic areas (e.g., the scope of and relationships between dietary ingredients, health conditions/outcomes, and study design); 2) characterize the methodologic approaches used in the NIH clinical dietary supplement research portfolio to identify areas of need and opportunities to increase support for high-quality and translatable dietary supplement research; and 3) update and clarify ODS recommendations for characterizing dietary supplement integrity (i.e., identity, purity, composition, dosage, and stability) [20] to ensure study interventions are replicable. The objectives of RIGOR align with broader NIH efforts to improve scientific rigor, reproducibility, and transparency [21] and complement recent consensus statements outlining best practices for rigorously designed experiments and transparent and comprehensive reporting of dietary supplement [[22], [23], [24], [25]] and general nutrition research [[26], [27], [28]].

Portfolio analysis projects will guide assessments of the strengths and limitations of the NIH dietary supplement research portfolio, with an emphasis on clinical research study designs and methodologies employed. ODS will characterize the conditions and dietary ingredients studied, demographics of the study participants, outcomes measures and the extent to which NIH supports dietary supplement clinical research focused on prevention, health optimization, resilience [29], safety, or disease management. These analyses will facilitate considerations of whether there is an overrepresentation or underrepresentation of certain dietary supplements, ingredients, or health conditions, and, importantly, if there are gaps in the NIH dietary supplement research portfolio that warrant further attention.

Future efforts that assess the design, populations, or end points in the dietary supplement biomedical literature, including for observational studies, are examples of where the tools and processes established by RIGOR will help facilitate new guidance for conducting translatable and reproducible dietary supplement research. A future, complementary analysis of dietary supplement intervention integrity could study how thoroughly NIH-funded dietary supplement clinical research reports the studied supplement’s identity, composition, and strength/dose and what, if any, assessments of ingredient bioavailability or bioaccessibility have been conducted. Such an analysis would help identify areas to enhance or develop new analytical resources to strengthen the capacity to conduct dietary supplement research.

Collectively, RIGOR portfolio and literature analyses and product integrity assessments will drive the development of ODS-led scientific workshops that consider and prioritize research and resource needs and opportunities. These state-of-the-science workshops can explore if there are knowledge or resource gaps in clinical research for certain dietary supplements, ingredients, or whether there are unmet needs for intervention studies for specific health outcomes. Such workshops will subsequently inform considerations of how ODS resources can improve dietary supplement research quality and promote new studies of efficacy and effectiveness.

A Coordinated Effort to Improve Public Trust in Dietary Supplement Research

The activities of RIGOR will aid NIH’s efforts to identify emerging scientific opportunities and scientific knowledge gaps that merit further research. When fully implemented, RIGOR’s activities will contribute to establishing priorities for dietary supplement research. Collectively, an overarching goal of RIGOR is to provide consolidated best practice recommendations for the design, conduct, and reporting of dietary supplement research and build a more trustworthy evidence base. As RIGOR’s initial activity outputs are realized, ODS will continue to advance the program and coordinate with its NIH partners to identify impactful activities that promote high-quality research on dietary supplements.

Author contributions

The authors’ responsibilities were as follows – SMP and AJK wrote the article; and both authors: reviewed and approved the final manuscript.

Funding

The authors reported no funding received for this study.

Conflict of interest

The authors report no conflicts of interest.