“As is true of much nutrition research, there are many studies that point to health effects, but not all are at the level of scientific evidence (e.g., randomized controlled interventions), rigor or quality needed for definitive statements of efficacy regarding clinical endpoints,” the authors wrote in The Journal of Nutrition.
In the paper, an expert panel led by Indiana University School of Public Health-Bloomington professor Paul Coates looks back at the evolution of regulation and science of dietary supplements and identifies needs, gaps, challenges and lessons learned to help advance policy and research in this field.
The contributions of government and industry
Informed by his tenure as director of the National Institutes of Health (NIH) Office of Dietary Supplements (ODS) from 1999 to 2018, Prof. Coates reviewed the historical context of the regulation and science of dietary supplements. Starting with James Lind’s observation of the relationship between scurvy and citrus fruit in 1753, he weaves his way through the development of Dietary Reference Intake (DRI) values to AI analysis of multi-omic and microbiome data for precision and personalized nutrition.
“The rationale for these policies evolved from starvation relief to health maintenance to chronic disease risk reduction, and hence, the research evidence base required to support these goals has substantially evolved,” Coates et al. noted. “Nonetheless, these historical events have established a precedent for nutrition research that continues to focus on single nutrients linked to a specific function or disease.”
Here, the paper highlights the role of the ODS—the creation of which was mandated by the Dietary Supplement Health and Education Act (DSHEA) of 1994 to strengthen knowledge and understanding of dietary supplements by evaluating scientific information, supporting research, sharing research results and educating the public.
“ODS leadership identified that the major contribution the office could make was to provide science-based, reliable and up-to-date information for policymakers, clinicians and, ultimately, the public,” Coates et al. wrote.
This has led to the creation of programs, collaborations and resources for evidence-based reviews, analytical methods and reference materials, grant co-funding, research databases and initiatives, population studies and initiatives on specific nutrients.
Given that the endpoints, such as disease occurrence, used in NIH-funded studies cannot be translated to dietary supplement label claims and that these studies tend to be all-inclusive with small effect sizes, the paper suggests that industry has a role to play.
“Larger investments in nutrition by industry and trade organizations might correct some of these problems,” Coates et al. wrote. “However, there is a need to educate academic researchers about the challenges companies face in conducting and supporting research or interpreting research findings.”
Also noted is the importance of accurately and transparently communicating study results by all stakeholders—whether research scientists, the media, policymakers, clinicians or companies.
Beyond the reductionist and deficiency approach
The paper notes that the reductionist approach has advanced the characterization of the mechanisms of action of nutrients that are common across individuals and populations. But when connecting inputs to health outcomes, the interactions in the array of bioactive nutrients need to be considered.
“Furthermore, this approach does not address the antagonistic and synergistic interactions among these dietary components that are critical to understand bioavailability and function in vivo,” Coates et al. wrote. “More simply stated, humans do not consume nutrients in isolation.”
Beyond this, there are the still the gaps in phytochemistry, pharmacognosy, safety, toxicology and standardization of active ingredients, not to mention “additional complexity of horticulture in terms of sustainability and managing issues related to biodiversity loss, as well as variation in the quality of the active compounds of interest,” they added.
As the science evolves towards precision nutrition so does the intricacy of studying the variation of individual and subgroup responses to similar dietary exposures when improvement of deficiency is not the endpoint.
“As we move towards precision nutrition, it is critical to identify the optimal combinations, amounts and forms of micronutrients that are required to promote human health,” the paper noted. “To this end, tools and technologies that accurately and reliably reflect the black box between complex dietary exposures and health outcomes are critical.”
To address these research gaps, the expert panel underlined the need to improve the accuracy of dietary assessment methods, establish validated surrogate or other markers to connect dietary exposures to responses in the body, and leverage the advanced technologies to collect and harmonize data sets.
“One critical aspect to note as dietary supplement research evolves is that we must ensure inclusivity and representativeness of the demographics of our society,” Coates et al. added, particularly in building algorithms for AI and personalized nutrition services.
This means looking beyond genetics to consider factors like epigenetics, lifestyle, dietary intakes, environmental exposures, socioeconomic status and access to drive dietary supplement research that resonates with all.
Source: The Journal of Nutrition
“The Evolution of Science and Regulation of Dietary Supplements: Past, Present, and Future”
doi: 10.1016/j.tjnut.2024.06.017
Authors: Paul M. Coates et al.
