The Evolution of Science and Regulation of Dietary Supplements: Past, Present, and Future.

Dietary supplement use in the United States is widespread and increasing, especially among certain population groups, such as older Americans. The science surrounding dietary supplements has evolved substantially over the last few decades since their formal regulation in 1994. Much has been learned about the mechanisms of action of many dietary supplement ingredients, but the evidence on their health effects is still building. 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. New technologies and approaches are being applied to the science of dietary supplements, including nutrigenomics and microbiome analysis, data science, artificial intelligence, and machine learning - all of which can elevate the science behind dietary supplements. Products can contain an array of bioactive compounds derived from foods as well as from medicinal plants, which creates enormous challenges in data collection and management. Clinical applications, particularly those aimed at providing personalized nutrition options for patients, have become more sophisticated as dietary supplements are incorporated increasingly into clinical practice and self-care. The goals of this paper are to provide historical context for the regulation and science of dietary supplements, identify research resources, and suggest some future directions for science in this field.

National Center for Complementary and Integrative Health Perspectives on Clinical Research Involving Natural Products.

The sales of dietary supplements continue to increase year after year. Despite their use by a large percentage of Americans, there is little evidence for the vast majority of products regarding their safety or efficacy. National Center for Complementary and Integrative Health supports a broad range of research on dietary supplements, including clinical trials. Our experience with these trials has shaped our current policies and priorities for clinical research. This perspective outlines those policies and priorities that are shaping our investments going forward. SIGNIFICANCE STATEMENT: The sales of dietary supplements continue to increase year after year. Despite their use by a large percentage of Americans, there is little evidence for the vast majority of products regarding their safety or efficacy. National Center for Complementary and Integrative Health supports a broad range of research on dietary supplements, including clinical trials. Our experience with these trials has shaped our current policies and priorities for clinical research. This perspective outlines those policies and priorities that are shaping our investments going forward.

Development of a symptom score for clinical studies to identify children with a documented viral upper respiratory tract infection.

The objective of this study was to develop a symptom scoring system for use in clinical studies that differentiates children with cold symptoms who have an identifiable viral etiology for their upper respiratory tract infection (URI) from those in whom no virus is detected. Nasal swabs for PCR testing for identification of respiratory viruses were obtained on children aged 2-11 y at baseline and when parents thought their child was developing a cold. Parental-recorded severity of specific symptoms in children with and without a documented viral URI were compared. Nasal swabs were obtained on 108 children whose parents reported their child was developing a cold. A viral etiology was identified in 62 of 108 (57.4%) samples. Symptom measures that best differentiated children with a viral etiology from those without were significant runny nose and significant cough on days 1-4 of the illness. A URI symptom score was developed based on these symptoms, with a sensitivity of 81.4%, specificity of 61.9%, and accuracy of 73.3%. Parental impression is only a moderately accurate predictor of viral URI in children. Our URI symptom score provided a more accurate method for identifying children with viral URIs for clinical studies.

Pragmatic clinical trials offer unique opportunities for disseminating, implementing, and sustaining evidence-based practices into clinical care: Proceedings of a workshop.

The National Institutes of Health (NIH) Health Care Systems (HCS) Research Collaboratory hosted a workshop to explore challenges and strategies for the dissemination, implementation, and sustainability of findings from pragmatic clinical trials (PCTs) embedded in HCS. PCTs are designed to assess the impact of interventions delivered in usual or real-world conditions and leverage existing infrastructure to answer important clinical questions. The goal of the workshop was to discuss strategies for conducting impactful future PCTs that bridge the gap between evidence, practice, and policy. This paper summarizes presentations about how to design and conduct PCTs embedded in HCS and use dissemination and implementation strategies during the planning and conduct of projects, emphasizing the ever-changing world of care delivery and the need for pragmatic trial operations to adapt at various levels of operation.

Evidence-Based Evaluation of Complementary Health Approaches for Pain Management in the United States.

Although most pain is acute and resolves within a few days or weeks, millions of Americans have persistent or recurring pain that may become chronic and debilitating. Medications may provide only partial relief from this chronic pain and can be associated with unwanted effects. As a result, many individuals turn to complementary health approaches as part of their pain management strategy. This article examines the clinical trial evidence for the efficacy and safety of several specific approaches-acupuncture, manipulation, massage therapy, relaxation techniques including meditation, selected natural product supplements (chondroitin, glucosamine, methylsulfonylmethane, S-adenosylmethionine), tai chi, and yoga-as used to manage chronic pain and related disability associated with back pain, fibromyalgia, osteoarthritis, neck pain, and severe headaches or migraines.

Complementary and alternative medicine use and quality of life in pediatric diabetes.

OBJECTIVES: The objectives of this study were to explore the association between complementary and alternative medicine (CAM) use as reported by youth, and parents' and children's reported quality of life in youth with diabetes. DESIGN: The study design was a cross-sectional survey. SETTING: Youth in Washington State participated in the SEARCH for Diabetes in Youth study, a national, multisite epidemiological study designed to assess the prevalence and incidence of diabetes in U.S. youth. Surveys assessing CAM utilization were mailed in January and April 2006. PARTICIPANTS: One thousand four hundred and thirty-nine (1439) youth were mailed a CAM survey. The final sample consisted of 467 youth with both CAM survey results and quality-of-life data. OUTCOME MEASURES: Difference in mean scores on Pediatric Quality of Life Inventory (PedsQL) between CAM users and nonusers overall, and specific CAM therapies were the outcome measures. RESULTS: Of the 1439 participants approached, 587 (40.8%) returned the CAM survey. In adjusted analyses, children reported any CAM use as associated with more barriers to treatment (difference in mean scores -3.48, 95% confidence interval [CI] -6.65, -0.31). Children following a CAM diet reported higher quality of life (PedsQL Core Total difference 4.01, 95% CI [0.10-7.91]; Core Psychosocial difference was 6.45, 95% CI [1.95 to 10.95]), but those using stress-reduction activities reported poorer quality of life (Diabetes Total difference -4.19, 95% CI [-8.35 to -0.04]). Parent-reported quality of life was lower for children who used "other supplements" (Core Total difference -6.26, 95% CI [-11.29 to -1.24]; Core Psychosocial difference was -5.92, 95% CI [-11.65 to -0.19]). CONCLUSIONS: CAM diets were associated with increased quality of life in youth with diabetes, whereas supplement use and stress-reduction activities were associated with decreased quality of life. The temporal sequence between CAM use and quality of life requires further study.