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Interest in botanicals, particularly as dietary supplement ingredients, is growing steadily. This growth, and the marketing of new ingredients and combination products as botanical dietary supplements, underscores the public health need for a better understanding of potential toxicities associated with use of these products. This article and accompanying template outline the resources to collect literature and relevant information to support the design of botanical toxicity studies. These resources provide critical information related to botanical identification, characterization, pre-clinical and clinical data, including adverse effects and interactions with pharmaceuticals. Toxicologists using these resources should collaborate with pharmacognosists and/or analytical chemists to enhance knowledge of the botanical material being tested. Overall, this guide and resource list is meant to help locate relevant information that can be leveraged to inform on decisions related to toxicity testing of botanicals, including the design of higher quality toxicological studies.
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Suplementos Dietéticos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Suplementos Dietéticos/toxicidadRESUMEN
While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a September, 2018 transdisciplinary workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research.
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Productos Biológicos/farmacología , Investigación Biomédica Traslacional/normas , Animales , Evaluación Preclínica de Medicamentos , Etnobotánica , HumanosRESUMEN
Objective: To describe the history, key features, recent enhancements, and common applications of the Dietary Supplement Label Database (DSLD). Background and History: Although many Americans use dietary supplements, databases of dietary supplements sold in the United States have not been widely available. The DSLD, an easily accessible public-use database was created in 2008 to provide information on dietary supplement composition for use by researchers and consumers. Rationale: Accessing current information easily and quickly is crucial for documenting exposures to dietary supplements because they contain nutrients and other bioactive ingredients that may have beneficial or adverse effects on human health. This manuscript details recent developments with the DSLD to achieve this goal and provides examples of how the DSLD has been used. Recent Developments: With periodic updates to track changes in product composition and capture new products entering the market, the DSLD currently contains more than 71,000 dietary supplement labels. Following usability testing with consumer and researcher user groups completed in 2016, improvements to the DSLD interface were made. As of 2017, both a desktop and mobile device version are now available. Since its inception in 2008, the use of the DSLD has included research, exposure monitoring, and other purposes by users in the public and private sectors. Future Directions: Further refinement of the user interface and search features to facilitate ease of use for stakeholders is planned. Conclusions: The DSLD can be used to track changes in product composition and capture new products entering the market. With over 71,000 DS labels it is a unique resource that policymakers, researchers, clinicians, and consumers may find valuable for multiple applications.
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Comercio , Bases de Datos Factuales , Suplementos Dietéticos , Difusión de la Información , Etiquetado de Productos , Humanos , Estados UnidosRESUMEN
Background: Non-nutrient bioactive ingredients of foods such as bee products are often of interest in preclinical and clinical research to explore their possible beneficial effects. The National Institute of Health's Dietary Supplement Label Database (DSLD) contains over 165,000 labels of dietary supplements marketed in the United States of America (US), including declarations on labels for many of these ingredients, including those in honeybee products which have been used in foods and traditional medicines for centuries worldwide and are now also appearing in dietary supplements. Methods: This article presents a use case for honeybee products that describes and tests the utility of the DSLD and other databases available in the US as research tools for identifying and quantifying the prevalence of such ingredients.. It focuses on the limitations to the information on product composition in these databases and describes how to code the ingredients using the LanguaL™ or FoodEx2 description and classification systems and the strengths and limitations of information on honeybee product ingredients, including propolis, bee pollen, royal jelly, beeswax, and bee venom. Results and Conclusions: Codes for the ingredients are provided for identifying their presence in LanguaL™ or FoodEx2 ontologies used in Europe and elsewhere. The prevalence of dietary supplement products containing these ingredients in DSLD and on the US market is low compared to some other products and ingredients. Unfortunately label declarations in DSLD do not provide quantitative information and so the data can be used only to screen for their presence, but cannot be used for quantitative exposure estimates by researchers and regulators .
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AREAS COVERED: This paper outlines the selection of NAMs, including in vitro assays using primary rat cortical neurons, zebrafish embryos, and Caenorhabditis elegans. These assays aim to assess neurotoxic endpoints such as neuronal activity and behavioral responses. Microelectrode array recordings of rat cortical neurons provide insights into the impact of botanical extracts on neuronal function, while the zebrafish embryos and C. elegans assays evaluate neurobehavioral responses. The paper also provides an account of the selection of botanical case studies based on expert judgment and existing neuroactivity/toxicity information. The proposed battery of assays will be tested with these case studies to evaluate their utility for neurotoxicity screening. EXPERT OPINION: The complexity of botanicals necessitates the use of multiple NAMs for effective neurotoxicity screening. This paper discusses the evaluation of methodologies to develop a robust framework for evaluating botanical safety, including complex neuronal models and key neurodevelopmental process assays. It aims to establish a comprehensive screening framework.
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Caenorhabditis elegans , Neuronas , Síndromes de Neurotoxicidad , Pruebas de Toxicidad , Pez Cebra , Animales , Neuronas/efectos de los fármacos , Caenorhabditis elegans/efectos de los fármacos , Ratas , Síndromes de Neurotoxicidad/diagnóstico , Síndromes de Neurotoxicidad/etiología , Humanos , Pruebas de Toxicidad/métodos , Extractos Vegetales/efectos adversos , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Evaluación Preclínica de Medicamentos/métodos , Preparaciones de Plantas/efectos adversos , Preparaciones de Plantas/toxicidad , Preparaciones de Plantas/farmacología , Embrión no Mamífero/efectos de los fármacosRESUMEN
The increased utilization of metrology resources and expanded application of its' approaches in the development of internationally agreed upon measurements can lay the basis for regulatory harmonization, support reproducible research, and advance scientific understanding, especially of dietary supplements and herbal medicines. Yet, metrology is often underappreciated and underutilized in dealing with the many challenges presented by these chemically complex preparations. This article discusses the utility of applying rigorous analytical techniques and adopting metrological principles more widely in studying dietary supplement products and ingredients, particularly medicinal plants and other botanicals. An assessment of current and emerging dietary supplement characterization methods is provided, including targeted and non-targeted techniques, as well as data analysis and evaluation approaches, with a focus on chemometrics, toxicity, dosage form performance, and data management. Quality assessment, statistical methods, and optimized methods for data management are also discussed. Case studies provide examples of applying metrological principles in thorough analytical characterization of supplement composition to clarify their health effects. A new frontier for metrology in dietary supplement science is described, including opportunities to improve methods for analysis and data management, development of relevant standards and good practices, and communication of these developments to researchers and analysts, as well as to regulatory and policy decision makers in the public and private sectors. The promotion of closer interactions between analytical, clinical, and pharmaceutical scientists who are involved in research and product development with metrologists who develop standards and methodological guidelines is critical to advance research on dietary supplement characterization and health effects.
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PURPOSE: Evidence from in vitro and in vivo studies suggests that Ginkgo biloba has cancer chemopreventive properties, but epidemiological evidence is sparse. We analyzed cancer as a secondary endpoint in the Ginkgo Evaluation of Memory (GEM) Study, the largest randomized, double-blind, placebo-controlled clinical trial of Ginkgo supplementation to date. METHODS: A total of 3069 GEM participants 75+ years of age were randomized to twice-daily doses of either 120 mg Ginkgo extract (EGb 761) or placebo and followed for a median 6.1 years. We identified hospitalizations for invasive cancer by reviewing hospital admission and discharge records for all reported hospitalizations over follow-up. Using an intention-to-treat approach, we compared the risk of cancer hospitalization between participants assigned to treatment and those assigned to placebo. RESULTS: During the intervention, there were 148 cancer hospitalizations in the placebo group and 162 in the EGb 761 group (Hazard ratio (HR), 1.09; 95% confidence interval (CI), 0.87-1.36; p = 0.46). Among the site-specific cancers analyzed, we observed an increased risk of breast (HR, 2.15; 95%CI, 0.97-4.80; p = 0.06) and colorectal (HR, 1.62; 95%CI, 0.92-2.87; p = 0.10) cancer, and a reduced risk of prostate cancer (HR, 0.71; 95%CI, 0.43-1.17; p = 0.18). CONCLUSIONS: Overall, these results do not support the hypothesis that regular use of Ginkgo biloba reduces the risk of cancer.
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Ginkgo biloba/química , Neoplasias/epidemiología , Extractos Vegetales/farmacología , Anciano , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Método Doble Ciego , Femenino , Estudios de Seguimiento , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Neoplasias/etiología , Neoplasias/prevención & control , Extractos Vegetales/efectos adversos , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/etiología , Neoplasias de la Próstata/prevención & controlRESUMEN
Inconsistent and contradictory results from nutrition studies conducted by different investigators continue to emerge, in part because of the inherent variability of natural products, as well as the unknown and therefore uncontrolled variables in study populations and experimental designs. Given these challenges inherent in nutrition research, it is critical for the progress of the field that researchers strive to minimize variability within studies and enhance comparability between studies by optimizing the characterization, control, and reporting of products, reagents, and model systems used, as well as the rigor and reporting of experimental designs, protocols, and data analysis. Here we describe some recent developments relevant to research on plant-derived products used in nutrition research, highlight some resources for optimizing the characterization and reporting of research using these products, and describe some of the pitfalls that may be avoided by adherence to these recommendations.
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Productos Biológicos/química , Investigación Biomédica/métodos , Suplementos Dietéticos/análisis , Análisis de los Alimentos/métodos , Ciencias de la Nutrición/métodos , Fitoquímicos/análisis , Plantas Comestibles/química , Animales , Investigación Biomédica/normas , Investigación Biomédica/tendencias , Congresos como Asunto , Exactitud de los Datos , Bases de Datos Factuales , Humanos , National Center for Complementary and Integrative Health (U.S.) , Ciencias de la Nutrición/tendencias , Reproducibilidad de los ResultadosRESUMEN
Energy drinks are relatively new to the United States but are the fastest growing segment of the beverage market. Humans have a long history of consuming caffeine in traditional beverages, such as cocoa, coffee, tea, and yerba maté, but 2 workshops held at the Institute of Medicine (http://www.iom.edu/Activities/Nutrition/PotentialHazardsCaffeineSupplements/2013-AUG-05.aspx) and the NIH (http://ods.od.nih.gov/News/EnergyDrinksWorkshop2013.aspx) in 2013 highlighted many critical gaps in understanding the biologic and behavioral effects of the mixtures of caffeine, vitamins, herbs, sugar or other sweeteners, and other ingredients that typify caffeine-containing energy drinks (CCEDs). For example, different surveys over the same 20102012 timeframe report discrepant prevalence of CCED use by teenagers, ranging from 10.3% in 1317 y olds to >30% of those in grades 10 and 12. Understanding of functional interactions between CCED ingredients, drivers of use, and biologic and behavioral effects is limited. The 4 speakers in the Experimental Biology 2014 symposium titled "Energy Drinks: Current Knowledge and Critical Research Gaps" described recent progress by their groups in extending our understanding of prevalence of CCED use, sources of caffeine in the United States, drivers of CCED use, and behavioral correlations and effects of CCEDs, including effects on attractiveness of both alcoholic and non-alcoholic beverages.
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Cafeína/análisis , Bebidas Energéticas/análisis , Adolescente , Congresos como Asunto , Ingestión de Energía , Humanos , Encuestas NutricionalesRESUMEN
Sales of energy drinks in the United States reached $12.5 billion in 2012. Emergency department visits related to consumption of these products have increased sharply, and while these numbers remain small relative to product sales, they raise important questions regarding biological and behavioral effects. Although some common ingredients of energy drinks have been extensively studied (e.g., caffeine, B vitamins, sugars, inositol), data on other ingredients (e.g., taurine) are limited. Summarized here are data presented elsewhere in this issue on the prevalence and patterns of caffeine-containing energy drink use, the effects of these products on alertness, fatigue, cognitive functions, sleep, mood, homeostasis, as well as on exercise physiology and metabolism, and the biological mechanisms mediating the observed effects. There are substantial data on the effects of some energy drink ingredients, such as caffeine and sugars, on many of these outcomes; however, even for these ingredients many controversies and gaps remain, and data on other ingredients in caffeine-containing energy drinks, and on ingredient interactions, are sparse. This summary concludes with a discussion of critical gaps in the data and potential next steps.