Published Conference Report on Bioactive Nutrients Highlights Safety Data, Need for Dietary Guidance Framework—Analysis of tolerable upper intake levels adds to body of scientific literature

Washington, D.C., February 16, 2017— The increasing interest in the roles that certain bioactive compounds can play in health and wellness warrants exploration of establishing recommended intakes or dietary guidance for selected bioactive nutrients, according to a conference report published in the March issue of Regulatory Toxicology and Pharmacology, “Bioactive nutrients—Time for tolerable upper intake levels to address safety.” 1

The report, from the July 2016 Toxicology Forum (Tox Forum) Meeting held in Salt Lake City, Utah, advises that evaluation of safety/toxicity is one key component in establishing dietary guidance, and adds to the case made in a 2016 European Journal of Nutrition article that calls on authoritative scientific bodies to set standards for bioactive nutrients, “Nutrient reference value: non-communicable disease endpoints—a conference report.” 2

James C. Griffiths, Ph.D., vice president, scientific & international affairs, for the Council for Responsible Nutrition (CRN), the leading trade association for the dietary supplement and functional food industry, chaired the Tox Forum session on this topic and co-authored both papers. Dr. Griffiths observed, “CRN and other key stakeholders that are attuned to the growing interest in bioactive nutrients are engaging in discourse over whether, and if so, how, dietary guidance or recommended intakes might be established for these substances. Safety evaluation is a key consideration in developing recommendations and our Tox Forum proceedings reviewed current and past approaches featuring case studies including lutein and green tea extracts.”

In addition, previously published papers co-authored by Dr. Griffiths looked at bioactives including the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),3 flavanols, lycopene, zeaxanthin, and soybean isoflavones.4

Among the possible approaches to establishing the safety of bioactives are those used to establish upper intake levels for essential nutrients, the Dietary Reference Intake (DRI) Upper Level (UL) model, as well as identification of the “no observed adverse effect level” (NOAEL) or “lowest observed adverse effect level” (LOAEL), the paper explained. However, the extent of available data regarding intakes of bioactive components and documented adverse effects, and available estimates of typical dietary intakes of the substances in the population must be considered. “Toxicologists need to be involved in both the development of the safety framework and in the evaluation of the science to establish maximum intake/upper limits,” Dr. Griffiths noted.

The conference report “Bioactive nutrients—Time for tolerable upper intake levels to address safety,” published in Regulatory Toxicology and Pharmacology, was authored by: Allison A. Yates, Ph.D., consultant to the Institute of Medicine Food and Nutrition Board; John W. Erdman Jr., Ph.D., of the University of Illinois at Urbana-Champaign; Andrew Shao, Ph.D., of Herbalife Nutrition, Ltd.: Laurie C. Dolan, Ph.D., of Burdock Group; and Dr. Griffiths.


Note to Editor: The Council for Responsible Nutrition (CRN), founded in 1973, is a Washington, D.C.-based trade association representing 150+ dietary supplement and functional food manufacturers, ingredient suppliers, and companies providing services to those manufacturers and suppliers. In addition to complying with a host of federal and state regulations governing dietary supplements and food in the areas of manufacturing, marketing, quality control and safety, our manufacturer and supplier members also agree to adhere to additional voluntary guidelines as well as to CRN’s Code of Ethics. Visit Follow us on Twitter @crn_supplements and @wannabewell and on Facebook.


  1. Yates, A.A., Erdman, J.W., Shao, A., Dolan, L.C., Griffiths, J.C., 2017. Bioactive nutrients - Time for tolerable upper intake levels to address safety. Regulatory Toxicology and Pharmacology 84, 94–101. doi:10.1016/j.yrtph.2017.01.002

  2. Lupton, J.R., Blumberg, J.B., L’Abbe, M. et al. Eur J Nutr (2016) 55(Suppl 1): 1. doi:10.1007/s00394-016-1195-z

  3. Biesalski HC, Erdman JW, Hathcock J, Ellwood K, Beatty S, Johnson E, Marchioli R, Lauritzen L, Rice HB Shao A, Griffiths J (2013) Nutrient reference values for bioactives: new approaches needed? A conference report. Eur J Nutr Suppl. doi:10.1007/s00394-013-0503-0

  4. Lupton JR, Atkinson SA, Chang N, Fraga CG, Levy J, Messina M, Richardson DP, van Ommen B, Yang Y, Griffiths JC, Hathcock J (2014) Exploring the benefits and challenges of establishing a DRI-like process for bioactives. Eur J Nutr Suppl. doi:10.1007/s00394-014-0666-3