Resources for Product Integrity for Dietary Supplement Research

Defining the Importance of Product Characterization
Recommendations for Designing and Reporting Natural Product Studies
Programs Aimed at Improving Product Characterization
NCCAM Policy: Natural Product Integrity
Resources for Investigators
Specifications and Methods of Analysis for Botanical and Nutritional Products

The Office of Dietary Supplements has compiled this list of resources for investigators, authors, and editors working in the area of natural products research.

Defining the Importance of Product Characterization

This review in The American Journal of Medicine provides information on quality-control issues that warrant attention prior to conducting clinical trials on herbal supplements. In an effort to examine the extent of inadequate characterization of popular herbal products that have been used in clinical studies, investigators at Kaiser Permanente, Tufts University School of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School identified 81 randomized controlled trials using herbal products and evaluated the level of documented product characterization.

Wolsko PM, Solondz DK, Phillips RS, Schachter SC, Eisenberg DM. Lack of herbal supplement characterization in published randomized controlled trials. Am J Med. 2005;118:1087-93.

Recommendations for Designing and Reporting Natural Product Studies

This commentary from The American Journal of Clinical Nutrition was written by ODS's Christine Swanson and recommends that the standards for designing and evaluating research on botanicals and other dietary supplements should be the same as for other test articles. Dr. Swanson addresses the need for establishing criteria for the identification and characterization of botanical preparations used in nutrition research.

Swanson CA. Suggested guidelines for articles about botanical dietary supplements. Am J Clin Nutr 2002;75:8-10.

This expanded Consolidated Standards of Reporting Trials (CONSORT) statement has been extended to trials using herbal product interventions. To improve the reporting of randomized controlled trials using herbal medicine interventions, members of the CONSORT Group elaborated on the original 22-item CONSORT checklist with nine additional items aimed specifically at randomized controlled trials of herbal medicines. This consensus statement is an informative reference for authors and journal editors.

Gagnier JJ, Boon H, Rochon P, Moher D, Barnes J, Bombardier C; CONSORT Group. Reporting randomized, controlled trials of herbal interventions: an eaborated CONSORT statement. Ann Intern Med 2006;144:364-7.

This article from HerbalGram by Joseph Betz and Mary Hardy discusses challenges associated with evaluating herbal clinical trials and provides recommendations to authors on seldom discussed aspects of trial design such as botanical nomenclature, justification of clinical endpoint, posology, and description of the product and placebo.

Betz JM, Hardy ML. Evaluating the botanical dietary supplement literature. HerbalGram 2014 Spring 101:58-67.

Programs Aimed at Improving Product Characterization

Betz JM., Fisher KD., Saldanha LG, Coates PM. The NIH analytical methods and reference materials program for dietary supplements. Anal Bioanal Chem 2007; 389:19-25.

Phillips MM, Rimmer CA, Wood LJ, Lippa KA, Sharpless KE, Duewer DL, Sander LC, Betz JM. Dietary supplement laboratory quality assurance program: the first five exercises. J AOAC Int 2011;94:803-14.

NCCAM Policy: Natural Product Integrity

The National Center for Complementary and Alternative Medicine (NCCAM) at the NIH has developed guidelines for the design and conduct of experiments that use bioactive constituents or natural products for all investigators seeking funding from the Center. An extensive array of information is provided on the NCCAM Web site.

Resources for Investigators

The Journal of Natural Products, jointly published by the American Society of Pharmacognosy and the American Chemical Society, publishes instructions for authors of natural product studies submitted to the journal. Failure to follow the instructions related to study article description are grounds for manuscript rejection. The instructions provide useful information on describing instrumentation as well as sources of specialized chemicals and natural products used in studies.

American Chemical Society. Preparation and submission of manuscripts. J Nat Prod 2006;69:10A-15A.

Establishing botanical identity is a key step in the scientific study of medicinal plants. This paper examines common taxonomic problems relevant to medicinal plant research and provides a basic guide to plant taxonomy for medicinal plant researchers. In addition to discussing voucher specimens, plant identification, and botanical nomenclature, it cites references and other resources that may be useful to researchers.

Bennett, BC, Balick MJ. Phytomedicine 101: plant taxonomy for preclinical and clinical medicinal plant researchers. J Soc Integr Oncol 2008;6:150-157.

Herbal products are widely used, and analytical methods are needed to ensure that botanical ingredients used in commercial products are correctly identified and that research materials are of adequate quality and are sufficiently characterized to enable research to be interpreted and replicated. When developing analytical methods, conscious efforts must be made to ensure that the botanical identity of test materials is rigorously confirmed. Use of material with an associated herbarium voucher that can be botanically identified is always ideal. Indirect methods of authenticating bulk material, such as organoleptic, anatomical, chemical, or molecular characteristics, are not always acceptable for the chemist's purposes. Familiarity with botanical and pharmacognostic literature is necessary to determine what potential adulterants exist and how they may be distinguished.

Applequist WL, Miller JS. Selection and authentication of botanical materials for the development of analytical methods. Anal Bioanal Chem 2013;405):4419-28.

Proving that indirect methods for botanical identification (such as chemical fingerprinting) give the right answer is necessary before the method and its results can be useful. AOAC International has published guidelines for validation of methods for botanical identification.

AOAC International; Guideline Working Group. AOAC INTERNATIONAL guidelines for validation of botanical identification methods. J AOAC Int 2012;95:268-72.

This document provides guidance for collecting, handling, and storing voucher plant specimens. Voucher specimens are botanical reference materials that are associated with specific batches of plant material and serve to document the authenticity of the bulk materials. Proper documentation of the original botanical source is a critical part of developing any standardized dietary supplement or herbal medicine used in research or commercially.

Hildreth J, Hrabeta-Robinson E, Applequist W, Betz J, Miller J. Standard operating procedure for the collection and preparation of voucher plant specimens for use in the nutraceutical industry. Anal Bioanal Chem 2007;389:13-7.

Assuring the accuracy and precision of quantitative measurements made on phytochemicals and nutrients is vital. Several approaches exist, ranging from evaluation of in-house or published methods against certified reference materials to performing formal validation studies on laboratory methods. The documents below provide information on the importance of data integrity and various approaches to assuring integrity.

Betz JM, Brown PN, Roman MC. Accuracy, precision, and reliability of chemical measurements in natural products research. Fitoterapia 2011 82:44-52.

Rimmer CA, Sharpless KE, Wise SA, Betz JM, Coates PM. Standard reference materials for dietary supplement analysis. Anal Bioanal Chem 2013;405:4337-44.

AOAC International. AOAC Guidelines for single-laboratory validation of chemical methods for dietary supplements and botanicals. In: Appendix K-Guidelines for dietary supplements and botanicals. official methods of Analysis of AOAC INTERNATIONAL. 19th ed. Gaithersburg, MD: AOAC International; 2012.

Specifications and Methods of Analysis for Botanical and Nutritional Products

Validated methods of analysis for constituents of a number of botanical and nutrient ingredients and finished products can be found in:

Official Methods of Analysis of AOAC INTERNATIONAL, 19th ed. Gaithersburg, MD: AOAC International; 2012.

Official raw material and finished product specifications for many botanicals and nutritionals along with tests for determining whether or not specifications are met are available in the United States Pharmacopeia’s Dietary Supplements Compendium (USP 36/NF 21 (2013) United States Pharmacopeial Convention, Rockville, MD USA). Specifications and tests are available in French and English editions of the European Pharmacopoeia 8.0 (European Pharmacopoeia Commission, EDQM, Strasbourg, France). An English version of the 10th edition of the Pharmacopoeia of the People’s Republic of China (9th Chinese Pharmacopoeia Commission, Beijing, PRC) is available and contains monographs for numerous botanicals used in the practice of Traditional Chinese Medicine.