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The Dietary Supplement Market

Botanical Safety Handbook

Botanical Safety Handbook



John A. Budny, PhD, CMI Certified Medical Investigator of Botanical Safety Handbook, Second Edition Published in the International Journal of Toxicology 2013 32: 466

The dietary supplement market in the United States, which has been monitored by the National Health and Nutrition Examination Survey (NHANES) program, is large and growing. According to the NHANES survey, approximately half of the population uses dietary supplements with botanical or herbal supplements being more popular in older segments of the population1. The 10 most popular botanical products ($1.5. billion in sales) make up 20% of the herbal supplement market ($5.5 billion) in a total dietary supplement market of $11.5 billion in the United States2. Consequently, the safety of plant-derived dietary supplements is an important consideration for society.

The multiplicity of products, diversity of suppliers, and compositional complexities3 of botanicals presents challenges for ascertaining human health risks. Whenever there are questions or compositional uncertainties about a material, the toxicologist’s brow becomes populated with beads of perspiration. However, in the case of quantifying toxicity and making a human health risk assessment for a botanical product or component the toxicologists can get help from the American Herbal Products Association’s Botanical Safety Handbook, Second Edition (BSH).

The BSH is hefty by any objective measure such as dimensions, weight and content; it will likely be judged by its users as comprehensive. BSH covers over 500 herbs within almost 1,100 pages. Twenty-nine pages of descriptive material precede the individual listings or entries that are addressed in the handbook. Five appendices (43 pages) and a 41-page Index follow the individual listings. While the Appendices and Index comprise only 8% of the book, these sections are important for using other sections of the BSH.

Appendix. 1 Herbal Constituent Profiles contains toxicity discussions of specific constituents that are found in many plants and became part of a vast number of herbal products. Rather than repeat the discussions for these recurring chemicals, the toxicity issues for these ubiquitous components appear one time in Appendix 1 and they are referred to in the individual herbal entries. Appendix 2. Herbal Action Profiles describes generic physiological and pharmacological actions that occur across many plant-derived materials. Appendix 3. Herbal Interaction Profiles discusses herbal interactions with drug metabolism processes, principally biotransformation and absorption of xenobiotics, as well as other interactions in which herbs are a component. Appendix 4. Safety of Botanicals in Pregnancy and Lactation identifies complications that may ensue when certain herbs are used during pregnancy and lactation. Appendix 5. Herb Listing by Classification provides a quick reference for all of the botanical entries as groups of herbs that have the same use pattern or contraindication according to their Safety Class and Interaction Class.

Two organizational units within the 29 pages that precede the herbal listings include an Introduction and a section entitled Organization of Data. These eight pages collectively provide two key elements for the users of the handbook: 1) how the process of determining botanical safety was conducted; and 2) how results from the safety determination process are organized in individual herbal listings. It is apparent that the described process for determining the safety and the organizational outline of the safety information for each herbal entry served as guidance to the Editors and their seven- member Expert Advisory Council as they prepared entries for the BSH. Once the user of the BSH understands how safety assessments were made, what limitations the editors understood to be relevant to the safety assessment and the description of how the results are presented, the BSH will serve as an appropriate guide for human health risk assessments. As in the First Edition, each botanical that is assessed is put into one of three Safety Classes and one of the three Interaction Classes.

Explaining how the safety of each botanical was determined is important for those who will use the handbook. While the Editors and their Advisory Panel have extensive experience and background in herbal medicine and therapeutics based on botanicals, a similar depth in toxicology and human health risk assessments in not so evident. Consequently, it is important for the Editors to describe the process that they used for determining the safety for the listed botanicals. For the experienced toxicologist, the limitation in describing toxicity and assessing risk is not a problem. Practicing toxicologists recognize that history of use and testimonials are not viable substitutes for defining toxicity, identifying target organs, defining dose-response and estimating no- effect-levels. However, for the practitioner of herbal medicine, the lack of depth of toxicological expertise in the Editors and their Advisory Panel will likely not be apparent.

Each of the entries in the handbook has as it core, the same basic structure with four major divisions: 1) entry listing by Latin name; 2) Quick Reference; 3) Review Details; and 4) Literature Cited.

The entry listing section which uses the Latin name as the entry heading identifier, also lists the SCN (standard common name) OCN (other common names), Ayurvedic names (AN) and pinyin (PN) for botanical ingredients commonly used in traditional Chinese medicine. The part of the plant for which the various the classifications are made is also contained in the initial section of the entry.

The Quick Reference Summary section contains, for most of the botanicals, information on Safety Class and Interaction Class along with Contraindications. The criteria for the various classes are defined in the Introduction and summarized in a block table on both inside covers of the Manual. Other sections, if information is available, include Precautions, Drug and Supplement Interactions, Adverse Events and Side Effects, Pharmacological Considerations and Pregnant and Lactation. For some botanicals for which the literature would support a warning that excessive doses should be avoided, there is Standard Dose information. Two additional sub-sections, which are located in the Quick Reference Summary, are included in some entries: Notice and Editor’s Notes. These two sections give additional information about the specific entry that may not be related to the process of determining safety. If components of the botanical product are known to have pharmacological activities or if important information is known to directly affect safety, that information is listed in the Notice sub- section. The Editor’s Notes section provides information on labeling, preparation, potential contaminants etc. The distinction between Notice and Editor’s Notes sections as to their content and purpose is often blurred.

The Review Details main section has five components or sub-sections: 1) Drug and Supplement Interactions; 2) Adverse Events; 3) Pharmacology and Pharmacokinetics; 4) Pregnancy and Lactation; and 5) Toxicity Studies.

Literature Cited, which is the fifth and final major section of each entry, has a purpose and content that is self-evident its name.

It is important for a book review to focus on issues that are important to the audience for whom the review was written. To that aim, I have accomplished that objective through two personal examples of how I used the BSH. As a toxicologist writing for toxicologists, I can share my first hand experiences as worthwhile examples of the BHS’s utility for a toxicologist.

As I was beginning to conduct this book review for the BSH, I was assessing, in my normal practice of toxicology, the toxicity and risks associated with two commonly used herbal products that contained widely recognized active ingredients: Ginko biloba and St. John’s Wort. Without an extensive description of how I used BSH in developing human health risk assessments for these two materials, I will share some important conclusions that that I drew from my experience.

I examined BSH’s Index to locate the page for the entry for St. John’s Wort. To my surprise, I was not able to locate an entry in the Index for St. John’s Wort. Following my initial disbelief, I reviewed resources other than BSH to locate synonyms and I found that St. John’s Wort is, by its Latin name, Hypericum perforatum L. Fortunately, I returned to BSH and found the Hypericum perforatum L. entry with its SCN of St. John’s Wort. I am glad I did return to the BSH because there were 11 pages of information that, while more than I needed, gave me important information for my analysis and report. The breadth and depth of the information confirmed my earlier conclusion that the BSH is intended for herbal medicine practitioners. An index is an important tool for toxicologists and the BSH should have had an entry for St. John’s Wort.

A similar but not identical experience occurred when I was assessing the toxicity of Ginko biloba. Unlike St. John’s Wort, Ginko biloba L. is the Latin name so it was in the Index. However, when I went to the Ginko biloba L. entry, I found that there are two types of herbal compositions made from Ginko biloba L.: one set of herbals made from leaves and another set made from seeds. While there were some legitimate toxicology references for assessing the Ginko biloba L. from leaves, there were no similar toxicology references for Ginko biloba L. from seeds. The references that were used to support the toxicity section for Ginko biloba L. seeds were other herbal medicine books. I quickly realized that I was about to be sucked into the vortex of a circumlocution that might seem reasonable to a non-toxicologist that practiced herbal medicine. I did, however, learn to ask whether the Ginko biloba L. that was the subject of my human health risk assessment was derived from leaves or seeds.

BSH is a valuable resource for a toxicologist to understand the arena in which he or she is practicing their profession; the Manual is not a resource that identifies the hazards (toxicity) of botanicals nor does it contain risk assessments of botanicals. A toxicologist is still required to identify the hazard (toxicity), determine the effect and the no-effect levels and provide a risk assessment for humans who would use the botanical. However, using BSH gives valuable background information located in one place, reducing the literature searching time for obtaining background information on a botanical.

Is BSG a good resource for every toxicologist to have in their personal library? No. Is the BSH the reference work a toxicologist can go to for human health risk assessments for botanicals? Not really. However, the BSH is a necessary reference in the personal library of toxicologists that routinely conduct hazard analyses and human health risk assessments of botanicals. Those toxicologists that assess the human health risks of botanicals will find a vast amount of generic background information that will supplement their activities. In addition, toxicologists will discover clear and valuable guidance and directions for making their human health risk assessments of botanicals.

1. Baily, RL, Gahche, JJ, Lentino, CV et al. Dietary Supplement use in the United States 2003 -2006. J Nutr. 2011; 141(2): 261-266.

2. “Supplemental sales hit $11.5 billion in U. S., report says. Nutrain

nutraingredients-  Accessed October 7, 2013.

3. Kemsley, J. “Analyzing Botanical Dietary Supplements.” Chem Eng News. 2013; 91(11): 12-17.