Use of herbal products by children is a relatively new area of interest and concern. Only very limited information regarding therapeutic efficacy and risk of adverse reactions to herbal products in adults is published in peer-reviewed medical and scientific journals. Even less is known regarding herbal products usage, efficacy, and risks in children.

The objectives in this chapter are to describe what herbal products are, why patients and parents use them, and their adverse effects and drug interactions, and to discuss some approaches to evaluating data and clinical trials, the lack of quality control of manufacture of some herbal products, the issue of standardization of dose and active ingredients, the lack of full dose-response curve data, and the lack of high-quality clinical trials.

Herbal products are drugs. They are complex mixtures of chemicals prepared from plants (1,2), or are parts of raw, uncooked plants. The identified or suspected active ingredients often are multichemical in nature (3). Herbal products are not required to be proven either safe or effective prior to marketing (4). The Food and Drug Administration (FDA) has minimal to no regulatory authority regarding the safety and efficacy of herbal products. The burden of proof for safety is on the FDA, not the manufacturer (5). This is the opposite situation to that of food additives and drugs. This situation likely results in an increased risk to the general public, and, unfortunately, it has been established by law. The 1994 Dietary Supplement Health and Education Act (DSHEA) categorizes herbal products as “dietary supplements.” Thus, consumers have little protection against misleading or fraudulent claims made by herbal manufacturers (6,7).

Herbal products are rarely sold in child-resistant packaging (8) and are exempt from regulations that mandate imprint code identification markings. Lack of product uniformity even among batches of product from a single manufacturer has been documented. Some herbal products may contain pesticides, heavy metals, or other chemicals leached from the ambient soil media (9). There is no guarantee even on the correct identity of herbal products being sold. Herbal products may be contaminated or misidentified at any stage from harvesting through packaging (4). Some herbal products (e.g., aconite roots) may vary greatly in their alkaloid content depending on the origin, the time of harvest, and the method of processing (10). There is a lack of quality control of manufacture of many herbal products, with standards in some cases far below what is generally recognized as necessary for therapeutic drugs (11,12). Standardization of dose and active ingredients is unknown for many, and perhaps most, herbal products. For example, St. John’s wort is “standardized” by its hypericin content, but hyperforin is the active ingredient. “Standardized” typically is not defined or the method stated on either the product label or a product monograph,
assuming a monograph or package insert exists. Labels for dietary supplements (herbal products) may contain statements of nutrition support without preauthorization by the FDA (13,14). On June 22, 2007, the FDA passed a final rule that established a set of Good Manufacturing Practices for certain dietary supplements. Distributors have up to 3 years to comply, and bulk suppliers and some individual practitioners are exempt, thus this may not have prevented some of the large-scale contamination issues. Because most herbal products have no high-quality clinical trial studies, there is a lack of full dose-response data. Even if a dose range is recommended, typically there is no dose-response information.

Children may have a different dose response than adults, as has been well established for some therapeutic drugs. Therapeutic indices vary for herbal products and may be unpredictable, particularly in children (15). Children’s doses cited by many herbal guides are strictly anecdotal (15).

About 7,000 species of plants are used in China as herbal remedies (10), and there are more than 5,000 kinds of Chinese medicinal herbs. There are more than 700 patent Chinese medicine factories, and there are more than 1,500 factories producing Chinese herbal pills and other dose forms (16). It is estimated that there are more than 20,000 herbal products on the market (17).

An estimated 30% to 35% of adult Americans use herbal products (18). Estimates for children are based on very limited data. Approximately 11% of parents used some form of alternative medicine for their children, based on a questionnaire sent to 2,000 parents with a 96% response rate (19). It has been stated that up to 50% of children with autism in the United States probably are being given some form of complementary/alternative medicine (20). One survey of emergency department visits identified that 14.5% of women used herbal products during pregnancy and 23.5% of children younger than 16 years were given herbal preparations (21). Among teenagers who use complementary and alternative therapies, nearly 75% use herbs (6). In 142 families that brought their children to an emergency department in 2001, 45% of caregivers reported giving their children an herbal product (22).

An estimated 15% of Americans visited a provider of herbal medicine in 1998. Approximately 25% of Western drugs are isolated from plants, and another approximately 25% are modifications of substances derived from plants. Internationally, approximately 120 prescription drugs are produced directly from plant extracts. The US commercial market for herbal products was projected to be $5 billion in the year 2000 (23).

Historically, the use of plants for medicinal purposes is documented in Chinese texts of the Yellow Emperor Huang Di in 2697 B.C.E. and in the Ebers papyrus in 1550 B.C.E. (more than 800 remedies, mostly botanical). Hippocrates (466 to 377 B.C.E.) used plants in his practice of medicine.

Typical adult users of herbal products are educated, middle class, white, and between the ages of 25 and 49 (24). They have a holistic belief in the integration of body, mind, and spirit. They report poorer perceived health status compared with matched nonusers of herbal products. They are not more dissatisfied with and are not more distrustful of conventional medical care. Some of these persons may be somatizers (24).

One potential use of herbal products by children and adolescents is to attempt to enhance sports performance, similar to the abuse of steroids, growth hormone analogues, and so-called supplements such as creatine (25). One published source recommends, for treatment of attention deficit hyperactivity disorder in children, use of St. John’s wort, kava kava, catnip, and kola nut, singly or in combination (15). A voluntary recall of ginseng products occurred after teachers reported that students were drinking ginseng extract that contained up to 24% alcohol (15). Other reports document the use of alternative medicine and/or herbal products in children for diagnoses such as juvenile arthritis, infant colic, enuresis, postoperative pain, agitation, and plantar warts (26,27,28,29,30,31,32).

Recently, adolescent abuse of herbal blends, purchased over the Internet, or in local alternative stores, has become epidemic. These products are distributed in Europe, and possibly manufactured in China, with common brand names of “Spice” or “Serenity”. While labeled to contain a variety of herbal plants with psychoactive activity, chemical analysis has uniformly shown them to have none of the labeled content, but instead to contain “designer” drugs that act on the THC receptor, sometimes 100 times as potent. These appear to cause a higher degree of toxicity and tolerance than THC, thus posing an emerging threat (33).

High-quality clinical trials can provide valid scientific evidence of the efficacy of herbal products, both for pediatric and adult therapeutic uses. One prospective double-blind clinical trial supported the potential efficacy of one herbal tea preparation in the treatment of infant colic (34); this study is worthy of confirmation and is an example of an herbal product clinical trial that may provide useful and scientifically valid information. However, much more additional safety information is required before this product could be recommended for widespread use and incorporated into routine treatment recommendations.

In order to obtain a United States Pharmacopeia (USP) designation and to place the letters “USP” on a label, a manufacturer must submit its product for testing by the
USP and must fulfill the standards set by the USP. Most herbal products do not have a USP designation, and it is likely that many herbal products would not meet USP standards because of factors such as batch-to-batch variability, lack of stability, and/or contaminants. A designation of NF (National Formulary) on a product without a USP designation means that the product fulfills the manufacturing quality standards set by the USP but does not have USP or FDA endorsement for the intended use (5). Most herbal products currently do not have an NF designation. The USP in the last few years has instituted a new program to certify herbal products that meet its standards, including a label designation to inform the consumer that an herbal product has met USP standards. Only a small number of herbal products have received certification by the USP.

The National Center for Complementary and Alternative Medicine (NCCAM) is a part of the National Institutes of Health, and the Office of Cancer Complementary and Alternative Medicine (OCCAM) is at the National Cancer Institute, also part of the National Institutes of Health. These units provide information and support research involving herbal products and other types of complementary/alternative medicine (35). The Web site for NCCAM is http://www.nccam.nih.gov.easyaccess1.lib.cuhk.edu.hk

The most commonly used herbal products in the United States are chamomile, echinacea, feverfew, garlic, ginger, ginkgo, ginseng, kava, saw palmetto, St. John’s wort, and valerian. The commercial claims for therapeutic benefit for these herbal products typically are not substantiated by prospective, randomized, placebo-controlled, double-blind clinical trials. The claims for therapeutic use include chamomile for gastric ulcers and as a sedative, echinacea for the common cold, feverfew for migraine headache prevention, garlic for hyperlipemia and hypertension, ginger as an antemetic, ginkgo for dementia and claudication, ginseng as a “tonic,” kava for anxiety, saw palmetto for prostate hypertrophy, St. John’s wort for mild endogenous depression, and valerian as a sedative. There has been a surge in recent years of the use of foods, candies, or beverages promoted as energy enhancement products to adolescents. These products typically contain caffeine derived from guarana or cola nut, in doses of up to 300 mg per serving, along with other ingredients such as ginseng, vitamins, amino acids, and Ginkgo biloba (36).

A number of adverse effects of herbal products have been reported (37,38). Some of these adverse effects are severe and potentially life-threatening (39,40). Some herbal products’ adverse effects have resulted in death. The World Health Organization Collaborating Center for International Drug Monitoring in Uppsala, Sweden, has had more than 5,000 reports of suspected adverse reactions that involve herbal medicines (10).