Related Terms

• Botanical products, capsules, dietary supplement labeling, extracts, functional foods, Good Manufacturing Practices, GMP, herbal product formulation, herbal product manufacturing, nutrient content claim, powders, raw materials validation, standardization, structure/function claim, tablets, teas, tinctures.

Background

• Herbal product design refers to the process of developing, standardizing, processing, and validating an herbal product for the market. This monograph covers pre-formulated or pre-packaged herbal products, which are marketed for sale. This monograph does not cover herbs, which are prepared at home or by an individual practitioner without widespread distribution (herbs that are not formulated, packaged, and marketed for sale).

• An herb (also called a botanical) is a plant or plant part used for its scent, flavor, and/or therapeutic properties. Herbal medicine products are dietary supplements that individuals consume for purposes such as improvement of health, improvement of physical appearance, weight loss, or enhancement of well-being. Many herbs have been used historically for various purported health benefits. For instance, tea tree oil is thought to have broad antifungal and antibacterial properties.

• Herbal products are sold in formulations such as tablets, capsules, powders, teas, extracts, tinctures, and as fresh or dried whole plants. It is often difficult to determine the quality or efficacy of a dietary supplement product from its label. The degree of quality control depends on the manufacturer, the supplier, and other parties involved in the production process.

• Consumers may need to exercise caution when considering which herbal products to purchase, as many herbs on the market are not proven to be effective, and may cause health problems or interact with other herbal products or pharmaceutical drugs.

• When considering which herbal product to recommend, health care providers typically take certain product characteristics into consideration, including: quality control procedures (such as protocols for drying, storage, or extraction procedures), product formulation, route of entry, possible toxicity, and interactions with other medications. Consumers may also benefit from inquiring if analysis procedures have been conducted to confirm the contents of the herbal product, or if standardization requirements were met by the manufacturer. Advocates of standardization claim that this process of quality control is important because it helps to assure that the ingredients in a product are identical between batches and may help to prevent adverse events.

• Issues that will be addressed in the future will most likely involve finding an agreeable balance between herbal product availability and safety.

Herbal Product Regulations and Formulation Processes

• GMP (Good Manufacturing Practices): The National Nutritional Foods Association (NNFA), the herb and supplement industry's largest trade association, has run a program since 2002 that examines products and factory conditions of member companies. The NNFA provides this service because the U.S. Food and Drug Administration (FDA) does not regulate these products as stringently as pharmaceutical drugs. Member companies who pass the inspection receive the right to display the GMP (Good Manufacturing Practices) seal of approval on their products. The GMP seal represents adequate NNFA standards of quality control in manufacturing and distribution of the herb or supplement product.

• The FDA is authorized to issue GMP regulations describing conditions under which dietary supplements must be prepared, packed, and stored. The FDA published a proposed rule in March 2003 that is intended to ensure that manufacturing practices will result in properly formulated dietary supplements and that dietary supplements are accurately labeled. GMPs are primarily concerned with safety and sanitation rather than dietary supplement standardization. Some herbal product manufacturers voluntarily follow pharmaceutical drug GMPs, which are more rigorous than GMPs for dietary supplements, but they are not required to do so.

• Standardization: Standardization is a process that manufacturers may use to ensure batch-to-batch consistency of their products. In some cases, standardization involves identifying specific chemicals (known as chemical markers) that can be used to manufacture a consistent product. If the chosen markers are present at about the same amounts between batches of the same product, then it is likely that all of the ingredients in that product are present in equal proportions between these batches. This process provides a measure of quality control.

• Standardization is achieved by choosing at least one chemical compound present in the herb or supplement and monitoring its concentration in each batch of product. Batches that do not meet the standard are modified accordingly. Standardization is not directly related to efficacy because it does not assess the total chemical composition of the product; rather, it only indicates consistency of contents. Further, consistency of contents is a separate measure from clinical efficacy.

• Previously, a legal or regulatory definition for the standardization of dietary and herbal supplements did not exist in the United States. Due to this, some manufacturers may use the term incorrectly to refer to uniform manufacturing practices, such as mixing equal proportions of several plant parts. However, mixing plants in equal proportions may not yield identical final products because the constituents of a plant may vary between batches. Therefore, following a recipe of proportions or similar procedures is not sufficient for a product to be considered standardized. As a result, the presence of the word "standardized" on a supplement label does not necessarily indicate product quality.

• The legal status of herbal ingredients varies by country.

• Dosage: Dosage is in general a crucial issue for herbal products. While most pharmaceutical drugs are extensively tested to determine the most effective and safest dosages (especially in relation to patient variables such as body weight, other medications, and allergies), there are few established dosage standards for herbal products. Generally, the dosages recommended for a dietary or herbal supplement may vary, and the exact therapeutic range is not well known. Experts in the field of complementary and alternative medicine may not agree upon the minimum and maximum dose needed for clinical efficacy.

• Product label claims: Previously, the FDA regulated dietary and herbal supplements as foods. Knowledge of the clinical efficacy of substances classified as foods was not necessary for a product to be sold. This meant that dietary supplements did not have to meet the same standards as pharmaceutical drugs and over-the-counter medications for proof of safety, effectiveness, and Good Manufacturing Practices (GMPs). Most often, classification as a dietary supplement is determined by the information that the manufacturer provides on the product label or in accompanying literature although many food and dietary supplement product labels do not include this information.

• Drug manufacturers may claim that their product will diagnose, cure, mitigate, treat, or prevent a disease. Such claims may not legally be made for dietary supplements.

• The label of a dietary supplement or food product may contain one of three types of claims: a health claim, nutrient content claim, or structure/function claim. Health claims describe a relationship between a food, food component, or dietary supplement ingredient and the reduction of risk for disease or health-related condition. Nutrient content claims describe the relative amount of a nutrient or dietary substance in a product in grams or ounces. A structure/function claim is a statement describing how a product may affect organs or systems of the body, and it cannot mention that it may treat, prevent, or cure any disease. Structure/function claims do not require FDA approval, but the manufacturer must provide the FDA with the text of the claim within 30 days of product release on the market. Product labels containing such claims must also include a disclaimer that reads, "This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease." Dietary supplements are not required to state any health claim on their packaging.

• The label of a dietary supplement product is required to be truthful and not misleading. If the label does not meet this requirement, then the FDA may remove the product from the marketplace. Additionally, the Federal Trade Commission (FTC) regulates the advertising of herbal products.

• The FDA has also implemented a requirement that dietary herbs and supplements must list the parts of the plant used in a product. Some products also include a very abbreviated form of nutrition information.

• In response to the overwhelming interest in the Internet, the FDA is looking at policy issues that address the type of information being placed on websites and the regulations that may need to be implemented in this area.

• Safety regulations: In addition to regulating label claims, the FDA regulates dietary supplements in other capacities. Supplement ingredients sold in the United States before October 15, 1994 are not required to be reviewed by the FDA for their safety before they are marketed because they are presumed to be safe based on their history of use. These older supplements are not required to present any evidence of clinical safety; the lack of reports on adverse effects is considered sufficient. For a new dietary ingredient (one not sold as a dietary supplement before 1994) the manufacturer must notify the FDA of its intent to market a dietary supplement containing the new dietary ingredient and provide information on how it determined that reasonable evidence exists for safe human use of the product. The evidence of safety for safe human use varies considerably between different products. The FDA can either refuse to allow new ingredients from entering the marketplace or remove existing ingredients for safety reasons.

• For herbs and supplements, once a dietary or herbal supplement has been marketed, the FDA has to prove that the product is not safe in order to restrict its sales or order that the product be removed from market. In contrast, for pharmaceutical drugs, manufacturers must obtain FDA approval by providing convincing evidence that the drug is both safe and effective before being marketed. Herbs and supplements are often presumed safe until proven otherwise, whereas drugs are not.

• The issue of regulation is an area of continuing controversy in the European Union and the United States. At one end of the spectrum, some integrative medicine practitioners such as herbalists maintain that many traditional herbal remedies have a long history of use and do not require the level of safety testing as pharmaceutical drugs or isolated plant constituents (single plant ingredients in an artificially concentrated form). On the other hand, some healthcare providers are in favor of legally enforced quality standards, safety testing, and prescription by a qualified practitioner. Some professional herbalist organizations have made statements calling for a specialized category of regulation specifically designed for herbal products.

• However, herbal remedies prescribed and dispensed either by an herbalist or a naturopathic physician (ND) are regulated as medicines. In order to obtain large amounts of herbs from a distributor, many companies require documentation of the practitioner's certification by a government body or advocacy organization.

• Raw materials validation: The chemical and herbal contents of a product may vary for a variety of reasons. For instance, natural botanical variations may exist between batches of herbs, and variations in manufacturing standards and practices may also alter the levels of plant chemicals and therefore the potential overall quality and medicinal efficacy of an herbal product.

• Species variation due to genetics may affect the proportions of constituents in the product. Factors such as growth and reproduction may influence the plant's state of development when it is harvested for medicinal use. Plant parts, such as the stems, leaves, fruits, roots, and flowers may vary in their potency for medicinal applications. Thus, selection of which plant parts are used will affect the chemical composition of the final product. Finally, the environment in which the plant was grown may vary from season to season. Examples of environmental variation include the temperature, rainfall, day length, altitude, atmospheric composition, and soil quality.

• Manufacturing processes: Variations in the manufacturing processes of an herbal product, such as drying and storage, might also affect its quality and medicinal efficacy. Drying factors include the time between collection and drying, the time allowed for drying, and the temperature used for drying. Storage may also affect the quality of the product as well, as moisture reabsorption and loss of volatile oils may occur during the storage process. Additionally, an herbal product may be inadvertently sterilized or may be infected with molds, bacteria, or insects during storage. Possibilities for adulteration include the mishandling of the product, and harvesting other plants or plant parts not intended for use in the final product.

• Delivery systems: Extraction procedures also have a significant effect on the quality and medicinal efficacy of the product. These factors include the type of solvent used, the amount of plant material exposed to the solvent, the degree of agitation, the temperature used during extraction, and the exposure of the solvent and herb to oxygen and light.

Theory/Evidence

• The gold standard for pharmaceutical testing is repeated, large-scale, randomized, double-blind tests.

• Scientists use several approaches to evaluate dietary supplements for their potential health benefits and safety risks, including an herb's history of use, as well as human, laboratory and animal studies. Studies involving humans (individual case reports, observational studies, and clinical trials) can provide information that is relevant to how dietary supplements are used. Researchers may conduct a systematic review to summarize and evaluate a group of clinical trials that meet certain criteria. A meta-analysis is a statistical review that includes data combined from many clinical trials. It provides an overall view of the relative significance of the findings in one trial as compared to the entire experimental history of an herb to treat a medical condition.

• Most herbal traditions have accumulated knowledge without modern scientific controls to distinguish between placebo effect, the body's natural ability to heal itself, and the actual benefits of the herbs themselves. Many herbs have shown positive results in animal models, in vitro studies, or small-scale clinical tests. The legitimacy of the available randomized, double-blind tests on herbal and dietary supplements may be questioned on methodological grounds. Studies published in peer-reviewed medical journals, such as the Journal of the American Medical Association, receive more consideration than those published in specialized herbal journals.

• Post-marketing monitoring of adverse events and product sampling have been reported in scientific literature.

Safety

• A qualified healthcare provider should be consulted before making decisions about therapies and/or health conditions.

• Many herbs have a long history of use for claimed health benefits. However, some herbs on the market are not proven to be effective and may cause health problems or interact with other herbal products or pharmaceutical drugs.

• Herbal products labeled "natural" have not been proven to be safe or to not have potential adverse effects. For example, the herbs kava and comfrey have been linked to serious liver damage in some clinical reports.

• Herbal supplements may function in the same way as pharmaceutical drugs. Therefore, they may cause medical problems if not used correctly or if taken in large amounts. In some cases, individuals have experienced negative effects even though they followed the instructions on the supplement label. The same dose of an herbal product may affect different individuals in completely different ways.

• Women who are pregnant or nursing should be especially cautious about using herbal supplements or any type of dietary supplement. In most cases, extra caution is also advised when giving dietary supplements or herbs to children and the elderly.

• It is important to consult a health care provider before using an herbal supplement, especially if the patient is taking any medications (whether prescription or over-the-counter). Some herbal supplements are known to interact with medications in ways that cause health problems. Even if a patient's health care provider does not know about a particular supplement, he/she can access the latest medical information on its uses, risks, and interactions.

• The active ingredients in many herbs and herbal supplements are not known. Patients should be aware that herbal and dietary supplements may interact with pharmaceutical medications.

• Herbal and dietary supplements may not always correctly list all the actual ingredients in the final product.

• Some herbal and dietary supplements may be contaminated with undesired substances, including metals, prescription drugs, and microorganisms.

• Patients who think they may be experiencing a reaction to an herbal product should discontinue their use of the product and contact a qualified health care provider immediately.

• The amount of active ingredient in a product may vary between batches of the product. Caution is warranted.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

1. National Nutritional Foods Association. www.nnfa.org

2. National Products Association. www.naturalproductsassoc.org

3. U. S. Food and Drug Administration (FDA). www.fda.gov