Herbals

Herbal Supplements: Considerations in Dental Practice

Richard P. Cohan, AB, DDS, MS, MA, MBA, and Peter L. Jacobsen, PhD, DDS

Copyright 2000 Journal of the California Dental Association.

Over-the-counter natural herb products constitute a rapidly growing market in the United States. As with conventional medications, the health care provider needs to be aware of these products’ effects, side effects, advantageous synergies, and possible or probable adverse drug reactions. This paper will present 20 of the most frequently used herbs in the United States and discuss appropriate precautions and herb-drug interactions of possible concern in clinical dental practice.

Plants (herbs) and naturally derived products from plants (herbal supplements) have been used to enhance health and for medicinal purposes for thousands of years.^a Currently, over-the-counter natural herb products constitute a rapidly growing market in the United States with sales exceeding $2.6 billion in 1999.¹ This is part of a growing consumer trend to embrace alternative or complementary health care modalities.^2,3 Most of these herbal supplements have been utilized for centuries based on empirical and testimonial support for their efficacy. Increasingly, the scientific evidence-based literature is supporting the efficacy and safety of numerous herbs, including St. John’s wort for depression, ginkgo biloba to prevent memory loss and saw palmetto for benign prostatic hyperplasia. In some countries, such as Germany, concentrated herbal extracts are produced under strict "good manufacturing practices" and are available only by prescription,^b whereas in the United State, sourcing, manufacturing practices, purity and potency vary widely, and herbals are primarily sold over the counter and through various types of health practitioners. In recent independent tests, only a minority of herbal and nutracentrical products tested were found to be satisfactory.^c

As with conventional medications, if a patient is using herbal supplements alone or in combination with conventional prescription medications, the health care provider needs to be aware of their effects, side effects, advantageous synergies, and possible or probable adverse drug reactions.^d

This paper will present 20 of the most frequently used herbs in the United States, according to sales data published in magazines such as "Whole Foods" and in the newsletter "Nutrition Business Journal."^e It will focus primarily on appropriate precautions and herb-drug interactions of possible concern in clinical dental practice. It must be emphasized that the adverse drug reactions noted in this paper are largely based on inferences drawn from the documented actions of the herbs. However some adverse drug reaction information is based on in vitro analyses, some on in vivo animal studies and some on in vivo human studies.

The most popular herbal supplements in the United States are promoted and utilized to minimize fatigue and/or depression, boost the immune system, improve circulation and memory, modify blood pressure, control cholesterol levels, and decrease pain. Some are reported to produce myriad effects and are recommended as "adaptogens" to support optimum health. All of these vague nonspecific health claims are based on allowable claims under the Dietary Supplement and Health Education Act of 1994 (Table I).

On Feb. 5, 2000, the claims allowable under the act were broadened to include the prevention, cure, or treatment of some specific "diseases." This change expands the originally allowed safety assertions and "structure/function" claims, such as "improves mental clarity," "enhances immune function," etc. Supplement manufacturer labels can now claim that their products can be used to treat various life-stage conditions such as hot flashes, acne, wrinkles associated with aging, or pregnancy-related morning sickness.

Ironically, as reported in the San Francisco Chronicle on Feb. 14, 2000, this recent expansion of claims comes just 16 months after the Food and Drug Administration announced that it had stopped tracking adverse drug reactions related to nutritional supplements. It had logged 2,621 such adverse events, including 184 deaths possibly associated with herbal supplementation (emphasis added). Of course, these numbers pale in comparison to the more than 100,000 Americans who die each year from "properly prescribed" prescription drugs, and thousands more who experience adverse drug reactions due to medication errors, as reported by various sources who reviewed a University of Toronto study published in 1998. A further warning appeared March 12, 2000, in the San Francisco Chronicle regarding Asian remedies in particular, which may have a higher incidence of impurities or become dangerous when ingested in the form of pills or powders in contrast to their safe use as teas for many centuries. A further concern is that raw or partially processed materials are misidentified with occasional deadly outcomes.

Table 3 lists 20 popular herbal supplements. The table describes some uses of these herbs, their potential for interfering with dental treatment, and known potential interactions with prescription drugs utilized in the dental setting. For example, just recently St. John’s wort was reported to interact with the immunosuppressant drug cyclosporine and the antiretroviral drug indinavir.⁴ Also, some patients may experience increased photosensitivity when St. John’s wort and tetracycline are combined. Patients taking Kava-Kava and alprazolam (a benzodiazapine) may experience a very dangerous synergistic effect, e.g., coma.⁵ If known to the authors, the American Herbal Products Association classification (Table 2) is noted in a separate column of Table 3.

The dentist should recognize that it is often difficult to distinguish the true cause of drug interactions because of the confluence of a variety of factors. These factors include those that are patient-related, such as genetics or comorbid conditions (e.g., sinus infection coexisting with chronic apical periodontitis), and those that are drug-related, including dosage regimens and pharmacokinetic considerations. The latter includes the fact that co-consumption of herbs and over-the-counter or prescription medications (agents) may influence the absorption, distribution, metabolism, or renal elimination of any of these agents. Further, pharmacodynamics (synergistic or antagonistic effects) may be a factor with certain combinations of herbs and mediations.

An excellent series of five articles was recently published in the Journal of the American Dental Association.⁶ The articles review adverse drug reactions in dental practice. Those authors have adapted a table from Tatro⁶ that they titled "Significance Ratings for Dental Drug Interactions" based on the quality of the information used to document the purported drug interactions and an assessment of the severity of these drug interactions, particularly those associated with the use of antibiotics, analgesics, sedatives, local anesthetics, and vasoconstrictors in dental practice. From these ratings, they propose a cumulative rating scale (Table 4). None of the herbal supplements included in Table 3 have been subjected to this sort of detailed scrutiny to date. The information in Table 3 is assembled from what the authors believe to be reliable sources.^8-21

The most common dental precautions are related to side effects of the herbal supplements alone. For example, certain herbals may cause direct effects on oral tissues, including tongue numbness with echinacea, burning of the tongue with garlic, and mouth/throat irritation with high doses of goldenseal. Indirect oral effects include halitosis secondary to garlic, excess saliva associated with goldenseal, and blood pressure increase and irritability secondary to Siberian ginseng.

Some herbal supplement side effects may be confused with side effects of prescription medications used in dentistry. For example, several of these supplements can cause stomach upset. Such gastrointestinal upset can be confused with stomach upset caused by erythromycin prescribed by the dentist. Depending on the situation, the dentist may request the patient discontinue their herbal supplement(s) so as not to cause confusing complications with necessary antibiotic therapy. Some patients may combat this problem by consuming probiotics in pills or powders or via cultured milk or milk-like (soy, rice, etc.) products.

Bleeding is a side effect of herbal supplement use that manifests either via direct effects on capillaries, by interfering with platelet adhesion, or by increasing fibrinolytic activity. Caution is advised regarding the prescribing of aspirin or other nonsteroidal anti-inflammatory drugs to dental patients on anticoagulant medication. But this caution is magnified particularly in patients who also are taking herbs associated with increased bleeding, such as bilberry, cayenne, feverfew, garlic, ginger, ginkgo and Asian (Panax) ginseng. When herbs and prescription drugs have similar biologic and/or pharmacokinetics, the potential for adverse effects is multiplied^f.

Another risk with herbal supplements, as with exposure to nearly all substances, is that of an allergic reaction that can manifest in the oral mucous membranes, gingiva, tongue, or elsewhere. Finally, since the self-dosing of herbal supplements is potentially more

variable than with doctor-prescribed medications, there is a distinct possibility that patients may

use "too much of a good thing," with unpredictable effects.

Discussion

Based on a review of the effects and side effects of these 20 herbal medications and the paucity of reports in the literature, the authors have concluded that there are a few significant herb-drug adverse drug reactions secondary to dental therapy and that, by-and-large, these problems are uncommon. A separate table (Table 5) delineates some of the more common herb-dental drug interactions with which the dentist should be familiar.

As always, dentists need to be vigilant regarding the potential for adverse drug reactions. Such problems may increase when patients taking high doses of herbs for prolonged periods undergo dental procedures that are physiologically stressful, such as dental extractions or periodontal surgery. The type of patient at greatest risk is a patient who is physiologically debilitated or who is on any type of medication that is closely titrated to ensure that it is in the proper physiologic/therapeutic range. Patients taking anticoagulants, some cardiac medications, antidepressants, and some diabetic drugs are at particular risk.

The most important first step in preventing any adverse drug reactions is to identify which conventional and/or natural therapies the patient is using. That information should be gathered as part of a good health history and laboratory tests as necessary to identify all relevant medical problems (Table 6). Appropriate evaluation of health status is fundamental to preventing future problems. In that regard, studies have shown that a surprising number of individuals are taking alternative products.^2,3 These studies have also documented that, for a variety of reasons, these patients do not inform their dentist or physician that they are taking these therapies.^2,3 Because of this lack of reporting, patients should be asked, either directly or as part of the health history form, about the use of herbal products. To facilitate this communication, the health care provider must ensure that the health history interview environment and interview questions are nonjudgmental relative to alternative dental and medical therapies. It is appropriate to specifically ask whether the patient is taking any natural, alternative, or complementary therapies, products or medications. When asked, patients are more likely to cooperate if the dentist is able to discuss why that information is relevant to being able to deliver safe and efficacious dental care. By following the protocol in Table 6, the dentist should effectively elicit potential drug-herb reactions of major concern.

Summary

In summary, some patients, especially those with chronic diseases, are using over-the-counter or provider-prescribed herbs and nutraceuticals. Patients using these agents may or may not alter their use of prescription medications, creating a potential for interactions between the herbs and their prescription drugs. Such interactions may bear directly or indirectly on a patient’s dental management. The dental practitioner should be aware of the most common herbal preparations and their effects, side effects and adverse drug reactions. There are more than a dozen other popular herbs and many other nutraceuticals that have not been evaluated here but may be the subject of a future article.

The practitioner should also create a nonjudgmental office environment and an appropriate health history form to ensure that vital information about the patient’s utilization of complementary drugs such as herbs as well as other treatment modalities is elicited. The medical history should include one or more queries regarding your patient’s use of herbs, vitamins, and other nutraceuticals. When appropriate, precautions should be taken such as medical consultations and blood coagulation studies. Finally, it is imperative to advise patients regarding discontinuation of herbal supplements, especially if any moderate to major adverse drug reactions with any drugs the dentist plans to prescribe are established, probable, or suspected.

Notes

a. Herbs and natural therapeutic products derived from them are classified as "food supplements" by the Food and Drug Administration, and they are referred to throughout this paper as herbs, herbal supplements or herbals. The dentist should be aware that some of the confusion surrounding their uses, efficacy, side effects, etc. is due to differences in the chemical agents present or absent and their concentrations in various preparations of the whole herb and its derivatives. Statements in the lay and medical literature suggesting that herbs are used by patients only to support health or for mild and/or chronic illness are also very misleading and completely discount the fact that some of the most potent prescription medications in the world pharmacopoeia, namely, digitalis, morphine and opium, are derived from plants. That herbs have medicinal actions is recognized worldwide; indeed, they are referred to as phytomedicines (phyto = plant) in Germany.

b. According to Integrative Medicine Communications, publisher of The Integrative Medicine Consult newsletter, in 1995 in Germany some 7 percent of prescription drugs covered by German health insurance were herbal preparations and in 462 monographs covering 360 herbs the German Commission E (equivalent to our FDA) had sorted the herbs into two groups: positive (expected to be safe and useful) and negative (expected to pose safety risks or to have no therapeutic effect).

c. See Consumerlab.com for results of tests on ginkgo biloba and saw palmetto products and DrTheo.com for results of Dr. Jason Theodosakis’ tests on glucosamine/chondroitin products.

d. In this regard, the dentist may wish to consult the Web site of the European Scientific Cooperative on Phytotherapy, which publishes peer-reviewed meta-analysis monographs seeking to establish a pan-European standard for the therapeutic use of botanical drugs throughout the European Union. The Web address is www.exeter.ac.uk/phytonet.

If the dentist is seeking a source closer to home, the American Herbal Products Association has developed a four-category safety rating guide. See Table 2 for a complete description of each classification.

e. The latest survey, published by NBJ in mid-March 2000, reflects results to December 1999. For the second year in a row, echinacea has been displaced by ginkgo biloba, and St. John’s wort has vaulted from 17th place to third place in total sales in four years.

^f Moore PA, et al. The previously referenced JADA article differentiates interaction responses as "summation" (increased, when drugs with similar effects are administered together) or "synergism" (exaggerated increase greater than could be achieved by either drug administered alone at its maximally effective dose).

Authors

Richard P. Cohan, AB, DDS, MS, MA, MBA, is an associate professor of oral diagnosis and treatment planning at the University of the Pacific School of Dentistry.

Peter L. Jacobsen, PhD, DDS, is the director of oral medicine at the University of the Pacific School of Dentistry.

References

1. Nutrition Business Journal, Industry Outlook. Nutrition Business International 4(12) :17, December 1999

2. Eisenberg DM, Kessler RC, et al, Unconventional medicine in the United States. N Engl J Med 328:246-52, Jan 29, 1993.

3. Eisenberg DM, Davis RB, et al, Trends in alternative medicine. Use in the United States, 1990-1997. Results of a follow-up national survey. JAMA 280(18):1569-75, November 11, 1998.

4. Jellin JM, Prescriber’s Letter. Stockton, Calif, Therapeutic Research Center 7(3)18, March 2000.

5. Almeida JC and Grimsley EW, Coma from the health food store: interaction between kava and aprazolam. Ann Intern Med 125(11) :940-41, December 1, 1996.

6. Moore PA, Gage TW et al, Adverse drug interactions in dental practice: professional and educational implications. JADA 130:47-54, January 1999.

7. Tatro DS, ed, Drug interaction facts. Facts and Comparisons, St. Louis, 1997, pp xiv-xvii.

8. Jellin JM, Batz F, Hitchens K, Pharmacist’s Letter/Prescriber’s Letter Natural Medicines Comprehensive Database. Therapeutic Research Faculty, Stockton, CA, 1999:1-1168

9. Brinker F, Herb contraindications and drug interactions. Eclectic Institute, Inc, Sandy, Ore, 1997.

10. The Review of Natural Products Facts and Comparisons, St Louis, Mo

1. Advice about herbal therapies. 1-2, Dec, 1998.
2. Potential herb-drug interactions. 1-5, Dec, 1998.
3. Specific herb-drug interactions. 1-8, Dec, 1998.
4. Therapeutic uses index. 1-15, Dec, 1998.

11. Blumenthal M, ed, The Complete German Commission E Monographs. Integrative Medicine Communications, Boston, 1998.

12. PDR for Herbal Medicines, 1st ed. Medical Economics Co, Montvale, NJ, 1998

13. A Physician’s Reference to Botanical Medicines: IMC’s Concise Review. Integrative Medicine Communications, Boston, Mass, 1999.

14. PhytoNet’s European commission BIOMED program: Determining European standards of safe and effective use of phytomedicines; and ESCOP, the European Scientific Cooperative on Phytotherapy, publisher of Monographs. Web address: www.ex.ac.uk/phytonet, email: phytoNET

16. Newall C, Anderson L, Phillipson JD. Herbal Medicine: A Guide for Health Care Professionals. Pharmaceutical Press, London, 1996

17. Pizzorno JE Jr, Murray MT. Textbook of Natural Medicine, 2nd ed. Churchill Livingstone, London, 1999.

18. McGuffin M, Hobbs C, et al, American Herbal Product Association’s Botanical Safety Handbook. CRA Press, Boca Raton, Fla, 1997.

19. Lininger S, Wright J, et al, The Natural Pharmacy. Prima Health, Rocklin, Calif, 1998.

20. Tyler VE, Herbs of Choice: the Therapeutic Use of Phytomedicinals. Pharmaceutical Press, New York, 1994, pp 182-5.

21. Upton R, St. John’s wort (Hypericum perforatum): Quality control, analytical and therapeutic monograph. American Herbal Pharmacopoeia, Santa Cruz, Calif, July 1997, pp 1-32

22. A Physician’s Reference to Botanical Medicines: IMC’s Concise Review. Integrative Medicine Communications, Boston, Mass, 1999, 1-32.

To request a printed copy of this article, please contact/Richard P. Cohan, AB, DDS, MS, MA, MBA, 2155 Webster St., San Francisco, CA 94115, or at rcohan@sf.uop.edu.

Table 1. Important Components of the Dietary Supplement and Health Education Act of 1994

A. Definition of dietary supplement (Section 3)

1. A product (other than tobacco) that contains one or more of vitamins, minerals, herbs, amino acids, etc.;

2. Is presented as capsules, tablets, liquids, powders, soft gels, etc.;

3. Is not a conventional food or sole item of a meal or diet;

4. Is labeled as a dietary supplement.

B. Safety of dietary supplements

1. Burden of proof is on the FDA

C. Supplement claims and labeling

1. Manufacturer must have evidence/research supporting claims, but they are not required to show it to anyone.

2. FDA has burden of proof that it does not work.

D. Statement of nutritional support (or label)

1. O.K. if a classical nutrient-deficiency benefit is claimed

2. O.K. if role of supplement is to affect structure or function of body

3. Characterizes documented mechanism of action

4. Describes general well-being from consuming the ingredients

5. Prominently displays a BOLD disclaimer that the statements have not been evaluated by the FDA.

E. Supplement Ingredient Labeling and Nutrition Information

1. Must include the following information (or will be removed and considered misbranded):

a. Name of each ingredient;

b. Quantity of each ingredient;

c. Total weight of those ingredients;

d. Identity of the part(s) of plant from which ingredients are derived; and

e. The term "dietary supplement."

Note: Adapted from Israelson L, Summary of the Dietary Supplement Health and Education Act of 1994. In Quarterly Review of Natural Medicine. Natural Product Research Consultants Inc, Seattle, Wash, Spring 1995.

Table 2. American Herbal Products Association Safety Ratings

Class 1 -- Herbs that are safe with appropriate use.

Class 2 -- Herbs that have restrictions:

2a -- For external use only unless otherwise directed by a professional with expertise using the particular substance;

2b -- Not for use during pregnancy unless otherwise directed by a professional with expertise about using the particular substance during pregnancy;

2c -- Not for use while breast-feeding unless otherwise directed by a professional with expertise about using the particular substance while nursing; and

2d -- Other restrictions according to professional guidance.

Class 3 -- Herbs that can be used only with the guidance of a qualified professional (equivalent to requiring a prescription from a physician).

Class 4 -- Herbs with insufficient data for classification.

Ratings adapted from McGuffin M, Hobbs C, et al, Botanical Safety Handbook, 1997.

Table 4. Cumulative Adverse Drug Reaction Ratings Based on Combined Severity and Documentation Ratings.⁶

Table 6. Screening Methods to Prevent Adverse Herb-Other Drug Reactions

Adequate health history, completed by patient, that lists the signs and symptoms of specific diseases and ongoing or prior therapies that can have an impact on dental management.

Questions related to the use of herbs:

1. How long have you been utilizing one or more herbal products?

2. Are you using any herbs specifically for the following purposes?

To promote oral health (teeth, gingiva, mucosa, bone, etc.)

To help manage oral health problems (such as infection, trauma)

3. Describe any side effects or unexpected reactions you have experienced while taking herbs.

4. Which herbs do you utilize on a regular basis (one or more times per week). (Include items such as echinacea, garlic, green tea, etc.)

5. Please indicate the dose and frequency of use of each herb you are utilizing regularly.

6. Have you discontinued the use of any herb product, and if so, why did you do so?

7. Have you substituted herbs for or combined them with over-the-counter or prescription drugs?

Note: Remarks, such as those below in quotations, help the patient to understand the reasons that answers to questions about their use of herbal supplements are important.

"Thank you for your cooperation in completing this health questionnaire. Given our awareness of certain side effects and adverse reactions associated with the use of herbs alone and/or in combination with prescription drugs, we continue to strive to minimize your risks and to provide you safe and effective dental care."

Health history interview, completed by the dentist, that reviews the specific categories such as cardiovascular, infections, hematologic, medications, and allergies that have the most likely impact on dental management.

Laboratory tests, or medical referral, as needed to reveal specific signs and symptom findings, indication of disease, and confirm proper medical control/management such as drug regimen modifications with anticoagulant therapy.