Letters to the Editor

Herbal Remedies

TO THE EDITOR: In Dr. Cupp's article, "Herbal Remedies: Adverse Effects and Drug Interactions,"¹ ginseng is implicated as a cause of decreased response to warfarin. Danshen, another widely used herbal medication, has the opposite effect when used with warfarin: it potentiates the anticoagulant action of warfarin.^2,3

Danshen is a popular herbal medication often used to treat various medical complaints, particularly those associated with coronary artery disease, in the Chinese community.^3,4 Thus, physicians should be alert to the possibility of this drug interaction when anticoagulation control becomes difficult or deviates from the optimum, and when no other causes are apparent.^3,5

TSUNG O. CHENG, M.D.
The George Washington University Medical Center
2150 Pennsylvania Ave., N.W.
Washington, DC 20037

REFERENCES

1. Cupp MJ. Herbal remedies: adverse effects and drug interactions. Am Fam Physician 1999;59: 1239-44.
2. Yu CM, Chan JC, Sanderson JE. Chinese herbs and warfarin potentiation by 'Danshen'. J Intern Med 1997;241:337-9.
3. Cheng TO. Warfarin danshen interaction [Letter]. Ann Thorac Surg 1999;67:894.
4. Huang M-X, Chen S-X, Cheng TO: Herbal pharmacology in cardiovascular therapeutics. In: Cheng TO, ed. The international textbook of cardiology. New York: Pergamon Press, 1986:1060-71.
5. Izzat MB, Yim AP, El-Zufari MH. A taste of Chinese medicine. Ann Thorac Surg 1998;66:941-2.

TO THE EDITOR: Complementary or alternative medicine has become increasingly popular among many patients, as evidenced by the fact that approximately one in three Americans uses herbal products as part of a therapeutic regimen.¹ Findings from a 1997 survey revealed that total patient visits to alternative medicine practitioners exceeded visits to primary care physicians during that year; the out-of-pocket expenses paid to alternative medicine practitioners surpassed the out-of-pocket expenditures for all hospitalizations in the United States.¹ Burgeoning interest in botanical medicine has led to greater scientific scrutiny concerning product safety and efficacy, and the adverse effect potential of drugs and herbs, as discussed in Dr. Cupp's article.²

Although touted as "natural," herbal medicines should not be considered inactive or benign. For example, many products contain several different compounds with variable concentrations depending on plant genetics, growth and harvest conditions, processing techniques and plant parts used. The potential for contamination and adulteration, which occurs more frequently with imported medicinals or raw herbs, must also be considered. The association between dosing and toxicity is especially problematic in pediatric patients.^3,4 Unfortunately, prospective studies of the long-term efficacy of alternative medicine are limited. However, the U.S. Food and Drug Administration has identified 250 herbs as "generally recognized as safe" by using information derived from their historical use and lack of reported side effects.⁵

It is crucial that primary care physicians ask patients about their use of botanical remedies, because most patients will not disclose such information. In some cases, having such information may be lifesaving, as evidenced by the following case. A young immigrant woman presented with a history suggestive of a viral syndrome. However, her vital signs were suspicious: blood pressure, 100/80 mm Hg; pulse rate, 47 beats per minute; respiratory rate, 16 breaths per minute; and temperature, 38.9°C (102°F). The patient was sent home with the reassurance that this was a benign illness, only to return several hours later with a deterioration of her condition. During her second visit, it was disclosed that she had been taking oleander leaves in tea in order to relieve her menstrual pain, which began at the same time as her upper respiratory complaints. The lesson from this case was clear: an appropriate history, especially in patients from different cultures, should include an inquiry about the use of home remedies.

The oleander plant is a beautiful, ubiquitous plant found in the western United States, which can cause bradycardia and heart block similar to that seen with digoxin toxicity. In this situation, the patient's slow heart rate should have raised concerns about another diagnosis, because most febrile illnesses cause tachycardia instead of low heart rate. Simply questioning the patient about what treatments had been used at home may have uncovered the reason for the abnormal cardiac response. The increased number of patients born outside of the United States who are using the U.S. health care system has brought an increased risk of adverse effects from traditional or indigenous therapies. In response, family physicians should learn about the most common herbal products and the toxic reactions they can cause.

KIM BULLOCK, M.D.
Providence Hospital
1150 Varnum Street, N.E.
Washington, DC 22017

REFERENCES

1. Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 1998;280: 1569-75.
2. Cupp MJ. Herbal remedies: adverse effects and drug interactions. Am Fam Physician 1999;59: 1239-45.
3. Kemper KJ. The holistic pediatrician: a parent's comprehensive guide to safe and effective therapies for the 25 most common childhood ailments. New York: HarperCollins, 1996.
4. Kemper KJ. Seven herbs every pediatrician should know. Contemp Pediatr 1996;13:79-93.
5. O'Hara M, Kiefer D, Farrell K, Kemper K. A review of 12 commonly used medicinal herbs. Arch Fam Med 1998;7:523-36.

TO THE EDITOR: Dr. Cupp's article begins the important task of addressing herb/drug interactions,¹ but her article may be misleading. For example, Dr. Cupp states that "herbal products are not tested with the scientific rigor required of conventional drugs . . ." and "herbal health products aren't tested to be sure they're safe, so they may cause problems (patient information sheet)."¹ However, she fails to address the many recent reviews and meta-analyses^2-5 that assess double-blind, placebo-controlled trials of botanical medicines that point to convincing evidence of efficacy. Also, a complete discussion of the subject should mention the many economic⁴ and political reasons for the historical lack of scientific studies on herbal medicines in the United States. Many of the science and efficacy reviews have taken place in other countries.⁶

We agree that patients and practitioners need to be educated about the safe use of herbal medicines. Special emphasis should be placed on plants that have well-documented adverse effects or contraindications, such as Ephedra species when taken in high dosages or in certain medical conditions. It is also the responsibility of scientists and specialists in botanical medicine to avoid confusion such as that created by Dr. Cupp's warnings (see patient information sheet) about the dangers of plant pollen adulterants (has any such problem ever been documented?) or by her pointing out that herbs "aren't natural to the human body," a statement that was not well defined and doesn't help patients learn how to stratify risk or make well-informed decisions about natural and synthetic substances.

Furthermore, it would be helpful to patients and practitioners if the herbal side effect profiles were qualified and put into the context of their pharmaceutical counterparts. Most herbal products are extremely safe in comparison with their pharmaceutical counterparts, and adverse outcomes, such as the list for St. John's wort, are rare. While the annual mortality rate attributable to conventional medicine numbers in the tens of thousands, herbal medicines cause a dozen or so deaths each year. With similar numbers of people at risk, there can be little doubt about which type of treatment poses a higher risk. We need this kind of objective information to help make intelligent decisions about current use of botanical medicines and to illustrate the need for future research.

DAVID S. KIEFER, M.D.
Swedish Family Medicine
1401 Madison St., Ste. 100
Seattle, WA 98104
BRUCE BARRETT, M.D., PH.D.
Department of Family Medicine
University of Wisconsin-Madison
Madison, WI 53706

REFERENCES

1. Cupp MJ. Herbal remedies: adverse effects and drug interactions. Am Fam Physician 1999;59: 1239-45.
2. O'Hara M, Kiefer D, Farrell K, Kemper K. A review of 12 commonly used medicinal herbs. Arch Fam Med 1998;7:523-36.
3. Kemper KJ. Seven herbs every pediatrician should know. Contemp Pediatr 1996;13:79-93.
4. Winslow LC, Kroll DJ. Herbs as medicines. Arch Intern Med 1998;158:2192-9.
5. Wilt TJ, Ishani A, Stark G, MacDonald R, Lau J, Mulrow C, et al. Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review. JAMA 1998;280:1604-9 [Published erratum appears in JAMA 1999;281:515].
6. Blumenthal M, ed. The complete German Commission E monographs: therapeutic guide to herbal medicines. Austin, Tex.: American Botanical Council, 1998.

IN REPLY: Drs. Kiefer and Barrett are correct that meta-analyses and clinical studies of some herbal products exist. Unfortunately, such information is unavailable for the vast majority of herbal products and therapeutic claims. The U.S. Food and Drug Administration requires studies that are appropriately designed to assess drug safety and efficacy. Usually, double-blind, placebo-controlled studies involving thousands of patients are required. Inclusion and exclusion criteria must be delineated, and statistical methods used to assess the data must be appropriate. Meta-analyses and reviews of studies that may not have been appropriately designed are not substitutes for this process. In addition, the results of studies using one herbal preparation may not be applicable to other herbal products that were prepared using a different method and by a different manufacturer.

Drs. Kiefer and Barrett state that "herbal medicines cause a dozen or so deaths each year," but do not reference this statement. This lack of data underscores the importance of clinicians reporting problems associated with herbal products via the U.S. Food and Drug Administration's MedWatch program. Previously undocumented adverse effects and drug interactions continue to be reported in association with herbal products. For example, although St. John's wort has been used for many years worldwide, its ability to induce theophylline metabolism was just recently recognized.¹

Drs. Kiefer and Barrett are not comfortable with my statement that herbs are not natural to the human body. My point was that "natural" is not synonymous with "safe." Just because the chemicals in herbs are manufactured by plants, it does not make them safer than chemicals manufactured in the laboratory. Patients have the right to know this.

Patients also have the right to know exactly what is in the products that they purchase. Drs. Kiefer and Barrett ask if there is documentation for the statement concerning pollen contamination. I do not have documentation for this because this information was added later by the editors. However, the warning does not state that this has occurred, only that it might occur. Furthermore, contamination of herbal products by heavy metals,² benzodiazepines,³ steroids, NSAIDs, hepatotoxic herbs⁴ and digitalis⁵ is well documented.

I appreciate the additional information provided by Drs. Cheng and Bullock regarding oleander and danshen, and caution readers that my article is not meant to be a comprehensive, all-inclusive review of all of the adverse effects and interactions that have been reported with herbal remedies.

MELANIE JOHNS CUPP, PHARM. D., BCPS
West Virginia University School of Pharmacy
1124 HSN, P.O. Box 9550
Morgantown, WV 26506-9550

REFERENCES

1. Nebel A, Schneider BJ, Baker RK, Kroll DJ. Potential metabolic interaction between St. John's wort and theophylline [Letter]. Ann Pharmacother 1999;33: 502.
2. Levitt C, Godes J, Eberhardt M, Ing R, Simpson JM. Sources of lead poisoning[Letter]. JAMA 1984;252: 3127-8.
3. Anonymous. FDA warns consumers against taking dietary supplement "Sleeping Buddha." Available from: http://vm.cfsan.fda.gov/~lrd/hhbuddha.html. Accessed 1999 May 17.
4. Bielory L, Lupoli K. Herbal interventions in asthma and allergy. J Asthma 1999;36:1-65.
5. Anonymous. FDA warns consumers against dietary supplement products that may contain digitalis mislabeled as "plantain." Available from: http://www.fda.gov/bbs/topics/NEWS/NEW00570.html. Accessed: 1999 May 17.

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Waddell Signs in the Evaluation of Back Pain

TO THE EDITOR: The recent article on the evaluation and treatment of herniated lumbar disc by Humpreys and Eck¹ is excellent in most respects, but clarification of a few points might be useful. The authors correctly note that bed rest is often overused for musculoskeletal disorders, but both studies they cited excluded patients with acute sciatica from their research populations.^2,3

The assertion that nonorganic physical signs (Waddell signs) "may identify patients with pain of a psychologic or socioeconomic basis" seems wide of the mark. Biologic and psychosocial factors often coexist; the presence of one does not exclude the other. Waddell and colleagues⁴ have cautioned medical personnel repeatedly about the hazards of overinterpreting the significance of the signs that bear his name; they state that "Isolated signs should not be overinterpreted. Multiple signs suggest that the patient does not have a straightforward physical problem, but that psychological factors also need to be considered. . . . Behavioral signs are not on their own a test of credibility or faking."

A more complete discussion of the straight-leg raising test would have been helpful. This test is classically performed with the patient lying in the supine position. The examiner places a hand under the patient's heel and lifts the fully extended leg until pain is reported or increasing resistance is felt. The normal limit in subjects without sciatic nerve embarrassment may be anywhere between 60 and 120 degrees depending on the patient's age, habitus and physical condition. The amount of pain-free flexion is less important than variation between legs. Dorsiflexing the foot of a patient with sciatica when the hip is flexed to the limit of comfort may make the pain worse; plantar flexion should not.

A patient's anxiety or other behavioral factors can lead to a falsely abnormal supine straight-leg raising test. This situation can usually be clarified by testing the patient in the seated position. It is sometimes helpful to note the supine test findings and move to other parts of the examination for a few minutes. Then, with the patient seated on the examining table with his or her legs hanging over the side, the examiner might say, "I need to cheek your knees," or something similar. While seeming to check the knee ligaments, or perhaps while actually doing so, the examiner extends each leg at the knee. The ability to extend the knee joint fully is the equivalent of a normal supine straight-leg raising test. A significant discrepancy between the results of the two procedures is the equivalent of a positive Waddell's sign.

ROBERT D. GILLETTE, M.D.
32 Audubon Ln.
Poland, OH 44514-1922

REFERENCES

1. Humphreys SC, Eck JC. Clinical evaluation and treatment options for herniated lumbar disc. Am Fam Physician 1999;59:575-82.
2. Deyo RA, Diehl AK, Rosenthal M. How many days of bed rest for acute low back pain? A randomized clinical trial. N Engl J Med 1986;315:1064-70.
3. Malmivaara A, Hakkinen U, Aro T, Heinrichs ML, Koskenniemi L, Kuosma E, et al. The treatment of acute low back pain--bed rest, exercises, or ordinary activity? N Engl J Med 1995;332:351-5.
4. Main CJ, Waddell G. Behavioral responses to examination. A reappraisal of the interpretation of "nonorganic signs." Spine 1998;23:2367-71.

Send letters to Jay Siwek, M.D., Editor, American Family Physician, 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672; fax:913-906-6080; e-mail: afplet@aafp.org. Please include your complete address, telephone number and fax number. Letters should be double-spaced, fewer than 500 words and limited to one table or figure and six references. Please submit a word count. Letters submitted for publication in AFP must not be submitted to any other publication. Possible conflicts of interest must be disclosed at time of submission. Submission of a letter constitutes transfer of copyright to the American Academy of Family Physicians. The editors may edit letters to meet style and space requirements.

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