More on Blue Cohosh and Perinatal Stroke
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《新英格兰医药杂志》
To the Editor: In their report on blue cohosh and perinatal stroke, Finkel and Zarlengo (July 15 issue)1 cite a case that is well known to medical herbalists in the United Kingdom and the United States, since it was originally reported to the Food and Drug Administration (FDA) 10 years ago. Furthermore, the suggestion that blue cohosh (Caulophyllum thalictroides) might produce cocaine metabolites is not plausible, given what is known about the plant's chemistry.
If the United States followed the current U.K. recommendations regarding the regulation of herbal medicine,2 it would be illegal for physicians or other practitioners to prescribe herbal medicines unless they had undertaken the equivalent of the training of a medical herbalist (or a naturopath in the United States). This training would also, one hopes, prevent physicians from giving inappropriate herbal advice and recommending inappropriate products.
David Potterton, N.D.
British Naturopathic Journal
Reading RG31 5EB, United Kingdom
bnj.editor@ntlworld.com
References
Finkel RS, Zarlengo KM. Blue cohosh and perinatal stroke. N Engl J Med 2004;351:302-303.
Key recommendations on the regulation of herbal practitioners in the UK: a report from the Herbal Medicine Regulatory Working Group. London: Prince of Wales's Foundation for Integrated Health, 2003.
To the Editor: We are concerned about the interpretation of a positive benzoylecgonine assay in the case reported by Finkel and Zarlengo. There is no published evidence that blue cohosh (C. thalictroides) contains benzoylecgonine or a product that is metabolized to benzoylecgonine. The positive assay in this patient most likely represents either exposure to a tea containing coca leaves (Erythroxylon coca) or to cocaine itself. Inca tea contains approximately 2 to 5 mg of cocaine per tea bag1,2 and unless taken in massive quantities, this tea is unlikely to cause acute harm to either the mother or the infant. Thus, it remains most likely that the patient used cocaine before delivery. Quantitation of the levels of benzoylecgonine in serum or urine would be helpful to differentiate between these two scenarios. It should be noted that the importation, purchase, and use of both coca tea and cocaine are illegal in the United States.
As an aside, the unproved recommendation of the use of cohosh tea for the induction of labor is alarming because of the potential medical and legal consequences, particularly given the relatively unregulated status of dietary supplements in the United States.
Gar M. Chan, M.D.
Lewis S. Nelson, M.D.
New York City Poison Control Center
New York, NY 10016
garchan@pol.net
References
Jackson GF, Saady JJ, Poklis A. Urinary excretion of benzoylecgonine following ingestion of Health Inca Tea. Forensic Sci Int 1991;49:57-64.
Siegel RK, Elsohly MA, Plowman T, Rury PM, Jones RT. Cocaine in herbal tea. JAMA 1986;255:40-40.
The authors reply: We appreciate the comments of Potterton and of Chan and Nelson in response to our report of a neonate with seizures and a stroke after maternal ingestion of blue cohosh tea to initiate labor. Three points warrant classification: was the blue cohosh preparation adulterated or did the mother purposefully take cocaine, what other causes of stroke can be considered in this case, and how should herbal supplements with active biologic properties be regulated and prescribed?
We agree that blue cohosh is not known to contain benzoylecgonine or to be metabolized to this cocaine metabolite. Studies are under way by others to address this possibility (Dentali S: personal communication). There are several possible explanations for the apparent detection of benzoylecgonine in the neonate's urine and meconium and in a decoction of the blue cohosh that the mother used and of a second source of the herb. Since these teas were not metabolized, neither adulteration of benzoylecgonine by cocaine or Inca tea nor maternal cocaine use is supported. Rather, we believe the results reflect detection of a cross-reacting substance by an insensitive immunoassay, an incorrect interpretation of the gas chromatography–mass spectrometry data by the reference laboratory, or both. Clearly, although the positive results of toxicologic testing for benzoylecgonine make it necessary to consider cocaine as a cause of the neonate's stroke, this is not the sole potential explanation and may be a confounding issue. Benzoylecgonine has direct vasoactive properties, presenting another plausible pathophysiologic mechanism for stroke in our case.
We agree that "herbal medicine," as used by Potterton, equates to a drug and warrants both regulatory oversight and proper training by practitioners. The FDA is taking an expanded look at its regulatory role with regard to herbal supplements.1 Health care professionals should be properly schooled in the pharmacology of anything prescribed. Understanding the indications for use, drug and herbal interactions, and potential adverse effects is as important for bioactive herbs as it is for medications. Benzoylecgonine is often recommended in the United States by nurse-midwives, who may have no formal education in this area.2 With the prevalent use of benzoylecgonine and with the recent attention to ephedra in the lay press,3 we thought it timely to report this case to a wide audience.
Richard S. Finkel, M.D.
Children's Hospital of Philadelphia
Philadelphia, PA 19104-4399
finkel@email.chop.edu
Karen M. Zarlengo, M.D.
Littleton Adventist Hospital
Littleton, CO 80122
References
Food and Drug Administration. Dietary supplements containing ephedrine alkaloids: final rule summary, February 2004. (Accessed October 29, 2004, at http://www.fda.gov/oc/initiatives/ephedra/february2004/finalsummary.html.)
McFarlin BL, Gibson MH, O'Rear J, Harman P. A national survey of herbal preparation use by nurse midwives for labor stimulation: review of the literature and recommendations for practice. J Nurse Midwifery 1999;44:205-216.
Stolberg SG. U.S. to prohibit supplement tied to health risks. New York Times. December 31, 2003:1, 14.
If the United States followed the current U.K. recommendations regarding the regulation of herbal medicine,2 it would be illegal for physicians or other practitioners to prescribe herbal medicines unless they had undertaken the equivalent of the training of a medical herbalist (or a naturopath in the United States). This training would also, one hopes, prevent physicians from giving inappropriate herbal advice and recommending inappropriate products.
David Potterton, N.D.
British Naturopathic Journal
Reading RG31 5EB, United Kingdom
bnj.editor@ntlworld.com
References
Finkel RS, Zarlengo KM. Blue cohosh and perinatal stroke. N Engl J Med 2004;351:302-303.
Key recommendations on the regulation of herbal practitioners in the UK: a report from the Herbal Medicine Regulatory Working Group. London: Prince of Wales's Foundation for Integrated Health, 2003.
To the Editor: We are concerned about the interpretation of a positive benzoylecgonine assay in the case reported by Finkel and Zarlengo. There is no published evidence that blue cohosh (C. thalictroides) contains benzoylecgonine or a product that is metabolized to benzoylecgonine. The positive assay in this patient most likely represents either exposure to a tea containing coca leaves (Erythroxylon coca) or to cocaine itself. Inca tea contains approximately 2 to 5 mg of cocaine per tea bag1,2 and unless taken in massive quantities, this tea is unlikely to cause acute harm to either the mother or the infant. Thus, it remains most likely that the patient used cocaine before delivery. Quantitation of the levels of benzoylecgonine in serum or urine would be helpful to differentiate between these two scenarios. It should be noted that the importation, purchase, and use of both coca tea and cocaine are illegal in the United States.
As an aside, the unproved recommendation of the use of cohosh tea for the induction of labor is alarming because of the potential medical and legal consequences, particularly given the relatively unregulated status of dietary supplements in the United States.
Gar M. Chan, M.D.
Lewis S. Nelson, M.D.
New York City Poison Control Center
New York, NY 10016
garchan@pol.net
References
Jackson GF, Saady JJ, Poklis A. Urinary excretion of benzoylecgonine following ingestion of Health Inca Tea. Forensic Sci Int 1991;49:57-64.
Siegel RK, Elsohly MA, Plowman T, Rury PM, Jones RT. Cocaine in herbal tea. JAMA 1986;255:40-40.
The authors reply: We appreciate the comments of Potterton and of Chan and Nelson in response to our report of a neonate with seizures and a stroke after maternal ingestion of blue cohosh tea to initiate labor. Three points warrant classification: was the blue cohosh preparation adulterated or did the mother purposefully take cocaine, what other causes of stroke can be considered in this case, and how should herbal supplements with active biologic properties be regulated and prescribed?
We agree that blue cohosh is not known to contain benzoylecgonine or to be metabolized to this cocaine metabolite. Studies are under way by others to address this possibility (Dentali S: personal communication). There are several possible explanations for the apparent detection of benzoylecgonine in the neonate's urine and meconium and in a decoction of the blue cohosh that the mother used and of a second source of the herb. Since these teas were not metabolized, neither adulteration of benzoylecgonine by cocaine or Inca tea nor maternal cocaine use is supported. Rather, we believe the results reflect detection of a cross-reacting substance by an insensitive immunoassay, an incorrect interpretation of the gas chromatography–mass spectrometry data by the reference laboratory, or both. Clearly, although the positive results of toxicologic testing for benzoylecgonine make it necessary to consider cocaine as a cause of the neonate's stroke, this is not the sole potential explanation and may be a confounding issue. Benzoylecgonine has direct vasoactive properties, presenting another plausible pathophysiologic mechanism for stroke in our case.
We agree that "herbal medicine," as used by Potterton, equates to a drug and warrants both regulatory oversight and proper training by practitioners. The FDA is taking an expanded look at its regulatory role with regard to herbal supplements.1 Health care professionals should be properly schooled in the pharmacology of anything prescribed. Understanding the indications for use, drug and herbal interactions, and potential adverse effects is as important for bioactive herbs as it is for medications. Benzoylecgonine is often recommended in the United States by nurse-midwives, who may have no formal education in this area.2 With the prevalent use of benzoylecgonine and with the recent attention to ephedra in the lay press,3 we thought it timely to report this case to a wide audience.
Richard S. Finkel, M.D.
Children's Hospital of Philadelphia
Philadelphia, PA 19104-4399
finkel@email.chop.edu
Karen M. Zarlengo, M.D.
Littleton Adventist Hospital
Littleton, CO 80122
References
Food and Drug Administration. Dietary supplements containing ephedrine alkaloids: final rule summary, February 2004. (Accessed October 29, 2004, at http://www.fda.gov/oc/initiatives/ephedra/february2004/finalsummary.html.)
McFarlin BL, Gibson MH, O'Rear J, Harman P. A national survey of herbal preparation use by nurse midwives for labor stimulation: review of the literature and recommendations for practice. J Nurse Midwifery 1999;44:205-216.
Stolberg SG. U.S. to prohibit supplement tied to health risks. New York Times. December 31, 2003:1, 14.