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Complementary and alternative medicine for the allergist-immunologist: Where do I start?

2009; Elsevier BV; Volume: 123; Issue: 2 Linguagem: Inglês

10.1016/j.jaci.2009.01.001

1097-6825

Renata J.M. Engler, Catherine M. With, Philip J. Gregory, Jeff M. Jellin,

Respiratory and Cough-Related Research

Complementary and alternative medicine (CAM) therapies present a growing information management challenge for physicians because nearly 40% of their patients may be using and another 50% may be considering use of CAM as part of their healthcare regimen. The National Health Statistics Reports for 2007 described the most commonly used nonvitamin, nonmineral therapy as natural products (eg, herbals at 17.7%). More than 5% of children under the age of 18 years used CAM for allergic conditions including asthma. The amount and quality of information available and concerns about liability risk represent a challenge for most physicians. This review focuses on considerations for approaching a CAM-related consultation, incorporating legal and logistic factors affecting how such an encounter should be approached. A 10-step process is presented that addresses different components of CAM consultations and what should be documented. Access to timely, high-quality information regarding product specific efficacy and safety data, as found in the Natural Medicines Comprehensive Database, is needed to support CAM consultation efficiently. Understanding of serious adverse events associated with CAM is limited; an international need exists for improved safety surveillance and information sharing. Allergy-immunology, as a specialty with expertise in adverse drug reaction evaluation and management, has a unique opportunity to support enhanced CAM-related adverse events evaluations, reporting, and research. Complementary and alternative medicine (CAM) therapies present a growing information management challenge for physicians because nearly 40% of their patients may be using and another 50% may be considering use of CAM as part of their healthcare regimen. The National Health Statistics Reports for 2007 described the most commonly used nonvitamin, nonmineral therapy as natural products (eg, herbals at 17.7%). More than 5% of children under the age of 18 years used CAM for allergic conditions including asthma. The amount and quality of information available and concerns about liability risk represent a challenge for most physicians. This review focuses on considerations for approaching a CAM-related consultation, incorporating legal and logistic factors affecting how such an encounter should be approached. A 10-step process is presented that addresses different components of CAM consultations and what should be documented. Access to timely, high-quality information regarding product specific efficacy and safety data, as found in the Natural Medicines Comprehensive Database, is needed to support CAM consultation efficiently. Understanding of serious adverse events associated with CAM is limited; an international need exists for improved safety surveillance and information sharing. Allergy-immunology, as a specialty with expertise in adverse drug reaction evaluation and management, has a unique opportunity to support enhanced CAM-related adverse events evaluations, reporting, and research. Health care workers trained in allopathic medicine frequently encounter patients who expect patient-centric holistic care with a potential to discuss complementary and alternative medicine (CAM) therapies. This discussion is not a topic that is included in any current medical competency training, and most health care workers have limited knowledge on the subject. Unfortunately, if there is a perceived reluctance or derogatory attitude from the provider, the patient may use CAM therapies without informing the health care team, potentially affecting the benefit and risk of traditional medicines. Ironically, as traditional/conventional medical practices are squeezed by reduced fees and insurance-related barriers to care delivery, the world of CAM therapists and therapies is enjoying an expanding market in which patients are willing to pay out of pocket.1Barnes P.M. Bloom B. Complementary and alternative medicine use among adults and children: United States, 2007.Natl Health Stat Rep. 2008; (Available at:) (Accessed December 22, 2008): 1-24http://nccam.nih.gov/news/2008/nhsr12.pdfPubMed Google Scholar In 2007, almost 4 of 10 adults had used CAM therapy in the past 12 months, with the most commonly used therapies (nonvitamin, nonmineral) including natural products (17.7%) and deep breathing exercises (12.7%).2Barnes P.M. Powell-Griner E. McFann K. Nahin R.L. Complementary and alternative medicine use among adults: United States, 2002.Adv Data. 2004; : 1-19PubMed Google Scholar Although mainstream physicians have confidence in the safety and efficacy of evidence-based medical practices, and managed care organizations cite such evidence in developing treatment pathways, patients seeking CAM treatment are often distrustful of these practices. The Institute of Medicine report on medical errors3Board on Health Care Services—Committee on Identifying and Preventing Medication Errors Preventing medication errors: quality chasm series. Institute of Medicine of the National Academies, the National Academies Press, Washington (DC)2007http://www.nap.eduGoogle Scholar shows that the safety of traditional medical practices can be questioned. Furthermore, a recent literature review of published managed care strategies designed to reduce cost and improve the quality of medication demonstrated an adverse outcome: patients with chronic illness had reduced access to essential medicines due to shift in the cost burden from the managed care organization to the patient.4Lu C.Y. Ross-Degnan D. Soumerai S.B. Pearson S.A. Interventions designed to improve the quality and efficiency of medication use in managed care: a critical review of the literature—2001-2007.BMC Health Serv Res. 2008; 8: 75-87Crossref PubMed Scopus (111) Google Scholar Taken together, these factors may contribute to an atmosphere in which patients may not fully discuss all therapeutic approaches taken with their allopathic healthcare providers. The unintended dilemma for the physician is a limited amount of time, energy, and resources to focus on conventional medicine and a distrust of CAM therapies in the face of limited knowledge and predominantly negative increased risk perceptions for unfamiliar CAM treatments. The unintended dilemma for the patient, who has rapid access to a bewildering array of unfiltered information via the Internet as well as vast promises of success through CAM (or natural) therapies, is a perception that traditional medicine is intimidating and unresponsive to holistic concerns, whereas CAM therapies and therapists are more approachable and/or trustworthy. Given the time and cost constraints found in mainstream medicine, incorporating within the traditional medical encounter the 6 interactive components of the patient-centered clinical method (exploring both disease and the patients' illness experience, understanding the whole person, finding common ground, enhancing the patient-doctor relationship, being realistic, and incorporating prevention and health promotion) is frequently difficult.5Stewart M. Gilbert B.W. Reflections on the doctor-patient relationship.Br J Gen Pract. 2005; 55: 793-801PubMed Google Scholar Ultimately, patients and their caregivers/guardians are seeking to optimize their quality of life and well being as an outcome with a desire to exhaust all treatment options that might improve disease management. The search for "remembered wellness" (p 194) or what many perceive as the placebo effect is frequently the focus of a patient-centric encounter.6Benson H. Friedman R. Harnessing the power of the placebo effect and renaming it "remembered wellness.".Annu Rev Med. 1996; 47: 193-199Crossref PubMed Scopus (128) Google Scholar The measurable clinical and quality of life benefits from the placebo effect may represent at least a part of this "remembered wellness" outcome. Allergy-immunology specialists are faced with the challenge of how to respond practically to the evolving information presented by the expanding world of CAM. The spectrum of positions on CAM within conventional medical practices ranges from "don't ask, don't tell" to establishing a partnership with the patient who may be seeking or is already using CAM therapies. A small percentage of practitioners are incorporating both conventional and nontraditional medical therapies, reflecting a movement toward integrative medicine. Many physicians and health care workers in general are interested in learning more about CAM but are overwhelmed by the amount of information and afraid of entering into any discussions with their patients because of a possible liability risk and/or time requirement. This review focuses on practical considerations for approaching a CAM-related consultation and incorporates updates on legal and logistic factors that affect how such an encounter could be managed and documented. In 1997, Eisenberg7Eisenberg D.M. Advising patients who seek alternative medical therapies.Ann Intern Med. 1997; 127 (Comment in: Ann Intern Med 1998;128:328; author reply 329-30. Ann Intern Med 1998;128:328; author reply 329-30. Ann Intern Med 1998;128:329; author reply 329-30. Ann Intern Med 1998;128:329; author reply 329-30): 61-69Crossref PubMed Scopus (385) Google Scholar published his landmark article titled "Advising patients who seek alternative medical therapies." The passionate responses in subsequent comment letters illustrate the trepidation generated by Eisenberg's step-by-step proposed strategy whereby "conventionally trained medical providers and their patients can proactively discuss the use or avoidance" (p 61) of CAM therapies. Concerns about time and expertise required, resource diversion from proven therapies, and physicians' ethical right to not participate in unproven therapies were just some of the issues. Strategies for shared decision-making that focused on doing no harm and documenting legally defensible behavior on the part of the physician were detailed and reinforced in subsequent articles, including an Institute of Medicine report titled "Complementary and Alternative Medicine in the United States."8Perlman A.I. Eisenberg D.M. Panush R.S. Talking with patients about alternative and complementary medicine.Rheum Dis Clin North Am. 1999; 25: 815-822Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar, 9Buettner C. Kroenke C.H. Phillips R.S. Davis R.B. Eisenberg D.M. Holmes M.D. Correlates of use of different types of complementary and alternative medicine by breast cancer survivors in the Nurses' Health Study.Breast Cancer Res Treat. 2006; 100: 219-227Crossref PubMed Scopus (89) Google Scholar, 10Weiger W.A. Smith M. Boon H. Richardson M.A. Kaptchuk T.J. Eisenberg D.M. Advising patients who seek complementary and alternative medical therapies for cancer.Ann Intern Med. 2002; 137: 889-903Crossref PubMed Scopus (225) Google Scholar, 11Committee on the Use of Complementary and Alternative Medicine by the American Public, Board on Health Promotion and Disease Prevention, Institute of Medicine of the National Academies Complementary and alternative medicine in the United States. National Academies Press, Washington (DC)2005http://www.nap.edu/catalog.php?record_id=11182#tocGoogle Scholar It is noteworthy that the Institute of Medicine report was strongly contested by some,12Barrett S. Institute of Medicine committee issues irresponsible "CAM" report. 2005. Available at: http://www.quackwatch.org/07PoliticalActivities/iomreport.html. Accessed November 2, 2008.Google Scholar but for many clinicians seeking more information and a more intellectually open approach to the study of unconventional therapies (if indicated by positive outcomes), the report represented a needed catalyst for examining CAM therapies for useful and valuable therapeutic options.13Eisenberg D.M. The Institute of Medicine report on complementary and alternative medicine in the United States—personal reflections on its content and implications.Altern Ther Health Med. 2005; 11: 10-16PubMed Google Scholar In the past 10 years, the presence of CAM therapies in different patient populations has increasingly affected a broad range of medical specialties. The 2002 National Health Information Survey, which was limited in the scope of CAM content, showed that 36% of adults used CAM (62% if prayer was included), with follow-up surveys demonstrating continued increases, particularly in the use of herbals.1Barnes P.M. Bloom B. Complementary and alternative medicine use among adults and children: United States, 2007.Natl Health Stat Rep. 2008; (Available at:) (Accessed December 22, 2008): 1-24http://nccam.nih.gov/news/2008/nhsr12.pdfPubMed Google Scholar, 2Barnes P.M. Powell-Griner E. McFann K. Nahin R.L. Complementary and alternative medicine use among adults: United States, 2002.Adv Data. 2004; : 1-19PubMed Google Scholar At the same time, health care provider knowledge of CAM or awareness of CAM use by their patients remains deficient, and an evolving need for a CAM-focused education curriculum in medical schools and residencies is presented in the literature.14Steyer T.E. Complementary and alternative medicine: a primer.Fam Pract Manag. 2001; 8: 37-42PubMed Google Scholar, 15Brokaw J.J. Tunnicliff G. Raess B.U. Saxon D.W. The teaching of complementary and alternative medicine in US medical schools: a survey of course directors.Acad Med. 2002; 77: 876-881Crossref PubMed Scopus (112) Google Scholar, 16Kemper K.J. Vincent E.C. Scardapane J.N. Teaching an integrated approach to complementary, alternative, and mainstream therapies for children: a curriculum evaluation.J Altern Complement Med. 1999; 5: 261-268Crossref PubMed Scopus (25) Google Scholar, 17Kligler B. Gordon A. Stuart M. Sierpina V. Suggested curriculum guidelines on complementary and alternative medicine: recommendations of the Society of Teachers of Family Medicine Group on Alternative Medicine.Fam Med. 2000; 32: 30-33PubMed Google Scholar, 18Maizes V. Schneider C. Bell I. Weil A. Integrative medical education: development of implementation of a comprehensive curriculum at the University of Arizona.Acad Med. 2002; 77: 851-860Crossref PubMed Scopus (73) Google Scholar, 19Prajapati S.H. Kahn R.F. Stecker T. Pulley L. Curriculum planning: a needs assessment for complementary and alternative medicine education in residency.Fam Med. 2007; 39: 190-194PubMed Google Scholar The fact that 50% of Americans would consider trying CAM therapy in addition to conventional therapies is a staggering statistic that makes the need for developing tools and resources to support clinicians in meeting this challenge ever more urgent. Avoidance and denial are no longer sustainable options for conventional practitioners.1Barnes P.M. Bloom B. Complementary and alternative medicine use among adults and children: United States, 2007.Natl Health Stat Rep. 2008; (Available at:) (Accessed December 22, 2008): 1-24http://nccam.nih.gov/news/2008/nhsr12.pdfPubMed Google Scholar Although Eisenberg's work7Eisenberg D.M. Advising patients who seek alternative medical therapies.Ann Intern Med. 1997; 127 (Comment in: Ann Intern Med 1998;128:328; author reply 329-30. Ann Intern Med 1998;128:328; author reply 329-30. Ann Intern Med 1998;128:329; author reply 329-30. Ann Intern Med 1998;128:329; author reply 329-30): 61-69Crossref PubMed Scopus (385) Google Scholar, 8Perlman A.I. Eisenberg D.M. Panush R.S. Talking with patients about alternative and complementary medicine.Rheum Dis Clin North Am. 1999; 25: 815-822Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar, 9Buettner C. Kroenke C.H. Phillips R.S. Davis R.B. Eisenberg D.M. Holmes M.D. Correlates of use of different types of complementary and alternative medicine by breast cancer survivors in the Nurses' Health Study.Breast Cancer Res Treat. 2006; 100: 219-227Crossref PubMed Scopus (89) Google Scholar has laid significant ground work for discussing CAM treatments with patients, controversy continues surrounding the evolving fiscal, ethical, and legal questions that may accompany such discussion. It has been argued that use of CAM treatments is analogous to the situation encountered when US Food and Drug Administration (FDA)–approved drugs are used for off-label indications. However, even when used for off-label indications, FDA-approved therapies have undergone quality control scrutiny and include a safety profile as required by the FDA licensure requirements. In the CAM arena, products such as herbal supplements may not have been manufactured with stringent quality controls, so content, amount, or contaminants present may be confounding variables that affect the outcome of a therapeutic trial. There is a need for standardizing clinical guidelines to address complex medical management, particularly when the level of evidence for a wide range of therapeutic options is variable and multidisciplinary competencies are involved. Yet when patients ask that CAM approaches be included in medical management, there are limited efficacy and safety data available to providers, and most CAM interventions have not been reviewed by broad-based national expert panels, like the National Heart, Lung, and Blood Institute panel, which has developed the National Asthma Education and Prevention Program asthma care guidelines. The National Center for Complementary and Alternative Medicine (NCCAM) at the National Institute of Health (NIH) has supported the development of expanded educational resources and funded research to address the questions related to the efficacy and safety of specific CAM therapies that are necessary for informed clinical choices.20Expanding Horizons of Health Care: Strategic Plan 2005-2009. National Center for Complementary and Alternative Medicine (NCCAM). 2005. Available at: http://nccam.nih.gov/about/plans/2005/strategicplan.pdf. Accessed December 21, 2008.Google Scholar Building on Eisenberg's6Benson H. Friedman R. Harnessing the power of the placebo effect and renaming it "remembered wellness.".Annu Rev Med. 1996; 47: 193-199Crossref PubMed Scopus (128) Google Scholar approach, this article's Table E1 in the Online Repository at www.jacionline.org presents a 10-step summary of the critical elements to be considered in developing a patient-provider partnership that includes CAM therapeutic options.7Eisenberg D.M. Advising patients who seek alternative medical therapies.Ann Intern Med. 1997; 127 (Comment in: Ann Intern Med 1998;128:328; author reply 329-30. Ann Intern Med 1998;128:328; author reply 329-30. Ann Intern Med 1998;128:329; author reply 329-30. Ann Intern Med 1998;128:329; author reply 329-30): 61-69Crossref PubMed Scopus (385) Google Scholar, 8Perlman A.I. Eisenberg D.M. Panush R.S. Talking with patients about alternative and complementary medicine.Rheum Dis Clin North Am. 1999; 25: 815-822Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar The key elements of physician-patient interactions that involve CAM questions and/or therapeutic impact include the following: (1) exploring factors driving interest in CAM; (2) documenting clinical reasons for seeking CAM options; (3) assessing current disease/health status and therapies to date; (4) documenting patient's preferences and reasons; (5) assessing and documenting adequacy of medical evaluation; (6) defining a plan for follow-up visits; (7) providing good risk communications with option for additional consultative visits; (8) acknowledging evolving expectations and goals; (9) educating about new safety and/or efficacy issues related to CAM choices during each visit; and (10) addressing need for further consultations and how these consultations can be optimized (see Table E2 in this article's Online Repository at www.jacionline.org). Nonetheless, significant issues and controversies confront licensed conventional health care providers when considering inclusion (or exclusion) of elements of CAM therapy in medical decision-making. Physicians cannot be forced to adapt any practice with which they do not feel comfortable or they believe is harmful, futile, or too much of an unknown. Providing consultation on CAM therapies may be complex and time-consuming with an initial steep learning curve for both patient and physician. The growing questions about reimbursement for such services cannot be ignored or minimized and require clarification because physicians are stressed by the business of medicine. Gathering reliable, unbiased, and comprehensive data about CAM therapies can be a challenge. In the early 1990s, when patient use of CAM therapies began to accelerate across North America, many clinicians sought data on these therapies to counsel patients better, but there simply was not an easy way to find information. In many cases, reliable information did not exist. It is noteworthy that the first Physicians' Desk Reference on herbal supplements did not appear until 1998.21Physicians' desk reference for herbal medicines.1st ed. Medical Economics, Montvale (NJ)1998Google Scholar Today, the landscape has changed, thanks to expanded research in the area of CAM and improved availability of new resources with rapid cycle information updating. One trustworthy source of information on a wide variety of CAM treatments and interventions is the NCCAM of the NIH. The NCCAM began as the Office for Alternative Medicine with a Congressional funding allocation in 1991. Since that time, support for objective research of CAM interventions has grown, and in 1998, NCCAM was authorized in its current form by Congress. NCCAM oversees a robust research portfolio designed to identify promising CAM approaches and show safety and efficacy. In addition, the NCCAM maintains a large database on CAM treatments, and this is easily available to providers and patients through the NCCAM website (http://nccam.nih.gov/). The Natural Medicines Comprehensive Database is another trustworthy resource for data on CAM treatments that was developed by the publishers of Prescriber's Letter and Pharmacist's Letter in the mid-1990s.22Jellin J. Gregory P. Natural medicines comprehensive database. Therapeutic Research Faculty, Stockton (CA)2008http://www.naturaldatabase.comGoogle Scholar This database provides evidence-based information (using standardized approach to evidence quality/ranking23Ebell M.H. Siwek J. Weiss B.D. et al.Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature.Am Fam Physician. 2004; 69: 548-556PubMed Google Scholar) on CAM that includes practical evidence-based reviews on nearly 1100 natural ingredients (representing many thousands of different generic names, depending on the culture in which it is used) as well as supplements and more than 30,000 commercially available brand name products. It cites more than 16,000 references and includes reviews of more than 2000 new scientific articles for potential inclusion every year. This database includes evidence-based information on traditional Chinese medicine, Kampo medicine, Ayurvedic medicine, and several alternative treatment modalities such as acupuncture, reflexology, and many others. The database also provides an evidence-based rating on commercially available CAM products based entirely on the evidence for safety and effectiveness for product ingredients plus evidence for product quality using data from international regulatory bodies. Research for the Natural Medicines Comprehensive Database is critically assessed on the basis of key factors such as randomization, allocation concealment, adequate blind, and other factors using the principles from the Cochrane Collaboration24Higgins J, Green S, editors. Cochrane handbook for systematic reviews of interventions. February 2008, Version 5.0.0. Available at: http://www.cochrane-handbook.org/. Accessed January 1, 2009.Google Scholar and is regularly maintained and updated. Research results are selected that have the potential to provide relevant information related to safety, effectiveness, and clinical use, mechanism of action or pharmacology, interactions with drugs, laboratory test interference, or other practice information that is relevant to health professionals. After the initial search and review of the literature, new research findings are identified through systematic searching of literature for updated data on specific CAM approaches. Examples of information regarding CAM approaches for allergic diseases, interactions of CAM treatments with FDA-approved drugs, and CAM treatments that exacerbate allergic disease are shown in Table I, Table II, Table III. A more complete description of this database can be found at http://www.naturaldatabase.com.Table ISelected natural medicines used for atopic conditionsNatural medicineUse/indicationEffectiveness ratingPractice pearlBifidobacteriaEczemaPossibly EffectiveSome evidence in infants only.Bitter orangeAsthma/allergic rhinitisInsufficient Evidence to RateBitter orange contains a stimulant similar to ephedra; linked to several reports of severe adverse events including myocardial infarction.ButterburAllergic rhinitisPossibly EffectiveSome evidence that a specific butterbur extract is comparable to Zyrtec (cetirizine; McNeil-PPC, Raritan, NJ) and Allegra (fexofenadine; Sanofi-Aventis, Bridgewater, NJ); a specific extract (Ze 339) standardized to 8 mg total petasine has been used.CholineAsthmaPossibly EffectiveFish oilAsthmaPossibly EffectiveBenefits seen in children but not adults.HoneyAllergic rhinitisInsufficient Evidence to Rate; preliminary evidence suggests that honey does not improve symptomsLactobacillusEczema/atopic diseasePossibly EffectiveSpecific product used in clinical trials – Lactobacillus GG (Culturelle, Amerifit Brands, Cromwoll, Conn)MagnesiumAsthmaPossibly EffectiveIntravenous magnesium beneficial for acute attacks; by mouth magnesium supplements do not improve chronic asthma.Phleum pratenseAllergic rhinitisPossibly EffectiveA specific standardized product (Grazax, ALK- Abelló, Denmark) has been used.PycnogenolAsthmaPossibly EffectiveBenefits seen in children.QuercetinAsthma/allergic rhinitisInsufficient Evidence to RateThought to work similarly to cromolyn; however, no clinical data to support use.SerrapeptaseBronchitis, sinusitisInsufficient Evidence to Rate; preliminary evidence suggests some benefitSinupret (Bionorica, San Clemente, Calif)SinusitisPossibly EffectiveThis is a brand name product containing 5 herbal ingredients.Stinging nettleAllergic rhinitisInsufficient Evidence to Rate; preliminary evidence suggests some benefit.If used, stinging nettle should be started at the first sign of symptoms.Tinospora cordifoliaAllergic rhinitisPossibly EffectiveA specific extract (Tinofend, Verdure Sciences, Noblesville, Ind) has been used.Vitamin C/citrus fruitsAsthmaInsufficient Evidence to Rate; preliminary evidence that eating vitamin C–rich fruits 1-2 times/wk improves lung function; some conflicting data; preliminary evidence that vitamin C supplements might decrease exercise-induced asthmaGrapefruit, kiwi fruit, orange, and other fruits.Whey proteinAtopic diseasePossibly EffectiveSome evidence in infants only.From Jellin J, Gregory P, editors. Natural medicines comprehensive database. Stockton (CA): Therapeutic Research Faculty; 2008. Available at: http://www.naturaldatabase.com.22Jellin J. Gregory P. Natural medicines comprehensive database. Therapeutic Research Faculty, Stockton (CA)2008http://www.naturaldatabase.comGoogle Scholar Accessed January 1, 2009. Not a complete list. For additional data, go to http://www.naturaldatabase.com. Open table in a new tab Table IIPotential interactions between selected natural medicines used for atopic conditions and conventional medicinesNatural medicineInteractionsMechanismInteraction ratingBitter orangeQT-interval–prolonging drugsStimulant drugsBitter orange contains a stimulant called synephrine. Combining bitter orange with drugs that prolong QT-interval might increase the risk of arrhythmia; combining with other stimulants can result in additive stimulant activity.Moderate; be cautious with this combination.Fish oilAntiplatelet/anticoagulant drugsOrlistat (Xenical, Roche, Nutley, NJ; Alli, GlaxoSmithKline, London, United Kingdom)High-dose fish oils (>3 g/day) can modestly inhibit platelet aggregation and might increase the risk of bleeding; however, there are conflicting data.Orlistat might decrease the absorption of fish oils when they are taken together.Moderate; be cautious with this combination.Grape extractCytochrome P450 1A2 substrations (eg, Plavix, Bristol-Myers Squibb, New York, NY; Valium, Roche; Zyprexa, Eli Lilly and Co, Indianapolis, Ind; warfarin, many others)Grape juice induces cytochrome P450 1A2 drug metabolism and might decrease levels of substrates of this enzyme; although grape juice might interact with these medications, it is not known whether grape extract has the same effect.Moderate; be cautious with this combination.Stinging nettleDiabetes drugsHypertension drugsWarfarin (Coumadin)Stinging nettle might lower blood glucose levels and could have additive effects when combined with diabetes drugs.Stinging nettle might lower blood pressure and could have additive effects when combined with blood pressure drugs.Stinging nettle contains vitamin K andtherefore might decrease the anticoagulant effects of warfarin.Moderate; be cautious with this combination.From Jellin J, Gregory P, editors. Natural medicines comprehensive database. Stockton (CA): Therapeutic Research Faculty; 2008. Available at: http://www.naturaldatabase.com.22Jellin J. Gregory P. Natural medicines comprehensive database. Therapeutic Research Faculty, Stockton (CA)2008http://www.naturaldatabase.comGoogle Scholar Accessed January 1, 2009. Not a complete list. For additional data, go to http://www.naturaldatabase.