Use of Herbal Products and Potential Interactions in Patients with Cardiovascular Diseases

Effects of commonly used herbal supplements in cardiovascular disease

By Douglas MacKay, ND, and Andrew Shao, PhD

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Reference

Tachjian A, Maria V, Jahangir A. Use of herbal products and potential interactions in patients with cardiovascular diseases. J Am Coll of Cardiol. 2010;55:515-525
 

Design

Review Article. A search of the PubMed and Medline databases was performed for the years 1966 to 2008 using the search terms “cardiovascular agents,” “complementary therapies,” “herb-drug interaction,” and “cardiovascular disease interactions” to identify citations, abstracts, and articles on herbs and cardiovascular disease.
 

Parameters Assessed

The authors of this review article report that the number of visits to complementary and alternative medicine (CAM) providers exceeds those to primary care physicians and that seniors represent a significant portion of CAM users. The authors hypothesize that because the use of herbal products forms the bulk of treatments provided by CAM practitioners, this means that herbal supplement use is particularly common amongst elderly people. In addition, because older individuals consume multiple prescription medications for comorbid conditions, the authors conclude that all of these factors together increase the risk of adverse herb-drug-disease interactions.
 
The authors further declare that despite the paucity of scientific evidence supporting the safety or efficacy of herbal products, their widespread promotion in the popular media and the unsubstantiated healthcare claims about their efficacy drive consumer demand and force even conventional medical practitioners to incorporate CAM therapies into their practices.
 
The aforementioned logic is the platform for the authors’ review, which attempts to highlight commonly used herbs and their interactions with cardiovascular drugs. The authors also discuss their opinions regarding the state of research on herbal dietary supplements, dietary supplement manufacturing, and dietary supplement regulation.
 

Key Findings

This article’s authors summarize their key findings:
Commonly used herbal supplements include St. John’s wort, motherwort, ginseng, ginkgo, grapefruit juice, saw palmetto, danshen, tetrandine and yohimbine, and licorice. St. John’s wort increases the hepatic cytochrome P450 system and thus can reduce levels of medications including cyclosporine. St. John’s wort may also reduce prothrombin time in patients talking warfarin. Motherwort can reduce platelet aggregation and increase risk of bleeding. Ginseng can affect blood pressure, causing both hypertension and hypotension. Ginkgo, when used in combination with antiplatelet agents, can increase bleeding time. Grapefruit juice can inhibit CYP3A4 enzyme and thus increase levels of calcium channel blockers, cyclosporine, and statins. Saw palmetto can increase bleeding risk among patients taking warfarin. Danshen reduces elimination of warfarin and may interfere with digoxin assays. Tetrandine is a vasoactive alkaloid, which can cause hepatotoxicity and renal toxicity. Yohimbine can increase blood pressure. Licorice is often used as an expectorant and can cause pseudoaldosteronism and hypokalemia.
 
Unfortunately, the article consists of numerous errors, unreferenced statements of opinion, outdated references and/or omitted information. It inappropriately extrapolates information on all of CAM use and applies it to herbal supplement use and incorrectly assumes these are one in the same. Perhaps the most egregious of these is the authors’ failure to acknowledge and understand dietary supplement regulation in the United States.1 Contrary to the authors’ assertion, dietary supplements are subject to postmarket surveillance; rigorous manufacturing standards to assure their identity, purity, strength, and composition; and a premarket review process for ingredients marketed after October, 1994.2,3,4,5 CAM therapies may include, but are not limited, to the use of herbal supplements. Other forms of CAM include acupuncture, yoga, and prayer, yet the authors incorrectly equate CAM solely to the use of herbal remedies.6 Furthermore, grapefruit juice (a conventional food), tetrandrine (a plant poison), and aconite (a homeopathic remedy) are all incorrectly categorized as herbal remedies, and the authors’ discussion of these items as “common herbal remedies that produce adverse events” demonstrates a clear lack of expertise that offers no practical or insightful information to the practicing physician.7,8
 
It is, however, agreed that drug-herbal product interactions can be serious and require vigilance on the part of both practitioners and patients.
The risk for potential interaction can be minimized through an open dialogue regarding all prescription and over-the-counter medications, as well as dietary supplements, that are being consumed.
 The risk for potential interaction can be minimized through an open dialogue regarding all prescription and over-the-counter medications, as well as dietary supplements, that are being consumed. Individuals consume greater amounts of all types of prescription and nonprescription products with increasing age.9,10 The authors fail to discuss the increased risk for all types of potential interactions that occur in elderly individuals who practice polypharmacy; instead they use this review as a platform to discuss their opinions and demonstrate their lack of expertise with herbal medicine. Overall, the authors’ failure to assess the totality of the evidence when making sweeping generalizations about the potential interactions, safety, and efficacy of various herbal products is appalling. This is matched only by unsupported statements of opinion (eg, “Widespread promotion of CAM products [is] forcing even conventional medical practitioners to incorporate CAM therapies into their practices.”) The absence of any credible data or references to support these and the many other opinions inserted into this review is disconcerting.
 
It is astonishing as to how the authors and the journal feel it worthy and credible to express unsupported opinions as accepted fact. The American Botanical Council (ABC), a global leader in botanical research and education, has published a letter that identifies additional significant errors in the article.11 ABC points out the lack of Latin names for herbs discussed in the article and the many direct and implied references to “commonly used herbs,” that incorrectly includes plants such as the toxic plant oleander (Nerium oleander, a toxic herb with cardioactive glycosides not sold to consumers in the U.S. dietary supplement market); chan su (presumably dried Chinese toad venom—neither an herb nor generally available as a dietary supplement); and uzara root (Xysmalobium undulatum, an antidiarrhea herbal drug approved in Germany.) None of these are commonly found in the US herbal dietary supplement market. ABC also points out that the authors list Capsicum in a table as being used for shingles, trigeminal, and diabetic neuralgia, when it is actually the U.S. Food and Drug Administration–approved over-the-counter and prescription drug capsaicin, the vanillanoid compound derived from chili peppers (Capsicum spp.), that is used for such purposes.
 

Practice Implications

There is a significant need for additional literature in the emerging field of drug-nutrient interactions and depletions. We have a great opportunity to identify and avoid the risk for unwanted interactions, as well as an opportunity to identify other beneficial synergistic interactions. This particular article has so many flaws and errors that it contributes little to the field and provides minimal practical information for clinicians or researchers. In fact, the authors’ lack of expertise in the subject results in the dissemination of misinformation and incomplete and overreaching conclusions.

About the Authors

Douglas ‘Duffy’ MacKay, ND, is senior vice president, scientific and regulatory affairs for CV Sciences, a market leader in consumer products that contain hemp extracts with cannabidiol (CBD). MacKay previously spent 10 years with the Council for Responsible Nutrition (CRN) where he served as the senior vice president, scientific and regulatory affairs. Before joining CRN, MacKay spent 8 years working as a medical and nutrition expert for 2 companies in the dietary supplement industry. MacKay has published articles in peer-reviewed journals and serves as an Associate Editor for the Journal of Dietary Supplements, as well as the Editorial Board for the Journal of Alternative and Complementary Medicine, Integrative Medicine: A Clinician's Journal, Current Topics in Nutraceutical Research, and the official publication of the American Association of Naturopathic Physicians, Natural Medicine Journal. MacKay also serves on the Advisory Board for the American Botanical Council. He earned his degree in Marine Biology from the University of California, Santa Cruz and his naturopathic medical degree from the National University of Natural Medicine in Portland, Oregon.

Andrew Shao, PhD, is senior vice president, scientific and regulatory affairs, for the Council for Responsible Nutrition (CRN). Shao has an extensive background in human nutrition research with expertise in nutrition policy and dietary supplement regulatory affairs and product development. He has authored or coauthored more than 30 peer-reviewed papers, abstracts, trade journal articles, and industry position papers on topics ranging from nutrient risk assessment to Good Manufacturing Practices. He holds a PhD in nutritional biochemistry and a master of science degree in human nutrition science from Tufts University, and a bachelor of arts in biology from Brandeis University. Shao is a member of the American Society for Nutrition, the American College of Nutrition, the Institute of Food Technologists, and the National Strength and Conditioning Association.

References

  1. Center for Food Safety and Applied Nutrition, Food and Drug Administration, Department of Health and Human Services http://www.fda.gov/Food/DietarySupplements/default.htm. Accessed February 26, 2010.
  2. Dietary Supplement and Nonprescription Drug Consumer Protection Act, Public Law 109–462, 109th Congress, Dec. 22, 2006.
  3. Frankos VH, Street DA, O'Neill RK. FDA regulation of dietary supplements and requirements regarding adverse event reporting. Clin Pharmacol Ther. 2010;87(2):239-244.
  4. 21 Code of Federal Regulations Part 111. Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements; Final Rule, Department of Health and Human Services, Food and Drug Administration. June 25, 2007.
  5. Federal Food, Drug and Cosmetic Act. Sec. 413 [21 USC §350b]. New Dietary Ingredients.
  6. National Center for Complementary and Alternative Medicine, National Institutes of Health, Department of Health and Human Services. http://nccam.nih.gov/health/whatiscam/overview.htm. Accessed February 26, 2010.
  7. Reist RH, Dey RD, Durham JP, Rojanasakul Y, Castranova V. Inhibition of proliferative activity of pulmonary fibroblasts by tetrandrine. Toxicol Appl Pharmacol. 1993;122(1):70-76.
  8. Lockie A. Encyclopedia of Homeopathy. New York, NY: Dorling Kindersley; 2000.
  9. Malone D, Bhandary D. Factors associated with medication use among the elderly. Abstr Acad Health Serv Res Health Policy Meet. 2001;18:157.
  10. Vogel JH, Bolling SF, Costello RB, et al. Integrating complementary medicine into cardiovascular medicine: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2005;46:184-221.
  11. ABC Responds to Article on Herb-Drug Interactions in Journal of the American College of Cardiology. http://cms.herbalgram.org/press/2010/Response_CardiologyArticle.html. Accessed February 11, 2010.