Dietary supplements are among the most commonly used complementary and alternative medical therapies in the United States, with sales reportedly exceeding $20 billion in 2005. Newspapers, magazines, and the mass media feed our curiosity for new supplements and ways to manage our health on a daily basis. New dietary supplement formulations flood the shelves of pharmacies, health food stores, retail chains, and Internet outlets. Consumers want to know what works and are willing to pay for products that may make them feel better. However, consumers are also growing frustrated with inconsistencies in product quality and perceived lack of regulatory oversight. Surveys indicate that health care professionals are both interested in learning about, and concerned over the widespread use of, dietary supplements. This is not surprising given the contradictory scientific data and provocative titles in medical journals linking supplements with dangerous adverse events and lack of efficacy. Although many supplements are safely used by the public, there is little question that the complex chemistry of botanicals and multi-ingredient formulations may have profound effects, both beneficial and harmful, on our human physiology.

Dietary supplements marketed in the United States before passage of the Dietary Supplements Health Education Act (DSHEA) in 1994 are not required to demonstrate safety or efficacy, an a priori belief that since these products were already in the marketplace, one could assume a certain level of safety. The assumption that these products are safe and free from adverse effects may lead to excessive dosing, concomitant use with prescription and over-the-counter (OTC) medications, and failure to disclose supplement use to health care providers. According to a large, federally sponsored survey, approximately 28 million Americans are taking dietary supplements with their prescription medications, and 69% of them have not told their primary care provider. As a physician who is also an herbalist, I find that patients generally feel comfortable talking to me about their use of supplements and alternative therapies. Yet, even with my training, I constantly brush up against the edge of my knowledge and experience when a patient asks if taking ginkgo, ginseng, saw palmetto, hawthorn, coenzyme Q10, magnesium, l-carnitine, multivitamin, and a Chinese herbal formulation called xin li shu kang wan will interact in any way with his quinapril, amiodarone, clopidrogel bisulfate, simvastatin, and esomeprazole! A difficult question for anyone to answer, but even more for those without any formal training in natural products and limited to the typical 12- to 15-minute patient encounter. As was shown with St. John's wort, however, herb-drug interactions can occur and can be very serious.

It would be easy to assume that if adverse events and interactions with drugs were really a problem, it would be glaringly apparent given the number of people using these products. However, as Chair of the United States Pharmacopoeia Dietary Supplements Information Expert Committee, I can attest to the difficulty in determining and establishing safety for many of the dietary supplement ingredients in the marketplace. Many botanicals and nutritional supplements lack detailed pharmacokinetic and pharmacodynamic data. The adverse event reporting systems that are currently in place for drugs are woefully inadequate for monitoring dietary supplement products, given the vast number of complex and unique formulations in the marketplace and the variety of names used on the label (i.e., Latin binomial, common, foreign language). This makes it almost impossible to enter, retrieve, or analyze information from electronic databases when an adverse event is suspected. Unlike prescription and OTC medications, it can be difficult to ascertain if the adverse event was caused by the ingredient(s) declared on the label, or actually resulted from the accidental or intentional adulteration, substitution, or contamination of the product with a toxic botanical, heavy metal, or pharmaceutical agent. Accurate identification of the dietary supplement is essential for determining causality; however, the point of contact for most serious adverse events is generally a physician who has neither the training nor the funds for collecting, submitting, and paying a laboratory with expertise in analyzing complex botanical or supplement products. This further complicates evaluation of adverse event reports in the medical literature, because product identity is seldom verified. In most cases, the evidence for causality is based primarily on the fact that the supplement cannot be excluded, rather than clear evidence of toxicity. And yet, in the absence of better pharmacological data and an optimal adverse event reporting system, case reports remain a necessary, if problematic, mechanism for monitoring safety.

With the primary emphasis on adverse interactions, the topic of beneficial interactions has received little attention. It is well recognized that statin medications deplete coenzyme Q10 in the body. Preliminary evidence suggests that administering 50 to 100 mg per day of the supplement may reduce the myopathies that are reported by about 20% of patients using this class of lipid-lowering medications. A growing body of evidence supports the administration of glutamine during chemotherapy to prevent neuropathy, whereas selenium was shown to reduce the nephrotoxicity associated with cisplatin. Low serum folate levels decrease the effectiveness of antidepressant medications. An integrative approach would utilize therapies that reduce or mitigate the adverse effects of medications deemed necessary for the patient whenever possible.
It is within this climate that I enthusiastically welcome this book, a collaboration written by experienced clinicians within the fields of conventional, integrative, and natural medicine for health professionals who wish to counsel their patients effectively on the safe and beneficial use of dietary supplements. As the title suggests, this book addresses herb-drug interactions, nutrient-drug interactions, and drug-induced nutrient depletions in a clinically oriented, integrative manner. The authors demonstrate an appropriate balance between recommendation and risk based on the overall strength of the scientific evidence and their own clinical experience. The text is well referenced, balanced, and objective, and the use of icons and summary tables allows the clinician to quickly identify areas of potential risk, as well as potential benefit. This book is a major contribution to the field of integrative medicine and an invaluable resource to practitioner and researcher alike.

Tieraona LowDog, MD
Director of Education, Program in Integrative Medicine
Clinical Assistant Professor, Department of Medicine
University of Arizona College of Medicine
Chair, United States Pharmacopoeia Dietary Supplements
Information Expert Panel

Dedication

To those who have inspired us, who have welcomed us, who have taught, and supported us, in our challenges, growth, shortcomings, and successes;
Those with whom we share our lives and work, with whom we play, create, grow, and endure, as we evolve together, in our understanding, appreciation, and respect for one another;

Those who come to us, who trust and challenge us, who ask difficult questions and want honest responses, who honor us with the challenge and privilege of serving them in their healing and self-discovery;
That we may care for each and all, including ourselves, just a little bit better, working together in a sincere effort toward healing, truth, and peace in every interaction.

Acknowledgments

Reviewers:

Ruth Bar Shalom, ND, LAc
Timothy C. Birdsall, ND
Carlo Calabrese, ND, MPH
Hyla Cass, MD
Subhuti Dharmananda, PhD
Michael F. Holick, PhD, MD
Alena M. Langsjoen, MS
Peter H. Langsjoen, MD, FACC
Rick Marinelli, ND, MAcOM, LAc
Russell B. Marz, ND, LAc
Lewis Mehl-Madrona, MD, PhD
William A. Mitchell, ND
Shauna Rey, ND
Peggy M. Rollo, ND, LAc
Kia Sanford, MS, CN
Lori Beth Stargrove, ND
Maret G. Traber, PhD
Don West, RPh

Special gratitude and appreciation for inspiration, participation, support, and patient perseverance to:

Lori Beth Stargrove, ND
Jillellen McKee, DO
Joanne Chase
The Bebel and Kopacz, Isenberg and Sternheim families
Raphael B. Stargrove
Tara R. Stargrove
Sage S. Stargrove
Richard W. Bebel
Mary A. Bebel
Norbert Isenberg, PhD
Edith Isenberg, RN
Stephanie Sandstrom
Owen Treasure
Kellie White
Jennifer Watrous
Anne Altepeter
Roger L. McWilliams
Inta Ozols
Linda Duncan
Sara Snyder
Larry Park
Claire de la Mer
Marilyn Wasson
Kelley Schaefer-Levi
Jacob S. Gill
Tatiana Lifshitz
David Weitzer, LMT
Janice Weitzer, LMT
Satya Ambrose, ND, LAc
Duncan Soule, MD
David Young, DC
Grant Dawson, DC
John Bastyr, ND
William Turska, ND
Robert Broadwell, ND, LAc
William A. Mitchell, ND
Joseph E. Pizzorno, Jr, ND
Jared L. Zeff, ND, LAc
Tieraona Low Dog, MD
Wayne Jonas, MD
David S. Riley, MD
Pamela Snider, ND
John Weeks
Robert Stern, DC, CFE
Bruce Canvasser, ND
Heiner Freuhauf, PhD, LAc
Clyde Jensen, PhD
Eric F. Stephens, DAOM, LAc
David M. Eisenberg, MD
Robert Scholten, MSLIS
Ted J. Kaptchuk, OMD
Steve Austin, ND
Timothy C. Birdsall, ND
Alan R. Gaby, MD
Jonathan V. Wright, MD
Christopher A. Foley, MD
Melvin R. Werbach, MD
Bruce N. Ames, PhD
Candace B. Pert, PhD
Michael R. Ruff, PhD
Leland Kaiser, PhD
Mildred S. Seelig, MD, MPH, FACN
Gonzalo Flores, MAcOM, LAc
John K. Chen, PhD, PharmD, OMD, LAc
Jerry Cott, PhD
Iris Bell, MD, PhD
Jackie Wootton, MEd
Joseph J. Jacobs, MD, MBA
Subhuti Dharmananda, PhD
Ethan Depweg, MAcOM, LAc
Peter Eschwey, MAcOM, LAc
Sheila Barnhart
Joseph E. Pizzorno, Jr, ND
Jared L. Zeff, ND, LAc
Tieraona LowDog, MD
Wayne Jonas, MD
David S. Riley, MD
Pamela Snider, ND
John Weeks
Robert Stern, DC, CFE
Bruce Canvasser, ND
Heiner Fruehauf, PhD, LAc
Clyde Jensen, PhD
Eric F. Stephens, DAOM, LAc
David M. Eisenberg, MD
Robert Scholten, MSLIS
Ted J. Kaptchuk, OMD
Steve Austin, ND
Nicki Scully
Mark Hallert
Terry L. Neal
Parvinder S. Kohli
James A. Spake, MEd, LMT
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Sri Dadaji Mahendranath
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Dr. T.H. Trismegistus
Prof. D. Mahalakshmi
Prof. Ganapati
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