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Natural ways to digestive health–interfaces between conventional and alternative medicine
GASTROENTEROLOGY 2001;121:498 – 499
PRINT AND MEDIA REVIEWS Ian S. Grimm, M.D. Print and Media Review Editor University of North Carolina at Chapel Hill Division of Digestive Diseases and Nutrition Chapel Hill, North Carolina
Drug Development: Molecular Targets for GI Disease. Edited by Timothy S. Gainella and Antonio Guglieta. 288 pp. $99.50. ISBN 0896065891. As clinicians, we can adopt the attitude that for a given condition, it matters less how a drug works than that it has a desired effect. The difficulty with this philosophy is that most illnesses do not fit neatly into the inclusion and exclusion criteria used to demonstrate a drug’s efficacy. Usually patients are taking multiple medications, and an understanding of each compound’s pharmacology can lead to undesired effects. A rudimentary understanding of a drug’s mechanism of action and the way in which illnesses respond to the compound is therefore needed for a clinician to tailor a therapy to a particular patient. Often, the response of an illness to a therapeutic agent can shed light on pathophysiologic processes that underpin the condition. The biologic revolution over the past half-century was based on the assumption that our increased understanding of fundamental processes could lead to better diagnostics and therapeutics. Unfortunately, the explosion of knowledge of biologic processes has created interesting perspectives on therapeutics too numerous for the busy clinician to readily appreciate. Knowledge is no longer confined to one specialty. For example, an understanding of constitutively expressed “housekeeping” proteins versus inducible ones such as nitric oxide synthetase (NOS) and cyclo-oxygenase (COX) has implications for treating a variety of diseases in virtually all specialties of medicine. As gastroenterologists, we often do not have the time or perspective to find out various aspects of this explosion in knowledge and to make optimum use of it to develop new and more effective therapeutic regimens. This volume contains 9 tightly woven and well-referenced reviews summarizing what is known about a number of potential targets for drug development and their potential relevance to gastrointestinal diseases. In addition to NOS and COX, topics covered in this book include the prostaglandins, leukotrienes, cytokines, tachykinins, and receptors for opioids, histamine, hydroxytryptamine, peptide hormones, and growth factors. This volume is relevant for someone who would like to obtain an overview of a particular molecular target before delving into the primary literature. Over the next decade, a variety of new drugs will be introduced that have applications for a seemingly unrelated series of indications. Unless the clinician has a rudimentary understanding of the potential targets for these compounds, the treatment of illnesses may
seem as confusing as attempting to learn organic chemistry by memorizing every single chemical reaction. Bottom Line: Although not light reading, this book contains concise reviews that serve as a focused introduction to emerging gastrointestinal therapeutics.
JEROME B. ZELDIS, M.D., Ph.D. Celgene Corporation Warren, New Jersey Natural Ways to Digestive Health–Interfaces Between Conventional and Alternative Medicine. By Stephen Holt. 322 pages. M. Evans and Co., Inc., New York, NY, 2001. ISBN 0871319098. I was looking forward to reading Dr. Stephen Holt’s latest book for two reasons: I hoped that the book would provide a comprehensive summary of the themes in alternative medicine as they apply to the digestive system, and I hoped that Dr. Holt would navigate these concepts with a reasoned voice that would provide practical advice which I would be comfortable bringing to the bedside. Although he satisfactorily achieved much of my first goal, he only partially achieved the second goal because I was left with many unanswered questions and concerns about how to safely integrate his observations into my therapeutic armamentarium. The need for Dr. Holt’s book is obvious to anyone who has had a digestive problem and to those who care for patients with digestive problems. Conventional approaches to common disorders, such as functional dyspepsia, irritable bowel syndrome, food intolerance, and inflammatory bowel disease, often fail to provide satisfactory and durable relief of symptoms and can be associated with a number of side effects. Furthermore, some basic and common-sense elements involved in the care of these patients (e.g., dietary recommendations) have been surprisingly poorly studied. The interaction between the ecology of the bowel and extraintestinal disorders, such as arthritis, is also poorly understood. However, the concept that there is a relationship and the idea of a “leaky-gut syndrome” (long-held tenets in alternative medicine) have begun to percolate into conventional thought and are beginning to undergo rigorous scientific scrutiny. Indeed, it is my impression that there is an exciting convergence of these themes. The benefits of “good bacteria” (i.e., probiotics) is an example. Evidence for the effectiveness of these agents is provided by an understanding of the role of microbes in the pathogenesis of inflammatory bowel disease and controlled trials, which have shown that probiotics may be effective in certain disorders (such as pouchitis and recurrent C. difficile infection), and is consistent with the alternative med-
August 2001
icine belief that the proper intestinal flora is essential for health. Are we finally going to truly understand why metronidazole is effective for patients with Crohn’s disease? Each of the 13 chapters in this 317-page book begins with a review of concepts about the pathogenesis and treatment of various digestive disorders based on the cannon of conventional medical knowledge. The summaries are accurate and reflect current practice, as would be expected from Dr. Holt, who is a board-certified gastroenterologist. The titles are frank and practical (such as chapter 6, “Belching, farting and bloating”). Toward the end of each chapter, Dr. Holt introduces alternative medicine concepts, many of which are thought provoking. As an example, Dr. Holt raises concerns about the potential deleterious effects of long-term gastric acid suppression. In addition to the commonly cited potential safety issues (such as a possible increased risk of enteric infections), Dr. Holt points out (citing data from the 1960s) that acid may have an important role in modifying dietary proteins so that macromolecules cannot gain access to the systemic circulation. He raises the question as to whether long-term acid suppression might therefore predispose to food allergies and possibly to systemic disorders (such as autoimmune diseases and inflammatory skin and joint disorders) incited by an immune response to circulating dietary macromolecules. The augmentation of stomach acid (by the consumption of acidic foods) is apparently a commonplace recommendation in some forms of alternative medicine. The chapters also contain specific recommendations about herbs, supplements, and other natural therapies for the treatment of various disorders and use numerous tables, references to other books, and web sites that deal with the specific topics. A general concern with these recommendations is that the distinction between what has been scientifically proven and what is anecdotal or (at best) speculative is often blurred. As an example, toward the end of the chapter on food allergies and intolerance, Dr. Holt writes “Again, the idea of giving hog (colonic or intestinal) mucosa to treat bowel disease is not a secret restricted to alternative medicine. Crude, powdered hog colonic mucosa is quite effective in the adjunctive management of inflammatory bowel disease.” To the best of my
PRINT AND MEDIA REVIEWS
499
knowledge, the efficacy of this type of therapy has not been established in well-performed controlled trials. Although Dr. Holt usually comments on what he believes to be effective and safe and what he believes is unproven, poorly substantiated statements like this one interspersed within the framework of conventional medical knowledge kept me skeptical as I read on. My concern was also fueled by the knowledge that Dr. Holt has founded a company that sells some of the supplements that he recommends in his book (the URL is conveniently provided at the end of the final chapter, along with other resources). Despite my concerns, this book left me much better informed about important themes in alternative medicine. Furthermore, I became more open-minded and am eager to have many of the suggested therapies validated by clinical studies so that I can feel more comfortable in recommending them to my patients. I would encourage Dr. Holt and his disciples to continue helping to achieve this goal. Although it is easy to complain that the establishment has overlooked the benefits of alternative therapies, I cannot think of a better way to bring attention to them than to study them scientifically. I might even consider using some of the recommendations as adjunctive therapy without further evidence, because they might help and seem to be innocuous enough. I would recommend this book as an easy, quick read for gastroenterologists with an interest in alternative medicine. Those who are not particularly interested might also benefit, because patients are increasingly interested in the topic. Because of the concerns discussed previously, I would not recommend the book to patients, but I would not attempt to dissuade them from reading it either. Bottom Line: An interesting, thought-provoking book that is easy to read. I will probably keep it around for future reference.
PETER A.L. BONIS, M.D. New England Medical Center Tufts University School of Medicine Boston, Massachusetts
PRINT AND MEDIA REVIEWS Ian S. Grimm, M.D. Print and Media Review Editor University of North Carolina at Chapel Hill Division of Digestive Diseases and Nutrition Chapel Hill, North Carolina
Drug Development: Molecular Targets for GI Disease. Edited by Timothy S. Gainella and Antonio Guglieta. 288 pp. $99.50. ISBN 0896065891. As clinicians, we can adopt the attitude that for a given condition, it matters less how a drug works than that it has a desired effect. The difficulty with this philosophy is that most illnesses do not fit neatly into the inclusion and exclusion criteria used to demonstrate a drug’s efficacy. Usually patients are taking multiple medications, and an understanding of each compound’s pharmacology can lead to undesired effects. A rudimentary understanding of a drug’s mechanism of action and the way in which illnesses respond to the compound is therefore needed for a clinician to tailor a therapy to a particular patient. Often, the response of an illness to a therapeutic agent can shed light on pathophysiologic processes that underpin the condition. The biologic revolution over the past half-century was based on the assumption that our increased understanding of fundamental processes could lead to better diagnostics and therapeutics. Unfortunately, the explosion of knowledge of biologic processes has created interesting perspectives on therapeutics too numerous for the busy clinician to readily appreciate. Knowledge is no longer confined to one specialty. For example, an understanding of constitutively expressed “housekeeping” proteins versus inducible ones such as nitric oxide synthetase (NOS) and cyclo-oxygenase (COX) has implications for treating a variety of diseases in virtually all specialties of medicine. As gastroenterologists, we often do not have the time or perspective to find out various aspects of this explosion in knowledge and to make optimum use of it to develop new and more effective therapeutic regimens. This volume contains 9 tightly woven and well-referenced reviews summarizing what is known about a number of potential targets for drug development and their potential relevance to gastrointestinal diseases. In addition to NOS and COX, topics covered in this book include the prostaglandins, leukotrienes, cytokines, tachykinins, and receptors for opioids, histamine, hydroxytryptamine, peptide hormones, and growth factors. This volume is relevant for someone who would like to obtain an overview of a particular molecular target before delving into the primary literature. Over the next decade, a variety of new drugs will be introduced that have applications for a seemingly unrelated series of indications. Unless the clinician has a rudimentary understanding of the potential targets for these compounds, the treatment of illnesses may
seem as confusing as attempting to learn organic chemistry by memorizing every single chemical reaction. Bottom Line: Although not light reading, this book contains concise reviews that serve as a focused introduction to emerging gastrointestinal therapeutics.
JEROME B. ZELDIS, M.D., Ph.D. Celgene Corporation Warren, New Jersey Natural Ways to Digestive Health–Interfaces Between Conventional and Alternative Medicine. By Stephen Holt. 322 pages. M. Evans and Co., Inc., New York, NY, 2001. ISBN 0871319098. I was looking forward to reading Dr. Stephen Holt’s latest book for two reasons: I hoped that the book would provide a comprehensive summary of the themes in alternative medicine as they apply to the digestive system, and I hoped that Dr. Holt would navigate these concepts with a reasoned voice that would provide practical advice which I would be comfortable bringing to the bedside. Although he satisfactorily achieved much of my first goal, he only partially achieved the second goal because I was left with many unanswered questions and concerns about how to safely integrate his observations into my therapeutic armamentarium. The need for Dr. Holt’s book is obvious to anyone who has had a digestive problem and to those who care for patients with digestive problems. Conventional approaches to common disorders, such as functional dyspepsia, irritable bowel syndrome, food intolerance, and inflammatory bowel disease, often fail to provide satisfactory and durable relief of symptoms and can be associated with a number of side effects. Furthermore, some basic and common-sense elements involved in the care of these patients (e.g., dietary recommendations) have been surprisingly poorly studied. The interaction between the ecology of the bowel and extraintestinal disorders, such as arthritis, is also poorly understood. However, the concept that there is a relationship and the idea of a “leaky-gut syndrome” (long-held tenets in alternative medicine) have begun to percolate into conventional thought and are beginning to undergo rigorous scientific scrutiny. Indeed, it is my impression that there is an exciting convergence of these themes. The benefits of “good bacteria” (i.e., probiotics) is an example. Evidence for the effectiveness of these agents is provided by an understanding of the role of microbes in the pathogenesis of inflammatory bowel disease and controlled trials, which have shown that probiotics may be effective in certain disorders (such as pouchitis and recurrent C. difficile infection), and is consistent with the alternative med-
August 2001
icine belief that the proper intestinal flora is essential for health. Are we finally going to truly understand why metronidazole is effective for patients with Crohn’s disease? Each of the 13 chapters in this 317-page book begins with a review of concepts about the pathogenesis and treatment of various digestive disorders based on the cannon of conventional medical knowledge. The summaries are accurate and reflect current practice, as would be expected from Dr. Holt, who is a board-certified gastroenterologist. The titles are frank and practical (such as chapter 6, “Belching, farting and bloating”). Toward the end of each chapter, Dr. Holt introduces alternative medicine concepts, many of which are thought provoking. As an example, Dr. Holt raises concerns about the potential deleterious effects of long-term gastric acid suppression. In addition to the commonly cited potential safety issues (such as a possible increased risk of enteric infections), Dr. Holt points out (citing data from the 1960s) that acid may have an important role in modifying dietary proteins so that macromolecules cannot gain access to the systemic circulation. He raises the question as to whether long-term acid suppression might therefore predispose to food allergies and possibly to systemic disorders (such as autoimmune diseases and inflammatory skin and joint disorders) incited by an immune response to circulating dietary macromolecules. The augmentation of stomach acid (by the consumption of acidic foods) is apparently a commonplace recommendation in some forms of alternative medicine. The chapters also contain specific recommendations about herbs, supplements, and other natural therapies for the treatment of various disorders and use numerous tables, references to other books, and web sites that deal with the specific topics. A general concern with these recommendations is that the distinction between what has been scientifically proven and what is anecdotal or (at best) speculative is often blurred. As an example, toward the end of the chapter on food allergies and intolerance, Dr. Holt writes “Again, the idea of giving hog (colonic or intestinal) mucosa to treat bowel disease is not a secret restricted to alternative medicine. Crude, powdered hog colonic mucosa is quite effective in the adjunctive management of inflammatory bowel disease.” To the best of my
PRINT AND MEDIA REVIEWS
499
knowledge, the efficacy of this type of therapy has not been established in well-performed controlled trials. Although Dr. Holt usually comments on what he believes to be effective and safe and what he believes is unproven, poorly substantiated statements like this one interspersed within the framework of conventional medical knowledge kept me skeptical as I read on. My concern was also fueled by the knowledge that Dr. Holt has founded a company that sells some of the supplements that he recommends in his book (the URL is conveniently provided at the end of the final chapter, along with other resources). Despite my concerns, this book left me much better informed about important themes in alternative medicine. Furthermore, I became more open-minded and am eager to have many of the suggested therapies validated by clinical studies so that I can feel more comfortable in recommending them to my patients. I would encourage Dr. Holt and his disciples to continue helping to achieve this goal. Although it is easy to complain that the establishment has overlooked the benefits of alternative therapies, I cannot think of a better way to bring attention to them than to study them scientifically. I might even consider using some of the recommendations as adjunctive therapy without further evidence, because they might help and seem to be innocuous enough. I would recommend this book as an easy, quick read for gastroenterologists with an interest in alternative medicine. Those who are not particularly interested might also benefit, because patients are increasingly interested in the topic. Because of the concerns discussed previously, I would not recommend the book to patients, but I would not attempt to dissuade them from reading it either. Bottom Line: An interesting, thought-provoking book that is easy to read. I will probably keep it around for future reference.
PETER A.L. BONIS, M.D. New England Medical Center Tufts University School of Medicine Boston, Massachusetts