Prevention and Reversal of Chronic Disease Copyright © 2019 RN Kostoff PREVENTION AND REVERSAL OF CHRONIC DISEASE: LESSONS LEARNED By Ronald N. Kostoff, Ph.D., School of Public Policy, Georgia Institute of Technology 13500 Tallyrand Way, Gainesville, VA, 20155 [email protected] KEYWORDS Chronic disease prevention; chronic disease reversal; chronic kidney disease; Alzheimer’s Disease; peripheral neuropathy; peripheral arterial disease; contributing factors; treatments; biomarkers; literature-based discovery; text mining ABSTRACT For a decade, our research group has been developing protocols to prevent and reverse chronic diseases. The present monograph outlines the lessons we have learned from both conducting the studies and identifying common patterns in the results. The main product of our studies is a five-step treatment protocol to reverse any chronic disease, based on the following systemic medical principle: at the present time, removal of cause is a necessary, but not necessarily sufficient, condition for restorative treatment to be effective. Implementation of the five-step treatment protocol is as follows: FIVE-STEP TREATMENT PROTOCOL TO REVERSE ANY CHRONIC DISEASE Step 1: Obtain a detailed medical and habit/exposure history from the patient. Step 2: Administer written and clinical performance and behavioral tests to assess the severity of symptoms and performance measures. Step 3: Administer laboratory tests (blood, urine, imaging, etc) Step 4: Eliminate ongoing contributing factors to the chronic disease Step 5: Implement treatments for the chronic disease This individually-tailored chronic disease treatment protocol can be implemented with the data available in the biomedical literature now. It is general and applicable to any chronic disease that has an associated substantial research literature (with the possible exceptions of individuals with strong genetic predispositions to the disease in question or who have suffered irreversible damage from the disease). To prevent any chronic disease, eliminate those contributing factors that serve as a basis for Step 4. 1 Prevention and Reversal of Chronic Disease Copyright © 2019 RN Kostoff CITATION TO MONOGRAPH Kostoff RN. Prevention and reversal of chronic disease: lessons learned. Georgia Institute of Technology. 2019. PDF. http://hdl.handle.net/1853/62019 COPYRIGHT AND CREATIVE COMMONS LICENSE COPYRIGHT Copyright © 2019 by Ronald N. Kostoff Printed in the United States of America; First Printing, 2019 CREATIVE COMMONS LICENSE This work can be copied and redistributed in any medium or format provided that credit is given to the original author. For more details on the CC BY license, see: http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License<http://creativecommons.org/licenses/by/4.0/>. DISCLAIMERS The views in this monograph are solely those of the author and do not represent the views of the Georgia Institute of Technology. This monograph is not intended as a substitute for the medical advice of physicians. The reader should regularly consult a physician in matters relating to his/her health and particularly with respect to any symptoms that may require diagnosis or medical attention. Any information in the monograph that the reader chooses to implement should be done under the strict guidance and supervision of a licensed health care practitioner. 2 Prevention and Reversal of Chronic Disease Copyright © 2019 RN Kostoff PREFACE Why did I write this monograph, what are its contents, what is new, who is the intended audience, and how will readers benefit from it? Motivation Non-communicable diseases have overtaken communicable diseases as the leading cause of global mortality. The impacts of non-communicable disease expansion on healthcare and associated costs have been dramatic. In the USA, these costs, and how to deal with them, have become a central political issue. The mainstream medical approach emphasizes treatments over prevention for non- communicable diseases. Given the expansion of non-communicable diseases, the present treatment- dominant approach is insufficient. Greater balance between treatment and prevention is required. Eliminating the actionable foundational causes of these diseases is at least as important as applying new treatments, if there is to be any hope for full or partial reversal of non-communicable diseases, as well as prevention. Toward that end, I developed a systemic medical principle that would form the bedrock of a healing protocol for diseases: at the present time, removal of cause is a necessary, but not necessarily sufficient, condition for restorative treatment to be effective (where "removal" encompasses "neutralization" in those cases where actual "removal" is not possible, and "restoration" encompasses restoration of health to the organ/tissue as well as restoration of function). To prevent diseases, the actionable foundational causes shown by the biomedical literature to potentially contribute to the diseases need to be removed as comprehensively, thoroughly, and rapidly as possible. To reverse diseases (if irreversible damage has not been done and genetic predisposition to the disease in question is not a dominant factor), the preventive steps above need to be implemented as well. If the preventive protocols alone are inadequate for reversing disease progression, they need to be augmented by treatments. The first step in either disease prevention or reversal is to identify the full spectrum of potential foundational causes/contributing factors for the disease(s) of interest. Based on our studies of three chronic diseases, we have found: 1) much of the information required to identify and eliminate these foundational causes of disease is in the biomedical literature already, but is not being extracted and exploited adequately; 2) the biomedical literatures for many chronic diseases are large, and extracting these foundational causes comprehensively from the literatures is a complex text mining problem; 3) the same holds true for treatments and biomarkers. Contents The overall theme of the present monograph is preventing and reversing chronic disease based on the systemic medical principle described above. The specific focus of the present monograph is 1) summarizing the methodologies used in our chronic disease studies to prevent and reverse these diseases, and 2) summarizing the lessons learned and patterns identified from these studies. 3 Prevention and Reversal of Chronic Disease Copyright © 2019 RN Kostoff There are lengthy appendices in the present monograph describing the text mining/information technology advances that allowed 1) the existing and potential chronic disease treatments and contributing factors to be extracted efficiently from the large numbers of journal articles retrieved from the premier biomedical literature, and 2) the impacts of these treatments and contributing factors to be extracted from the literature. Major advances were made in the text mining approach for extracting both existing and potential treatments and contributing factors from the biomedical literature (and their impacts). Novelty While the individual existing and potential chronic disease contributing factors and treatments identified in this monograph are "known", in the sense that they exist scattered throughout the published literature (although the potential chronic disease contributing factors and treatments have not been previously associated with the chronic disease in the literature), they have not been integrated to the extent they are integrated in this monograph. The new "insights" in this monograph are: 1) the sheer number of existing and potential chronic disease contributing factors, biomarkers, and treatments; 2) the sheer number of potential combinations of chronic disease contributing factors and treatments that have to be identified and researched (many of whose individual components have not yet been identified); 3) the sheer number of chronic disease biomarkers and symptoms that can be used as diagnostics to identify causes and treatments for individual patients; 4) the approach for discovering treatments from the non-chronic disease literature, which allows both the re-purposing of drugs that have been used for treating other diseases and identification of non-drug substances that will correct the abnormal chronic disease biomarker values; 5) the chronic disease treatment protocol that can be tailored to any individual patient. Audience There are three communities to whom this monograph is targeted. First is the "chronic disease prevention and reversal" community. This encompasses the public health community, the chronic disease research community, medical practitioners involved clinically with chronic disease prevention and reversal, caretakers for chronic disease patients, and individuals interested in what the present approach has to offer (they should heed the warnings in the Disclaimer). Second is the text mining and information technology community. This would cover the full spectrum of researchers interested in extraction of useful information from any type of text, since the techniques developed in this monograph can be readily adapted to extracting useful information from myriad types of biomedical and non-biomedical text. Third is the broader medical and health policy community. The methodology is applicable to prevention and reversal of any disease that has an associated substantial research literature. 4 Prevention and Reversal