Diet, Inflammation, and Health

Diet, Inflammation, and Health introduces concepts of inflammation, the role of acute inflammatory responses in good health, and the association of chronic systemic inflammation with mental distress, cognitive decline, and chronic diseases, ranging from diabetes to cardiovascular diseases, stroke, and cancer. The book also describes the pathophysiology of inflammation and its effects on insulin insensitivity and blunted immune response to carcinogenesis. Researchers and allied health care professionals working in dietetics and medicine, as well as students studying related fields will benefit from this reference and its recommendations on areas where future research is needed.

• Addresses the role of acute inflammatory responses in achieving and maintaining good health
• Covers the association of chronic system inflammation with various conditions and diseases
• Describes the effect of inflammation on mechanisms ranging from insulin insensitivity and immune response to carcinogenesis

• Language: English
• Publisher: Academic Press
• Release date: Apr 28, 2022
• ISBN: 9780128221655

Book preview

Diet, Inflammation, and Health

Editors

James R. Hébert

South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina

Connecting Health Innovations LLC (CHI), Columbia, SC, United States

Lorne J. Hofseth

Center for Colon Cancer Research, College of Pharmacy, University of South Carolina, Columbia, SC, United States

Table of Contents

Cover image

Title page

Copyright

List of contributors

Preface

Chapter 1. Inflammation in the long arc of history

1. Introduction: inflammatory responses are universal

2. Our evolving understanding of immune and inflammatory responses

3. Looking way back in time to understand why inflammation is a universal property of living systems

4. What is the relationship between inflammation and immune response?

5. How we have coopted inflammatory and immune responses from other organisms over our evolutionary history

6. Conclusion

Chapter 2. History of nutrition and inflammation

1. Introduction

2. Natural history of nutrition and inflammation

3. Human history of nutrition and inflammation

4. Other nutrients

5. This emergence of chemoprevention in the last decades of the 20th century

6. Special/vulnerable populations

7. The demographic, epidemiologic, and nutrition transitions and the age of excess

Chapter 3. Diet and acute and chronic, systemic, low-grade inflammation

1. Acute versus chronic inflammation

2. The nutrition connections

3. Evidence that chronic inflammation drives disease

4. Covert systemic inflammatory load and tissue-specific simmering inflammation

5. Obesity is associated with a high inflammatory load

6. Conclusion

Chapter 4. Resolving acute inflammation; what happens when inflammation goes haywire? How can it get back in line?

1. Acute inflammation

2. How can inflammation get back in line?

3. Resolution of inflammation

4. Resolution pharmacology: proresolving lipid mediators

5. Dietary intervention with omega-3 PUFA

6. Lipoxins

7. Docosahexaenoic acid (DHA)

8. Maresins

9. Resolvins

10. SPM pharmacology—resolution indices

11. SPM are protective in preclinical studies

12. Failure of resolution

13. Resolution pharmacology—synthetic derivatives

14. Clinical trials and SPM: market prospective

15. Concluding remarks

Chapter 5. Methods and tools used to describe and quantify the associations between diet, inflammation, and health

1. Introduction

2. Methodologic concepts

3. The study

4. Exposure estimates

5. Outcomes/endpoints

6. Important covariates

7. Study design: allocating treatment and alternative methods of assessing efficacy and effectiveness

8. Analyzing data to determine whether there is an association between diet and putative endpoints/outcomes

9. Publication bias

10. Conclusion

Chapter 6. Diet, inflammation, and the itises (including musculoskeletal and gastrointestinal conditions)

1. Introduction

2. Inflammatory diseases of the digestive system

3. Inflammation of the skin

4. Diseases of the musculoskeletal system and connective tissue

5. Neuroinflammatory conditions

6. Conclusion

Chapter 7. Dietary patterns and type 2 diabetes—relationship to metabolic syndrome and inflammation

1. Introduction

2. Influence of dietary patterns on type 2 diabetes development

3. Individual food constituents and type 2 diabetes and underlying risk factors

4. Dietary indices assessing dietary intake and interventions

5. Mechanistic aspects of the relationship between diet, inflammation, and type 2 diabetes

6. Intervention approaches to reduce type 2 diabetes and MetS as part of therapeutic approaches

7. Conclusions and perspectives

Chapter 8. Diet, inflammation, and cardiovascular disease

1. Introduction

2. Brief overview of cardiovascular diseases and their connections to diet and inflammation

3. Dietary patterns and cardiovascular diseases

4. Epidemiological studies—focus on food groups

5. Mechanistic effects linking nutrients and dietary patterns to cardiovascular diseases

6. Summary

Chapter 9. Diet, inflammation, and cancer

1. Introduction

2. Linking inflammation and cancer

3. Dietary indices

4. Nasopharyngeal cancer

5. Esophageal and other cancers of the upper aerodigestive tract

6. Gastric cancer

7. Colorectal cancer

8. Hepatocellular carcinoma

9. Pancreatic cancer

10. Lung cancer

11. Breast cancer

12. Prostate cancer

13. Cancer is increasing in the young in the last quarter century

14. Inflammation—at the mechanistic crossroads of diet and cancer

15. Diet–microbiome–inflammation–cancer link

16. The inflammation-to-cancer sequence

17. The arachidonic acid cascade and free-radical production

18. Cytokines

19. Conclusions

Chapter 10. Inflammatory potential of diet in mental disorders and psychosocial stress

1. Introduction

2. The role of inflammation in mental disorders

3. The role of diet in mental disorders: an overview of the current evidence with a focus on depression

4. The role of healthy diet patterns as an anti-inflammatory agent

5. The dietary inflammatory index (DII)

6. The role of individual dietary components in mental health and inflammation

7. Conclusion

Chapter 11. Inflammatory potential of diet and aging

1. Introduction

2. Frailty

3. Bone health

4. Diet, inflammation, and the pathophysiology of the aging eye

5. Cognitive decline

6. Conclusion

Chapter 12. Inflammatory potential of diet and health outcomes in pregnancy, infancy, and childhood

1. Introduction

2. Maternal dietary inflammation during pregnancy and perinatal outcomes

3. Maternal dietary inflammation during pregnancy and associations with fetal outcomes

4. Maternal dietary inflammation during lactation and associations with breast milk composition

5. Maternal dietary inflammation during pregnancy and associations with offspring childhood outcomes

6. Dietary inflammation during childhood and associations with childhood health outcomes

7. Conclusions and future perspectives

Chapter 13. Physical activity and inflammation: acute and chronic considerations

1. Introduction to inflammation and physical activity

2. Acute exercise and inflammation

3. Workload matters

4. (Anti-)inflammation and adaptation—strategies to aid recovery

5. Exercise reduces chronic inflammation

6. Conclusions

Chapter 14. The role of diet and physical activity in influencing the microbiota/microbiome

1. Introduction

2. Microbiota/microbiome

3. Diet and microbiota

4. Physical activity and microbiota

5. Conclusions

Chapter 15. Inflammatory potential of the diet: role of circadian rhythms and sleep

1. Introduction

2. Overview of circadian rhythms

3. Chrononutrition

4. Chrononutrition and inflammation

5. Chrononutrition and anthropometric measurements

6. Chrononutrition and metabolic markers

7. Sleep and diet

8. Chronotype and diet

9. Shift work and diet

10. Conclusion

Chapter 16. What constitutes an antiinflammatory diet? How does this contrast with a proinflammatory diet?

1. Introduction

2. Perceptions of foods: their chemical characteristics and inflammatory potential

3. Describing patterns of intake

4. Specific recommendations

5. Characteristics of specific diets

6. Caveats and idiosyncrasies

7. Summary and Conclusion

Chapter 17. Following the long arc of history: where do we go from here?

1. Introduction

2. Keeping it in perspective: the need to evaluate evidence on the role of diet in inflammation and health

3. Controversies in addressing this growing problem of chronic disease

4. The dawn of a new epoch in which humans exert dominion and control

5. Environmental changes that have begun to affect food production and nutrition in the anthropocene

6. Human health, inflammation, and diet in the anthropocene

7. Using our knowledge to set the stage for making effective change

8. Action that can be taken now by individuals based on current knowledge

9. Addressing looming global threats based on existing scientific knowledge

10. Summary and Conclusion

Index

Copyright

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Notices

Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.

Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.

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List of contributors

Ala'a Alkerwi,     Directorate of Health, Service Epidemiology and Statistics, Hamm, Luxembourg

Chloe Andrews,     Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, MA, United States

Shawn M. Arent,     Sport Science Laboratory, Department of Exercise Science, University of South Carolina, Columbia, SC, United States

Hajara Aslam,     Deakin University, IMPACT – The Institute for Mental and Physical Health and Clinical Translation, Food & Mood Centre, School of Medicine, Barwon Health, Geelong, Australia

Torsten Bohn,     Nutrition and Health Research Group, Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg

Emily Brigham,     Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, United States

James B. Burch,     Department of Family Medicine and Population Health, Division of Epidemiology, Virginia Commonwealth University, Richmond, VA, United States

Chiara Cecconello,     The William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, United Kingdom

Alexa J. Chandler,     Sport Science Laboratory, Department of Exercise Science, University of South Carolina, Columbia, SC, United States

Ling-Wei Chen,     School of Public Health, Physiotherapy and Sports Science, University College Dublin, Dublin, Ireland

David Chiriboga,     Department of Medicine, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA, United States

Alexander A. Chumanevich

Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, United States

Center for Colon Cancer Research, College of Pharmacy, University of South Carolina, Columbia, SC, United States

Harry P. Cintineo,     Sport Science Laboratory, Department of Exercise Science, University of South Carolina, Columbia, SC, United States

Pol Clària Ribas,     The William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, United Kingdom

Jessica A. Davis,     Deakin University, IMPACT – The Institute for Mental and Physical Health and Clinical Translation, Food & Mood Centre, School of Medicine, Barwon Health, Geelong, Australia

Sarah J. Eustis,     Tufts University School of Medicine, Boston, MA, United States

Yueh-Ying Han,     Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, United States

Corrine Hanson,     Division of Medical Nutrition Education, College of Allied Health Professions, University of Nebraska Medical Center, Omaha, NE, United States

James R. Hébert

Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, United States

Center for Colon Cancer Research, College of Pharmacy, University of South Carolina, Columbia, SC, United States

South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, United States

Lorne J. Hofseth

Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, United States

Center for Colon Cancer Research, College of Pharmacy, University of South Carolina, Columbia, SC, United States

South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, United States

Felice N. Jacka,     Deakin University, IMPACT – The Institute for Mental and Physical Health and Clinical Translation, Food & Mood Centre, School of Medicine, Barwon Health, Geelong, Australia

Rachel E. Kopec,     Foods for Health Discovery Theme, Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH, United States

Augusto Litonjua,     Division of Pediatric Pulmonary Medicine, Golisano Children's Hospital at Strong, University of Rochester Medical Center, Rochester, NY, United States

Matthew C. Lohman,     Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, United States

Wolfgang Marx,     Deakin University, IMPACT – The Institute for Mental and Physical Health and Clinical Translation, Food & Mood Centre, School of Medicine, Barwon Health, Geelong, Australia

Bridget A. McFadden,     Sport Science Laboratory, Department of Exercise Science, University of South Carolina, Columbia, SC, United States

Carmen Monthé-Drèze

Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, MA, United States

Harvard Medical School, Boston, MA, United States

E. Angela Murphy

Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, SC, United States

Center for Colon Cancer Research, University of South Carolina, Columbia, SC, United States

Lucy V. Norling

The William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, United Kingdom

Centre for Inflammation and Therapeutic Innovation, Queen Mary University of London, London, United Kingdom

Tonya S. Orchard,     Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH, United States

Catherine M. Phillips,     School of Public Health, Physiotherapy and Sports Science, University College Dublin, Dublin, Ireland

Kinga Polańska,     Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Łódź, Poland

Justin Roberts,     Centre for Health Performance and Wellbeing, Anglia Ruskin University, Cambridge, United Kingdom

Hanen Samouda,     Nutrition and Health Research Group, Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg

Sarbattama Sen

Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, MA, United States

Harvard Medical School, Boston, MA, United States

Lee Smith,     Centre for Health Performance and Wellbeing, Anglia Ruskin University, Cambridge, United Kingdom

Malory Spicer

Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, United States

Center for Colon Cancer Research, College of Pharmacy, University of South Carolina, Columbia, SC, United States

Mike Trott,     Centre for Health Performance and Wellbeing, Anglia Ruskin University, Cambridge, United Kingdom

Farhad Vahid,     Nutrition and Health Research Group, Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg

Kandy T. Velázquez

Department of Pathology, Microbiology & Immunology, School of Medicine, University of South Carolina, Columbia, SC, United States

Center for Colon Cancer Research, University of South Carolina, Columbia, SC, United States

Nicola Veronese,     National Research Council, Neuroscience Institute, Aging Branch, Institute of Clinical Research and Education in Medicine, Padova, Italy

Michael D. Wirth

College of Nursing, University of South Carolina, Columbia, SC, United States

Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, United States

Preface

James R. Hébert ¹ , ² ,      ¹ Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, United States,      ² South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, Unites States

Very early in my career, I learned that serious academics in the sciences do not write books. Rather, they write research papers for publication in the peer-reviewed literature. That viewpoint reflects both the reward systems in academic medicine and public health and the simple and obvious fact that by the time a book is published, any finding that may have been novel or unique at the time of writing has fallen victim to old age by the time the book is published. Furthermore, experts are asked to write books in a way that reflects their accumulated knowledge, so the focus is not on specific novel findings, but rather specific findings are presented and invoked in a manner that places them in the larger historical context of scientific inquiry, discovery, and evolution. The process, ideally, results in a more compelling and coherent case regarding the relationships being presented. Although the result of this summarization, review, and synthesis may be interesting, it does not provide a compelling reason to invest the enormous amount of effort required to write a book. So, why did my colleagues and I decide to write this book? The answer is complicated and multifaceted. Here I endeavor to lay out our rationale in a way that will entice you to read Diet, Inflammation, and Health.

Over the past several decades, there has been an explosion of interest in inflammation. According to a recent review of the National Library of Medicine database, the literature on inflammation and health has increased about 2.5-fold in the past 10years, from 222,231 articles through 2010 to 582,163 by mid-summer 2021. The literature on diet in combination with inflammation has grown even more quickly, from 6647 citations through 2007, which formed the basis for the first generation of the dietary inflammatory index (DII) to 10,298 through 2010, which formed the basis for the second and current generation of the DII, to 44,984 by mid-summer 2021. During the same decade-long period that the overall size of the literature on inflammation and health increased by 2.52-fold, the corresponding literature on diet and inflammation increased nearly fourfold (i.e., 3.82 times), or about 1.5-times faster than the inflammation literature in general. By all accounts, public interest in inflammation and the role of diet in modulating inflammation has kept pace [1]. This public interest is not fueled entirely by reports that originate in the scientific literature. Because the hallmarks of inflammation—pain, redness, swelling, and heat—are so obvious and pervasive in the lives of practically all humans [2–8], inflammation is a topic to which virtually anyone can relate. Likewise, dietary exposures are ubiquitous. Most people eat every day, often several or more times per day. Even for people who fast occasionally for health, religious, or other purposes, going without food for very long results in unfortunate outcomes, including death. Just as inflammation is a universal consequence of living so, too, is eating a basic need of the living—to use the epidemiologic terminology—a set of ubiquitous exposures. So, if you are reading this book as a health scientist, health practitioner, or an informed and interested citizen and consumer, know that you are not alone.

Underscoring the importance of this topic to scientific inquiry are the facts that, in the United States alone, chronic, systemic inflammation is responsible for: (1) consuming vast resources (over $1trillion/year) to treat inflammation-related chronic diseases and conditions, many of which can be prevented or reversed [9]; (2) large losses in productivity, totaling more than $300billion, which occur because of these conditions [10]; and (3) significant suffering that occurs because of both preclinical disease (e.g., the unnecessary musculoskeletal aches and pains of everyday life associated with chronic, systemic inflammation) and a wide variety of inflammation-related chronic diseases (as noted above). While all of these medical expenses are being incurred and people are living with disability [11], more than $2.5trillion is simultaneously being spent in the United States per year on foods [12,13] that primarily increase inflammation [14] and supplements that primarily decrease inflammation [15]. So, the public is clearly paying attention, both in terms of the popularity of these topics in the media (a Google search in mid-summer 2021 returned over 312million results with top hits for news articles published in 2020–21 alone pertaining to diet and inflammation from US News and World Report, BBC, the Washington Post, Consumer Reports, CNN, and The New York Times, among very many others) and through the costs incurred in terms of monetary expense and mental and physical suffering and pain. Thus, the link between diet and inflammation seems to be an important enough topic to take some time to explore, apart from activities aimed primarily at creating academic products based on primary research.

Supporting and amplifying millennia-old observations about inflammation in both the Eastern and Western traditions [5–7,16–23], the corollary and consonant explosion of interest in the role of inflammation in health over the past three decades have demonstrated that inflammation has a ubiquitous role as the substrate for a wide variety of biological mechanisms relevant to the health of the individual. These include oxidative and nitrosative DNA damage [24–31], changes in gene expression and genetic instability [24,32–38], insulin resistance [39–45], foam cell formation [46], and blunted immune responses [47–52]. Because of its pervasive role in metabolism, inflammation is associated with conditions ranging from depression [2,53–58], more severe mental illnesses [59,60], and cognitive decline [61–64] to asthma [65–67], prediabetes [42,45,68–70], type II diabetes mellitus (T2DM) [40,70–72], cardiovascular diseases [70,73,74], and cancers of a variety of anatomic sites [51,70,75].

Although the diet–health literature is fraught with controversy, as we mentioned in our highly cited 2014 paper in Advances in Nutrition [76] and subsequent interchanges on this subject [77], the evidence linking certain aspects of diet with health outcomes is remarkably consistent (a matter that we discuss in greater detail in Chapter 5). The over 1.5million scientific papers published in the biomedical literature on diet and health thus provide an additional strong basis and rationale for embarking on this ambitious undertaking.

We were approached by the publisher to write this book largely because of the growing popularity of the DII. Therefore, that is the primary lens through which I have looked at this project. However, it is not the only one. More on that later.

Most of chapter authors have worked collaboratively in using the DII in their work. They were invited because of their expertise and the excellent working relationships that we have built over the years. I am grateful that they accepted our offer. Both Dr. Hofseth and I have learned so much from these individuals as we have completed all of the chapters that constitute the book. Our work with the DII makes clear that diet is centrally important in modulating chronic systemic inflammation [78–84], aging (including telomere shortening and cognitive decline) [84–87], and the many diseases with which they are associated [88–120]. Over the ≈7years since the paper describing the design and development of the current DII version [121] and the first validation study of the new version [81] were first published, we have monitored the literature very carefully. In the nearly 7years since the initial validation using the longitudinal SEASONS data, which consisted of five sets of measures from two different dietary assessments (i.e., up to three 24hour recalls, a 7-day diet recall, and hs-CRP values at baseline and quarterly thereafter [81]), the DII, E-DII, or C-DII has been construct validated against inflammatory biomarkers in 36 different populations [45,78,80,82–85,107,122–146]. This includes, as markers, hs-CRP, IL-4, 6, 8, and 10, TNF-α, calprotectin, fibrinogen, homocysteine, interferon-γ, and WNT signaling. One report, from the Melbourne Collaborative Cohort Study, showed that the DII was related to 14 biomarkers of inflammation, including five components of the kyurenine pathway [147]. The C-DII has been construct validated with hs-CRP in the NHANES [142] and with leptin, adiponectin/leptin ratio, and hsCRP concentrations in Mexican children [148].

Also over this period, 56 systematic review/meta-analyses based on the DII have been published on health outcomes ranging from attention deficit-hyperactivity disorder to cardiovascular diseases, depression, diabetes and metabolic syndrome, inflammatory metabolic markers, aging, frailty, and cancers of many different anatomic sites [53,58,74,75,149–200]. In addition to these systematic approaches to examining the data, we have also carefully monitored each and every one of the 621 papers that have been published using the DII between August 2014 and September 2021. It is important to note that while there is some variability regarding null results (i.e., due to imprecision resulting from, among other things, occasional small sample sizes) appearing alongside negative and positive results, there is no instance of a result that inverts entirely across two or more studies (i.e., a negative result following a positive result in a previous study, or vice versa). Clearly, the literature is extraordinarily consistent [70,201]. As an epidemiologist who is well aware (and quite appreciative) of the Criteria for Judging Causality that was developed by Bradford Hill in the 1950s [202] and popularized in the 1964 Surgeon General's Report on Smoking and Health [203], I recognize the importance of consistency in judging whether relationships or associations are causal, especially when we must rely either exclusively (in the case of tobacco) or predominantly (in the case of diet) on evidence from observational studies, as opposed to randomized controlled trials [204].

As you will see, the chapters contained in this book represent a wide array of topics. Roughly the first third of the book provides background to the reader on the history of inflammation, the role of diet in inflammation, the distinction between acute and chronic systemic or tissue-specific simmering inflammation, means of resolving acute inflammatory responses, and the methods that we use to describe diet-inflammation associations. Chapter 1, Inflammation in the Long Arc of History, describes the very long natural history of inflammation, and provides perspectives on what inflammation is and why it is important. It also explains the close connection between inflammatory responses and immune responses. In Chapter 2, we focus our attention specifically on the history of nutrition and inflammation. While much of this focuses on observations made in the last 3000years of human history, as in Chapter 1, we also discuss the much more ancient biological history of these relationships. Underlying all of what we know regarding inflammation and the inflammatory responses that are necessary to induce biological pathways essential to maintaining health or, when things go badly, can cause disease, it is important to understand the connection between acute and chronic inflammation. Hence, in Chapter 3, we distinguish acute, usually localized, inflammatory responses from chronic systemic inflammation. We also discuss chronic, simmering tissue-specific chronic inflammation. Then, in Chapter 4, we focus on resolving the acute inflammatory response and understanding what goes wrong when this does not happen. In Chapter 5, we describe the tools that we use, mainly in epidemiology, to describe diet–health relationships and to make inferences regarding the diet–inflammation link.

The middle third of the book focuses on specific health outcomes and mechanisms through which inflammation exerts its effect. These outcomes were chosen largely because of their public health significance, which is reflected in the fact that each of them is now the subject of at least one DII-related systematic review/meta-analysis (as noted above). Chapter 6 focuses on the itises, conditions that often share what has become a common suffix for inflammation (i.e., itis) in their very name. These itises include conditions such as arthritis, bronchitis, bursitis, colitis, conjunctivitis, dermatitis, diverticulitis, encephalitis, esophagitis, gastritis, gingivitis, hepatitis, mastitis, meningitis, and tendonitis. These are incredibly important conditions because they cause so much pain, and it is this pain that is the main driver of patients into medical care delivery systems all around the world. Clearly, the conventional allopathic medical solutions to the itises do not work well in the long term and often cause harmful side effects (e.g., gastrointestinal symptoms associated with NSAID use). So, this chapter provides a new way of thinking about itises in relation to nutrition. Chapter 7 focuses on type 2 diabetes and metabolic syndrome. Though not new to human experience, the rapidly increasing incidence and prevalence of these conditions have become the scourge of the modern age. Chapter 8 focuses on cardiovascular disease, which remains among the most important causes of mortality around the world and is closely related to type 2 diabetes and metabolic syndrome. Chapter 9 focuses on cancer, which is rapidly becoming a major health concern virtually everywhere. Chapter 10 focuses on mental illnesses and disorders and psychological stress that now constitute a major source of diminution of health-related quality of life. Chapter 11 focuses on aging and related conditions that are becoming increasingly more important as populations continue to age around the world. Finally, Chapter 12 focuses on pregnancy and maternal and child health, which are so important for ensuring the future health of humanity.

Clearly, people do not obtain food and eat in a vacuum. So, the final third of the book focuses on the connection between diet and inflammation in relation to physical activity (Chapter 13), other lifestyle factors and the microbiome (Chapter 14), and circadian rhythms, including chrononutrition and sleep (Chapter 15). In Chapter 16, we describe the specific characteristics of diet that modulate inflammation (i.e., those foods and nutrients that are, dependably, consistent with an appropriate inflammatory response versus those that contribute to chronic systemic inflammation). We tie everything up in Chapter 17, in which we talk about other health outcomes not covered in Chapters 6 to 12 and what we see as the future implications and directions in this important and rapidly growing field. For this, we have invoked a wide range of perspectives, including those as far-reaching as farming and agricultural practices, resource allocation and use, global climate change, and policies that can be put into place to ensure optimal health for human beings, other animals, plants, microorganisms, and the current state of our planet.

Our goal in writing this book is to provide unique perspectives that can shed new light on old problems that have grown worse over the decades. Many of these have remained or become refractory to conventional efforts at treatment and symptom control at the level of the individual and amelioration and remediation at a systemic level. This has been an amazing learning experience for us. We hope that you enjoy the fruits of this experience. Read on.

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101. Peres L.C, Bandera E.V, Qin B, Guertin K.A, Shivappa N, Hebert J.R, Abbott S.E, Alberg A.J, Barnholtz-Sloan J, Bondy M, et al. Dietary inflammatory index and risk of epithelial ovarian cancer in African American women.  Int J Cancer . 2017;140:535–543.

102. Neufcourt L, Assmann K.E, Fezeu L.K, Touvier M, Graffouillere L, Shivappa N, Hebert J.R, Wirth M.D, Hercberg S, Galan P, et al. Prospective association between the dietary inflammatory index and cardiovascular diseases in the SUpplementation en VItamines et Mineraux AntioXydants (SU.VI.MAX) Cohort.  J Am Heart Assoc . 2016;5:e002735. .

103. Lu Y, Shivappa N, Lin Y, Lagergren J, Hebert J.R. Diet-related inflammation and oesophageal cancer by histological type: a nationwide case-control study in Sweden.  Eur J Nutr . 2016;55:1683–1694.

104. Hodge A.M, Bassett J.K, Shivappa N, Hebert J.R, English D.R, Giles G.G, Severi G.Dietary inflammatory index, Mediterranean diet score, and lung cancer: a prospective study.  Cancer Causes Control . 2016;27:907–917.

105. Graffouillere L, Deschasaux M, Mariotti F, Neufcourt L, Shivappa N, Hebert J.R, Wirth M.D, Latino-Martel P, Hercberg S, Galan P, et al. The dietary inflammatory index is associated with prostate cancer risk in French middle-aged adults in a prospective study.  J Nutr . 2016;146:785–791.

106. Deng F.E, Shivappa N, Tang Y, Mann J.R, Hebert J.R. Association between diet-related inflammation, all-cause, all-cancer, and cardiovascular disease mortality, with special focus on prediabetics: findings from NHANES III.  Eur J Nutr . 2016;56:1085–1093.

107. Zamora-Ros R, Shivappa N, Steck S.E, Canzian F, Landi S, Alonso M.H, Hebert J.R, Moreno V.Dietary inflammatory index and inflammatory gene interactions in relation to colorectal cancer risk in the Bellvitge colorectal cancer case-control study.  Genes Nutr . 2015;10:447.

108. Wirth M.D, Shivappa N, Steck S.E, Hurley T.G, Hebert J.R. The dietary inflammatory index is associated with colorectal cancer in the National Institutes of Health-American Association of Retired Persons Diet and Health Study.  Br J Nutr . 2015;113:1819–1827.

109. Tabung F.K, Steck S.E, Ma Y, Liese A.D, Zhang J, Caan B, Hou L, Johnson K.C, Mossavar-Rahmani Y, Shivappa N, et al. The association between dietary inflammatory index and risk of colorectal cancer among postmenopausal women: results from the Women's Health Initiative.  Cancer Causes Control . 2015;26:399–408.

110. Shivappa N, Zucchetto A, Serraino D, Rossi M, La Vecchia C, Hebert J.R. Dietary inflammatory index and risk of esophageal squamous cell cancer in a case-control study from Italy.  Cancer Causes Control . 2015;26:1439–1447.

111. Shivappa N, Zucchetto A, Montella M, Serraino D, Steck S.E, La Vecchia C, Hebert J.R. Inflammatory potential of diet and risk of colorectal cancer: a case-control study from Italy.  Br J Nutr . 2015;114:152–158.

112. Shivappa N, Sandin S, Lof M, Hebert J.R, Adami H.O, Weiderpass E. Prospective study of dietary inflammatory index and risk of breast cancer in Swedish women.  Br J Cancer . 2015;113:1099–1103.

113. Shivappa N, Jackson M.D, Bennett F, Hebert J.R. Increased Dietary Inflammatory Index (DII) Is associated with increased risk of prostate cancer in Jamaican Men.  Nutr Cancer . 2015;67:941–948.

114. Shivappa N, Hebert J.R, Rashidkhani B. Dietary inflammatory index and risk of esophageal squamous cell cancer in a case-control study from Iran.  Nutr Cancer . 2015;67:1253–1259.

115. Shivappa N, Bosetti C, Zucchetto A, Serraino D, La Vecchia C, Hebert J.R. Dietary inflammatory index and risk of pancreatic cancer in an Italian case-control study.  Br J Nutr . 2015;113:292–298.

116. Shivappa N, Blair C.K, Prizment A.E, Jacobs Jr. D.R, Steck S.E, Hebert J.R.Association between inflammatory potential of diet and mortality in the Iowa Women's Health study.  Eur J Nutr . 2016;55:1491–1502.

117. Maisonneuve P, Shivappa N, Hebert J.R, Bellomi M, Rampinelli C, Bertolotti R, Spaggiari L, Palli D, Veronesi G, Gnagnarella P.Dietary inflammatory index and risk of lung cancer and other respiratory conditions among heavy smokers in the COSMOS screening study.  Eur J Nutr . 2015;55:1069–1079. .

118. Ge I, Rudolph A, Shivappa N, Flesch-Janys D, Hebert J.R, Chang-Claude J. Dietary inflammation potential and postmenopausal breast cancer risk in a German case-control study.  Breast . 2015;24:491–496.

119. Shivappa N, Prizment A.E, Blair C.K, Jacobs Jr. D.R, Steck S.E, Hebert J.R.Dietary Inflammatory Index (DII) and risk of colorectal cancer in Iowa Women's Health Study.  Cancer Epidemiol Biomarkers Prev . 2014;23:2383–2392.

120. Shivappa N, Bosetti C, Zucchetto A, Montella M, Serraino D, La Vecchia C, Hebert J.R. Association between dietary inflammatory index and prostate cancer among Italian men.  Br J Nutr . 2014;113:278–283.

121. Shivappa N, Steck S.E, Hurley T.G, Hussey J.R, Hebert J.R. Designing and developing a literature-derived population-based dietary inflammatory index.  Public Health Nutr . 2014;17:1689–1696.

122. Vahid F, Shivappa N, Hekmatdoost A, Hebert J.R, Davoodi S.H, Sadeghi M. Association between Maternal Dietary Inflammatory Index (DII) and abortion in Iranian women and validation of DII with serum concentration of inflammatory factors: case-control study.  Appl Physiol Nutr Metabol . 2017;42:511–516.

123. Boden S, Wennberg M, Van Guelpen B, Johansson I, Lindahl B, Andersson J, Shivappa N, Hebert J.R, Nilsson L.M.Dietary inflammatory index and risk of first myocardial infarction; a prospective population-based study.  Nutr J . 2017;16:21.

124. Kotemori A, Sawada N, Iwasaki M, Yamaji T, Shivappa N, Hebert J.R. Association between dietary inflammatory index and high-sensitivity C-reactive protein levels in cancer screening in Japanese.  Rev Epidemiol Sante Publique . 2018;66:S347.

125. Kizil M, Tengilimoglu-Metin M.M, Gumus D, Sevim S, Turkoglu I, Mandiroglu F.Dietary inflammatory index is associated with serum C-reactive protein and protein energy wasting in hemodialysis patients: a cross-sectional study.  Nutr Res Pract . 2016;10:404–410.

126. Na W, Kim M, Sohn C. Dietary inflammatory index and its relationship with high-sensitivity C-reactive protein in Korean: data from the health examinee cohort.  J Clin Biochem Nutr . 2018;62:83–88.

127. Sen S, Rifas-Shiman S.L, Shivappa N, Wirth M.D, Hebert J.R, Gold D.R, Gillman M.W, Oken E.Dietary inflammatory potential during pregnancy is associated with lower fetal growth and breastfeeding failure: results from Project Viva.  J Nutr . 2016;146:728–736.

128. Shivappa N, Wirth M.D, Murphy E.A, Hurley T.G, Hebert J.R. Association between the Dietary Inflammatory Index (DII) and urinary enterolignans and C-reactive protein from the National Health and Nutrition Examination Survey-2003-2008.  Eur J Nutr . 2019;58:797–805.

129. Mayr H.L, Itsiopoulos C, Tierney A.C, Ruiz-Canela M, Hebert J.R, Shivappa N, Thomas C.J.Improvement in dietary inflammatory index score after 6-month dietary intervention is associated with reduction in interleukin-6 in patients with coronary heart disease: The AUSMED heart trial.  Nutr Res . 2018;55:108–121.

130. Shivappa N, Bonaccio M, Hebert J.R, Di Castelnuovo A, Costanzo S, Ruggiero E, Pounis G, Donati M.B, de Gaetano G, Iacoviello L. Association of proinflammatory diet with low-grade inflammation: results from the Moli-sani study.  Nutrition . 2018;54:182–188.

131. Shin D, Lee K.W, Brann L, Shivappa N, Hebert J.R. Dietary inflammatory index is positively associated with serum high-sensitivity C-reactive protein in a Korean adult population.  Nutrition . 2018;63–64:155–161.

132. Kotemori A, Sawada N, Iwasaki M, Yamaji T, Shivappa N, Hebert J.R, Ishihara J, Inoue M, Tsugane S.Validating the dietary inflammatory index using inflammatory biomarkers in a Japanese population: a cross-sectional study of the JPHC-FFQ validation study.  Nutrition . 2020;69:110569. .

133. Corley J, Shivappa N, Hebert J, Starr J, Deary I. Associations between dietary inflammatory index scores and inflammatory biomarkers among older adults in the Lothian Birth Cohort 1936 Study.  J Nutr Health Aging . 2019;23:628–636.

134. Coheley L.M, Shivappa N, Hebert J.R, Lewis R.D. Dietary inflammatory index(R) and cortical bone outcomes in healthy adolescent children.  Osteoporos Int . 2019;30:1645–1654.

135. Cervo M.M.C, Scott D, Seibel M.J, Cumming R.G, Naganathan V, Blyth F.M, Le Couteur D.G, Handelsman D.J, Ribeiro R.V, Waite L.M, et al. Proinflammatory diet increases circulating inflammatory biomarkers and falls risk in community-dwelling older men.  J Nutr . 2020;150:373–381.

136. Bondonno N.P, Blekkenhorst L.C, Bird A.L, Lewis J.R, Hodgson J.M, Shivappa N, Hebert J.R, Woodman R.J, Wong G, Kerr D.A, et al. Dietary inflammatory index and the aging kidney in older women: a 10-year prospective cohort study.  Eur J Nutr . 2019;59:3201–3211.

137. Wirth M.D, Shivappa N, Khan S, Vyas S, Beresford L, Sofge J, Hébert J.R. Impact of a 3-month anti-inflammatory dietary intervention focusing on watermelon on body habitus, inflammation, and metabolic markers: a pilot study.  Nutr Metab Insights . 2020;13 1178638819899398.

138. Suzuki K, Shivappa N, Kawado M, Yamada H, Hashimoto S, Wakai K, Iso H, Okada E, Fujii R, Hebert J.R, et al. Association between dietary inflammatory index and serum C-reactive protein concentrations in the Japan Collaborative Cohort Study.  Nagoya J Med Sci . 2020;82:237–249.

139. Yang Y.Q, Hozawa A, Kogure M, Narita A, Hirata T, Nakamura T, Tsuchiya N, Nakaya N, Ninomiya T, Okuda N, et al. Dietary inflammatory index positively associated with high-sensitivity C-reactive protein level in Japanese From NIPPON DATA2010.  J Epidemiol . 2020;30:98–107.

140. Byrd D.A, Judd S.E, Flanders W.D, Hartman T.J, Fedirko V, Bostick R.M. Development and validation of novel dietary and lifestyle inflammation scores.  J Nutr . 2019;149:2206–2218.

141. Mirmajidi S, Izadi A, Saghafi-Asl M, Vahid F, Karamzad N, Amiri P, Shivappa N, Hébert J.R.Inflammatory potential of diet: association with chemerin, omentin, lipopolysaccharide-binding protein, and insulin resistance in the apparently healthy obese.  J Am Coll Nutr . 2018;38:302–310.

142. Khan S, Wirth M.D, Ortaglia A, Alvarado C.R, Shivappa N, Hurley T.G, Hebert J.R.Design, development and construct validation of the children’s dietary inflammatory index.  Nutrients . 2018;10:E993.

143. Suhett L.G, Hermsdorff H.H.M, Ribeiro S.A.V, Filgueiras M.S, Shivappa N, Hébert J.R, de Novaes J.F. The dietary inflammatory index is associated with anti- and pro-inflammatory adipokines in Brazilian schoolchildren.  Eur J Nutr . 2021;60:2841–2849.

144. Wallace M.K, Shivappa N, Wirth M.D, Hébert J.R, Huston-Gordesky L, Alvarado F, Mouzon S.H, Catalano P.M.Longitudinal assessment of relationships between health behaviors and IL-6 in overweight and obese pregnancy.  Biol Res Nurs . 2021;23:481–487.

145. Saghafi-Asl M, Mirmajidi S, Asghari Jafarabadi M, Vahid F, Shivappa N, Hébert J.R, Ebrahimzadeh Attari V. The association of dietary patterns with dietary inflammatory index, systemic inflammation, and insulin resistance, in apparently healthy individuals with obesity.  Sci Rep . 2021;11:7515.

146. Malcomson F.C, Willis N.D, McCallum I, Xie L, Shivappa N, Wirth M.D, Hébert J.R, Kocaadam-Bozkurt B, Özturan-Sirin A, Kelly S.B, et al. Diet-associated inflammation modulates inflammation and WNT signaling in the rectal mucosa, and the response to supplementation with dietary fibre.  Cancer Prev Res . 2021;14:337–346. .

147. Li S, Hodge A, MacInnis R, Bassett J, Ueland P, Midttun Ø, Ulvik A, Rinaldi S, Meyer K, Navionis A, et al. Inflammation-related marker profiling of dietary patterns and all-cause mortality in the Melbourne Collaborative Cohort Study.  J Nutr . 2021 Online ahead of print:nxab231.

148. Barragán-Vázquez S, Ariza A.C, Ramírez Silva I, Pedraza L.S, Rivera Dommarco J.A, Ortiz-Panozo E, Zambrano E, Reyes Castro L.A, Shivappa N, Hébert J.R, et al. Pro-inflammatory diet is associated with adiposity during childhood and with adipokines and inflammatory markers at 11 years in Mexican children.  Nutrients . 2020;12:E3658.

149. Ruiz-Canela M, Bes-Rastrollo M, Martinez-Gonzalez M.A. The role of dietary inflammatory index in cardiovascular disease, metabolic syndrome and mortality.  Int J Mol Sci . 2016;17:E1265.

150. Shivappa N, Hebert J.R, Kivimaki M, Akbaraly T. Alternative Healthy Eating Index 2010, Dietary Inflammatory Index and risk of mortality: results from the Whitehall II cohort study and meta-analysis of previous Dietary Inflammatory Index and mortality studies.  Br J Nutr . 2017;118:210–221.

151. Shivappa N, Godos J, Hebert J.R, Wirth M.D, Piuri G, Speciani A.F, Grosso G.Dietary inflammatory index and colorectal cancer risk-a meta-analysis.  Nutrients . 2017;9:E1043.

152. Fowler M.E, Akinyemiju T.F. Meta-analysis of the association between dietary inflammatory index (DII) and cancer outcomes.  Int J Cancer . 2017;141:2215–2227.

153. Kim J.H, Kim J. Index-based dietary patterns and the risk of prostate cancer.  Clin Nutr Res . 2017;6:229–246.

154. Zhong X, Guo L, Zhang L, Li Y, He R, Cheng G. Inflammatory potential of diet and risk of cardiovascular disease or mortality: a meta-analysis.  Sci Rep . 2017;7:6367.

155. Fan Y, Jin X, Man C, Gao Z, Wang X. Meta-analysis of the association between the inflammatory potential of diet and colorectal cancer risk.  Oncotarget . 2017;8:59592–59600.

156. Sardo Molmenti C.L, Steck S.E, Thomson C.A, Hibler E.A, Yang J, Shivappa N, Greenlee H, Wirth M.D, Neugut A.I, Jacobs E.T, et al. Dietary inflammatory index and risk of colorectal adenoma recurrence: a pooled analysis.  Nutr Cancer . 2017;69:238–247.

157. Du M, Liu S.H, Mitchell C, Fung T.T. Associations between diet quality scores and risk of postmenopausal estrogen receptor-negative breast cancer: a systematic review.  J Nutr . 2018;148:100–108.

158. Zahedi H, Djalalinia S, Sadeghi O, Asayesh H, Noorozi M, Gorabi A.M, Mohammadi R, Qorbani M.Dietary inflammatory potential score and risk of breast cancer: a systematic review and meta-analysis.  Clin Breast Cancer . 2018;18:e561–e570.

159. Jayedi A, Emadi A, Shab-Bidar S. Dietary inflammatory index and site-specific cancer risk: a systematic review and dose-response meta-analysis.  Adv Nutr . 2018;9:388–403.

160. Varkaneh H.K, Fatahi S, Tajik S, Rahmani J, Zarezadeh M, Shab-Bidar S. Dietary inflammatory index in relation to obesity and body mass index: a meta-analysis.  Nutr Food Sci . 2018;48:702–721.

161. Lassale C, Batty G.D, Baghdadli A, Jacka F, Sanchez-Villegas A, Kivimaki M, Akbaraly T.Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies.  Mol Psychiatry . 2019;24:965–986.

162. Lu D.L, Ren Z.J, Zhang Q, Ren P.W, Yang B, Liu L.R, Dong Q. Meta-analysis of the association between the inflammatory potential of diet and urologic cancer risk.  PLoS One . 2018;13:e0204845.

163. Moradi S, Issah A, Mohammadi H, Mirzaei K. Associations between dietary inflammatory index and incidence of breast and prostate cancer: a systematic review and meta-analysis.  Nutrition . 2018;55–56:168–178. .

164. Namazi N, Larijani B, Azadbakht L. Association between the dietary inflammatory index and the incidence of cancer: a systematic review and meta-analysis of prospective studies.  Public Health . 2018;164:148–156.

165. Namazi N, Larijani B, Azadbakht L. Dietary inflammatory index and its association with the risk of cardiovascular diseases, metabolic syndrome, and mortality: a systematic review and meta-analysis.  Horm Metab Res . 2018;50:345–358.

166. Wang J, Zhou Y, Chen K, Jing Y, He J, Sun H, Hu X. Dietary inflammatory index and depression: a meta-analysis.  Public Health Nutr . 2019;22:654–660.

167. Wang L, Liu C, Zhou C, Zhuang J, Tang S, Yu J, Tian J, Feng F, Liu L, Zhang T, et al. Meta-analysis of the association between the dietary inflammatory index (DII) and breast cancer risk.  Eur J Clin Nutr . 2019;73:509–517.

168. Mohseni R, Abbasi S, Mohseni F, Rahimi F, Alizadeh S. Association between dietary inflammatory index and the risk of prostate cancer: a meta-analysis.  Nutr Cancer . 2019;71:359–366.

169. Kheirouri S, Alizadeh M. Dietary inflammatory potential and the risk of incident depression in adults: a systematic review.  Adv Nutr . 2019;10:9–18.

170. Liu Z.Y, Gao X.P, Zhu S, Liu Y.H, Wang L.J, Jing C.X, Zeng F.F. Dietary inflammatory index and risk of gynecological cancers: a systematic review and meta-analysis of observational studies.  J Gynecol Oncol . 2019;30:e23.

171. Garcia-Arellano A, Martinez-Gonzalez M.A, Ramallal R, Salas-Salvado J, Hebert J.R, Corella D, Shivappa N, Forga L, Schroder H, Munoz-Bravo C, et al. Dietary inflammatory index and all-cause mortality in large cohorts: the SUN and PREDIMED studies.  Clin Nutr . 2019;38:1221–1231.

172. Farhangi M.A, Nikniaz L, Nikniaz Z, Dehghan P. Dietary inflammatory index potentially increases blood pressure and markers of glucose homeostasis among adults: findings from an updated systematic review and meta-analysis.  Public Health Nutr . 2020;23:1362–1380.

173. Zhu Y, Li Q, Xu X. Dietary inflammatory index and the risk of prostate cancer: a dose-response meta-analysis.  Eur J Clin Nutr . 2019;25:25.

174. Du S.H, Li Y, Su Z.Q, Shi X.G, Johnson N.L, Li P, Zhang Y, Zhang Q, Wen L.Z, Li K.X, et al. Index-based dietary patterns in relation to gastric cancer risk: a systematic review and meta-analysis.  Br J Nutr . 2020;123:964–974.

175. Zhu J.H, Ling Y.X, Mi S, Chen H.Z, Fan J.Y, Cai S.F, Fan C.H, Shen Q, Li Y.J.Association between dietary inflammatory index and upper aerodigestive tract cancer risk: A systematic review and dose-response meta-analysis.  Oral Oncol . 2020;103:8.

176. Fernandez-Villa T, Alvarez-Alvarez L, Rubin-Garcia M, Obon-Santacana M, Moreno V.The role of dietary patterns in colorectal cancer: a 2019 update.  Expert Rev . 2020;14:281–290.

177. Suhett L.G, Hermsdorff H.H.M, Cota B.C, Ribeiro S.A.V, Shivappa N, Hébert J.R, Franceschini SdCC, de Novaes J.F. Dietary inflammatory potential, cardiometabolic risk and inflammation in children and adolescents: a systematic review.  Crit Rev Food Nutr . 2020;61:407–416.

178. Liang Y, Jiao H.Y, Qu L.B, Liu H. Positive association between dietary inflammatory index and gastric cancer risk: a systematic review and meta-analysis.  Nutr Cancer . 2019 E-Published:7.

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180. Ji M.X, Hong X.F, Chen M.Y, Chen T.J, Wang J, Zhang N. Dietary inflammatory index and cardiovascular risk and mortality a meta-analysis of cohort studies.  Medicine . 2020;99:7. .

181. Hua R.Y, Liang G.M, Yang F.Y. Meta-analysis of the association between dietary inflammatory index (DII) and upper aerodigestive tract cancer risk.  Medicine . 2020;99:9.

182. Moradi S, Hadi A, Mohammadi H, Asbaghi O, Zobeiri M, Marx W, Entezari M.H. Dietary inflammatory index and the risk of frailty among older adults: a systematic review and meta-analysis.  Res Aging . 2020 EPub:9.

183. Fang Y, Zhu J, Fan J, Sun L, Cai S, Fan C, Zhong Y, Li Y. Dietary Inflammatory Index in relation to bone mineral density, osteoporosis risk and fracture risk: a systematic review and meta-analysis.  Osteoporosis Int . 2020 EPub:11.

184. Farhangi M.A, Vajdi M. The association between dietary inflammatory index and risk of central obesity in adults: An updated systematic review and meta-analysis.  Int J Vitam Nutr Res . 2020;90:535–552.

185. Aslani Z, Sadeghi O, Heidari-Beni M, Zahedi H, Baygi F, Shivappa N, Hébert J.R, Moradi S, Sotoudeh G, Asayesh H, et al. Association of dietary inflammatory potential with cardiometabolic risk factors and diseases: a systematic review and dose-response meta-analysis of observational studies.  Diabetol Metab Syndr . 2020;12:86.

186. Lertxundi N, Molinuevo A, Valvi D, Gorostiaga A, Balluerka N, Shivappa N, Hebert J, et al. Dietary inflammatory index of mothers during pregnancy and Attention Deficit-Hyperactivity Disorder symptoms in the child at preschool age: a prospective investigation in the INMA and RHEA cohorts. Eur Child Adolesc Psychiatry.

187. Chen L.W, Aubert A.M, Shivappa N, Bernard J.Y, Mensink-Bout S.M, Geraghty A.A, Mehegan J, Suderman M, Polanska K, Hanke W, et al. Associations of maternal dietary inflammatory potential and quality with offspring birth outcomes: An individual participant data pooled analysis of 7 European cohorts in the ALPHABET consortium.  PLoS Med . 2021;18:e1003491.

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Chapter 1: Inflammation in the long arc of history

James R. Hébert ¹ , ² , ³ , and Lorne J. Hofseth ² , ³ , ⁴       ¹ Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, United States      ² South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, United States      ³ Center for Colon Cancer Research, College of Pharmacy, University of South Carolina, Columbia, SC, United States      ⁴ Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, United States

Abstract

In this chapter, we describe the converging lines of evidence indicating that organisms have had the ability to mount inflammatory and related immune responses since the beginning of life on earth. We can trace our own ability to mount inflammatory and related immune responses through the lineages of our predecessors and symbiotic relationships that we have formed with other organisms over the hundreds of millions of years of our evolutionary history. This has culminated in a repertoire of classic inflammatory responses consisting of pain, redness, heat, and swelling that humans described many thousands of years ago. We describe the great variability and common threads that exist across all life forms that undergird their ability to detect and defend themselves against threats coming from a wide variety of forces. We also describe important connection between the inflammatory response and the innate immune response that we see in all animals, including humans. Going back in time, it becomes clear that our own adaptive abilities are related to both progenitors (organisms that are now considered to be well established as part of our genetic and evolutionary lineage) and microorganisms with which we have developed commensal/symbiotic relationships over our evolutionary histories. The descriptions of inflammation from ancient human history provide an observational framework on which scientific developments over the last several hundred years have begun to fill in the blanks of how these complex systems are coordinated. This includes an understanding of how our inflammatory and innate immune systems have evolved, how the adaptive immune system has developed as part of a highly successful system of immunological reconnaissance, and the intercellular messaging necessary to orchestrate these complicated response systems that can react quickly and effectively to danger and threats. Finally, we set the stage for understanding the role of nutrition in determining whether an acute inflammatory/innate immune response occurs or whether the organism is doomed (or, rather, dooms itself) to live in a state of chronic, systemic inflammation wherein a competent inflammatory and immune response is compromised, and quality and duration of life are diminished.

Keywords

Biological evolution; Chemokines; Cytokines; Evolution; Immune response; Inflammation; Innate immunity; Molecular; Natural history; Nuclear factor Kappa-B; Symbiosis

Take Home Messages

• The highly effective inflammatory responses that we see in humans and other higher organisms reflect a long evolutionary history of a universal ability to respond to threats.

• Our inflammatory machinery also reflects symbiotic relationships that we have established with single-celled organisms over our long evolutionary history.

• The intercellular messaging that we now understand occurs in humans also is evident in virtually every other animal and similar in striking ways to systems used in plants.

• The inflammatory response is expressed in the ability to mount an innate immune response.

• The processes that lead to common chronic diseases can be explained through an understanding of cell messaging that includes oxidative stress, cytokines, and chemokines that influence susceptibility states such as insulin resistance.

• As an important way that we experience our environment and as the virtually exclusive source of the raw materials on which metabolic machinery is built, diet is the most important modulator of inflammatory and immune responses.

1. Introduction: inflammatory responses are universal

Most books and scholarly articles on inflammation focus attention on how individuals respond to factors in the environment that present a challenge to well-being. Those that focus on the history of our knowledge of inflammation concentrate on written records describing how we have experienced inflammation during the course of human history. In Eastern medical traditions, such as Ayurvedic Medicine and Chinese Traditional Medicine, we can see references to the phenomenon of inflammation and to inflammation-related conditions, including type II diabetes mellitus (T2DM), which go back many thousands of years [1–4]. Certainly, there is a strong history of considering the role of inflammation in diseases such as cancer in the Ayurvedic tradition [2,5]. In the Western tradition, we also see a somewhat more recent and better-known reference to the four hallmarks of inflammation (dolor, rubor, calor, tumor—i.e., pain, redness, heat, and swelling) by Aulus Cornelius Celsus, who lived in Rome from around 25BC to 50AD [6,7].

Though our central focus on the human experience of inflammation represents a rational way to approach the subject, all evidence points toward inflammation and related innate immune responses being a ubiquitous feature of life [6,8–12], and converging lines of evidence indicate that mounting inflammatory, and related immune, responses, were part of the repertoire of even primitive organisms that represent the earliest forms of life on earth [8,11,13]. Consider the wide expanse of life forms that can mount an inflammatory response. We see it in the most primitive of beings—including single-cell organisms [11,14]. While its manifestations vary widely from single-cell organisms such as bacteria and Protista (e.g., ameba) to widely divergent members of the animal and plant kingdoms with complicated organ systems, it is essentially and inextricably tied up with protection. What seems to be a common biological thread that connects all forms of life is the close association between the inflammatory response and the innate immune response [15,16].

1.1. Plant immune response

Plants do not have inflammatory response systems that resemble what we observe in very primitive animals or unicellular organisms [17–19]. For example, plants cannot move to escape predation or disease. Also, they lack chemotactic cells that can migrate to the site of an infection. So, to compensate, they have evolved sophisticated mechanisms to recognize that they are being attacked and to respond appropriately. Despite the absence of chemotactic cells or the ability to move, they can respond to environmental stimuli by, for example, walling off an infection or injury. We can see this as we walk in nature (Fig. 1.2). A tree may be attacked by insects, struck by lightning, or experience physical damage from, for example, another tree falling on it. In response, the tree will defend itself. While a tree may not mount what we would consider a classic inflammatory response (i.e., characterized by redness, swelling, heat and, from what we can tell, pain [7]), its ability to respond is a universal characteristic of all living beings.

Figure 1.1  (A). Ameba versus macrophage similarities. (B). Summary of animal and plant innate immune systems. The inflammatory response triggered by pathogens in the animal host with pattern recognition receptor-triggered immunity and effector-triggered immunity triggered by pathogens in the plant host are shown. CCL, C–C motif chemokine ligand; CXCL, chemokine (C–X–C motif) ligand; ETI, effector-triggered immunity; G-CSF, granulocyte-colony stimulating factor; GM-CSF, Granulocyte-macrophage colony-stimulating factor; IL, Interleukin; NO, nitric oxide; PAMPs, pathogen-associated molecular patterns; PRR, Pattern recognition receptor; PTI, PAMP triggered immunity; ROS, Reactive oxygen species; T3SS, type III secretion system; TNFα, Tumor necrosis factor alpha are also common across kingdoms to defend pathogens. From (A) Siddiqui, Khan. Acanthameba is an evolutionary