Feldman and Pike’s Vitamin D

Volume Two: Disease and Therapeutics

5th Edition - October 28, 2023
Editors: Martin Hewison, Roger Bouillon, Edward Giovannucci, David Goltzman, Mark Meyer B., JoEllen Welsh
Language: English
Hardback ISBN:
9 7 8 - 0 - 3 2 3 - 9 1 3 3 8 - 6
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 9 1 3 3 9 - 3

Vitamin D deficiency is a worldwide problem linked to numerous diseases affecting men, women, and children of all ages. Enormous progress in the study of vitamin D has been made si… Read more

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Vitamin D deficiency is a worldwide problem linked to numerous diseases affecting men, women, and children of all ages. Enormous progress in the study of vitamin D has been made since the first edition of this highly-acclaimed book was published nearly 20 years ago, and current research continues to draw headlines. Feldman and Pike’s Vitamin D, Fifth Edition continues to build on the successful formula from previous editions, taking the reader from the basic elements of fundamental research to the most sophisticated concepts in therapeutics. The two comprehensive volumes provide investigators, clinicians, and students with a comprehensive, definitive, and up-to-date compendium of the diverse scientific and clinical aspects of vitamin D, where each area is covered by both basic and clinical experts in the field.

In Volume I: Biochemistry, Physiology and Diagnostics, international experts in endocrinology, bone biology, and human physiology take readers through the basic research of vitamin D. This impressive reference presents a comprehensive review of the multi-faceted actions of vitamin D relating both to skeletal and extra-skeletal action. Researchers from all areas of vitamin D will gain insight into how clinical observations and practices can feed back into the research cycle and will, therefore, be able to develop more targeted genomic and proteomic insights into the mechanisms of disease.

Volume II: Health, Disease and Therapy authoritatively covers the evidence for new roles of vitamin D, ranging from organ transplantation to cancer, diabetes, inflammatory bowel disease, multiple sclerosis, and renal disease. The coverage is appropriately broad, drawing on aspects of internal medicine, pediatrics, nutrition, orthopedics, oncology, neurology, obstetrics and gynecology, and immunology, as well as, new areas for vitamin D including sports medicine, opthalmology, veterinary medicine and ICU care – including COVID-19. Clinical researchers will gain a strong understanding of the molecular basis for a particular disease and better understand future directions for research in this still-growing field.

Cover image
Title page
Table of Contents
Copyright
List of contributors
In memoriam
Preface to the fifth edition
List of abbreviations
Relevant lab values in adults and children
Chapter 51. Defining thresholds for vitamin D I: scientific rationale for serum 25-hydroxyvitamin D cutoffs of 25 and 50nmol/L
1. Introduction
2. Justification for serum 25(OH)D concentration >25nmol/L
3. Justification for serum 25(OH)D concentration >50nmol/L
4. Issues with reaching 25(OH)D thresholds for specific groups
5. Other issues surrounding definition of thresholds for vitamin D
6. Conclusion
7. Summary points
Chapter 52. Defining thresholds for vitamin D II
1. Introduction
2. Human biology
3. Nutrition clinical trials cannot match the quality of evidence achieved with drugs
4. Cancer
5. Mortality
6. Cardiovascular
7. Toxicity
8. Multiple sclerosis
9. COVID-19
10. Conclusion
11. Summary points
Chapter 53. Methods of evaluating population studies of vitamin D: strengths and weaknesses
1. Introduction
2. Methods of assessing vitamin D status
3. Main challenges in the epidemiologic study of vitamin D and disease
4. Summary of study designs of vitamin D
5. Conclusions
6. Summary points
Chapter 54. Worldwide vitamin D status
1. Introduction
2. Assessment of vitamin D status
3. Study selection
4. Multicenter and global studies using a central laboratory facility
5. Ethnicity/migration
6. Nutrition
7. Risk groups
8. Trends in vitamin D status
9. Implications
10. Conclusions
11. Summary points
Chapter 55. Vitamin D in food—Compounds, stability, sources
1. Introduction
2. Chemical structure of vitamin D vitamers
3. Stability of vitamin D
4. Analytical methodology
5. Vitamin D in food
6. Conclusion
7. Summary points
Chapter 56. Determinants of vitamin D levels from sun exposure: a global perspective
1. Introduction
2. Vitamin D production from solar UVB exposure
3. Factors affecting 25-hydroxyvitamin D concentrations
4. Endogenous characteristics
5. Behavioral determinants
6. Predicting vitamin D deficiency
7. Nonvitamin D benefits from solar UV exposure
8. Conclusion
9. Summary points
Chapter 57. Vitamin D supplement use as a public health strategy to augment diet and sustain population adequacy
1. Introduction
2. Thresholds for 25(OH)D
3. Country-level guidelines for supplements use
4. Supplement use improves vitamin D status: Canada as a case study
5. Characteristics of vitamin D supplement users
6. Considerations when choosing to take a vitamin D supplement
7. Safety of vitamin D supplements
8. Guidance is needed for use of vitamin D supplements
9. Conclusion
10. Summary points
Chapter 58. Vitamin D and food fortification
1. Introduction
2. Current intakes of vitamin D in young and adult populations in North America and Europe and how these compare against dietary targets
3. Dietary strategies for increasing vitamin D intake: bridging the gap by food fortification
4. Consideration of other vitamin D–fortified foods
5. Vitamin D–biofortified foods
6. Safety considerations and prerequisite data required prior to initiating public health measures
7. Conclusions
8. Summary points
Chapter 59. Bariatric surgery, vitamin D, and bone loss
1. Introduction
2. Skeletal effects of bariatric surgery
3. Potential mechanisms of bone loss
4. Prevention and treatment of skeletal effects
5. Summary points
Chapter 60. Genetic determinants of 25-hydroxyvitamin D concentrations
1. Introduction
2. 25(OH)D synthesis and metabolism
3. Heritability of serum 25(OH)D levels
4. Genome-wide association studies of 25(OH)D
5. Variants with evidence for replicated association with 25(OH)D
6. Gene–environment interaction
7. Applications and practical implications
8. Conclusions
9. Summary points
Chapter 61. Effect of vitamin D on health and disease: evidence from Mendelian randomization
1. Introduction
2. Type 2 diabetes
3. Risk of cancers
4. Risk of cardiovascular events
5. Hypertension
6. Musculoskeletal outcomes
7. Lung function and respiratory conditions
8. Immune disorders
9. Pregnancy-related outcomes
10. Neuropsychiatric outcomes
11. COVID-19
12. Mortality risk and aging
13. Other outcomes
14. Nonlinear MR studies
15. Conclusion
16. Summary points
Chapter 62. Growth plate histology, bone histomorphometry, and radiologic features of nutritional rickets and osteomalacia
1. Introduction
2. Terminology related to bone formation and mineralization
3. The growth plate
4. Mineralization
5. Bone histomorphometry in osteomalacia
6. Bone mineral density distribution in osteomalacia
7. Radiological features of rickets and osteomalacia
8. Radiographic differences between various forms of rickets
9. Imaging choice in rickets and osteomalacia
10. Conclusion
11. Summary points
Chapter 63. Vitamin D deficiency and nutritional rickets in infants and children
Index terms
1. Introduction
2. Historical perspective
3. The epidemiology of vitamin D deficiency and nutritional rickets
4. Clinical presentation
5. Biochemical abnormalities
6. Biomarkers of active rickets
7. Radiologic changes
8. The growth plate in rickets
9. Treatment
10. Prevention
11. Dietary calcium deficiency
12. Rickets of prematurity or metabolic bone disease of prematurity
13. The pathogenetic spectrum of nutritional rickets
14. Conclusion
Chapter 64. Clinical disorders of phosphate homeostasis
1. Introduction
2. Phosphate homeostasis
3. Disorders of phosphate homeostasis
4. Conclusion
5. Summary points
Chapter 65. The hypocalcemic disorders
1. Introduction
2. Physiology of hypocalcemia
3. Clinical manifestations of hypocalcemia
4. Differential diagnosis of hypocalcemia
5. Parathyroid hormone–independent hypocalcemia
6. Genetic forms of vitamin D–dependent rickets
7. Dietary calcium deficiency
8. Hyperphosphatemia-mediated hypocalcemia
9. Hypocalcemia due to accelerated skeletal mineralization
10. Medical illness
11. Treatment of hypocalcemia
12. Conclusion
13. Summary points
Chapter 66. Vitamin D hydroxylation–deficient rickets, type 1A
1. Introduction
2. Clinical manifestations
3. Biochemical findings
4. Genetic and molecular studies
5. Treatment of VDDR1A
6. Evolution of VDDR1A under treatment from childhood to adulthood
7. Conclusion
8. Summary points
Chapter 67. The role of genetic variation in CYP2R1, the principal vitamin D 25-hydroxylase, and CYP3A4 in vitamin D homeostasis
1. Introduction
2. CYP2R1 is the principal human vitamin D 25-hydroxylase
3. CYP2R1 and vitamin D–dependent rickets
4. CYP3A4 and vitamin D–dependent rickets
5. In vitro and in silico analyses of CYP2R1 function
6. Associations between CYP2R1 variants and disease
7. Regulation of CYP2R1 in health and disease
8. Conclusion
9. Summary points
Chapter 68. Hereditary 1,25-dihydroxyvitamin D resistant rickets (VDDR-2A)
1. Introduction
2. Clinical features
3. Mechanism of 1,25(OH)2D action relevant to HVDRR(VDDR-2A)
4. Cellular basis of HVDRR (VDDR-2A)
5. Mutations that cause HVDRR (VDDR-2A)
6. Therapy of HVDRR (VDDR-2) patients
7. Hypothesis regarding the mechanism for spontaneous healing: outgrowing the need for substantial calcium supplementation in many HVDRR patients after puberty
8. Alopecia
9. Extra-skeletal actions of vitamin D in HVDRR (VDDR-2A) patients
10. Conclusions
11. Summary points
Chapter 69. Infantile hypercalcemia and CYP24A1 mutations
1. Introduction
2. Historical notes
3. The genetic basis of the disease: molecular genetics of CYP24A1 mutations
4. The pathophysiology of the disease: mutated CYP24A1 in the vitamin D metabolism
5. Clinical features
6. Diagnosis
7. Therapy
8. Conclusion
9. Summary points
Chapter 70. Vitamin D and osteoporosis
1. Introduction
2. Effects of vitamin D on the skeleton
3. The role of vitamin D genetic factors in osteoporosis and possible interactions with vitamin D therapy
4. Seasonal variation in vitamin D status
5. Determining optimal serum 25-hydroxyvitamin D concentrations for musculoskeletal health
6. Effects of vitamin D alone or calcium and vitamin D on bone mineral density and falls
7. Primary fracture prevention with vitamin D or calcium and vitamin D
8. Metaanalyses
9. Safety
10. Effects of active vitamin D analogs on fractures
11. Large randomized controlled trials of vitamin D supplementation
12. Mendelian randomization studies
13. Conclusions and future directions
14. Summary points
Chapter 71. Adult vitamin D deficiency—fracture and fall prevention: findings from randomized controlled trials
1. Introduction
2. Vitamin D and falls
3. Vitamin D and fracture risk
4. Conclusions
5. Summary points
Chapter 72. Randomized clinical trials of vitamin D and bone health
1. Introduction: clinical and public health importance
2. Findings from systematic reviews and metaanalyses
3. Current recommended intakes based on bone health goals
4. RCTs of effects of vitamin D supplementation on bone density
5. RCTs of effects of vitamin D supplementation on fracture risk
6. Implications for clinical practice
7. Conclusion
8. Summary points
Chapter 73. Calcifediol as a therapeutic
1. Introduction
2. Treatment of vitamin D insufficiency with calcifediol
3. Calcifediol treatment of secondary hyperparathyroidism associated with chronic kidney disease
4. Calcifediol treatment of microbial disease to boost the human innate and adaptive immune responses
5. Conclusion
6. Summary points
Chapter 74. Vitamin D and organ transplantation
1. Introduction
2. Effects of vitamin D on immunity and graft rejection
3. Vitamin D deficiency prior to organ transplant
4. Vitamin D deficiency following organ transplant
5. Treatment of posttransplant bone loss with vitamin D and analogs
6. Conclusions
7. Summary points
Chapter 75. Vitamin D, obesity, the metabolic syndrome and its sequelae
1. Introduction
2. Adipose tissue as a vitamin D reserve
3. Obesity and vitamin D deficiency
4. Obesity, DBP, and “free” vitamin D concentrations
5. The effect of weight loss on serum 25(OH)D concentrations
6. Can vitamin D supplementation prevent, or reduce, obesity?
7. Obesity and the efficacy of oral vitamin D supplementation
8. Brown adipose tissue, obesity, and vitamin D
9. Obesity, vitamin D, and metabolic syndrome
10. Importance of early-life vitamin D status for later obesity and subsequent risks of metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease
11. Obesity, vitamin D, and cancer
12. Obesity, COVID-19, and vitamin D
13. Conclusions
14. Summary points
Chapter 76. The role of vitamin D in type 2 diabetes
1. Introduction
2. Epidemiology and burden of type 2 diabetes
3. Biologic plausibility of the link between vitamin D and type 2 diabetes
4. Observational studies on vitamin D and type 2 diabetes
5. Vitamin D supplementation in people with normal glucose tolerance or type 2 diabetes
6. Vitamin D for prevention of type 2 diabetes in people with prediabetes
7. Optimizing blood 25(OH)D levels and the concept of “treat-to-target”
8. Effect modification of vitamin D supplementation by BMI
9. Safety of vitamin D supplementation for prevention of type 2 diabetes
10. Conclusions
11. Summary points
Chapter 77. Liver metabolism and disease
1. Introduction
2. Vitamin D/VDR signaling and antiinflammatory responses in the liver
3. Vitamin D/VDR signaling in liver fibrosis and NASH
4. Conclusions
5. Summary points
Chapter 78. Vitamin D, hypertension, and cardiovascular disease
1. Introduction
2. Vitamin D metabolism and regulation with special reference to cardiovascular disease
3. Vitamin D effects on cardiovascular cells
4. Vitamin D effects in experimental animals
5. Rickets, osteomalacia, and cardiovascular disease
6. Vitamin D status and cardiovascular outcomes in observational studies
7. Genetic studies on vitamin D and cardiovascular outcomes
8. Vitamin D supplementation studies
9. Cardiovascular events in large vitamin D supplementation trials in general populations
10. Vitamin D in end-stage organ failure
11. Adverse vitamin D effects on the cardiovascular system
12. Conclusion
13. Summary points
Chapter 79. Vitamin D and renal disease
1. Introduction
2. Renal regulation of the vitamin D endocrine system
3. Alterations in vitamin D bioactivation to 25(OH)D in chronic kidney disease
4. Alterations in renal 1,25(OH)2D synthesis and 25(OH)D and 1,25(OH)2D catabolism in chronic kidney disease
5. Alterations in 1,25(OH)2D production by extrarenal 1α-Hydroxylases in chronic kidney disease
6. Alterations in 1,25(OH)2D/VDR endocrine and autocrine/paracrine actions in CKD
7. Vitamin D control of secondary hyperparathyroidism
8. Vitamin D control of skeletal health in CKD unrelated to the attenuation of secondary hyperparathyroidism
9. Vitamin D maintenance of renal FGF23/klotho axis: relevance for renal and cardiovascular protection
10. Vitamin D control of hypertension and systemic inflammation conferring renal and cardiovascular protection independently of renal or systemic klotho levels
11. Progress to improve current recommendations for the evaluation of vitamin D status and for the design of safe and effective vitamin D interventions
12. Summary points
Chapter 80. Vitamin D and kidney stones
1. Introduction
2. Calcium kidney stones
3. Vitamin D metabolism
4. Idiopathic hypercalciuria
5. Vitamin D supplementation and kidney stone risk
6. Conclusions
7. Summary points
Chapter 81. Hypercalcemia due to vitamin D toxicity
1. Introduction
2. Forms of exogenous vitamin D toxicity
3. Forms of endogenous Vitamin D toxicity
4. Mechanisms of vitamin D toxicity
5. Clinical manifestations of vitamin D toxicity
6. Conclusions
7. Summary points
Chapter 82. Vitamin D and Paget's disease
1. Introduction
2. Mechanism of action of 1,25(OH)2D3 on osteoclast formation
3. Increased levels of TAF12 in osteoclast precursors from Paget's disease patients contribute to their hyperresponsivity to 1,25(OH)2D3
4. Mechanism of action of TAF12 in the increased 1,25(OH)2D3 responsivity of OCL precursors from Paget's patients
5. Marrow stromal cells derived from P62P394L knock-in mice and P62P392L Paget's patients are hyperresponsive to 1,25(OH)2D3 and display enhanced RANKL production in response to 1,25(OH)2D3
6. Deleting TAF12 in mouse OCLs inhibits bone destruction and bone-remodeling
7. Serum concentration of 1,25(OH)2D3 in Paget's patients
8. Conclusions
9. Summary points
Chapter 83. Vitamin D metabolism and disorders in companion animals
1. Introduction
2. Dog
3. Cat
4. Conclusions and future directions
5. Summary points
Chapter 84. Overview of vitamin D actions in cancer
1. Introduction
2. Vitamin D and cancer
3. Vitamin D effects on tumor cells
4. Combination therapy
5. Resistance and vitamin D metabolism
6. Stimulation of proliferation
7. Conclusions
8. Summary points
Chapter 85. Vitamin D status and cancer incidence, mortality, and prognosis
1. Introduction
2. Cancer incidence
3. Cancer mortality and survival
4. Genetic variation and gene expression in the vitamin D pathway
5. Conclusions
6. Summary points
Chapter 86. Antiproliferative and immunoregulatory actions of vitamin D derivatives on hematological malignancies: control of differentiation, proliferation, and cell death
1. Differentiation of myeloid leukemia cells by vitamin D derivatives
2. Signaling and execution of monocytic differentiation induced by VDDs
3. Transcription factors in VDD-induced differentiation
4. Effects of VDDs on the cell cycle and proliferation of human leukemia cells
5. Effects of VDDs on cell survival and cell death
6. Effects of VDDs on lymphoid lineage cells and immunity
7. Clinical applications of VDD actions against hematopoietic malignancies
8. Significance of basic and clinical studies of VDDs inhematopoietic malignancies: from bench to bedside
9. Conclusions
10. Summary points
Chapter 87. Vitamin D, inflammation, and cancer
1. Introduction
2. Vitamin D and the vitamin D system
3. Inflammation
4. Inflammation-associated cancer
5. Conclusions
6. Summary points
Chapter 88. Vitamin D actions in mammary gland and breast cancer
1. Introduction
2. Observational and interventional studies on vitamin D and breast cancer
3. Expression and function of the vitamin D pathway in normal and neoplastic breast cells/tissues
4. Impact of vitamin D signaling in animal models of breast cancer
5. Genomic profiling of VDR agonists in breast cancer model systems
6. Mechanistic insight into vitamin D actions in breast cancer
7. Conclusion
8. Summary points
Chapter 89. Vitamin D and colorectal cancer
1. Introduction
2. Human observational and intervention studies
3. Expression of vitamin D hydroxylases and the vitamin D receptor in colorectal cancer
4. Mechanism of action of 1,25(OH)2D3 in colorectal cancer
5. Animal models
6. Conclusion
7. Summary points
Chapter 90. Vitamin D in the management of lung cancer: influence of tumor stage, tumor genotype, and treatment modality
1. Introduction
2. Vitamin D may have tumor cell intrinsic and tumor cell extrinsic activities in lung cancer
3. The role of vitamin D in the chemoprevention of non–small-cell lung cancer
4. The role of vitamin D in management of early-stage lung cancer
5. The role of vitamin D in the management of advanced lung cancer
6. Strategies to maximize vitamin D signaling in lung cancer
7. Conclusions
8. Summary points
Chapter 91. Vitamin D and prostate cancer
1. Introduction: prostate cancer is a heterogenous disease
2. Epidemiologic associations between prostate cancer and vitamin D metabolites
3. The rationale to treat prostate cancer by targeting the VDR
4. High-dimensional data approaches to understanding VDR functions in the prostate
5. Lessons from PCa clinical trials with vitamin D compounds
6. Conclusion
7. Summary points
Chapter 92. Vitamin D and pancreatic cancer
1. Pancreatic cancer: an overview
2. Pancreatic cancer and vitamin D: epidemiological studies
3. The biology and genetics of pancreatic cancer
4. The biology of vitamin D in pancreatic cancer: experimental studies
5. Vitamin D and prognosis in patients with PC
6. Vitamin D intervention studies in patients with PC
7. Conclusions
8. Summary points
Chapter 93. Sunlight, skin cancer and vitamin D
1. Introduction
2. UV-induced DNA damage, repair, and immune suppression
3. The vitamin D system and skin cancers
4. Mechanisms of protection from UV-induced skin tumors
5. Conclusions
6. Summary points
Chapter 94. Vitamin D and antibacterial immunity
1. Introduction
2. 1,25(OH)2D, barrier integrity, and complement activation
3. 1,25(OH)2D induces antimicrobial peptides implicated in antibacterial immunity
4. 1,25(OH)2D and autophagy
5. 1,25(OH)2D promotes expression of pattern recognition receptors and cytokines
6. 1,25(OH)2D regulates release of reactive oxygen species
7. Evolutionary aspects of 1,25(OH)2D induction of AMPs and PRRs
8. 1,25(OH)2D and neutrophils
9. 1,25(OH)2D and natural killer cells
10. 1,25(OH)2D and nonclassical immune cells
11. In vivo evidence for 1,25(OH)2D regulation of antibacterial innate immunity
12. Conclusion
13. Summary points
Chapter 95. Vitamin D and antiviral immunity
1. Introduction
2. Association between vitamin D insufficiency and viral disease in epidemiological and interventional studies
3. Immunological mechanisms of viral control
4. Vitamin D and immunomodulation
5. Innate immune sensing of viruses and 1,25(OH)2D
6. Antimicrobial peptides in antiviral immunity and 1,25(OH)2D
7. Antiviral cytokine and chemokine responses and 1,25(OH)2D
8. Natural killer cell responses and 1,25(OH)2D
9. Antiviral CD4 T cell immunity and 1,25(OH)2D
10. Antiviral CD8 T cell immunity and 1,25(OH)2D
11. B cell responses to viruses and 1,25(OH)2D
12. Conclusions
13. Summary points
Chapter 96. Vitamin D and adaptive immunity in health and disease
1. Introduction
2. Epidemiological and other evidence supporting a role of vitamin D in immune disease
3. Translational studies as a window to study effects of vitamin D on adaptive immunology
4. Actions of vitamin D on proinflammatory T lymphocyte responses
5. Naïve T cells
6. Effects of vitamin D on CD4+ T cell subsets
7. γδ T cells
8. CD8+ T cells
9. Actions of vitamin D on regulatory T lymphocyte responses
10. Actions of vitamin D on B lymphocytes
11. Actions of vitamin D on the immune microenvironment and the function of APCs
12. Effects of vitamin D upon immunometabolism in APC and T cells
13. Translational aspects of vitamin D regulation of adaptive immunity—vitamin D and vaccine responses
14. Disparity between association, translational, and clinical studies
15. Protection from exacerbation of airway disease by vitamin D
16. UVB and vitamin D at the skin—how does this compare with oral supplementation
17. Conclusions
18. Summary points
Chapter 97. Vitamin D, microbiota, and inflammatory bowel disease
1. Introduction
2. What is inflammatory bowel disease?
3. Who gets inflammatory bowel disease?
4. The immune system and inflammatory bowel disease
5. Experimental models of inflammatory bowel disease
6. Current treatments for inflammatory bowel disease
7. Vitamin D as a treatment option for inflammatory bowel disease
8. Conclusions
9. Summary points
Chapter 98. Vitamin D and tuberculosis
1. Introduction
2. The immune response in tuberculosis
3. Influence of vitamin D on the immune response to MTB
4. Historical studies
5. Studies with MTB infection as an end point
6. Studies with active TB disease as end point
7. Studies of treatment outcome
8. Conclusions
9. Summary points
Chapter 99. The role of vitamin D in COVID-19
1. Introduction
2. Vitamin D and immunity and inflammation: relevance to COVID-19 infection
3. Vitamin D and respiratory tract infections
4. Vitamin D and COVID-19: geographical latitude and UV radiation
5. Vitamin D and COVID-19: community observational studies
6. Vitamin D and COVID-19: hospital observational studies
7. Vitamin D and COVID-19: effects of polymorphisms in VDR and vitamin D–binding protein genes
8. Vitamin D and SARS-CoV-2 vaccination response
9. Vitamin D supplementation and COVID-19
10. Current guidance of COVID-19 and vitamin D and future research
11. Conclusions
12. Summary points
Chapter 100. Vitamin D and type 1 diabetes
1. Introduction
2. Effect of vitamin D deficiency on type 1 diabetes presentation
3. Relation between vitamin D–related genes and the genetic predisposition to type 1 diabetes
4. Vitamin D and the beta cell
5. Vitamin D as an immune modulator in type 1 diabetes
6. Interventions using vitamin D to prevent or arrest type 1 diabetes
7. Immune effects of interventions with vitamin D in type 1 diabetes
8. Vitamin D analogs and type 1 diabetes
9. Vitamin D in combination therapy to prevent or arrest type 1 diabetes
10. Conclusion
11. Summary points
Chapter 101. Vitamin D mechanisms of protection in multiple sclerosis
1. Introduction
2. Vitamin D and MS genetics
3. MS sexual dimorphism
4. CD4+FOXP3+ T regulatory cells and hormonal regulation of FOXP3
5. Interplay between vitamin D and CD4+ type 1 regulatory T cells in MS
6. Oligodendrocytes, DNA methylation, and the methionine cycle
7. Some reflections on vitamin D3 supplementation trials in MS
8. Conclusion
9. Summary points
Chapter 102. Vitamin D and the epidemiology of multiple sclerosis
1. Introduction
2. Descriptive epidemiology
3. Vitamin D and MS—historical perspective
4. Vitamin D and risk of MS
5. Vitamin D, race, and MS risk
6. Vitamin D and MS disease activity and progression
7. Pediatric onset MS
8. Conclusion
9. Summary points
Chapter 103. Vitamin D and rheumatoid arthritis
1. Introduction
2. Antiinflammatory effects of vitamin D
3. Vitamin D and mouse models of RA
4. Vitamin D deficiency and RA disease risk, severity, and progression
5. Genetic variation in the vitamin D system and RA
6. Effects of supplementary vitamin D on RA
7. Conclusions
8. Summary points
Chapter 104. Psoriasis and other skin disorders
1. Introduction/historical overview
2. Pathogenesis of psoriasis
3. The vitamin D system in normal and psoriatic skin
4. Physiological and pharmacological actions of vitamin D analogs in normal and psoriatic skin
5. Clinical use of 1,25(OH)2D3 and its analogs in psoriasis and other skin diseases
6. Vitamin D in prevention and therapy of other skin diseases
7. Evaluation of new vitamin D analogs, with less calcemic activity, which can be used for the treatment of hyperproliferative skin disorders
8. Conclusion
9. Summary points
Chapter 105. Vitamin D, acute respiratory infection, and Asthma/COPD
1. Introduction
2. Common respiratory disorders
3. Vitamin D and lung development
4. Vitamin D and acute respiratory infection
5. Vitamin D and asthma
6. Vitamin D and Copd
7. Potential mechanisms
8. Future research
9. Conclusion
10. Summary points
Chapter 106. Vitamin D and acute illness
1. Introduction
2. Prevalence of vitamin D deficiency in the critically ill patient
3. Vitamin D deficiency risk factors in the critically ill
4. Vitamin D mechanisms in critical illness
5. Vitamin D and critical care patients
6. Conclusions
7. Summary points
Index for Volume 2

Martin Hewison

Prof. Hewison’s work focuses on different facets of vitamin D physiology, including classical skeletal effects and non-classical extra-skeletal effects. He has a particular interest in the interaction between vitamin D and the immune system, where antigen-presenting cells such as dendritic cells and macrophages synthesize active vitamin D (calcitriol) and also express the nuclear receptor for calcitriol (VDR). Vitamin D can therefore act as an endogenous regulator of both innate and adaptive immunity by enhancing antibacterial activity, and modulating antigen presentation and T lymphocyte function. Crucially these responses are highly dependent on the bioavailability of vitamin D, and Prof. Hewison has hypothesized that immune function is influenced by vitamin D status in humans. His group is using a variety of models to test this hypothesis including basic molecular and cell analyses, and vitamin D supplementation trials in human cohorts. A key objective of his work is to increase awareness of vitamin D-deficiency in the UK population.

Affiliations and expertise

Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

Roger Bouillon

Roger Bouillon, MD, PhD, FRCP, biography Roger Bouillon is professor (emeritus since 2010) in endocrinology (internal medicine) at the University and University Hospital of the Catholic University of Leuven (K.U.Leuven) in Belgium. He is a member of the Royal Academy of Medicine (Belgium) and a Fellow of the Royal College of Physicians (London). He was a founding member and later President of the European Board of Endocrinology (UEMS 1988-2002). He was a member of several European Science Foundation Committees (Board member of the European Medical Research Council) and of the European Space Agency Life Science working group till 2012. He is past-president of the International Bone and Mineral Society (2011-13 ) and is co-organizer of the vitamin D workshop. He was vice president for research of the University of Leuven from 1995-2005. He is coauthor of more than 500 peer reviewed articles that generated about 26,000 ISI citations and a H index of 82. The topics of his research deal with (1) several aspects of diabetes an endocrinology in general but his main research focus deals with (2) hormonal aspects of bone and calcium homeostasis and this spans the spectrum of basic, translational and clinical research. (3) Vitamin D is a major research focus throughout his scientific career. Papers:

Affiliations and expertise

Professor in Endocrinology, University and University Hospital, Catholic University of Leuven (K.U.Leuven), Belgium

Edward Giovannucci

Edward Giovannucci's research focuses on how nutritional, genetic, environmental and lifestyle factors relate to various malignancies, especially those of the prostate and large bowel. Much of his work is centered on large ongoing cohort studies, including the Nurses Health Study, the Health Professionals Follow-Up Study and the Physicians Health Study. A specific area of interest is the etiologic mechanisms underlying the relation between modifiable factors and cancer risk. His work has included the study of how nutrition and other lifestyle factors impact on cancer risk and progression by influencing levels of insulin, insulin-like growth factors, vitamin D metabolites, and steroid hormones. Another area of interest is how nutrients may interact with genetic susceptibilities in determining an individual's risk.

Affiliations and expertise

Harvard TH Chan School of Public Health, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

David Goltzman

David Goltzman is Professor in the Departments of Medicine and Physiology of McGill University, Director of the McGill Centre for Bone and Periodontal Research, and Senior Physician in the Endocrine Division of the Department of Medicine of the McGill University Health Centre. His research has focused on the hormonal regulation of mineral and skeletal homeostasis, and he has made many important contributions to our knowledge of parathyroid hormone (PTH), PTH related peptide and vitamin D, which have had major impact on our understanding of a variety of metabolic bone diseases. He is also principal investigator of the Canadian Multicentre Osteoporosis Study (CaMos) which examines the demographics, development, risk factors and outcomes of osteoporosis. Dr. Goltzman has received various honours and awards, including the Aurbach Award of the US Endocrine Society, the Raisz Award of the American Society for Bone and Mineral Research (ASBMR), fellowship in the Royal Society of Canada and in the Canadian Academy of Health Sciences, the Order of Canada, an honorary professorship from Nanjing University and the degree of Doctor Honoris Causa from the University of Athens. He is a past President of the ASBMR, the Canadian Society of Clinical Investigation and the Canadian Society of Endocrinology and Metabolism.

Affiliations and expertise

Professor, Departments of Medicine and Physiology of McGill University, Director of the McGill Centre for Bone and Periodontal Research, and Senior Physician, Endocrine Division, Department of Medicine of the McGill University Health Centre, Canada

Mark Meyer B.

Dr. Mayer is Senior Scientist and Associate Lecturer at the Department of Biochemistry, University of Wisconsin, USA. His research interest includes the characterization of several key genes modulated by the vitamin D hormone and the vitamin D receptor. These genes range from bone remodeling factors to calcium transport mechanisms in the intestine.

Affiliations and expertise

Senior Scientist, University of Wisconsin at Madison, Department of Biochemistry, University of Wisconsin at Madison Fitchburg, USA

JoEllen Welsh

Dr. Welsh is a preeminent researcher on the role of Vitamin D in breast cancer and studies nuclear receptors in health and disease. The Welsh lab has particular expertise in studying the role of dietary-derived ligands for nuclear receptors in cancer prevention and therapy. Recent projects have focused on the molecular mechanisms by which vitamin D and its nuclear receptor modulate adiposity, stem cell function and cancer development. Dr. Welsh recently received funding from the National Cancer Institute to examine the impact of vitamin D and other natural products on hyaluronic acid metabolism and signaling in triple negative breast cancer.

Affiliations and expertise

University at Albany, Cancer Research Center, Rensselear, NY, USA

Life Sciences

Physical Sciences & Engineering

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Health

Feldman and Pike’s Vitamin D

Volume Two: Disease and Therapeutics

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Martin Hewison

Roger Bouillon

Edward Giovannucci

David Goltzman

Mark Meyer B.

JoEllen Welsh