Feldman and Pike’s Vitamin D

Volume One: Biochemistry, Physiology and Diagnostics

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 8 6 - 7
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 9 1 3 9 0 - 4

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, proteomic and metabolomic 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 liver metabolism, 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 1. Book introduction: Major trends in vitamin D research
1. History of the Vitamin D book
2. Major trends in the vitamin D field
3. Mechanism of action
4. Mutations in the VDR and critical metabolic enzymes cause childhood rickets
5. Vitamin D assays
6. Extra-skeletal actions
7. Population studies and clinical trials
8. Controversy: what constitutes normal or adequate concentrations of vitamin D?
9. Vitamin D and autoimmune disease
10. Vitamin D and COVID-19
11. Vitamin D and cancer
12. Is vitamin D useful for the prevention or treatment of colorectal cancer?
13. Closing comments with thanks and appreciation to the many authors, the critical Elsevier staff, and the many readers that made this undertaking possible
Chapter 2. Evolution of human skin pigmentation and vitamin D
1. Introduction
2. The solar context of human skin color evolution
3. The nature of the selective factors leading to the evolution of skin pigmentation in early Homo
4. Folate conservation and the evolution of permanent protective pigmentation
5. Early hominin dispersal out of the tropics and vitamin D production
6. The evolution of skin pigmentation in Homo sapiens
7. The effects of cultural buffering, rapid migrations, and modern lifestyles on skin color and vitamin D
8. Summary points
Chapter 3. Photobiology of vitamin D
1. Introduction
2. Historical perspective
3. Photobiology of vitamin D
4. Role of sunlight and dietary vitamin D in bone health, overall health, and well-being
5. Ultraviolet devices for producing vitamin D
6. Alternative pathways generating noncanonical active forms of vitamin D and their photoderivatives
7. Sunlight, vitamin D, and skin cancer
8. Conclusions
9. Summary points
Chapter 4. The activating enzymes of vitamin D metabolism (25- and 1α-hydroxylases)
1. Introduction
2. General information regarding vitamin D hydroxylases
3. Vitamin D3-25-hydroxylases
4. 25-Hydroxyvitamin D-1α-hydroxylase
5. Additional topics
6. Conclusions
7. Summary points
Chapter 5. CYP24A1: structure, function, and physiological role
1. Introduction
2. CYP24A1-catalyzed pathways
3. C24-oxidation pathway
4. C23-hydroxylation pathway
5. CYP24A1, a multifunctional enzyme
6. Biological relevance of the C24-oxidation pathway
7. Structure–function relationships
8. Mutations of CYP24A1 in infantile hypercalcemia type 1
9. Preclinical models of infantile hypercalcemia type 1
10. CYP24A1 involvement in other systems
11. 24,25(OH)2D3 and chondrocyte maturation
12. 24,25(OH)2D3 and fracture repair
13. Conclusions
14. Summary points
Chapter 6. Alternative pathways for vitamin D metabolism
1. Introduction
2. Cytochrome P450scc (CYP11A1): an overview
3. Introduction to the skin in a photobiology context
4. CYP11A1 mediated metabolism of 7DHC with local and systemic implications
5. CYP11A1-mediated metabolism of vitamin D
6. Enzymatic activation of lumisterol and tachysterol
7. Phenotypic activity of CYP11A1-derived hydroxyderivatives and their mechanism of action
8. C3-epimerization of vitamin D metabolites
9. Phase II conjugation of vitamin D metabolites
10. Conclusions
11. Summary points
Chapter 7. Vitamin D–binding protein
1. Introduction
2. Vitamin D-binding protein: gene and protein structure
3. Functions of vitamin D–binding protein
4. The vitamin D–binding protein–actin complex
5. DBP binds fatty acids
6. The role of vitamin D–binding protein in inflammatory processes and in the immune system
7. Conclusions
8. Summary points
Chapter 8. Regulation of renal vitamin D metabolism
1. Introduction
2. Major physiologic regulators of renal vitamin D metabolism
3. Genomic structure and deletion of the CYP27B1 and CYP24A1 genes
4. Genomic mechanisms for CYP27B1 regulation
5. Genomic mechanisms for CYP24A1 regulation
6. Conclusions
7. Summary points
Chapter 9. Regulation of extra-renal synthesis of 1,25(OH)2D
1. Introduction
2. 1α-OHase and the CYP27B1 gene
3. Macrophage 1α-OHase
4. Macrophage 1α-OHase and responsiveness to immune cell regulators
5. Molecular mechanisms for regulation of extrarenal 1α-OHase
6. 1α-OHase in cells other than macrophages
7. Dysregulated synthesis of 1,25(OH)2D and human disease
8. Conclusions and future prospects
9. Summary points
Chapter 10. Structural basis for ligand activity in vitamin D receptor
1. Introduction
2. Conclusions and perspectives
3. Summary points
Chapter 11. Genome-wide perspectives on vitamin D receptor actions
1. Introduction
2. Target genes involved in the regulation of mineral metabolism
3. The production of 1,25(OH)2D3 in diverse nonrenal target cells
4. Transcriptional mechanism of action of 1,25(OH)2D3
5. New insights into transcriptional activation of vitamin D
6. Current advances in transcriptional regulation
7. Analogs of vitamin D
8. Pharmacology of vitamin D analogs
9. Recent possibilities for enhancing vitamin D analog SAR potential
10. Highlights of transcriptional mechanisms
11. Returning to vitamin D analogs—a new analytical approach
12. Conclusions
13. Summary points
Chapter 12. Vitamin D, chromatin, and epigenetics
1. Introduction
2. The impact of chromatin
3. The impact of epigenetics
4. The nuclear receptor superfamily member VDR
5. Genome-wide location of VDR-binding sites
6. CTCF as organizer of vitamin D–dependent chromatin domains
7. Vitamin D–triggered epigenetic changes
8. A chromatin model of vitamin D signaling emerges
9. Epigenetic effects of vitamin D in vivo
10. Conclusion
11. Summary points
Chapter 13. The diverse genomic mechanisms of action of the vitamin D receptor
1. Overview
2. The VDR and the hairless repressor: regulation of transcription in the absence of 1,25(OH)2D
3. Crosstalk between the VDR and TGF-β signaling
4. The VDR and the AP-1 family of transcription factors
5. JAK/STAT signaling and the VDR in immunity
6. Wnt signaling and the VDR: evidence for cancer prevention
7. Interplay between FoxO proteins and the VDR
8. Vitamin D signaling regulates the function of the oncogenic transcription factor c-MYC
9. Widespread crosstalk between NF-κB and vitamin D signaling
10. Insights into VDR-dependent transcriptional regulation from genomics studies
11. Conclusions
12. Summary points
Chapter 14. Vitamin D and microRNAs
1. Introduction
2. MicroRNAs: the posttranscriptional age
3. Complexity of miRNA regulation, biogenesis, and posttranscriptional regulatory functions
4. Nuclear receptors and miRNAs
5. The relationship between miRNAs and the vitamin D synthesis, metabolism, and signaling systems
6. Interplay between vitamin D and miRNAs in biological systems
7. Translational aspects of miRNAs
8. Strategies for miRNA and target identification for vitamin D research
9. Conclusions
10. Summary points
Chapter 15. Pathway based-analysis of transcriptomic data from vitamin D studies
1. Introduction
2. Transcriptomic data
3. Vitamin D3-related pathways in online pathway databases
4. Workflow pathway-based analysis for transcriptomic data
5. The six steps in the pathway-based analysis workflow of transcriptomic data
6. Example case—immunometabolic effect of vitamin D3 in dendritic cells and monocytes
7. Conclusion
8. Summary points
Chapter 16. Vitamin D and the kidney
1. Introduction
2. Calcium handling by the kidney
3. Phosphate handling by the kidney
4. Role of the kidney in the metabolism of 25(OH)D
5. Effects of vitamin D, 25(OH)D, and 1,25(OH)2D on the renal handling of calcium and phosphate
6. Distribution and regulation of vitamin D–dependent proteins in the kidney
7. Mechanisms of altered vitamin D metabolism in kidney disease
8. Conclusion
9. Summary points
Chapter 17. Vitamin D and the calcium-sensing receptor
1. Introduction
2. Development of the parathyroid glands
3. The parathyroid hormone gene
4. The calcium-sensing receptor
5. Overview of systemic Ca2+ homeostasis
6. Actions of CaSR and VDR in tissues uninvolved in extracellular Ca2+ homeostasis
7. Summary points
Chapter 18. Regulation of intestinal calcium and phosphate absorption by vitamin D
1. Introduction
2. Intestinal calcium absorption
3. Molecular models of calcium absorption
4. Physiologic regulation of vitamin D-mediated intestinal calcium absorption
5. Genomic and genetic studies of vitamin D-regulated intestinal calcium absorption
6. Conclusions regarding the role of vitamin D on intestinal calcium absorption
7. An overview of intestinal phosphate absorption
8. Conclusion regarding the role of vitamin D on phosphate absorption
9. Summary points
Chapter 19. Vitamin D and FGF23
1. Introduction
2. FGF23 signaling
3. Role of vitamin D signaling in the regulation of FGF23 production
4. Regulation of renal 1,25(OH)2D production by FGF23
5. Role of FGF23-mediated regulation of vitamin D metabolism in health and disease
6. Conclusion
7. Summary points
Chapter 20. Osteoclastogenesis and vitamin D
1. Introduction
2. Regulation of mineral metabolism by vitamin D, parathyroid hormone, and fibroblast growth factor 23
3. Phenotypes of vitamin D receptor knockout mice
4. Osteoclast lineage-specific vitamin D receptor knockout mice
5. Regulation of osteoclastogenesis by the receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factor-κB/osteoprotegerin system
6. In Vitro regulation of osteoclastogenesis by vitamin D
7. In Vivo regulation of osteoclastogenesis by vitamin D
8. Conclusion
9. Summary points
Chapter 21. Vitamin D activity in osteoblasts and osteocytes
1. Introduction
2. Properties of osteoblasts and osteocytes
3. The local and endocrine effects of 1,25(OH)2D3 on osteoblast and osteocyte function
4. Conclusion
5. Summary points
Chapter 22. Cartilage
1. Introduction
2. Properties of cartilage tissues
3. Regulation by vitamin D
4. Conclusion
5. Summary points
Chapter 23. Vitamin D and bone: an integrated approach
1. Introduction: a link between bone metabolism, calcium homeostasis, and 1,25(OH)2D3 activity
2. 1,25(OH)2D3 and bone metabolism during a positive calcium balance
3. Negative calcium balance resulting from insufficient vitamin D action
4. Negative calcium balance with sufficient vitamin D
5. Vitamin D and FGF23
6. Conclusion
7. Summary points
Chapter 24. Vitamin D in dentoalveolar and oral health
1. Introduction
2. A brief primer on dentoalveolar cells and tissues
3. Vitamin D metabolism and mechanisms of action on dental cells
4. Vitamin D, rickets, and the oral tissues
5. Hereditary vitamin D–related diseases affecting dentoalveolar tissues
6. Other inherited rachitic conditions affecting vitamin D metabolism
7. Vitamin D and oral health
8. Conclusions
9. Summary points
Chapter 25. Role of vitamin D in skin and hair biology
1. Introduction
2. Cutaneous production of vitamin D and its biologically active metabolites
3. Regulation of keratinocyte differentiation
4. Role of vitamin D signaling in skin cancer
5. Role of vitamin D signaling in epidermal wound repair
6. Role of vitamin D signaling in hair follicle cycling
7. Summary points
Chapter 26. Vitamin D and the cardiovascular system
1. Introduction
2. Vascular physiology
3. Identification of the VDR in the vascular system
4. Vascular relaxation
5. Structural vascular changes
6. Vascular inflammation
7. Angiogenesis
8. Blood coagulation and fibrinolysis
9. Animal models
10. Clinical studies in cardiovascular disease
11. Conclusion
12. Summary points
Chapter 27. Vitamin D, brain development and function
1. Introduction
2. Vitamin D signaling in the brain
3. Dietary vitamin D deficiency, effect on brain development, and function
4. Vitamin D regulates essential processes in normal brain development
5. Possible neuroprotective mechanisms of vitamin D in the developing brain
6. Developmental vitamin D deficiency and neuropsychiatric disorders
7. Vitamin D supplementation and neurodevelopmental outcomes
8. Conclusions
9. Summary points
Chapter 28. Vitamin D, VDR, and adipose tissue: focus on cellular mechanisms
1. Introduction
2. Storage of vitamin D metabolites in adipose tissue
3. Effects of 1,25(OH)2D on adipogenesis at the cellular level (Table 28.1)
4. Effect of 1,25(OH)2D on human mesenchymal precursors
5. Vitamin D receptor regulation of thermogenesis in cell systems
6. Impact of vitamin D signaling on adiposity in mouse models (Table 28.2)
7. Effect of vitamin D deficiency and supplementation on adiposity and metabolism in animal models
8. Effect of the vitamin D pathway on inflammation in adipocytes and adipose tissue
9. Conclusions
10. Summary points
Chapter 29. Vitamin D and skeletal muscle
1. Introduction
2. Skeletal muscle physiology
3. Vitamin D receptor in muscle
4. Vitamin D and calcium signaling in muscle
5. Vitamin D and phosphate signaling in muscle
6. Vitamin D uptake in skeletal muscle
7. Vitamin D, insulin signaling, and metabolism in muscle
8. Vitamin D, muscle contraction, and strength
9. Vitamin D, muscle development, and mass
10. Vitamin D, muscle injury, and repair
11. Vitamin D and age-related changes in muscle
12. Vitamin D and bone muscle crosstalk
13. Conclusions
14. Summary points
Chapter 30. Understanding vitamin D from mouse knockout models
1. Introduction
2. Vitamin D metabolism
3. Mineral and skeletal homeostasis
4. Calcium transport in intestine and kidney
5. Intestinal calcium absorption
6. Renal calcium reabsorption
7. Intestinal phosphate transport
8. Regulation of parathyroid gland function
9. Interaction of PTH and 1,25(OH)2D on calcium and phosphate homeostasis
10. Regulation of FGF23 production
11. Anabolic effects of vitamin D on the skeleton: role of VDR and 1α-OHase in chondrocytes
12. Effects on skeletal mineralization
13. Effects on bone turnover
14. Effects on bone resorption
15. Effects on skeletal aging
16. Calcitriol and teeth
17. Extraskeletal actions of 1,25(OH)2D
18. Ectopic calcification
19. Cancer
20. Skin and hair follicles
21. Epidermal differentiation and the immune system
22. Conclusion
23. Summary points
Chapter 31. Pharmacology and pharmacokinetics of vitamin D
1. Overview
2. Vitamin D absorption
3. Kinetics of cutaneous synthesis
4. Tissue distribution
5. Metabolism and determinants of metabolic fate of vitamin D
6. Half-lives of vitamin D metabolites
7. Factors influencing half-life of vitamin D metabolites
8. The pharmacokinetics of bound and free vitamin D metabolites
9. Influence of DBP genotype and concentration on vitamin D metabolism and 25(OH)D half-life
10. Dose-response to vitamin D supplementation
11. The 3-epimer of 25(OH)D and 1,25(OH)2D
12. Catabolism and excretion
13. Vitamin D toxicity
14. Summary points
Chapter 32. Vitamin D as a modifier of genomic function and phenotypic expression during pregnancy
1. Introduction
2. Defining a “normal” circulating 25(OH)D concentration in humans
3. Unique vitamin D metabolism during pregnancy
4. Placental transfer of vitamin D to the fetus and its function
5. Vitamin D deficiency during pregnancy: Animal models and human studies
6. Vitamin D deficiency during pregnancy: Human studies
7. Conclusions
8. Summary points
Chapter 33. The role of vitamin D physiology in regulating calcium and bone metabolism in mother and child: pregnancy, lactation, postweaning, fetus, and neonate
1. Introduction
2. Pregnancy
3. Lactation and postweaning recovery
4. The fetus
5. Neonate and infant
6. Conclusion
7. Summary points
Chapter 34. Vitamin D and the placenta
1. Introduction
2. The human placenta
3. Vitamin D, pregnancy, and the human placenta
4. Vitamin D effects on the placenta
5. Vitamin D, the placenta, and lifelong health
6. Conclusion
7. Summary points
Chapter 35. Consequences of perinatal vitamin D deficiency on later bone health
1. Introduction
2. Vitamin D physiology and epidemiology in pregnancy
3. The lifecourse determinants of osteoporosis
4. In utero vitamin D deficiency and bone health
5. Conclusion
6. Summary points
Chapter 36. Adolescence and acquisition of peak bone mass
1. Introduction
2. Pubertal bone acquisition
3. Serum 25(OH)D in children and adolescents
4. Vitamin D and intermediate endpoints of vitamin D and bone metabolism
5. Vitamin D and other predictors of calcium retention
6. Vitamin D and bone
7. Vitamin D and muscle
8. Vitamin D requirements in children and adolescents
9. Conclusions
10. Summary points
Chapter 37. The role of vitamin D in orthopedic surgery
1. Introduction
2. Impact on orthopedic trauma
3. Impact on pediatric orthopedics
4. Impact on total joint arthroplasty
5. Conclusions
6. Summary points
Chapter 38. Vitamin D and muscle performance in athletes and older adults
1. Introduction
2. Vitamin D–deficient myopathy
3. Vitamin D and athletic performance
4. Vitamin D and muscle strength and performance in older adults
5. Conclusion
6. Summary points
Chapter 39. Role in reproductive biology and dysfunction in women
1. Introduction
2. Relevance of vitamin D for female reproductive biology: experimental models
3. Relevance of vitamin D for female reproductive biology: gynecological disorders
4. Relevance of vitamin D for human female reproductive biology: human data
5. Relevance of vitamin D in female reproductive disorders
6. Conclusions
7. Summary points
Chapter 40. Vitamin D, reproductive endocrinology, and male reproductive organ function in health and disease
1. Introduction
2. Effects on Leydig cell function and estrogen signaling
3. Vitamin D and sex steroids
4. Vitamin D and Sertoli cell function
5. Vitamin D and germ cell function
6. Vitamin D in human sperm
7. Vitamin D and sperm function
8. Vitamin D, epididymis, prostate, and seminal vesicle
9. Vitamin D and reproductive hormones
10. Vitamin D, semen quality, and fertility: Functional models
11. Vitamin D, semen quality, and fertility: Human studies
12. Testicular germ cell tumors
13. Concluding remarks and future perspectives
14. Summary points
Chapter 41. Vitamin D and the renin–angiotensin system
1. Introduction
2. Overview of the renin–angiotensin system
3. Vitamin D regulation of the renin–angiotensin system
4. Vitamin D and the renin–angiotensin system in disease
5. Conclusion
6. Summary points
Chapter 42. Vitamin D: presence and function in the eye
1. Introduction
2. Vitamin D and the eye
3. Ocular infection
4. Dry eye disease
5. Cataract
6. Glaucoma
7. Uveitis
8. Age-related macular degeneration
9. Diabetic retinopathy
10. Conclusion
11. Summary points
Chapter 43. Adult vitamin D deficiency and adverse brain outcomes
1. Introduction
2. Mechanisms of vitamin D action in the brain
3. Vitamin D and adverse brain outcomes in humans
4. Vitamin D and adverse brain outcomes in animals
5. Conclusions
6. Summary points
Chapter 44. Vitamin D and the lung
1. Introduction
2. Vitamin D in early life
3. Role of vitamin D in the defense against respiratory infections
4. Vitamin D and lung infections
5. COVID-19
6. Conclusion
7. Summary points
Chapter 45. Design and synthesis of vitamin D analogs
1. Introduction
2. Synthetic approaches to vitamin D trienic system
3. 19-Nor/21-epi/C-2 substituted analogs of 1,25(OH)2D3
4. Side chain analogs of 1,25(OH)2D3
5. A-ring analogs of 1,25(OH)2D3
6. CD-ring modified analogs of 1,25(OH)2D3
7. Fluorinated analogs of 1,25(OH)2D3
8. 14-epi analogs of 1,25(OH)2D3
9. Non-steroidal compounds
10. Miscellanea
11. Advances in synthetic methodologies
12. Conclusion
13. Summary points
Chapter 46. Structure function relationships of VDR ligands
1. Introduction
2. Agonist-bound structures of the VDR-LBD
3. Apo structure of the VDR-LBD
4. Antagonist-bound structures of the VDR-LBD
5. Partial agonist–bound structures of the VDR-LBD
6. Conclusions and perspectives
7. Summary points
Chapter 47. Modulating vitamin D receptor–coregulator binding with small molecules
1. Introduction
2. VDR coactivators
3. VDR corepressors
4. Peptide-based inhibitors of VDR–coregulator interactions
5. Small molecule–based inhibitors of VDR–coregulator interactions
6. Conclusion
7. Summary points
Chapter 48. Mass spectrometry assays of vitamin D metabolites
1. Introduction
2. Approaches and utility of vitamin D metabolite measurements in the clinical laboratory setting
3. Overview of methodology for analysis of circulating vitamin D
4. Application of LC–MS/MS to the study of vitamin D metabolism in animal models
5. Conclusions
6. Summary points
Chapter 49. Measurement and quality assessment of total and free 25-hydroxyvitamin D
1. Introduction section 1: 25-hydroxyvitamin D assay standardization
2. Vitamin D standardization program (VDSP) objectives
3. Introduction to performance testing (PT)/external quality assessment schemes (EQA)
4. Prospective standardization
5. Protocol for retrospective standardization
6. Performance testing/quality assessment of assays for vitamin D metabolites
7. Beyond standardization
8. Vitamin D standardization program efforts—into the future
9. Summary and conclusions
10. Section 2: Free and bioavailable 25-hydroxyvitamin D
11. Summary points
Chapter 50. Vitamin D tissue distribution by mass spectrometry imaging
1. Introduction
2. Vitamin D
3. Mass spectrometry imaging
4. Mass spectrometry imaging methods for spatial distribution of vitamin D metabolites in tissues
5. Future MSI platforms and technological developments
6. Conclusion
7. Summary points
Index for Volume 1

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

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Feldman and Pike’s Vitamin D

Volume One: Biochemistry, Physiology and Diagnostics

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Martin Hewison

Roger Bouillon

Edward Giovannucci

David Goltzman

Mark Meyer B.

JoEllen Welsh