Vitamin D

1. Introduction - p. 15 2. Vitamin D Status in North America (Including Canada and Mexico) - p. 16 3. Vitamin D Status in South America - p. 21 4. Vitamin D Status in Europe - p. 21 5. Vitamin D Status in Middle East - p. 21 6. Vitamin D Status in Asia - p. 21 7. Vitamin D Status in Africa - p. 21 8. Vitamin D Status in Oceania - p. 26 9. Multicenter and Global Studies Using a Central Laboratory Facility - p. 26 10. Ethnicity/Migration - p. 34 11. Nutrition - p. 34 12. Risk Groups - p. 34 13. Implications - p. 34 14. Conclusions - p. 35 15. Chapter 60. Vitamin D in Foods: An Evolution of Knowledge - p. 41 16. Introduction - p. 41 17. Challenges in Assessing the Vitamin D Content of Foods - p. 42 18. Methods of Analysis for Vitamin D in Foods - p. 47 19. Food Composition Data - p. 54 20. Implications and Future Directions - p. 61 21. Appendix A - p. 62 22. Chapter 61. Determinants of Vitamin D Deficiency From Sun Exposure: A Global Perspective - p. 79 23. Chapter 62. Vitamin D Fortification and Supplementation Policies to Correct Vitamin D Insufficiency/Deficiency Globally - p. 91 24. Chapter 63. Vitamin D and Food Fortification - p. 109 25. Chapter 64. Bariatric Surgery, Vitamin D, and Bone Loss - p. 129 26. Introduction - p. 129 27. Skeletal Effects of Bariatric Surgery - p. 131 28. Potential Mechanisms of Bone Loss - p. 134 29. Prevention and Treatment of Skeletal Effects - p. 143 30. Chapter 65. Genetics of the Vitamin D Endocrine System - p. 151 31. Chapter 66. Randomized Clinical Trials of Vitamin D for the Primary Prevention of Cancer and Cardiovascular Disease With a Focus on the VITamin D and OmegA-3 TriaL (VITAL) - p. 167 32. Section VIII. Disorders - p. 176 33. Chapter 67. Vitamin D Deficiency and Nutritional Rickets in Children - p. 179 34. Introduction - p. 179 35. Historical Perspective - p. 179 36. The Epidemiology of Vitamin D Deficiency and Nutritional Rickets - p. 180 37. Clinical Presentation - p. 182 38. Biochemical Abnormalities - p. 184 39. Radiologic Changes - p. 185 40. The Growth Plate in Rickets - p. 186 41. Treatment and Prevention - p. 187 42. Dietary Calcium Deficiency - p. 190 43. The Pathogenetic Spectrum of Nutritional Rickets - p. 192 44. Conclusions - p. 193 45. Chapter 68. Vitamin D and Osteoporosis - p. 203 46. Effects of Vitamin D on the Skeleton - p. 204 47. The Role of Vitamin D Genetic Factors in Osteoporosis and Possible Interactions With Vitamin D Therapy - p. 205 48. Determining Optimal Serum 25 Hydroxyvitamin D Concentrations for Musculoskeletal Health - p. 207 49. Effects of Vitamin D Alone or Calcium and Vitamin D on Bone Mineral Density - p. 207 50. Primary Fracture Prevention With Vitamin D or Calcium and Vitamin D - p. 209 51. Effect of Vitamin D Alone on Fractures - p. 209 52. Single High Annual or Monthly Doses of Vitamin D - p. 210 53. Primary Fracture Prevention With Calcium and Vitamin D - p. 211 54. Metaanalyses - p. 212 55. Safety - p. 213 56. Secondary Fracture Prevention With Vitamin D or Calcium and Vitamin D - p. 214 57. Effects of Active Vitamin D Analogs on Fractures - p. 215 58. The Anabolic Vitamin D Analogs, 2MD - p. 215 59. The Vitamin D Analogs, Eldecalcitol - p. 215 60. Ongoing Large Randomized Controlled Trials of Vitamin D Supplementation - p. 216 61. Future Directions for Vitamin D in Osteoporosis - p. 216 62. Chapter 69. Adult Vitamin D Deficiency: Fracture and Fall Prevention - p. 221 63. Chapter 70. Clinical Disorders of Phosphate Homeostasis - p. 229 64. Phosphate Homeostasis - p. 229 65. Regulation of Phosphate Homeostasis - p. 230 66. Phosphate and Vitamin D Metabolism - p. 231 67. Clinical Symptoms of Hypophosphatemia and Hyperphosphatemia - p. 231 68. Disorders of Phosphate Homeostasis - p. 232 69. Genetic Hypophosphatemic Disorders With Low Fibroblast Growth Factor 23 Levels - p. 239 70. Acquired Hypophosphatemic Disorders With Elevated Fibroblast Growth Factor 23 Levels - p. 239 71. Genetic Hyperphosphosphatemic Disorders - p. 240 72. Disorders of Altered Phosphate Load - p. 240 73. Chapter 71. Vitamin D Hydroxylation–Deficient Rickets, Type 1A: CYP27B1 Mutations - p. 249 74. Chapter 72. Hereditary 1,25-Dihydroxyvitamin D Resistant Rickets - p. 263 75. Introduction - p. 264 76. The Clinical Features of HVDRR - p. 264 77. Mechanism of 1,25(OH)2D Action - p. 270 78. Cellular Basis of HVDRR - p. 272 79. Molecular Basis for HVDRR - p. 278 80. Therapy of HVDRR - p. 289 81. Alopecia - p. 292 82. Concluding Remarks - p. 293 83. Chapter 73. The Role of Genetic Variation in CYP2R1, the Principal Vitamin D 25-Hydroxylase, in Vitamin D Homeostasis - p. 303 84. Chapter 74. Infantile Hypercalcemia and CYP24A1 Mutations - p. 317 85. Chapter 75. Drug and Hormone Effects on Vitamin D Metabolism - p. 331 86. Introduction - p. 331 87. Hormone Effects on Vitamin D Metabolism - p. 333 88. Drug Effects on Vitamin D Metabolism - p. 342 89. Conclusion - p. 354 90. Chapter 76. Vitamin D and Organ Transplantation - p. 375 91. Chapter 77. The Role of Vitamin D in Type 2 Diabetes and Hypertension - p. 387 92. Epidemiology and Burden of Type 2 Diabetes and Hypertension - p. 388 93. Biologic Plausibility of an Association Between Vitamin D and Type 2 Diabetes and Hypertension - p. 388 94. Evidence From Human Studies for a Link Between Vitamin D and Type 2 Diabetes - p. 391 95. Evidence From Human Studies for a Link Between Vitamin D and Hypertension - p. 406 96. Summary of Evidence From Human Studies on Type 2 Diabetes and Hypertension and Limitations in the Study of Vitamin D - p. 410 97. Optimal Intake of Vitamin D in Relation to Type 2 Diabetes and Hypertension - p. 414 98. Conclusions - p. 415 99. Chapter 78. Vitamin D, Obesity, and the Metabolic Syndrome - p. 425 100. Introduction - p. 425 101. Adipose Tissue as a Vitamin D Reserve - p. 426 102. Obesity and Vitamin D Deficiency - p. 426 103. Obesity, Vitamin D-Binding Proteins, and “Free” Vitamin D Concentrations - p. 428 104. The Effect of Weight Loss on Serum 25(OH)D Concentrations - p. 429 105. Can Vitamin D Supplementation Prevent, or Reduce, Obesity? - p. 430 106. Obesity and the Efficacy of Vitamin D Supplementation - p. 431 107. Brown Adipose Tissue, Obesity, and Vitamin D - p. 433 108. Obesity, Vitamin D, and Metabolic Syndrome - p. 433 109. Importance of Early Life D Status for Obesity and Subsequent Risks of Metabolic Syndrome, Type 2 Diabetes Mellitus, and Cardiovascular Disease - p. 437 110. Conclusions and Future Directions - p. 439 111. Chapter 79. Vitamin D and Renal Disease - p. 445 112. Introduction - p. 445 113. Renal Maintenance of the Vitamin D Endocrine System - p. 448 114. Critical Calcitriol/VDR Actions to Improve Parathyroid, Skeletal, Renal, and Cardiovascular Outcomes in CKD - p. 456 115. Chapter 80. Calcitriol and Analogs in the Treatment of Chronic Kidney Disease - p. 471 116. Chapter 81. Idiopathic Hypercalciuria and Nephrolithiasis - p. 485 117. Chapter 82. Hypercalcemia Due to Vitamin D Toxicity - p. 507 118. Introduction - p. 507 119. Forms of Exogenous Vitamin D Toxicity - p. 508 120. Forms of Endogenous Vitamin D Toxicity - p. 511 121. Clinical Manifestations - p. 517 122. Summary and Conclusions - p. 519 123. Chapter 83. The Hypocalcemic Disorders - p. 527 124. Physiology - p. 527 125. Clinical Manifestations of Hypocalcemia - p. 530 126. Differential Diagnosis of Hypocalcemia - p. 530 127. Treatment of Hypocalcemia - p. 538 128. Conclusion - p. 541 129. Chapter 84. Vitamin D: Cardiovascular Effects and Vascular Calcification - p. 549 130. Introduction - p. 549 131. Vitamin D Signaling in Myocardial Remodeling and Function - p. 550 132. Vitamin D Actions in Atherosclerosis andArteriosclerosis - p. 552 133. Vitamin D and Human Cardiovascular Disease: Compelling Epidemiology and Physiology, Emerging but Less Compelling Evidence of Interventional Benefit Still Persists - p. 554 134. Vitamin D Intoxication and Cardiovascular Calcification: Pharmacological Considerations - p. 555 135. The Impact of Calcium, Phosphate, and Vitamin D Excesses on Smooth Muscle Matrix Vesicle Physiology and Vascular Calcification - p. 556 136. The FGF23/Klotho/Vitamin D Axis, Nephrocalcinosis, and Cardiovascular Calcification - p. 558 137. Vitamin D, Vascular Parathyroid Hormone Receptor Signaling, and Arteriosclerotic Calcium Accrual: Lessons Learned From Preclinical Models and Patients With End-Stage Renal Disease - p. 560 138. Defining Cardiovascular Toxicity Thresholds for Vitamin D: Critical Clues From the Clinical Literature - p. 561 139. Vitamin D, the Calcium-Sensing Receptor, and Cardiovascular Disease - p. 561 140. Summary, Conclusions, and Future Directions - p. 562 141. Chapter 85. Vitamin D and Paget’s Disease - p. 571 142. Section IX. Vitamin D Analogs - p. 579 143. Chapter 86. Analogs of Calcitriol - p. 583 144. Chapter 87. Nonsecosteroidal Ligands and Modulators of Vitamin D Receptor - p. 615 145. Chapter 88. Bile Acid-Derived Vitamin D Receptor Ligands - p. 629 146. The Vitamin D Receptor is a Dual-Functional Receptor for Vitamin D and Bile Acids - p. 629 147. Bile Acids and Nuclear Receptors - p. 631 148. Development of Bile Acid Derivatives - p. 635 149. X-Ray Crystal Structures of Vitamin D Receptor in Complex With Lithocholic Acid and Its Derivatives - p. 637 150. Perspectives - p. 641 151. Chapter 89. Bifunctional Vitamin D Hybrid Molecules - p. 647 152. Chapter 90. Modulating Vitamin D Receptor–Coregulator Binding With Small Molecules - p. 657 153. Chapter 91. Extended-Release Calcifediol in Renal Disease - p. 667 154. Chapter 92. Vitamin D Receptor Antagonists - p. 679 155. Chapter 93. Eldecalcitol and Osteoporosis - p. 695 156. Section X. Vitamin D and Cancer - p. 707 157. Chapter 94. Overview of Vitamin D Actions in Cancer - p. 711 158. Introduction - p. 711 159. Vitamin D and Cancer - p. 711 160. Vitamin D Effects on Tumor Cells - p. 718 161. Combination Therapy - p. 724 162. Resistance and Vitamin D Metabolism - p. 726 163. Stimulation of Proliferation - p. 727 164. Conclusions - p. 728 165. Chapter 95. Vitamin D Status and Cancer Incidence, Mortality, and Prognosis - p. 743 166. Introduction - p. 743 167. Cancer Incidence - p. 744 168. Cancer Mortality and Survival - p. 746 169. Chapter 96. Effects of Vitamin D Derivatives on Differentiation, Cell Cycle, and Apoptosis in Hematological Malignancies - p. 761 170. Differentiation of Myeloid Leukemia Cells by Vitamin D Derivatives - p. 762 171. Signaling and Execution of Monocytic Differentiation Induced by Vitamin D Derivatives - p. 763 172. Transcription Factors in Vitamin D Derivative–Induced Differentiation - p. 768 173. Role of Micro-RNAs in Hematopoiesis, Differentiation, and Cell Cycle Block - p. 769 174. Vitamin D Derivatives–Induced Progression of Monocytic to Macrophage Differentiation - p. 770 175. Effects of Vitamin D Derivatives on the Cell Cycle and Proliferation of Human Leukemia Cells - p. 771 176. Efects of Vitamin D Derivatives on Cell Survival and Cell Death - p. 778 177. Effects of Vitamin D Derivatives on Lymphoid Lineage Cells - p. 779 178. Clinical Applications of Vitamin D Derivatives' Actions Against Hematopoietic Malignancies - p. 780 179. Conclusions - p. 787 180. Chapter 97. Vitamin D Actions in Mammary Gland and Breast Cancer: Genomics, Metabolism, and Stem Cells - p. 801 181. Introduction to Breast Cancer - p. 802 182. Observational and Interventional Studies on Vitamin D and Breast Cancer - p. 803 183. Expression and Function of the Vitamin D Pathway in Normal and Neoplastic Breast Cells/Tissues - p. 805 184. Impact of Vitamin D Signaling in Animal Models of Breast Cancer - p. 807 185. Genomic Profiling of Vitamin D Receptor Agonists in Breast Cancer Model Systems - p. 809 186. New Mechanistic Insight Into Vitamin D Actions in Breast Cancer - p. 811 187. Overall Conclusions and Remaining Research Questions - p. 814 188. Chapter 98. The Antitumor Effects of Vitamin D in Genitourinary Cancer - p. 821 189. Introduction - p. 821 190. Prostate Cancer - p. 822 191. Bladder Cancer - p. 828 192. Renal Cell Carcinoma - p. 829 193. Summary - p. 830 194. Chapter 99. Vitamin D and Colon Cancer - p. 837 195. Introduction - p. 838 196. Human Studies - p. 841 197. Expression of Vitamin D Hydroxylases and the Vitamin D Receptor in Colon Cancer - p. 842 198. Mechanism of Action of 1,25(OH)2D3 in Colon Cancer - p. 844 199. Animal Models - p. 852 200. Conclusions - p. 855 201. Chapter 100. Vitamin D and Skin Cancer - p. 863 202. Chapter 101. Vitamin D and Lung Cancer - p. 875 203. Lung Cancer Overview - p. 876 204. Etiology of Lung Cancer - p. 876 205. Vitamin D and Chronic Obstructive Pulmonary Disease - p. 877 206. Variation in Vitamin D Signaling Pathway Components and Lung Cancer Risk/Outcomes - p. 878 207. Vitamin D and the Chemoprevention of Nonsmall Cell Lung Cancer - p. 879 208. Vitamin D Actions in Nonsmall Cell Lung Cancer - p. 880 209. Vitamin D-Based Combination Therapies for Advanced Nonsmall Cell Lung Cancer: Preclinical Rationale and Clinical Studies - p. 884 210. Activity of Calcitriol Analogs in Nonsmall Cell Lung Cancer Models - p. 884 211. Conclusions - p. 885 212. Chapter 102. Vitamin D Inflammation and Cancer - p. 891 213. Introduction - p. 892 214. Vitamin D and the Vitamin D System - p. 893 215. Inflammation - p. 893 216. Inflammation-Associated Cancer - p. 896 217. Conclusions - p. 904 218. Section XI. Immunity, Inflammation and Disease - p. 911 219. Chapter 103. Vitamin D and Tuberculosis - p. 915 220. Introduction - p. 915 221. The Immune Response in Tuberculosis - p. 916 222. Influence of Vitamin D on the Immune Response to Mycobacterium tuberculosis - p. 916 223. Historical Studies - p. 919 224. Studies With Mycobacterium tuberculosis Infection as an End Point - p. 920 225. Studies With Active Tuberculosis Disease as End Point - p. 921 226. Studies of Treatment Outcome - p. 927 227. Conclusions - p. 929 228. Chapter 104. Vitamin D and Adaptive Immunology in Health and Disease - p. 937 229. Chapter 105. Vitamin D and Innate Immunity - p. 951 230. Introduction - p. 951 231. Mycobacteria - p. 951 232. Mechanisms for Pathogen Sensing - p. 952 233. Barrier Function and Associated Infectious Diseases - p. 954 234. Innate Immune Activity of 1,25-Dihydroxyvitamin D - p. 954 235. Vitamin D Pathway and Tuberculosis - p. 957 236. Vitamin D Pathway and Leprosy - p. 959 237. History of Vitamin D, Sunshine, and Tuberculosis Treatment - p. 960 238. Conclusion - p. 961 239. Chapter 106. Vitamin D and Diabetes - p. 969 240. Introduction - p. 969 241. Vitamin D and Genetic Predisposition to Diabetes - p. 970 242. Vitamin D, the Beta Cell, and Insulin Resistance in Type 2 Diabetes - p. 971 243. Vitamin D as an Immune Modulator in Type 1 Diabetes - p. 974 244. Conclusions and Clinical Perspectives - p. 980 245. Chapter 107. Vitamin D and Multiple Sclerosis - p. 989 246. Introduction - p. 990 247. Genes and Environment in Multiple Sclerosis - p. 991 248. Vitamin D and Multiple Sclerosis Risk and Severity - p. 992 249. Vitamin D Signaling in the Immune and Nervous Systems - p. 995 250. Vitamin D Mechanisms of Immune Regulation - p. 997 251. Vitamin D Mechanisms of Neuroprotection - p. 1000 252. Rising Multiple Sclerosis Incidence in Women - p. 1002 253. Sex-Based Differences in Multiple Sclerosis and the Role of Estrogen - p. 1002 254. Vitamin D and Estrogen Synergy for T Cell Self-Tolerance - p. 1003 255. Declining Vitamin D Status and Rising Multiple Sclerosis Incidence - p. 1005 256. Vitamin D and Multiple Sclerosis Prevention - p. 1007 257. Conclusions and Unanswered Questions - p. 1009 258. Chapter 108. Vitamin D and Inflammatory Bowel Disease - p. 1025 259. Chapter 109. Psoriasis and Other Skin Diseases - p. 1037 260. Section XII. Therapeutic Applications and New Advances - p. 1051 261. Chapter 110. Sunlight Protection by Vitamin D Compounds - p. 1055 262. Introduction - p. 1056 263. DNA Damage by Ultraviolet Radiation - p. 1056 264. DNA Repair - p. 1058 265. Ultraviolet-Induced Immune Suppression - p. 1060 266. Synthesis and Metabolism of Vitamin D Compounds in Skin - p. 1061 267. The Vitamin D System and Photocarcinogenesis - p. 1061 268. Vitamin D Compounds Reduce Several Types of Ultraviolet-Induced DNA Damage - p. 1063 269. Vitamin D Compounds and UV-Induced Immune Suppression - p. 1065 270. Pathways—Evidence for Involvement of Nonclassical Pathways - p. 1066 271. Conclusions - p. 1068 272. Chapter 111. Vitamin D, Cardiovascular Disease, and Hypertension - p. 1077 273. Introduction - p. 1077 274. Historical Perspective - p. 1078 275. Mechanistic Effects - p. 1078 276. Observational Studies - p. 1080 277. Mendelian Randomization Studies - p. 1082 278. Randomized Controlled Trials - p. 1083 279. Future Perspective - p. 1085 280. Conclusions - p. 1086 281. Chapter 112. Vitamin D, Acute Respiratory Infection, and Asthma/Chronic Obstructive Pulmonary Disease - p. 1095 282. Introduction - p. 1096 283. Common Respiratory Disorders - p. 1096 284. Vitamin D and Lung Development - p. 1099 285. Vitamin D and Acute Respiratory Infection - p. 1100 286. Vitamin D and Asthma - p. 1103 287. Vitamin D and Chronic Obstructive Pulmonary Disease - p. 1107 288. Potential Mechanisms - p. 1109 289. Future Research - p. 1112 290. Summary - p. 1114 291. Chapter 113. Vitamin D and Muscle Performance in Athletes - p. 1121 292. Chapter 114. Vitamin D: Presence and Function in the Eye - p. 1131 293. Chapter 115. Adult Vitamin D Deficiency and Adverse Brain Outcomes - p. 1147 294. Chapter 116. Vitamin D in Pregnancy and Lactation: Moving Into the Future - p. 1159 295. Chapter 117. Vitamin D and Critically Ill Intensive Care Unit Patients - p. 1177 296. Introduction - p. 1177 297. Prevalence of Vitamin D Deficiency in the Critically Ill Patients - p. 1178 298. Vitamin D Deficiency Risk Factors in the Critically Ill Patients - p. 1178 299. Vitamin D Mechanism in Critical Illness - p. 1179 300. Antimicrobial Peptides - p. 1180 301. β-Defensin 2 - p. 1181 302. Cathelicidin - p. 1181 303. Inflammasome Activation - p. 1181 304. Metabolomics, Transcriptomics, and Epigenetics of Vitamin D - p. 1182 305. Assay - p. 1183 306. Observational Data - p. 1183 307. Vitamin D and Critical Illness Outcomes - p. 1183 308. Sepsis - p. 1183 309. Acute Kidney Injury - p. 1183 310. Acute Lung Injury - p. 1184 311. Interventional Data - p. 1184 312. Dose in Critical Illness - p. 1186 313. Is Vitamin D Supplementation Safe? - p. 1186 314. Conclusions - p. 1187 315. Index for Volume 2 - p. 1195