Handbook of Vitamin D in Human Health: Prevention, Treatment and Toxicity (Human Health Handbooks)

Research and clinical application of vitamin D has increased dramatically over the past decade stimulated by novel health promotion discoveries and documentation. This book brings together key researchers with their views focusing on the health promotion role of vitamin D. Such information is vital to clinicians, users of vitamin D supplements of all ages and those interested in public policy. The authors document and define many of the key health related roles of vitamin D. Its traditional application in bone and muscle health as well as therapy of arthritis is expanded and clarified with new research. A better understanding of the effects of vitamin D inadequacy is modelled using problems ranging from infant growth retardation to chronic kidney and periodontal disease. Uniquely the vitamin's role in resistance and treatment of infectious diseases is shown in examples ranging from HIV/AIDS to tuberculosis. Mechanistic understanding of vitamin D's actions is enhanced by looking into its effects on immune modulation and inflammation. Expansion of the role of sunlight in stimulating vitamin D production is discussed relative to the reduction in a variety of cancers. Clearly vitamin D is like a two edged sword with great benefits but also some risks. This book provides carefully defined examples of both situations. Table of contents......Page 8 Overview of key vitamin D modified conditions......Page 12 Abstract......Page 14 1.1 Vitamin D: yesterday......Page 15 1.2.2 Defining vitamin D deficiency... not as easy as it sounds......Page 18 1.2.4 Prevalence of hypovitaminosis D......Page 19 1.2.5 Why has this become a problem again?......Page 20 1.2.6 Supplementation regimens......Page 22 1.3.1 Beyond bone health......Page 23 1.3.2 Personalized medicine......Page 26 References......Page 27 Abstract......Page 39 2.1 Epidemiology of the vitamin-D deficiency......Page 40 2.2 Vitamin D and mortality in older persons......Page 41 2.3 Vitamin D and falls in older persons......Page 42 2.3.1 Examining effects of vitamin D on bone......Page 44 2.3.2 Examining effects of vitamin D on skeletal muscle......Page 45 2.4 Options for vitamin D therapy in older persons......Page 46 References......Page 47 Abstract......Page 53 3.2 Epidemiology......Page 54 3.3 Sources of vitamin D......Page 55 3.4.2 Fortification......Page 56 3.4.3 Supplementation......Page 57 3.5 Recommended supplementation......Page 58 3.7.1 North America......Page 59 3.7.2 Europe......Page 60 3.7.3 Asia......Page 61 3.9 Conclusion......Page 62 References......Page 63 Vitamin D and musculoskeletal health......Page 65 Abstract......Page 67 4.1 Introduction......Page 68 4.2 Vitamin D and falls......Page 70 4.3 Potential mechanisms......Page 71 4.4 Extent of fall risk reduction with vitamin D......Page 72 4.5 Type, dose and toxicity of vitamin D......Page 73 4.6 Conclusions......Page 76 References......Page 77 Abstract......Page 83 5.1 Introduction......Page 84 5.2 Effects of vitamin D status on bone growth in children and adolescents......Page 85 5.3 Effects of adequate vitamin D levels on muscular strength in children and adolescents......Page 87 5.4 Recommended daily intake of vitamin D for children and adolescents......Page 89 5.5 Dietary sources of vitamin D......Page 90 References......Page 91 Abstract......Page 96 6.1 Introduction......Page 97 6.2 The vitamin D endocrine system......Page 98 6.3 The vitamin D receptor......Page 99 6.4 Vitamin D deficiency and hypovitaminosis D......Page 100 6.5 Osteomalacic myopathy and hypovitaminosis D myopathy......Page 103 6.6 Genomic and non-genomic effects of vitamin D on muscle......Page 105 6.8 Therapeutic implications......Page 107 Reference......Page 108 Abstract......Page 114 7.1 Introduction......Page 115 7.3 Rickets and growth......Page 116 7.4 Maternal vitamin D status, fetal bone mineralization and growth......Page 117 7.5 Maternal vitamin D status, bone density and growth in childhood......Page 119 7.6 Infant vitamin D supplementation, bone density and growth in childhood......Page 120 7.7 Vitamin D supplementation and childhood growth: intervention studies......Page 121 7.8 Vitamin D and growth: animal models......Page 123 7.9 Genetic studies in humans: association with growth and bone outcomes......Page 125 7.10 Insights in to mechanisms of action......Page 126 7.11 Summary......Page 127 References......Page 128 Abstract......Page 136 8.2 Vitamin D and rheumatoid arthritis......Page 137 8.3 Vitamin D and osteoarthritis......Page 141 References......Page 142 Abstract......Page 146 9.1 Introduction......Page 147 9.2 Pharmacodynamics of vitamin D......Page 148 9.2.2 25-hydroxyvitamin D response to sustained doses......Page 149 9.2.3 Determinants of 25-hydroxyvitamin D response......Page 153 9.3 Efficacy of high-dose vitamin D in elderly......Page 155 9.3.1 Musculoskeletal efficacy......Page 156 9.4.1 Vitamin D toxicity......Page 160 9.4.2 Calcaemic effects of high vitamin D doses......Page 161 9.4.3 Other risks for elderly people......Page 162 References......Page 163 Vitamin D and chronic disease......Page 172 Abstract......Page 174 10.2 Human vitamin D status......Page 175 10.3.2 General adult population......Page 177 10.3.4 Possible preventive mechanisms......Page 178 10.4.1 General adult population......Page 179 10.4.3 Possible preventive mechanisms of vitamin D against cardiovascular disease......Page 181 10.5.2 Prospective cohort studies......Page 182 10.5.4 Possible anticancer actions of vitamin D......Page 184 References......Page 185 Abstract......Page 191 11.1 Vitamin D in patients with chronic kidney disease......Page 192 11.2 Secondary hyperparathyroidism in patients with chronic kidney disease......Page 193 11.3 Chronic kidney disease mineral and bone disorder......Page 194 11.4.1 Alfacalcidol......Page 196 11.4.5 Falecalcitriol......Page 197 11.4.6 Mechanisms for vitamin D analog selectivity......Page 198 11.5 Clinical outcomes and treatment with vitamin D in patients with chronic kidney disease......Page 199 11.5.2 Cardiovascular disease......Page 200 References......Page 201 Abstract......Page 205 12.1 Introduction......Page 206 12.2.1 Cancer......Page 207 12.2.3 Dental caries......Page 209 12.2.5 Multiple sclerosis......Page 210 12.2.7 Type 1 diabetes mellitus......Page 211 12.2.9 Cardiovascular disease......Page 212 12.2.10 Anaphylaxis......Page 213 12.4 Summary and conclusion......Page 214 References......Page 215 Abstract......Page 224 13.1 Evidence for ultraviolet radiation-induced immunosuppression......Page 225 13.2.2 DNA, urocanic acid and membrane phospholipids......Page 226 13.3.1 Vitamin D associations and increased immune disease......Page 227 13.3.3 Similar pathways of immunoregulation by UVR and vitamin D......Page 228 13.3.6 Induction and activation of T regulatory cells......Page 229 13.3.9 Summary......Page 230 13.4.2 Further discordance between ultraviolet radiation and vitamin D......Page 231 Acknowledgements......Page 233 References......Page 234 Abstract......Page 239 14.2 Periodontal disease pathogenesis and the relationship with vitamin D......Page 240 14.3 The effect of vitamin D on oral health......Page 241 14.4 The potential benefit of vitamin D on periodontal disease......Page 242 14.4.1 Effects of vitamin D supplementation on periodontal disease......Page 243 14.4.2 Mechanisms to explain the role of vitamin D in reducing the risk of periodontitis......Page 244 14.5 The potential impact of vitamin D on periodontal disease treatment......Page 245 References......Page 246 Abstract......Page 251 15.1 Cystic fibrosis......Page 252 15.2 Cystic fibrosis-related low bone mineral density and vitamin D......Page 253 15.3 Vitamin D insufficiency in cystic fibrosis......Page 254 15.4 Current vitamin D supplementation guidelines in cystic fibrosis and future challenges......Page 255 15.5 Extra-skeletal effects of vitamin D in cystic fibrosis......Page 259 15.6 Ongoing research......Page 261 Acknowledgements......Page 262 References......Page 264 Vitamin D and infectious disease......Page 271 Abstract......Page 273 16.1 Introduction......Page 274 16.2.1 Maternal status of vitamin D levels......Page 275 16.2.2 Vitamin D status in infants......Page 278 16.2.3 Vitamin D status in toddlers......Page 279 16.3.1 Lung development......Page 282 16.3.2 Vitamin D and innate immune protection......Page 284 16.4 Evidence for vitamin D status and risk of respiratory infections & childhood wheezing......Page 285 16.4.2 Case-control studies......Page 286 16.4.3 Interventional trials......Page 287 References......Page 288 Abstract......Page 295 17.1 Introduction......Page 296 17.2 Vitamin D insufficiency in HIV-infected persons......Page 297 17.3 Factors associated with vitamin D insufficiency in HIV-infected persons......Page 300 17.4 Vitamin D and long-term non-AIDS defining complications and comorbidities......Page 305 17.5 Vitamin D insufficiency and HIV disease clinical progression......Page 306 17.6 Testable hypotheses towards establishing causal relationships......Page 307 17.7 Vitamin D supplementation in HIV-infected persons......Page 308 References......Page 309 Abstract......Page 316 18.1 Introduction......Page 317 18.2.1 Environmental factors......Page 318 18.2.2 Genetic factors......Page 320 18.3 The role of vitamin D in tuberculosis......Page 327 References......Page 332 Abstract......Page 350 19.1. Introduction......Page 351 19.2.1 Definition, nomenclature, and epidemiology......Page 352 19.2.2 Biological mechanisms of action of vitamin D in gingival tissue......Page 353 19.3.1 Definition, nomenclature, and epidemiology......Page 354 19.3.2 Review of studies correlating vitamin D and periodontitis......Page 355 19.4.1 Definition, nomenclature, and epidemiology......Page 358 19.4.3 Review of studies correlating vitamin D and caries......Page 359 19.5 Vitamin D toxicity in the oral cavity......Page 360 19.6 Summary and conclusions......Page 362 References......Page 363 Abstract......Page 368 20.1 Introduction......Page 369 20.2.1 Enzyme metabolism......Page 370 20.2.2 Role and expression of the vitamin D receptor......Page 371 20.2.4 Effects on myeloid dendritic cells......Page 372 20.2.5 Effects on T cells......Page 373 20.3 Vitamin D and inflammatory diseases......Page 374 20.3.1 Rheumatoid arthritis......Page 375 20.3.3 Systemic lupus erythematosus......Page 376 20.4 Therapeutic implications......Page 377 References......Page 378 Vitamin D and cancer......Page 386 Abstract......Page 388 21.1 Introduction......Page 389 21.2.2 The origin and progression of pancreatic adenocarcinoma......Page 391 21.2.3 Therapies for pancreatic cancer......Page 392 21.3.2 Sources and metabolism of vitamin D......Page 393 21.3.4 The mechanisms of anti-cancer effects of vitamin D......Page 394 21.4.1 Overview......Page 397 21.4.3 Ecological and epidemiological studies of vitamin D and pancreatic cancer......Page 398 References......Page 400 Abstract......Page 413 22.2 Melanoma susceptibility genes......Page 414 22.3 Sun exposure and risk......Page 415 22.4 Vitamin D and the skin......Page 418 22.5 Genetic data......Page 419 22.7 Advice to the general public on prevention of melanoma and vitamin D......Page 421 22.8 Melanoma progression/prognosis and vitamin D......Page 422 References......Page 429 Abstract......Page 438 23.1 Introduction......Page 439 23.2 Overview of human cytochrome P450 system......Page 440 23.3 Vitamin D metabolism......Page 441 23.4 Study of vitamin D-25-hydroxylases in prostate cells (CYP2R1)......Page 442 23.5.1 Differential expression of CYP27B1 activity in prostate cells......Page 444 23.6 Study of 24-hydroxylation by CYP24A1 in prostate cells......Page 445 23.6.1 Expression and the regulation of CYP24A1 in prostate cancer cells......Page 446 23.6.3 Inhibitors of CYP24A1......Page 447 23.7 25(OH)D can be active without 1a-hydroxylation......Page 448 23.8 Summary and conclusions......Page 449 References......Page 450 Abstract......Page 458 24.1 Introduction......Page 459 24.2 Epidemiology of esophageal cancer and vitamin D: generating hypotheses......Page 460 24.3 Vitamin D intake and esophageal cancer......Page 461 24.4 Vitamin D status and esophageal cancer......Page 462 24.5 Vitamin D receptor, related genetic variants and esophageal cancer......Page 463 References......Page 464 Abstract......Page 468 25.1 Introduction......Page 469 25.2 Multiple sclerosis......Page 470 25.3 Multiple sclerosis and vitamin D......Page 471 25.5 Vitamin D as an immune modulator......Page 472 25.6 Vitamin D status, vitamin D supplementation and the effect on immune regulation......Page 473 25.6.2 Cytokines and chemokines in the circulation......Page 474 25.6.3 Cytokine excretion by PBMC in supernatants......Page 483 25.6.5 Phenotyping PBMC directly......Page 484 25.7 Discussion and conclusion......Page 486 References......Page 487 Vitamin D in chronic diseases......Page 494 Abstract......Page 496 26.1 Vitamin D metabolism......Page 497 26.2 Insulin resistance......Page 498 26.3.1 Glucose homeostasis, insulin sensitivity and 25(OH)D levels......Page 501 26.3.3 Relationship between vitamin D and insulin resistance in children......Page 502 26.4 Results of clinical interventions......Page 503 26.5 Association of vitamin D with muscle mass and function......Page 504 26.6 Molecular mechanisms underlying vitamin D action on insulin sensitivity......Page 505 26.6.1 Vitamin D increases protein expression of the insulin receptor......Page 506 26.7.2 Adiponectin......Page 507 26.7.4 Osteocalcin......Page 508 26.8 Conclusion......Page 509 References......Page 510 Abstract......Page 519 27.1.1 Vitamin D......Page 520 27.1.2 Diabetes mellitus......Page 521 27.2.1 Vitamin D deficiency definition......Page 523 27.2.2 Vitamin D deficiency and type 1 diabetes mellitus......Page 524 27.2.3 Vitamin D deficiency and type 2 diabetes mellitus......Page 525 27.3.1 Bone size and diabetes mellitus......Page 527 27.3.2 Serum 25(OH)D levels, femur bone size and type 2 diabetes mellitus......Page 528 References......Page 530 Abstract......Page 540 28.1 Vitamin D: a brief overview......Page 541 28.4 Defining vitamin D deficiency......Page 542 28.5 Vitamin D deficiency: an international epidemic?......Page 543 28.7 Proposed mechanisms of cardiovascular risk......Page 544 28.8 Reported associations between vitamin D deficiency and cardiovascular risk......Page 545 28.9 Can vitamin D supplementation reduce cardiovascular risk?......Page 548 28.10 Not all the evidence is positive......Page 549 28.12 Testing for vitamin D, costs and coverage......Page 550 28.15 Vitamin D and cardiovascular risk: conclusions......Page 551 References......Page 552 Abstract......Page 557 29.2 Vitamin D insufficiency after transplantation......Page 558 29.3 Vitamin D supplementation after transplantation......Page 559 29.4 Vitamin D and bone loss after transplantation......Page 560 type 2 diabetes mellitus after transplantation......Page 561 29.6 Vitamin D and cardiovascular risk after transplantation......Page 562 29.7 Vitamin D and cancer risk after transplantation......Page 563 29.8 Vitamin D and infections after transplantation......Page 564 29.9 Vitamin D and graft rejection......Page 565 29.10 Renoprotective effects of vitamin D after transplantation......Page 566 29.12 Conclusion and perspectives......Page 567 References......Page 568 Abstract......Page 579 30.2 Epilepsy terminology......Page 580 30.3 Prevalence of vitamin D insufficiency among people with epilepsy......Page 581 30.5.1 Nutritional status......Page 582 30.5.2 Impaired mobility......Page 583 30.6 Epilepsy treatments......Page 584 30.6.2 Carbamazepine......Page 585 30.6.3 Valproate......Page 586 30.7.1 Oxcarbazepine......Page 587 30.7.3 Topiramate......Page 588 30.8 Suggested screening and treatment for insufficient vitamin D status among people with epilepsy......Page 589 References......Page 591 Women and children......Page 596 Abstract......Page 598 31.1 Introduction......Page 599 31.2 Neonatal vitamin D physiology......Page 600 31.3.1 Bone, calcium and other classic vitamin D actions......Page 601 31.3.3 Securing achievement of growth potential......Page 602 31.3.4 Infection/immunity/allergy/asthma......Page 603 31.3.5 Type 1 diabetes......Page 606 31.4 Special circumstances for preterm and small for gestational age infants......Page 607 31.5 Recommendations for vitamin D in the perinatal period are highly variable......Page 608 31.5.4 North America......Page 609 31.6 Making recommendations work......Page 610 References......Page 612 Abstract......Page 622 32.2 Vitamin D and calcium physiology during lactation......Page 623 32.3 Vitamin D recommendations for infants......Page 625 32.4 Prevalence of vitamin D deficiency in breastfeeding infants......Page 627 32.5 Effects of vitamin D deficiency in breastfeeding infants......Page 628 32.6 Direct vitamin D supplementation to the breastfeeding infant......Page 629 32.7 Vitamin D supplementation of mother to support the breastfed infant......Page 631 References......Page 634 Abstract......Page 640 33.1 Introduction......Page 641 33.2.2 Characteristics of developing countries......Page 642 33.2.3 Magnitude and impact......Page 643 33.3 Vitamin D supplementation......Page 648 33.4 Areas of uncertainty and progress......Page 651 References......Page 652 Abstract......Page 659 34.2 Adaptations of vitamin D metabolism during pregnancy......Page 660 34.3 Prevalence of vitamin D inadequacy during pregnancy......Page 661 34.5.2 Preeclampsia......Page 662 34.5.3 Gestational diabetes......Page 663 34.5.7 Other......Page 664 34.6.2 Intrauterine growth......Page 665 34.6.3 Immune maturation......Page 666 34.7.1 Childhood asthma and wheezing......Page 667 34.7.3 Schizophrenia......Page 668 34.8 Recommended intakes and monitoring of vitamin D status in pregnancy......Page 669 34.9 Supplementation and toxicity in pregnancy......Page 670 References......Page 671 Abstract......Page 681 35.1 Introduction......Page 682 35.2.1 Overview......Page 683 35.2.3 Vitamin D intervention......Page 685 35.2.4 Study population......Page 686 35.2.5 Recruitment, run-in, randomization, follow-up, and endpoint determination procedures......Page 687 35.2.7 Assessment of compliance......Page 689 35.2.9 Data analysis and statistical power......Page 690 35.2.11 Strengths and limitations......Page 691 35.3 Conclusion......Page 692 References......Page 693 Index......Page 698 Acknowledgments......Page 715