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

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