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Index* A DRIs, 7, 349, 351, 352, 354–355, 393– 394, 464, 1104, 1108, 1114 Abscesses, 171 estimated intake, 465, 466, 467, 480 Acceptable Macronutrient Distribution retention, 268 Range (AMDR), 3 DRI development, 24, 385–387, 393–394, Achlorhydria, 37 445 Acronyms and abbreviations, 523–526 EARs, 7, 9, 349, 351, 354–355, 385, 387, Adequate Intake (AI), 3, 8, 20, 21–22, 393, 394, 464, 469, 1104–1105 489–490. See also Calcium, AIs; elements, 1108–1109, 1114–115 Vitamin D, AIs growth spurts, 8, 24, 39, 53, 354, 421 Adipokines, 491 lactation, 7, 57, 257, 282, 283, 349, 361, Adipose tissue, 83, 84, 87–88, 106, 490, 491, 362, 363, 393, 394, 424, 446, 518 464, 469 Adiposity, 11, 84, 105–106, 143, 152, 156, macronutrients, 1110–1111 490–491. See also Obese or multiple sclerosis and serum 25OHD, overweight persons; Weight 173 loss or dieting pregnancy, 56, 57, 250, 257, 278, 361, Adolescents, 14 through 18 years. See also 362, 393, 394, 424, 446, 469 Puberty RDAs, 7, 9, 349, 351, 354–355, 385, 387, bone health, 53–54, 195, 202–208, 218, 393, 394, 464, 469, 1106-1110 226, 280 ULs, 7, 9, 419, 420, 421, 441, 445, 464, calcium 469, 1112–1115 absorption, 39, 265 vitamin D, 9, 95, 385–387, 393–394, 441, accretion, 61, 269 445, 469, 470–473, 475, 1106, balance, 58, 61 1112 deposition, 53–54 vitamins, 1104–1105, 1112–1115 water, total, 1110 *Appendixes B through K (pp. 537-1074) are not included in this index. 1075

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1076 INDEX Adults, 19 through 30 years EARs, 7, 9, 167, 349, 356, 357, 359, 387– bone health, 218, 242, 270, 382–383, 388, 389, 392, 393, 394, 464, 384 469, 1104–1105 calcium, 7, 39, 54, 269, 349, 355, 421– elements, 1108–1109, 1114–1115 424, 464, 465, 466, 467, 1104, macronutrients, 1110–1111 1108, 1114 RDAs, 7, 9, 349, 356, 357, 359, 387–388, DRI development, 24, 355–356, 387–389, 389, 393, 394, 464, 469, 393–394, 421–422, 423–424, 1106–1110 443–445 ULs, 7, 9, 421, 423, 443, 445, 464, 469, EARs, 7, 9, 349, 355, 387–388, 389, 393, 1112–1115 394, 464, 469, 1104–1105 vitamin D, 9, 389, 392–394, 443–445, 469, elements, 1108–1109, 1114–1115 470–473, 475, 1106, 1112 macronutrients, 1110–1111 vitamins, 1106–1107, 1112–1113 RDAs, 7, 9, 349, 355, 387–388, 389, 393, water, total, 1110 394, 464, 469, 1106–1110 Adults, 70+ years. See also Elderly population ULs, 7, 9, 421, 423, 443, 445, 464, 469, bone health, 219, 226–234, 235, 360, 1112–1115 382–383, 384, 439 vitamin D, 9, 95, 387–389, 393–394, calcium, 7, 349, 356, 359–361, 421–423, 443–445, 469, 470–473, 475, 1106, 464–465, 466, 467, 1104, 1108, 1112 1114 vitamins, 1106–1107, 1112–1113 cognitive function, 183, 185–186 water, total, 1110 DRI development, 359–361, 389–392, Adults, 31 through 50 years 443–445 bone health, 218–219, 242, 382–383, 384 EARs, 7, 9, 349, 356, 360–361, 389, 392, calcium, 7, 39, 54–55, 349, 355–356, 464, 469, 1104–1105 421–424, 464, 465, 466, 467, elements, 1108–1109, 1114–1115 1104, 1108, 1114 macronutrients, 1110–1111 DRI development, 24–25, 355–356, RDAs, 7, 9, 349, 356, 361, 389–390, 392, 387–389, 393–394, 421–424, 464, 469, 1106–1110 443–445 ULs, 7, 9, 421, 423, 443, 445, 464, 469, EARs, 7, 9, 349, 355, 387–388, 389, 464, 1112–1115 469, 1104–1105 vitamin D, 9, 389–392, 439, 443–445, 469, elements, 1108–1109, 1114–1115 470–473, 475, 1106, 1112 macronutrients, 1110–1111 vitamins, 1106–1107, 1112–1113 RDAs, 7, 9, 349, 355, 387–388, 389, 464, water, total, 1110 469, 1106–1110 Adverse effects ULs, 7, 9, 421, 423, 443, 445, 464, 469, calcium, 22, 42, 404, 405–424, 481, 488, 1112–1115 500–501 vitamin D, 9, 95–96, 387–389, 393–394, chronic, vs. acute toxicity, 404 443–445, 469, 470–473, 475, due to nutrient deficiency. See Calcium, 1106, 1112 deficiency; Phosphorus, vitamins, 1106–1107, 1112–1113 deficiency; Vitamin D, water, total, 1110 deficiency Adults, 51 through 70 years ethical issues, 404, 425, 488, 518 bone health, 219, 226–234, 235, 382–383, indicators. See Indicators of adverse 384 outcomes for excess intake calcium, 7, 349, 356–359, 421–423, 463– research needs, 517–518 464, 465, 466, 467, 480–481, in risk assessment approach to DRI 1104, 1108, 1114 development, 27, 403, 515 dementia, 183 use in determination of benchmark DRI development, 24–25, 355–356, 389, intake, 17, 418 421–423, 443–445 vitamin D, 6, 10, 404, 405, 424–440, 486, 488

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1077 INDEX African Americans Ankylosis, 174 breast-fed infants and vitamin D, 385, Anorexia, 406, 425 494–495 Anti-angiogenic action, 92, 146 calcitriol levels, 260–261, 296 Antibody-based assays, 107, 108, 109, 365 “calcium economy,” 294, 517 Anticonvulsants, 87, 504 cardiovascular mortality, 438 Anti-inflammatory action, 92, 146, 184, 517 cognitive function, 186 Antimicrobial activity, 177, 178, 179, 181 diabetes, 153 Antirachitic, 80 limited data for DRI development, 347 Apoptosis, 77, 92, 140, 143 multiple sclerosis, 174 Appetite loss, 171–172 puberty, 24 Arrhythmia, 147, 406, 425 serum 25OHD levels Arsenic, 1114 atherosclerotic plaque, 438, 444 Arthralgia, 176 bone health, 106, 208, 260–261, 295, Arthritis, 176. See also Osteoarthritis; 298, 439, 493 Rheumatoid arthritis effects of skin pigmentation, 374, Asian ancestry or Asians, 179, 199, 231, 252, 493, 494–495 254, 268, 347, 439. See also vitamin D dose–response, 431 Chinese ancestry or Chinese; systemic lupus erythematosus, 177 East Asian ancestry; South Africans, 179, 244. See also Gambians; Asian ancestry or South Asians Nigerians Assay shift and drift, 107–111, 365–366, Agency for Healthcare Research and 460–461 Quality (AHRQ) Asthma, 4, 129, 168–170, 181, 182 Methods Reference Guide for Atherosclerosis, 147, 438, 444 Effectiveness and Comparative Atmospheric conditions, 104, 105, 492 Effectiveness Reviews, 127, 128 Autism, 4, 129, 182–183 overview of AHRQ-Ottawa and AHRQ- Autoimmune disease, 4, 5, 78, 91, 170–177, Tufts reports, 5, 30–31, 97–98, 181–182, 189, 192. See also 100, 126–127 Crohn’s disease; Diabetes Albumin. See Serum albumin (type 1); Inflammatory bowel Alcohol consumption, 64, 140, 143, 230, disease; Multiple sclerosis; 434 Osteoarthritis; Rheumatoid Allergies, 169, 496–498 arthritis; Systemic lupus All-laboratory trimmed mean (ALTM), 109 erythematosus Alopecia, 94 Alpha-Tocopherol Beta-Carotene Cancer B Prevention Study (ATBC), 147, 415, 436 B cells, 91, 170 Altitude, 105 Background intake. See Benchmark intake Alzheimer’s disease, 183, 185 Balance (calcium). See Calcium balance Amenorrhea, 502 Balance (physical), 166 American Academy of Dermatology, 495 Beck Depression Inventory (BDI), 187 American Academy of Pediatrics, 95, 258 Behavior, 182, 184, 186, 295 American Dietetic Association, 497 Benchmark intake (BI), 17, 418, 440, 519 American Indians, 197, 439 Bioavailability, 29, 37, 39, 62–63, 498, 503, American Institute for Cancer Research, 516, 521 415 Bioequivalence, 29, 516, 521 Amsterdam Growth and Health Biomarkers Longitudinal Study, 274 for colon carcinogenesis, 144 Anemia, 176 of effect, 25–26 Angiotensin II, 190

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1078 INDEX of exposure, 25 vitamin D supplementation, 161, inflammatory, 169–170 234–235, 236–242, 275, serum 25OHD as biomarker of vitamin D 277, 290–292, 358, 390– effect, 13–14, 96–97, 263–264, 392, 438–439 291, 293, 439, 484, 517, 520 maintenance, 283–284, 292–294, serum 25OHD as biomarker of vitamin 387–388 D exposure, 8, 12–13, 96, 99, modeling, 45, 53 293, 363, 381–382, 384, 480, organic matrix (osteoid), 43, 49–50, 62, 483 94, 275–276 use of term, 25 pain, 49, 50 Biotin, 1107, 1113 remodeling, 45–46, 52, 54, 59, 62, 272, Bloating, 37, 497 409 Blood pressure, 152, 154, 190. See also resorption during lactation, 45n.3, 57, Hypertension 96, 256, 259, 281–282, 362 Blood volume, extracellular, 407 serum 25OHD levels and. See Serum Body mass. See Lean body mass or lean mass 25-hydroxyvitamin D, bone Body mass index, 48, 88, 141, 155, 211, 212, health 228, 231, 434, 435, 490 trabecular, 45, 46, 249, 270 Bone. See also Bone health; Skeleton types, 45 accretion, 46–47, 53, 54, 55, 95, 267–272, Bone health, as indicator of nutrient 292–294, 351 adequacy. See also under specific accretion rate, 268, 269–270 life-stage groups calcium content at maturity, 54 African Americans, 208, 294–298 composition, 43–44 bone maintenance, 283–284, 292–294, cortical, 45, 46, 249 387–388 disorders. See Bone, fracture; Bone loss; effects of adiposity, 490–491 Osteomalacia; Osteoporosis; integration of evidence, 262–277, 292– Rickets 294, 370–371 effects of menopause, 47–48, 52 lactation, 282–283, 362 formation or mineralization, 44–45, 242, menopausal status, 209–218, 226, 234– 253, 276–277, 296 242, 360–361 fracture overview, 4, 5, 193–194, 298 African Americans, 294, 296, 493 pregnancy, 277–282, 361–362 BMD, 50, 51, 273, 285–292, 298, selection as, 298, 345, 480 357–358 Bone loss. See also Osteoporosis bone loss as risk factor, 48, 60, African Americans, 296, 298 359–360 age-related, 52, 54, 55, 95–96, 193, 284, calcium supplementation, 285–290, 285, 356, 361 358, 360, 390–392 calcium balance and, 284–285 as indicator of adverse outcomes for calcium intake and, 35, 40, 274, 285–292, excess intake, 6, 405 356 as indicator of nutrient adequacy, 4, effects of caffeine intake, 64 9, 129 effects of menopause, 47–48, 52, 54–55, from military training, 234n.3, 242, 58, 360–361 275 effects of soft drink intake, 64 with osteomalacia, 49, 50, 276–277 integration of evidence, 262–277, 292– with osteoporosis, 50–52 294, 370–371 during pregnancy, 278 serum 25OHD and, 195 and serum 25OHD, 195, 215, 226– spaceflight, 46 234, 276, 366–367, 390 vitamin D intake and, 96, 292–294 vegans diet and risk for, 497 Bone marrow, 43, 46

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1079 INDEX Bone mass vitamin D intake and supplementation, calcium intake and, 35, 47, 53, 54, 273– 95, 175, 271, 274–275, 274, 417 279–280, 290–292, 386–387, measures associated with calcium, 57–62. 392–393 See also Bone mineral content; Boron, 1114 Bone mineral density; Calcium Bowel obstruction, 171. See also balance Inflammatory bowel disease peak, 47, 54, 250, 270, 282, 296 Brain development, 182, 184 physical activity and, 46, 54, 273, 287, Brain tissue, 184 490–491 Breast cancer, 139–142, 435–436 protein intake and, 63 Breastfeeding. See Human milk; Infants, reduction. See Bone loss; Osteoporosis breast-fed; Lactation Bone mineral apparent density (BMAD), British Paediatric Association, 431, 432, 441 206 Bone mineral content (BMC) C calcium intake and supplementation, 47, 60–62, 219–226, 270–271 Caffeine, 64 definition, 60 Calcidiol. See 25-Hydroxyvitamin D effects of adiposity, 491 Calcifediol. See 25-Hydroxyvitamin D as indicator of nutrient adequacy, 4, 129 Calcification of soft tissue (calcinosis), 6, 44, infant, 195, 196–201 61, 88, 405, 406, 409–410, 422, measurement, 60–62 425, 426 postmenopausal women and elderly Calcitonin, 40, 41, 90 men, 214, 216 Calcitriol (1,25-dihydroxyvitamin D). See also pregnancy and lactation, 249, 254, 255, Serum calcitriol 259, 278, 279–280, 283 cancer, 77, 91–92, 139, 146 serum 25OHD and, 195, 196–205, 218, cardiovascular disease, 78, 150–151 219, 393–394 extra-renal production, 90, 177, 189, vitamin D intake and supplementation, 518–519 271, 279–280 falls and physical performance, 157 Bone mineral density (BMD) fetal, 252 African Americans, 295–296 formation in the kidney, 77, 84, 90, 481 bone fracture and, 50, 51, 273, 285–292, functions 298, 357–358 bone formation, 44 calcium intake and supplementation, calcium absorption, 35, 38, 39, 89, 60–62, 175, 219–226, 270–271, 253, 260, 264, 267 273–274, 284–290, 392–393 calcium excretion, 42 effects of adolescent pregnancy, 56, 362 calcium regulation, 40–41, 89–90, effects of lactation, 57, 256, 257, 259, 157, 253 282, 283 cytokine production, 189 effects of menopause, 47–48, 52 glucose transport in the brain, 184 effects of oral contraceptive use, 501–503 immune response, 167–168 effects of pregnancy, 7, 8, 249, 250, 254, phosphorus regulation, 64, 77, 89 255, 256, 278, 279–280, 361, vascular reactivity enhanced by, 148 362 gene regulation, 90, 170 as indicator of nutrient adequacy, 4, 129 half-life, 97 measurement, 60–62 interactions with prescription drugs, 504 serum 25OHD and, 195, 196–207, 209, during lactation, 91, 259 210–216, 218–219, 226–234, multiple sclerosis treatment, 173, 174 275, 283, 368–369, 386–387 not used as a measure of vitamin D use of term, 60 nutriture, 97

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1080 INDEX in the placenta, 90, 189 bone health and, 194, 292. See also in pleural fluid, 177 Supplements, calcium, and during preeclampsia, 189 bone health during pregnancy, 56, 96, 174, 250–251, cancer, 5, 135, 137, 139, 140, 141, 143, 252, 254 144–145, 147, 414–416 rheumatoid arthritis treatment, 175 cardiovascular disease, 148, 149 rickets and osteomalacia, 49, 94 cognitive function, 186 systemic lupus erythematosus treatment, deficiency, 35, 40, 48–50, 243–248, 254, 176 271, 386 tuberculosis, 178 depression, 188 use of term, 78 diabetes, 155, 156 vitamin D intoxication, 427 DRIs Calcium. See also Calcium balance; Serum adolescents, 7, 351, 352, 354–355, calcium 1104, 1108, 1114 absorption. See also Calcium, adults, 7, 355–361, 1104, 1108, 1114 bioavailability background of current report, 346 adolescents, 95, 352 children, 7, 351, 352, 353–355, 1104, African Americans, 260–261, 296 1108, 1114 children, 352 infants, 7, 348–351, 1104, 1108, 1114 dietary factors, 63–64 in IOM 1997 report, 16, 58–60, 61, fractional, 38–39 346, 350, 351, 404 from the gut, and increased risk for lactation, 7, 361, 362, 1104, 1108, nephrolithiasis, 411, 500 1114 impaired with rickets, 94 pregnancy, 7, 361–362, 1104, 1108, as indicator of nutrient adequacy, 1114 4, 129 summary tables, 7–8, 349, 464, 1104, infants, 52, 253, 350, 503, 505 1108, 1114 methods of measurement, 264–265 EARs. See also Calcium, AIs overview, 38–40 and accretion/retention, 58n.4, 268, during pregnancy or lactation, 242, 272, 292 249, 250, 253, 256–257, 259, adolescents, 7, 351, 354, 356, 357, 277, 279, 281–282, 292, 361, 359, 1104 424 adults, 7, 355, 356, 357, 359, 360–361, relationship with vitamin D, 35, 1104 40–41, 143, 279 children, 7, 351, 353, 354, 1104 role of calcitriol, 35, 38, 39, 89, 253, lactation, 7, 9, 349, 361, 362, 464, 260, 264, 267 1104 and serum 25OHD, 213, 257, 259, pregnancy, 7, 9, 349, 361, 362, 464, 264–267, 271, 277, 284, 292, 1104 366, 368, 388–389 summary tables, 7, 349, 464, 1104 accretion, 53–54, 269, 350, 351–353, elemental, 37 354, 503. See also Bone, excretion accretion adolescents, 95, 352 adverse effects with. See Adverse effects, children, 352 calcium; Calcium, ULs dietary factors, 63–64 AIs, 7, 8, 58n.4, 345, 346, 348–351. See infants, 8 also Calcium balance, studies; during lactation, 256, 257, 282 Calcium retention overview, 41–42 autism, 183 postmenopausal women, 55 bioaccumulation, 35, 43 during pregnancy, 189, 250 bioavailability, 37, 39, 62–63, 498, 503 reduction with diuretics, 407

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1081 INDEX relationship with calcium intake, 42, during pregnancy or lactation, 249, 256, 257, 413–414 277–278, 282, 362 relationship with hypercalciuria, regulated by calcitriol. See Calcitriol, 406–407 functions, calcium regulation by route, 38, 61, 352 studies, 57–60, 58n.4, 350, 351, 352 food sources of, 36, 62–63, 413, 466, 497, Calcium bicarbonate, 43, 407 498 Calcium carbonate, 37, 63, 407, 408, 417. homeostatic regulation, 35, 40–41, 49, See also Supplements, calcium 56, 84, 89–90, 153, 157, 253 Calcium citrate, 37, 43, 63, 417. See also in human milk, 39, 52–53, 56, 57, 256, Supplements, calcium 257 “Calcium economy,” 294–298, 517 intake. See Calcium intake Calcium glucoheptonate, 37n.2 interactions with other nutrients. See Calcium gluconate, 37n.2 Calcium interactions Calcium hydroxyapatite, 35, 37n.2, 43, ionized, 35, 43, 56, 250, 257, 424 44–45 during lactation, 7, 8, 45n.3, 56–57, Calcium intake. See also Supplements, 256–257, 362 calcium metabolism, 35, 38–42, 43, 56. See also absorption of lipids and, 148 Calcium balance assessment mobilization or transport, 153, 177–178, approach, 462–463 249, 254, 356, 361 Canadian estimated, 465–468 physiological role, 35, 42–52, 157, 184 Canadian surveys, 461–462 during pregnancy, 7, 189, 190, 242, estimates from national surveys, 10, 249–250, 361–362 458–460 RDAs, 7, 272, 292, 351, 353, 354, 355, from food sources only, 465, 466 356, 357, 359, 361, 1108 summary, 477, 480–481 retention. See Calcium retention U.S. estimated, 463–465, 466 rheumatoid arthritis, 175 water, 36 sources, 36–37 assumption of adequacy for vitamin D supplements. See Supplements, DRI, 347–348 calcium bone health and through the life stages, 7–8 BMC/BMD, 47, 60–62, 175, 195, ULs, 7, 8, 418–420, 421–424, 464, 488, 219–226, 270–274, 285–290, 500–501, 1114–1115 392–393 umbilical cord level, 251, 254 bone accretion, 47, 53–54, 292 units of measurement, 31 bone loss, 35, 40, 274, 356 Calcium-alkali syndrome, 407–409, 418, bone mineralization, 276 422, 423 dose–response relationship, 360 Calcium balance. See also Calcium, during pregnancy, 278–279 homeostatic regulation skeletal recovery after weaning, 57, adolescents, 58 256–257, 258, 282, 283, 285 adults, 355 cancer, 144–145, 146, 147, 414–416 bone remodeling and, 45–46, 272 cardiovascular disease, 148 definition, 57 diabetes, 155, 156 estimation methods, 58, 62 excess, 37, 42, 150, 517–518. See also as indicator of nutrient adequacy, 4, 129 Indicators of adverse outcomes infants, 58 for excess intake models, 58–60 excretion of calcium and, 42, 414 negative, 284–285 falls and physical performance, 157 neutral, 272–273, 285, 292 inadequate. See Calcium, deficiency outcomes, 58 infants, daily, 53, 349, 350–351

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1082 INDEX for neutral calcium balance, 58, 273, 285 Canadian Institute for Health Information, plateau intake, 58 461 preeclampsia and pregnancy-induced Canadian Multicentre Osteoporosis Study, hypertension, 189, 190, 250 270 relationship with calcium absorption, Canadian Nutrient File (CNF), 462 38–39, 56 Cancer/neoplasms. See also specific histological relationship with calcium retention, 269 sites rheumatoid arthritis, 175 calcitriol and, 77, 91–92, 139 systemic lupus erythematosus, 176 calcium and, 136, 137, 139 Calcium interactions as indicator of adverse outcomes for foods and food components, 62–64 excess intake, 6, 405 iron, 6, 37, 405, 416–417 as indicator of nutrient adequacy, 4, 5, magnesium, 37 129, 134–139 prescription drugs, 422 overview, 134, 135–136 vitamin D, 5, 6, 35, 60, 136, 358, 360, 369, serum 25OHD and, 138, 139 388, 484, 517 vitamin D and, 91–92, 135–139, 486 zinc, 6, 37, 405, 417 Cancer Prevention Study II Nutrition Calcium lactate, 37n.2 Cohort, 142, 414, 436 Calcium retention Carbohydrate, 83, 1104, 1110, 1111 adolescents, 53–54 Carcinogenesis, 91–92, 135, 143, 144 bone mass measurements, 61–62 Cardiovascular diseases calcium intake and, 58–60, 269, 270 calcitriol and, 78, 150–151 children, 268, 353 calcium and, 148, 149, 150, 407, 410, effects of dietary protein, 63 481 infants, 350, 503 as indicator of adverse outcomes for integration of evidence, 292 excess intake, 6, 405 plateau intake, 58 as indicator of nutrient adequacy, 4, 5, race considerations, 296, 297 129 regression modeling, 58 mortality, 148, 149, 150, 438 Canada overview, 147–148 calcium intake assessment, 37, 465–468 serum 25OHD and, 148–149, 150–152, changes in diet of indigenous Canadian 437–438 populations, 11, 498–500 vitamin D and, 88, 148, 149, 425, 426, compared with the U.S., 474, 476–477 437–438 national intake surveys, 10–11, 110–111, Carotenoids, 1113 457–458, 461–462, 521 Cartilage, 44, 48, 94, 174, 175 Recommended Nutrient Intakes, 15 Caucasian ancestry use of DRIs, 15 calcium accretion, 268–269 vitamin D puberty, 24 deficiency, 13–14, 486–488, 494 serum 25OHD levels, 101, 103, 104, in formula, 81 155, 173, 174, 203, 205–206, intake assessment and serum 25OHD 211–213, 215, 216 levels, 10–11, 110–111, 474– Celiac disease, 254 477, 478 Cell cycle, 91, 140, 143, 146 in milk, 79 Cell differentiation, 77, 91, 140, 143, 146, supplementation, 81 157, 176 Canadian Community Health Survey Cell proliferation, 77, 90, 140, 146, 157 (CCHS), 461, 467, 474, 475 Centers for Disease Control and Prevention Canadian Food Inspection Agency (CFIA), (CDC), 420, 460, 477 79 Cerebrovascular disease, 147 Canadian Health Measures Survey (CHMS), Cesarean section, 192 462, 474, 476, 478, 499

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1083 INDEX Children, ages 1 through 3 years ULs, 7, 9, 419, 420, 421, 441, 445, 464, bone health, 218, 382–383, 384, 386 469, 1112–1115 calcium, 7, 61, 268, 349, 351, 352, 353, vitamin D, 9, 385–387, 441, 445, 469, 413–414, 420, 463, 464, 465, 470–473, 475, 1106, 1112 466, 467, 1104, 1108, 1114 vitamins, 1106–1107, 1112–1113 DRI development, 23, 385–387, 445 water, total, 1110 EARs, 7, 9, 349, 351, 353, 385, 387, 464, Chills, 180 469, 1104–1105 Chinese ancestry or Chinese, 188, 216, 228, elements, 1108–1109, 1114–1115 268 growth rate, 23 Chloride, 1109, 1115 macronutrients, 1110–1111 Cholecalciferol. See Vitamin D3 RDAs, 7, 9, 349, 351, 353, 385, 387, 464, Cholestasis, 505 469, 1106–1110 Cholesterol, 83, 84, 148, 434, 435, 1111 ULs, 7, 9, 420, 441, 445, 464, 469, Choline, 1107, 1113 1112–1115 Chondrocytes, 44, 175 vitamin D, 9, 95, 169, 385–387, 441, 445, Chromium, 1108, 1114 469, 470–473, 475, 1106, 1112 Chronic disease and DRI development, 2, 5, vitamins, 1106–1107, 1112–1113 16, 28, 486, 489. See also specific water, total, 1110 diseases Children, ages 4 through 8 years Chylomicrons, 83–84, 106 bone health, 195, 202–208, 218, 382–383, Clothing, 81, 100, 105, 494 384, 386 CLUE, 436 calcium, 7, 47, 53, 61, 265, 268, 349, 351, Cognitive function, 4, 129, 183–186, 188 353–354, 385, 387, 464, 465, Collagen, 43, 44, 175 466, 467, 1104, 1108, 1114 Colorectal cancer/colon polyps, 135, DRI development, 24, 385–387, 445 142–144 EARs, 7, 9, 349, 351, 385, 387, 464, 469, Communication deficits, 182 1104–1105 Competitive protein-binding assays elements, 1108–1109, 1114–1115 (CPBAs), 107, 108, 109 macronutrients, 1110–1111 Computed tomography, 61, 62 RDAs, 7, 9, 349, 351, 354, 385, 387, 464, Constipation, 6, 37, 405, 417, 422 469, 1106–1110 Contraceptives, oral, 11, 501–503 ULs, 7, 9, 420, 421, 441, 445, 464, 469, Convulsions, 94 1112–1115 Copper, 1105, 1108, 1114 vitamin D, 9, 95, 169, 385–387, 441, 445, Cord, blood chemistry, 192, 251, 252, 254, 469, 470–473, 475, 1106, 1112 281 vitamins, 1106–1107, 1112–1113 Coronary artery disease, 147 water, total, 1110 Corpuscular indexes, 417 Children, ages 9 through 13 years Cramping, 171 bone health, 53–54, 195, 202–208, 218, Craniotabes, 255, 280 226, 280 C-reactive protein, 152, 435 calcium, 39, 53–54, 265, 354–355, 386, Creatinine, 176, 406, 408, 409, 428–429, 434 417, 465, 466, 467, 1104, 1108, Crohn’s disease, 4, 129, 171–173 1114 Cross-cultural differences. See Race/ DRI development, 24, 354–355, 385–387, ethnicity 445 Cubilin-megalin receptor system, 88 EARs, 7, 9, 349, 351, 464, 469 Cut-point, 13, 14, 144, 462, 480, 486–488, elements, 1108–1109, 1114–1115 522 macronutrients, 1110–1111 CYP enzymes, 84–87, 90 RDAs, 7, 9, 349, 351, 464, 469, 1106–1110 Cytochrome P450, 77, 85 Cytokines, 175, 189, 491

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1084 INDEX D Depression, 4, 129, 186–188 Dermatitis, 168 Dairy products Diabetes (type 1), 4, 5, 170–171, 189, 192, autism, 183 255 calcium, 36, 62, 414–415 Diabetes (type 2), 4, 5, 129, 151, 152–156 cancer risk, 142, 146, 414–415 Diarrhea, 171, 497 constipation from, 417 DiaSorin, 110–111, 111n.12, 476, diabetes, 155 476n.17–18 lactose intolerance or cow’s milk allergy, Dietary intake. See also Supplements; specific 496–498, 501 nutrients protective compound against kidney assessment. See Intake assessment, dietary stones, 500 effects on asthma, 168 vitamin D–fortified, 79–80, 431–432, 497 fat, 83, 148, 168, 498, 1110, 1111 Data fiber, 62, 417, 1110 assignment of “race” in study design, 295 of indigenous Canadian populations, 11, associations vs. causal or predictive 498–500 relationships, 263–264, 480, of peoples in the far north, 492 485, 517 protein, 63, 1104, 1110, 1111 challenges research needs, 521 graded doses, 12, 484, 515, 519 self-reported, 459, 460, 497 isolation of effects of single nutrient, total intake, 457, 459, 474, 483 5, 6, 11, 12, 35, 346, 485 tuberculosis, 179 limited or incomplete. See Research use of term, 457 needs; Uncertainties vegetarian or vegan, 11, 63, 179, 496–498 pre-existing disease conditions, 406, Dietary Reference Intakes (DRIs) 422 AI and, 345 standardization, 109, 516, 521 background, 15–16, 18 statistical analysis/synthesis calcium. See Calcium, DRIs methodology, 158–159, 519 components, 3, 15–16, 20. See also extrapolation Adequate Intake; Estimated from animal studies, 96 Average Requirements; from EAR and UL values, 27 Recommended Dietary from observed data to general Allowance; Tolerable Upper population, 404 Intake Levels from one life stage to another, 23, 24, criteria for, 30–31, 485 346, 355, 393 decision making, 18–19, 26 inconsistency in measured outcomes, 181 definitions, 19–22 interpolation, 354, 423 development observational, 22, 130 and chronic disease, 2, 5, 16, 28, 486, postmortem, 275, 350, 367, 388 489 quality, and hierarchy of study design, IOM initiative, 15–16, 91 127, 128, 130, 131–132, 133 and public health. See Public health scaling, 29, 346 considerations, in DRI uncertainties in analysis, 158–159 development uncertainties in collection, 11–12, 167 rationale and assumptions, 16–17, weighted, 519 347–348, 351, 369, 370, 385. Decision making, 18–19, 26 See also Sun exposure, DRI 7-Dehydrocholesterol, 75, 81, 95, 100, 101, development, assumption of 104, 496 minimal Dementia, 4, 183–186 risk assessment in, 17, 18, 26–29, 30, Deoxyribonucleic acid (DNA), 105, 143 32, 345, 403, 481–482, 488– 490, 514–516

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1085 INDEX EAR and, 2, 17, 22–23, 294 Duel-energy X-ray absorptiometry (DXA), elements, 1108–1109, 1114–1115 56, 57, 61–62, 199–201, 205– extrapolation. See Data, extrapolation 206, 210–216, 229, 231, 233 framework, 17–19, 488 Dyslipidemias, 152 IOM committee. See Institute of Dysthymic disorder, 186, 187 Medicine, committee macronutrients, 1110–1111 E measures. See Indicators of adverse outcomes for excess intake; East Asian ancestry, 101, 103 Indicators of nutrient Eating disorders, 406, 407, 425 adequacy Eczema, 168, 169, 192 overview, 7, 12, 18–19, 23–25, 457, 458, Elderly population. See also Adults, 70+ years 479–481 bone health and serum 25OHD, 209– RDA and, 23, 345 218, 226–234, 496 total water, 1110 cognitive function, 183–186 uses, 2, 19–20, 22–23 diabetes, 154 vitamin D. See Vitamin D, DRIs falls, 157, 160–161, 166 vitamins, 1106–1107, 1112–1113 indoor environment or institution, 11, Dietary Reference Intakes for Calcium, 37, 241, 496 Phosphorus, Magnesium, Vitamin Elements, 1108–1109, 1114–1115 D, and Fluoride (IOM, 1997) Emesis (vomiting), 407, 409 calcium, 16, 58–60, 61, 346, 350, 351, Encephalomyelitis, 173 404, 416, 420–421 Endocrine system, 35, 40–41, 84, 89, 153, ULs, 404, 420–421 156 vitamin D, 9, 16, 97, 346, 404, 425, 487 Endpoints, 25, 158, 263, 489, 505 Dieting. See Weight loss or dieting Energy metabolism, 24 Dietitians of Canada, 497 Epidemiological studies, 63, 131, 132, 135, 1,25-Dihydroxyvitamin D. See Calcitriol 145, 176–177, 185, 278, 361 24,25-Dihydroxyvitamin D, 78, 86, 109, 504 Epidémiologie de l’Ostéoporose (EPIDOS), Diuretics, 407, 409 185 Dose–response relationships Ercalcitriol, 78 calcium intake, 269, 360 Ergocalciferol. See Vitamin D2 intake–response assessment, 17, 28–29, Estimated Average Requirements (EARs). 31, 403, 418–424, 440–446, See also specific nutrients 515–516, 519–520 calcium. See Calcium, EARs public health approach vs. medical coefficient of variation, 21 approach, 482, 521 cut-point method, 462, 480, 486–487 research needs, 12, 159, 346, 359, 360, definition, 3, 20, 482 482, 519–520 development, 2, 8–9, 20–21, 26 serum 25OHD DRI and, 2, 17, 22–23, 294 and bone health, 364, 366 of females. See Females, EARs and cardiovascular disease, 148, 149, during lactation. See Lactation, EARs 437–438 of males. See Males, EARs and vitamin D, 98, 364–365, 381, 431, during pregnancy. See Pregnancy, EARS 439 RDA and, 2, 3, 20, 21, 23, 369 vitamin D selection of indicators of nutrient and bone health, 159–160, 161, 167, adequacy, 27–28, 31, 125–127, 291, 363, 364, 365–383, 390 129, 130–134, 298–299 and colorectal cancer, 145 serum 25OHD level and, 294 and serum 25OHD levels, 98, 364– summary table, 1104–1105 365, 381, 431, 439 throughout the life cycle. See under specific and type 1 diabetes, 171 life stages

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1092 INDEX risk with excess calcium, 286, 410–414, as indicator of nutrient adequacy, 4, 129 422, 481 overview, 49–50, 94, 156 risk with excess vitamin D, 286, 426 during pregnancy, 253 Nerve transmission, 35, 43, 89, 173 serum 25OHD and, 8, 195, 275, 284, 292, Neuroblastoma cells, 184 293, 367, 368, 470–471n.16, Neurological manifestations, 176 494 Neuropsychological functioning, 4, 5, 182– Osteopenia, 175, 503 188. See also Autism; Cognitive Osteophyte, 61 function; Depression Osteoporosis New York University Women’s Health with adolescent pregnancy, 250 Study, 436 African Americans, 294–295, 296, 493 Niacin, 1104, 1107, 1113 effects of lactation, 57, 256 Nickel, 1115 FDA primary outcome, 167 Nigerians, 246–248, 265 fracture risk and, 50–52 No observed adverse effect level (NOAEL), inclusion in bone health measures, 489 418. See also Calcium, ULs; low calcium intake and vitamin D levels, Vitamin D, ULs 49 No observed effect level (NOEL), 28 with osteomalacia, 50 Northern Finland Birth Cohort of 1966, 191 postmenopausal, 48, 52 Norwegians, 154, 187, 244, 437 serum PTH as risk factor, 260 Numbness, in the limbs, 173 serum 25OHD and, 231 Nurses’ Health Study (NHS), 141, 142, 155, Osteoporotic Fractures in Men Study 177, 412–413, 436 (MrOS), 185, 356, 367 Nutrient–nutrient interactions, 5, 6, 7, 11, Oxalic acid (oxalate), 62, 411, 413, 498, 500 12, 35, 37, 346, 405, 416–417, Ozone, 104, 492 485 P O Pacific Islanders, 155 Obese or overweight persons. See also Pakistani ancestry or Pakistanis, 202, 209, Adipose tissue; Adiposity; 218, 244, 275, 493–494 Metabolic syndrome Pancreatic cancer, 425, 436–437, 486 bariatric surgery, 88, 106, 518 Pancreatic endocrine function, 153, 156 calcium absorption, 39 Pancreatic insufficiency, 254 challenges with bone mass measurement, Pantothenic acid, 1107, 1113 62 Paralysis, 173 definition, 490 Parathyroid gland (PTG), 35, 40, 41 diabetes, 154, 155–156 Parathyroid hormone (PTH) metabolic syndrome, 152 as biomarker for bone resorption, 55, vitamin D storage, 88, 105–106, 156, 490, 111 518 bone health and Organ transplant recipients, 158 African Americans, 296 Osteoarthritis, 216 children and adolescents, 205 Osteoblast, 44, 45, 46, 49, 50, 256, 491 fractures, 276, 390 Osteocalcin, 44 infants, 198 Osteoclast, 44, 45, 46, 89, 256, 491 postmenopausal women and elderly Osteoid. See Bone, organic matrix men, 210, 214–215, 227 Osteomalacia serum 25OHD, 198, 208, 246, cannot be corrected by increased 260–262 calcitriol, 49 calcitriol regulation, 77, 84, 85

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1093 INDEX calcium and, 35, 38, 40–41, 42, 49, 56, Preeclampsia and pregnancy-induced 62, 89, 407 hypertension, 4, 5, 189–191, fetal, 252 250 as indicator of nutrient adequacy, 4, 129, Pregnancy. See also Lactation 260–262 adolescents, 56, 57, 250, 257, 278, 361, multiple sclerosis, 174 362, 393, 394, 424, 469 osteomalacia, 50 bone health vitamin D and, 111, 426, 518 BMC/BMD, 249, 250, 254, 255, 256, Parathyroid hormone-related protein 278, 279–280, 361, 362 (PTHrP), 256, 257 fracture, 278 Parkinson’s disease, 158 serum 25OHD and, 192–193, 205, Periosteal expansion, 44, 46, 53 218–219, 251, 255, 279–280, Peripheral artery disease or peripheral 281 vascular disease, 147, 150, calcium, 7, 8, 39, 55–56, 96, 242, 249– 152, 437 250, 277–278, 279, 292, 349, Phosphate, 44, 49, 64, 77, 84, 89–90, 407, 361–362, 424, 464, 1104, 1108 409, 426, 500 DRI development, 24, 361–362, 393–394 Phosphorus EARs, 7, 9, 349, 361, 362, 363, 393, 394, absorption, 64 464, 469, 1104–1105 BMD and, 62 elements, 1108–1109, 1114–1115 bone formation, 44 hypercalciuria during, 424, 501 calcium regulation, 41, 49 increase in calcitriol, 90–91 deficiency, 44, 48, 50 macronutrients, 1110 EARs, 1105 multiple sclerosis remission, 174 fetal, 56, 252 non-skeletal reproductive outcomes, in human milk, 503 192–193 in milk with cream, 407 preeclampsia and pregnancy-induced RDAs, 1109 hypertension, 4, 5, 189–191, regulation by calcitriol, 64, 77, 89 250 serum, 40, 41, 50, 77, 90, 407, 426 RDAs, 7, 9, 349, 361, 362, 363, 393, 394, ULs, 1115 464, 469, 1106–1110 Physical activity. See also Falls and physical ULs, 7, 9, 419, 424, 441, 446, 464, 469, performance 1112–1115 bone fracture and, 286 vitamin D, 9, 96, 169, 182, 192, 193, 250– bone mass and, 46, 54, 273, 287, 490–491 260, 279–281, 363, 393–394, cancer, 140, 141, 142 441, 469, 1106, 1112 diabetes, 155 vitamins, 1106–1107, 1112–1113 serum 25OHD and, 105 water, total, 1110 vitamin D synthesis in the skin, 105 Prescription drugs, interactions with, 11, 87, Physiotherapy, 160–161 422, 504, 505 Phytic acid, 62 Profile of Mood States (POMS), 188 Pigmentation. See Skin pigmentation Prohormone, vitamin D as, 75, 84, 481, 484 Placenta, 52, 55, 90, 189, 251, 252 Proinflammatory state, 152 Pneumonia, 180 Project VIVA, 169 Polynesians, 155 Prostate, Lung, Colorectal, and Ovarian Polyuria, 406, 425 Cancer Screening Trial Population segments and conditions (PLCO), 141, 436 of interest, 11, 17, 29, 31, Prostate cancer, 6, 145–147, 405, 414–416, 490–505 422, 437 Portuguese, 186, 244, 245 Protein, dietary, 63, 1104, 1110, 1111 Potassium, 63–64, 1109 Proteinuria, 176, 189

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1094 INDEX Prothrombotic state, 152 vitamin D. See Vitamin D, RDAs Proton-pump inhibitors, 37, 407 vitamins, 1106–1107 Provitamin D. See 7-Dehydrocholesterol water, total, 1110 Puberty, 8, 24, 39, 47, 262, 354. See also Recommended Nutrient Intakes (RNIs), 15 Adolescents Rectal mucosa cancer, 135 Public health considerations Renal function cancer, 134 calcitriol formation and, 77, 84, 90, 481 cardiovascular disease, 147 renal failure, 407, 409n.1 in DRI development renal insufficiency calcium, 359, 360, 421, 423, 477 cardiovascular disease, 426 overview, 29, 293, 298, 404, 479, 482, chronic kidney disease–mineral 488–489, 522 disorder, 55 vitamin D, 370, 388, 420, 440, 442, hypercalcemia, 42, 406, 407–409, 445, 483, 485, 488, 494 410, 425 percent of N. Amer. population with, 406 R renal dialysis patients, 91 vitamin D intoxication, 88, 426 Race/ethnicity Reproductive outcomes, non-skeletal, 4, assignment of “race” in study design, 295 192–193. See also Preeclampsia breast-fed infants and vitamin D, 385, and pregnancy-induced 494–495 hypertension calcitriol levels, 260–261 Research needs “calcium economy,” 294, 517 adverse effects of vitamin D, 424–425 calcium retention, 296, 297 background diet to calculate total level cardiovascular mortality, 438 of intake, 346 clothing and sun exposure, 105, 494 calcium intake and BMD, 273 fractures, 439 chronic diseases, 5, 486, 489 limited data for DRI development, 347 clinical trials, 5, 12, 22, 135, 404, 486 onset of breast development, 24 context, 17, 18–19 relationship between serum 25OHD and dose–response relationships, 12, 159, PTH, 260–261 346, 359, 360, 482, 484, research needs, 347, 516–517 489, 519–520. See also Sun serum 25OHD levels, 101, 103, 104, 106, exposure, DRI development 174, 260–261, 374, 431, 438, ethnic/racial considerations, 347, 439, 444, 493 516–517 Radioimmunoassay (RIA), 110–111, 198 indicator review and selection, 515, Randomised Evaluation of Calcium and/Or 516–519 vitamin D (RECORD), 154 intake assessment, 22, 516, 520–521 Recommended Dietary Allowances (RDAs) intake response–assessment, 519–520 applicable population, 21 isolation of effects of single nutrient, 5, background, 15 6, 11, 12, 35, 346, 485 calcium. See Calcium, RDAs long-term data, 12, 425, 485, 518 defined, 3, 21, 482 reproducibility, 26, 109 development, 3, 8, 9–10, 21 serum 25OHD, 12, 139, 181, 517, 518, EAR and, 2, 3, 20, 21, 23, 369 519, 520, 521 elements, 1108–1109 summary, 513–522 macronutrients, 1110 sun exposure, 12, 484, 516, 520 throughout the life cycle. See under specific vitamin D as a hormone, 12 life stages Rheumatoid arthritis (RA), 4, 129, 174–175, uses, 15 177, 189

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1095 INDEX Rhinitis, 169 diabetes, 153 Riboflavin, 1104, 1107, 1112 effects of excess vitamin D, 405, 426, Rickets 428–429, 430–431 hereditary vitamin D–resistant (VDDR hypercalcemia, 38, 406, 408, 426 II), 49, 94, 252, 254, 260, 276 as indicator of adverse outcomes for as indicator of nutrient adequacy, 4, 129 excess intake, 6, 405 neonatal or vitamin D–deficiency, 75, during lactation, 257, 424 252, 254, 256, 280–281 during pregnancy, 56, 249–250, 253 premature infants, 503 regulation, 35, 40–41, 77, 89–90, 426 prevention with vitamin D–fortified Serum 25-hydroxyvitamin D (25OHD) foods, 79 assays for, 107–111, 476, 484, 516, 521 serum 25OHD, 49, 235, 237, 243–248, asthma, 169–170, 181 271, 293, 366, 368, 386, 470– autism, 183 471n.16, 494 as biomarker vitamin D–dependent (VDDR I), 49, 94, of vitamin D effect, 13–14, 96–97, 252, 254, 260, 276 263–264, 291, 293, 439, 484, Risk, use of term, 26 517, 520 Risk analysis, basic assumptions, 18–19, of vitamin D exposure, 8, 12–13, 96, 347–348 99, 293, 363, 381–382, 384, Risk assessment 480, 483, 486–488, 520 definition, 18 bone health and in DRI development, 17, 18, 26–29, 30, African Americans, 106, 208, 260– 32, 345, 403, 479, 488–490, 261, 295, 298, 439, 493 514–516 BMC, 195, 196–205, 210–218 four steps, 27 BMD, 195, 196–207, 209–218, 275, overview, 3 368, 386–387 population segments and conditions of bone loss, fractures, osteomalacia, interest, 11, 490–505 195, 275 role of dietary intake assessment, 457 calcium absorption, 213, 257, 259, Risk characterization, 11, 17, 26, 27, 29, 479 264–267, 271, 277, 284, 292, Risk communication, 18 366, 368, 388–389 Risk management, 18 children and adolescents, 195, 202– 208, 382–383, 384 distribution in healthy populations, S 294 DRI development Sarcoidosis, 91, 409 analysis and outcomes, 263–264, Saudi Arabians, 251, 259, 283 380–383 Scarring and scar tissue, 171, 173 conclusions, 366–370, 381–382, Schizophrenia, 182 486–488 School meals, 15, 354 integration of evidence, 292–294, Scleroderma, 409 370–379 Seasonal affective disorder, 186, 187 interpretation of data in the Selenium, 1105, 1109, 1115 literature, 365–366 Sensitive populations. See Special concerns non-linear relationship with Serum albumin, 215, 229, 249–250, 257, vitamin D intake, 12, 99, 379– 434, 435 383, 384, 484 Serum calcitriol, 38, 78, 150–151, 177, 191 fractures, 195, 231, 235, 236–237, Serum calcium 291–292, 366–367, 390, colorectal cancer, 143 438–439 decline with rickets, 49 infants, 195, 196–201, 257–258, 281, 283

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1096 INDEX mineralization, 275–276 race/ethnicity considerations, 101, 103, osteomalacia, 195, 275, 284, 292, 293, 104, 106, 174 367, 368, 470–471n.10, 494 relationship with BMD, 95 overview, 4, 5, 129, 193–194 relationship with body fat, 88, 105–106 postmenopausal women and elderly relationship with PTH, 111, 260–262 men, 209–218, 226–234 research needs, 517, 518, 519, 520, 521 pregnancy and lactation, 192–193, rheumatoid arthritis, 175 205, 218–219, 251, 255, systemic lupus erythematosus, 177 257–259, 279–280, 281, 283, toxicity, 404, 443–444 393–394 tuberculosis, 178, 179, 180, 494 PTH, 198, 208, 246, 260–262 uncertainties associated with, 12, 13, 97, rickets, 49, 235, 237, 243–248, 271, 381–382 293, 366, 368, 386, 470n.10, units of measurement, 32, 487 494 vaginosis, 192 cancer, 5, 138, 139, 140–141, 143–145, vitamin D and 146, 436–437 effects of sun exposure. See Sun cardiovascular disease and hypertension, exposure, relationship 148–149, 150–152 between 25OHD and vitamin cognitive function, 185–186 D depression, 187–188 effects of supplementation, 98, 106, desired level for population median, 8, 179, 180, 243–248, 251–252, 470–471n.16 266, 379, 381–382, 426–430, diabetes, 151, 154–156 431 factors affecting, 88, 97–107 intake, 10–11, 97–100, 110–111, 364, falls and physical performance, 157, 370–383, 386–387, 468–477 158–160, 162–165, 166, 167 intake assessment data, 468–477, half-life, 263 484 infants, 195, 196–201, 257–258, 281, 283, intoxication, 426–430, 443 504–505 Serum 25-hydroxyvitamin D2 (25OHD2), inflammatory bowel disease and Crohn’s 107, 108 disease, 172–173 Serum 25-hydroxyvitamin D3 (25OHD3), insulin sensitivity, 154 107, 108 intake assessment process Serum parathyroid hormone, 111, 174, levels for U.S. and Canada, 10–11, 260–262 13, 476 Serum phosphate, 407, 409 methodological considerations, 463, Serum phosphorus, 40, 41, 50, 77, 90, 407, 476 426 in national surveys, 460–461, 462, Serum vitamin D3, 104 474, 477–478 Shanghai Women’s and Men’s Health review of national survey data, 31, Studies, 436 477–478, 480 Signal transduction, 43, 93 vs. plasma 25OHD, 461n.10 Silicon, 1115 interactions with prescription drugs, Skeleton. See also Bone; Bone health 504 bone types, 45 mortality, all-cause, 425, 432–435, 444 gestational development, 55–56, 57, 193, multiple sclerosis, 173, 174 242, 249, 281, 393–394 neonatal, 109, 258, 280–281, 283 three functions, 42–43 population baseline, 99 timeframe for turnover, 45 preeclampsia and pregnancy-induced Skin cancer, 6, 12, 136, 363, 370, 481, 491, hypertension, 189, 190, 191 496 public health considerations, 521 Skin eruptions, 176

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1097 INDEX Skin pigmentation, 101–104, 174, 370, 481, relationship between serum 25OHD 493–495 and vitamin D, 98–105, 172, Smoking, 147, 415, 434, 435, 436 187, 364, 370–383, 430, 468, Social withdrawal, 182, 186 471–473, 477–478. See also Sun Sodium, 62, 63–64, 168, 1109, 1115 exposure, reduced vitamin D South Asian ancestry or South Asians, 101, synthesis; Sun exposure, skin 103, 154, 493–494 cancer; Vitamin D, synthesis in Special concerns the skin limited or incomplete data. See Data, seasonal affective disorder, 187 challenges; Uncertainties seasonal considerations, 100–101, 102, population segments and conditions 104, 174, 200, 371, 378–383, of interest, 11, 17, 29, 31, 471–473, 478, 484, 492 490–505 skin cancer, 6, 12, 136, 363, 370, 481, Sri Lankans, 244, 493–494 491, 496, 520 Stakeholders, 2, 3, 19, 29, 126, 127, 479, type 1 diabetes, 170–171 513, 521 Sun protection factor (SPF), 495 Staphylococcus, 178 Sunscreen, 11, 105, 370, 495–496, 516, STATA regression analysis software, 520 159 Supplements Statistics Canada, 461, 467, 475, 476, 477 calcium Stem cells, 43 adverse effects with, 22, 42, 404, Steroids, 53, 58 405–424, 481, 500–501. See also Stroke, 147, 149, 150, 152, 158, 160, 185 Calcium, ULs Study of Osteoporotic Fractures, 213, 296 bioavailability, 63 Sugars, 1111. See also Fructose; Glucose and bone health, 209, 210–211, 217, Sun exposure 218, 219–226, 234–242, 243, altitude, 105 246, 274, 285–290, 358, 360, atmospheric conditions, 104, 105, 492 391, 417 cardiovascular diseases, 148 cancer, 137, 139, 141, 142, 144–145, Crohn’s disease, 172 147, 414–416 DRI development cardiovascular disease, 149–150 assumption of minimal, 8, 98, 364, diabetes, 153, 154–155 370–371, 378–379, 389, 481, falls and physical performance, 158, 482–483 162–165 research needs, 12, 484, 516, 520 during lactation, 256 latitude considerations, 11, 98–99, percent of population which takes, 100, 101, 104–105, 136, 170, 37 174, 202, 371–383, 477–478, preeclampsia and pregnancy-induced 491–492 hypertension, 190, 191, 250 multiple sclerosis, 173, 174 rickets, 49, 243–248, 260 during pregnancy, 254 role in intake assessment, 460, 463– prostate cancer, 147 464, 466 radiation. See Ultraviolet A radiation; and serum 25OHD levels, 243, 266 Ultraviolet B radiation with vegan diet, 498 reduced vitamin D synthesis dosage issues, 1 clothing, 105, 494 phosphate, 414 indoor environment, 11, 37, 496 self-reported use, 36, 37, 460 skin pigmentation, 11, 100–104, 174, vitamin D 370, 481, 493–495, 520 adverse effects with, 6, 10, 404, 405, sunscreen, 11, 105, 370, 495–496, 412, 427, 486. See also Vitamin 516, 520 D, ULs

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1098 INDEX and bone health, 196–208, 209–226, Total intake. See Dietary intake, total intake 234–235, 236–242, 243–248, Transient receptor potential cation 285–286, 290–292, 358, channel, vanilloid family 390–392 member 5 (TRPV5), 42 cancer, 136, 137, 141, 142 Transient receptor potential cation cardiovascular disease, 148, 149 channel, vanilloid family depression, 187–188 member 6 (TRPV6), 38, 253 diabetes, 153–154, 171 Triglycerides, 83, 84 dosage issues, 81, 106–107 Tuberculosis (TB), 4, 5, 91, 177–180, 430, effects on serum 25OHD level, 87–89, 494 98, 106, 179, 180, 243–248, Tufts Medical Center Evidence-based 251–252, 266, 379, 381–382, Practice Center, 513 426–430, 431, 468, 471 Turks, 230, 243, 244 falls and physical performance, 157– Tympanosotomy tube placement, 181 165, 167, 438 and infant birthweight or length, 192, U 193, 251–252, 283 for infants, 95, 96, 258, 495 Ulcerative colitis, 172, 173 influenza and upper respiratory Ulcers, 407 infections, 180 Ultraviolet A radiation (UVA), 105 during lactation, 258 Ultraviolet B radiation (UVB), 105, 179, preeclampsia, 190 254, 430, 491–492, 494. See during pregnancy, 9, 96, 169, 182, also Sun exposure 190, 192, 193, 251–252 Uncertainties. See also Data; Research needs rheumatoid arthritis, 175 calcium-vitamin D interactions and tuberculosis, 177, 178–179 independent effects, 5, 6, 60, with vegan diet, 498 358, 360, 369, 388, 405, 484 Surrogates, 8, 25, 144, 145, 264 in the context of risk assessment, 3, 18, Synovial fibroblasts, 175 19, 29 Synovitis of the joints, 174 in data analysis, 158–159 Systemic lupus erythematosus (SLE), 4, 129, in data collection, 11–12, 167 176–177 dose–response relationships, 12, 159, 346, 355, 359, 360, 482, 484, 489, 515, 519. See also Sun T exposure, DRI development T cells, 91, 170 due to pre-existing disease conditions, Tachysterol, 81, 82 406, 422 Teeth, 35, 193 meta-regression analysis methods, Testosterone, 145, 213, 230 158–159 Tetany, 49, 94 methods for serum 25OHD assay, Thiamin, 1104, 1106, 1112 107–111, 476, 484. See 3-epi series, 86, 109 also Methodological Threshold effect, 141, 515, 516 considerations, assay shift and Thrombogenicity, 148 drift Thyroid gland, 40 need for long-term data, 12, 425, 485, 518 Toddlers. See Children, ages 1 through 3 non-linear relationship between serum years 25OHD and vitamin D intake, Tolerable Upper Intake Levels (ULs), 3, 12, 99, 379–383, 384, 484 5–6, 8, 10, 12, 22, 403–405, summary, 483–486 1112–1115. See also Calcium, UL development, 404–405, 485 ULs; Vitamin D, ULs vitamin D as a prohormone, 75, 84, 481, 484

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1099 INDEX Uncertainty factor (UF), 29, 404–405, 420, asthma, 169–170, 181 421, 422, 442 bioaccumulation, 84, 87–88 United States as biomarker of total intake, 12–13 calcium intake assessment, 37, 463–465, calcium regulation, 35, 40–41 466 cancer compared with Canada, 474, 476–477 breast, 140–142, 435–436 national intake surveys, 10–11, 110, 457, colorectal, 143 458–461, 521 overview, 135–139 vitamin D deficiency, 13–14, 480, pancreatic, 425, 436–437, 486 486–488 prostate, 146–147, 437 vitamin D intake assessment and serum role in carcinogenesis, 91–92 25OHD levels, 10–11, 110, cardiovascular disease, 148, 149, 152 468–473 cognitive function, 183–86, 188 Units of measurement, 31–32, 78, 487 deficiency Upper Levels of Intake (ULs). See Tolerable autism, 182, 183 Upper Intake Levels and bone metabolism, 35. See also Upper respiratory infections, 4, 5, 129, 169, Osteomalacia; Rickets 180–181 and cognitive function, 184, 185 U.S. Department of Agriculture (USDA), colon cancer, 143 36, 38, 79, 458, 459, 462 conclusions, 13–14, 293, 480, 486–488 U.S. Food and Drug Administration (FDA), defined by cut-point value, 480 80, 167 indoor environments and institutionalized older persons, 241, 496 V inflammatory bowel disease, 172 influenza and upper respiratory Vaginosis, 192 infections, 180 Vanadium, 1115 multiple sclerosis, 173 Vascular endothelial growth factor (VEGF), muscle weakness, 156–157 92 normal calcitriol levels, 97 Vasodilation, 35, 43, 89 pregnancy or lactation, 218, 251, Vdr gene, 140, 168, 170, 172, 173, 178, 182, 253–256, 259–260, 279–280 184 prostate cancer, 146–147 Vdr-null mice, 91, 143, 148, 171, 173, 184, and serum 25OHD all-cause 251, 253, 259–260, 279 mortality, 432–435 Vegetarian or vegan diet, 11, 63, 179, and skin pigmentation, 481, 493–495 496–498 systemic lupus erythematosus, 176 Vision loss, 173 type 1 diabetes, 171 Vitamin A, 180, 1104, 1106, 1112 diabetes and, 153–155, 170, 171 Vitamin B6, 1105, 1107, 1113 DRI development Vitamin B12, 1105, 1107, 1113 analysis and outcomes, 380–383 Vitamin C, 1104, 1106, 1112 conclusions, 366–370, 480 Vitamin D. See also Calcitriol; integration of evidence, 292–294, 25-Hydroxyvitamin D; Serum 370–379 25-hydroxyvitamin D interpretation of data in the absorption, 83–84, 96 literature, 292–294, 365–366, adverse effects. See Adverse effects, 370–379 vitamin D; Vitamin D, ULs in IOM 1997 report, 9, 16, 97, 346, AIs, 9, 363, 383, 385, 469 404, 425, 487 anti-bacterial activity, 178, 181 DRIs associations vs. causal or predictive adolescents, 385–387, 469, 1104 relationships, 263–264, 480, adults, 387–394, 469, 1104 485, 517

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1100 INDEX background of current report, 16, RDAs 346 adolescents, 9, 363, 385, 387, 469, children, 385–387, 469, 1104 1106 in IOM 1997 report, 9, 16, 97, 346, adults, 9, 363, 389–390, 392, 393, 394, 404, 425, 487 469, 1106 lactation, 9, 363, 393, 394, 441, 446, children, 9, 363, 385, 387, 469, 1106 469, 1104 infants, 1106 pregnancy, 9, 363, 393, 394, 441, 446, lactation, 9, 363, 393, 394, 469, 1106 469, 1104 pregnancy, 9, 363, 393, 394, 469, 1106 EARs summary tables, 9, 363, 469, 1106 adolescents, 9, 363, 385, 387, 469, reference value development, 293–294, 1104 480 adults, 9, 363, 389, 392, 393, 394, 469, rheumatoid arthritis, 175 1104 serum 25OHD and. See Serum children, 9, 363, 385, 387, 469, 1104 25-hydroxyvitamin D, vitamin lactation, 9, 363, 393, 394, 469, 1104 D and and outcome of physical storage, 84, 87–88, 105–106, 156, 173, performance, 167 370, 490, 492, 498, 518 pregnancy, 9, 363, 393, 394, 469, 1104 submariners, 83 summary tables, 9, 363, 469, 1104 summary, 8–10, 363, 480 elderly population and, 87, 219, 234–235, sun exposure and. See Sun exposure 496 supplementation. See Supplements, excretion, 86, 88 vitamin D food sources of, 79–83, 498 synthesis in the skin, 6, 11, 81–83, 95, formation, 6, 75–77, 84–85 100–105, 481, 493–495, 520 functions and physiological actions, synthetic analogues, 78, 81n.5 77–78, 89–94, 143, 153, 156, systemic lupus erythematosus, 176–177 176, 177, 180, 184, 251 threshold effect, 141, 515, 516 hormonal action and regulation, 6, 12, ULs 515 adolescents, 441, 469, 1112 in human milk, 80, 94 adults, 441, 443–445, 469, 1112 infants, 9, 363, 383, 385, 469, 504 children, 441, 445, 469, 1112 influenza and upper respiratory development, 10, 440–446, 488 infections, 180 infants, 440–442, 1112 intake. See Vitamin D intake lactation, 441, 446, 469, 1112 intoxication, 6, 10, 88–89, 93, 405, 425, pregnancy, 441, 446, 469, 1112 426–430, 443, 518 summary tables, 9, 441, 469, 1112 irritable bowel syndrome, 172 uncertainties, 14, 486 during lactation, 9, 96, 257–260, 282– units of measurement, 31–32 283, 393, 394 use of term, 78 lifetime, 86 Vitamin D binding protein (DBP), 77, 84, media coverage, 1, 16, 480 86, 88, 107, 251, 427 metabolism, 35, 83–89, 92–93, 189 Vitamin D External Quality Assurance multiple sclerosis, 173–174 Scheme (DEQAS), 109–110, neuroprotective effects, 183–184 365 non-linear relationship with serum Vitamin D intake 25OHD levels, 12, 99, 379– adverse effects. See Adverse effects, 383, 384, 484 vitamin D; Vitamin D, ULs during pregnancy, 191, 250–256, 279– assessment 281, 393–394 approach, 462–463, 483 as a prohormone, 75, 84, 481, 484 Canadian estimated, 474, 478

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1101 INDEX Canadian surveys, 461–462, 499 expressed in the prostate, 146, 147 estimates from national surveys, infants lacking, 254 10–11, 459–460 lactation and, 91 food sources only, 470, 474, 475, 476 muscle tissue, 157 summary, 477–478 regulation of expression by calcitriol, 38, U.S. estimated, 468–473 90, 91 U.S. surveys, 458–461 rickets due to genetic absence of (VDDR assumption of adequacy for calcium DRI, II), 49, 94, 252, 254, 260, 276 347 use of term, 140n.1 asthma, 169–170, 181 Vitamin D response element (VDRE), 77, BMC/BMD and, 95, 175, 271, 274–275, 140 279–280, 386–387, 392–393 Vitamin D2 cardiovascular disease, 148, 149, 152 equivalence issues with vitamin D3, Crohn’s disease, 172 92–93, 97, 519 diabetes, 155 fortified foods, 80 excess, 88–89, 424–449, 481, 486, metabolism, 86–87, 92–93 517–518. See also Adverse overview, 78 effects, vitamin D; Indicators serum level as biomarker of total intake, of adverse outcomes for excess 107, 108 intake supplementation, 81 falls and physical performance, 157–165, toxicity, 93, 426 167, 438 Vitamin D3 fractures, 390, 438–439. See also deprivation, and autism, 182 Bone, fracture, vitamin D equivalence issues with vitamin D2, supplementation 92–93, 97, 519 indigenous Canadian populations, fortified foods, 80 498–499 metabolism, 86–87, 92–93 intoxication, 6, 10, 88–89, 93, 405, 425, overview, 78 426–430, 443, 518 serum level, not used to estimate during pregnancy, 169, 182, 279–281 synthesis in the skin, 104 rheumatoid arthritis, 175 serum level as biomarker of total intake, serum 25OHD. See Serum 107, 108 25-hydroxyvitamin D, vitamin storage, 105 D and; Sun exposure, supplementation, 81, 107 relationship between serum synthesis in the skin. See Vitamin D, 25OHD and vitamin D synthesis in the skin from supplements. See Supplements, toxicity, 93, 426 vitamin D Vitamin E, 180, 1104, 1106, 1112 through the life stages, 8–10, 94–96 Vitamin K, 1106, 1112 tuberculosis, 178, 179, 494 Vitamins, 1106–1107, 1114–1115 Vitamin D interactions Vomiting (emesis), 407, 409 calcium, 5, 6, 35, 60, 136, 358, 360, 369, 388, 405, 484, 517 W prescription drugs, 11, 87, 504, 505 Vitamin D receptor (VDR) Water, 36, 411, 417, 1110 in the brain, 184 Weight, 140, 153, 192–193, 254, 406, 420, cancer, 91, 140, 146, 147 425. See also Growth rate expressed in cells with rheumatoid Weight loss or dieting, 39, 106, 172, 518 lesions, 175 West Indians, 245 expressed in the duodenum, 38 What We Eat in America (WWEIA), 459, expressed in the fetus, 252–253 473

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1102 INDEX White-matter hyperintensity volume, 185 rheumatoid arthritis, 175 Women. See also Females; Gender serum 25OHD level and cardiovascular differences; Lactation; risk, 437 Menopausal status; Pregnancy systemic lupus erythematosus, 177 bone health Women’s Health Initiative (WHI), 138, 141, fractures, 234–242, 257, 285–286, 185, 220, 234, 285, 298, 358, 357–358, 391, 392, 438, 439 393, 411–412, 413, 422 and serum 25OHD, 209–218, 226– World Cancer Research Fund, 415 234, 235 vitamin D and calcium X supplementation, 226, 234–242 X-ray. See Duel-energy X-ray absorptiometry calcium, 40, 58, 162, 226, 234–242, 356, 357–359, 360–361, 477, 480–481 Y cognitive function, 185 depression, 188 Young adults. See Adults, 19 through 30 EARs, 356, 359, 360–361 years falls, 157, 161, 162, 166, 438 glucose tolerance, 154 Z mean age of puberty, 24 nephrolithiasis, 411–412 Zinc, 6, 37, 405, 417, 1105, 1109, 1115 RDAs, 356, 359