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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc Index A Abortions, spontaneous, 248 Absorption of nutrients. See also Bioavailability of nutrients; Malabsorption syndromes; individual nutrients adults, 40, 86, 474, 479 and adverse effects, 73 aging and, 40, 86, 146, 474 ascorbic acid interactions, 311-312, 521 assessment methods, 445, 455, 472 calcium interactions, 455-456 carotenoids, 86-93, 107 dietary fat and, 70, 106-107, 118, 121, 163 foods affecting, 521 form of intake and, 267, 373, 395, 483 form of nutrient and, 73 n.2, 87, 88-89, 227-228, 455-456, 529 fractional, 15, 447-448, 449, 450, 462, 463, 464-465, 468, 469, 472, 473, 474, 476, 478, 572 gender and, 402 human milk vs infant formula, 238, 404 infections and, 107 interaction of nutrients and, 70, 106-107, 118, 121, 163, 311-312, 455-456, 482-483 interindividual variation in, 69, 397, 402 intestinal environment and, 311-312, 454-455 lactation and, 244 level of intakes and, 242, 399, 422, 445, 473 menaquinones, 164 phytates and, 572, 576 pregnancy and, 243 processing of foods and, 107, 112, 146, 174, 211 solubility of compound and, 504 Aceruloplasminemia, 227, 377 Achlorhydria, 311 Achromotrichia, 435 Acid phosphatase activity, 529 Acrodermatitis enteropathica, 445, 477 Adenosine triphosphate (ATP), 225, 226 Adenosyl diphosphate, 357 S-Adenyl homocysteine, 509 S-Adenyl methionine, 509 Adequate intakes (AIs). See also individual nutrients appropropriateness of intakes above, 77 criteria used to derive, 36, 37 defined, 3, 6, 30, 34 EAR distinguished from, 37 extrapolation from other age groups, 35, 51-52, 53, 111 group applications, 554, 561, 564

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc individual applications, 554, 557-558, 562-563 methods used to set, 30, 50-51, 53 RDA compared to, 4, 6, 31, 35 uses, 4, 5, 34-35, 554, 557-558, 561, 562-563, 564, 577 Adolescents, ages 14 through 18 years. See also Life-stage groups; Pubertal development; individual nutrients age of menarche, 339-340, 573 AIs, 35, 39, 562-563 anemia, 335 basal losses of nutrients, 330, 331, 332, 337 bioavailability of nutrients, 337 blood volume, 331 EARs, 39 evidence considered in setting EAR, 271-272, 330-338, 427 extrapolation of data for, 269, 272, 282, 331, 406, 413, 427, 430-431, 437 goiter, 271-272 growth velocity, 39, 53, 331, 338, 339 hemoglobin concentrations, 305, 330, 331-333, 335, 336, 338 hypervitaminosis A, 144 lactation, 117, 184, 211, 244-245, 250, 251, 407, 413-414, 431-432, 479, 487, 519, 528 median weights, by age, 332 menstrual losses, 332, 334-337, 338 method used to set AIs, 180, 207, 404-405 method used to set EAR, 112, 238 oral contraceptive use, 335, 336, 350, 700, 702 pregnancy, 116, 117, 142, 183, 184, 210-211, 243-244, 276, 277, 348-349, 406-407, 413-414, 430-431, 477, 487, 519, 528 reference weights and heights, 41, 42, 210, 338 serum transferrin, 304 special considerations, 330, 339-340, 358, 573 variability of requirements, 330-331, 337-338 Adrenal glands, 522 Adults, ages 19 through 50 years. See also Life-stage groups; Men; Women; individual nutrients AIs, 34-35, 562-563 balance studies, 309-310, 405-406, 428-429 biochemical indicators, 239-240 bone mineral density, 126-128 depletion/repletion studies, 224, 228, 229, 231, 232, 239-240, 430 EARs, 52 energy expenditure, 40 factorial analysis, 240-242, 340 hyperthyroidism, 283 hypothyroidism, 283 peak bone mass, 40 reference weights and heights, 41, 114 supplement use, 246, 278 thyroid iodine accumulation and turnover, 273-274 Adults, ages 51+ years. See also Life-stage groups; individual nutrients AIs, 40 absorption of nutrients, 40, 86, 474, 479 γ-carboxyglutamyl excretion, 167 dietary intakes, 186 EARs, 40 energy expenditure, 40 energy needs, 209 institutionalized, 171 nickel, 523 physical activity, 40 physiological functioning, 40 renal function, 40, 69 silicon, 532 vanadium, 533, 534 vegetarian diets, 479-480 vitamin K, 166, 167, 182, 186 zinc, 451, 474-475, 479, 559, 562 Adverse effects. See also individual nutrients absorption of nutrients, 73 aging and, 508 defined, 60, 72, 704 evidence of, 72 form of intake and, 358, 374, 409, 410, 433, 482, 524 gender differences, 482 knowledge gaps, 584 nutrient interactions, 61, 72, 129, 358, 482-483

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc population distribution at risk of, 79-80 thresholds, 65-66 Aging. See also Adults (51+ years); Life-stage groups; individual life stages and absorption of nutrients, 40, 86, 146, 474 and adverse effects of nutrients, 508 and bone mineral density, 40 and γ-carboxyglutamyl residues, 167 and chromium concentrations, 200 food consumption and, 47, 186 and glucose tolerance, 209 and iodine requirements, 274 and liver function, 69 and PIVKA-II, 168 and plasma phylloquinone, 166 and vitamin K, 166, 167, 168, 170 Albumin, 227, 260, 395, 445, 446, 454, 473, 474, 522 Alcohol consumption and alcoholism chromium and, 215 iron and, 302, 376 serum ferritin and, 302 special considerations, 118, 145, 376-377, 480 and superoxide dismutase activity, 231, 401 vitamin A, 109, 118, 128, 133, 134-139, 145 zinc and, 475, 480 Aldehyde oxidase, 420 Alkaline phosphatase activity, 443, 453, 477, 529 Alopecia, 477, 514 Aluminum, 200 Alzheimer’s disease, 532 Amenorrhea, 372 American Academy of Pediatrics, 37, 50, 51, 97, 317 α-Amidating monooxygenase, 225 Amine oxidases, 224-225 Amino acid metabolism, 13, 44, 204, 394, 420-421, 446 Amiodarone, 259, 268 Amyotrophic lateral sclerosis (Lou Gehrig’s disease), 225-226 Analytic epidemiological studies, 47 Anemia adolescents, 335 arsenic and, 506 of chronic disease, 303, 304 copper deficiency, 11, 226, 227-228, 486 infants, 296-297, 298, 300, 317 iron deficiency, 12-13, 22, 44, 226, 295-299, 300, 301, 303, 305-306, 317, 352, 378, 583 macrocytic normochromic, 228 microcytic, 305 molybdenum and, 433 normocytic hypochromic, 11, 227 pregnancy and, 297-299 reproductive effects, 295, 297-298 vanadium and, 536 women, 297-299, 305 Angular stomatitis, 300 Animal studies arsenic, 45, 503, 505-506, 507, 508 boron, 45, 510, 511-512, 514-517 carotenoids, 94 chromium, 199-200, 213, 214-215, 458 copper, 226-227, 228-229, 232, 234-235, 244, 246 dose-response assessment for ULs, 71, 75-76, 78, 436, 710, 711, 712 extrapolation of data from, 63, 71, 74, 78, 436, 518, 526, 541, 710, 711, 712 for hazard identification, 71-72, 73, 409-411, 433-434, 514-515, 524 iodine, 279, 280 iron, 108, 121, 293, 296, 300 manganese, 396, 401, 406, 409-411 methodological considerations, 45, 71, 246, 279, 517, 712 molybdenum, 421, 424, 433, 435, 436 of neurotoxicity, 409-411 nickel, 524, 525, 526 relevance of, 45, 73, 234-235, 246, 279, 410, 433 reproductive effects, 406, 434-435 uncertainties in, 63, 78, 436, 540, 710, 711 vanadium, 532, 535-537, 539-540 vitamin A, 85, 95-96, 98, 104, 105, 108, 109, 121, 126 vitamin E, 175-176 vitamin K, 172, 173, 175-176, 188 zinc, 108, 455 Antacids, 204, 311, 531 Antibiotics, 164, 165, 166 Anticoagulants, 172, 174-175

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc Antihistamine, 224-225 Antioxidant activity ceruloplasmin, 225 copper, 225-226, 229 superoxide dismutase, 225-226 Antithyroid antibodies, 281, 283 α-1-Antitrypsin deficiency, 248 Antiviral activity, 85-86 β-Apocarotenals, 87 Apolipoprotein B100, 94 Apolipoprotein E, 163 Apoprotein E, 93 Apoptosis, 444 Apotransferrin, 200 Arginase activity, 394, 401 Arsenic absorption, 504 acute effects, 506 adverse effects, 7, 18, 505-508 and anemia, 506 animal studies, 45, 503, 505-506, 507, 508 and blackfoot disease, 506, 508 and cancer, 507-508, 509 developmental toxicity, 503, 507 in drinking water, 507, 508, 509 DRIs, 1, 6, 7, 36, 76, 78, 576 erythrocyte binding, 506 excretion, 504 exposure assessment, 509 food sources, 504, 509 forms, 504, 505, 509 functions, 45, 503 gastrointestinal symptoms, 506 gender and, 505, 658-659 and gene regulation, 503 genotoxicity, 507 and growth, 45, 503 hepatotoxicity, 506, 507 in human milk, 505 inorganic, 504, 505 intakes, 57, 504-505, 509, 658-659 international comparisons, 508 and keratosis, 506, 508 by life-stage group, 504, 658-659 malnutrition and, 506 maximum contaminant level, 508, 509 metabolism, 504 and methionine metabolism, 45 methyltransferase activity, 506 and peripheral neuropathy, 506-507 research recommendations, 28, 509-510, 583 risk characterization, 509 and skin pigmentation, 506, 507-508 teratogenicity, 507 trimethylated, 504 ULs, 18, 505-510 units, 709 zinc deficiency and, 506 Arsenicism, 506 Arsenite, 503, 504, 507 Arthralgias, 434 Arthritis, 372 Ascaris lumbricoides infection, 107 Ascorbic acid, 200, 204, 225, 292, 311-312, 313, 314, 315, 521 Aspirin, 204 Atherogenesis, 529 Atherosclerosis, 173, 532 Athletes iron requirements, 295, 296, 300, 305, 352-353, 574 vanadium supplements, 535, 537, 539 Autoimmune thyroid disease, 278, 283, 284 B Bacillus subtilis, 507 Balance studies adults, 309-310, 405-406, 428-429 children, 270, 404-405, 423 chromium, 198, 202 copper, 233, 241 design, 423, 581 infants, 269 iodine, 265, 275, 269, 270, 272, 274, 275 iron, 292, 308, 309-310, 314, 378 manganese, 395, 397-399, 404-406 methodological considerations, 45, 46, 49, 233, 265, 274, 309, 397 molybdenum, 14, 420, 423, 428-429 pregnancy, 274, 275 uses, 423 zinc, 445, 448, 455, 456, 458, 472, 474, 480 Basal losses of nutrients adolescents, 330, 331, 332, 337 children, 324, 325, 327 copper, 233, 240-242

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc extrapolation of data, 331 gender differences, 340 infants, 319, 320, 322, 325 iodine, 274 iron, 290, 295, 307-308, 320, 322-323, 324, 325, 327, 329, 330, 331, 332, 337, 340, 341, 342, 343, 344-345, 347, 349, 569 and lactation, 349 pregnancy and, 344-345, 347, 348 Bilirubin IXa, 293 Bioavailability of nutrients. See also individual nutrients adolescents, 337 algorithms for estimating, 314-316, 458 in cow milk, 427, 457 data and database issues, 173, 174 defined, 69-70, 704 dietary fat and, 173-174 dietary intakes and, 233-234 digestion and, 444-445 excretory losses and, 70 food matrix and, 68, 87-90, 107, 174, 312, 351, 359, 411, 414, 424, 429-430, 479, 530 form of intake and, 70, 87-89, 163, 173-174 form of nutrient and, 70, 88-89, 107, 186, 311, 568 in human milk, 457, 557-558 in infant formulas, 4, 38, 50, 112, 180, 206, 238, 267, 270, 317, 322, 427, 462, 557-558, 561 lactation and, 349 level of intake and, 315, 572 nutrient-nutrient interactions and, 70, 108, 173-174, 292, 311-312, 313, 314, 315, 582-583 nutritional status of individuals and, 70, 174 pregnancy and, 346-347 processing of foods and, 87, 313 and risk assessment, 69-70, 75 from supplements, 30, 88-89, 70, 173-174, 568 in vegetarian diets, 479, 572, 574 Biomarkers of bone turnover, 169 methodological issues, 47 Birth defects, 128-133 Bitot’s spots, 95, 105 Blackfoot disease, 506, 508 Bladder cancer, 507, 508 Blood. See also Plasma; Serum; other components boron concentrations, 511-512, 515 cholesterol, 228 coagulation, 10, 44, 163, 164, 165-168, 175, 176, 177, 181-182, 229; see also Coagulation factors; Prothrombin donation and, 352, 574 glucose, 24-25, 203-204, 510 manganese, 400, 401, 409 molybdenum, 421, 434 pressure, 229, 537 provitamin A carotenoids, 83, 90-91, 103, 107, 118 transfusions, 358 volume, 325-326, 331, 337-338 Body Mass Index, 41, 42, 302, 582, 694 Body pools. See also individual nutrients kinetic modeling of, 446, 582 size and turnover rates, 450-451 Body size considerations, 47 Body weight. See also Metabolic weight ratio method extrapolation on basis of, 42, 51, 52, 53, 54, 78, 142, 144, 250, 270, 282, 321, 404, 413, 437, 463, 487, 519, 569 gender and, 52, 332, 333 and iron losses, 308, 322-323, 327, 329, 331, 332, 333, 338, 340, 343, 582 loss, 201 median, by age, 332 nickel and, 525 pregnancy-related gains, 54, 210, 298, 407, 430, 518 reference weights and heights, 41-42, 52, 114, 210, 329, 338, 468 Bone formation and growth biomarkers of turnover, 169 copper and, 227, 228, 229 manganese and, 13, 44, 394, 396 molybdenum and, 433, 435 peak bone mass, 40 silicon and, 45, 529, 530 vitamin K and, 10, 23-24, 162, 169, 170-171, 172, 189, 583-584 Bone mineral density adults, 126-128 aging and, 40

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc anticoagulation therapy and, 172 carotenoids and, 127-128 copper and, 228 manganese and, 396 menaquinones and, 170, 172 osteocalcin γ-carboxylation and, 169, 170-171 vitamin A and, 126-128, 133 vitamin K and, 24, 169, 170-171 women, 126-128, 171, 172 Borax, 513, 514 Boric acid, 511, 513, 514, 518 Boron absorption and transport, 511-512, 520 adolescents, 519 adults, 16, 26, 517-518 adverse effects, 18, 514-517 animal studies, 45, 510, 511-512, 514-517 blood concentrations, 511-512, 515 and blood glucose, 510 body pools, 511-512 calcium and, 511 children, 513, 519 and cognitive and neurophysiological function, 511, 521 data selection, 517 developmental effects, 510, 512, 514-515, 518 dose-response assessment for ULs, 517-519 in drinking water, 512, 514, 520 DRIs, 2, 6, 512, 576 and epilepsy, 514 and estrogen, 45, 511, 520-521 excretion, 511, 512, 515 exposure assessment, 520 and extramedullary hematopoiesis, 515 food sources, 512 forms, 510 functions, 45, 510-511 gastrointestinal effects, 514 gender and, 511, 520, 618-621, 644-647 genotoxicity, 514 hazard identification, 513-517 in human milk, 513 human studies, 514 and hyperkeratosis, 515 and immune function, 511 infants, 514, 519 and insulin secretion, 510-511 intakes, 55-56, 57, 512-513, 520, 618-621, 644-647 interaction with other nutrients, 45, 510-511, 520 lactation, 513, 519 by life-stage group, 26, 512, 517-519, 618-621, 644-647 metabolism, 511-512 methodological issues, 517 NOAEL/LOAEL, 515, 516, 517-518 pharmacokinetics, 515 pregnancy, 513, 519, 520 reproductive effects, 512, 514-517 research recommendations, 28, 520-521, 583 risk characterization, 520 supplements, 57, 513, 514, 520, 620-621 and testicular atrophy, 515, 515-517 ULs, 16, 18, 26, 513-520, 576 uncertainty assessment, 518 units, 513, 709 vegetarians, 520 and vitamin D metabolism, 45, 510-511, 520 Boron Nutrient Database, 55-56, 512-513 C Calcium, 24, 172, 313, 314, 396, 401, 455-456, 457, 458, 462, 479, 480, 511 Canada arsenic, 504 cancer, 214 chromium, 212, 214 dietary intakes, 56, 57, 212, 356, 467, 474, 481, 674-679 infant food recommendations, 317 iodine, 261 iron, 57, 676-677 nickel, 522 Recommended Nutrient Intakes, 1, 37-38, 554, 588 reference weights and heights, 41-42 stomach cancer in gold miners, 214 vitamin A, 57, 94, 674-675 vitamin K, 176, 177-178 zinc, 57, 451, 452, 467, 474, 481, 678-679 Canadian Paediatric Society, 37, 50, 51, 317

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc Cancer/carcinogenicity. See also individual sites arsenic and, 507-508, 509 ceruloplasmin and, 230 childhood, 176-177, 188 chromium, 214 copper and, 248 iodine and, 259, 262, 266, 279, 280, 284 iron and, 302, 303, 370-372, 373 men, 370-371, 377 molybdenum and, 435 serum ferritin and, 302 serum transferrin receptors, 304, 370 silicon, 531 vanadium, 538 vitamin A and, 85, 96 vitamin K and, 176-177, 187-188 women, 371 zinc, 483 Carbohydrate metabolism, 13, 44, 201, 204, 394, 396, 444 Carbon monoxide, 293 Carbonic anhydrase, 443 γ-Carboxyglutamyl residues, 163, 167, 172, 173, 174, 189 Cardiovascular disease copper and, 226, 228-229 gender and, 359, 377-378 iron and, 303, 359, 364-371, 372, 373, 377-378 nickel and, 529 serum ferritin and, 365-367, 370, 377-378 silicon and, 532 total iron-binding capacity and, 303, 370-371 vanadium and, 537 vitamin K and, 173 α-Carotene, 2, 10, 82, 91-92, 122, 123, 564, 594-597 β-Carotene. See also Carotenoids absorption, 86-93, 109 animal studies, 94 bioavailability, 87, 107 bioconversion to vitamin A, 2, 82-83, 86-93, 565 blood concentrations, 83, 90-91, 107, 118 body stores, 94 and bone mineral density, 127-128 and chronic diseases, 83 depletion/repletion studies, 88-89 excretion, 88 food sources, 88-90, 112, 122, 124, 562 fortified foods, 565 gender and, 598-599 intakes, 119, 123, 124, 598-599 interaction with other nutrients, 109 international units, 565-566 by life-stage group, 598-599 provitamin A activity, 2, 82-83 RAEs, 10, 82, 87-93, 564 supplements, 88-91, 95, 107, 565 Carotenoids. See also β-Carotene; Provitamin A carotenoids; other individual carotenoids competitive interactions among, 109 intakes, 123, 597-605 Casein, 317, 457, 462 Catecholamines, 225, 229 Cellular retinoic acid-binding protein (CRABP-1 and -II), 85 Cellular retinol-binding protein (CRBP), 85 Central nervous system. See also Neurological abnormalities defects, 128 function, 225, 226, 297 Ceruloplasmin antioxidant activity, 225 and copper status, 224, 225, 227-228, 229, 230, 231, 235, 239-240, 484 deficiency, 227, 377 infants, 235 and iron, 225, 293 and liver disease, 230 pregnancy and, 230 Children, ages 1 through 13 years. See also Life-stage groups; individual nutrients accretion of new tissue, 464, 467, 468 AIs, 34, 35, 39, 51-52, 562-563 balance studies, 270, 404-405, 423 basal losses of nutrients, 324, 325, 327 blood volume, 325-326 calcium, 313 cancer, 176-177, 188 copper deficiency anemia, 486 diarrhea, 96, 97 dietary intakes, 466, 467 EARs, 32, 39, 42, 51-52

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc factorial analysis, 463, 467, 468 food sources for, 184-185, 698 fractional absorption of nutrients, 464-465 growth, 39, 53, 309, 324, 327, 328, 449-450, 465-466, 467-468 hemoglobin mass, 324, 325-326 hypervitaminosis A, 144 idiopathic copper toxicosis, 248, 251 Indian childhood cirrhosis, 248, 251 infectious diseases, 96-97 intestinal losses of nutrients, 463-464 iron deficiency in infancy, 297 liver damage, 250 malnourished, 97, 270, 454 measles, 96, 97 methodological considerations, 32, 39, 51-52, 53, 112, 180 mortality, 96-97, 262, 357 osteoporosis, 227 Plasmodium falciparum malaria, 96 poisoning deaths, 357 RDA, 52 reference weights and heights, 41-42, 468 supplement use, 96 supplementation studies, 465-466 thyroid gland monitoring, 284 ULs, 42, 53 variability of requirements, 327-328 water consumption, 247 xerophthalmia, 95, 97, 99 Cholesterol copper and, 228 manganese and, 396, 410-411 plasma, 396 serum, 359 zinc and, 481, 482, 486 Chromium III absorption, 198-199, 204, 209, 210, 211, 213, 216 adolescents, 207, 210-211 adults (19-50), 56-57, 208-210 adults (51+), 202, 208-209 aging and, 200 AIs, 12-13, 197, 207, 208, 209, 210, 211, 558, 561, 562-563, 564, 569 amino acids and, 204 animal studies, 199-200, 213, 214-215, 458 ascorbic acid and, 200, 204 balance studies, 198, 202 bioavailability, 211 blood glucose and, 24-25, 203-204 body stores, 200, 205, 209-210 and carbohydrates, 201, 204 carcinogenicity, 214 children, 207 deficiency, 200-201 and diabetes, 24-25, 200, 201, 216, 584 dietary fiber and, 204, 209 dose response assessment for ULs, 215-216 energy intakes and, 11, 205, 208-209, 212 excretion, 199-200, 202, 207, 210 exposure assessment, 216 factors affecting requirement, 204 food composition analysis, 54, 569, 583 food sources, 211, 216 forms of, 197, 213 function, 11, 44, 197, 198 gender and, 11, 56-57, 202, 207, 208, 209, 212, 216, 620-621 genotoxicity, 197, 214 and glucose tolerance, 44, 198, 199, 201, 203-204, 209, 213, 216, 584 hazard identification, 213-215 and hepatic dysfunction, 214-215 in human milk, 205, 206, 209, 210 indicators of adequacy, 11, 12-13, 22, 24-25, 202-204 infants, 198, 205-207, 209-210 and insulin activity, 11, 24-25, 197, 198, 199, 203-204, 213, 216, 584 intakes, 11, 202, 205, 212-213, 216, 620-621 interaction with drugs, 204, 209 interaction with other nutrients, 200, 204, 209 intervention trials, 201, 213 iron and, 200 lactation and, 210-211, 212, 216 by life-stage group, 12-13, 205-211, 620-621 metabolism, 200, 216 method used to set AIs, 11, 51-52, 54, 197, 205-207, 208-210 methodological issues, 25, 51-52, 54, 202, 211, 212, 214, 583 NOAEL/LOAEL, 215-216 oxalate and, 204

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc physical exercise and, 199, 207, 215 phytate and, 204 picolinic complexes, 458 plasma concentration, 202 pregnancy and, 54, 209-210, 216 and renal failure/disease, 213, 215 reproductive effects, 215 research recommendations, 216, 583 and rhabdomyolysis, 215 risk characterization, 216 sensitive subpopulations, 215 special considerations, 207 supplements, 25, 56-57, 198, 200, 212-213, 216, 458, 620-621 ULs, 7, 18, 36, 76, 78, 213-216 units, 709 Chromium IV, 197, 213 Chromosomal damage and aberrations, 214 Chronic disease carotenoids and, 83 evidence on prevention of, 9 micronutrients and, 300, 583-584 Chronic gastritis, 300 Chronic mucocutaneous candidiasis, 300 Chylomicron secretion, 87, 93, 163 Circulating lipid levels Citric acid, 200, 312, 357 Coagulation factors antibiotics and, 164, 165, 166 II, see Prothrombin V, 229 VII, 163, 166 VIII, 229 IX, 163 X, 163 manganese and, 396 Cognitive function boron and, 511, 521 copper and, 252 development in infants, 295, 300 iron and, 13, 295, 296-297, 300, 378, 583 manganese and, 410 zinc and, 444, 445, 449 Collagen metabolism, 45, 225, 529, 530 Colon cancer, 371-372 Colorectal cancer, 371, 372 Common cold, 477 Congenital atransferrinemia, 377 Conjunctival impression cytology, 105 Conjunctival xerosis, 95 Connective tissue synthesis, 44, 225, 226 Continuing Survey of Food Intakes by Individuals (CSFII) arsenic, 504-505 boron, 57, 512-513, 644-647 carotenoids, 122, 566, 568 copper, 57, 648-649 defined, 55, 705 food composition data, 697-698 iodine, 278 iron, 21, 57, 650-651, 697-703 reference weights and heights, 329 supplement data, 57 vitamin A, 122, 566 zinc, 57, 481, 575, 652-653 Copper absorption and transport, 226-227, 233-234, 238, 242, 243, 246-247 adolescents, 238-239, 243-244, 245, 250, 251 adverse effects, 18, 224, 247-248 adults (19+), 16, 26, 56-57, 224, 228, 234, 239-243, 246, 249-250, 251, 252 AIs, 238 and anemia, 11, 226, 227-228 animal studies, 226-227, 228-229, 232, 234-235, 244, 246 antioxidant activity, 225-226, 229 balance studies, 233, 241 bioavailability, 233-234, 243, 244, 252 biochemical indicators, 11-12, 230-233, 239-240, 242 and blood coagulation, 229 and blood pressure, 229 body stores/retention, 226, 233, 234, 235, 243 and bone formation and growth, 227, 228, 229 and cancer, 248 and cardiovascular disease, 226, 228-229 and catecholamine metabolism, 225, 229 and central nervous system function, 225, 226 ceruloplasmin concentration and, 224, 225, 227-228, 229, 230, 231, 235, 239-240, 484 children, 51-52, 227, 238-239, 247, 248, 250, 251, 252 and cholesterol (blood), 228

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc and connective tisse synthesis, 225, 226 critical endpoint, 249 and cytochrome c oxidase activity, 225, 230, 231, 240 data selection, 249 deficiency effects, 226, 227-230, 238, 252, 424 depletion/repletion studies, 224, 228, 229, 231, 232, 239-240, 242 and diamine oxidase activity, 224-225, 232-233 and dietary protein, 246-247 dose-response assessment for ULs, 249-251 in drinking water, 247, 249, 251-252 EARs, 14-15, 238-239, 242, 244, 245 energy expenditure and, 238 evidence considered in setting EAR, 239-242, 243, 244 excretion, 226, 227, 231-232, 233, 234, 240-242, 424 exposure assessment, 251-252 factorial analysis, 233, 240-242 factors affecting requirement, 233-235 and ferroxidases, 225, 293 fetal, 243 food sources, 245 in formula, 234, 238 fructose and, 234-235 functions, 11, 44, 224-226, 443 gastric acidity and, 226 gastrointestinal effects, 247, 248, 249 gender and, 56-57, 228, 245, 251, 622-625, 648-649, 660-661 and glucose tolerance, 229 hazard identification, 246-249 hereditary defects in homeostasis, 248 in human milk, 235, 236-237, 244 human studies, 247 and idiopathic copper toxicosis, 248, 251 and immune function, 226, 229 and Indian childhood cirrhosis, 248, 251 indicators of adequacy, 11-12, 14-15, 224, 229-233 infants, 51, 226, 227, 234, 235-238, 250 intakes, 57, 224, 233-234, 235-237, 241, 245-246, 251-252, 622-625, 648-649, 660-661 interaction with drugs, 225 interaction with other nutrients, 225, 226, 227, 231, 234, 246-247, 424, 434 and iron utilization, 225, 226, 227, 234, 246 lactation, 235, 244-245, 250, 251 leukocyte concentration, 232 by life-stage group, 14-15, 26, 235-245, 249-251, 622-625, 648-649, 660-661 liver damage, 224, 248, 249, 251 and lysyl oxidase activity, 225, 232 and Menkes’ disease, 226, 232 metabolism, 226-227, 246-247, 433 metalloenzymes, 11, 224-226, 456 method used to set AI, 51-52, 235, 237 method used to set EAR, 11-12, 51-52, 238-239 methodological considerations, 51-52, 232, 246, 247 molybdenum and, 246, 424, 433, 434, 435, 436, 437, 438 NOAEL/LOAEL, 249 and osteoporosis, 227 and peptidyl glycine α-amidating monooxygenase activity, 225, 232 plasma concentration, 224, 229, 239-240 platelet concentration, 224, 230, 231, 239-240 pregnancy, 226, 229-230, 243-244, 250, 251 RDAs, 2, 12, 14-15, 224, 239, 242-243, 244, 245 renal dysfunction and, 227 reproductive effects, 248 research recommendations, 252 risk characterization, 252 serum concentration, 229, 230, 235, 484 special considerations, 238, 251, 438 and superoxide dismutase activity in erythrocytes, 224, 225-226, 229, 231, 239-240 supplements, 56-57, 227, 228, 229, 230, 232-233, 246, 247, 248, 252 ULs, 2, 16, 18, 26, 224, 246-252, 562 uncertainty assessment, 249 units, 709 and Wilson’s disease, 227, 234, 248, 251, 456 zinc and, 225, 234, 246, 443, 456, 458, 482, 484-488, 558

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc Corneal ulceration, 95 Corneal xerosis, 95 Coronary heart disease, 359, 365, 368-369 Cow milk, 38, 179-180, 207, 227, 238, 270, 283, 317, 404, 425, 427, 457, 462 Cranial neural crest (CNC) defects, 128-129, 138 Craniofacial malformations, 128 Cretinism, 44, 261-262 Critical endpoints defined, 76 identification of, 70, 75-76, 249 Crohn’s disease, 446 β-Cryptoxanthin, 2, 10, 82, 91, 122, 123, 600-601 CSFII. See Continuing Survey of Food Intakes by Individuals Cysteine, 443 Cytochrome c oxidase activity, 225, 230, 231, 240 Cytochromes, iron and, 12, 291-292 Cytokines, 445 D Dark adaptation vitamin A and, 10, 21, 87-89, 95, 97-99, 121, 123, 300-301, 568 zinc and, 108-109 Data and database issues. See also Extrapolation of data on bioavailability of nutrients, 173, 174 for dietary intakes, 53-58, 104, 173, 556 for dose-response assessment for ULs, 66, 75-76, 77, 122, 133, 142-143, 249, 281, 373, 375, 412, 436, 483-484, 486, 517 food composition databases, 54, 55-56, 184, 512-513, 560, 569, 583, 697-698 methodological issues, 2, 7, 8, 32, 39, 48-49, 173 nutrients intakes, 54, 55-57, 556 quality and completeness of data, 2, 7, 8, 32, 39, 48-49, 54, 66, 74, 77, 173, 184, 560, 569 supplement use, 57-58 types of data used, 45-49 Depletion/repletion studies adults, 224, 228, 229, 231, 232, 239-240, 430 carotenoids, 88-89 copper, 224, 228, 229, 231, 232, 239-240, 242 design, 581 manganese, 396, 397, 399, 400 methodological considerations, 45, 46 molybdenum, 430 vitamin A, 88-89, 122 vitamin K, 167 zinc, 108, 473-474 Developing countries iron, 351-352, 359, 377, 378 vitamin A, 94, 95, 96-97, 112, 118-122, 145 zinc, 488 Developmental effects boron, 510, 512, 514-515, 518 iron, 295, 296-297, 300 Developmental toxicity, 503, 507 Diabetes mellitus, 302, 372 chromium and, 24-25, 200, 201, 216, 584 vanadium and, 532, 534, 535, 536, 539, 542 Diamine oxidase, 224-225, 232-233 Diarrhea, 96, 97, 107, 118, 477 Dietary intakes. See also Canada; Food sources; Nutrient intakes; Supplements; individual nutrients and bioavailability of nutrients, 233-234 data and database issues, 53-58, 104, 173, 556 elderly people, 47, 186 geographic location and, 512 infants, 37, 111 measurement errors, 182, 406, 559 methodological issues, 47, 54-55, 166, 182, 186, 212, 432, 466, 556, 559, 572, 583 provitamin A carotenoid conversion factor and, 122-123 research recommendations, 583 self-reported, 47, 54-55, 556, 583 survey data, 54-58, 245, 356, 560-561 underreporting of, 20, 47, 54-55, 208, 209, 353, 556, 560-561, 583 Dietary Reference Intakes (DRIs) applicable population, 2, 30 approach for setting, 7-9, 29-30, 576, 589-590

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc Reactive oxygen species, 507 Recommended Dietary Allowances (RDAs). See also individual nutrients AI compared, 4, 6, 31, 35 appropropriateness of intakes above, 77 children, 52 coefficient of variation, 3, 32-33, 52 criteria used to derive, 7, 8-9, 30 defined, 3, 6, 8, 30-31, 32 EAR and, 2, 6, 31, 32-34, 35 group applications, 20, 554, 561 individual applications, 554, 555-557, 562 infants, 6, 37 method used to set, 2-4, 31, 32-34, 35, 52 transition to DRIs, 554-555 uses, 1, 4, 5, 31, 554, 555-557, 561, 562, 577 Reference weights and heights, 41-42, 52, 114, 210, 329, 338, 468 Relative dose response test, 103-104, 105 Renal diseases/failure aging and, 40, 69 cancer, 507 chromium and, 213, 215 copper and, 227 molybdenum and, 433-434 silicon and, 529 vanadium and, 535-536, 538-539, 540, 541 Reproductive effects. See also Pregnancy animal studies, 406, 434-435 boron, 512, 514-517 chromium, 215 copper, 248 impotence, 372, 477 iodine, 261, 262 iron deficiency anemia, 295, 297-298 manganese, 396 molybdenum, 420, 433, 434-435, 436, 438 nickel, 524, 525-526 spontaneous abortions, 248 testicular atrophy, 515, 515-517 vanadium, 532, 537 vitamin A-related risks, 10, 82, 130-131, 133, 138-139 zinc, 444, 447, 476, 483 Requirement, defined, 29, 30 Research recommendations. See also individual nutrients approach to setting, 580-581 dietary intakes, 583-584 functional and biochemical endpoints, 27, 488-489 gender issues, 582 interactions, 27, 582-583 nonnutritional influences on bioindicators, 28, 582 pregnancy-related requirements, 582 priorities, 26-28, 584-585 Retinitis pigmentosis, 146 Retinoic acid receptors, 443 Retinoids defined, 83 vitamin K and, 176 Retinol gender and, 686-687, 692-693 intakes, 99, 102-103, 104, 105, 106-107, 112, 124, 565, 606-607, 686-687, 692-693, 709 international units, 565-566 iron and, 108 plasma/serum concentration, 99, 102-103, 104, 105, 106-107, 112 Retinol activity equivalents (RAEs) calculation, 565 and dietary intake changes, 123, 568, 610-611 rationale for developing, 82, 87-93 REs for provitamin A carotenoids compared, 10, 564 Retinol-binding protein, 93, 99, 108, 112, 119, 454, 473 Retinol equivalents vitamin A intakes by, 564, 608-609 Retinyl esters, 83, 87, 90-91, 93, 94, 125, 688-689 Rhabdomyolysis, 215 Rhodopsin, 85, 95, 97, 108-109 Risk assessment models. See also Dose-response assessment for ULs; Exposure assessment; Hazard identification; Risk characterization application to nutrients, 67-71 basic concepts, 16, 62-63 bioavailability considerations, 69-70, 75 case-by-case judgments, 712, 713 default options, 712 defined, 62, 707

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc EPA guidelines, 712 and food safety, 62-67 inference options, 63, 66, 710, 712-713 methodological considerations, 46-47 nutrient interactions, 70 process, 63-65 sensitivity of individuals, 69 special problems with nutrients, 67-68 thresholds, 65-67, 711 uncertainties, 63, 65, 67, 710-713 Risk characterization. See also individual nutrients chromium, 216 defined, 64, 79, 707 process, 64, 65, 79-80 uncertainties in, 710 Risk management, 63, 65, 79-80, 707-708, 713 RNA polymerases, 443 S Seasonal variation, in thyrotoxicosis, 280 Selenium deficiency, 260, 268, 284 Sensitive subpopulations, 61, 66, 69. See also Special considerations chromium, 215 identification of, 74-75, 79 iron, 372-373, 377-378 Sensitivity to nutrients. See also Hypersensitivity to nutrients; Special considerations dermal, 524 interindividual variability, 69, 77-78, 139, 143, 144 interspecies variability, 246 Serotonin, 410 Serum. See also individual nutrients ceruloplasmin, 239-240 diamine oxidase activity, 232-233 ferritin, 21, 299, 301-303, 306, 311, 313, 314, 315, 351, 352, 353-354, 359, 365-367, 370, 373, 395, 402, 572, 684-685, 694, 695, 696 IGF-1, 474 lipoprotein, 482 retinol, 686-687 retinyl esters, 688-689 thyroglobulin, 266-267, 276 thyroptropin, 258 transferrin, 303-304, 370, 682-683 TSH, 265, 266, 276, 279, 281 urea and creatinine, 535, 540 uric acid, 422, 423, 434 Short bowel syndrome, 446 Silicon absorption and transport, 529 and atherogenesis, 529 bioavailability, 530 and bone formation, 45, 529, 530 carcinogenicity, 531 and collagen formation, 529, 530 dietary fiber and, 530 dose-response assessment for ULs, 531-532 DRIs, 1, 6, 7, 36, 76, 78, 530, 576 elderly people, 532 excretion, 529-530 food sources, 530 function, 45, 529 gender and, 530, 634-635, 670-671 hazard identification, 531 in human milk, 530 infants, 530 intakes, 57, 530-531, 634-635, 670-671 interactions with other nutrients, 530 by life-stage group, 530, 634-635, 670-671 metabolism, 529 and renal failure, 529 research recommendations, 28, 532, 583 serum concentrations, 529 supplements, 57, 531, 634-635 ULs, 18, 531-532 units, 709 and urolithiasis, 531 Simulator of iron transport (SFT), 294 Skin cancer, 507-508 lysyl oxidase activity, 232 pigmentation, 506, 507-508 Sp1, 443 Special considerations adolescents, 330, 339-340, 358, 573 age of menarche, 339-340, 573 alcohol consumption, 118, 145, 376-377, 480 athletes, 574 autoimmune thyroid disease, 283 blood donation, 352, 574 chromium, 207

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc copper, 238, 251, 438 cow milk, 112, 179-180, 207, 238, 270, 317, 404, 427, 462 developing countries, 118-122, 377 diarrhea, 118-119 drinking-water levels of nutrients, 414 drug interactions, 121 elderly people, 479-480 growth spurts, 339, 573 hemochromatosis, 376-377 hormone replacement therapy, 350-351, 573 hyperlipidemia, 145 hypersensitivity to nutrient, 528 identification of, 30 idiopathic copper toxicosis, 251 Indian childhood cirrhosis, 251 infant formula, 179-180, 207, 238, 270, 317, 404, 427, 462 infants, 179-180, 238, 317, 573 intestinal parasites, 118-119, 351-352 iodine, 270, 278, 283 iron, 121, 317, 339-340, 350-353, 376-377, 572, 573-574 kidney dysfunction, 528 lactation, 121 liver disease, 145, 376-377, 414 manganese, 404, 414 Menke’s disease, 488 molybdenum, 427, 438 nickel, 528 nutrient interactions, 438, 480 oral contraceptives, 350, 573 parasites and infections, 118-119, 121 physical exercise/endurance training, 352-353 in pregnancy, 573 protein energy malnutrition, 119, 145 supplement use, 377, 414 ULs, 145, 488 vegetarian diets, 118, 119, 120, 351, 414, 479-480, 574 vitamin A, 112, 118-122, 145 vitamin K, 179-180 Wilson’s disease, 251, 488 zinc, 462, 479-480, 487 Sprue, 446 Stomach cancer, 214, 372 Stress response, 444, 445, 489 Sulfite oxidase, 420, 421, 422 Sulfur, 434 Superoxide dismutase alcohol consumption and, 231, 401 antioxidant activity, 225-226 cupro/zine, 224, 225-226, 229, 231, 239-240, 442, 443, 453, 482, 483 mangano, 225, 394, 401, 412, 414 Supplements. See also individual nutrients bioavailability of nutrients, 30, 70, 88-89, 173-174, 568 body-building, 520 children, 96, 465-466 composition data, 560 data sources on intakes, 57-58, 125, 246 form of nutrient in, 375, 568 gender differences, 56-57, 187, 246, 278, 488, 612-613 intakes from, 57, 65, 125, 187, 212-213, 216, 246, 278, 356, 408, 414, 432, 439, 481, 488, 513, 520, 523, 575, 612-613, 620-621, 626-627, 632-633, 693 intervention trials, 48 multivitamin/mineral, 401, 557, 575 sustained release, 375 therapeutic doses, 95-96, 145 ULs and, 65, 79, 145 usage, 56-58, 246, 278, 481, 612-613 T Tannic acid, 312, 313 Temperature regulation, 300 Teratogenicity arsenic, 507 vitamin A, 128-133 zinc and, 444 Testicular atrophy, 515-517 Testosterone, 454 Tetraiodotyrosine, 260 Thalassemias, 306, 377 Thiocyanate, 267 Thyroglobulin, 259-260, 264, 266-267, 276 Thyroid gland cancer, 262, 280, 284 iodine accumulation and turnover, 262-263, 273-274 iodine transport, 259 molybdenum and, 433 monitoring in children, 284 newborns, 275

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc nickel stores, 522 size, 259, 264-265, 275-276, 279-280, 284; see also Goiter Thyroid hormones. See also Iodine; specific hormones absorption, 259 goitrogens and, 267 and iodine deficiency disorders, 261 and metabolism, 268, 272 radiocontrast media and, 268 secretion measurements, 274 selenium deficiency and, 260 synthesis, 259 zinc and, 454, 473 Thyroid stimulating hormone (thyrotropin, TSH), 258, 260, 264, 265, 266, 268, 276, 279, 280, 281, 707 Thyroiditis, 263, 279, 283 Thyroperoxidase, 260, 532 Thyrotoxicosis, 280 Thyrotropin. See Thyroid stimulating hormone (TSH) Thyroxine, 258, 267, 454, 473 Thyroxine-binding globulin, 260 Tissue cultures menaquinone, 162 α-Tocopherol, 175 α-Tocopherol quinone, 175 Toddlers, ages 1 through 3 years, 21, 39, 112, 121, 122, 180, 238, 270, 272, 313, 321, 404 Tolerable, defined, 7, 35, 60 Tolerable Upper Intake Levels. See also Dose-response assessment; Hazard identification; Risk assessment models; individual nutrients adolescents, 142, 145 adults, 16, 26-27, 53 appropropriateness of intakes above, 17-18, 36, 60, 61, 125, 145-146, 246, 278, 284, 356, 408, 433, 513, 523-524, 531, 534, 542 children, 42, 53 critical endpoints, 7-8, 70 defined, 3, 6, 7, 35, 60, 68, 125, 213, 246, 356, 408, 433, 513, 523, 531, 534 derivation of, 35, 42, 53, 62, 67-70, 75, 78-79, 126, 139, 143, 144, 250, 282, 373, 374, 376, 412, 437, 486, 488, 518 development steps, 71-79 fortification of foods and, 7, 36, 61, 68, 575 group applications, 554, 561-562, 563-564 individual applications, 558 by life-stage groups, 69 pregnancy and lactation, 139, 142 prevalence of intakes above, 562 supplement use and, 7, 36, 61, 68, 79, 143, 145, 562, 575 uses, 5, 7, 35-36, 61, 554, 558, 561-562, 563-564 Total Diet Study arsenic, 57, 658-659 copper, 57, 660-661 description of, 56 iodine, 57, 283-284, 662-663 iron, 57, 664-665 manganese, 57, 394, 404, 405, 406, 407, 408, 414, 666-667 molybdenum, 432 nickel, 57, 523, 668-669 silicon, 57, 530, 670-671 vanadium, 533 vitamin K, 57, 178, 183, 185, 654-657 zinc, 57, 672-673 Total parenteral nutrition (TPN), 198, 200-201, 227, 241, 396, 409, 421, 422 Transcription factors, 44 Transferrin, 199-200 gender and, 682-683 iron and, 291, 293, 294, 302, 303-304, 306, 357, 359, 368-369, 370-371, 682-683 manganese and, 395, 409 vanadium and, 533 Transferrin receptors, 294 and cancer, 304, 370 density and, 409, 411 iron and, 302, 304-305, 306 manganese and, 409, 411 Transthyretin, 93, 99, 260 Triglycerides, 86, 166, 510 Triiodothyronine, 258, 260, 267 Trimethylated arsenic, 504 Tryptopham, 458 TSH-releasing hormone, 279 Tungsten, 424 Tyrosinase, 225 Tyrosine kinase activity, 25, 198, 443

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc U Ubiquinone, 292 Ultrasonography, 265, 275, 284 Uncertainty in animal studies, 63, 78, 436, 540, 710, 711 assessment, 76, 77-78, 139, 143, 144, 249, 281, 374, 376, 412, 436, 486-487, 710, 711 in dietary assessment methods, 567 extrapolation of data, 77-78, 436, 518, 526, 540 factor, 63, 66, 76, 77-78, 139, 143, 144, 249, 281, 374, 412, 486, 518, 526, 540-541, 708 in physiological significance of diet-induced changes, 170 in risk assessment, 63, 65, 66, 67, 710-713 sources of, 35, 77-78, 526, 540 vitamin A, 139, 143, 144, 567 United Nations Children’s Fund, 263 Units, conversion of international units, 709 REs to RAEs, 2, 82-83, 86-93, 123, 564-568 vitamin A, 92-93, 565-566, 709 Urea and uric acid, 535, 540 Urinary excretion boron, 511, 515 copper, 241, 424 creatinine ratios, 263, 400 extrapolation of daily intakes from, 264, 272 hydroxyproline, 24, 172 hypoxanthine, 423 iodine, 259, 260-261, 263-264, 266, 269, 271-272, 273-274, 275, 279, 281, 284, 690-691 iron, 295 manganese, 395, 400 molybdenum, 421, 422-423, 435 nickel, 521, 522 sulfate, 422, 423 sulfite, 423 thiosulfate, 422 uric acid, 422, 423, 434, 437 xanthine, 423 zinc, 446, 463, 471, 480 Urolithiasis, 531 U.S. Department of Agriculture, 55, 278, 329, 504 U.S. Department of Health and Human Services, 55 U.S. Environmental Protection Agency (EPA), 251, 538 V Vanadium absorption and transport, 533 acute toxicity, 535 adolescents, 534, 542 adults, 17, 27, 533, 534, 539-541, 542 adverse effects, 534, 535-539 animal studies, 532, 535-537, 539-540 athletes’ use of, 535, 537, 539 body pools, 533 carcinogenicity, 538 cardiovascular effects, 537 children, 534, 541 data selection, 539-540 and diabetes, 532, 534, 535, 536, 539, 542 dose-response assessment for ULs, 539-542 in drinking water, 535 DRIs, 2, 6, 533, 576 elderly people, 533, 534 EPA oral reference dose, 538 excretion, 533 exposure assessment, 542 and fatigue and lethargy, 538 and ferritin, 533 food sources, 533-534 function, 45, 532, 543 gastrointestinal effects, 536, 539 gender and, 636-637 and glucose metabolism, 532 and green tongue, 538 hazard identification, 534-539 hematological effects, 536-537 and hormone metabolism, 532 human studies, 535, 536, 537-538 infants, 534, 541 insulin-like properties, 45, 532, 534 intakes, 57, 534, 542, 636-637 lactation, 542 by life-stage group, 27, 533, 539-542, 636-637 and lipid metabolism, 532

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc and liver congestion, 535 metabolism, 533 neurological effects, 538 NOAEL/LOAEL, 540 and plasma urea and uric acid, 535, 540 pregnancy, 542 renal toxicity, 535-536, 538-539, 540, 541 reproductive effects, 532, 537 research recommendations, 28, 543, 583 risk characterization, 542 and serum urea and creatinine, 535, 540 supplements, 57, 532, 534, 535, 539, 542, 543, 636-637 thyroperoxidase and, 532 toxic compounds, 535 and transferrin, 533 ULs, 17, 27, 534-542, 576 uncertainty assessment, 540-541 units, 709 Vegetarians bioavailability of nutrients, 479, 572, 574 boron, 520 elderly people, 479-480 iron, 315, 351, 574 lacto-ovo, 451, 706 manganese, 408, 412, 414 vitamin A, 106-107, 119, 120, 123, 134-135, 568 Very low density lipoproteins vitamin A and, 93-94 vitamin K and, 163 Vision, 10, 44, 82, 84-85, 87-88, 95, 119 Vitamin A. See also Provitamin A carotenoids absorption and transport, 70, 85, 86-94, 106-107, 108, 116 adolescents, 112-113, 116, 117, 122, 125, 142, 144-145 adults, 10, 16, 21, 26, 56-57, 82, 94-95, 100-102, 113-115, 121, 123, 125, 126-129, 142-143 adverse effects, 18, 118, 125, 126-132, 140-141 AIs, 111, 145 alcohol consumption and, 109, 118, 128, 133, 134-139, 145 animal studies, 85, 95-96, 98, 104, 105, 108, 109, 121, 126 bioavailability, 87-90, 107, 146 bioconversion of carotenoids to, 2, 82-83, 86-93, 565 and birth defects, 128-133 body stores, 10, 21, 85, 94-95, 99, 103-104, 108, 109, 112, 114, 123 and bone mineral density, 126-128, 133 and cancer, 85, 96 children, 21, 51-52, 95, 96, 97, 99, 102, 106-107, 108, 112-113, 121, 122, 125, 129, 132, 144-145 conjunctival impression cytology, 105 critical endpoint, 146 and dark adaptation, 10, 21, 87-89, 95, 97-99, 121, 123, 300-301, 568 data selection, 133, 142-143 deficiency effects, 82, 87-88, 95-97, 119, 268 depletion/repletion studies, 88-89, 122 in developing countries, 94, 95, 96-97, 112, 118-122, 145 and diarrhea, 96, 97, 107, 118 dietary fat and, 70, 106-107, 118, 121 dose-response assessment for ULs, 133, 138-145 EARs, 8-9, 82, 103, 113, 115, 116, 117, 567, 568 eldely people, 166, 167, 182, 186 and embryonic development, 82, 85, 95-96 epidemiological studies, 126-128, 133 and epithelial cell integrity, 44, 85, 96, 105 evidence considered in setting EAR, 83, 113-117, 121 excretion, 93-94, 114, 118-119 exposure assessment, 145 factors affecting requirement, 106-110 fetal, 116, 128-129 food composition determinations, 124, 565-566 food sources, 82, 84, 104, 122, 132, 562, 565 forms of, 83 in fortified foods, 119, 145 function, 10, 44, 82, 84-86, 568 gastroenteritis and, 107 gender and, 8-9, 10, 56-57, 82, 83, 95, 96, 113, 114, 115, 122, 132, 144-145, 608-613, 674-675, 686-689, 692-693

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc and gene expression, 44, 82, 85 and growth, 44, 82 half-life, 115 hazard identification, 125-133 hepatitis and, 129, 133, 134-139 in human milk, 110-111, 117 hyperlipidemia and, 145 and immune function, 10, 44, 82, 85-86, 96, 98, 99, 105-106, 121 indicators of adequacy, 10, 97-106, 146, 686-689 infants, 51, 95, 96-97, 110-112, 119, 125, 129, 130-132, 140-141, 143-144, 145 and infectious morbidity and mortality, 96-97, 107, 121 intakes, 8-9, 82, 83, 111, 114, 119, 122-125, 145, 146, 562, 564-568, 608-613, 674-675, 692-693 interaction with drugs, 129, 133 interaction with other nutrients, 97, 99, 104, 106, 108-109, 118, 121, 129, 143, 146, 176, 268, 284 interconversion of units, 2, 82-83, 86-93, 123, 564-568 intervention trials, 90-91, 97, 108, 119, 121, 125 intestinal parasites and, 107, 118-119, 121 iodine and, 268, 284 iron and, 108, 118, 121 lactation and, 111, 117, 121, 142, 145, 146 and LDLs, 93-94 by life-stage group, 8-9, 26, 110-117, 126-132, 608-613, 674-675, 686-689, 692-693 and liver abnormalities, 109, 125, 129, 132-133, 134-139, 142, 145 malabsorption of, 107, 118-119 and measles, 96, 97 menu for omnivorous diet, 123, 124 metabolism, 93-94, 146 method used to set AIs, 51-52, 110-111 method used to set EARs, 10, 51-52, 112-115, 122 methodological considerations, 51-52, 106, 127, 143 modified relative dose response test, 104 NOAEL/LOAEL, 133, 138, 139, 143-144 periconceptional intakes, 129 physical exercise and, 127 and Plasmodium falciparum malaria, 96 pregnancy and, 97, 116-117, 128-133, 142, 145, 146 prevalence of inadequate intakes, 21, 566-567 processing of foods and, 107, 111, 112, 146 protein energy malnutrition and, 97, 99, 104, 106, 108, 118, 119, 145 pupillary response test, 98-99 radioisotopic methods, 94, 95, 103, 114 RDAs, 8-9, 10, 82, 113, 115, 116-117, 123 relative dose response test, 103-104, 105 and reproductive risk, 10, 82, 130-131, 133, 138-139 research recommendations, 146, 582 retinol, 99, 102-103, 104, 105, 106-107, 112, 124, 565, 686-687, 692-693, 709 retinyl esters, 83, 87, 90-91, 93, 94, 125, 688-689 risk characterization, 145-146 special considerations, 112, 118-122, 145 structure, 83-84 supplements, 26, 56-57, 95-97, 102, 105, 119, 125, 128, 133, 136-137, 143, 145, 612-613, 693 teratogenicity, 128-133 toxicity, 118 ULs, 2, 16, 18, 26, 82, 125-146, 562 uncertainty assessment, 139, 143, 144, 567 units of activity, 92-93, 565-566, 709 vegetarians, 106-107, 119, 120, 123, 134-135, 568 and vision, 10, 44, 82, 84-85, 87-88, 95, 119 vitamin K antagonism, 176 and xerophthalmia, 10, 85, 95, 97, 105, 108-109, 112 zinc and, 97, 99, 104, 106, 108-109 Vitamin A2 (dehydroretinol), 104 Vitamin B12, 521, 529 Vitamin C, 231. See also Ascorbic acid

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc Vitamin D, 45, 510-511, 520 Vitamin E, 175-176 Vitamin K. See also Menaquinones; Phylloquinones absorption and transport, 163-164, 174, 176 adolescents, 180, 183, 184 adults (19-50), 162, 166, 180-182, 184, 186 adults (51+), 166, 167, 181, 182, 186 aging and, 166, 167, 168, 170 AIs, 10-11, 162, 177, 179, 180, 182, 183, 558, 561, 562-563, 564 animal studies, 172, 173, 175-176, 188 and atherosclerosis, 173 bioavailability, 163, 173-174, 186, 189, 568 and blood coagulation, 10, 163, 164, 165-168, 175, 176, 177, 181-182 body stores, 164 and bone metabolism, 10, 23-24, 162, 169, 170, 172, 189, 583-584 and calcium excretion, 24, 172 and cancer, 176-177, 187-188 γ-carboxyglutamyl residues, 163, 167, 172, 173, 174, 189 children, 176, 180, 184-185 deficiency, 164-165, 174, 176, 180, 396 dependency, 177 depletion/repletion studies, 167 dietary fat and, 163, 173-174, 185-186 dose-response assessment for ULs, 188 epidemiological studies, 171, 188 excretion, 24, 163-164, 167 exposure assessment, 188 and factor VII activity, 163, 166 factors affecting requirement, 173-176 fetal, 182 food sources, 163, 173-174, 184-186 forms of, 24, 162, 163, 173, 174, 185 function, 10, 44, 162, 163 gender and, 10-11, 162, 167, 182, 186, 614-617, 654-657 hazard identification, 187-188 human feeding studies, 164-165 in human milk, 177-180, 183-184 indicators of adequacy, 22-24, 165-173 infants, 176-180, 184-185, 187-188 intakes, 10-11, 57, 174, 175, 177, 181-182, 183-185, 186-187, 188, 614-617, 654-657 interaction with drugs, 172, 174-175, 568 interaction with other nutrients, 24, 163, 172, 173-174, 175-176 international comparisons, 187 intervention trials, 24, 168, 171-173 laboratory assays, 168 lactation, 177, 183-184 by life-stage group, 10-11, 176-184, 614-617, 654-657 malabsorption syndromes and, 174, 180 manganese and, 396 metabolism, 163-164 method used to set AIs, 10-11, 177-179, 180-184 methodological issues, 23-24, 166, 168, 169, 171, 172, 184, 186 and osteocalcin γ-carboxylation, 23, 163, 168-170, 172, 173, 189 and osteoporosis, 23-24, 170-173 plasma/serum concentrations, 166, 170, 174 pregnancy, 182-183, 188 prevalence of inadequacy, 561 processing of foods and, 184-186 and prothrombin, 163, 164, 165-168, 175, 176, 177, 181-182 research recommendations, 189, 583-584 retinoids and, 176 special considerations, 179-180 supplements, 167, 169, 172, 173-174, 187, 189, 396, 568, 616-617 synthetic, 162, 164, 187 ULs, 7, 18, 36, 76, 78, 162, 187-189 unit conversion, 709 and vitamin A, 176 vitamin E antagonism, 175-176 W Warfarin, 172, 174-175, 568 Water purification tablets, 268 Weight. See Body weight Wilson’s disease, 227, 234, 248, 251, 456, 488 Women. See also Gender; Lactation; Pregnancy anemia, 305 atherosclerosis, 173

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc athletes, 352 autoimmune thyroid disease, 283 blood donation, 352 bone mineral density, 126-128, 171, 172 boron, 511 cancer, 371 chromium, 212 copper, 240, 245, 246 ethanol metabolism, 475 hemoglobin concentrations, 305, 342 hormone replacement therapy, 350-351, 573 institutionalized, 171 iodine, 278, 283 iron, 21, 290, 291, 305, 309, 332, 333, 334-337, 339-340, 341-343, 371, 378, 570-572, 700, 703 LDL concentrations, 482 manganese, 399, 400, 401, 409 menopause, 333 molybdenum, 424 night blindness, 95 oral contraceptives, 334-335, 343, 350, 700, 703 osteocalcin γ-carboxylation, 172, 173 osteoporosis, 172, 396 postmenopausal, 127, 172, 173, 343, 350-351, 359, 378, 475, 511, 573, 700, 703 serum ferritin, 302-303 serum transferrin, 304 smokers, 371 supplements, 378, 409 vitamin A, 95, 126-128, 133, 138 vitamin K, 172, 173, 186, 187, 188 zinc, 474, 475, 481, 482, 488 World Health Organization copper recommendations, 248 definition of adverse effect, 60 definition of requirement, 29-30 iodine deficiency data, 262, 263, 265 vitamin A recommendations, 97 Working Group on Infant Growth, 320 xerophthalmia classifications, 95 zinc recommendations, 458, 572 X Xanthine dehydrogenase, 422 Xanthine oxidase, 420 Xerophthalmia, 10, 85, 95, 97, 105, 108-109, 112 Xylosyltransferases, 394 Z Zeaxanthin, 123, 602-603 Zinc absorption and transport, 15, 357-358, 445, 447-449, 450-451, 454-458, 462, 464-465, 472-473, 479, 483 acute effects, 482 adolescents, 451, 469-470, 476-479, 486-487 adults, 17, 27, 56-57, 234, 442, 471-475, 483-486, 574 adverse effects, 18, 482-483, 558 AIs, 24-25, 462 albumin and, 445, 446, 454, 473, 474 alcohol consumption and, 475, 480 and alkaline phosphatase activity, 443, 453, 477 animal studies, 108, 455 arsenic and, 506 balance studies, 445, 448, 455, 456, 458, 472, 474, 480 bioavailability, 444-445, 447, 448, 454-455, 457, 458, 462, 473, 479, 572, 574-575, 576 body pool size and turnover rate, 357, 445, 446, 450-451, 463 calcium and, 455-456, 457, 458, 462, 479, 480 and carbohydrate utilization, 444 carcinogenicity, 483 catalytic activities, 15, 443, 452-453 cellular accumulation, 443 children, 449-450, 452, 454, 463-469, 486-487 and cholesterol, 481, 482, 486 and cognitive function, 444, 445, 449 and copper status, 225, 234, 246, 443, 456, 458, 481, 482, 484-488, 558 in cow milk, 457, 462 and dark adaptation, 108-109 data selection, 483-484, 486 deficiency effects, 15, 97, 99, 108-109, 442, 444, 446-447, 462, 506 defined, 443 depletion/repletion studies, 108, 473-474

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc in developing countries, 488 dietary fiber and, 458, 480 dietary protein and, 457, 458 dose-response assessment for ULs, 483-488 in drinking water, 483 EARs, 24-25, 466, 468, 469, 470, 475, 477, 479 elderly people, 451, 474-475, 479, 559, 562 endogenous losses, 446, 448, 449, 462, 463, 469, 471-473, 476 and enzyme (zinc-dependent) activity, 15, 443, 452-453 in erythrocytes, 442, 451, 452, 453, 473, 482 evidence considered in setting EAR, 463-466, 467-470, 471-475, 476-479 excretion, 446, 448, 463-464, 471-473 exposure assessment, 487 factorial analysis, 15, 442, 447, 462, 463, 467, 468, 469-470, 471-473, 476 factors affecting requirement, 454-458 fasting/starvation and, 446, 448, 451 fetal, 477 finger proteins, 443, 444, 454 folate and, 456 food composition data, 560 food sources, 463, 479, 480 fortified foods, 480, 575 fractional absorption method, 15, 447-448, 449, 450, 462, 463, 468, 469, 472, 473, 474, 476, 478 functions, 15, 44, 108, 442-444 and gastrointestinal distress, 482 gender and, 15, 56-57, 442, 469, 470, 471-472, 473-474, 475, 480-481, 482, 488, 638-641, 652-653, 672-673, 678-679 and gene expression, 15, 442, 443, 454 gene markers of status, 453 and growth velocity, 444, 446-447, 449-450, 452, 454, 462, 464, 465-466, 467-468 in hair, 452, 480 hazard identification, 481-483 and hepatic proteins, 454 and hormone metabolism, 443, 444, 454 in human milk, 6, 51, 457, 460-462, 463, 465, 477-478 and immune function, 443, 444, 447, 449, 453, 474-475, 481, 482, 488 indicators of adequacy, 24-25, 447-454, 488-489 infants, 51, 234, 458-466, 486-487 and infection, 445 intakes, 57, 442, 463, 466, 467, 480-481, 487, 559, 562, 574-575, 638-641, 652-653, 672-673, 678-679 interactions with other nutrients, 108-109, 455-457, 458, 462, 479, 480, 482-483, 506 international comparisons, 476 intestinal losses, 448, 456, 463-464, 472, 476 and iron, 304, 357-358, 373, 455, 458, 482-483 laboratory assays, 452, 471, 474 lactation, 477-479, 487, 488 by life-stage group, 24-25, 27, 458-480, 483-487, 638-641, 652-653, 672-673, 678-679 and lipoproteins, 482 malabsorption syndromes, 445, 446, 457 and Menke’s disease, 488 menstrual losses, 446, 448, 469, 471-472 metabolism, 445-446, 474 metalloenzymes, 443 and metallothionein, 234, 443, 444, 453, 456, 473 method used to set AI, 459, 462 method used to set EAR, 15, 442, 463, 467, 468, 469-470, 476, 572 methodological issues, 452, 476 MTF1 binding, 443 NOAEL/LOAEL, 484-486 and 5'-nucleotidase activity, 453, 473-474 phosphorus and, 455-456, 457 phytic acid/phytates and, 444, 451, 452, 456, 457-458, 479, 480, 572, 576 picolinic acid and, 458 plasma concentrations, 445-446, 447, 450-452, 455, 473, 476, 480 pre-albumin and, 454, 473 pregnancy, 447, 476-477, 487, 488 protein-energy deficiency and, 108 radiotracer studies, 357-358, 455, 472, 489 RDAs, 15, 24-25, 442, 466, 468, 469, 470, 475, 477, 479, 557, 574 regulatory role, 15, 443-444, 454

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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc reproductive effects, 444, 447, 476, 483 research recommendations, 487-488 and retinol binding protein, 454, 473 risk characterization, 487 serum concentrations, 454, 474, 476, 480 special considerations, 462, 479-480, 487 and stress response, 444, 445, 489 structural role, 15, 443 superoxide dismutase activity, 442, 443, 453, 482, 483 supplements, 56-57, 108, 234, 401, 444, 447, 449-450, 452, 453, 454, 456, 465-466, 467, 476, 478-479, 481, 482, 483, 488, 489, 557, 560, 562, 575 and teratogenesis, 444 and testosterone, 454 and thyroxin, 454, 473 trauma and, 445, 446 and tyrosine kinase, 443 ULs, 18, 2, 17, 27, 442, 481-488, 561-562, 574 uncertainty assessment, 486-487 units, 709 urinary losses, 446, 463, 471, 480 vegetarianis, 451, 479-480, 572, 574 and vitamin A, 97, 99, 104, 106, 108-109 WHO requirements, 458 and Wilson’s disease, 234, 456, 488