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

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

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

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

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

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

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

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

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

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

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

categories, 2-7, 29, 30-36;

see also Adequate Intakes;

Estimated Average Requirements;

Recommended Dietary Allowances;

Tolerable Upper Intake Levels

criteria for, 8-27, 36

defined, 2, 6, 29-30, 42

extrapolation from other age groups, 32, 35, 39, 41, 51-53, 78

framework, 555, 587-590

group applications, 5, 19-22, 34, 123, 554, 558-562, 563-564, 566-567, 577-578

individual applications, 5, 554, 555-558, 562-563, 577-578

nutrient-specific considerations, 564-576

origin, 587-588

parameters for, 36-42;

see also Life-stage group;

Reference weights and heights

precision of values, 9

prevalence of inadequacy, 21-22

sources of data, 2, 20-22, 45-49;

see also Methodological considerations

transition from RDAs, 554-555

uses, 2, 5, 19-22, 30, 554-578

2′,3′-Dihydrophylloquinone, 185-186

Dihydroxyphenylacetic acid, 410

Diiodotyrosine, 260

Dimethylarsenic acid, 504

Dimethylprostaglandin E₂, 204

Disinfectants, 268

Divalent metal transporter protein (DMT1), 293, 294

DNA damage and repair chromium and, 214

Dopa, 225

Dopamine, 225, 410

Dopamine β-monooxygenase, 225

Dose-response assessment for ULs.

See also individual nutrients

adolescents, 142, 144-145, 375-376, 413, 414, 437-438, 486-487, 519

adults (19-50 years), 142-143, 249-250, 281-282, 373-375, 412-413, 436-437, 483-486, 517-518, 525-527, 539-541

animal studies, 71, 75-76, 78, 436, 710, 711, 712

children, 144-145, 375-376, 413, 437-438, 486-487, 519

components and process, 72, 75-79

critical endpoints, 75-76

data selection, 75-76, 122, 142-143, 249, 281, 373, 375, 412, 436, 483-484, 486, 517, 525, 539-540

defined, 64, 705

extrapolation from animals to humans, 78, 711

infants, 143-144, 375-376, 413, 437, 486-487, 519

interindividual variation in sensitivity and, 77-78, 711

lactation, 375, 413, 414, 438, 487, 519

NOAEL/LOAEL identification, 76-77, 133, 138, 143-144, 249, 281, 374, 375-376, 412, 436, 484-486, 517-518, 525-526, 540

pregnancy, 133, 138, 375, 413, 414, 438, 487, 519

special considerations, 79, 145, 283, 376-377, 414, 438, 488, 528

UL derivation from, 64-65, 78, 126, 139, 143, 144, 250, 282, 373, 374, 376, 412, 437, 488, 518, 526-527, 541

uncertainty assessment, 76, 77-78, 139, 143, 144, 249, 281, 374, 376, 412, 436, 486-487, 518, 526, 540-541, 710, 711

Down’s syndrome, 231

Drinking water, 267-268, 284, 642-643

arsenic in, 507, 508, 509

boron, 512, 514, 520

children’s intakes, 247

copper, 247, 249, 251-252

manganese, 410, 411, 414

molybdenum, 434-435

nickel, 524, 528

vanadium, 535

zinc, 483

Drug interactions

chromium, 204, 209

copper, 225

iodine, 268

vitamin A, 129, 133

vitamin K, 172, 174-175, 568

Dwarfism, 44

E

Elastin, 225

Elderly people. See Adults ages 51+ years

Electrooculorgram, 98

Electroretinogram, 98

Embryonic development, 44, 82, 85, 95-96

Endogenous losses

copper, 241-242

zinc, 446, 448, 449, 462, 463, 469, 471-473, 476

Energy

chromium and, 11, 205, 208-209, 212

expenditures, 40, 238, 427

intakes, 11, 47, 55, 205, 208-209, 212

metabolism, 40, 54

requirements, 209

Enteral diets, 227-228

Enzyme cofactor deficiency, 14, 420, 423, 424

Epilepsy, 514

Epinephrine, 225

Epithelial cell integrity, 44, 85, 96, 105

Erythrocyte

arsenic binding to, 506

defined, 705

indexes, 305-306

iron, 290, 301, 302, 304, 305-306, 309, 313, 346, 347, 352

mean corpuscular volume, 706

metallothionein, 444, 453, 473

molybdenum in, 421

protoporphyrin concentration, 304, 306

superoxide dismutase activity, 224, 225-226, 229, 231, 239-240, 442, 482

zinc in, 442, 451, 452, 453, 473, 482

Erythrosine, 268

Escherichia coli WP2, 507

Esophageal webs, 300

Estimated Average Requirements (EARs).

See also individual nutrients

adolescents, 699

AI distinguished from, 37

children, 32, 51-52, 699

coefficient of variation, 32-33

criteria used to derive, 7, 8-9, 36

defined, 3, 6, 8, 30, 31-32

distribution of, 699, 700

extrapolation to/from other age groups, 32, 49, 51-52

group applications, 5, 20, 554, 558-561, 563-564, 568, 570-572

individual applications, 554, 555-557

infants, 6

knowledge gaps, 581-583

methods used to set, 32, 49, 265, 569, 583

and RDA, 3, 6, 32-34, 35

reference weights and heights and, 42

risk of inadequacy, 556, 570

standard deviation, 563

uses, 4, 5, 32-34, 49, 554, 555-557, 558-561, 563-564, 568, 577

validation of, 353-355

Estimated safe and adequate daily dietary intakes (ESADDI), 576

Estrogen, 45, 511, 520-521

Excretion.

See also Endogenous losses;

Urinary excretion;

individual nutrients

calcium, 24, 172

γ-carboxyglutamyl, 167

fecal, 260, 295, 352, 395, 421, 446, 472

gastrointestinal losses, 241, 295, 325, 352

human milk, 269

measurement of, 463

menstrual losses;

see Menstrual cycle

obligatory (basal) losses;

see Basal

losses of nutrients

sweat, 260

Expert Scientific Working Group, 306

Exposure

duration of, 73, 76, 360-363

route of, 73, 75-76, 246, 410, 509, 711

Exposure assessment.

See also individual nutrients

defined, 64, 65, 79

process, 64, 65

supplements, 65

Extramedullary hematopoiesis, 515

Extrapolation of data

from animal studies, 63, 71, 74, 78, 436, 518, 526, 540, 541, 710, 711, 712

basal losses, 331

body surface area basis, 325, 569

body weight basis, 42, 51, 52, 53, 54, 78, 142, 144, 250, 270, 282, 321, 404, 413, 437, 463, 487, 519, 569

caloric intake basis, 228

daily intakes from urinary losses, 264, 272

growth factors by age group, 51, 53, 331

from human milk intakes, 463

metabolic weight ratio method, 53, 238, 272, 426, 427

NOAEL from LOAEL, 143, 144, 281, 374, 486, 540, 541

from one gender group to another, 341

from other age groups, 32, 35, 39, 41, 51-53, 78, 111, 112, 122, 144, 178, 179, 206-207, 237-238, 250, 269, 270, 272, 282, 321, 331, 404, 406, 413, 437, 463, 465, 467, 469, 470, 487, 519

from subchronic to chronic intake, 78, 711

uncertainties in, 77-78, 436, 518, 526, 540

F

Factorial analysis, 49, 51

adults, 240-242, 340

children, 463, 467, 468

copper, 233, 240-242

infants, 463

iron, 13, 41, 290, 307-309, 319, 324, 330, 340-343, 344, 347, 348, 569

manganese, 397

pregnancy, 476

zinc, 15, 442, 447, 462, 463, 467, 468, 469-470, 471-473, 476

Fasting/starvation, 267, 373, 446, 448, 451

Fat, dietary

and absorption of nutrients, 70, 106-107, 118, 121, 163

hydrogenated, 174, 185-186

malabsorption syndromes, 164, 174

and manganese-superoxide dismutase activity, 401

and vitamin A, 70, 106-107, 118, 121

and vitamin E bioavailability, 173-174

and vitamin K, 163, 173-174, 185-186

Ferritin

and cancer, 302

and cardiovascular disease, 365-367, 370, 377-378

gender differences, 395, 684-685, 694, 695

and iron, 21, 225, 291, 294, 299, 300, 301-303, 306, 307, 311, 313, 314, 315, 351, 352, 353-355, 357, 359, 365-367, 370, 371-372, 373, 377-378, 572, 684-685, 694, 696

and manganese, 395, 401, 402, 405

vanadium, 533

Ferroxidases, 225, 293

Fetal

copper, 243

death, 299

folate, 456

hemoglobin, 316

hypothyroidism, 261-262

iodine, 261-262, 275

iron, 290, 299, 300, 309, 316, 345-346, 347

manganese, 406, 411

molybdenum, 436

neurobehavioral development, 477

nickel toxicity, 524, 526

resorption, 95

sensitivity to nutrients, 69, 507

vitamin A, 116, 128-129

vitamin K, 182

Fiber, dietary

and chromium, 204, 209

and silicon, 530

and zinc, 458, 480

Fibrocystic breast disease, 259, 284

Flavoproteins, 291

Folate, 521, 529

Follicular hyperkeratosis, 96

Food additives, 268, 277, 530

Food and Agriculture Organization, 29-30, 60

Food and Drug Administration. See Total Diet Study

Food coloring, 268

Food composition data

analytical methods, 54, 56, 184, 560, 569, 583

carotenoids, 93, 124

chromium, 54, 569, 583

iodine, 277

iron, 697-698

quality and completeness of, 54, 184, 569

recommendations, 564

vitamin A, 124, 565-566

vitamin K, 184, 185

zinc, 560

Food matrix and bioavailability of nutrients, 68, 87-90, 107, 174, 312, 351, 359, 411, 414, 424, 429-430, 479, 530

Food safety, risk assessment and, 62-67

Food sources.

See also individual nutrients

for children, 184-185, 698

goitrogens, 267-268

major contributors, 58

methodological issues, 58

Formulas, infant

absorption of nutrients in, 238, 404

AIs, 562

bioavilability of nutrients, 4, 38, 50, 112, 180, 206, 238, 267, 270, 317, 322, 427, 462, 557-558, 561

chromium, 207

copper, 234, 238

cow milk-based, 38, 227, 404, 462

dephytinized, 402

DRIs, 37-38

iodine and, 267, 270

iron in, 4, 234, 317, 322-323

manganese in, 397, 402, 404

molybdenum in, 425

soy-based, 267, 402, 404, 462

supplemented/fortified, 238, 317, 322, 462

toxicity of nutrients in, 486

vitamin K, 178, 179-180, 185-186

Fortification of foods, 119, 145, 355-356, 358, 378, 563, 565

Free fatty acids, 201

Fructose and, 234-235

Functional isolation paradigm, 297

G

Gastric acidity, 226, 292, 311

Gastric cancer, 259

Gastroenteritis, 107

Gastrointestinal effects

arsenic poisoning, 506

boron, 514

copper, 247, 248, 249

iron, 290, 352, 358, 360-365, 373-377

vanadium, 536, 539

zinc, 482

Gender.

See also Men;

Women;

individual nutrients

and absorption of nutrients, 402

and adverse effects of nutrients, 482

and γ-carboxyglutamyl residues, 167

and cardiovascular disease, 359

dietary intakes, 122, 202, 354, 594-641, 644-653, 654-673, 674-679

and drinking water intakes, 642-643

and energy balance, 212

extrapolation of data on basis of, 341

and ferritin, 395, 684-685, 694, 695

and growth velocity, 331

and hemoglobin, 333, 336, 680-681

and iodine excretion, 690-691

and plasma glucose, 695

reference weights and heights, 41, 52

and relative body weight, 52, 332, 333

and retinol, 686-687, 692-693

and retinyl esters, 688-689

serum values for biochemical indicators by, 680-689

and supplement use, 56-57, 187, 278, 612-613, 620-621, 626-627, 632-637

and transferrin, 682-683

Gene expression, 15, 44, 82, 85, 442, 443, 454, 521

Gene regulation, 503

Genetic defects, 248

Genetic markers, 46, 453

Genotoxicity, 197, 214, 507, 514

Glossitis, 300

Glucagon, 446

Glucose tolerance

aging and, 209

chromium and, 44, 198, 199, 201, 203-204, 209, 213, 216, 584

copper and, 229

manganese and, 396

nickel and, 521

vanadium and, 532

Glucuronide conjugation, 164

Glutamine synthetase, 394

Glycotransferases, 394

Goiter, 12, 44, 261, 264-265, 266, 267, 271-272, 276, 279-280, 283, 284

Green tongue, 538

Growth velocity

adolescents, 39, 53, 331, 338, 339

arsenic and, 45, 503

children, 39, 53, 309, 324, 327, 328, 449-450, 465-466, 467-468

infants, 37, 38, 50, 53, 317, 320, 462, 465-466

iron and, 290, 309, 317, 320, 324, 328, 331, 333, 338, 339, 573

manganese and, 396

molybdenum and, 433, 435

nickel, 521

vitamin A and, 44, 82

zinc and, 444, 446-447, 449-450, 452, 454, 462, 464, 465-466, 467-468

H

Hazard identification.

See also individual nutrients

adverse effects, 72, 125, 126-133, 213-215, 247-248, 357-372, 409-412, 433-435, 482-483, 514-517, 524-525, 535-538

animal studies, 71-72, 73, 409-411, 433-434, 514-515, 524

causality, 46, 71, 72

components of, 64, 71-75

data quality and completeness and, 74

defined, 64, 705

duration of exposure and, 73

experimental data on nutrient toxicity and, 73

human studies, 71, 434, 514, 524

mechanisms of toxicity and, 74, 435, 515

pharmacokinetic and metabolic data and, 73-74, 435

route of exposure and, 73

sensitive subpopulations, 74-75, 215, 372-373

Hemachromatosis, 200, 358, 359, 370, 372-373, 376, 378

Hematological disorders, 358, 372, 536-537

Hematopoiesis, 316, 515

Hematuria, 352

Heme-flavoproteins, 291

Heme oxygenase enzyme, 293-294

Heme proteins, 291, 292, 293-294, 304, 311, 312, 314, 315, 327, 356, 374, 455, 483

Hemianopsia, transient, 524

Hemoglobin

adolescents, 305, 330, 331-333, 335, 336, 338

children, 324, 325-326

gender and, 333, 336, 680-681

infants, 316, 319, 320-321, 322-323

iron and, 12, 22, 44, 290, 291, 292, 295, 299, 302, 303, 305, 306, 307, 308, 316, 319, 320-321, 322-323, 324, 325-326, 329, 330, 331-333, 335, 336, 337-338, 342, 345-346, 349, 680-681

mean corpuscular, 706

molybdenum and, 435

nickel in, 521

Hemoglobinuria, 352

Hemolysis, 400

Hemorrhagic disease of the newborn (HDNB), 176, 177

Hemorrhagic syndrome, 175

Hemosiderin, 291, 294, 357

Hepatitis, 129, 133, 134-139

Hepatocellular carcinoma, 370, 372

Hephaestatin, 225

Histidine, 443

Homocysteine, 521

Homovanillic acid, 410

Hookworm, 351

Hormone metabolism, 443, 444, 454, 532

Hormone replacement therapy, 350-351, 573

Human immunodeficiency virus, 443

Human milk.

See also Lactation

absorption of nutrients in, 238, 404

adequacy for infants 0 to 6 months, 37-38, 50, 316, 557-558, 561, 562

analysis of nutrient content, 227

arsenic in, 505

bioavailability of nutrients in, 457, 557-558

boron in, 513

carotenoids in, 111, 117

chromium, 205, 206, 209, 210

colostrum, 177, 178-179

copper, 235, 236-237, 244

excretion quantity, 269

extrapolation of data from intakes of, 463

and hemorrhagic disease of the newborn, 177

intakes, 37, 110, 111, 177, 178, 205, 318-319, 463

iodine, 268-269, 277, 283

iron, 6, 51, 316-317, 318-319, 320, 322-323, 349, 697

manganese, 402, 403, 404, 407

molybdenum, 425, 426, 431

nickel, 523

silicon, 530

vitamin A, 110-111, 117

vitamin K, 177-180, 183-184

zinc, 6, 51, 457, 460-462, 463, 465, 477-478

Human studies.

See also Observational studies

boron, 514

children, 465-466

copper, 247

for dose-response assessment for ULs, 75

ethical considerations, 50, 61, 71

for hazard identification, 71

manganese ecological studies, 411

methodological considerations, 45-46, 67-68

molybdenum, 434

nickel, 524

vanadium, 535, 536, 537-538

Hydroxyapatite, 168

5-Hydroxyindole acetic acid, 410

Hydroxylysine, 225

Hydroxyproline, 24, 172

Hyperglycemia, 213

Hyperkeratosis, 515

Hyperlipidemia, 145, 213

Hypersensitivity to nutrients, 524, 526, 528

Hypertension, 532

Hyperthyroidism, 260, 262, 263, 279, 280, 283

Hyperuricemia, 434

Hypervitaminosis A, 125, 133, 134-139, 144

Hypocholesterolemia, 396, 410-411

Hypoprothrombinemia, 164-165

Hypothyroidism, 260, 261-262, 263, 264, 266, 267, 279, 280, 283

I

Idiopathic copper toxicosis, 248, 251

Immune function

boron and, 511

copper and, 226, 229

indexes of, 453

iodine and, 259, 284

iron and, 300, 302

vitamin A and, 10, 44, 82, 85-86, 96, 98, 99, 105-106, 121

zinc and, 443, 444, 447, 449, 453, 474-475, 481, 482, 488

Impotence, 372, 477

Indian childhood cirrhosis, 248, 251

Indicators of nutrient adequacy.

See also specific indicators, life stages, and nutrients

biochemical, 11-12, 230-233, 239-240, 242, 301-306, 423, 572, 680-691

functional, 300-301

risk reduction-based, 22-25

Infant Growth Study, 328

Infants, premature, 227, 297, 298, 425, 573

Infants, ages 0 through 12 months.

See also Formulas, infant;

Human milk

accretion of new tissue, 464

ages 0 through 6 months, 4, 37, 38, 50, 110, 177-178, 205, 235, 268-269, 316-319, 403, 425, 458-463, 486, 562

ages 7 through 12 months, 6, 37, 38, 51, 111, 178-179, 205-207, 235, 237-238, 269-270, 319-323, 404, 425-426, 463-466, 562

AI derivation for, 4, 34, 35, 37, 38, 50-51, 53, 110-111, 557-558, 561, 562, 564

antiseptic toxicity, 280

Apgar scores, 300

balance studies, 269

basal losses of nutrients, 319, 320, 322, 325

bulging fontanel, 125, 132, 140-141, 143, 144, 145

caloric intakes, 205

ceruloplasmin concentrations, 235

choleostatic liver disease, 396

cognitive development, 295, 300

complementary weaning foods, 38, 51, 111, 178-179, 205, 237, 312, 322, 404, 426, 462, 463, 465, 697

cow milk allergy, 317

cranial neural crest defects, 128-129, 138

defined, 37

developmental delays, 295, 296-297, 300

diarrhea, 227

dietary intakes, 38, 110, 111, 117, 322-323, 463

extrapolation of data to and from, 51-53

factorial analysis, 463

goiter, 280

growth velocity, 37, 38, 50, 53, 317, 320, 462, 465-466

hematopoiesis, 316

hemoglobin concentrations, 316, 319, 320-321, 322-323

hemorrhagic disease of the newborn, 176, 177

hypercalcemia, 140-141

hypervitaminosis A, 140-141, 143-144, 145

hypothyroidism, 280

intestinal losses of nutrients, 463-464

iron deficiency anemia, 296-297, 298, 300, 317

low birth weight, 297, 298, 348

malnourished, 198, 227

method used to set AI, 110-111, 177-179, 205-206, 235, 237, 268-269, 402-404, 425-426, 459, 462

methodological considerations, 38, 50-51, 53, 110-111

nutrient intakes, 51, 561

osteoporosis, 227

recommended food sources, 4, 34, 35, 37, 50, 250, 282, 317

reference weight, 41, 320, 404

skeletal abnormalities, 128-133

small for gestational age, 298, 299

special considerations, 112, 179-180, 206, 238, 270, 317, 404, 427, 462-463

thyroid gland of newborns, 275, 280

TSH screening for hypothyroidism, 261, 266

ULs, 69

urinary losses of nutrients, 464

vitamin K prophylaxis, 176-178

Infectious diseases, 230, 302, 303, 304, 305, 488

and absorption of nutrients, 107

children’s morbidity and mortality, 96-97

vitamin A and, 96-97, 107, 121

zinc and, 445

Inflammatory diseases, 230, 302, 303, 304, 305

Inositol hexaphosphate, 312

Institute of Medicine, 51

Insulin activity, 11, 24-25, 45, 197, 198, 199, 203-204, 213, 216, 510-511, 532, 534, 584

Interleukin-1, 85

Interleukin-6, 445

International Atomic Energy Agency (IAEA), 29-30, 60-61

International comparisons

arsenic, 508

iodine deficiency, 261, 262-263, 271, 276, 279, 284

vitamin K, 187

zinc, 476

International Council for the Control of Iodine Deficiency Disorders, 262, 263

International Programme on Chemical Safety, 248

Intervention trials

chromium, 201, 213

intakes above ULs, 125

iodine, 279

iron, 108, 313

methodological issues, 48

vitamin A, 90-91, 97, 108, 119, 121, 125

vitamin K, 24, 168, 171-173

Intestinal.

See also Gastrointestinal effects

damage, 233

environment and absorption, 311-312, 454-455

iron absorption, 292-293

losses of nutrients, 463-464

menaquinone synthesis, 162

parasites, 107, 118-119, 121, 351-352

zinc losses, 448, 456, 463-464, 472, 476

Intrauterine devices, 334

Iodate, 259

Iodermia, 280

Iodine

absorption and transport, 259, 267

accumulation and turnover, 12, 258, 262-263, 269, 273-274, 275

acute responses, 279

adolescents, 264, 269, 270-273, 276, 277, 282, 283

adults (19+), 16, 26, 56-57, 258, 264, 273-275, 278, 281-282, 283

adverse effects, 18, 279-280

aging and, 274

AIs, 16-17, 270

animal studies, 279, 280

autoimmune thyroid disease and, 278, 283, 284

balance studies, 265, 269, 270, 272, 274, 275

bioavailability, 264, 267, 270

body stores, 260

and cancer, 259, 262, 266, 279, 280, 284

children, 12, 51-52, 262, 264, 265, 269, 270-273, 282, 284

and cretinism, 261-262

data selection, 281

deficiency, 12, 109, 259, 260, 261-268, 275-276, 278, 283, 284

dose-response assessment for ULs, 281-283

EARs, 16-17, 272-273, 274, 276, 277

evidence considered in setting EAR, 258, 270-272, 273-274, 275-276

excretion, 259, 260-261, 263-264, 266, 269, 271-272, 273, 275, 279, 281, 284, 583

exposure assessment, 283-284

factors affecting requirement, 267-268

fetal, 261-262, 275

and fibrocystic breast disease, 259, 284

food sources, 261, 275-276, 277, 283

function, 12, 44, 258-259

gender and, 56-57, 258, 278, 626-627, 662-663, 690-691

and goiter, 12, 44, 261, 264-265, 266, 267, 271-272, 276, 279-280, 283, 284

goitrogens and, 267-268

hazard identification, 278-281

in human milk, 268-269, 277, 283

and hyperthyroidism, 260, 262, 263, 279, 280, 283

and hypothyroidism, 260, 261-262, 263, 264, 266, 267, 279, 280, 283

and immune function, 259, 284

indicators of adequacy, 16-17, 262-267, 690-691

infants, 51-52, 261, 266, 268-270, 275, 280, 282

intakes, 57, 261, 264, 270, 272, 278, 279, 283-284, 626-627, 662-663

interaction with drugs, 268

interaction with other ingested substances, 267-268

interaction with other nutrients, 260, 268, 284

international comparisons, 261, 262-263, 271, 276, 279, 284

intervention studies, 279

and iodermia, 280

iron deficiency and, 268, 284

laboratory assays, 261, 266, 583

lactation, 277, 282, 283

by life-stage group, 16-17, 26, 268-277, 281-283, 626-627, 662-663, 690-691

and mammary dysplasia, 258-259

and mental retardation, 261-262

metabolism, 259-260, 279

method used to set AI, 51-52, 268-269

method used to set EAR, 12, 51-52, 265, 277

methodological considerations, 51-52, 265, 274, 284

NOAEL/LOAEL, 281, 282

pregnancy, 261, 274, 275-277, 280, 282, 283

RDAs, 12, 16-17, 51-52, 258, 271, 273, 274-275, 276, 277

and reproductive outcomes, 261, 262

research recommendations, 284, 583

risk characterization, 284

selenium deficiency and, 260, 268, 284

special considerations, 270, 278, 283

supplements, 56-57, 275-276, 278, 279, 280, 281, 284, 626-627

and thyroglobulin, 259-260, 264, 266-267, 276

and thyroid size, 259, 264-265, 275-276, 279-280, 284

and thyroid stimulating hormone (thyrotropin, TSH), 258, 260, 264, 265, 266, 268, 276, 279, 280, 281, 707

and thyroiditis, 263, 279, 283

and thyotoxicosis, 280

and thyroxine, 258, 267

and triiodothyronine, 258, 260, 267

ULs, 2, 16, 18, 26, 258, 278-284, 562

uncertainty assessment, 281

units, 709

urinary, 259, 260-261, 263-264, 266, 269, 271-272, 273-274, 275, 279, 281, 284, 690-691

vitamin A and, 268, 284

Iron

absorption and transport, 21, 291, 292-294, 301, 303, 308, 311-313, 314, 315, 317, 321, 322-323, 327, 337, 342, 347, 351, 357, 372, 378, 455, 483, 521, 697

accretion, 21, 227, 309, 324, 372

acute toxicity, 357

adolescents, 21, 292, 302, 304, 305, 309, 316, 319, 330-340, 341, 348-349, 350, 353, 355, 375-376, 573, 699, 700, 702

adults, 16, 27, 56-57, 301, 316, 319, 340-344, 353, 355, 373-375, 694, 699, 700, 703

adverse effects, 18, 290, 357-372

AIs, 18-19, 317

alcohol consumption and, 376

and anemia, 12-13, 22, 44, 226, 295-299, 300, 301, 303, 305-306, 317, 352, 378, 583

animal studies, 108, 121, 293, 296, 300

ascorbic acid and, 292, 311-312, 313, 314, 315

athletes, 295, 296, 300, 305, 352-353, 574

balance studies, 292, 308, 309-310, 314, 378

basal losses, 290, 295, 307-308, 320, 322-323, 324, 325, 327, 329, 330, 331, 332, 337, 340, 341, 342, 343, 344-345, 347, 349, 569

bioavailability, 4, 292, 311, 312-313, 314-316, 317, 322-323, 327, 337, 346-347, 349, 351, 355, 359, 378

biochemical indicators of deficiency, 301-306, 572, 680-685

blood donation and, 352, 574

body stores, 290, 291, 293, 294, 299, 301-303, 306, 308, 311, 314, 316, 319, 321, 323, 324, 327, 330, 332, 341, 358-359, 365, 378

body weight and, 308, 322-323, 327, 329, 331, 332, 333, 338, 340, 343, 582

calcium and, 313, 314

and cancer, 302, 303, 370-372, 373

and cardiovascular disease, 359, 364-371, 372, 373, 377-378

and central nervous system processes, 297

cerruloplasmin and, 225, 293

children, 108, 292, 297, 301, 309, 313, 316, 319, 321, 322-323, 324-340, 353-355, 357, 375-376, 698, 699, 701

and chromium, 200

citric acid and, 312, 357

and cognitive function, 13, 295, 296-297, 300, 378, 583

copper and, 225, 226, 227, 234, 246

and coronary heart disease, 359, 365, 368-369

and cytochromes, 12, 291-292

data selection, 373, 375

deficiency, 108, 121, 226, 268, 284, 291, 293-300, 354, 355, 455

in developing countries, 351-352, 359, 377, 378

and development delays, 295, 296-297, 300

distribution of requirements, 327-329, 337-338, 348, 350, 559, 563, 569, 572, 573-574, 576, 699, 700

dose-response assessment for ULs, 373-377

early deficiency, 301, 303-305, 306, 335

EARs, 18-19, 323-324, 328, 329, 338-339, 344, 349, 350

enhancers of nonheme iron absorption, 311-312

and erythrocytes, 290, 301, 302, 304, 305-306, 309, 313, 346, 347, 352

evidence considered in setting EAR, 319-323, 324-329, 330-338, 340-348, 349-350

excretion, 21, 295, 307-309, 319, 322-323, 352

exposure assessment, 377

factorial modeling, 13, 41, 290, 307-309, 319, 324, 330, 340-343, 344, 347, 348, 569

factors affecting requirement, 311-316

FAO/WHO values, 345

and ferritin, 21, 225, 291, 294, 299, 300, 301-303, 306, 307, 311, 313, 314, 315, 351, 352, 353-355, 357, 359, 365-367, 370, 371-372, 373, 377-378, 572, 684-685, 694, 696

and ferroxidases, 225

fetal, 290, 299, 300, 309, 316, 345-346, 347

and flavoproteins, 291

food composition data, 697-698

food sources, 312, 314, 355-356, 697-698

in formula, 234, 317, 322-323

in fortified foods, 355-356, 358, 378

functions, 12-13, 44, 290, 291-292, 300-301

gastric acidity and, 292, 311

gastrointestinal effects, 290, 352, 358, 360-365, 373-377

gender and, 13, 56-57, 290-291, 304, 324, 333, 336, 338-339, 340-344, 354, 356, 359, 628-631, 650-651, 664-665, 676-677, 680-685, 694, 696, 702, 703

growth velocity and, 290, 309, 317, 320, 324, 328, 331, 333, 338, 339, 573

hazard identification, 357-373

heme, 291, 292, 293-294, 304, 311, 312, 314, 315, 327, 356, 374, 455, 483

and heme-flavoproteins, 291

hemochromatosis, 200, 358, 359, 370, 372-373, 376, 378

and hemoglobin (hematocrit), 12, 22, 44, 290, 291, 292, 295, 299, 302, 303, 305, 306, 307, 308, 316, 319, 320-321, 322-323, 324, 325-326, 329, 330, 331-333, 335, 336, 337-338, 342, 345-346, 349, 680-681

and hemosiderin, 291, 294, 357

hormone replacement therapy and, 350-351, 573

in human milk, 6, 51, 316-317, 318-319, 320, 322-323, 349, 697

and immune response, 300, 302

indicators of adequacy, 18-19, 21, 300-310, 311, 680-685

infants, 51, 234, 295, 296-297, 300, 312, 316-324, 325, 353, 375-376, 378, 573, 697, 701

inhibitors of nonheme iron absorption, 312-313

intakes, 57, 290, 322-323, 352, 353-355, 356, 377, 559, 628-631, 650-651, 664-665, 676-677, 696

interaction with other nutrients, 108, 200, 225, 226, 227, 234, 246, 268, 284, 292, 304, 311-313, 314, 315, 357-358, 373, 401, 455, 458, 482-483, 521

intervention studies, 108, 313

intestinal parasitic infection and, 351-352

and iodine, 268, 284

and koilonychia, 300

laboratory measurements, 301-306

lactation, 318-319, 349-350, 375, 377, 455

lactic acid and, 312

and lactoferrin, 291

by life-stage group, 18-19, 27, 316-355, 373-376, 628-631, 650-651, 664-665, 676-677, 680-685, 696

liver disease and, 370, 372, 376

malic acid and, 312

and manganese absorption, 395, 401, 402, 405, 409

menstrual losses, 290, 291, 292, 295, 301-302, 309, 330, 332, 334-337, 338, 339-340, 341-343, 350, 355, 570-572, 700

metabolism, 225, 294, 521

method used to set AI, 316-317

method used to set EAR, 13, 18-19, 290, 307-310, 314-316, 340-343, 569

methodological issues, 41, 307, 309

and mucosal integrity, 300

and myoglobin, 12, 44, 290, 291, 292, 296, 333

nickel and, 521

NOAEL/LOAEL, 374, 375-376

nonheme, 291, 292, 311-312, 313, 314, 315, 351, 374, 375, 376, 455

oral contraceptives and, 334-335, 343, 350, 573, 700, 702, 703

oxidation states, 291

and pagophagia, 300

physical exercise and endurance training and, 295, 296, 300, 305, 352-353, 574

phytates and, 312-313, 314

and pica, 300

plasma glucose and, 302, 582

polyphenols and, 313, 314

pregnancy, 13, 22, 292, 295, 297-300, 302, 304, 305, 309, 344-349, 356, 375, 377, 378, 455, 573

prevalence of inadequate intakes, 21, 22, 353-355, 570, 576

probabilities of inadequate intakes, 570-572, 576, 701-703

and protoporphyrin, 291, 304, 306

race/ethnicity and, 302-303, 308, 694

RDAs, 3-4, 18-19, 33-34, 290, 307, 324, 328, 329, 339, 344, 349, 350, 569

research recommendations, 377, 582, 583

and retinol, 108

risk characterization, 377-378

secondary iron overload, 358-359, 372, 373, 377, 378

sensitive subpopulations, 372-373, 377-378

serum concentration, 368-369, 371

special considerations, 317, 319, 339-340, 350-353, 376-377, 572, 573-574, 576

supplements, 56-57, 108, 121, 297, 300, 305, 313, 351, 352, 353, 356, 357, 360-363, 373, 377, 378, 401, 455

surrogate laboratory indicators, 306

tannic acid and, 312, 313

tissue content (nonstorage), 290, 291, 295, 296, 306, 319, 321, 323, 324, 327, 329, 330, 332, 333-334, 349

total iron-binding capacity, 303, 370-371

and transferrin, 291, 293, 294, 302, 303-304, 306, 357, 359, 368-369, 370-371, 682-683

and transferrin receptors, 302, 304-305, 306

ULs, 2, 16, 18, 27, 290, 356-378, 562

uncertainty assessment, 374, 376

units, 709

validation of requirement estimates, 353-355

variability of requirements, 327-329, 337-338, 348, 350, 559, 563, 569, 572, 573-574, 699, 700

vegetarianism and, 315, 351, 574

vitamin A and, 108, 118, 121

and work performance, 295-296

and zinc absorption, 304, 357-358, 373, 455, 458, 482-483

Iron-binding proteins, 317

Iron-deficient erythropoiesis, 301, 303-305, 306

Iron response element (IRE), 293

Iron response proteins (IRP), 293, 294

Iron-sulfur enzymes, 291, 292

Ischemic heart disease, 228-229, 359

Isotope dilution method, 103, 114

J

Joint FAO/WHO Expert Committee on Food Additives, 66

K

Keratosis, 506, 508

Koilonychia, 300

Kwashiorkor, 119

L

Laboratory assays/values

analytical considerations, 46-47, 168, 266

iodine, 261, 266, 583

iron, 301-306

methodological considerations, 46, 168, 169, 202, 211, 266, 306, 434, 452, 583

surrogate indicators, 306

vitamin K, 168

Lactation.

See also Human milk;

individual nutrients

and absorption efficiency, 244

basal losses of nutrients and, 349

bioavailability of nutrients, 349

derivation of DRIs for, 40-41, 54

evidence considered in setting EAR, 117, 244, 349-350, 431

and hemoglobin mass, 349

method used to set AIs, 183-184, 210, 407

methodological considerations, 54

stage of, 50, 110-111, 206, 235-237, 269, 318-319, 403, 425, 459-461, 478

supplement use, 177

ULs, 145

variability of requirements, 350

zinc, 452, 471, 474

Lactic acid, 312

Lactoferrin, 291

β-Lactoglobulin, 112

Lead poisoning, 304

Lean body mass, 69

Leukemia, 176, 188, 509

Leukocyte copper concentration, 232

Leukopenia, 11, 227

Lewis acid, 443

Life-stage group.

See also Adolescents;

Adults;

Children;

Infants;

Lactation;

Pregnancy;

individual nutrients

Body Mass Index categories by, 41

and derivation of DRIs, 36-41, 50-54

and drinking water intakes, 642-643

and ferritin, 684-685, 695

and hemoglobin, 680-681

intakes of nutrients by, 8-27, 354, 594-641, 644-653, 654-673, 674-679

and iodine excretion, 690-691

and plasma glucose, 695

reference weights and heights by, 41

and retinol, 686-687, 692-693

and retinyl esters, 688-689

serum values of biochemical indicators, 680-689, 695

supplement use by, 612-613, 620-621, 626-627, 632-637, 693

and transferrin, 682-683

ULs by, 26-27, 69, 73

Linamarin, 267

Lipid metabolism, 13, 44, 394, 396, 532

Lipid peroxidation, 357

Lipiodol, 259

Lipoproteins, 482

Liver disease/abnormalities

and arginase activity, 401

arsenic and, 506, 507

cancer, 372, 507

ceruloplasmin and, 230

children, 250

chromium and, 214-215

choleostatic, 396

cirrhosis, 248, 251, 370, 372, 376, 409

copper and, 224, 248, 249, 251

Indian childhood cirrhosis, 248, 251

infants, 396

iron overload and, 370, 372, 376

manganese and, 395-396, 401, 409, 414

menadione and, 187

serum ferritin and, 302

vanadium and, 535

vitamin A and, 109, 125, 129, 132-133, 134-139, 142, 145

Liver function, aging and, 69

Lou Gehrig’s disease, see Amyotrophic lateral sclerosis

Low-density lipoproteins, 93-94

Low-fat diets, 106-107

Low-molecular weight chromium-binding substance (LMWCr), 198, 199

Lowest-Observed-Adverse-Effect Level (LOAEL)

defined, 66, 706

extrapolation of NOAEL from, 143, 144, 281, 374, 486

identification of, 76-77, 133, 138, 143-144, 249, 281, 374, 375-376, 412, 436, 485-486

used instead of NOAEL, 78, 143-144

uncertainty factors, 77

vitamin A

Lung cancer, 507

Lutein, 109, 123, 602-603

Lycopene, 84, 109, 123, 604-605

T-Lymphocyte development and activation, 443

Lymphocyte 5′-nucleotidase activity, 453, 473-474

Lymphocytic thyroiditis, 283

Lysine, 225

Lysyl oxidase activity, 225, 232

M

α-2-Macroglobulin, 395, 421, 446

Magnesium trisilicate, 531

Malabsorption syndromes, 164, 180, 445

and vitamin A, 107, 118-119

and vitamin K, 174, 180

and zinc, 445, 446, 457

Malic acid and, 312

Malnutrition, 30.

See also Protein energy malnutrition

and blackfoot disease, 506

children, 97, 270, 454

chromium and, 198

and creatinine excretion, 263

and hypoptothrombinemia, 164

infants, 198

iodine and, 270

and triiodothyronine concentrations, 267

vitamin A deficiency and, 97, 99, 145

wasting, 97

Mammary dysplasia, 258-259

Manganese

absorption and transport, 395, 401-402, 404, 409

adolescents, 397, 404-405, 406-407, 413, 414

adults, 16, 27, 56-57, 398-399, 405-406, 411, 412-413

adverse effects, 18, 395, 409-411

AIs, 14, 20-21, 404, 405, 407, 558, 561, 562-563, 564

and amino acid metabolism, 13, 394

animal studies, 396, 401, 406, 409-411

and arginase activity, 394, 401

balance studies, 395, 397-399, 404-406

bioavailability, 401-402, 411, 414

blood concentration, 400, 401, 409

and bone formation, 13, 44, 394, 396

calcium and, 401

and carbohydrate metabolism, 13, 394, 396

children, 404-405, 413

and cholesterol, 396, 410-411

in cow milk, 404

data selection, 412

deficiency, 396

depletion/repletion studies, 396, 397, 399, 400

dietary protein and, 397, 401

dose-response assessment for ULs, 412-414

in drinking water, 410, 411, 414

and estrous cycle, 396

excretion, 395-396, 397, 400-401

exposure assessment, 414

factorial analysis, 397

factors affecting requirement, 401-402

ferritin and, 395, 401, 402, 405

fetal, 406, 411

food sources, 407-408

in formula, 397, 402, 404

function, 13, 44, 394

gender and, 20-21, 56-57, 394, 395, 401, 402, 405, 406, 408, 632-633, 666-667

and glucose tolerance, 396

and growth, 396

hazard identification, 409-412

human ecological studies, 411