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DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids
Index
A
Abetalipoproteinemia, 202
Abnormal Involuntary Movements Scale score, 223
Absorption of nutrients.
See also Bioavailability of nutrients;
Malabsorption syndromes
aging and, 31, 147-148, 238, 305
alpha-tocopherol, 196-198, 238, 251
carotenoids, 326, 328, 330, 354, 355, 356
food matrix and, 355
form of nutrient and, 191, 355
iron, 129, 158, 159, 161
selenium, 285-286, 306
vitamin C, 99-100, 103, 108, 128, 140, 147-148, 155, 157
vitamin E (all forms), 191, 193, 196, 243
Adequate intakes (AIs).
See also individual nutrients
defined, 3, 4, 7, 22, 25
extrapolation from other age groups, 26, 65-66, 138
methods used to set, 6-11, 22, 63-66
RDA compared, 4, 25-26
uses, 4, 15, 25, 383, 386, 391, 392, 398
Adolescents, ages 14 through 18 years.
See also Life-stage groups;
Puberty, pubertal development;
individual nutrients
EARs, 65-66
growth factors, 66
Kashin-Beck disease, 287
lactation, 151-152, 163-164, 240-241, 258-259, 307-308, 315
pregnancy, 149-150, 163-164, 239-240, 258-259, 306-307, 315
RDAs, 66
reference weights and heights, 32-33
special considerations, 358
ULs, 14
Adults, 19 through 50 years.
See also Life-stage groups;
individual nutrients
circulating lipid levels, 234-235
depletion/repletion studies, 143-145, 233-234, 236
EARs, 31
peak bone mass, 30-31
PUFA intake, 235
reference weights and heights, 32
supplement use, 70
ULs, 14
Adults, 51+ years.
See also Life-stage groups;
individual nutrients
absorption of nutrients, 31, 147-148
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age-related macular degeneration, 49, 348-350
asthma, 126
cardiovascular disease, 47-49, 121-122, 211-217, 241-242, 346-348
cataracts, 49, 125-126, 221, 350
EARs, 31
immune function, 51, 117-119, 220-221, 338
institutionalized, 147
lean body mass, 148
oxidative stress in, 51, 148, 242
supplement use, 51, 70
ULs, 14
Advanced glycosylation end products, 50-51
Adverse effects, 3, 4-6
alpha-tocopherol, 249, 251-255
carotenoids, 366-368
defined, 73
evidence of, 85
knowledge gaps, 406
nutrient-nutrient interactions, 74
selenium, 311-313
vitamin C, 155-161
Age-related macular degeneration (AMD) carotenoids and, 18-19, 49, 348-350
smoking and, 18, 49
Aging.
See also Life-stage groups;
individual life stages
and absorption of nutrients, 31, 147-148, 238, 305
alpha-tocopherol and, 51, 235
carotenoids and, 330
food consumption and, 51
and immune function, 51, 220
oxidative stress and, 44, 51
and serum cholesterol, 235
Alcohol and drug abuse, 101, 150, 330, 360, 368
Aldosterone, 99
Allergic response to nutrients, 160, 161, 368
Alpha-1-antiprotease, 108, 140
Alpha-carotene, 325, 329, 330, 332-333, 342, 343, 347, 348, 349, 350-351, 356, 358, 360-365, 366, 371, 450-451
Alpha-tocopherol, 186-283.
See also Vitamin E
absorption, 196-198, 238, 251
adolescents, 230-231, 239-241, 258, 259, 260-261
adults (19-50 years), 228-229, 231-237, 239-241, 255-257, 258, 259, 397
adults (51+ years), 220, 238-239, 241-242, 249, 259-260
adverse effects, 249, 251-255, 396
AIs, 8-9, 65, 226-230, 393, 394, 507
animal studies, 197, 203, 212, 216, 221, 252, 254, 255
antioxidant activity, 195, 224-225
and ataxia, 199, 202-203, 204-209
bioavailability, 224, 238, 243, 251
body pool, 209-210, 225
body size and composition and, 242
and cancer, 196, 213-214, 218-220, 241
and cardiovascular disease, 36-41, 203, 206-207, 211-217, 225, 238, 241-242, 248, 252, 261
and cataracts, 221
and central nervous system disorders, 221-223, 252
children, 202, 230-231, 258, 260-261
and cholestatic hepatobiliary disease, 202, 203
and circulating lipoproteins, 193, 197, 199, 216, 234-235, 261
critical endpoint, 254
deficiency, 186, 199, 202-203, 204-209, 210-211, 220, 221, 231, 235, 239, 240
defined, 187, 192, 468
depletion/repletion studies, 203, 232, 233-234, 236
and diabetes mellitus, 217-218
and DNA damage and repair, 208
dose-response assessment for ULs, 255-259
EARs, 2, 8-9, 10-11, 194, 230-237, 238, 239, 240, 393, 394
excretion, 200, 208-209
exposure assessment, 259-260
factors affecting requirements, 224-226
fetal, 239, 243, 394
food sources, 224, 243, 244, 245, 248, 250, 396
in fortified foods, 190-191, 194, 243, 394
functions, 12, 43, 186, 195-196
gender and, 2, 231, 237, 245, 249
hazard identification, 249, 251-255
hemorrhagic toxicity, 13, 252, 253-254, 255-256
in human milk, 226, 227, 228-229, 240
and hydrogen peroxide-induced hemolysis, 12, 43, 203, 210-211, 231, 232-233, 234, 235, 402
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and immune function, 51, 219, 220-221
indicators of adequacy, 8-9, 203, 208-224
infants, 65, 226-230, 239, 240, 253-254, 258, 259, 386, 392
intakes, 16, 230, 243-249, 250, 395-397, 424-425
interaction with drugs, 252, 259
interaction with other antioxidants, 195, 290
interaction with other nutrients, 36-41, 98-99, 102, 109, 128, 129, 213, 221, 222, 224-225, 232, 252, 254-255, 259
international comparisons, 204-209, 212-214, 216
international units converted to, 192, 244-245, 395, 396, 397
intervention trials, 2, 36-41, 213-217, 219-220, 221, 223-224, 226, 238, 241-242, 252, 254, 261-262, 367, 405
kinetic modeling, 209-210
laboratory values, 67
lactation and, 67, 228-229, 240-241, 258, 259
and LDLs, 211-212, 217, 226
by life-stage group, 8-9, 14, 226-243, 255-258, 422-427, 436-437, 444-445
and lipid peroxidation, 12, 43, 45, 195, 203, 211, 221, 222, 223, 225, 226, 243, 261
metabolism, 199-200, 208-210, 261
methodological considerations, 65, 67, 68-69
method used to set AIs, 226-230
and neuropathy, 202, 204-207, 218, 220, 221, 231, 232
NOAEL/LOAEL, 255-257
observational epidemiological studies, 212-213, 219, 221
and oxidative stress, 44-45, 51, 52, 203, 211, 217-218, 221, 222, 223, 242, 261
physical exercise and, 242
plasma concentrations, 197, 210, 232-237, 251, 444-445
platelet effects, 196, 211, 212, 218, 253
preferential secretion by liver, 197-199, 243
pregnancy and, 67, 239-240, 258, 259
and PUFAs, 195, 215, 225-226, 235, 248
RDAs, 2, 8-9, 12, 231, 237, 238-241, 248, 393, 394, 507
research recommendations, 20, 260-262
and retinopathy, 202, 208-209, 259
risk characterization, 260
serum concentrations, 236, 444-445
and skeletal myopathy, 202
smokers, 36-37, 213-214, 216, 219, 238, 242-243, 252
special considerations, 241-243, 259
storage, 201-202
supplement use, 70, 190-191, 194, 244-245, 249, 251, 258-260, 394-395, 396, 397
synthetic, 190-191, 192, 193, 244-245, 393-397
transport, 196-199
ULs, 13, 14, 249, 251-260, 396-397
uncertainty assessment, 91, 256-257
and vasodilation, 196, 210
vitamin C and, 98-99, 102, 109, 110-113, 128, 129, 213, 224-225
Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, 36-37, 49, 213-214, 216-217, 219, 221, 238, 241, 242, 252, 254, 345, 366-368, 369, 406
Alpha-tocopherol equivalents
conversion to alpha-tocopherol intakes, 16, 244, 394-395, 397
intakes, 230, 243, 244, 245-248, 422-423, 426-427, 436-437
usefulness of, 394
Alpha-tocopherol transfer protein (alpha-TTP)
form of vitamin E and affinity of, 193, 195, 197-198, 243, 262
function, 186, 197-198
genetic defects, 199, 202, 204-209
Alzheimer's disease, 19, 50, 222, 252
American Academy of Pediatrics, 28, 29, 65, 74, 259
Amino acids.
See also individual amino acids
biosynthesis, 96
Aminotransferases, 163
Amyloid beta-peptide, 222
Amyotrophic lateral sclerosis, 19, 50
Anemia, hemolytic, 239, 259, 355
Angina, 47, 341, 347
Angiotensin-converting enzyme inhibitor, 38-39
Animal studies
alpha-tocopherol, 51, 59, 91, 197, 203, 212, 216, 251, 252, 254, 255, 396
of cardiovascular disease, 48-49, 212, 216
carotenoids, 59
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extrapolation of data from, 91, 257, 301
for hazard identification, 84-85, 86
methodological considerations, 58-59
relevance of, 86
selenium, 287, 290
uncertainties in, 459
vitamin C, 103, 120, 131, 140
Anticoagulants, 252, 253, 259
Antioxidants.
See Dietary antioxidants
Aquocobalamin, 158
Arachidonic acid cascade, 196
Asbestos workers, 36-37, 367, 371
Ascorbic acid.
See Vitamin C
Aspirin, 150
Asthma, 126
Ataxia with vitamin E deficiency, 199, 202-203, 204-209
Atherogenesis, 47, 48, 50, 121-122, 212, 218, 225
Atherosclerosis, 18, 36-37, 48, 103, 109, 122, 203, 213, 340-341, 347-348
Atherosclerosis Risk in Communities Study, 122
Athletes, 117, 153, 242, 403
Attention-deficit disorder, 163
B
Balance studies, 59
Baltimore Longitudinal Study on Aging, 125
Basel Prospective Study, 121, 342, 343, 346-347
Benign breast disease, 219
Benzo[α]pyrene, 360
Beta-carotene, 325-382.
See also Carotenoids
absorption, 326-328, 355
adolescents, 358
adverse effects, 366-368, 405, 406
and alcohol consumption, 360, 361, 368
antioxidant activity, 36-37, 43-45, 98-99, 102, 109, 110-111, 325, 331-333, 334-337
bioavailability, 328, 331, 354-355, 356, 357, 369-371
blood concentrations, 330, 332-333, 353, 369, 372, 448-449
body stores, 329-330
and cancer, 36-41, 213-214, 290, 330, 339, 343, 344, 345-346, 366-368, 369-371, 405, 406
and cardiovascular disease, 36-41, 336-337, 346-347
carotenodermia, 366, 368, 369
and cystic fibrosis, 331, 336-337
depletion/repletion studies, 331, 332, 334-337, 371, 403
and DNA damage and repair, 109, 110-111, 331-332
erythropoietic protoporphyria, 366, 371
excretion, 328-329
and eye diseases, 49, 348, 349, 350-351
food sources, 331, 332, 334, 353, 355-356, 360-363, 398-399
and immune function, 338
infants, 361, 362-365
intakes, 361, 364-366, 369
interaction with drugs, 357
interaction with other nutrients, 36-41, 102, 109, 110-111, 290, 357-358
international comparisons, 334-337
intervention trials, 36-41, 213-214, 216-217, 219, 221, 238, 241, 242, 252, 254, 345, 366-368, 369, 372, 405
by life-stage group and, 358-360, 448-449
and lipid peroxidation, 332, 334-337
and oxidative stress, 332
provitamin A activity, 12-14, 36-37, 325, 356, 366, 367
research recommendations, 2, 20, 371-372
smokers, 36-39, 330, 331, 334-337, 345, 347, 359, 366-368, 372, 405, 406
supplement use, 325-326, 355, 357, 366
transport, 329
ULs, 5-6, 13-14, 27, 368-369
vitamin C and, 102, 109, 110-111
Beta-Carotene and Retinol Efficacy Trial, 36-37
Beta-cryptoxanthin, 13, 44, 325, 330, 332-333, 345, 348, 349, 350-351, 358, 360-365, 366, 452-453
Beta-glucuronidase, 106-107, 116
Bioavailability of nutrients
alpha-tocopherol, 224, 243, 251, 394
carotenoids, 328, 331, 344, 354-357, 369-371, 403
defined, 463
dietary fat and, 68, 224, 248, 356
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drug interactions and, 357
food matrix and, 354, 355-356, 404
form of intake and, 83, 251, 354
form of nutrient and, 193, 194-195, 357, 369-371
in infant formulas, 29, 64
iron in, 129
nutrient-nutrient interactions and, 83, 357-358
nutritional status of individuals and, 83, 356
processing of foods and, 29, 354, 356
and risk assessment, 82-83
selenium, 291-292, 306, 307, 399
vitamin C, 99, 128
vitamin E (all forms), 16, 193, 194-195, 224, 243
Biomarkers
of cancer, 113-116
of DNA damage, 45, 46-47, 109-111, 116
of lipid peroxidation, 45, 104-105, 116, 132, 151, 203, 211
Bladder cancer, 106-107, 113, 116
Bleomycin, 112, 114-115
Blood coagulation, 99, 101
Body Mass Index, 32, 33, 330
Body pools
alpha-tocopherol, 201-202, 225
carotenoids, 329-330, 351-353
kinetic modeling of, 209-210, 403
selenium, 286, 313
vitamin C, 100, 103, 132, 140, 142, 145, 152-153, 166, 225, 403
vitamin E (all forms), 210
Body size considerations, 133, 146, 242
Body water considerations, 133, 138, 146
Body weight.
See also Reference body weight ratio method
reference weights, 31-33
Bone formation and growth, 98, 101, 202
Boston Nutritional Status Survey of the Elderly, 154, 155, 242, 249
Breast cancer, 123, 219
Breast Cancer Serum Bank cohort study, 219
Breastfeeding.
See Human milk;
Lactation
Breath ethane, 132, 150-151, 203, 211, 231
Breath pentane, 334-337
C
Cambridge Heart Antioxidant Study, 36-37, 214-215, 241
Canada
antioxidant intervention trials, 38-39
cancer, 124
cardiovascular disease, 38-39
dietary intakes, 16, 154, 284, 309, 438-439
Food Guide for Healthy Eating, 351-352
Recommended Nutrient Intakes, 28, 383, 410
reference weights and heights, 32, 33
selenium, 284, 293
vitamin C, 69, 124, 154
Canadian Paediatric Society, 28, 29, 63-65
Cancer.
See also individual sites
alpha-tocopherol and, 36-37, 196, 213-214, 218-220, 241, 290, 366, 367
antioxidant intervention trials, 36-41, 218-219, 339, 357-358
biomarkers, 113-116
carotenoids, 14, 36-41, 213-214, 290, 326, 330, 333, 339, 340-341, 342-346, 351, 352, 357, 360, 366-372, 405, 406
DNA damage and, 218-219
gap junctional communication and, 333, 338
mortality, 14, 339
oxidative stress and, 17, 46-47, 218-219
selenium and, 36-41, 290-291, 319, 367
vitamin C and, 36-37, 40-41, 106-107, 113-116, 123-125, 127, 128, 160
Cardiomyopathy, 159, 206-207, 287, 288
Cardiovascular disease.
See also Coronary artery disease;
Coronary heart disease
alpha-tocopherol and, 18, 36-41, 48-49, 187, 203, 206-207, 211-217, 225, 238, 241-242, 248, 252, 261, 406
animal studies, 48-49, 212, 216
carotenoids and, 18, 36-41, 326, 331, 336-337, 339, 340-341, 346-348, 351, 371
diabetes mellitus and, 50
intervention trials, 48, 213-216
iron and, 159
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LDLs and, 47-48, 50, 211-212
lipid peroxidation and, 225
mortality, 339
observational studies, 212-213
oxidative stress and, 18, 47-49, 50, 101-102, 225
RNA/ROS and, 216
selenium and, 40-41, 287, 288
smokers, 37-39, 48-49, 103, 106-107, 216, 238, 252, 347
vitamin C and, 18, 38-41, 101-102, 106-107, 109, 121-122, 127, 128, 346-347
women, 38-41, 121, 122, 212, 347
Carnitine biosynthesis
iron and, 120
vitamin C and, 95, 96, 99, 120, 153, 166
Carotene and Retinol Efficacy Trial (CARET), 36, 345, 367, 368, 369
Carotenodermia, 366, 368, 464
Carotenoids, 325-382.
See also Beta-carotene;
other individual carotenoids
absorption, 326, 328, 330, 354, 355, 356
adolescents, 355, 358
adults (19-50 years), 330-331, 334-337, 339-345, 364-365
adults (51+ years), 336-337, 338, 340-341, 347, 348-351
adverse effects, 366-368, 405, 406
and age-related macular degeneration, 18-19, 49, 326, 340-341, 348-350, 371, 403
aging and, 330
alcohol consumption and, 330, 360, 361, 368
allergic reactions, 368
antioxidant activity, 36-37, 43-45, 98-99, 102, 109, 110-111, 325, 326, 331-333, 334-337
bioavailability, 328, 331, 344, 354-357, 369-371
blood concentrations, 329-330, 332-333, 338, 346, 351-353, 358, 368, 448-457
body mass index and, 330
body stores, 329-330, 351-353
and cancer, 36-41, 213-214, 290, 326, 330, 333, 339, 340-341, 342-346, 351, 352, 357, 360, 366-372, 405, 406
and cardiovascular disease, 18, 36-41, 326, 331, 336-337, 340-341, 346-348, 351, 371
and cataracts, 18, 326, 340-341, 350-351
children, 338, 355, 356, 358, 368
cholesterol and, 330
and cystic fibrosis, 331, 336-337
depletion/repletion studies, 331, 332, 334-337, 371, 403
dietary fat and, 356
and DNA damage and repair, 109, 110-111, 331-332, 336-337
dose-response assessment for ULs, 368-369
DRIs, 12-13, 16, 325
excretion, 328-329
exposure assessment, 369
fat substitutes and, 357
food sources, 325, 331, 332, 334, 342, 344-345, 346, 349-350, 351-352, 353, 354, 355-356, 360-363, 368, 371, 398-399
functions, 12, 43, 325, 326
and gap junctional communication, 333, 338
gender and, 330, 351, 364-365
hazard identification, 366-368
health effects, 326, 338-351, 403-404
in human milk, 361, 362-366
and immune function, 326, 338
indicators of adequacy, 325, 331-353
infants, 361, 362-366, 368
intakes, 361, 364-366, 369
interactions with drugs, 357
interactions with other nutrients, 36-41, 102, 109, 110-111, 290, 325, 326, 327, 328, 330, 331, 332, 338, 343, 352, 355, 356, 357-358, 366, 367
international comparisons, 334-337
intervention trials, 2, 14, 36-41, 213-214, 216-217, 219, 221, 238, 241, 242, 252, 254, 345-346, 353, 366-368, 369, 372, 405
lactation, 355, 362, 363
by life-stage group and, 358-360, 448-457
and lipid peroxidation, 332, 334-337
lipoproteins and, 329, 330, 332, 334-337
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metabolism, 328-329
methodological issues, 16, 68-69, 339, 359, 404
and mortality from chronic disease, 14, 339-342, 351
nonprovitamin A, 326, 327, 346, 351
observational epidemiological studies, 338-339, 342-345, 346-347
and oxidative stress, 332
provitamin A activity, 12-14, 36-37, 43-44, 325, 326, 327, 328, 330, 331, 338, 343, 352, 355, 356, 366, 367, 371, 372, 403, 467
research recommendations, 2, 20, 371-372, 403-404
risk characterization, 369-371
smokers, 18, 36-39, 49, 330, 331, 334-337, 344, 345, 347, 351, 359, 366-371, 372, 405, 406
special considerations, 358-360
structure, 326, 327
supplement use, 325-326, 355, 357, 366
transport, 329
ULs, 5-6, 13-14, 27, 366-371, 407
Catalase, 45
Cataracts, 18, 49, 340-341
alpha-tocopherol and, 18, 49, 221
carotenoids and, 18, 326, 340-341, 350-351
oxidative stress and, 18, 49, 350
smoking and, 351
vitamin C and, 18, 98, 125-126, 127
Catecholamines, 96, 127, 222-223
Central nervous system disorders, 19, 50, 127, 221-223
Ceruloplasmin oxidase activity, 129, 160
Cervical cancer, 17, 123, 340-341, 345, 346
Children, ages 1 through 13 years.
See also Life-stage groups;
individual nutrients
abetalipoproteinemia, 202
AIs, 65-66
anemia, 355
attention-deficit disorder, 163
cardiomyopathy, 287, 288, 292
cholestasis, 235
common colds, 163
cystic fibrosis, 202, 210-211, 336-337
EARs, 30, 33, 65-66
growth factors, 66
Keshan disease, 287, 288, 292, 299-300, 301-302
reference weights and heights, 31-32
supplement use, 163, 260
ULs, 14, 33
vitamin A deficiency, 338, 356
Cholestasis, 235
Cholestatic hepatobiliary disease, 202, 203
Cholesterol
aging and, 235
carotenoids and, 330
dietary, 99, 248
LDL, 47, 330
serum, 235
vitamin C and, 99
Cholesterol Lowering Atherosclerosis Study, 213
Cholestyramine, 357
Chromosomal damage and aberrations, 109, 110-111, 112, 114-115
Chronic cholestatic hepatobiliary disease, 202, 203
Chronic obstructive pulmonary disease, 126, 127
Chylomicron secretion, 196-197, 224, 330
Circulating lipid levels, 234-235
Cobalamins, vitamin C and, 158
Cognitive function, 19, 50, 127
Collagen metabolism
iron and, 118-119
vitamin C and, 95, 96, 98, 99, 101, 118-119, 166
Colorectal cancer, 36-37, 113, 116, 123-124
Colorectal polyps, 113, 114-115, 219-220
Common cold, 117, 126-127
Complementary DNA (cDNA), 197
Conjugated dienes, 104-105, 203
Connective tissue synthesis, 98, 101
Continuing Survey of Food Intakes by Individuals (CSFII)
alpha-tocopherol, 68, 240, 245, 247, 248, 396, 436-437
carotenoids, 361, 364
design, 69
vitamin C, 135, 138, 432-435
Copper
infants, 129, 159-160
and LDL oxidation, 211
metabolism, 129
and oxidative stress, 203
vitamin C and, 96, 97-98, 128, 129, 156, 159-160, 161
Coronary artery disease, 106-107, 121, 122, 241, 248, 336-337
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Coronary heart disease, 18, 49, 121, 122, 212, 214-215, 238, 241, 261, 341, 347, 351
Corticosteroids, 99
Coxsackie B3 virus, 287
Cretinism, 287
Critical endpoints, identification of, 88-89, 254, 313
CSFII.
See Continuing Survey of Food Intakes by Individuals
Cyclooxygenase-1, 196, 212, 223
Cystic fibrosis, 202, 210–211, 331, 336–337
D
Data and database issues
alpha-tocopherol, 232, 243-248, 255, 393-396
for dose-response assessment for ULs, 88-89, 161, 255, 313, 315
food compostion data, 16, 19, 67-68, 309, 360-361, 393-394, 396-397, 398, 399
nutrient intakes, 16, 68, 69-70, 194-195, 243, 309, 385
quality and completeness of data, 8-9, 61-62, 67-68, 87, 309, 385, 390
selenium, 309, 310, 398-399
supplement use, 70
types of data used, 58-63
vitamin C, 139-140, 143, 161
vitamin E.
See Alpha-tocopherol
Dehydroascorbic acid (DHA)
absorption and transport, 99
chemical structure, 96, 97
in smokers, 130
Delayed dermal sensitivity, 117, 118-119, 220
Dental enamel erosion, 156, 160, 161
Depletion/repletion studies
alpha-tocopherol, 203, 232, 233-234, 236, 402
carotenoids, 331, 332, 334-337, 371
limitations of, 59, 402-403
vitamin C, 108, 117, 140, 143-145, 402-403
Diabetes mellitus
alpha-tocopherol and, 217-218
cardiovascular complications, 50
LDLs and, 50
oxidative stress and, 19, 50-51, 217-218
and platelet hyperactivity, 218
type I, 106-107
type II, 50, 106-107
Diabetic neuropathy, 218
Diacylglycerol, 196
Diarrhea.
See Osmotic diarrhea
Dietary antioxidants
alpha-tocopherol activity, 43, 44-45, 98-99, 102, 109, 110-113, 186, 195, 224-225
carotenoid activity, 36-37, 43-45, 98-99, 325, 326, 331-333, 334-337
criteria for, 43-44
defined, 17, 42
and immune function, 407
interaction among, 195, 224-225, 290, 332, 367, 404
intervention trials, 36-41, 50, 219-220, 339, 348-350, 357-358
mechanisms of action, 44-46
selenoprotein activity, 43, 44-45, 284, 285
supplement efficacy, 45, 48, 49
vitamin C activity, 43, 44-45, 96, 98-99, 101-109, 116, 124-125, 139-143, 146, 154, 166
Dietary intakes.
See also Canada;
Food sources of nutrients;
Nutrient intakes;
Supplements;
individual nutrients
data and database issues, 16, 68, 69-70, 194-195, 243, 309, 385
day-to-day variation, 69, 385
infants, 28, 65, 135, 138, 230, 307
measurement errors, 68, 69, 313, 359, 385-386
research recommendations, 165-166, 406
self-reported, 60, 68, 385, 396
smokers, 130, 359, 360
survey data, 245-247
underreporting of, 16, 60, 68, 69, 186, 232, 240, 247-248, 385, 390, 393, 395-396
Dietary Reference Intakes (DRIs)
applicable population, 22
categories, 2, 3, 22-27;
See also Adequate Intakes;
Estimated Average Requirements;
Recommended Dietary Allowances;
Tolerable Upper Intake Levels
criteria for, 6-11, 12-13, 42
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defined, 2-6, 21-22, 33
extrapolation from other age groups, 65-67, 91
framework, 384, 410-412
group applications, 14-16, 25, 387-391, 392-393, 398
individual applications, 4, 15, 22, 384-386, 392, 398
nutrient-specific considerations, 393-399
origin, 409-410
parameters for, 27-33;
See also Life-stage groups;
Reference weights and heights
precision of values, 8-11
risk of inadequacy, 15-16
sources of data, 6-7;
See also Methodological considerations
uses, 4, 14-16, 383-399
DNA damage and repair
adduct formation, 106-107, 116, 208
alpha-tocopherol and, 109, 110-113, 208
biomarkers of, 45, 46-47, 109-111, 116
and cancer, 46-47, 113-116, 218-219
carotenoids and, 109, 110-111, 331-332, 336-337, 360
ex vivo, 112-113, 114-115, 116, 130
in gastric mucosa, 106-107, 116
glutathione and, 109-110
ionizing radiation and, 46, 112, 130
iron and, 109, 160
lymphocytes, 110-111, 112, 114-115
oxidative stress and, 46-47, 109
repair enzymes, 106-107, 116
RNS and, 116
smoking and, 110-113, 130-131, 360
vitamin A and, 112-113
vitamin C and, 98, 109-115, 116, 130-131, 160
Dopamine, 222-223
Dopamine-β-hydroxylase, 96, 98
Dose-response assessment for ULs
adolescents, 162-164, 258, 315-316
adults (19-50 years), 161-162, 255-257, 313-315
alpha-tocopherol, 255-259
carotenoids, 368-369
children, 162-164, 258, 315-316
components and process, 85, 88-92
critical endpoints, 88-89, 161, 254, 313
data selection, 88-89, 161, 255, 313, 315
defined, 77-78, 464
infants, 162, 258, 315-316
lactation, 164, 258, 315
NOAEL/LOAEL identification, 89-90, 161-162, 255-256, 314, 316
pregnancy, 163-164, 258, 315
selenium, 313-316
special considerations, 92, 164-165, 259
UL derivation from, 91-92, 162, 257, 315, 316
uncertainty assessment, 90-91, 162, 256-257, 315, 316
vitamin C, 161-165
vitamin E.
See Alpha-tocopherol
Down's syndrome, 222
Drinking water, 309-310, 311, 317, 399
Drug abuse.
See Alcohol and drug abuse
Drug interactions
with alpha-tocopherol, 40-41, 252, 259
with carotenoids, 357
with vitamin C, 99, 150
Dyspepsia, 106-107, 116
E
Elastin, 98
Elderly people.
See Adults, 51+ years
Embryogenesis, 285
Emotional stress, 153
Endothelial cells
dysfunction, 103, 106-107, 131
monocyte adhesion to, 103
Endothelium-dependent vasodilation, 106-107, 131
Endothelium-derived relaxing factor, 103
Energy expenditures, 24-25
Energy intakes, 60, 68, 69, 247, 396
Energy status
and antioxidant interactions, 224-225
and PUFA metabolism, 226
Epinephrine, 96
Erythrocyte
glutathione, 128
hydrogen peroxide-induced lysis, 210-211, 231
vitamin C, 140
Erythropoietic protoporphyria, 366, 371
Esophageal cancer, 367
Established Populations for Epidemiological Studies of the Elderly , 122, 213
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Estimated Average Requirements (EARs).
See also individual nutrients
children, 30, 33, 65-66
coefficient of variation, 3, 24-25
criteria used to derive, 6-7, 8-11
defined, 3, 5, 23, 24
evidence considered, 10-11, 25
extrapolation to/from other age groups, 65-66
group applications, 15, 387-390, 392
knowledge gaps, 402-404
methods used to set, 25, 43, 65-66, 402-404
and RDA, 2-4, 23-25
reference weight and height and, 31-33
risk of inadequacy, 24
standard deviation, 3, 23-24
uses, 15, 23, 25, 383, 384-386, 387-390, 392-393
Ethane, 132, 150-151, 203, 211, 231
Ethical considerations, 84
European Commission Concerted Action on Fundamental Food, 42
Exposure
duration of, 86
route of, 86, 256
Exposure assessment
alpha-tocopherol, 259-260
carotenoids, 369
defined, 77, 78
process, 92
selenium, 317
supplements, 92
vitamin C, 165
Extrapolation of data
from animal studies, 91, 257
body weight basis, 65-66, 138-139, 163-164, 230-231, 258-259, 299-300, 315-316
from one gender group to another, 146-147, 235, 237
from other age groups, 25, 26, 65-66, 138-139, 163-164, 166, 230, 231, 258-259, 299-300, 315-316
NOAEL from LOAEL, 162, 256-257
from subchronic to chronic intake, 257
Eye Disease Case-Control Study, 348
Eye diseases.
See also Age-related macular degeneration;
Cataracts
alpha-tocopherol and, 18, 49, 221
antioxidant intervention trials, 40-41, 348-350
carotenoids and, 49, 348, 349, 350-351
vitamin C and, 18, 125-126
F
Familial hypercholesterolemia, 47
Fat, dietary
and alpha-tocopherol, 68, 225-226, 235, 248, 396
and carotenoid, 356
intakes, 16, 68, 69, 232, 247, 248, 261, 396
malabsorption syndromes, 202, 404
and MOPD, 349
Fat substitutes, 357
Fatty streak lesions, 47
F2-isoprostanes, 45, 48, 203, 217-218, 464
Ferritin, 159
Ferrous oxidation/xylenol orange (FOX) assay, 46
Fetal nutrition.
See also Pregnancy
alpha-tocopherol, 67, 239, 243, 258, 394
selenium, 67, 306, 315
vitamin C, 67, 149, 150, 163
Fibrillin, 98
Fibronectin, 98
Flavonoids, 98-99, 102, 128, 129, 225
Foam cells, 47-48
Food and Agriculture Organization, 22, 73-74, 79
Food and Drug Administration, 309
Food composition data
analytical methods, 67
carotenoids, 360-361, 364-365, 369
quality and completeness of, 68-69, 309, 390, 393-394, 399
recommendations, 19, 396-397
selenium, 309, 398-399
vitamin C, 154, 390
vitamin E, 19, 68-69, 244-248, 393-394
Food matrix and bioavailability of nutrients, 250, 354, 355-356, 404
Food sources.
See also Fortified foods
alpha-tocopherol, 224, 243, 244, 245, 248, 250, 396
carotenoids, 325, 331, 332, 334, 342, 344-345, 346, 349-350, 351-352, 353, 354, 355-356, 360-363, 368, 371, 398-399
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selenium, 286, 292, 298-299, 308, 309, 397
vitamin C, 101, 130, 154, 392
Formulas, infant
AIs, 386, 391, 392
alpha-tocopherol, 230
bioavailability of nutrients, 29, 64
carotenoids, 361
DRIs, 28-29
selenium, 310, 399
vitamin C, 101, 135
Fortified foods.
See also Formulas, infant
alpha-tocopherol in, 12, 16, 190-191, 243, 394
selenium in, 286
ULs and, 5, 26, 74
Fruits and vegetables, 17, 18, 45, 47, 130, 133, 154, 245, 342, 344-345, 346, 351, 353, 355, 368, 371
Furunculosis, 117, 118-119
G
Gastric cancer, 36-37, 106-107, 113, 114-115, 116, 124-125, 196, 290, 367
Gastric mucosa
DNA damage, 106-107, 116
nitrotyrosine, 102, 106-107, 116
oxidant scavengers, 95, 102, 116, 124
Gastritis, 102, 106-107, 113, 116, 124-125
Gastrointestinal effects
of vitamin C, 95, 100, 102, 106-107, 124-125, 156, 161-162, 163, 166, 386, 393
Gender.
See also Men;
Women;
individual nutrients
and cataracts, 351
dietary intakes, 15-16, 154, 165, 245-247, 259-260, 364-365
extrapolation of data on basis of, 146-147, 235, 237
and Keshan disease, 299, 304
and lean body mass, 2, 65, 146-147
and metabolism, 20, 133, 403, 407
reference weights and heights, 32
and relative body weight, 65-66, 138
and supplement use, 70, 260
Genetic defects, in alpha-TTP, 199, 202, 204-209
Genetic markers of disease susceptibility, 60
Geographic differences in nutrient intakes, 309, 311-312, 315, 316, 317, 318-319
Gingivitis, 120
GISSI Prevention Trial, 38-39, 215, 216, 217, 238, 241, 242, 252
Glial cells, 98
Glucose-6-phosphate dehydrogenase deficiency, 160-161, 164
Glutathione
and asthma, 126
deficiency, 128
and DNA damage, 109-110
erythrocyte, 128
and oxidative stress, 128, 129, 224
reduced, 104-105, 128, 225
vitamin C and, 43, 96, 98, 99, 103, 105, 109-110, 126, 128, 129
Glutathione peroxidase activity, 12, 45, 284, 285, 286, 289-290, 293, 299, 301-302, 303, 304, 318
Growth factors, 66
Growth velocity, 28, 64
Gulonolactone oxidase, 95-96
Gun blue, 312, 465
H
Hazard identification
adverse effects, 85, 155-161, 249, 251-255, 311-313, 366-368
alpha-tocopherol, 249, 251-255
animal studies, 84-85, 86
carotenoids, 366-368
causality, 85-86
components of, 85-88
data quality and completeness and, 87
data sources, 84-85
defined, 77, 465
experimental data on nutrient toxicity and, 86
mechanisms of toxicity and, 87
pharmacokinetic and metabolic data and, 86-87
selenium, 311-313
sensitive subpopulations, 87-88
vitamin C, 155-161
Health Canada, 410, 438-439
Heart Outcomes Prevention Evaluation Study, 38-39, 216, 217, 241, 242, 252
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in smokers, 104-105, 130, 131, 132, 150-151, 153
vitamin C and, 45, 95, 98, 102, 104-105, 109, 116, 130, 131, 132, 146, 150-151, 153, 159
Lipid Research Clinics Coronary Primary Prevention Trial, 347
Lipoprotein lipase, 330
Lipoproteins.
See also High-denisty lipoproteins;
Low-density lipoproteins
alpha-tocopherol and, 193, 197, 199, 216, 234-235, 261, 405
carotenoids and, 329, 330
Liver fluke infection, 106-107
Liver necrosis, 287
Low-density lipoproteins (LDLs)
alpha-tocopherols and, 211, 217, 226
and cardiovascular disease, 47-48, 50, 211-212
carotenoids and, 329, 332, 334-337
copper and, 211
defined, 79, 466
and diabetes mellitus, 50
oxidation, 18, 47-48, 50, 211, 226, 405
smoking and, 130, 132, 153
vitamin C and, 98, 101-102, 104-105, 109, 132, 153
Low-fat diets, 226, 248, 356
Lowest-Observed-Adverse-Effect Level (LOAEL)
alpha-tocopherol, 255-257
extrapolation of NOAEL from, 162, 256-257
identification of, 89-90, 161-162, 255-256, 314
instead of NOAEL, 91
selenium, 314, 318
sensitive subpopulations and, 92
vitamin C, 161-162, 163
Lung cancer
beta-carotene and, 13-14, 340-341, 342-343, 345-346
smoking and, 36-39, 124, 213-214, 219, 360, 366-371, 372, 405, 406
Lung lesions, 254
oxidant scavengers, 95, 108
Lutein, 18, 44, 49, 329, 330, 332-333, 343, 348, 349, 350-351, 353, 355, 357, 358, 360-365, 366, 371, 454-455
Lycopene, 44, 329, 332-333, 344-345, 347, 349, 350, 353, 356, 357, 358, 360-365, 366, 368, 371, 456-457
Lycopenodermia, 368, 466
Lymphatic leukemia, 196
Lymphocytes
DNA damage, 110-111, 112, 114-115
vitamin C in, 99-100
Lysine, 98, 118-119
M
Macular Pigment Optical Density (MOPD), 349-350, 371
Major histocompatibility complex II, 338
Malabsorption syndromes, 202, 210-211, 404
Malnutrition, protein-energy, 202, 404
Malondialdehyde, 104-105, 116, 203, 334-335
Marathon runners, 117, 118-119
Margarine, plant sterol-enriched, 357
Men.
See also Gender
alcohol consumption, 361, 368
alpha-tocopherol, 49, 232-233, 235, 237, 245, 249, 260
carotenoids, 49, 338, 349, 351, 353, 359, 361, 368
cataracts, 49, 351
dietary intakes, 154, 165, 245
immune response, 338
Keshan disease, 301-302
kidney stone formation, 157
MOPD values, 349
smokers, 359
supplement use, 249, 260
vitamin C, 95, 117, 118-119, 121, 126, 133, 146, 148, 149, 154, 157, 165
Metabolism of nutrients
aerobic, 46
alpha-tocopherol, 195, 199-200, 208-210, 261
basal rate considerations, 24-25
carotenoids, 328-329, 350
copper, 129
drug, 99
gender differences, 20, 133, 292, 403, 407
iron, 129
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selenium, 285, 286, 299, 308
vitamin C, 12, 43, 95, 100, 108, 130, 133, 148, 152-153, 157, 158
Metalloenzyme reduction, 96, 97-98
Methionine, 284
Methionine sulfoxide, 45
Methodological considerations.
See also Data and database issues;
Extrapolation of data;
Indicators of nutrient adequacy;
Uncertainty
AIs, 63-66
alpha-tocopherol, 59, 65, 67, 68-69
animal studies, 58-59, 459
carotenoids, 16, 68-69, 339, 359, 404
children, 65-66
data limitations, 62-63
depletion/repletion studies, 59, 402-403
dietary intakes, 68, 69, 313, 359, 385-386
EARs, 65-66, 402-404
epidemiological studies, 127-128
in extrapolation of data, 62, 65-66
human feeding studies, 59
infants, 63-65, 66
intervention trials, 58, 61
kinetic modeling of body pools, 209-210, 403
laboratory assays, 67, 160, 404
lactation, 67
measurement errors, 68, 69, 313, 359, 385-386
nutrient intake estimates, 67-69, 247, 339, 385, 404-405
observational studies, 59-61, 127-128
pathways to nutrient requirements, 63
pregnancy, 67
randomized clinical trials, 61
RDAs, 66
in risk assessment, 458-461
types of data used, 58-63
vitamin C, 67, 68-69, 127-128, 139-140
weighing the evidence, 61-62
Minnesota Cancer Prevention Research Unit, 353
Monocyte adhesion, 103
Monounsaturated fatty acids, 226
Mortality from chronic disease, 14, 339-342, 351
MRC/BHF Heart Protection Study, 38-39
Multiple Risk Factor Intervention Trial, 343
Multiple sclerosis, 50
Myelin, 98
Myeloperoxidase, 108, 109, 140
Myocardial infarction, 36-41, 47, 159, 214-215, 216, 238, 241, 312, 347
Myocarditis, 287
N
National Cancer Institute, 154
Five-a-Day for Better Health Program, 351
National Health and Nutrition Examination Survey I (NHANES I), Epidemiological Follow-up Study, 122, 124, 126, 219
National Health and Nutrition Examination Survey II (NHANES II), 121, 152, 235, 248
National Health and Nutrition Examination Survey III (NHANES III)
anthropometric data, 31, 32-33
carotenoids, 330, 358, 361, 364, 369, 448-457
defined, 466
design, 69
energy intakes, 68, 69
fat intakes, 68, 69, 247, 396
selenium, 16, 69-70, 309, 310, 399, 428-431, 446-447
serum values of nutrients, 440-457
supplement data, 70
total intakes, 388, 389, 420-421, 426-427, 430-431
vitamin C, 15-16, 69-70, 133, 155, 165, 387-390, 391, 416-421, 440-443
vitamin E (all forms), 16, 68, 69-70, 210, 230, 233, 244, 245-246, 247, 248, 259-260, 394, 422-427, 444-445
National Health Interview Survey, 70, 249, 260, 310-311, 364-365
National Health Interview Survey Epidemiological Supplement, 249
National Nutrition Monitoring System, 383
Necrotizing enterocolitis, 253
Nervous system, 19, 50, 96, 98, 131, 153, 202
Neurodegenerative diseases
alpha-tocopherol and, 19, 50, 186, 202, 204-207, 218, 220, 221, 222, 231, 232
iron and, 221
lipid peroxidation and, 221-223
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oxidative stress and, 19, 50, 221-222
ROS and, 222-223
Neuroleptic drugs, 222-223
Neurons, 98, 131, 202
Neuropeptide biosynthesis, 98
Neurotransmitters, 95, 98, 153, 222-223
Neutrophils
vitamin C in, 12, 43, 95, 98, 99-100, 139, 140, 141, 143, 144-146, 150, 385
New York State Cohort Study, 123, 124
Niacin, 225
Nicotinamide adenine dinucleotide (NADH), 43, 96, 98, 224-225
Nicotinamide adenine dinucleotide phosphate (NADPH), 43, 96, 98, 224-225
Nitric oxide scavengers, 262
Nitric oxide synthesis, 103
Nitrosoproline, 106-107
Nitrotyrosine, 45, 102, 106-107, 116
No-Observed-Adverse-Effect Level (NOAEL)
alpha-tocopherol, 255-257
defined, 79, 466
extrapolation from LOAEL, 162, 256-257
identification of, 89-90, 255-256, 316
LOAEL used instead of, 91
selenium, 314, 316
sensitive subpopulations and, 92
subchronic to predict chronic, 91
vitamin C, 163
Norepinephrine, 96, 98
Normative requirement, 22
Nurses Health Study, 123, 125-126, 212, 351
Nutrient intakes.
See also Dietary intakes;
Exposure assessment;
individual nutrients
Canadian, 69, 154, 309, 438-439
cooking losses, 154, 356
day-to-day variation adjustments, 69, 385, 387, 390
extrapolation from subchronic to chronic, 257
form of, 83
geographic differences in, 284, 288, 309, 311-312, 315, 316, 317, 318-319
interpretation of, 385-359
methodological considerations, 67-69, 247, 339, 385, 404-405
public health implications, 404-405
quality of data, 385, 390
from supplements, 70, 155, 244-245, 249, 366
total calculated, 388, 389
U.S., 70, 416-431, 432-437
Nutrient-nutrient interactions.
See also specific entries under individual nutrients
adverse, 74
and bioavailability of nutrients, 83, 357-358
energy status and, 224-225
research recommendations, 20, 407
risk assessment, 83
Nutrition Canada Survey, 32
Nutrition During Lactation report, 28, 29
Nutrition labels, 16, 68, 194, 243, 393-394, 396
Nutritional Factors in Eye Disease Study, 365
Nutritional Prevention of Cancer Study, 38-39
O
O6-alkyltransferase, 106-107, 116
Obese individuals, 60, 385
Observational studies
alpha-tocopherol, 212-213, 219, 221
cancer, 219
of cardiovascular disease, 212-213
carotenoids, 338-339, 342-345, 346-347
hazard identification, 84
methodological issues, 59-61, 127-128
Oils, edible, 16, 68, 245, 246, 250, 396
Olestra, 357
Ophthalmoplegia, 202
Oropharyngeal cancers, 17, 341, 344, 346
Osmotic diarrhea, 13, 95, 100, 154, 161-162, 163, 166, 386, 393
Oxalate excretion, 156
Oxidant damage, 44-51
Oxidant scavengers, 95, 102, 108, 116, 124
Oxidative stress
in adults (51+ years), 51, 148, 242
and age-related macular degeneration, 18-19, 49
aging and, 44, 51
alpha-tocopherol and, 44-45, 51, 52, 203, 211, 217-218, 221, 222, 223, 242, 261
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and asthma, 126
and cancer, 17, 46-47, 218-219
and cardiovascular disease, 18, 47-49, 50, 101-102, 225
carotenoids and, 332
and cataracts, 18, 49, 350
cholestatic liver disease and, 202, 203
copper and, 203
defined, 44, 466
and diabetes mellitus, 19, 50-51, 217-218
and DNA damage, 46-47, 109
glutathione and, 128, 129, 244
indicators of, 20, 45-52, 102, 103, 109, 126, 128, 203, 217, 223, 407
mechanisms in, 44-45, 46, 47, 50
and neurodegenerative disease, 19, 50, 221-222
physical exercise and, 242
protective enzymes, 45
selenium, 41, 43, 44-45, 52, 285
smoking and, 43, 48, 102, 130, 131, 132
vitamin C and, 12, 43, 95, 101-102, 109, 126, 128, 130, 131, 132, 148, 152, 162, 166
8-Oxy-7,8-dihydro-2′deoxyguanosine (8-oxodG), 46, 110, 112, 466
Oxygen demand, 156, 161
Oxygen radical absorbance capacity (ORAC) assay, 46
Ozone, 108
P
Pancreatic cancer, 124
Parkinson's disease, 19, 50, 221-222
Passive smokers, 132, 146, 153
Pauling, Linus, 126-127
Pectin, 357
Pentane, 203, 231, 334-337
Peptide hormones, amidation of, 96, 98
Peptidyl-glycine monoxygenase, 96
Periodontal health, 120, 156, 160, 161, 166
Peripheral artery disease, 216
Peroxynitrate, 45
Phospholipase A2, 196, 212, 223
Phospholipid transfer protein, 197
Photosensitivity disorders, 366
Physical exams, 164
Physical exercise, 153, 242
Physicians' Health Study I, 38-39, 345-346, 367
Physicians' Health Study II, 40-41, 252
Plant phenolic compounds, 225
Plasma concentration of nutrients.
See individual nutrients
Platelet effects, 196, 211, 212, 218, 253
Polyp Prevention Study, 36-37
Polyunsaturated fatty acids (PUFAs)
alpha-tocopherol and, 38-39, 195, 215, 225-226, 233, 235, 248
metabolism, 226
Pregnancy.
See also Lactation;
individual nutrients
alcohol and drug abuse, 150
aspirin use, 150
derivation of DRIs for, 67
eclampsia, 149
lipid peroxidation and, 150-151
methodological considerations, 67
premature birth, 149
and smoking, 132, 149, 150-151
special considerations, 150-151
ULs, 82
Probucol, 357
Proline, 98, 99, 106-107, 118-119
Pro-oxidant effects of nutrients, 129, 156, 159-160, 161, 166
Prostacyclin, 196, 212, 223
Prostaglandin synthesis, 99
Prostate cancer, 213-214, 219, 220, 290-291, 344-345, 368, 371
Protein, dietary
oxidation, 222
requirements for growth, 66
Protein-energy malnutrition, 202, 404
Protein kinase C inhibitors, 196, 211, 223
Proteoglycans, 98
Puberty.
See also Adolescents
pubertal development, 30, 33
Q
Quercetin, 129
R
Race/ethnicity
and puberty onset, 30
and smoking, 132
and vitamin C, 132
Radiation, ionizing, 46, 112, 130
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Randomized clinical trials, 61
Reactive nitrogen species (RNS)
and cardiovascular disease, 216
and DNA damage, 116
measure of activity, 102, 106-107, 116
mechanism of action, 44
myeloperoxidase-derived, 109, 140
vitamin C and, 98, 102, 106-107, 109, 124, 140
Reactive oxygen species (ROS)
and cardiovascular disease, 216
and gastric cancer, 106-107, 116, 124
and infectious and inflammatory stresses, 103
mechanism of action, 44
and neurodegenerative diseases, 222-223
smoking and, 131
sources of, 46
vitamin C and, 98, 102, 103, 106-107, 116, 124, 131
Recommendations.
See also Research recommendations
food composition data, 19, 396-397
Recommended Dietary Allowances (RDAs).
See also individual nutrients
AI compared, 4, 25-26, 138
children, 66
coefficient of variation, 66
criteria used to derive, 10-11
defined, 3, 5, 7, 22, 23, 24
EAR and, 2-4, 23-25
indicators of nutrient adequacy, 6-13
method used to set, 23-25, 66
uses, 4, 15, 23, 383, 391, 392
Recommended Dietary Allowances (reports), 21
Reference body weight ratio method, 65-66
alpha-tocopherol, 231
selenium, 299
vitamin C, 138
Reference weights and heights, 31-32
Renal disease/failure, 31, 50, 312
vitamin C and, 157, 160, 164
Reproductive disorders, 368
Requirement, defined, 21
Research recommendations
adverse effects, 21, 406
alpha-tocopherol, 2, 20, 260-262, 406-407
approach to setting, 19-20, 401-402
carotenoids, 2, 20, 371-372, 403-404, 406-407
dietary intakes, 165-166, 406
kinetic modeling of body pools, 403
priorities, 20, 140, 406-407
selenium, 2, 20, 318-319, 406-407
vitamin C, 2, 20, 140, 165-166, 406-407
Respiratory burst, 108
Respiratory distress syndrome, 108, 312
Retinaldehyde binding protein, 197
Retinol/retinoic acid, 36-37, 328, 332, 355, 356, 367
Retinopathy, 50, 202, 208-209, 259, 368
Rheumatoid arthritis, 108
Riboflavin, 225
Risk assessment, defined, 75, 467
Risk assessment models.
See also Dose-response assessment;
Exposure assessment;
Hazard identification;
Risk characterization
application to nutrients, 80-83
basic concepts, 13, 75-76
bioavailability considerations, 82-83
default options, 460
defined, 75, 467
and food safety, 75-80
inference options, 460
methodological considerations, 458-461
nutrient interactions, 83
process, 76-78
sensitivity of individuals, 82
special problems with nutrients, 80-81
thresholds, 78-80
uncertainties, 76, 79-80, 458-461
Risk characterization, 92-94
alpha-tocopherol, 260
carotenoids, 369-371
defined, 75, 77, 78, 467
process, 92-93
selenium, 13, 317-318
vitamin C, 165
Risk management, 76, 467
S
Scurvy
infants, 135, 159, 161, 162, 163-164, 166
rebound, 156, 158-159, 162, 163, 166
vitamin C deficiency and, 98, 100, 101, 119, 120, 135, 139, 145, 150, 156, 158-159, 162, 163, 166
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Selenium, 284-324
absorption, 285-286, 306
adolescents, 287, 299-300, 306, 307, 308, 315-316
adults (19-50 years), 284, 300-305, 306-308, 313-315, 399
adults (51+ years), 70, 305-306
adverse effects, 284, 311-313, 399, 407
AIs, 10-11, 65, 292-299, 507
animal studies, 287, 290, 301, 302
bioavailability, 284, 291-292, 306, 307, 399
in blood, 288-289, 301-302, 310, 312, 313, 314, 318, 446-447
body stores, 286, 313
breath excretion, 313
and cancer, 36-41, 290-291, 319, 367
and cardiovascular disease, 40-41, 287, 288
children, 25, 65, 287, 288, 292, 299-300, 301-302, 315-316, 318, 403
critical endpoint, 313
deficiency, 43, 287, 298
dose-response assessment, 313-316
in drinking water, 309-310, 311, 317, 399
EARs, 10-11, 25, 299-304, 305, 306, 307
excretion, 285, 286-287, 291, 313
exposure assessment, 317
factors affecting requirements, 291-292
fetal, 67, 306
food sources, 286, 292, 298-299, 308, 309, 397
forms of, 285-286, 308, 312, 314, 468
in fortified foods, 286, 310, 399
functions, 43, 284, 285, 302
gender and, 292, 299, 403
geographic differences, 284, 309, 311-312, 315, 316, 317, 318-319
in hair and nails, 288, 313, 399
hazard identification, 311-313
in human milk, 292-298, 307, 315, 316, 386
indicators of adequacy, 10-11, 12, 43, 287-291, 301-302, 312-313, 318
infants, 65, 287, 292-299, 307, 315-316, 386, 392, 399
intakes, 16, 284, 308-311, 317, 397-399, 428-431
interaction with other nutrients, 36-37, 40-41, 285, 290, 367
intervention studies, 2, 36-41, 290, 303-304, 311, 318, 319, 367, 405
and Kashin-Beck disease, 12, 43, 287, 465
and Keshan disease, 12, 43, 287, 288, 292, 299-300, 301-302, 304, 403, 465
lactation, 67, 293, 294-297, 307-308, 315
by life-stage group, 10-11, 14, 292-308, 313-316, 428-431, 446-447
and lipid peroxidation, 287
metabolism, 285, 286, 299, 308
method used to set AI, 65, 292-298
NOAEL/LOAEL, 314, 316, 318
and oxidative stress, 41, 43, 44-45, 52, 285
pregnancy, 67, 287, 306-307, 315
radiolabeled, 291
RDAs, 2, 10-11, 12, 284, 300, 304-307, 308, 318, 507
research recommendations, 20, 318-319
smokers, 367
soil content, 16, 293, 298, 308, 397
supplements, 286, 292, 310-311, 312, 317, 399
and thyroid disorders, 287
ULs, 13, 14, 26-27, 284, 311-318, 391, 399
uncertainty assessment, 314, 315, 316
Selenocysteine, 284, 285, 286, 289, 291-292, 308, 399, 468
Selenomethionine, 284-285, 286, 289, 291, 303, 307, 308, 312, 313, 314, 399, 468
Selenophosphate synthetase, 285
Selenoprotein P, 289, 290, 301-302
Selenoproteins
absorption, 285
antioxidant role, 41, 44-45, 284, 285
in blood, 288, 289-290, 303, 304, 310
defined, 285
functions, 12, 43, 285, 318
as indices of selenium status, 12, 43, 301-302, 312-313
sources, 284-285
synthesis, 286, 289, 291, 301
Selenosis, 284
acute, 312
biochemical indicators of, 312-313, 315
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chronic, 311-312
defined, 468
form of intake and, 312, 314
overt signs of, 315
risk characterization, 13, 317-318
Semen, 98
Sensitivity
delayed dermal, 117, 118-119, 220
interindividual variability, 91, 82, 257
Sepsis, 253
Serum
alpha-carotene, 450-451
alpha-tocopherol, 236, 444-445
beta-carotene, 448-449
beta-cryptoxanthin, 452-453
cholesterol, 235
lutein and zeaxanthin, 454-455
lycopene, 456-457
vitamin C, 121, 132, 133, 152, 153, 156, 440-443
vitamin E (all forms), 444-445
Sjögren's syndrome, 101
Skeletal myopathy, 202
Skin cancer, 36-39, 290, 339
Skin Cancer Prevention Study, 36-37
Smokers and smoking
and alpha-tocopherol, 36-37, 213-214, 216, 219, 238, 242-243, 252, 367, 406
AMD, 18, 49
cardiovascular disease, 37-39, 48-49, 103, 106-107, 131, 216, 238, 252, 347
and carotenoids, 18, 36-39, 49, 330, 331, 334-337, 344, 345, 347, 351, 359, 366-371, 372, 405, 406
cataracts, 351
dietary intakes, 130, 359, 360
DNA damage, 110-113, 130-131, 360
endothelium dependent vasodilation, 106-107, 131
lactating, 132
LDLs, 130, 132, 153
lipid peroxidation, 104-105, 130, 131, 132, 150-151
lung cancer, 36-39, 124, 213-214, 219, 360, 366-371, 372, 405, 406
metabolism of nutrients, 43
organic free radicals per puff, 132
and oropharyngeal cancers, 344
oxidative stress, 43, 48, 102, 130, 131, 132
passive, 132, 146, 153
pregnant, 132, 149, 150-151
prostate cancer, 219
racial/ethnic differences, 132
research needs, 403
and ROS, 131
and selenium, 367
special considerations, 150-151, 152-153, 160-161, 164-165
and vitamin C, 12, 43, 95, 102, 103, 104-105, 108, 110-113, 124, 130-132, 146, 149, 150-151, 152-153, 242, 390, 393
Socioeconomic status, and nutrient status, 101, 136-137
Special considerations
adolescents, 358
alcohol and drug abusers, 150, 360
alpha-tocopherol, 241-243, 259
body size and composition extremes, 242
cancer, 241
cardiovascular disease, 241-242
carotenoids, 358-360
drug interactions, 150, 259
emotional stress, 153
glucose-6-phosphate dehydrogenase deficiency, 160-161, 164
hemochromatosis, 160, 164
identification of, 87-88
infants, 160, 259
and NOAEL/LOAEL, 92
passive smokers, 153
physical exercise, 153, 242
in pregnancy, 150
renal disorders, 160, 164
smokers, 150-151, 152-153, 242-243, 359-360
ULs, 87-88, 92, 164-165, 259
vitamin C, 150-151, 152-153, 160-161, 164-165
vitamin K deficiency, 259
Sperm, 8-oxodG, 109, 110-111
Spinocerebellar ataxia, 202
Steroid hormone biosynthesis, 96, 98, 99, 153
Stomach cancer.
See Gastric cancer
Stroke, 36-41, 121, 214, 216, 252, 254, 346-347, 406
Superoxide, 103, 140-141, 211, 223
Superoxide dismutase, 45, 222
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Supplements, dietary.
See also individual nutrients
bioavailability of nutrients, 191, 224, 251, 355, 357, 399
data sources on intake, 70
form of nutrient in, 192, 251, 286, 292, 312, 399
gender differences, 70, 246-247, 260
intakes from, 70, 155, 244-245, 249, 310-311
multivitamin, 244, 246-247, 310, 386, 395
quality of, 317
shelf life, 190-191
ULs and, 5, 26, 74, 155, 165, 249, 259, 310, 317, 396, 397
units, 191, 244-245, 394-397
usage, 70
SUVIMAX, 40-41
Systemic conditioning, 156, 158-159, 161
T
Tardive dyskinesia (TD), 222-223
Teratogenicity of nutrients, 315
Thiobarbituric acid reactive substances (TBARS), 45, 103, 104-105, 131, 203, 217, 334-335, 468
Thioredoxin reductases, 285
Thrombin, 211, 223
Thrombophlebitis, 253
Thromboxane, 217
Thyroid disorders, 287, 315
Tocopherol.
See Alpha-tocopherol;
Vitamin E
Tocotrienols.
See Vitamin E
Toddlers, 29-30
Tolerable, defined, 26, 73
Tolerable Upper Intake Levels.
See also Dose-response assessment;
Hazard identification;
Risk assessment models;
individual nutrients
appropropriateness of intakes above, 13, 27, 74, 155, 165, 249, 260, 311, 317-318, 369-371
children, 33
critical endpoints, 88-89
defined, 3, 4, 5, 7-8, 26, 73, 91-92, 468
derivation of, 7-8, 13, 26, 75, 80-83, 91-92, 162, 257, 315, 316
development steps, 84-92
fortification of foods and, 5, 26, 74
by life-stage groups, 14
supplement use and, 5, 26-27, 80-81
uses, 5-6, 15, 74, 383, 386, 391, 392-393, 398
Total Antioxidant Capacity, 104-105
Total radical-trapping antioxidant capability (TRAP) assay, 45
Toxicity
experimental data, 86
mechanism of action, 87
Triiodothyronine, 315
Trolox equivalent antioxidant capacity (TEAC) assay, 46
Tropical sprue, 220
Tumor necrosis factor-alpha, 338
Tyrosine metabolism, 45, 96
U
Ubiquinols, 224
Uncertainty
alpha-tocopherol, 91, 231-232, 256-257
assessment, 90-91, 162, 256-257, 315, 316
dose-response assessment for ULs, 88-92
in dietary assessment methods, 68, 248, 385, 396
extrapolation from experimental animals to humans, 76, 79, 91
factor, 79, 89, 90-91, 162, 256-257, 315, 468
in risk assessment, 76, 79-80, 458-461
selenium, 315, 316
sources of, 256, 314, 386
vitamin C data, 139-140, 162
United States Pharmacopeia, 191
Uric acid excretion, 156, 157
U.S. Department of Agriculture, 69, 135, 154, 343, 361
U.S. Department of Health and Human Services, 69
U.S. Dietary Guidelines, 351
U.S. Health Professionals Follow-up Study, 122, 290, 344, 347, 351
V
Vascular cell adhesion molecule-1 (VCAM-1), 196, 212, 223
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Vasodilation
alpha-tocopherol and, 196, 210
endothelium-dependent, 106-107, 131
smoking and, 131
vitamin C and, 103, 106-107, 131
Vegans/vegetarians, 247, 297, 309
Vegetables.
See Fruits and vegetables
Very low density lipoproteins, 104-105, 197
Vitamin A
carotenoids and, 12-14, 36-37, 43-44, 325, 326, 327, 328, 330, 331, 338, 343, 352, 355, 356, 366, 367, 371, 372, 403, 467
children, 338, 356
deficiency, 43, 325, 338, 356, 371
and DNA damage and repair, 112-113
intakes, 352
and lactation, 355
vitamin C and, 112-113
Vitamin B12, 156, 158, 161
Vitamin C (ascorbic acid), 95-185.
See also Dehydroascorbic acid
absorption and transport, 99-100, 103, 108, 128, 140, 147-148, 155, 157
adolescents, 65, 138-139, 149-151, 162-163
adults (19-50 years), 12, 95, 121-122, 126, 139-147, 149-151, 154, 157, 161-162, 386, 387-390, 391, 392, 393, 438-439
adults (55+ years), 101, 118-119, 121, 133, 147-149, 154, 155, 157, 438-439
adverse effects, 13, 95, 100, 155-161, 386, 407
AIs, 6-7, 134-138, 507
and alcohol/drug abuse, 101, 150
allergic response, 160, 161
animal studies, 59, 103, 120, 131, 140
antioxidant role, 43, 44-45, 52, 95, 96, 98-99, 101-109, 116, 124-125, 139-143, 146, 154, 166
and asthma, 126
and attention-deficit disorder, 163
and beta-carotene, 102, 109, 110-111
bioavailability, 99, 128
and blood coagulation, 99, 101
body pool, 100, 103, 132, 140, 142, 145, 152-153, 166, 225, 403
and bone growth, 101
and cancer, 36-37, 40-41, 106-107, 113-116, 123-125, 127, 128, 160
and cardiovascular disease, 18, 38-41, 101-102, 103, 106-107, 109, 121-122, 127, 128, 131, 346-347
and carnitine biosynthesis, 95, 96, 99, 120, 153, 166
and cataracts, 18, 98, 125-126, 127
chemistry, 95-96, 97
children, 25, 65, 138-139, 161, 162-163, 166
and cholesterol, 99
and chronic obstructive pulmonary disease, 126, 127
and cognitive function, 19, 50, 127
and collagen metabolism, 95, 96, 98, 99, 101, 118-119, 166
and common cold, 117, 126-127, 163
and connective tissue synthesis, 98, 101
and copper, 96, 97-98, 128, 129, 156, 159-160, 161
data selection, 161
deficiency effects, 98, 99, 101, 108, 119, 120, 145, 148, 149
and dental enamel erosion, 156, 160, 161
dependence, 156, 158-159, 162, 163, 166
depletion/repletion studies, 108, 117, 140, 143-145, 148, 402-403
and DNA damage and repair, 98, 106-107, 109-115, 116, 130-131, 160
dose-response assessment for ULs, 161-165
EARs, 6-7, 23, 45, 65, 139, 146-151, 390
emotional stress and, 153
and endothelial dysfunction, 103, 106-107, 131
erythrocyte, 140
excretion, 12, 43, 95, 100, 140, 142, 144, 147, 148, 151, 157, 158, 164
exposure assessment, 165
and factors affecting requirement, 128-133
fetal, 67, 149, 150, 163, 166
and flavonoids, 98-99, 102, 128, 129
food sources, 101, 130, 154, 392
functions, 12, 43, 95, 96-99, 165-166
gastrointestinal effects, 95, 100, 102, 106-107, 124-125, 156, 161-162, 163, 166, 386, 393
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gender and, 2, 12, 65, 95, 101, 121, 122, 124, 126, 133, 146-147, 154, 387-390
and glucose-6-phosphate
dehydrogenase deficiency, 160-161, 164
and glutathione, 43, 96, 98, 99, 103, 105, 109-110, 126, 128, 129
hazard identification, 155-161
and hemostatic dysfunction, 131
and high-altitude resistance, 160
in human milk, 101, 132, 134-138, 151, 164, 386
and immune function, 108, 117-119, 127
indicators of adequacy, 6-7, 11, 101-128
infants, 65, 101, 129, 134-138, 159-160, 161, 162, 163-164, 386, 392
and inflammatory stress, 103, 108, 130
intakes, 15-16, 95, 135, 138, 154-155, 165-166, 387-390, 393, 416-421, 432-435, 438-439
interaction with drugs, 99, 150
interaction with other nutrients, 38-41, 96, 97-99, 102, 109, 110-113, 118-119, 120, 128-129, 156, 158, 159, 160, 161, 164, 166, 224-225, 285, 332
international comparisons, 121, 123, 124, 127, 135, 153
intervention trials, 38-39, 405
intracellular recycling, 108
and iron, 96, 97-98, 99, 109, 118-119, 120, 128, 129, 158, 159, 160, 161, 164, 166
and kidney stone formation, 156, 157, 160, 161
laboratory values, 67
and lactation, 67, 134-135, 136-137, 151-152, 164
and LDLs, 98, 101-102, 104-105, 109, 132, 153
in leukocytes, 43, 95, 103, 108-109, 110-111, 130, 133, 139, 140, 141, 142, 144, 146, 147, 148, 150
by life-stage group, 6-7, 14, 134-153, 161-164, 416-421, 432-435, 440-443
and lipid peroxidation, 45, 95, 98, 102, 104-105, 109, 116, 130, 131, 132, 146, 150-151, 153, 159
in lymphocytes, 99-100
metabolism, 12, 43, 95, 100, 108, 130, 133, 148, 152-153, 157, 158
method used to set AIs, 134-138
method used to set EARs, 139-145, 147-148, 149-151
methodological issues, 67, 68-69, 127-128, 402-403
and nervous system, 19, 50, 96, 98, 131, 153
in neutrophils, 12, 43, 95, 98, 99-100, 139, 140, 141, 144, 145, 146, 150, 385
NOAEL/LOAEL, 161-162, 163
and osmotic diarrhea, 13, 95, 100, 154, 161-162, 163, 166, 386, 393
and oxalate excretion, 156
and oxidative stress, 12, 43, 95, 101-102, 109, 126, 128, 130, 131, 132, 148, 152, 162, 166
and oxygen demand, 156, 161
passive smokers, 132, 146, 153
and periodontal health, 120, 156, 160, 161, 166
and physical exams, 164
and physical exercise, 153
plasma concentrations, 100, 101, 121, 123, 126, 127, 128, 130, 132, 133, 134-135, 140, 141, 142, 144, 146, 147, 148, 155, 158
and pregnancy, 67, 82, 132, 149-151, 159, 161, 163-164, 166
pro-oxidant effects, 129, 156, 159-160, 161, 166
race/ethnicity and, 132
RDAs, 2, 6-7, 12, 43, 95, 138, 139, 147, 149, 150, 151-152, 386, 392, 507
and renal disease, 157, 160, 164
research recommendations, 2, 20, 140, 165-166
and respiratory distress syndrome, 108
and rheumatoid arthritis, 108
risk characterization, 165
RNS/ROS and, 98, 102, 103, 106-107, 109, 116, 124, 131, 140
and scurvy, 98, 100, 101, 119, 120, 135, 139, 145, 150, 156, 158-159, 162, 163, 166
serum concentrations, 121, 132, 133, 152, 153, 156, 440-443
smokers, 12, 43, 95, 102, 103, 104-105, 108, 110-113, 124, 130-132, 146, 149, 150-151, 152-153, 242, 390, 393
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socioeconomic status and, 101, 136-137
special considerations, 150-151, 152-153, 160-161, 164-165
and steroid hormone biosynthesis, 96, 98, 99, 153
supplements, 70, 155
systemic conditioning, 156, 158-159, 161
turnover, 43, 95, 130-131, 152-153, 158
ULs, 13, 14, 26-27, 82, 95, 155-165, 391, 393
uncertainties in data, 140, 162
and uric acid excretion, 156, 157
and vitamin A, 112-113
vitamin E and, 98-99, 102, 109, 110-113, 128, 129, 213, 224-225
and vitamin B12, 156, 158, 161
Vitamin E (all forms), 186-293.
See also Alpha-tocopherol
absorption, 191, 193, 196, 243
affinity of alpha-TTP to forms of, 2, 12, 19, 193, 195, 197-198, 243, 262
bioavailability, 193, 194-195, 243, 404
body pools, 210
conversion factors, 244-245, 394-395
defined, 187, 393
food composition data, 68-69, 393-394
forms of, 2, 12, 16, 186, 187-190, 193, 194-195, 210, 243, 262, 393-394, 404, 406
in human milk, 227, 228-229
intakes, 68, 69-70, 186, 194, 232, 243, 393-394, 395-396, 404, 406, 422-423
interconversion of units, 191-192, 244, 246
serum values, 444-445
shelf life, 190-191
structure, 187-195
units of activity, 186, 190 n.1, 191-195
Vitamin K, 252, 254-255, 256, 259
W
Warfarin therapy, 252
Weight.
See Body weight;
Reference weights and heights
Western Electric cohort study, 121-122, 341
Women.
See also Gender;
Lactation;
Pregnancy
alpha-tocopherol, 40-41, 212, 219, 226, 237, 245, 246-247, 249, 259-260
aspirin, 40-41
breast cancer, 123, 219
cardiovascular disease, 38-41, 121, 122, 212, 347
carotenoids, 38-41, 330-331, 349, 351
cataracts, 126, 351
cervical cancer, 17, 123, 340-341, 345, 346
dietary intakes, 154, 165, 245
fish oil supplements, 226
Keshan disease, 292, 304
kidney stone formation, 157
MOPD values, 349
postmenopausal, 122, 123, 212, 219, 226, 259-260, 330-331, 347
selenium,292
supplement use, 249, 260
vitamin C, 40-41, 95, 118-119, 122, 123, 126, 133, 146-147, 149, 154, 157, 165, 386
Women's Antioxidant Cardiovascular Study, 40-41, 252
Women's Health Study, 40-41, 252
World Health Organization
definition of adverse effect, 73
Monitoring Cardiovascular Project, Vitamin Substudy, 346
uncertainty factors, 79
X
Xanthophylls, 329, 330
Z
Zeaxanthin, 18, 44, 49, 329, 330, 348, 349, 350, 351, 358, 360-361, 364, 366, 371, 454-455
Zinc, 40-41
Representative terms from entire chapter:
oxidative stress
