Index
A
Abortion, spontaneous, 258
Absorption of nutrients. See also Bioavailability of nutrients;
Malabsorption syndromes
biotin, 376
choline, 392–393
folate, 1, 8–9, 198, 211, 212, 233, 256, 259
niacin, 124–125
sensitivity considerations, 48
vitamin B12, 33, 306, 307–309, 313, 317, 318, 320, 322, 328, 330, 331, 333, 334, 339, 429
Acetaldehyde, 164
Acetaminophen, 212
Acne, 346
Adenosine diphosphate (ADP) ribosylation, 127, 145
Adequate Intakes (AIs). See also specific nutrients
applicable population, 18
derivation of, 5, 21, 29–31, 33
extrapolation from other age groups, 21, 31–33
increasing consumption of nutrients, 14–15
indicators used to set, 7, 10, 11, 22–23
methods used to set, 5, 22–23, 31–33
risk of inadequacy, 19
weight and height and, 26
Adolescents, 14 through 18 years. See also Children;
Life-stage groups;
Puberty/pubertal development;
individual nutrients
EARs, 31–32
lactation, 78, 112, 136–137, 143–144, 178–179, 186–187, 238–240, 280–281, 341–342, 368, 383, 406, 412
pregnancy, 76–78, 110–111, 135–136, 143–144, 176–178, 186–187, 233–238, 280–281, 339–341, 367, 382–383, 404– 406, 412
RDAs, 32–33
Adults, 19 through 50 years
AIs, 21
derivation of DRIs for, 21, 32
EARs, 8–9
extrapolation of data to other age groups, 31–33, 66
supplement use, 272
Adults, 51 through 70 years
AIs, 21
ULs, 48–49
Adults, >70 years
EARs, 8–9
pernicious anemia in, 317, 332–333
supplement use, 18, 79, 81, 113, 182, 273, 346, 462–465
ULs, 48
biotin, 384–385
defined, 41
evidence of, 50–51
folate, 273–277
interindividual variability in sensitivity, 48–49
nutrient-nutrient interactions, 41, 49, 51, 273–274
pantothenic acid, 370
research recommendations, 15, 441–442
source of nutrient and, 47–48
vitamin B12, 346
African Americans. See Blacks
Aging. See also Life-stage groups;
individual life stages
and energy metabolism, 75, 110
and metabolism of nutrients, 213–214, 228–229, 233
and nutrient requirements, 318–320
and nutrient toxicity, 48
and plasma homocysteine, 159, 203, 518–519
Alanine aminotransferase, 157, 390, 394, 395, 403
Alcohol consumption and alcoholism and folate, 204, 211, 240, 263, 266, 268, 276, 525
and vitamin B6, 164
and vitamin B12, 347
Allergic sensitivity, 81–82
American Academy of Pediatrics, 30, 31
Amino acid metabolism, 58, 88, 150, 151, 161, 196, 197, 358.
See also individual amino acids
Aminopterin, 246
Anaphylaxis, 81
Anemia, 90, 153, 200, 201, 233, 234, 267, 329, 334.
See also Pernicious anemia
Aneurin. See Thiamin
Animal studies
choline, 396, 397, 398, 399, 413–414
considerations in use of data from, 53
extrapolation of data from, 28, 43–44, 46, 52, 55, 56, 153
neural tube defects, 244, 245, 523–525
vitamin B12 deficiency, 274, 310, 346
Anticonvulsants, 212, 240, 246, 276, 380, 525
Anti-inflammatory drugs (nonsteroidal), 212
Apotyrosine decarboxylase assay, 156
Arnold Chiari malformation, 241
Asians, pernicious anemia, 317
Aspartate aminotransferase, 157
Aspirin, 212
Atherosclerosis, 260
Atrophic gastritis, 200, 312, 317, 318, 320, 331, 337, 340, 341, 342, 527
B
Betaine, 392, 393, 398, 399, 413
Bioavailability of nutrients
factors affecting, 18, 62, 309, 338, 342, 375
folate, 8–9, 15, 16, 196, 208–210, 211, 221, 227, 235, 239, 256, 428
form of intake and, 15, 16, 88, 208– 210, 211, 221, 235, 239, 343, 428
methodological issues, 210, 225
nutrient-nutrient interactions and, 15
pantothenic acid, 361
from supplements, 1, 9, 18, 49, 208, 210, 235, 256, 259, 331, 334
thiamin, 62
vitamin B6, 150, 160–161, 165, 177
vitamin B12, 309, 328, 338, 342, 343
BioRad Quantaphase Radioassay, 206
Biotin, 374–389
absorption, 376
adults (19–50 years), 374, 380, 382–383, 385
adverse effects, 384–385
AIs, 6, 11, 21, 374, 380–383, 566–567
assay methods, 379
children, 381
dose-response assessment for ULs, 385
elderly (>70 years). See Adults, >70 years
exposure assessment, 385
factors affecting requirement, 380
food composition data, 35, 36, 37, 459
food sources, 384
gender differences, 382
hazard identification, 384–385
and 3-hydroxyisovalerate, 375, 378–379, 382, 383
indicators of adequacy, 11, 378–379
infants, 6, 56, 374, 377–378, 380–381
laboratory values, 452, 457, 459
lactation and, 383
life-stage group and, 38–39, 380–383
metabolism, 377
methods used to set AIs, 380–383
neurological disorders, 377
and odd-chain fatty acid composition of plasma lipids, 379
older adults (51+ years), 382
plasma concentrations, 379
pregnancy and, 33, 380, 382–383, 385
research recommendations, 385–386, 440
risk characterization, 385
special considerations, 383
transport, 376–377
unit conversions, 452
Biotin deficiency facies, 377–378
Blacks
glucose-6-dehydrogenase status, 108
homocysteine levels, 158
pernicious anemia, 317
vitamin B6, 174
Blood pressure. See Hypertension
Body weight. See also Reference body weight ratio method
and nutrient deficiency development, 129 n.1
reference weights, 24–26
thiamin pyrophosphate and, 75
Boston Nutritional Status Survey, 36–37, 79, 81, 138, 181, 182, 272, 273, 345, 346, 369, 384, 407, 460–465
Breastfeeding. See Human milk;
Lactation
“Burning feet” syndrome, 359
C
Canada
dietary intake data, 37, 58, 74, 79, 113, 123, 138, 150, 181, 272, 282, 306, 343, 369, 384, 502–506
neural tube defects, 242
weights and heights, reference, 24
Canadian Paediatric Society, 30, 31
Cancer. See also individual sites
dysplasia and metaplasia, 264–265
folate and, 12, 196, 204, 205, 264–266, 269, 276
vitamin B12 and, 264, 317, 346
Carbohydrate metabolism, 58, 63, 94, 95– 96
Cardiovascular disease. See Coronary heart disease;
Vascular disease and thrombosis
Carpal tunnel syndrome, 182, 184, 187
Cataracts, 94
Causality, 51
Cervical neoplasia, 264–265, 266
Children, ages 1 through 8 years. See also Life-stage groups;
individual nutrients
derivation of DRIs for, 21, 31–33
ULs, 56
Choline, 390–422
absorption, 392–393
adolescents, 56, 402–403, 404–406, 411– 412
adults (19–50 years), 2, 21, 390, 403– 404, 410–411
adverse effects, 390, 408–410, 411
AIs, 6, 21, 33, 390, 401–406, 566–567
and alanine aminotransferase levels, 390, 394, 395, 403
animal studies, 396, 397, 398, 399, 413– 414
and betaine, 392, 393, 398, 399, 413
bioavailability, 400, 402, 413
and cardiovascular disease, 398
chemistry, 391
children, 56, 392, 402–403, 411–412
and chronic disease risk reduction, 397–398
critical endpoint, 410
data selection, 410
and dementia, 397
dose-response assessment for ULs, 410– 412, 413–414
drug interactions, 399
elderly (>70 years). See Adults, >70 years
and embryogenesis, 404–405
excretion, 392
exposure assessment, 412–413
factors affecting requirements, 398–400
food composition data, 35, 36, 37, 459
food sources, 406–407
function, 11, 27, 390–391, 392
gender differences, 399–400, 403, 404
hazard identification, 408–410, 411
homocysteine and, 27, 398, 413
indicators of adequacy, 11, 23, 390, 396–398
infants, 6, 392, 393, 401–402, 406, 411– 412
intakes, 406–407
interaction with other nutrients, 391– 392, 394, 398–399, 400, 413
life stage and, 400–406, 410–412
and liver dysfunction, 11, 390, 391–392, 393, 394, 396–397, 398, 408, 409
method used to set AIs, 21, 33, 401– 404, 406
neurological disorders, 407
NOAEL/LOAEL, 410
older adults (51+ years), 392, 403–404
physical exercise and, 400
plasma concentrations, 11, 395–396, 397, 405
pregnancy, 33, 400, 404–406, 411–412
research recommendations, 413–414, 440
risk characterization, 413
serum concentrations, 392
special considerations, 402, 409, 412
uncertainty assessment, 410
unit conversions, 452
Chrome detoxification, 116
Chronic disease. See also specific diseases
risk reduction as indicator of nutrient adequacy, 7, 12, 15, 23, 28, 94, 159– 160, 205, 397–398, 441
Chronic ulcerative colitis, 213, 265–266
Clomiphene, 246
Cognitive function, 160, 268, 311
Colorectal cancer, 12, 265–266
Congenital anomalies (non-NTD), 183, 186, 259–260
Continuing Survey of Food Intakes by Individuals (CSFII)
choline, 407
quality of food composition data, 36, 37, 38
vitamin B6, 179, 180–181, 472–473
vitamin B12, 342–343, 344, 345, 476–477
Convulsions, 153, 166–167, 178, 187
Coronary heart disease, 159–160, 260
Creatinine excretion, 34, 63, 67, 92, 109, 126, 364, 365
Critical endpoints
choline, 410
defined, 53
folate, 277
vitamin B6, 183
Crohn’s disease, 342
CSFII. See Continuing Survey of Food Intakes by Individuals
Cystathionine β-synthase, 244, 245, 260
D
Data and database issues
availability of data, 2, 11, 13, 15, 37–38
choline, 11, 392, 398, 407, 412–413
food composition data, 37–38, 206–207, 368–369, 434
nutrient intakes, 35–36, 37, 265, 272
quality and completeness of data, 7, 28–29, 35–36, 52, 265, 337, 366
search strategies, 453–455
selection for dose-response assessment for ULs, 53, 142, 184, 277, 410
Defined nutritional states, 21
Dementia, 397
Depletion-repletion studies
folate, 221–225, 226–227, 228–229
methodological issues, 34, 438–439
vitamin B6, 153–154, 155, 157, 158, 164, 172
Depression, 153, 267–268, 378, 409, 412
Developmental disability, 11–12, 441.
See also Neural tube defects
Diabetes mellitus, 90, 144, 260, 321
Diabetic neuropathy, 184
Dietary folate equivalents (DFEs), 1, 14
defined, 10–11
recommendations, 434
uses, 432–435
Dietary intakes. See also Canada;
Nutrient intakes;
Supplements;
specific nutrients
and bioavailability, 15, 16, 343
food composition databases, 15, 35–36
food frequency questionnaires, 225, 247
gender differences, 8–9, 79, 180, 181, 306, 344, 345, 460–506
overreporting of, 247
self-reported, 35
Dietary Reference Intakes (DRIs)
applicable population, 18
categories, 2, 6–7, 17, 18–23, 423, 424;
see also Adequate Intakes;
Estimated Average Requirements;
Recommended Dietary Allowances;
Tolerable Upper Intake Levels
extrapolation from other age groups, 20, 31–33
framework, 446
group applications, 4, 8, 14, 20, 427– 432, 434
individual applications, 4, 6, 18, 424– 425, 432–435
origin, 443–444
parameters for, 23–26;
see also Life-stage groups;
Reference weights
risk of inadequacy, 19
rounding of values, 23 n.2
see also Methodological considerations
Diphenylhydantoin, 212
Diphyllobothrium lactum, 317
DNA replication and repair, 124, 127, 145, 196, 265
DNA synthesis, 27, 197, 258, 265, 311
Dose-response assessment for ULs
adults, 142–143, 184–186, 277–280, 410
biotin, 385
components and process, 44, 45, 51
critical endpoints, 49, 53–54, 183, 277, 410
data selection, 53, 142, 184, 277, 410
defined, 537
derivation of ULs from, 46–47, 52, 55– 56, 143, 186, 280, 410
folate, 277–281
by life-stage group, 143–144, 184–187, 277–281, 410–412
niacin, 142–144
NOAEL/LOAEL identification, 53–54, 142–143, 184–185, 277–279, 410
riboflavin, 116
special considerations, 56, 144, 187, 281, 412
thiamin, 82
uncertainty assessment, 54–55, 143, 186, 279–280, 410
vitamin B6, 184–187
vitamin B12, 347
Drug interactions
with choline, 399
with folate, 212–213, 240, 246, 265–266, 276
with riboflavin, 94
with vitamin B6, 162
E
Elderly people. See Adults, >70 years
Electroencephalogram (EEG)
Embryogenesis, 16, 241–242, 404–405
Energy metabolism
exercise and, 97
gender differences, 108
niacin and, 27, 28, 129–130, 133, 135– 136
pantothenic acid, 27
pregnancy and, 33, 77, 96, 111, 130, 135–136
and RDA derivation, 20
riboflavin and, 27, 28, 88, 94, 96, 97, 108, 110, 111
thiamin and, 27, 28, 62–63, 75, 77, 78
Erythrocyte
aminotransferase, 154, 157, 161, 167, 168–169, 172–173, 174–175, 177
flavin, 91–92, 95, 98–102, 107
folate concentrations, 199, 200, 201, 208, 209, 213, 214–215, 216, 219, 221–225, 227, 229, 230–231, 234, 235–237, 238, 239, 256–259, 264–265, 266, 267–268, 269, 514–515
glutathione reductase activity, 10, 87, 90–91, 94–95, 96–97, 98–102, 104, 106, 107, 108, 110, 116
pantothenic acid, 360–361, 364–365
pyridine nucleotides, 127, 132
pyridoxal 5′-phosphate, 154–156
thiamin concentrations, 60, 62, 64, 67, 74
transketolase activity, 10, 58, 60, 61, 64, 67, 69, 71, 73, 74, 75, 76
Estimated Average Requirements (EARs).
See also individual nutrients
coefficient of variation, 3, 5, 20
energy expenditure and, 20
extrapolation to/from other age
group applications, 14, 427–432
indicators used to set, 6–7, 10, 22–23, 29
and RDA, 3, 6–7, 18, 19–20, 22
reference weight and height and, 25– 26
risk of inadequacy, 19
Estrogen, 129, 163–164, 213, 400
Ethnic background. See Race/ethnicity
Etretinate, 246
Exposure
duration of, 52
Exposure assessment
biotin, 385
choline, 412–413
derivation of ULs, 46, 48, 412–413
folate, 229–232, 248–253, 281–282
niacin, 144
pantothenic acid, 370
riboflavin, 116
thiamin, 82
vitamin B6, 187
vitamin B12, 347
Extrapolation of data
from animal studies, 28, 43–44, 46, 52, 55, 56, 153
from one gender group to another, 32, 403
from other age groups, 20, 29, 31–33, 56, 66, 103–104, 105, 106, 131, 167, 215, 217, 220, 325, 326, 362–363, 364, 381, 382, 401–402
F
Fat, dietary, 95–96
Fetal. See also Neural tube defects;
Pregnancy
folate, 233
sensitivity to nutrients, 48
thiamin, 76
vitamin B12, 339–340
Fish and shellfish, 139
Flavin-adenine dinucleotide (FAD), 87–88, 89, 91–92, 94, 95, 96, 116, 129
Flavin mononucleotide (FMN), 87–88, 89, 92, 95, 96, 116, 129
Flavokinase, 89
Folate, 196–305.
See also Dietary folate equivalents;
Folic acid
absorption and transport, 1, 198, 211, 212, 233, 259
adolescents, 220, 233–238, 239, 240, 280–281
adults (19–50 years), 9, 196–197, 220– 228, 234–240, 270–272, 277–281
adverse effects, 273–277
AIs, 214–217
alcohol and, 204, 211, 240, 263, 266, 268, 276
bioavailability, 8–9, 15, 16, 196, 208– 210, 211, 227, 235, 239, 256, 428
body stores, 198
and cancer, 12, 196, 204, 205, 264–266, 269, 276
chemistry, 197
and congenital anomalies (non-NTD), 259–260
controlled trials, 250–253
critical endpoint, 277
data sources, 277
deficiency, 11, 12, 16, 199–200, 210– 211, 215, 221, 233, 234, 311
dietary fiber and, 211
dose-response assessment for ULs, 277– 281
drug interactions, 212–213, 246, 265– 266, 276
EARs, 8, 9, 217, 220–228, 229–233, 234– 240, 427
elderly (>70 years). See Adults, >70 years
and embryogenesis, 16, 241–242
erythrocyte concentrations, 199, 200, 201, 208, 209, 213, 214–215, 216, 219, 221–225, 227, 229, 230–231, 234, 235–237, 238, 239, 256–259, 264–265, 266, 267–268, 269, 514–515
excretion, 198–199, 204, 211, 237–238
exposure assessment, 229–232, 248–253, 281–282
factors affecting requirement, 207–214
fetal, 233
food (naturally occurring), 1, 10, 12, 14, 15, 16, 196, 197, 198, 209–210, 215, 222, 223, 224, 227, 239, 247, 269–272, 281
food composition data, 35, 36, 206– 207, 459
fortified foods, 269–272, 281–282, 428, 435
function, 10, 197, 240–269, 273
gender differences, 202–203, 213–214, 220, 260, 428
genetic considerations, 203, 213–214, 259, 263
hazard identification, 273–277
hematological status and, 204–205
and homocysteine levels, 11, 12, 159, 196, 197, 199, 200, 201–203, 214, 221, 223, 224, 225, 228–232, 234, 239, 244–245, 246, 260–261, 262, 268, 314
hypersensitivity, 276–277
indicators of adequacy, 10–11, 16, 196, 200–205, 234
infants, 214–217, 218–219, 276, 277, 280–281
intakes, 38–39, 196–197, 269–273, 281– 282, 428, 430, 460–461, 464–465, 474–475, 494–497, 504, 506
interaction with food components, 211
interaction with other nutrients, 158, 159, 199, 202, 210–211, 273–276, 277, 307, 321, 391, 394–395, 398– 399, 400, 413
life-stage group and, 38–39, 214–240, 277–281, 474–475, 494–497, 504, 506, 512–515
measurement of blood values, 205–206
mental function, 12, 16, 196, 204, 205, 267–269, 276
metabolism, 198–199, 211, 213–214, 221–225, 226–227, 228–229, 233, 235– 237, 238, 398–399
method used to set AIs, 214–216
method used to set EARs, 210, 217, 220, 238–239
methodological considerations, 205– 207, 210, 214, 237, 268, 272, 456– 459
and neural tube defects, 16, 23, 196, 205, 233, 240–259, 269, 276, 283, 284, 435, 524
neurological/neuropsychiatric effects, 12, 16, 196, 205, 267–269, 273–276, 277–279, 280, 281
observational studies, 248–251
older adults (51+ years), 9, 200, 201, 228–233, 268, 272, 273, 277–280, 460–461, 464–465
oral contraceptives and, 212, 213
periconceptional use, 204, 247–256, 276
plasma concentrations, 196, 200, 214, 216, 221, 223, 229, 232, 261–262, 267
population-based studies, 234–235, 238
pregnancy and, 2, 11–12, 16, 23, 197, 204, 209, 228, 233–238, 240–260, 273, 276, 277, 278–279, 280–281, 435
race/ethnicity and, 203, 242–243, 245
RDAs, 2, 11–12, 23, 196, 217, 220, 228, 233, 238, 240
research recommendations, 1, 2, 16, 283–284, 439, 440, 441
risk characterization, 16, 282–283
serum concentrations, 199, 200, 201, 203–204, 209, 214–215, 216, 219, 221, 223, 224, 225, 229, 234, 235, 261, 267, 277, 307, 512–513
smoking and, 211–212, 260, 276
special considerations, 217, 240, 281
supplement use, 1, 38–39, 196, 197, 208, 238, 242, 247–256, 258–259, 263, 272–273, 283, 464–465, 496–497, 524
synthesis by intestinal bacteria, 211
uncertainty assessment, 279–280
unit conversions, 451
and vascular disease, 12, 16, 159, 196, 203, 204, 205, 260–264, 269
and vitamin B12, 199, 202, 210–211, 273–274, 277–279, 280, 281, 307, 311, 314, 321
Folic acid
absorption, 1
neural tube defects and, 11–12, 16
neurotoxicity, 276
research recommendations, 16
ULs, 13, 22, 197, 273–283, 427
unit conversions, 452
Food and Agriculture Organization, 41
Food component interactions, 211, 322
Food composition analysis, 35, 368–369, 413, 458–459
Food composition databases, 15, 35–36, 434
Food Guide Pyramid, 283
Food sources. See also Fortified foods
biotin, 384
choline, 406–407
folate, 269–272
pantothenic acid, 368–369
types of information, 37–38
vitamin B6, 179–181
vitamin B12, 306, 309, 342–343, 344– 345, 435
Formiminoglutamic acid, 314
Formulas, infant
bioavailability of nutrients from, 30, 402
cow milk, 402
soy-derived, 402
special considerations, 167, 217, 402
vitamin B6 deficiency, 166–167
Fortified foods, 15.
See also Formulas, infant
folate in, 1, 2, 8–9, 12, 14, 196, 197, 208–209, 235, 240, 247, 256, 257– 258, 269–272, 281–282, 428, 435
niacin in, 128
riboflavin in, 113
Framingham Heart Study, 175, 336
G
Gastrointestinal complaints, 141, 144, 276, 312, 318, 320, 359, 408
Gender differences, 23.
See also Men;
Women;
individual nutrients
dietary intakes, 8–9, 79, 180, 181, 306, 344, 345, 460–506
extrapolation between groups, 32, 403
and metabolism of nutrients, 108, 213– 214
and plasma homocysteine, 203
supplement intakes, 38–39, 113, 257, 462–465
in vascular disease, 260
Genetic influences
choline, 409
folate, 16, 203, 213–214, 244–245, 259, 263
neural tube defects, 244–245
special considerations, 347, 383, 409
thiamin, 61
Glucose intolerance, 141
Glucose 6-phosphate dehydrogenase deficiency, 91, 108
Glutathione reductase activity, 10, 87, 90– 91, 94, 95
Gout, 144
Grain products, 14, 79, 113, 114, 128, 137– 138, 139, 208–209, 270
H
Hazard identification
adverse effects, 50–51, 81–82, 182–183, 273–277, 346, 370, 408–409
biotin, 384–385
components of, 44, 45, 50–52, 538
derivation of UL, 46
folate, 273–277
pantothenic acid, 370
riboflavin, 115–116
special considerations, 52, 347, 370, 409
thiamin, 81–82
vitamin B6, 182–183
vitamin B12, 346–347
Health Canada, 444
Hemodialysis patients, 18, 79, 112, 137, 383, 385
Holotranscobalamin II, 314
Homocysteine
catabolism, 158–159, 170–171, 175
and choline status, 27, 398, 413
gender differences, 518–519
and folate status, 11, 12, 159, 196, 197, 199, 200, 201–203, 214, 221, 223, 224, 225, 228–232, 234, 239, 244– 245, 246, 260–261, 262, 268, 314
life stage and, 159, 203, 518–519
methionine synthesis, 27, 88, 155–156, 268, 306, 307, 399, 521
and neural tube defects, 244–245, 246, 524
in older adults, 314
and riboflavin status, 27
and vascular disease, 12, 154, 159–160, 175, 260–261, 262, 398, 520
and vitamin B6 status, 151, 154, 155–156, 158–159, 170–171, 175, 244, 314
and vitamin B12 status, 12, 88, 158, 159, 306, 307, 314, 316, 336
Homocystinuria, 244–245, 260, 398
Human immunodeficiency virus, 342
Human milk, 5.
See also Lactation
AIs, 29–30
antivitaminic metabolites, 103
biotin, 380–381
choline, 401–402
intakes, 104
niacin, 130–131
pantothenic acid, 362–363, 368
thiamin, 65–66
tryptophan content, 130
vitamin B6, 165–166
Human papillomavirus-16, 264–265
Huntington’s disease, 410
Hydrocephalus, 241
2-Hydroxyethylflavin, 103
3-Hydroxyisovalerate, 375, 378–379, 382, 383
Hyperbilirubinemia, 116
Hypercholesterolemia, 141, 145
Hyperhomocysteinemia, 154, 159, 202, 260
Hyperlipidemia, 140
Hypersensitivity to nutrients, 276–277, 409
Hypoglycemia, 359
I
Ibuprofen, 212
Immune response, 175
Immunoglobulins, 89
Inborn errors of metabolism, 12
Indicators of nutrient adequacy. See also specific indicators, nutrients, and life stages
concurrent analyses, 94–95, 97
deficiency-based, 6–7, 16, 22–23, 94
methodological considerations, 16, 29, 60–62, 438–439
research recommendations, 438–439
risk reduction-based, 7, 12, 15, 23, 28, 94, 159–160, 205, 397–398, 441
Infants, premature, 166
Infants, 0 through 12 months. See also Formulas, infant;
Human milk
ages 0 through 6 months, 30, 33
ages 7 through 12 months, 30–31, 33
AI derivation for, 5, 6, 21, 29–31, 33
bioavailability of nutrients, 30
EAR derivation for, 31–32
formula-fed, 30, 166–167, 216, 217, 218–219, 402
growth spurts, 30
methylmalonic acid concentrations, 323–324
reference weight, 65
sensitivity to nutrients, 48, 116
solid foods, 30, 31, 66, 105, 112, 131, 406
special considerations, 167, 217, 325– 326, 402
Inflammatory bowel disease, 144, 212
Inositol, 524–525
Insulin sensitivity, 359
Intake assessment to derive ULs. See Exposure assessment
Interactions. See Nutrient-nutrient interactions
International Atomic Energy Agency (IAEA), 41
International comparisons
neural tube defects, 242–243
Intrinsic factor, 306, 307–308, 310, 315, 317, 318, 330, 333
Isotretinoin, 246
K
Kloeckera brevis bioassay, 379
Kynurenine hydroxylase, 88
L
Laboratory values
analytic considerations, 34, 205–206, 272, 313, 315, 407, 456–459
conversion between tradition and SI units, 451–452
interlaboratory differences, 206–207, 268, 315
interpretation of study results, 34
sensitivity and specificity, 34–35, 379, 407
Lactation. See also Human milk;
individual nutrients
derivation of DRIs for, 33
energy metabolism, 78, 96, 130
laboratory values during, 34
methodological considerations, 34
special considerations, 240
twins/multiple infants, 79, 112, 137, 240
ULs, 48
Lactic acid values, 62, 64, 94
Lactobacillus assays, 315, 333, 358
L-DOPA, 162
Latin Americans, pernicious anemia, 317, 323
Lean body mass, and sensitivity to nutrients, 48
Leber’s optic atrophy, 346
Lecithin, 392, 395, 398, 400, 406–407, 408
Life-stage groups. See also Adolescents;
Adults;
Children;
Infants;
individual nutrients
Body Mass Index by, 25
categories, 24
and derivation of DRIs, 23–24, 29
intakes of nutrients by, 8–9, 466–506
recommended intakes by, 566–567
and supplement use, 38–39
ULs by, 13
Liver function/disease/toxicity
choline and, 11, 306–307, 370, 390, 391–392, 393, 394, 396–397, 398, 408, 409
folate and, 212
vitamin B6 and, 164
Lowest-Observed-Adverse-Effect Level (LOAEL)
choline, 410
folate, 277–280
niacin, 142–143
thiamin, 82
vitamin B6, 184–185
Lung cancer, 266
M
Malabsorption syndromes, 16, 18, 79, 112, 137, 308, 310, 318, 320, 331, 334, 342, 377
Malaria, 213
Men. See also Gender differences
energy metabolism, 133
folate, 201, 260, 270–271, 272
indicators used to set EARs, 170–171
niacin, 14, 123, 127, 133, 135, 138, 139, 144
pantothenic acid, 358, 359, 360
riboflavin, 14, 87, 97, 100–102, 107, 109, 113, 114
thiamin, 14, 61, 71–74, 79, 80, 82
vitamin B6, 150, 152, 153–154, 155, 170– 171, 180–181
vitamin B12, 14, 306, 343, 344, 345
Meningocele, 241
Meningomyelocele, 241, 243, 248–249
Menstrual cycle and vitamin concentrations, 156
Metabolism of nutrients, 48
amino acid, 58, 88, 150, 151, 161, 196, 197, 358
biotin, 377
carbohydrate, 58, 63, 94, 95–96
depletion-repletion studies, 69, 70–73, 75, 153–154, 155, 157, 158, 164, 172, 221–225, 226–227, 228–229, 438– 439
and EAR, 20
folate, 198–199, 211, 213–214, 221–225, 226–227, 228–229, 233, 235–237, 238, 398–399
niacin, 125
and sensitivity to nutrients, 48
smoking and, 320–321
vitamin B6, 151–152, 153–154, 155, 157, 158, 162, 164, 172
Methionine
choline and, 391, 394–395, 398–399, 400, 413
folate and, 158, 197, 201–202, 214, 244, 261, 391, 394–395, 398–399, 400, 413
homocysteine conversion to, 27, 88, 155–156, 158, 159, 197, 201–202, 268, 306, 307, 399, 521
and neural tube defects, 244, 524
riboflavin and, 88
and vitamin B6 status, 154, 155–156, 158, 159, 413
Methodological considerations. See also Data and database issues;
Extrapolation of data;
Indicators of nutrient adequacy;
Uncertainty
adequate intakes for infants, 29–33
bioavailability estimates and assumptions, 210, 225
blood nutrient measurement, 205–206
data sources, 28–29, 50, 51, 52
depletion-repletion study design, 438– 439
experimental studies, 28
food composition data, 206–207, 225, 407, 458–459
high-performance liquid
chromatography, 92
kinetic modeling of body pools, 439
laboratory values, 34–35, 205–206, 268, 272, 315, 456–459
load tests, 93–94
normalization to baseline, 164–165
in nutrient intake estimates, 8–9, 14, 16, 35–36, 206–207, 210, 237, 265, 272, 337, 429
observational studies, 28
radioligand binding assays, 315
research recommendations, 440
retention studies, 315–316
in risk assessment, 45
risk reduction as indicator of nutrient
adequacy, 7, 12, 15, 23, 28, 159–160, 205
statistical association, 29
Methotrexate, 212–213, 240, 399
Methylcitrate, 314
5,10-Methylenetetrahydrofolate reductase (MTHFR)
and choline, 398
folate metabolism and, 214, 244, 245, 259, 263, 266, 520–521
and methionine formation, 88, 214, 244
and neural tube defects, 244, 245, 259
riboflavin and, 88
and vascular disease, 263, 398, 520
Methylmalonic acid, 244, 246, 313–314, 316, 318, 323–324, 335–337
Microbial synthesis of nutrients, 152
Migraine headaches, 144
Multiple Risk Factor Intervention Trial, 262
N
National Health and Nutrition Examination Survey II (NHANES II), 31, 206, 232, 384
National Health and Nutrition Examination Survey III (NHANES III)
biotin, 384
choline, 407
defined, 539
folate, 206, 221, 272, 273, 281, 282, 428, 430, 494–497, 512–515
homocysteine, 518–519
pantothenic acid, 369
vitamin B12, 347, 431, 498–501, 516–517
National Health Interview Survey, 37, 38– 39, 138, 369, 384
Nationwide Food Consumption Survey, 282–283
Neoplastic tranformation, 16.
See also Cancer
Neural tube defects, 10, 11–12
anatomy, 241–242
animal studies, 244, 245, 523–525
classification, 241–242
erythrocyte folate and, 258–259
etiology, 233, 243–246, 523–525
folate and, 16, 23, 196, 205, 233, 240– 259, 269, 276, 283, 284, 435, 524
forms of, 241
genetic evidence, 244–245
homocysteine and, 244–245, 246, 524
inositol and, 524–525
levels of dietary folate and, 247, 276
maternal folate intake and, 246–253, 435
maternal folate status and, 256–257
mechanism of folate action, 258
methionine and, 524
and methyl malonic acid, 246
nutrition studies, 524–525
periconceptional folate supplement use and, 247–256
prevalence, 242–243
research recommendations, 283, 284
risk of, 254–256
race/ethnicity and, 242–243, 245
recommendations for risk reduction, 196, 258–259, 269
screening for, 242
socioeconomic status and, 245–246
vitamin B12 and, 246
Neurological/neuropsychiatric disorders
biotin and, 377
choline and, 407
folate and, 12, 16, 196, 205, 267– 269, 273–276, 277–279, 280, 281
niacin and, 126
pantothenic acid and, 359
thiamin and, 59
vitamin B6 and, 12, 153–154, 160
vitamin B12 and, 12, 273–274, 277–279, 280, 308, 311–312, 313, 316, 328, 329, 347
Niacin, 123–149
absorption and transport, 124–125
adolescents, 56, 131–137, 143–144
adults (19–50 years), 9, 123, 126, 127, 132–137, 138, 139, 142–143
adverse effects, 123, 138, 140–142
and adenosine diphosphate
ribosylation, 127
AIs, 130–131
bioavailability, 123, 128–129, 133
chemistry, 123–124
children, 56, 131–132, 143–144
data selection, 142
deficiency, 125–126
dose-response assessment for ULs, 142– 144
drug interactions, 128, 129, 137
elderly (>70 years). See Adults, >70 years
energy intake and expenditure and, 27, 28, 129–130, 133, 135–136
and erythrocyte pyridine nucleotides, 127, 132
excretion, 10, 123, 125, 126–127, 132, 133, 134
factors affecting requirement, 128–130
food composition data, 458
food sources, 128, 137–138, 139
function, 10, 27, 123, 124, 127, 128, 130
gender differences, 130, 133, 135, 138, 144
hazard identification, 138, 140–142
indicators of adequacy, 10, 123, 126– 128, 132, 134, 145
intakes, 38–39, 123, 137–138, 144, 460– 463, 470–471, 486–489, 503, 506
interactions with other nutrients, 88, 94, 96, 124, 125, 126, 128, 129, 370
lactation, 130, 136–137, 143–144
by life-stage group, 38–39, 130–137, 142– 144, 470–471, 486–489, 503, 506
LOAEL, 142–143
metabolism, 125
method used to set AIs, 130–131
method used to set EARs, 131, 132– 133, 136
neurological/neuropsychiatric
disorders, 126
older adults (51+ years), 9, 132–135, 138, 142–143, 460–463
and oral contraceptives, 129
and pellagra, 125–126, 127–128, 132– 133
plasma concentrations, 127
preformed, 123, 128, 130, 131, 136, 138
pregnancy, 126, 128–129, 130, 135–136, 137, 143–144
protein intake and, 10, 125, 126, 128, 129, 132
RDAs, 123, 131–132, 135, 136, 137, 566– 567
research recommendations, 145
risk assessment, 145
special considerations, 137, 144
supplement use, 38–39, 138, 462–463, 488–489
tryptophan intake and, 10, 123, 124, 125, 126, 128–129, 130, 132, 135, 137, 138
ULs, 13, 22, 56, 123, 138, 140–145, 427
uncertainty assessment, 143
unit conversions, 451
Niacin equivalents, 10
Nicotinamide, 124, 125, 127, 140, 142, 256
Nicotinamide adenine dinucleotide (NAD), 123–124, 125, 127, 128, 132, 145
Nicotinamide adenine dinucleotide phosphate (NADP), 123–124, 125, 127, 128, 132
Nicotinic acid, 124, 140, 141, 143
Nitrogen balance, 94
N1-Methylnicotinamide, 126, 132–133, 134
No-Observed-Adverse-Effect Level (NOAEL)
choline, 410
niacin, 142–143
thiamin, 82
vitamin B6, 184–185
Nutrient intakes. See also Dietary intakes;
Exposure assessment;
specific nutrients
Canadian, 37, 58, 74, 79, 113, 123, 138, 150, 181, 272, 282, 306, 343, 384, 502–506
day-to-day variation, 36, 37, 428–429
form of, 52, 125, 140–141, 142, 209
gender differences, 270–271, 460–506
increasing, strategies for, 14–15
by life stage group, 466–506
methodological considerations, 8–9, 14, 16, 35–36, 206–207, 210, 237, 265, 272, 337, 429
quality of data, 35–36, 265, 337, 366
from supplements, 87, 182, 407, 462– 465
U.S., 38–39, 460–465, 466–477, 478–480
Nutrient-nutrient interactions. See also specific entries under nutrients
and bioavailability, 15
and chronic disease risk reduction, 94
composition of diet and, 95–96, 211
research recommendations, 413
risk assessment, 49
Nutrition Canada Survey, 24, 261
O
Obesity, 174
Ocular effects, 94, 141–142, 346
Omeprazole treatment, 342
Oral contraceptives
niacin and, 129
pantothenic acid and, 362
riboflavin and, 97
Orofacial clefts, 259
P
Pantothenic acid, 357–373
adolescents, 359, 360, 364–365, 367– 368, 369
adults (19–50 years), 357, 365–366, 367– 368, 369
adverse effects, 370
AIs, 6, 11, 21, 357, 362–368, 566–567
bioavailability, 361
blood levels, 360, 361, 364–365
elderly (>70 years). See Adults, >70 years
energy metabolism and, 27
erythrocyte concentrations, 360–361, 364–365
excretion, 11, 357, 358, 359–361, 362, 363–364, 365–366, 367, 368
exposure assessment, 370
factors affecting requirement, 361–362
food composition data, 368–369, 459
food sources, 368–369
gender differences, 364–365, 366
hazard identification, 370
indicators of adequacy, 11, 359–361
intakes, 38–39, 368–369, 370, 505
interactions with other nutrients, 358, 361–362, 370
lactation and, 368
by life-stage group, 38–39, 505
method used to set AIs, 362–364
neurological disorders, 359
older adults (51+ years), 366–367
oral contraceptives and, 362
pregnancy and, 367
research recommendations, 371
risk characterization, 370
socioeconomic status and, 363
special considerations, 370
supplement use, 38–39, 362, 366, 369
uncertainties, 366
unit conversions, 452
Pellagra, 125–126, 127–128, 132–133
Pepic ulcer disease, 144
Peritoneal dialysis patients, 18, 79, 112, 137, 383
Pernicious anemia
vitamin B12 and, 308, 310, 311, 312, 316, 317–318, 319, 323–324, 327, 328, 329–330, 331, 332–333, 342, 346, 527
Phenobarbitol, 212
Photosensitivity, 115–116
Physical activity
choline and, 400
energy metabolism and, 97
Physicians’ Health Study, 261–262, 266
Picolinate carboxylase, 128
Plasma concentrations of nutrients. See individual nutrients
Pneumosystis carinii infections, 213
Population-based studies, folate, 234–238
Pregnancy. See also Lactation;
Neural tube defects;
individual nutrients
and absorption of nutrients, 33
derivation of DRIs for, 33
energy utilization, 33, 77, 96, 111, 130, 135–136
hyperhomocysteinemia and, 202
indicators of nutrient adequacy, 23
intakes of nutrients, 144
laboratory values during, 34
metabolic studies, 235–237
methodological considerations, 33, 34
multiple fetuses, 79, 112, 137, 240
population-based studies, 234–238
preeclampsia, 164
smoking and, 321
supplements during, 187, 234, 235, 236–237
ULs, 48
Premenstrual syndrome, 182, 185, 187
Propionate, 314
Prostaglandin, 141
Protein, dietary
niacin and, 10, 125, 126, 128, 129, 132
requirements for growth, 20, 32, 33
vitamin B6 and, 28, 161–162, 163, 169, 170, 172, 173, 174, 175
Protein kinase C, 398
Psoriasis, 246
Psychotropic drugs, 94
Puberty/pubertal development, 25.
See also Adolescents
Pyrimethamine, 213
Q
Quinolinate phosphoribosyltransferase, 128
R
Race/ethnicity. See also Asians;
Blacks;
Latin Americans;
Whites
and neural tube defects, 242–243, 245
and pernicious anemia, 280, 317
and plasma homocysteine, 203
Radioligand binding assays, 315
Recommendations. See also Research recommendations
food composition data, 15, 434
Recommended Dietary Allowances (RDAs). See also individual nutrients
applicable population, 18, 424–425
coefficient of variation, 32–33
criteria used to derive, 3, 6–7, 10
derivation of, 5, 18, 19–20, 22
increasing consumption of nutrients, 14–15
indicators of nutrient adequacy, 7, 10, 23
group applications, 14, 424–425
risk of inadequacy, 19
uncertainty in, 425
uses, 4, 5, 6, 21, 423, 424–425
weight and height and, 26
Reference body weight ratio method, 31, 33
biotin, 381
choline, 412
pantothenic acid, 362–363
thiamin, 66
vitamin B6, 167
Reference weights, 24–26, 56, 65, 425
Renal disease/failure/insufficiency
folate and, 203
thiamin and, 60
Requirement, defined, 17
Research recommendations
agenda development, 437–438
chronic disease risk reduction, 15, 16, 441
depletion-repletion study design, 438– 439
developmental disorders, 441
folate, 1, 2, 16, 283–284, 439, 440, 441
indicator of nutrient status, 188, 438– 439, 441–442
interrelationships among nutrients, 413, 440
kinetic modeling of body pools, 439
knowledge gaps and, 439–440
methodologies, 16, 440, 438–439
neural tube defects, 283, 284, 441
niacin, 145
public health implications of intakes, 441
requirements studies, 439–440
riboflavin, 116
thiamin, 82–83
toxicity of nutrients, 15, 441–442
vitamin B12, 2, 16, 348, 439, 441–442
Rheumatoid arthritis, 212–213
Riboflavin, 87–122
adolescents, 105–106, 110–112, 116
adults (19–70 years), 8, 87, 92, 107–109, 110–112, 114
AIs, 103–105
deficiency, 90, 91, 107, 111, 127–128
dose-response assessment for ULs, 116
drug interactions, 94
EARs, 8, 97–102, 105–106, 107–112, 116, 427
elderly (>70 years). See Adults, >70 years
and energy metabolism, 27, 28, 88, 94, 96, 97, 108, 110, 111
erythrocyte flavin, 91–92, 95, 98–102, 107
erythrocyte glutathione reductase activity, 10, 87, 90–91, 94–95, 96–97, 98–102, 104, 106, 107, 108, 110, 116
excretion, 10, 87, 89–90, 92–94, 95, 96– 97 , 98–102, 107–108, 109, 110
exposure assessment, 116
factors affecting requirement, 95–97
food composition data, 458
gender differences, 14, 87, 96, 106, 107, 108, 113
glucose 6-phosphate dehydrogenase deficiency and, 91, 108
hazard identification, 115–116
indicators of adequacy, 10, 87, 90–95, 97–102, 116
infants, 31, 56, 89–90, 103–105, 107, 112, 116
intakes, 31, 38–39, 87, 113–114, 116, 460–463, 468–469, 482–485, 503, 506
interactions with other nutrients, 88, 90, 94, 95–96, 129, 361–362
lactation, 96, 103–104, 112, 116
life-stage group and, 38–39, 103–112, 116, 427, 468–469, 482–485, 503, 506
methods used to set AIs, 103–105
methods used to set EARs, 97–102, 105– 106, 112
and neural tube defects, 256
older adults (>70 years), 8, 91, 95–96, 97, 100–101, 102, 108, 109–110, 113, 114, 116, 460–463
oral contraceptives and, 97
and photosensitivity to UV light, 115– 116
physical activity and, 64, 94, 96–97, 116
pregnancy, 89, 91, 96, 110–111, 112, 115, 116
RDAs, 87, 106, 109, 111, 112, 566–567
research recommendations, 117
risk characterization, 116
safety factor, 10
special considerations, 112, 116
supplement use, 38–39, 87, 103, 113, 462–463, 484–485
unit conversions, 451
Risk, defined, 539
Risk assessment, defined, 42, 539
Risk assessment models. See also Doseresponse assessment;
Exposure assessment;
Hazard identification;
Risk characterization
application to nutrients, 12–13, 47–49
bioavailability considerations, 49, 53
and food safety, 42–47
nutrient interactions, 49
process, 44–45
sensitivity of individuals, 48–49
thresholds, 45–47
uncertainties, 13, 43–44, 46, 47–48, 507– 511
Risk characterization
biotin, 385
choline, 413
derivation of UL, 46–47
niacin, 145
pantothenic acid, 370
riboflavin, 116
thiamin, 82
vitamin B6, 187
vitamin B12, 347
S
S-adenosylmethionine (SAM), 268, 391, 393, 399
Seborrheic dermatitis, 153
Self-medicating with nutrients, 41
Sensitive subpopulations. See Special considerations
Sensitivity. See also Hypersensitivity
allergic, 81–82
defined, 34–35
fetal, 48
interindividual variability in, 48–49
Sensory neuropathy, 150, 182–183, 184– 185, 187
Serum levels of nutrients. See individual nutrients
Sickle cell disease, 187
Skiers, 64
Socioeconomic status and nutrient intake, 245–246, 363
Special considerations
alcohol consumption 240
biotin, 383
breastfeeding twins, 79, 137, 240
in dose-response assessment for ULs, 56, 144, 187, 281, 412
drug interactions, 128, 137, 240, 246, 342
formula-fed infants, 167, 217, 402
genetic disorders, 347, 383, 409
high-protein diets, 176
identification of, 52, 347, 370, 409
malabsorption syndromes, 16, 18, 79, 112, 137, 320, 342
multiple infants/births, 79, 112, 137, 240
pantothenic acid, 370
in risk assessment, 48, 347, 412
thiamin, 79
vitamin B12, 325–326, 342, 347
Specificity, 34–35
Spina bifida. See Meningomyelocele
Supplements, dietary. See also individual nutrients
bioavailability of nutrients, 1, 9, 18, 49, 62, 208, 210, 235, 256, 259, 331, 334
data sources on intakes, 37
gender differences in use, 113
supraphysiological doses, 264
timing of, 256
ULs and, 5–6, 22, 47–48, 82, 138, 140– 142
usage, 38–39, 79, 81, 182, 462–465
usefulness of, 15
T
Tetrahydrofolate, 307
Tetrahydropterin, 268
Thiamin, 58–86
adolescents, 61, 63, 67–68, 76–78, 82
adults, 8, 58, 61, 66, 69–74, 76–78, 80, 82
AIs, 65–66
bioavailability, 62
chemistry, 58–59
deficiency, 58, 59–60, 62, 63, 65, 67–68, 69, 74–75
dose-response assessment for ULs, 82
EARs, 8, 62, 66, 67–68, 69–73, 74–77, 78, 427
elderly (>70 years). See Adults, >70 years
energy utilization and, 27, 28, 62–63, 75, 77, 78
erythrocyte concentrations, 60, 62, 64, 67, 74
erythrocyte transketolase activity, 10, 58, 60, 61, 64, 67, 69, 71, 73, 74, 75, 76
excretion, 10, 58, 59, 60–61, 64, 67, 68, 69, 72, 73, 75, 77, 82
exposure assessment, 82
factors affecting requirement, 62–64
fetal, 76
food composition data, 458
gender differences, 14, 72, 81, 82
genetic factors, 61
hazard identification, 81–82
indicators of adequacy, 10, 60–62, 67, 69, 82
infants, 31, 56, 60, 65–66, 78
intakes, 31, 38–39, 58, 79–81, 82, 460– 463, 466–467, 478–481, 502, 506
interactions with other nutrients, 88, 361–362
and lactic acid values, 62, 64
life-stage group and, 38–39, 65–79, 427, 466–467, 478–481, 502, 506
methods used to set AIs, 65–66
methods used to set EARs, 60–61, 66, 76–77, 78
neurological disorders, 59
NOAEL/LOAELs, 82
and neural tube defects, 256
older adults (51+), 8, 61, 74–76, 79, 81, 82, 460–463
parenteral administration, 81
physical activity and, 62, 63–64
and pyruvic acid values, 62
RDAs, 58, 66–67, 68, 73–74, 76, 77–78, 566–567
research recommendations, 82–83
risk characterization, 82
special considerations, 79
supplement use, 38–39, 58, 79, 81, 82, 462–463, 480–481
unit conversions, 451
Thiamin pyrophosphate (TPP), 58–59, 60, 61, 62, 63, 74, 75, 76–77
Tinnitus, 409
Tolerable, defined, 22, 41, 43
Tolerable Upper Intake Levels (ULs), 1, 17, 32.
See also Dose-response
assessment;
Hazard identification;
Risk assessment models;
individual nutrients
defined, 2, 5, 7, 13, 22, 41, 47, 54, 424
derivation of, 5–6, 7, 12–13, 22, 46–47, 52, 55–56
by life-stage group, 13
risk of excess, 19, 22, 41, 53–54, 82, 116
supplement use and, 5–6, 22, 47–48
Toxicity, mechanism of action, 52
Transcobalamin II (TCII), 308, 315, 339
Transketolase activity, 10, 58, 60, 61, 64, 69, 71, 73, 74, 75, 76
Triamterene, 213
Trimethoprim, 213
Trimethylaminuria (fishy body odor), 390, 408, 409, 411, 412
Trimetrexate, 213
abnormal metabolites, 153
catabolites, 154, 157–158, 162, 163–164, 170, 173, 177
conversion to niacin, 10, 123, 124, 125, 126, 128–129, 130, 132, 135, 137, 138
Tuberculosis patients, 162
U
Uncertainty
approaches for dealing with, 507–511
assessment, 54–55
in dietary intake estimates, 69, 72, 366
dose-response assessment for ULs, 54– 55
extrapolation from experimental animals to humans, 43–44, 46, 55
interindividual variability in sensitivity, 55
in LOAEL, 55
in RDAs, 425
in risk assessment, 13, 43–44, 46, 47–48, 55, 507–511
subchronic NOAEL to predict chronic
NOAEL, 55
Unit conversions for nutrients, 451–452
U.S. Department of Agriculture, 207, 272, 282–283, 343, 369, 384
U.S. Food and Drug Administration, 282– 283
V
Vascular disease and thrombosis
choline and, 398
folate and, 12, 16, 159, 196, 203, 204, 205, 259, 260–264, 269
homocysteine values and, 12, 154, 159– 160, 175, 260–261, 262, 398, 520
niacin and, 144
riboflavin and, 90
thiamin and, 59–60
vitamin B6 and, 12, 154, 159–160, 262– 263
Vasodilatory effects (flushing), 123, 140– 141
Vegans/vegetarians
folate, 281
vitamin B12, 310, 317, 323–324, 325– 326, 327–328, 330, 331, 337, 340, 341, 343, 527
Vitamin A, 256, 358, 361–362, 525
Vitamin B1. See Thiamin
Vitamin B2. See Riboflavin
Vitamin B6, 150–195
absorption and transport, 151, 160–161
adolescents, 167–169, 176–179, 186–187
adults (19–50 years), 2, 9, 150, 153, 161, 170–174, 176–179, 180–181, 184– 187
adverse effects, 150, 182–183, 186
alcohol consumption and, 164
bioavailability, 150, 160–161, 165, 177
body stores, 152–153
and chronic disease, 159–160
and cognitive function, 160
data sources, 184
deficiency, 153–154, 164, 166–167, 168, 176, 178
dietary equivalents, 165
dose-response assessment for ULs, 184– 187
drug interactions, 162
EARs, 9, 161, 167–169, 170–179, 427
EEG abnormalities, 153–154, 155, 172
elderly (>70 years). See Adults, >70 years
energy metabolism and, 27, 160
and erythrocyte aminotransferase, 154, 157, 161, 167, 168–169, 172–173, 174–175, 177
excretion, 152, 156–158, 161, 168, 173
exposure assessment, 187
factors affecting requirements, 160–164
food composition data, 458
food sources, 179–181
forms of, 150–151
function, 10, 27, 150, 151, 161
gender differences, 152, 153–154, 155, 170–174, 175–176, 181
hazard identification, 182–183
and homocysteine catabolism, 158–159, 170–171, 175, 244
indicators of adequacy, 10, 16, 23, 150, 154–160, 161, 164, 165, 168–169, 176, 177, 188
infants, 150, 156, 164, 165–167, 178, 183, 186–187
intakes, 38–39, 150, 166–167, 168, 179– 182, 187, 460–463, 472–473, 490–493, 504
interaction with other nutrients, 28, 88, 90, 96, 128, 129, 158, 159, 161– 162, 202, 413
laboratory values, 333, 456, 458
lactation and, 165, 166–167, 178–179, 183, 186–187
life-stage group and, 38–39, 164–179, 181, 184–187, 427, 472–473, 490–493, 504
metabolism, 151–152, 153–154, 155, 157, 158, 164, 172
methods used to set AIs, 153, 165–167
methods used to set EARs, 153, 165
microbial synthesis, 152
and neural tube defects, 244, 256
and neurological/neuropsychiatric
NOAEL/LOAELs, 184–186
older adults (51+ years), 9, 160, 174– 176, 181, 182, 184–186, 460–463
oral contraceptives and, 158, 162–164
physical activity and, 64, 162
plasma concentrations, 154–156, 161, 162, 164, 165, 166, 170, 175
preeclampsia and, 164
pregnancy and, 156, 158, 164, 176–178, 183, 186–187
protein intake and, 28, 161–162, 163, 169, 170, 172, 173, 174, 175
race/ethnicity and, 158–159, 174
RDAs, 150, 169, 171, 174, 176, 178, 179, 566–567
research recommendations, 16, 188
risk characterization, 187
and sensory neuropathy, 182–183, 184– 185, 187
special considerations, 167, 176, 187
supplement use, 2, 38–39, 160, 182, 187, 462–463, 492–493
and tryptophan catabolism, 154, 157– 158, 162, 163–164, 166, 170, 172, 173, 175, 177
unit conversions, 451–452
and vascular disease, 12, 154, 159–160, 262–263
Vitamin B12, 306–356
absorption and utilization, 33, 306, 307–309, 313, 317, 318, 320, 322, 328, 330, 331, 333, 334, 339, 429
adolescents, 56, 326–327, 339–342
adults (19–50 years), 2, 9, 306, 327–338, 339–342, 343, 344–345, 347
adverse effects, 346
aging and, 318–320
AIs, 322–326
and atrophic gastritis, 317, 318, 320, 331, 334, 338, 342, 527
bioavailability, 309, 328, 338, 342, 343
body stores, 308, 309–310, 313, 315– 316, 318, 324, 327, 331, 334, 340, 527–530
deficiency, 13, 16, 210–211, 267, 307, 310, 311–312, 313, 316–317, 330
depletion, 324
dose-response assessment for UL, 347
EARs, 9, 326, 327–337, 338–342, 427
elderly (>70 years). See Adults, >70 years
enterohepatic circulation, 309–310
exposure assessment, 347
factors affecting requirements, 318, 320–322
fetal, 339–340
folate and, 199, 202, 210–211, 273–274, 277–279, 280, 281, 307, 311, 314, 321
food-bound, 320
food composition data, 459
food interactions with, 322
food sources, 306, 309, 342–343, 344– 345, 435
and formiminoglutamic acid, 314
function, 11, 27, 158, 306, 307, 311
gastrointestinal effects, 312
gender differences, 14, 321, 343, 345, 346, 347
genetic considerations, 322, 347
hazard identification, 346–347
hematological status/response, 306, 311, 312–313, 327–329
and holotranscobalamin II, 314
and homocysteine levels, 158, 159, 306, 314, 316, 336
indicators of adequacy, 11, 23, 312– 316 , 327–331, 335–337
intakes, 38–39, 306, 313, 330–331, 334– 335, 337, 342–346, 347, 429, 431, 460–461, 464–465, 476–477, 498–501, 505
interaction with other nutrients, 88, 158, 199, 210–211, 273–274, 307, 321, 391, 413
intrinsic factor and, 306, 307–308, 310, 315, 317, 318, 330, 333, 339
lactation and, 322–325, 341–342
life-stage group and, 38–39, 322–342, 427, 476–477, 498–501, 505, 516–517
malabsorption disorders, 16, 308, 310, 318, 320, 331, 334, 342
and mental function, 267, 311, 313
methodological issues, 313, 315–316, 456–459
methods used to set AIs, 322–325
methods used to set EARs, 326, 327– 331, 335–337
and methylcitrate, 314
and methylmalonic acid
concentrations, 313–314, 316, 318, 323–324, 326, 335–337
and neural tube defects, 246
neurological/neuropsychiatric effects, 12, 273–274, 277–279, 280, 308, 311– 312, 313, 316, 328, 329, 347
older adults (51+), 9, 16, 18, 306, 313, 314, 317, 318, 320, 332–333, 336– 337, 338–339, 343, 344, 346, 429, 460–461, 464–465
and pernicious anemia, 308, 310, 311, 312, 316, 317–318, 319, 323–324, 327, 328, 329–330, 331, 332–333, 342, 346, 527
plasma concentrations, 313, 324, 325, 341
pregnancy and, 33, 321, 339–341
and propionate, 314
RDAs, 306, 326–327, 337–338, 339, 340– 341, 342, 566–567
research recommendations, 2, 16, 348
risk characterization, 347
safety factor, 10
serum levels, 306, 313, 316, 321, 327– 329, 333, 335–337, 347, 516–517
smoking and, 320–321
special considerations, 325–326, 342, 347
supplement use, 2, 18, 38–39, 337, 346, 347, 464–465, 500–501
unit conversions, 451
and vascular disease, 12
vegans/vegetarians, 310, 317, 323, 324, 325–326, 327–328, 330, 331, 337, 340, 341, 343, 527
Vitamin C, 256, 321, 358, 361–362, 370
W
Weight. See Body weight;
Reference weights
Wernicke-Korsakoff syndrome, 58
Whites
pernicious anemia, 317
riboflavin, 106
Women. See also Gender differences;
Lactation;
Pregnancy
biotin, 384
energy metabolism, 133
folate, 14, 23, 201, 224, 229, 260, 270– 271, 272
indicators used to set EARs, 98–102, 171–174
niacin, 123, 133, 135, 138, 139, 144
obese, 174
postmenopausal, 400
riboflavin, 87, 96–97, 98–100, 107, 108, 109–110, 113, 114
thiamin, 72–73, 75, 79, 80, 82
vitamin B6, 150, 152, 153, 155, 171–174, 180–181
vitamin B12, 306, 343, 344, 345
weight-reducing/exercise training, 96– 97, 108
World Health Organization, 41
X
Xanthurenic acid, 157–158, 172, 175
Z
FOOD AND NUTRITION BOARD, INSTITUTE OF MEDICINE-NATIONAL ACADEMY OF SCIENCES DIETARY REFERENCE INTAKES: RECOMMENDED INTAKES FOR INDIVIDUALS
Riboflavin (mg/d) |
Niacin (mg/d)c |
Vitamin B6 (mg/d) |
Folate (µg/d)d |
Vitamin B12 (µg/d) |
Pantothenic Acid (mg/d) |
Biotin (µg/d) |
Cholinee (mg/d) |
0.3* |
2* |
0.1* |
65* |
0.4* |
1.7* |
5* |
125* |
0.4* |
4* |
0.3* |
80* |
0.5* |
1.8* |
6* |
150* |
0.5 |
6 |
0.5 |
150 |
0.9 |
2* |
8* |
200* |
0.6 |
8 |
0.6 |
200 |
1.2 |
3* |
12* |
250* |
0.9 |
12 |
1.0 |
300 |
1.8 |
4* |
20* |
375* |
1.3 |
16 |
1.3 |
400 |
2.4 |
5* |
25* |
550* |
1.3 |
16 |
1.3 |
400 |
2.4 |
5* |
30* |
550* |
1.3 |
16 |
1.3 |
400 |
2.4 |
5* |
30* |
550* |
1.3 |
16 |
1.7 |
400 |
2.4f |
5* |
30* |
550* |
1.3 |
16 |
1.7 |
400 |
2.4f |
5* |
30* |
550* |
0.9 |
12 |
1.0 |
300 |
1.8 |
4* |
20* |
375* |
1.0 |
14 |
1.2 |
400g |
2.4 |
5* |
25* |
400* |
1.1 |
14 |
1.3 |
400g |
2.4 |
5* |
30* |
425* |
1.1 |
14 |
1.3 |
400g |
2.4 |
5* |
30* |
425* |
1.1 |
14 |
1.5 |
400 |
2.4f |
5* |
30* |
425* |
1.1 |
14 |
1.5 |
400 |
2.4f |
5* |
30* |
425* |
1.4 |
18 |
1.9 |
600h |
2.6 |
6* |
30* |
450* |
1.4 |
18 |
1.9 |
600h |
2.6 |
6* |
30* |
450* |
1.4 |
18 |
1.9 |
600h |
2.6 |
6* |
30* |
450* |
1.6 |
17 |
2.0 |
500 |
2.8 |
7* |
35* |
550* |
1.6 |
17 |
2.0 |
500 |
2.8 |
7* |
35* |
550* |
1.6 |
17 |
2.0 |
500 |
2.8 |
7* |
35* |
550* |
e Although AIs have been set for choline, there are few data to assess whether a dietary supply of choline is needed at all stages of the life cycle, and it may be that the choline requirement can be met by endogenous synthesis at some of these stages. f Because 10 to 30 percent of older people may malabsorb food-bound B12, it is advisable for those older than 50 years to meet their RDA mainly by consuming foods fortified with B12 or a supplement containing B12. g In view of evidence linking folate intake with neural tube defects in the fetus, it is recommended that all women capable of becoming pregnant consume 400 µg from supplements or fortified foods in addition to intake of food folate from a varied diet. h It is assumed that women will continue consuming 400 µg from supplements or fortified food until their pregnancy is confirmed and they enter prenatal care, which ordinarily occurs after the end of the periconceptional period—the critical time for formation of the neural tube. |