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PAPERBACK + PDF your price: $56.50 add to cart PAPERBACK list:$47.95 Web:$43.16 add to cart HARDBACK list:$69.95 Web:$62.96 add to cart PDF BOOK your price: $37.00 add to cart PDF CHAPTERS your price: $1.80 select Rights & Permissions Free Resources PDF EXECUTIVE SUMMARY Display this book on your site! Related Titles Other Related Titles Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (1998) Institute of Medicine (IOM) Web Search Builder Use this book's key terms to search within this book, across our collection, or across the Web. Skim This Chapter Skim this chapter and use this chapter's key terms to search within this book. Reference Finder Paste in your own text to find books that relate to your topic. Page 541   E-mail  Facebook  Digg  Stumble  Twitter More The following HTML text is provided to enhance online readability. Many aspects of typography translate only awkwardly to HTML. Please use the page image as the authoritative form to ensure accuracy. 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 pantothenic acid, 358, 366 pregnancy and, 33, 89 riboflavin, 88–89, 102, 115 sensitivity considerations, 48 thiamin, 59, 62, 81–82 vitamin B6, 151, 160–161 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 defined, 2, 5, 17–18, 21, 424 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 RDAs compared, 6, 21–22 risk of inadequacy, 19 uses, 2, 4, 5, 21, 425–426 weight and height and, 26 Adolescents, 14 through 18 years. See also Children; Life-stage groups; Puberty/pubertal development; individual nutrients AIs, 21, 31–32 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 ULs, 13, 56 Page 541 Front Matter (R1-R24) Summary (1-16) 1 Introduction to Dietary Reference Intakes (17-26) 2 The B Vitamins and Choline: Overview and Methods (27-40) 3 A Model for the Development of Tolerable Upper Intake Levels (41-57) 4 Thiamin (58-86) 5 Riboflavin (87-122) 6 Niacin (123-149) 7 Vitamin B6 (150-195) 8 Folate (196-305) 9 Vitamin B12 (306-356) 10 Pantothenic Acid (357-373) 11 Biotin (374-389) 12 Choline (390-422) 13 Uses of Dietary Reference Intakes (423-436) 14 A Research Agenda (437-442) A Origin and Framework of the Development of Dietary Reference Intakes (443-447) B Acknowledgments (448-450) C Système International d'Unités (451-452) D Search Strategies (453-455) E Methodological Problems Associated with Laboratory Values and Food Composition Data for B Vitamins (456-459) F Dietary Intake Data from the Boston Nutritional Status Survey, 1981–1984 (460-465) G Dietary Intake Data from the Continuing Survey of Food Intakes by Individuals (CSFII), 1994–1995 (466-477) H Dietary Intake Data from the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994 (478-501) I Daily Intakes of B Vitamins by Canadian Men and Women, 1990, 1993 (502-506) J Options for Dealing with Uncertainties in Developing Tolerable Upper Intake Levels (507-511) K Blood Concentrations of Folate and Vitamin B12 from the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994 (512-519) L Methylenetetrahydrofolate Reductase (520-522) M Evidence from Animal Studies on the Etiology of Neural Tube Defects (523-526) N Estimation of the Period Covered by Vitamin B12 Stores (527-530) O Biographical Sketches (531-536) P Glossary and Abbreviations (537-540) Index (541-567)

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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 pantothenic acid, 358, 366 pregnancy and, 33, 89 riboflavin, 88–89, 102, 115 sensitivity considerations, 48 thiamin, 59, 62, 81–82 vitamin B6, 151, 160–161 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 defined, 2, 5, 17–18, 21, 424 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 RDAs compared, 6, 21–22 risk of inadequacy, 19 uses, 2, 4, 5, 21, 425–426 weight and height and, 26 Adolescents, 14 through 18 years. See also Children; Life-stage groups; Puberty/pubertal development; individual nutrients AIs, 21, 31–32 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 ULs, 13, 56

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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 cognitive function, 160, 268 EARs, 8–9 pernicious anemia in, 317, 332–333 supplement use, 18, 79, 81, 113, 182, 273, 346, 462–465 ULs, 48 Adverse effects, 2, 5–6 biotin, 384–385 choline, 390, 408–410, 411 defined, 41 evidence of, 50–51 folate, 273–277 interindividual variability in sensitivity, 48–49 niacin, 123, 138, 140–142 nutrient-nutrient interactions, 41, 49, 51, 273–274 pantothenic acid, 370 research recommendations, 15, 441–442 riboflavin, 87, 115–116 source of nutrient and, 47–48 thiamin, 58, 81–82 vitamin B6, 150, 182–183, 186 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 Albumin, 89, 152, 198 Alcohol consumption and alcoholism and folate, 204, 211, 240, 263, 266, 268, 276, 525 and niacin, 126, 144 and thiamin, 58, 60 and vitamin B6, 164 and vitamin B12, 347 Allergic sensitivity, 81–82 Alopecia, 377, 378 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 Anencephaly, 241, 243 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 relevance of, 50, 51, 211 vitamin B12 deficiency, 274, 310, 346 Antibiotics, 94, 313, 320 Anticonvulsants, 212, 240, 246, 276, 380, 525 Anti-inflammatory drugs (nonsteroidal), 212 Apotyrosine decarboxylase assay, 156 Ariboflavinosis, 90, 111 Arnold Chiari malformation, 241 Asians, pernicious anemia, 317 Aspartate aminotransferase, 157 Aspirin, 212 Asthma, 187, 212 Atherosclerosis, 260 Athletes, 64, 97, 400 Atrophic gastritis, 200, 312, 317, 318, 320, 331, 337, 340, 341, 342, 527 Avidin, 375–376, 379, 380

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline B Beriberi, 58, 59–60, 63, 65 Betaine, 392, 393, 398, 399, 413 Bioavailability of nutrients biotin, 375–376, 378 choline, 400, 402, 413 correction factor, 328, 338 defined, 49, 537 factors affecting, 18, 62, 309, 338, 342, 375 folate, 8–9, 15, 16, 196, 208–210, 211, 221, 227, 235, 239, 256, 428 folic acid, 225, 235 form of intake and, 15, 16, 88, 208– 210, 211, 221, 235, 239, 343, 428 from infant formula, 30, 402 methodological issues, 210, 225 niacin, 123, 128–129, 133 nutrient-nutrient interactions and, 15 pantothenic acid, 361 riboflavin, 88, 95 and risk assessment, 49, 53 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 adolescents, 381, 382–383 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 avidin and, 375–376, 379, 380 bioavailability, 375–376, 378 children, 381 deficiency, 375, 377–378 dose-response assessment for ULs, 385 elderly (>70 years). See Adults, >70 years excretion, 377, 378 exposure assessment, 385 factors affecting requirement, 380 fetal, 377, 385 food composition data, 35, 36, 37, 459 food sources, 384 function, 11, 27, 374–375 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 intakes, 38–39, 374, 384 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 supplement use, 38–39, 384 transport, 376–377 ULs, 13, 56, 374, 384–385 unit conversions, 452 Biotin deficiency facies, 377–378 Biotinidase, 375, 380, 383 Blacks glucose-6-dehydrogenase status, 108 homocysteine levels, 158 pernicious anemia, 317 riboflavin, 91, 106 vitamin B6, 174 Blood pressure. See Hypertension Body Mass Index, 24, 25, 260 Body odor, 408, 411 Body weight. See also Reference body weight ratio method and nutrient deficiency development, 129 n.1 reference weights, 24–26 thiamin pyrophosphate and, 75

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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 Calcium, 124, 370 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 choline and, 265, 398 dysplasia and metaplasia, 264–265 folate and, 12, 196, 204, 205, 264–266, 269, 276 riboflavin and, 90, 94 vitamin B12 and, 264, 317, 346 Carbamazepine, 246, 525 Carbohydrate metabolism, 58, 63, 94, 95– 96 Carcinoid syndrome, 128, 137 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 AIs, 21, 31–32 derivation of DRIs for, 21, 31–33 EARs, 20, 31–32 RDAs, 20, 32–33 supplement use, 38, 39 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 cancer, 265, 398 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 deficiency, 265, 394–395 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 fetal, 404, 405 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 laboratory values, 407, 457, 459

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline lactation, 400, 406, 411–412 life stage and, 400–406, 410–412 and liver dysfunction, 11, 390, 391–392, 393, 394, 396–397, 398, 408, 409 metabolism, 391, 392–393 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 supplement use, 407, 412–413 ULs, 13, 22, 56, 390, 408–413 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) biotin, 384, 407, 466–477 choline, 407 folate, 269–272, 281, 474–475 niacin, 137–138, 139, 470–471 quality of food composition data, 36, 37, 38 riboflavin, 113, 114, 468–469 thiamin, 79, 80–81, 466–467 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 Craniorachischisis, 241, 243 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 folate, 15, 16, 206–207 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 supplement intakes, 37, 407 Defined nutritional states, 21 Dementia, 397 Depletion-repletion studies folate, 221–225, 226–227, 228–229 methodological issues, 34, 438–439 thiamin, 69, 70–73, 75 vitamin B6, 153–154, 155, 157, 158, 164, 172 Depression, 153, 267–268, 378, 409, 412 Dermatitis, 183, 377, 409 Developmental disability, 11–12, 441. See also Neural tube defects Diabetes mellitus, 90, 144, 260, 321 Diabetic neuropathy, 184 Dietary fiber, 18, 211, 322

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline Dietary folate equivalents (DFEs), 1, 14 defined, 10–11 derivation, 196, 221, 227 EAR derivation, 1, 210 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 sources of data, 36–37, 113 underreporting of, 36, 272 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 criteria for, 6–7, 10, 423 defined, 2–3, 17–18 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 sources of data, 2, 6; see also Methodological considerations uses, 2, 3, 4, 14, 423–435 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 adolescents, 187, 281, 412 adults, 142–143, 184–186, 277–280, 410 biotin, 385 children, 187, 281, 412 choline, 410–412, 413–414 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 infants, 186, 281, 411–412 lactation, 187, 281, 412 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 pregnancy, 186, 187, 281, 412 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 niacin, 128, 129, 137 with riboflavin, 94 with vitamin B6, 162 with vitamin B12, 313, 342 E Elderly people. See Adults, >70 years Electroencephalogram (EEG) abnormalities, 153–154, 155, 172

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline Embryogenesis, 16, 241–242, 404–405 Energy intakes, 15, 36 Energy metabolism aging and, 75, 110 exercise and, 97 gender differences, 108 lactation and, 78, 96, 130 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 vitamin B6 and, 27, 160 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 Esophageal cancer, 94, 266 Estimated Average Requirements (EARs). See also individual nutrients availability of data, 15, 29 coefficient of variation, 3, 5, 20 defined, 2, 17–19, 424 energy expenditure and, 20 extrapolation to/from other age groups, 20, 29, 31–32 group applications, 14, 427–432 indicators used to set, 6–7, 10, 22–23, 29 methods used to set, 19, 29 and RDA, 3, 6–7, 18, 19–20, 22 reference weight and height and, 25– 26 risk of inadequacy, 19 standard deviation, 3, 19–20 uses, 4, 20, 427–432 Estrogen, 129, 163–164, 213, 400 Ethnic background. See Race/ethnicity Etretinate, 246 Euglena gracilis, 315, 323 Exposure duration of, 52 route of, 51–52, 53 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 process, 44, 45 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 biotin, 377, 385 choline, 404, 405 folate, 233 growth retardation, 277, 385

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline riboflavin, 91, 110–111 sensitivity to nutrients, 48 thiamin, 76 vitamin B6, 156, 166, 176–177 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 children, 217, 220, 280–281 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 equivalents, 10–11, 196, 210 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 laboratory values, 205–206, 268, 272, 457, 459 lactation and, 238–240, 280–281

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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 NOAEL/LOAELs, 277–279, 280 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 bioavailability, 225, 235 chemistry, 197, 213 intakes, 15, 223, 224, 227 neural tube defects and, 11–12, 16 neurotoxicity, 276 research recommendations, 16 supplements, 1, 210 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 niacin, 128, 137–138, 139 pantothenic acid, 368–369 riboflavin, 113, 114 thiamin, 79, 80 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 choline, 402, 407 cow milk, 402

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline folate, 216, 217, 218–219 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 thiamin in, 79, 80 ULs and, 5, 22, 47–48 343–345 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 biotin, 380, 383 choline, 409 folate, 16, 203, 213–214, 244–245, 259, 263 neural tube defects, 244–245 special considerations, 347, 383, 409 thiamin, 61 vitamin B6, 16, 168 vitamin B12, 16, 322, 347 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 Growth factors, 32, 106 Growth retardation, 277, 385 H Hartnup’s disease, 128, 137 Hazard identification adverse effects, 50–51, 81–82, 182–183, 273–277, 346, 370, 408–409 biotin, 384–385 choline, 408–410, 411 components of, 44, 45, 50–52, 538 data sources, 50, 51 derivation of UL, 46 folate, 273–277 niacin, 138, 140–142 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

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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 colostrum, 65, 323 folate, 214–219, 239 intakes, 104 niacin, 130–131 pantothenic acid, 362–363, 368 riboflavin, 103, 104 thiamin, 65–66 tryptophan content, 130 vitamin B6, 165–166 vitamin B12, 322–326, 341 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 Hypertension, 75, 213, 260 Hypoglycemia, 359 Hypotension, 390, 408 I Ibuprofen, 212 Immune response, 175 Immunoglobulins, 89 Inborn errors of metabolism, 12 biotin-related, 378, 384, 385 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 Apgar scores, 177, 277 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 ULs, 13, 48–49, 55–56 vegan mothers, 323–324, 326 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 Iron, 129, 177, 210 Isoniazid, 128, 137, 162 Isotretinoin, 246

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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 and riboflavin, 64, 94, 96–97 and thiamin, 62, 63–64 and vitamin B6, 64, 162 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 Pruritis, 81, 409 Psoriasis, 246 Psychotropic drugs, 94 Puberty/pubertal development, 25. See also Adolescents Pyrimethamine, 213 Pyruvic acid values, 62, 94 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 AIs compared, 6, 21–22 applicable population, 18, 424–425 coefficient of variation, 32–33 criteria used to derive, 3, 6–7, 10 defined, 2, 3, 17–18 derivation of, 5, 18, 19–20, 22 EAR and, 3, 18, 19–20, 22 increasing consumption of nutrients, 14–15 indicators of nutrient adequacy, 7, 10, 23 gender differences, 2, 3, 5 group applications, 14, 424–425 for pregnancy, 11, 23 risk of inadequacy, 19 uncertainty in, 425 uses, 4, 5, 6, 21, 423, 424–425 weight and height and, 26 Recommended Dietary Allowances (reports), 2, 17

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline Reference body weight ratio method, 31, 33 biotin, 381 choline, 412 folate, 215, 280 niacin, 130, 143 pantothenic acid, 362–363 riboflavin, 104–105, 106 thiamin, 66 vitamin B6, 167 Reference weights, 24–26, 56, 65, 425 Renal disease/failure/insufficiency choline and, 409, 412 folate and, 203 thiamin and, 60 vitamin B6 and, 159, 160 vitamin B12 and, 313, 336 Requirement, defined, 17 Research recommendations adverse effects, 15, 441–442 agenda development, 437–438 biotin, 385–383, 440 choline, 413–414, 440 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 pantothenic acid, 371, 440 priorities, 413, 442 public health implications of intakes, 441 requirements studies, 439–440 riboflavin, 116 thiamin, 82–83 toxicity of nutrients, 15, 441–442 vitamin B6, 16, 188 vitamin B12, 2, 16, 348, 439, 441–442 Retinoids, 246, 525 Rheumatoid arthritis, 212–213 Riboflavin, 87–122 absorption, 88–89, 102, 115 adolescents, 105–106, 110–112, 116 adults (19–70 years), 8, 87, 92, 107–109, 110–112, 114 AIs, 103–105 bioavailability, 88, 95 and cancer, 90, 94 chemistry, 87–88, 95 children, 92, 105–106, 116 and chronic disease, 90, 94 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 fetal, 91, 110–111 food composition data, 458 food sources, 95, 113, 114 function, 10, 27, 87–88, 96 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

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline interactions with other nutrients, 88, 90, 94, 95–96, 129, 361–362 laboratory values, 456, 458 lactation, 96, 103–104, 112, 116 life-stage group and, 38–39, 103–112, 116, 427, 468–469, 482–485, 503, 506 metabolism, 89, 92, 98–102 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 race/ethnicity and, 91, 106 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 ULs, 13, 56, 87, 115–116 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 basic concepts, 12–13, 42–44 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 defined, 43, 540 derivation of UL, 46–47 folate, 16, 282–283 intake data and, 46–47, 145 niacin, 145 pantothenic acid, 370 process, 44, 45 riboflavin, 116 thiamin, 82 vitamin B6, 187 vitamin B12, 347 Risk management, 43, 44, 540 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 Smoking, 211–212, 320–321 Socioeconomic status and nutrient intake, 245–246, 363 Special considerations alcohol consumption 240 biotin, 383 breastfeeding twins, 79, 137, 240 choline, 402, 409, 412 chronic disease, 144, 342, 409, 412 dialysis patients, 18, 79, 112, 137, 383

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline in dose-response assessment for ULs, 56, 144, 187, 281, 412 drug interactions, 128, 137, 240, 246, 342 folate, 217, 240, 281 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 niacin, 137, 144 pantothenic acid, 370 riboflavin, 112, 116 in risk assessment, 48, 347, 412 thiamin, 79 vitamin B6, 167, 176, 187 vitamin B12, 325–326, 342, 347 Specificity, 34–35 Spina bifida. See Meningomyelocele Starvation, 63, 129 Stomach cancer, 266, 317 Sulfasalazine, 213, 265–266 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 doses, 264, 273 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 Tardive dyskinesia, 408, 410 Teratogenicity, 183, 186 Tetrahydrofolate, 307 Tetrahydropterin, 268 Thiamin, 58–86 absorption, 59, 62, 81–82 adolescents, 61, 63, 67–68, 76–78, 82 adults, 8, 58, 61, 66, 69–74, 76–78, 80, 82 adverse effects, 58, 81–82 AIs, 65–66 bioavailability, 62 chemistry, 58–59 children, 66–68, 82 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 food sources, 79, 80 function, 10, 27, 58, 63 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 laboratory values, 456, 458 lactation, 63, 78, 79, 82 and lactic acid values, 62, 64 life-stage group and, 38–39, 65–79, 427, 466–467, 478–481, 502, 506

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline metabolism, 59, 69–73, 75 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 pregnancy, 63, 76–78, 82 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 ULs, 13, 56, 58, 81–82 unit conversions, 451 Thiamin pyrophosphate (TPP), 58–59, 60, 61, 62, 63, 74, 75, 76–77 Thiochrome analysis, 67, 74 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 critical endpoints, 49, 53–54 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 uses, 4, 22, 426–427 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 Tryptophan, 88, 90, 96 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 riboflavin and, 88, 90, 96 Tuberculosis patients, 162 U Uncertainty approaches for dealing with, 507–511 assessment, 54–55 in data, 43, 46 in dietary intake estimates, 69, 72, 366 dose-response assessment for ULs, 54– 55 extrapolation from experimental animals to humans, 43–44, 46, 55 factor, 54–55, 540 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 Valproate, 246, 525 Vascular disease and thrombosis choline and, 398 folate and, 12, 16, 159, 196, 203, 204, 205, 259, 260–264, 269

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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 AIs, 153, 165–167 alcohol consumption and, 164 bioavailability, 150, 160–161, 165, 177 body stores, 152–153 children, 167–169, 186–187 and chronic disease, 159–160 and cognitive function, 160 data sources, 184 deficiency, 153–154, 164, 166–167, 168, 176, 178 dependency, 183, 186 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 fetal, 156, 166, 176–177 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 disorders, 12, 153–154, 160 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

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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 teratogenicity, 183, 186 and tryptophan catabolism, 154, 157– 158, 162, 163–164, 166, 170, 172, 173, 175, 177 ULs, 13, 22, 150, 182–187 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 animal studies, 274, 310, 346 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 and cancer, 264, 317, 346 chemistry, 306, 307 children, 56, 326–327 deficiency, 13, 16, 210–211, 267, 307, 310, 311–312, 313, 316–317, 330 depletion, 324 dose-response assessment for UL, 347 drug interactions, 313, 342 EARs, 9, 326, 327–337, 338–342, 427 elderly (>70 years). See Adults, >70 years enterohepatic circulation, 309–310 excretion, 310, 320–321, 331 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 infants, 56, 322–326, 339–340 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 laboratory values, 457, 459 lactation and, 322–325, 341–342 life-stage group and, 38–39, 322–342, 427, 476–477, 498–501, 505, 516–517

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline malabsorption disorders, 16, 308, 310, 318, 320, 331, 334, 342 and mental function, 267, 311, 313 metabolism, 250–255, 320–321 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 race/ethnicity and, 317, 323 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 ULs, 13, 56, 306, 346–347 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 Vitamin D, 256, 358, 361–362 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 choline, 390, 399–400 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 pantothenic acid, 362, 365 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 Zinc, 277, 524

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline FOOD AND NUTRITION BOARD, INSTITUTE OF MEDICINE-NATIONAL ACADEMY OF SCIENCES DIETARY REFERENCE INTAKES: RECOMMENDED INTAKES FOR INDIVIDUALS Life Stage Group Calcium (mg/d) Phosphorus (mg/d) Magnesium (mg/d) Vitamin D (µg/d)a,b Fluoride (mg/d) Thiamin (mg/d) Infants 0–6 mo 210* 100* 30* 5* 0.01* 0.2* 7–12 mo 270* 275* 75* 5* 0.5* 0.3* Children 1–3 y 500* 460 80 5* 0.7* 0.5 4–8 y 800* 500 130 5* 1* 0.6 Males 9–13 y 1,300* 1,250 240 5* 2* 0.9 14–18 y 1,300* 1,250 410 5* 3* 1.2 19–30 y 1,000* 700 400 5* 4* 1.2 31–50 y 1,000* 700 420 5* 4* 1.2 51–70 y 1,200* 700 420 10* 4* 1.2 > 70y 1,200* 700 420 15* 4* 1.2 Females 9–13 y 1,300* 1,250 240 5* 2* 0.9 14–18 y 1,300* 1,250 360 5* 3* 1.0 19–30 y 1,000* 700 310 5* 3* 1.1 31–50 y 1,000* 700 320 5* 3* 1.1 51–70 y 1,200* 700 320 10* 3* 1.1 > 70y 1,200* 700 320 15* 3* 1.1 Pregnancy ≤ 18y 1,300* 1,250 400 5* 3* 1.4 19–30 y 1,000* 700 350 5* 3* 1.4 31–50 y 1,000* 700 360 5* 3* 1.4 Lactation ≤ 18y 1,300* 1,250 360 5* 3* 1.4 19–30 y 1,000* 700 310 5* 3* 1.4 31–50 y 1,000* 700 320 5* 3* 1.4 NOTE: This table presents Recommended Dietary Allowances (RDAs) in bold type and Adequate Intakes (AIs) in ordinary type followed by an asterisk (*). RDAs and AIs may both be used as goals for individual intake. RDAs are set to meet the needs of almost all (97 to 98 percent) individuals in a group. For healthy breastfed infants, the AI is the mean intake. The AI for other life-stage and gender groups is believed to cover needs of all individuals in the group, but lack of data or uncertainty in the data prevent being able to specify with confidence the percentage of individuals covered by this intake. a As cholecalciferol. 1 µg cholecalciferol = 40 IU vitamin D. b In the absence of adequate exposure to sunlight. c As niacin equivalents (NE), 1 mg of niacin = 60 mg of tryptophan; 0–6 months = preformed niacin (not NE). d As dietary folate equivalents (DFE). 1 DFE = 1 µg food folate = 0.6 µg of folic acid from fortified food or as a supplement consumed with food = 0.5 µg of a supplement taken on an empty stomach.

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline 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.