|
|
Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline
Standing Committee on the Scientific Evaluation of Dietary Reference Intakes
Panel on Folate, Other B Vitamins, and Choline
NATIONAL ACADEMY PRESS
NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This project was funded by the U.S. Department of Health and Human Services Office of Disease Prevention and Health Promotion, Contract No. 282-96-0033, T01; the National Institutes of Health Office of Nutrition Supplements, Contract No. N01-OD-4-2139, T024, the Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Division of Nutrition and Physical Activity; Health Canada; the Institute of Medicine; and the Dietary Reference Intakes Corporate Donors' Fund. Contributors to the Fund include Roche Vitamins Inc, Mead Johnson Nutrition Group, Daiichi Fine Chemicals, Inc, Kemin Foods, Inc, M&M Mars, Weider Nutrition Group, and Natural Source Vitamin E Association. The opinions or conclusions expressed herein do not necessarily reflect those of the funders. Library of Congress Cataloging-in-Publication Data
Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitaminB12, pantothenic acid, biotin, and choline / a report of the Standing Committee on the
Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B
Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients, Food
and Nutrition Board, Institute of Medicine.
QP772.V52 D53 2000 612.3´99--dc21 00-028380 Additional copies of this report are available from National Academy Press, 2101 Constitution Avenue, N.W., Lock Box 285, Washington, DC 20055. Call (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area), or visit the NAP's on-line bookstore at http:/www.nap.edu. For more information about the Institute of Medicine or the Food and Nutrition Board, visit the IOM home page at http://www.nas.edu/iom. Copyright 1998 by the National Academy of Sciences. All rights reserved. Printed in the United States of America The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The image adopted as a logotype by the Institute of Medicine is based on a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.
The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce M. Alberts is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. William A. Wulf is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. William A. Wulf are chairman and vice chairman, respectively, of the National Research Council.
PANEL ON FOLATE, OTHER B VITAMINS, AND CHOLINE
ROY M. PITKIN (Chair), Department of Obstetrics and Gynecology, University of California, Los Angeles (Professor Emeritus) and Obstetrics & Gynecology (Editor), Los Angeles LINDSAY H. ALLEN, Department of Nutrition, University of California, Davis LYNN B. BAILEY, Food Science and Human Nutrition Department, University of Florida, Gainesville MERTON BERNFIELD, Department of Pediatrics, Harvard Medical School, Boston PHILLIPE De WALS, Department of Community Health Sciences, University of Sherbrooke, Quebec RALPH GREEN, Department of Pathology, University of California at Davis Medical Center, Sacramento DONALD B. McCORMICK, Department of Biochemistry, Emory University School of Medicine, Atlanta ROBERT M. RUSSELL, Department of Medicine and Nutrition at the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston BARRY SHANE, Department of Nutritional Sciences, University of California, Berkeley STEVEN H. ZEISEL, Department of Nutrition, University of North Carolina School of Public Health and School of Medicine, Chapel Hill IRWIN H. ROSENBERG, Clinical Nutrition Division, the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University and New England Medical Center, Boston, Liaison to the Panel from the Subcommittee on Upper Reference Levels of Nutrients Staff CAROL W. SUITOR, Study Director ELISABETH A. REESE, Research Associate ALICE L. KULIK, Research Assistant MICHELE RAMSEY, Project Assistant
SUBCOMMITTEE ON UPPER REFERENCE LEVELS OF NUTRIENTS
IAN C. MUNRO (Chair), CanTox, Inc., Mississauga, Ontario WALTER MERTZ, Retired, U.S. Department of Agriculture Human Nutrition Research Center, Rockville, Maryland RITA B. MESSING, Division of Environmental Health, Minnesota Department of Health, St. Paul SANFORD A. MILLER, Graduate School of Biomedical Sciences, University of Texas Health Sciences Center, San Antonio SUZANNE P. MURPHY, Department of Nutritional Sciences, University of California, Berkeley JOSEPH V. RODRICKS, ENVIRON Corporation, Arlington, Virginia IRWIN H. ROSENBERG, Clinical Nutrition Division, the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University and New England Medical Center, Boston STEVE L. TAYLOR, Department of Food Science and Technology and Food Processing Center, University of Nebraska, Lincoln ROBERT H. WASSERMAN, Department of Physiology, College of Veterinary Medicine, Cornell University, Ithaca Consultants SHEILA DUBOIS, Food Directorate, Health Canada, Ottawa HERBERT BLUMENTHAL, Retired, Food and Drug Administration, Washington, D.C. Staff SANDRA SCHLICKER, Study Director ELISABETH A. REESE, Research Associate GERALDINE KENNEDO, Project Assistant
STANDING COMMITTEE ON THE SCIENTIFIC EVALUATION OF DIETARY REFERENCE INTAKES
VERNON R. YOUNG (Chair), Laboratory of Human Nutrition, School of Science, Massachusetts Institute of Technology, Cambridge JOHN W. ERDMAN, JR. (Vice-Chair), Division of Nutritional Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana-Champaign JANET C. KING (Vice-Chair), University of California, Berkeley, and U.S. Department of Agriculture Western Human Nutrition Research Center, Presidio of San Francisco LINDSAY H. ALLEN, Department of Nutrition, University of California, Davis STEPHANIE A. ATKINSON, Department of Pediatrics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario JOHANNA T. DWYER, Frances Stern Nutrition Center, New England Medical Center and Tufts University, Boston JOHN D. FERNSTROM, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh SCOTT M. GRUNDY, Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas CHARLES H. HENNEKENS, Department of Medicine, Ambulatory Care and Prevention and Division of Preventive Medicine, Harvard Medical School, Boston SANFORD A. MILLER, Graduate School of Biomedical Sciences, University of Texas Health Science Center, San Antonio U.S. Government Liaison LINDA MEYERS, Office of Disease Prevention and Health Promotion, U.S. Department of Health and Human Services, Washington, D.C. Canadian Government Liaison PETER W.F. FISCHER, Nutrition Research Division, Health Protection Branch, Health Canada, Ottawa Staff ALLISON A. YATES, Study Director SANDRA SCHLICKER, Senior Program Officer CAROL W. SUITOR, Senior Program Officer ELISABETH A. REESE, Research Associate ALICE L. KULIK, Research Assistant GAIL E. SPEARS, Administrative Assistant GERALDINE KENNEDO, Project Assistant MICHELE RAMSEY, Project Assistant
FOOD AND NUTRITION BOARD
CUTBERTO GARZA (Chair), Division of Nutrition, Cornell University, Ithaca JOHN W. ERDMAN, JR. (Vice-Chair), Division of Nutritional Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana-Champaign LINDSAY H. ALLEN, Department of Nutrition, University of California, Davis BENJAMIN CABALLERO, Center for Human Nutrition, Johns Hopkins School of Hygiene and Public Health, Baltimore ROBERT J. COUSINS, Center for Nutritional Sciences, University of Florida, Gainesville FERGUS M. CLYDESDALE, Department of Food Science, University of Massachusetts, Amherst MICHAEL P. DOYLE, Department of Food Science and Technology, Center for Food Safety and Quality Enhancement, University of Georgia, Griffin JOHANNA T. DWYER, Frances Stern Nutrition Center, New England Medical Center and Tufts University, Boston SCOTT M. GRUNDY, Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas CHARLES H. HENNEKENS, Department of Medicine, Ambulatory Care and Prevention and Division of Preventive Medicine, Harvard Medical School, Boston JANET C. KING, University of California, Berkeley, and U.S. Department of Agriculture Western Human Nutrition Research Center, Presidio of San Francisco SANFORD A. MILLER, Graduate School of Biomedical Sciences, University of Texas Health Science Center, San Antonio ROSS L. PRENTICE, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle A. CATHARINE ROSS, Department of Nutrition, The Pennsylvania State University, University Park ROBERT E. SMITH, R.E. Smith Consulting, Inc., Newport, Vermont VIRGINIA A. STALLINGS, Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia VERNON R. YOUNG, Laboratory of Human Nutrition, School of Science, Massachusetts Institute of Technology, Cambridge Ex-Officio Member STEVE L. TAYLOR, Department of Food Science and Technology and Food Processing Center, University of Nebraska, Lincoln Staff ALLISON A. YATES, Director GAIL E. SPEARS, Administrative Assistant CARLOS GABRIEL, Financial Associate
Preface
This report is the second in a series that presents a comprehensive set of reference values for nutrient intakes for healthy U.S and Canadian populations. It is a product of the Food and Nutrition Board of the Institute of Medicine (IOM) working in cooperation with scientists from Canada. The report establishes a set of reference values for the B vitamins and choline to replace previously published Recommended Dietary Allowances (RDAs) for the United States and Recommended Nutrient Intakes (RNIs) for Canada. It considers evidence concerning the prevention of disease and developmental disorders along with more traditional evidence of sufficient nutrient intake; and examines data about choline, a food component that in the past has not been considered essential in the human diet. Although the reference values are based on data, the data were often scanty or drawn from studies that had limitations in addressing the question. Thus, scientific judgment was required in setting the reference values. The reasoning used is described for each nutrient in Chapters 4 through 12. Evidence concerning the use of these nutrients for the amelioration or cure of disease or disability was not considered because that was beyond the project's scope of work. The B vitamins appear second in the series largely because recommendations for folate intake have been a subject of controversy for many years. The RDA for folate has shifted up and down. Recently, low folate intake has been linked with vascular disease and other chronic conditions as well as risk of neural tube defects and other congenital malformations in the offspring of women of reproductive age. However, high folate intake has also been implicated in delaying the diagnosis of pernicious anemia until after irreversible neurological damage has occurred. A major task of the Panel on Folate, Other B Vitamins, and Choline; the Subcommittee on Upper Reference Levels of Nutrients (UL Subcommittee); and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes (DRI Committee) was to analyze the evidence on beneficial and adverse effects of different folate intakes--in the context of setting Dietary Reference Intakes (DRIs) for all the B vitamins and choline. Many of the questions raised about requirements for and recommended intakes of B vitamins and choline cannot be answered fully because of inadequacies in the present database. Apart from studies of overt deficiency disease, there is a dearth of studies that address specific effects of inadequate B vitamin intakes on health status. For most of the B vitamins, there is no direct information that permits estimating the amounts required by children and adolescents. For five of the B vitamins, data useful for the setting of Tolerable Upper Intake Levels (ULs) are sparse, precluding reliable estimates of how much can be ingested safely. For some of these nutrients, there are questions about how much is contained in the food North Americans eat. Thus, another major task of the report was to outline a research agenda to provide a basis for public policy decisions related to recommended intakes of the B vitamins and choline and ways to achieve those intakes. The process for establishing DRIs is an iterative process and is thus evolving as the conceptual framework is applied to new nutrients and food components. With more experience, the proposed models for establishing reference intakes for use with nutrients and food components that play a role in health will be refined and, as new information or new methods of analysis are adopted, these reference values will be reassessed. The DRI Committee and its UL Subcommittee are developing plans to explore ways to address the safety of high nutrient intakes in other age groups or situations where data are lacking. For example, although the panel chose to use metabolic body weight (kg0.75) as the basis for adjusting all DRIs, including ULs for children for establishing intakes of the vitamins reviewed in this report, the proposed risk assessment model of the UL Subcommittee uses body weight directly as the default for extrapolation to children because of its more conservative result. Considerations of bioavailability and nutrient-nutrient interactions played a key role in the decision-making process for several B vitamins. For example, the concept of dietary folate equivalents is introduced to help estimate folate requirements, and limitations on the absorption of vitamin B12 were considered when recommending B12 intake for the elderly. Because the project is ongoing as indicated above, and many comments were solicited and have been received on the first report in the series (Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride), it has been possible to introduce refinements in introductory material (Chapters 1 through 3) and in the discussion of uses of DRIs (Chapter 13 in this report). For example, it is now clearly stated that a detrimental nutrient-nutrient interaction could be used as the critical adverse effect in setting a UL for a nutrient. Among the comments have been requests for additional guidance in the practical application of DRIs. The newly formed Subcommittee on the Interpretation and Uses of Dietary Reference Intakes will work toward that end. This report reflects the work of the Food and Nutrition Board's DRI Committee; the expert Panel on Folate, Other B Vitamins, and Choline; and the UL Subcommittee. The support of the government of Canada and Canadian scientists in this initiative represents a pioneering first step in the standardization of nutrient reference intakes at least within one continent. A brief description of the overall project of the DRI Committee and of the panel's task are given in Appendix A. It is hoped that the critical, comprehensive analyses of available information and of knowledge gaps in this initial series of reports will greatly assist the private sector, foundations, universities, government laboratories, and other institutions with their research interests and with the development of a productive research agenda for the next decade. The DRI Committee; the Panel on Folate, Other B Vitamins, and Choline; and the UL Subcommittee wish to extend sincere thanks to the many experts who have assisted with this report by giving presentations, providing written materials, participating in discussions, analyzing data, and other means. Many, but far from all, of these people are named in Appendix B. Special thanks go to Robert A. Jacob and Donald M. Mock, who made major contributions to chapters on niacin and biotin, respectively, and to staff at the National Center for Health Statistics, the Food Surveys Research Group of the Agricultural Research Service, and the Department of Statistics at Iowa State University for extensive analyses of survey data. The respective chairs and members of the panel and subcommittee have performed their work under great time pressure. Their dedication made the completion of this report possible. All gave of their time willingly and without financial reward; both the science and practice of nutrition are major beneficiaries. This report has been reviewed by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council's Report Review Committee. The purpose of this independent review is to provide candid and critical comments to assist the authors and the IOM in making the published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The content of the review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their participation in the review of this report: Frederick C. Battaglia, M.D., University of Colorado Health Sciences Center; Enriqueta C. Bond, Ph.D., Burroughs Wellcome Fund; Patricia K. Crumrine, M.D., Children's Hospital; Krishnamurti Dakshinamurti, Ph.D., University of Manitoba; Gary Flamm, Ph.D., Flamm Associates; Theresa Glanville, Ph.D., Mount Saint Vincent University; John Hathcock, Ph.D., Council for Responsible Nutrition; James Marshall, Ph.D., Arizona Cancer Center; Deborah O'Connor, Ph.D., Ross Laboratories; Claire Regan, M.S., R.D., Grocery Manufacturers of America; Eric Rimm, Sc.D., Harvard School of Public Health; Killian Robinson, M.D., Cleveland Clinic Foundation; Robert Rucker, Ph.D., University of California-Davis; Robert F. Schilling, M.D., University of Wisconsin; John Scott, Ph.D., Sc.D., M.A., University of Dublin, Trinity College. Although the individuals listed above have provided many constructive comments and suggestions, responsibility for the final content of this report rests solely with the authoring committee and the IOM. The DRI Committee wishes to acknowledge, in particular, the commitment shown by Roy Pitkin, chair of the panel, who steered this difficult project through what at times seemed to some of us like dangerous and uncharted waters. His ability to keep the effort and our various biases moving in a positive direction is very much appreciated. Special thanks go to the staff of the Food and Nutrition Board and foremost to Carol Suitor, who was the study director for the panel and without whose assistance, both intellectual and managerial, this report would neither have been as polished nor as timely in its initial release. She now moves on to enjoy the peace of her new home in beautiful Vermont and we wish her well. It is, of course those at the Food and Nutrition Board who get the real work completed and so the committee wishes to thank Allison Yates, Director of the Food and Nutrition Board, for constant assistance and it also recognizes, with appreciation, the contributions of Sandra Schlicker, Elisabeth Reese, Kimberly Brewer, Alice Kulik, Sheila Moats, Gail Spears, Diane Johnson, Michele Ramsey, and Geraldine Kennedo. We also thank Judith Grumstrup-Scott and Judith Dickson for editing the manuscript and Mike Edington and Claudia Carl for assistance with publication.
Contents
Summary
This report on folate, other B vitamins, and choline is one of a series that presents dietary reference values for the intake of nutrients by Americans and Canadians. The overall project is a comprehensive effort undertaken by the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes (DRI Committee) of the Food and Nutrition Board, Institute of Medicine, National Academy of Sciences, with active involvement of Health Canada. (See Appendix A for a description of the overall process and its origins.) This study was requested by the U.S. Federal Steering Committee for Dietary Reference Intakes and coordinated by the U.S. Department of Health and Human Services Office of Disease Prevention and Health Promotion; with funding from the Office of Dietary Supplements, National Institutes of Health; Division of Nutrition and Physical Activity, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention; the Agricultural Research Service, U.S. Department of Agriculture; and Health Canada. Additional funding was provided by contributors to the DRI Corporate Donors Fund. Major new recommendations in this report include the following:
WHAT ARE DIETARY REFERENCE INTAKES?
Dietary Reference Intakes (DRIs) are reference values that are quantitative estimates of nutrient intakes to be used for planning and assessing diets for healthy people. They include RDAs but also three other types of reference values (see Box S-1). Although the reference values are based on data, the data were often scanty or drawn from studies that had limitations in addressing the question. Thus, scientific judgment was required in setting the reference values. The reasoning used is described for each nutrient in Chapters 4 through 12.
The development of DRIs expands on the periodic reports called Recommended Dietary Allowances, which have been published since 1941 by the National Academy of Sciences. The chart on the inside back cover gives the recommended intake levels, whether RDAs or AIs, for the B vitamins and choline by life stage and gender group. Uses of DRIs appear in Box S-2. The transition from using RDAs alone to using all the DRIs appropriately will require time and effort by health professionals and others.
Recommended Dietary Allowances
The Recommended Dietary Allowance (RDA) is the average daily dietary intake level that is sufficient to meet the nutrient requirement of nearly all (97 to 98 percent) healthy individuals in a particular life stage (life stage considers age and, when applicable, pregnancy or lactation) and gender group.
Process for Setting the RDA
The process for setting the RDA depends on being able to set an Estimated Average Requirement (EAR). That is, the RDA is derived from the nutrient requirement; therefore, if an EAR cannot be set, no RDA will be set. The EAR is the daily intake value of a nutrient that is estimated to meet the nutrient requirement of half the healthy individuals in a life stage and gender group. Before setting the EAR, a specific criterion of adequacy is selected based on a careful review of the literature. When selecting the criterion, contemporary concepts of the reduction of disease risk are considered along with many other health parameters. If the standard deviation (SD) of the EAR is available and the requirement for the nutrient is normally distributed, the RDA is set at 2 SDs above the EAR: RDA = EAR + 2 SDEAR. If data about variability in requirements are insufficient to calculate an SD, a coefficient of variation for the EAR of 10 percent is ordinarily assumed in this report. The resulting equation for the RDA is then RDA = 1.2 x EAR. If the estimated coefficient of variation is 15 percent, the formula would be RDA = 1.3 x EAR. If the nutrient requirement is known to be skewed for a population, other approaches are used to find the ninety-seventh to ninety-eighth percentile to set the RDA. The RDA for a nutrient is a value to be used as a goal for dietary intake by healthy individuals. As discussed in Chapter 13 of the report, the RDA is not intended to be used to assess the diets of either individuals or groups or to plan diets for groups.
Adequate Intakes
The Adequate Intake (AI) is set instead of an RDA if sufficient scientific evidence is not available for calculating an EAR. The AI is based on observed or experimentally determined estimates of nutrient intake by a group (or groups) of healthy people. For example, the AI for young infants, for whom human milk is the recommended sole source of food for the first 4 to 6 months, is based on the daily mean nutrient intake supplied by human milk for healthy, full-term infants who are exclusively breastfed. The main intended use of the AI is as a goal for the nutrient intake of individuals. Other possible uses of AIs will be considered by another expert group.
Tolerable Upper Intake Levels
The Tolerable Upper Intake Level (UL) is the highest level of daily nutrient intake that is likely to pose no risk of adverse health effects to almost all individuals in the general population. As intake increases above the UL, the risk of adverse effects increases. The term tolerable intake was chosen to avoid implying a possible beneficial effect. Instead, the term is intended to connote a level of intake that can, with high probability, be tolerated biologically. The UL is not intended to be a recommended level of intake. There is no established benefit for healthy individuals if they consume nutrient intakes above the RDA or AI. ULs are useful because of the increased interest in and availability of fortified foods and the increased use of dietary supplements. ULs are based on total intake of a nutrient from food, water, and supplements if adverse effects have been associated with total intake. However, if adverse effects have been associated with intake from supplements or food fortificants only, the UL is based on nutrient intake from those sources only, not on total intake. The UL applies to chronic daily use. For some nutrients, there are insufficient data on which to develop a UL. This does not mean that there is no potential for adverse effects resulting from high intake. When data about adverse effects are extremely limited, extra caution may be warranted.
COMPARISON OF RECOMMENDED DIETARY ALLOWANCES AND ADEQUATE INTAKES
Although the Recommended Dietary Allowance (RDA) and Adequate Intake (AI) are used for the same purpose--setting goals for intake by individuals--the RDA differs from the AI. Intake of the RDA for a nutrient is expected to meet the needs of 97 to 98 percent of the individuals in a life stage and gender group. If the EAR is not known, as is the case when an AI is set, it is not known what percentage of the individuals are covered by the AI. The AI for a nutrient is expected to exceed the average requirement for that nutrient, and it might even cover the needs of more than 98 percent of the individuals, but it might cover the needs of far fewer (see Figure S-1). The degree to which an AI exceeds the average requirement is likely to differ among nutrients and population groups.
For people with diseases that increase requirements or who have other special health needs, the RDA and AI may each serve as the basis for adjusting individual recommendations; qualified health professionals should adapt the recommended intake to cover higher or lower needs. In this report, AIs rather than RDAs are being proposed for all nutrients for infants to age 1 year and for pantothenic acid, biotin, and choline for persons of all ages (see Table S-1).
TABLE S-1 Estimated Average Requirements (EARs) and Reported Dietary Intakes of Six B Complex Vitamins by Gender for Young (19-30 years) and Older (> 70 years) Adults
NOTE: The EAR can be used to assess the adequacy of nutrient intakes by groups. To do this, one determines the percentage of individuals whose usual intakes are less than the EAR. From this table it can be seen that less than 5 percent of young men have thiamin intakes less than the EAR, but more than half of young women have reported folate intakes less than the EAR. Appendixes G and H allow more accurate estimates of percentages for all age groups than does this excerpted table. a Dietary folate equivalents for the EAR but not for reported dietary intakes. Reported intakes are likely to underestimate true intakes because of limitations of the methods used to analyze the folate content of food (see Chapter 8) and because adjustment has not been made for the higher bioavailability of the folic acid consumed in fortified foods and supplements: 1 dietary folate equivalent = 1 µg food folate = 0.6 µg of folate from fortified food or as a supplement consumed with food = 0.5 µg of a supplement taken on an empty stomach. b SOURCE: Continuing Survey of Food Intakes by Individuals (CSFII) data on B vitamin intake from food, unpublished data, A. Carriquiry, Iowa State University, 1997. c SOURCE: Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994, unpublished data on B vitamin intake from food, C.L. Johnson and J.D. Wright, National Center for Health Statistics, Centers for Disease Control and Prevention, 1997.
APPROACH FOR SETTING DIETARY REFERENCE INTAKES
The scientific data used to develop DRIs have come from observational and experimental studies. Studies published in peer-reviewed journals were the principal source of data. Life stage and gender were considered to the extent possible, but for some nutrients the data did not provide a basis for proposing different requirements for men and women or for adults in different age groups. Three of the categories of reference values (Estimated Average Requirement [EAR], Recommended Dietary Allowance [RDA], and Adequate Intake [AI]) are defined by specific criteria of nutrient adequacy; the fourth (Tolerable Upper Intake Level [UL]) is defined by a specific indicator of excess if one is available. In all cases, data are examined closely to determine whether reduction of risk of a chronic degenerative disease or developmental abnormality could be used as a criterion of adequacy. The quality of studies was examined by considering study design; methods used for measuring intake and indicators of adequacy; and biases, interactions, and confounding factors. After careful review and analysis of the evidence, including examination of the extent of congruence of findings, scientific judgment was used to determine the basis for establishing the values. In this report, the scientific evidence was judged to be too weak to use the prevention of chronic degenerative disease as the basis for setting any of the recommended levels of intake. Thus, for the B vitamins and choline, EARs and RDAs, or AIs if applicable, are based on criteria related to their general functions. For the B vitamins the EAR is somewhat higher than the amount needed to prevent deficiency disease (allowing a moderate safety margin) and there is laboratory evidence of sufficiency, but there is no observable health benefit beyond the prevention of signs and symptoms of deficiency. However, a special recommendation is included to address reduction of the risk of neural tube defects. The indicators used in deriving the RDAs and AIs are described below.
Nutrient Functions and the Indicators Used to Estimate the Requirements for the B Vitamins
Thiamin functions as a coenzyme in the metabolism of carbohydrates and branched-chain amino acids. Estimations of the requirement are based on the amount of thiamin needed to achieve and maintain normal erythrocyte transketolase activity while avoiding excessive thiamin excretion. Riboflavin functions as a coenzyme in numerous oxidation-reduction reactions. Intake in relation to a combination of indicators is used to estimate the requirement for riboflavin. These indicators include the excretion of riboflavin and its metabolites, blood values for riboflavin, and the erythrocyte glutathione reductase activity coefficient. Niacin functions as a cosubstrate or coenzyme with numerous dehydrogenases for the transfer of the hydride ion. The primary method used to estimate the requirement for niacin relates intake to the urinary excretion of niacin metabolites. The requirement is expressed in niacin equivalents, allowing for some conversion of the amino acid tryptophan to niacin. Vitamin B6 functions as a coenzyme in the metabolism of amino acids, glycogen, and sphingoid bases. To estimate the requirement, many types of biochemical data were examined; however, when possible, priority was given to the amount of B6 consistent with maintenance of an adequate plasma pyridoxal phosphate concentration. Folate functions as a coenzyme in single-carbon transfers in the metabolism of nucleic and amino acids. Folate is a generic term used to cover both the naturally occurring form of the vitamin (food folate) and the monoglutamate form (folic acid), which is used in fortified foods and supplements. To estimate the requirement the primary focus for all adults was on the amount of Dietary Folate Equivalents (DFEs) (values adjusted for differences in the absorption of food folate and folic acid) needed to maintain erythrocyte folate, but ancillary data on plasma homocysteine and plasma folate concentrations were also considered. Vitamin B12 functions as a coenzyme in the metabolism of fatty acids of odd-chain length and in methyl transfer. To estimate the requirement, the primary focus was on the amount of B12 needed for the maintenance of hematological status and serum B12 values. Pantothenic acid functions as a component of coenzyme A and phosphopantetheine, which are involved in fatty acid metabolism. The AI is based on data on pantothenic acid intake sufficient to replace urinary excretion. Biotin functions as a coenzyme in bicarbonate-dependent carboxylations. The AI is based on limited intake data. Choline functions as a precursor for acetylcholine, phospholipids, and the methyl donor betaine. The AI is based on the intake required to maintain liver function as assessed by measuring serum alanine aminotransferase levels. 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.
Consideration of the Risk of Developmental Abnormalities and Chronic Degenerative Disease
Close attention was given to evidence relating intake of B vitamins and choline to reduction of the risk of developmental disability and chronic disease. Conclusions on four of these relationships follow.
Neural Tube Defects
Because pregnancy affected by a neural tube defect (NTD) occurs in only a very small fraction of the population of women in their childbearing years, reduction of the risk of NTDs is not considered compatible with the setting of the RDA for folate. That is, by definition, the EAR would need to prevent fetal NTD in 50 percent of all women in the age group and the RDA would need to prevent it in 97 to 98 percent of the women, but NTD occurrence is already much lower than this--less than 1 percent of all pregnancies. The RDA for folate recommended in this report for women ages 19 through 50 years (400 µg/day of dietary folate equivalents) is consistent with some recommendations for the prevention of NTDs. However, the amount and form of folate demonstrated in currently available studies to minimize NTD risk is 400 µg/day of folic acid in addition to food folate. Therefore, the recommendation for women capable of becoming pregnant is to take 400 µg/day of folate from fortified foods and/or a supplement as well as food folate from a varied diet. It is not known whether the same level of protection could be achieved by using food that is naturally rich in folate. Neither is it known whether lower intakes would be protective or whether there is a threshold below which no protection occurs.
Vascular Disease and Thrombosis
Elevated homocysteine values have been associated with increased risk of vascular disease, and intakes of folate and vitamins B6 and B12 have been inversely related to homocysteine values. However, conflicting evidence exists and it is premature to conclude that increasing the intake of these B vitamins could reduce the risk of vascular disease and thrombosis. Randomized trials among high-risk, healthy individuals and among patients with vascular disease are expected to provide evidence useful in resolving this matter.
Cancer
Many studies have investigated relationships between folate status and carcinogenesis. The data suggesting an inverse relationship between folate status and the occurrence of colorectal cancer are stronger than for other forms of cancer (e.g., cancer of the cervix, esophagus, stomach, and lung) but are not conclusive.
Neuropsychiatric Disorders
Although available information suggests that a link may exist between folate deficiency and abnormal mental function, more than three decades of research have not produced a definitive connection. Other than for relatively rare inborn errors of metabolism, it is not known whether low folate or vitamin B6 status increases the risk of neuropsychiatric disorders or results from them. Neither is it known definitively how vitamin B12 status above that usually presumed to be adequate relates to psychiatric disturbances.
CRITERIA AND PROPOSED VALUES FOR TOLERABLE UPPER INTAKE LEVELS
A risk assessment model is used to derive the Tolerable Upper Intake Levels (ULs). The model consists of a systematic series of scientific considerations and judgments. The hallmark of the risk assessment model is the requirement to be explicit in all the evaluations and judgments made. Primarily as a result of database limitations, ULs are set for very broad age groups. The UL values in Table S-2 for niacin, vitamin B6, folate, and choline were set to protect the most sensitive individuals in the general population (such as those light in weight).
TABLE S-2 Tolerable Upper Intake Levels (ULsa), by Life Stage Group
a UL = maximum level of daily nutrient intake that is likely to pose no risk of adverse effects. Unless otherwise specified, the UL represents total intake from food, water, and supplements. Because of the lack of suitable data, ULs could not be established for thiamin, riboflavin, vitamin B12, pantothenic acid, or biotin. In the absence of ULs, extra caution may be warranted in consuming levels above recommended intakes. b The ULs for niacin and folate apply to forms obtained from supplements, fortified foods, or a combination of the two. c ND: Not determinable because of lack of data for adverse effects in this age group and concern with regard to lack of ability to handle excess amounts. Source of intake to prevent high levels of intake should be from formula and food only. The ULs for folate and niacin apply to forms obtained from supplements, fortified foods, or a combination of the two. As described in Chapter 8, the UL for folate is based on examination of case studies of progression of neurological effects in vitamin B12-deficient patients taking folate supplements. Because of lack of suitable data, ULs could not be established for infants or for thiamin, riboflavin, vitamin B12, pantothenic acid, or biotin. This signifies a need for data. It does not signify that people can tolerate chronic intakes of these vitamins at levels exceeding the Recommended Dietary Allowance (RDA) or Adequate Intake (AI). Like all chemical agents, nutrients can produce adverse effects if intakes are excessive. Therefore, when data are extremely limited, extra caution may be warranted.
USING DIETARY REFERENCE INTAKES TO ASSESS THE NUTRIENT INTAKE OF GROUPS
For statistical reasons that will be addressed in a future report, the Estimated Average Requirement (EAR) is greatly preferred over the Recommended Dietary Allowance (RDA) for use in assessing the nutrient intake of groups. Table S-1 shows, for example, that fewer than 5 percent of young men have dietary intakes of thiamin, riboflavin, niacin, or vitamin B12 that are less than the EARs for these nutrients. This indicates that dietary intake of these five B vitamins by young men has a high probability of being sufficient to meet their needs. A large proportion of the individuals in the population, especially women, reportedly has a total folate intake less than the EAR. However, because the reported folate content of foods is considered to be substantially underestimated (in part because of methodological problems, content not being reported in dietary folate equivalents, and data being obtained before the fortification of cereal grains was required), it is not known to what extent this discrepancy between the EAR and intake represents a problem. The determination of ways to increase dietary intake of a nutrient should include examination of the foods that are the major contributors of the nutrient to the U.S. or Canadian diet and the specific foods that are rich in the nutrient. U.S. data on both are provided in this report.
HOW TO MEET RECOMMENDED DIETARY ALLOWANCES OR ADEQUATE INTAKES
A primary question that must be answered is How can individuals consume the Recommended Dietary Allowance (RDA) or Adequate Intake (AI) if surveys indicate that typical diets contain lower amounts? This becomes a policy issue with regard to choosing methods to increase consumption of that nutrient in order to decrease the number of individuals at risk because of inadequate dietary intakes. Such methods include educating consumers to change their food consumption behavior, fortifying foodstuffs with the nutrient, providing dietary supplements, or a combination of the three methods. It is not the function of this report, given the scope of work outlined, to provide an analysis of the impact of using these three methods. Obtaining recommended intakes from unfortified foodstuffs has the advantage of providing intakes of other beneficial nutrients and of food components for which RDAs and AIs may not be determined. Another advantage is the potential enhancement of nutrient utilization through simultaneous interactions with other nutrients. It is recognized, however, that the low energy intakes reported in recent national surveys may mean that it would be unusual to see changes in food habits to the extent necessary to maintain intakes by all individuals at levels recommended in this report. Eating fortified food products represents one method by which individuals can increase or maintain intakes without major changes in food habits. For some individuals at higher risk, use of nutrient supplements may be desirable in order to meet reference intakes. It is not the function of this report (see Appendix A, Origin and Framework of the Development of Dietary Reference Intakes) to address in detail the applications of the DRIs, including considerations necessary for the assessment of adequacy of intakes of various population groups and for planning for intakes of populations or for groups with special needs. However, some uses for the different types of DRIs are described briefly in Chapter 13. A subsequent report is expected to focus on the uses of DRIs in various settings.
RECOMMENDATIONS
Reporting Data
Because of the difference in the bioavailability of food folate and the monoglutamate form of folate, it is recommended that both food folate and folic acid be included in tables of food composition and in reports of intake. That is, the content or intake of naturally occurring food folate should be reported separately from that of folate provided by fortified foods and supplements.
Research
Four major types of information gaps were noted: (1) a dearth of studies designed specifically to estimate average requirements; (2) a nearly complete lack of usable data on the nutrient needs of infants, children, and adolescents; (3) a lack of appropriately designed studies to determine the role of selected B vitamins and choline in reducing the risk of certain chronic diseases; and (4) a lack of studies designed to detect adverse effects of chronic high intakes of some B vitamins. In the judgment of the DRI Committee and its panel and subcommittees, highest priority should be given to research that has potential to prevent or retard human disease processes and to prevent deficiencies with functional consequences, as follows:
The requirements that appear to be the most productive to study are vitamin B12 requirements of the elderly and how they may be met; folate requirements, by trimester of pregnancy; and indicators on which to base vitamin B6 requirements.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
||
 |
 |
 |
