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 EXAMINING
SPECIAL
NUTRITIONAL
REQUIREMENTS
IN DISEASE STATES

PROCEEDINGS OF A WORKSHOP

Anne Brown Rodgers, Rapporteur

Food and Nutrition Board

Health and Medicine Division

THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC
20001

This activity was supported by contracts between the National Academy of

Sciences and the Academy of Nutrition and Dietetics; American Society for
Nutrition; Crohn’s & Colitis Foundation; Health Canada; National Institutes of
Health; and U.S. Food and Drug Administration. Any opinions, findings,
conclusions, or recommendations expressed in this publication do not necessarily
reflect the views of any organization or agency that provided support for the
project.

International Standard Book Number-13: 978-0-309-47837-3

International Standard Book Number-10: 0-309-47837-5
Digital Object Identifier: https://doi.org/10.17226/25164
Epub ISBN: 978-0-309-47840-3

Additional copies of this publication are available from the National Academies
Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or
(202) 334-3313; http://www.nap.edu.

Copyright 2018 by the National Academy of Sciences. All rights reserved.

Printed in the United States of America

Suggested citation: National Academies of Sciences, Engineering, and Medicine.

2018. Examining special nutritional requirements in disease states: Proceedings of
a workshop. Washington, DC: The National Academies Press. doi: https://doi.org/1
0.17226/25164.
The National Academy of Sciences was established in 1863 by
an Act of Congress, signed by President Lincoln, as a private,
nongovernmental institution to advise the nation on issues related to
science and technology. Members are elected by their peers for
outstanding contributions to research. Dr. Marcia McNutt is
president.

The National Academy of Engineering was established in 1964

under the charter of the National Academy of Sciences to bring the
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D. Mote, Jr., is president.

The National Academy of Medicine (formerly the Institute of

Medicine) was established in 1970 under the charter of the National
Academy of Sciences to advise the nation on medical and health
issues. Members are elected by their peers for distinguished
contributions to medicine and health. Dr. Victor J. Dzau is president.

The three Academies work together as the National Academies of

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increase public understanding in matters of science, engineering,
and medicine.

Learn more about the National Academies of Sciences, Engineering,

and Medicine at www.nationalacademies.org.
Consensus Study Reports published by the National Academies of
Sciences, Engineering, and Medicine document the evidence-based
consensus on the study’s statement of task by an authoring
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Proceedings published by the National Academies of Sciences,

Engineering, and Medicine chronicle the presentations and
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other participants, the planning committee, or the National
Academies.

For information about other products and activities of the National

Academies, please visit www.nationalacademies.org/about/whatwed
o.
 PLANNING COMMITTEE ON EXAMINING SPECIAL
NUTRITIONAL REQUIREMENTS FOR DISEASE
STATES—A WORKSHOP1

BARBARA O. SCHNEEMAN (Chair), Professor Emerita, University

of California, Davis
PATSY M. BRANNON, Professor, Division of Nutritional Sciences,
Cornell University, Ithaca, NY
STEVEN K. CLINTON, Professor, Department of Internal Medicine,
Division of Medical Oncology, The Ohio State University,
Columbus
ALEX R. KEMPER, Chief of the Division of Ambulatory Pediatrics,
Nationwide Children’s Hospital, Columbus, OH
ERIN MACLEOD, Director of Metabolic Nutrition, Division of
Genetics and Metabolism, Children’s National Health System,
Washington, DC
BERNADETTE P. MARRIOTT, Professor, Division of
Gastroenterology and Hepatology, Department of Medicine, and
Professor, Military Division, Department of Psychiatry, Medical
University of South Carolina, Charleston
PATRICK J. STOVER, Vice Chancellor and Dean for Agriculture and
Life Sciences at Texas A&M AgriLife, College Station
DAVID L. SUSKIND, Professor of Pediatrics, Division of
Gastroenterology, Seattle Children’s Hospital, Washington
GARY D. WU, Ferdinand G. Weisbrod Professor in Gastroenterology,
Perelman School of Medicine, University of Pennsylvania,
Philadelphia

Health and Medicine Division Staff

MARIA ORIA, Study Director
ALICE VOROSMARTI, Research Associate
CYPRESS LYNX, Senior Program Assistant
ANN L. YAKTINE, Director, Food and Nutrition Board
__________________
1 The National Academies of Sciences, Engineering, and Medicine’s planning
committees are solely responsible for organizing the workshop, identifying topics,
and choosing speakers. The responsibility for the published Proceedings of a
Workshop rests with the workshop rapporteur and the National Academies.
 Reviewers

This Proceedings of a Workshop was reviewed in draft form by

individuals chosen for their diverse perspectives and technical
expertise. The purpose of this independent review is to provide
candid and critical comments that will assist the National Academies
of Sciences, Engineering, and Medicine in making each published
proceedings as sound as possible and to ensure that it meets the
institutional standards for quality, objectivity, evidence, and
responsiveness to the charge. The review comments and draft
manuscript remain confidential to protect the integrity of the
process.
We thank the following individuals for their review of this
proceedings:

JOHN W. ERDMAN, Emeritus, University of Illinois at Urbana-

Champaign
DENISE M. NEY, University of Wisconsin–Madison
ROBERT M. RUSSELL, Emeritus, Tufts University School of
Medicine
DAVID L. SUSKIND, Seattle Children’s Hospital

Although the reviewers listed above provided many constructive

comments and suggestions, they were not asked to endorse the
content of the proceedings nor did they see the final draft before its
release. The review of this proceedings was overseen by A.
CATHERINE ROSS, The Pennsylvania State University. She was
responsible for making certain that an independent examination of
this proceedings was carried out in accordance with standards of the
National Academies and that all review comments were carefully
considered. Responsibility for the final content rests entirely with the
rapporteur and the National Academies.
 Contents

ACRONYMS AND ABBREVIATIONS

1 INTRODUCTION AND WORKSHOP OVERVIEW

Organization of This Proceedings of a Workshop
Welcoming Remarks
What Defines a Special Nutritional Requirement?
The Underlying Biological Processes of Special Nutritional
Requirements
Moderated Panel Discussion and Q&A
References

2 ADDRESSING NUTRIENT NEEDS DUE TO LOSS OF

FUNCTION IN GENETIC DISEASES
Understanding the Basis of Nutritional Needs in Phenylketonuria
Nutritional Inadequacies in Mitochondrial-Associated Metabolic
Disorders
Contribution of Nutrients in Complex Inborn Errors of Metabolism:
The Case of Methylmalonic Acidemia
Lessons Learned: What Is Known About Nutrition Management for
Inborn Errors of Metabolism
Moderated Panel Discussion and Q&A
References
3 DISEASE-INDUCED LOSS OF FUNCTION AND TISSUE
REGENERATION
Examples of Gastrointestinal Dysfunction and Malabsorption of
Nutrients: Intestinal Failure
Examples of Gastrointestinal Dysfunction and Malabsorption of
Nutrients: Cystic Fibrosis
Nutritional Requirements for Inflammatory Bowel Disease
Blood–Brain Barrier Dysfunction and Resulting Brain Nutrient
Deficiencies
Macro- and Micronutrient Homeostasis in the Setting of Chronic
Kidney Disease
Moderated Panel Discussion and Q&A
References

4 DISEASE-INDUCED DEFICIENCY AND CONDITIONALLY

ESSENTIAL NUTRIENTS IN DISEASE
Arginine as an Example of a Conditionally Essential Nutrient: Sickle
Cell Anemia and Surgery
Traumatic Brain Injury: Pathophysiological Mechanisms and
Potential Nutrient Needs
Metabolic Turnover, Inflammation, and Redistribution: Impact on
Nutrient Requirements
Moderated Panel Discussion and Q&A
References

5 BUILDING THE EVIDENCE BASE: RESEARCH APPROACHES

FOR NUTRIENTS IN DISEASE STATES
Type and Strength of Evidence Needed for Determining Special
Nutrient Requirements
Identification and Validation of Biomarkers in Disease States
Innovative Causal Designs for Efficacy: What Type of Evidence Is
Needed?
Examples of a Complex Disease: Inflammatory Bowel Disease
Examples of a Complex Disease: Cancer
Moderated Panel Discussion and Q&A
References
6 EXPLORING POTENTIAL OPPORTUNITIES
Panel Discussion
Open Discussion and Q&A
Closing Remarks
Reference

APPENDIXES
A WORKSHOP AGENDA
B SPEAKER AND MODERATOR BIOGRAPHICAL SKETCHES
 Boxes, Figures, and Tables

BOXES

1-1 Statement of Task

1-2 What Constitutes a Distribution Outside of the Dietary Reference
Intakes?

FIGURES

1-1 Traditional DRIs: Distribution of requirement and risk of adverse

outcome in a “healthy” population
1-2 Classifying and evaluating human nutrient needs

2-1 Mitochondrial disease: Molecular pathways affected by genetic

disorders
2-2 Novel treatment strategies in mitochondrial disease
2-3 Daily protein intake by patients with methylmalonic acidemia
mut subtype, sorted by age

3-1 Prevalence of micronutrient deficiencies during parenteral

nutrition weaning
3-2 Survival in children with cystic fibrosis at various weight-for-age
percentiles
3-3 Influence of disease on whole-body nutrient status and tissue-
specific nutrient status
4-1 The arginine metabolome
4-2 Mechanisms of vasculopathy and endothelial dysfunction

5-1 Risk assessment approach to setting Dietary Reference Intake

values
5-2 Establishing adequacy: Biomarkers of exposure on the causal
pathway, using folate as an example
5-3 Nutrient requirements in disease states
5-4 Example of complex relationships in cystic fibrosis
5-5 The relationship among diet, the gut microbiota, and
inflammatory bowel disease

TABLES

1-1 Comparison of Dietary Reference Intakes and Special Nutritional

Needs

3-1 Summary of Nutrient Requirements in Chronic Kidney Disease

 Acronyms and Abbreviations

AI Adequate Intake
AND Academy of Nutrition and Dietetics
ASN American Society for Nutrition
ATP adenosine triphosphate

BBB blood–brain barrier

BMI body mass index
BOND Biomarkers of Nutrition for Development
BRINDA Biomarkers Reflecting Inflammation and
Nutritional Determinants of Anemia

CF cystic fibrosis
CFD cerebral folate deficiency
CFTR cystic fibrosis transmembrane conductance
regulator
CHOP Children’s Hospital of Pennsylvania
CKD chronic kidney disease
CRP C-reactive protein
CSF cerebrospinal fluid

DHA docosahexaenoic acid

DNA deoxyribonucleic acid
DoD Department of Defense
DRI Dietary Reference Intake

EAR Estimated Average Requirement

EEN exclusive enteral nutrition
EPA eicosapentaenoic acid

FARMM Food and Resulting Microbial Metabolites

FDA U.S. Food and Drug Administration
FODMAP fermentable oligosaccharides, disaccharides,
monosaccharides, and polyols

GFR glomerular filtration rate

GI gastrointestinal
GMP glycomacropeptide
GRADE Grading of Recommendations Assessment,
Development and Evaluation

IBD inflammatory bowel disease

IOM Institute of Medicine

MELAS mitochondrial encephalopathy, lactic acidosis, and

stroke-like episodes
MMA methylmalonic aciduria

NAD+ nicotinamide adenine dinucleotide

NADH nicotinamide adenine dinucleotide + hydrogen
NADPH nicotinamide adenine dinucleotide phosphate
NHANES National Health and Nutrition Examination Survey
NIH National Institutes of Health
NOS nitric oxide synthase

PAH phenylalanine hydroxylase

PEW protein energy wasting
Phe phenylalanine
PICO Population, Intervention, Comparisons, Outcomes
PKU phenylketonuria
PLP pyridoxal phosphate

RCT randomized controlled trial

RD registered dietitian
RDA Recommended Dietary Allowance

TBI traumatic brain injury

UL Tolerable Upper Intake Level

WCRF-AICR World Cancer Research Fund and the American

Institute for Cancer Research
WHO World Health Organization
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