Table Of ContentNUTRITION AND IMMUNOLOGY
NUTRITION AND
IMMUNOLOGY
PRINCIPLES AND PRACTICE
EDITED BY
M.
ERIC GERSHWIN, MD
DIVISION OF RHEUMATOLOGY/ALLERGY AND CLINICAL
IMMUNOLOGY, DEPARTMENT OF INTERNAL MEDICINE
UNIVERSITY OF CALIFORNIA AT DAVIS, DAVIS, CA
J.
BRUCE GERMAN, PhD
DEPARTMENT OF FOOD SCIENCE AND TECHNOLOGY
UNIVERSITY OF CALIFORNIA AT DAVIS, DAVIS, CA
L.
CARL KEEN, PhD
DEPARTMENT OF NUTRITION
UNIVERSITY OF CALIFORNIA AT DAVIS, DAVIS, CA
SPRINGER SCIENCE+BUSINESS
MEDIA, LLC
Dedications
The editors and authors write this book in the hope that the knowledge it provides will help to achieve the day when no child on
this planet will go to bed hungry. Wish it were so.
This book is also dedicated by MEG in the memory of the late Dr. Orval L. Hamm, a farm boy from western Kansas who spent
his life sharing his knowledge of medicine and his love of people in Sialkot, Pakistan.
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Nutrition and immunology: principles and practice / edited by M. Eric
Gershwin. 1. Bruce German, Carl L. Keen
p. cm.
Includes bibliographical references
ISBN 978-1-61737-148-6 ISBN 978-1-59259-709-3 (eBook)
DOI 10.1007/978-1-59259-709-3
I.Nutrition. 2. Immunity--Nutritional aspects. I. German. Bruce
II. Gershwin. M. Eric, 1946- III. Keen, Carl L.
[ONLM: I. Nutrition. 2. Nutritional Requirements. 3. Immunity.
QU 145 N97172 1999]
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Foreword
It is a pleasure to write the foreword to Nutrition and Table 1
Immunology: Principles and Practice. In fact, this book Nutritional Status and Outcome of Infection
comes at a timely moment, when the impact of nutrition and
Definite adverse outcome
immunology is being widely felt because of the AIDS epi Measles, diarrhea, tuberculosis
demic. This is particularly of note in Africa, where large Probable adverse outcome
sums of money are being spent on nutritional intervention HIV, malaria, pneumonia
programs in the hopes of improving immune responsive Little or no effect
Poliomyelitis, tetanus, viral encephalitis
ness. We should not forget, however, early advances in our
understanding of protein energy malnutrition (PEM). PEM Note: HIV= human immunodeficiency virus
can be used as a model to understand the nutritional basis of
immunity, as well as the immunological influences on nutri
tional status. Despite advances in agricultural production, tance. However, both in vitro studies and tests in laboratory
PEM continues to affect hundreds of millions ofthe world's animals may have little resemblance to what is experienced
population. The functional impact of undernutrition varies in humans under field conditions.
from mild morbidity to life-threatening infection. The pref
INFECTIONS IN PROTEIN-ENERGY
ace to the classic World Health Organization monograph on
MALNUTRITION
Interactions of Nutrition and Infection (1) stated, "That mal
nutrition increases susceptibility to infectious disease seems The enormous collection of clinical and epidemiologic
a reasonable assumption, and clinical observation in areas data now available suggest that PEM is associated with an
where malnutrition is common has generally lent support to increase in the severity and duration of most infectious dis
this belief. Equally reasonable is the supposition that infec eases. In some cases, incidence and prevalence are also
tious diseases have an adverse effect on the nutritional state." increased. Only rarely has an antagonism between PEM and
It is only recently, however, that the pathogenetic and casual infection been reported. Table 1 gives a few examples of the
role of impaired immunity has been examined in systematic interactions between nutritional status and infection.
studies (2). Since the early 1970s, there has been a geometric
IMMUNOLOGICAL CHANGES
increase in the interest in nutritional immunology and a cor
responding plethora of original articles, reviews, and mono Beisel has provided a historical account of successive
graphs on the subject (3-12). findings in this area (6). From early historical accounts and
anecdotal observations, there have been comprehensive sys
HETEROGENEITY OF SYNDROMES
temic studies in humans and laboratory animals. These have
AND MULTIFACTORIAL CAUSALITY
led to many clinical and public health applications. Lym
In laboratory animals, it is possible to produce isolated phoid atrophy is a prominent feature in PEM. Anatomical
nutrient deficiencies. In contrast, human malnutrition is changes in lymphoid tissues in malnutrition have been des
almost always a syndrome of multiple nutrient deficiencies cribed for decades. The term "nutritional thymectomy"
compounded by genetic influences, age, gender, and the illustrates the profound changes that occur in the thymus in
superadded effect of infection. malnutrition. The size and weight of the thymus are reduced.
Also, distinct dietary habits in various parts of the world Histologically, there is a loss of corticomedullary differen
may play an additional role. Furthermore, the timing and tiation, there are fewer lymphoid cells, and the Hassal bodies
duration of nutritional deprivation has a significant impact are enlarged, degenerated, and, occasionally, calcified.
on the extent and duration of immunological impairment. These changes are easily differentiated from findings in
It is important to state at the outset that the results of primary immunity deficiency, such as DiGeorge's syn
controlled animal experiments have great scientific impor- drome. In the spleen, there is a loss oflymphoid cells around
v
vi FOREWORD
Table 2 Table 3
Delayed Cutaneous Hypersensitivity Responses Complement System
in Young Children with PEM
Protein-energy
Candida Trichophyton Tetanus DNCB Healthy malnutrition
Baseline 38 29 43 68 Total hemolytic
After 8 wk of complement activity
nutrition Support 63 59 78 92 CH50 (kU/L) 116 ± 19 67 ± 12
C3 (giL) 1.43±0.15 0.61 ± 0.09
Note: DNCB= 2,4 dimitrochlorobenzene. Figures refer to percent
C5 (giL) 0.081 ± 0.003 0.049 ± 0.002
positive responses.
Factor B (giL) 2.29±0.17 1.21 ±O.ll
Note: Values are shown as mean ± standard deviation.
small blood vessels. In lymph nodes, the thymus-dependent
paracortical areas show depletion of lymphocytes.
Protein-energy malnutrition (PEM) is associated with an nourished. This may provide an explanation for a higher
impairment of most of the host barriers. Delayed cutaneous frequency of antigen-antibody complexes found in such
hypersensitivity responses both to recall and new antigens patients. As opposed to serum antibody responses, secretory
are indicators of in vivo cell-mediated immunity and are immunoglobulin A (sIgA) antibody concentrations are
markedly depressed in PEM (Table 2). These changes are decreased after immunization with viral vaccines; there is a
observed in moderate deficiencies as well. Findings in selective reduction in sIgA concentrations. This may have
patients with kwashiorkor are more striking than findings in several clinical implications, including an increased fre
patients with marasmus. The skin reactions are restored after quency ofs epticemia commonly observed in undernourished
appropriate nutritional therapy for several weeks and months children.
(Table 2). One possible reason for reduced cell-mediated Phagocytosis is also affected in PEM. Complement is an
immunity in PEM is the reduction in mature fully differenti essential opsonin and the concentrations and activity of most
ated T lymphocytes. The reduction in serum thymulin activ complement components are decreased. The best docu
ity observed in primary PEM may underlie the impaired mented is a reduction in complement C3, C5, factor B, and
maturation of T lymphocytes. There is an increase in the total hemolytic activity (Table 3). There is a reduction in
amount of deoxynucleotidyl transferase activity in leuko opsonic activity of plasma when tests are run using plasma
cytes, a feature of immaturity. The proportion of helper and/ diluted 1: 10 or more. Although the ingestion of particles by
or inducer T lymphocytes recognized by the presence of the phagocytes is intact, subsequent metabolic activation and
CD4+ antigen on the cell surface is markedly decreased. destruction of bacteria is reduced. Finally, recent work in
There is a slight reduction in the number of suppressor and/ humans and animals demonstrated that the production of
or cytotoxic CD8+ cells. Thus, the ratio CD4+:CD8+ is sig several cytokines, including interleukins 2 and 6 and y-inter
nificantly decreased compared with that in well-nourished feron, is decreased in PEM. Moreover, malnutrition alters
control subjects. Moreover, coculture experiments showed the ability of T lymphocytes to respond appropriately to
a reduction in the number of antibody-producing cells and in cytokines. There is some work on the effect of malnutrition
the amount of immunoglobulin secreted. This is largely on the integrity of physical barriers, quality of mucus, or
because of the decreased help provided by T lympho several other innate immune defenses. For example, lyso
cytes. Lymphocyte proliferation and synthesis of DNA zyme concentrations are decreased, largely the result of
are reduced, especially when the autologous plasma from reduced production by monocytes and neutrophils increased
a patient is used in cell cultures. This may be the result of excretion in the urine. Adherence of bacteria to epithelial
inhibitory factors as well as deficiency of essential nutrients cells is a first step before invasion and infection can occur.
lacking in the patient's plasma. Another aspect oflympho The number of bacteria adhering to respiratory epithelial
cyte function that changes in PEM is the traffic and homing cells is increased in PEM fetal malnutrition.
pattern. For example, lymphocytes derived from mesenteric
FETAL MALNUTRITION
lymph nodes of immunized rodents revert back to the intes
tine in large numbers, whereas this homing is reduced in Any insult during the critical developmental period is
malnutrition. likely to have a greater and more prolonged impact on physi
Serum antibody responses are generally intact in PEM, ological functions. The immune system is no exception.
particularly when antigens in adjuvant are administered or Preterm appropriate-for-gestation low-birth-weight
for materials that do not evoke T-cell response. Rarely, the (LBW) infants have reduced levels oflgG, largely a result of
antibody response to some organisms, such as Salmonella the shorter time available for mother-to-infant transfer. The
typhi, may be decreased. However, before impaired anti number of T lymphocytes is decreased but this responds
body response can be attributed to nutritional deficiency, dramatically to small supplements of zinc.
one must carefully rule out infection as a confounding fac Small-for-gestational age (SGA) LBW infants have a
tor. Antibody affinity is decreased in patients who are mal- higher morbidity because of infection in the first 2-3 yr after
FOREWORD vii
birth. This correlates with impaired immunity. The majority areas treated in this book that illustrate the changing tides
of SGA infants show atrophy of the thymus and prolonged and the great need to understand the molecular basis of inter
impairment of cell-mediated immunity. Delayed cutaneous actions, in addition to understanding and performing simple
hypersensitivity to a variety of microbial recall antigens is dietary assessment. A goal for all of us should be to recruit
impaired. Serum thymic factor activity is lower in SGA more researchers into this area and especially to increase the
infants tested at age 1 mo or later. In contrast to preterm low dialog between nutritional and food scientists and immu
birth-weight infants who recover immunologically by nologists.
approx 2-3 mo of age, SGA infants continue to exhibit
Ranjit Kumar Chandra, DSc, PhD, MD
impaired cell-mediated immune responses for up to 12 yr.
This is particularly true of those infants whose weight-for REFERENCES
height continues to remain <80% of standard. The pro
I. Scrimshaw NS, Taylor CEo Gordon JE. Interactions of
longed immunosuppression in some SGA infants correlates
Nutrition and Infection. WHO, Geneva; 1968.
with clinical experience of infectious illness and, thus, may 2. Chandra RK. Immunocompetence in undernutrition. J
have considerable biological significance. In animal models Pediatr 1972;81: 1194-200.
of intrauterine nutritional deficiency, PEM results in reduced 3. Chandra RK, Newberne PM. Nutrition, immunity and
immune responses in the offspring. infection. In: Mechanisms of Interactions. Plenum, New
Phagocyte function is deranged in low-birth-weight York; 1977.
infants. There is a slight reduction in ingestion of particulate 4. Victora CG, Barros FC, Kirkwood BR, Vaughan JP.
Pneumonia, diarrhea, and growth in the first 4 y of life:
matter and a significant reduction both in metabolic activity
a longitudinal study of 5914 urban Brazilian children.
and bactericidal capacity.
Am J Clin Nutr 1990; 52:391--6.
IgG from the mother, acquired through placental transfer,
5. Gershwin ME. Beach RS, Hurley LS. Nutrition and
is the principal immunoglobulin in cord blood. The half-life
Immunity. Academic, New York; 1984.
of IgG is 21 d, thus all infants show physiological hypo 6. Beisel WR. The history of nutritional immunology. J
immunoglobulinemia between ages 3 and 5 mo. This is pro Nutr Immunol 1991; I: 16-24.
nounced and prolonged in low-birth-weight infants because 7. Chandra RK, ed. Nutrition and immunology. Alan R.
their concentration ofIgG at birth is significantly lower than Liss, New York, 1988.
that of full-term infants. In SGA low-birth-weight infants 8. Kirby DF. Enteral nutrition in immunocompromised
patients. Nutr Clin Prac 1997;12:S25-7.
the cord blood concentrations of IgG 1 are reduced much
9. Pomeroy C, Mitchell J, Eckert E, Raymond N, Crosby R,
more than those of other subclasses. Thus the ratio of infant
Dalmasso AP. Effect of body weight and caloric restric
to maternal concentrations is significantly low for IgG 1 but
tion on serum complement proteins, including Factor DI
not for IgG2. The number of immunoglobulin-producing cells
adipsin: studies in anorexia nervosa and obesity. Clin
and the amount of immunoglobulin secreted is decreased in
Exper Immunol 1997;108: 507-15.
SGA infants who are symptomatic (i.e., those who have recur 10. Zaman K, Baqui AH, Yunus M, Sack RB, Bateman OM,
rent infections). In the second year oflife, SGA infants show Chowdhury HR, et aJ. Association between nutritional
a marked reduction in IgG2 concentrations and often show status, cell-mediated immune status and acute lower
infections with organisms that have a polysaccharide capsule. respiratory infections in Bangladeshi children. Eur Clin
The SGA group is also at risk of developing infection with Nutr 1996;50:309-14.
opportunistic microorganisms, such as Pneumocystis carin ii, 11. Marcos A, Varela P, Toro 0, Lopez-Vidriero I, Nove E,
Madruga D, et al. Interactions between nutrition and
as observed in postnatal malnutrition also.
immunity in anorexia nervosa: a l-y follow-up study. Am
Clearly, protein-energy malnutrition is not a paradigm
J Clin Nutr 1997;66: 485S-490S.
for all of the areas covered in Nutrition and Immunology:
12. Scrimshaw NS, SanGiovanni JP. Synergism of nutrition,
Principles and Practice. However, it is perhaps the best stud
infection, and immunity: an overview. Am J Clin
ied and the most understood. There are a number of novel Nutr 1997;66:464S-477S.
Preface
Nutrition and immunology are at the focus of a scien the past half century, these knowledge gaps have been
tific revolution. The food supply as a source of nutrients has addressed and it is now possible to more closely assess the
evolved dramatically over the past two centuries, but never nutritional requirements of various aspects of immunity.
before has there been such a promise for innovation. The Assembling this information is a second important goal of
genetic revolution has provided the promise to truly change Nutrition and Immunology: Principles and Practice.
the food supply as never before imagined. Plant geneticists Appreciating the nutritional requirements of the
and physiologists are providing the capability, and immune system has been gained from various directions.
agribusiness is poised to dramatically change the chemical Overt dietary deficiency of virtually all nutrients com
makeup of food commodities. With this capability has come promises the quality, speed, and integrity of the immune
the compelling question: To what should it be changed? response, leading most obviously to increases in suscepti
Unquestionably, if the food supply is to be improved nutri bility to infectious disease. The insights gained from the
tionally, the needs of the immune system need to be a major quality of the immune response associated with nutrient
target of that improvement. Establishing the framework to deficiencies are the subject of several chapters in Nutrition
direct this new revolution is a considered goal of Nutrition and Immunology: Principles and Practice. Intriguingly, in
and Immunology: Principles and Practice, and we have thus the context of infectious disease, microbial pathogens them
brought together experts from around the world in nutrition selves are sensitive to the nutritional status of the host, and
and immunology to provide the consensus state-of-the-art in chapters address this burgeoning issue including the influ
these fields. ence of nutrition on viral evolution. The immune system,
The first great nutritional age of this century brought however, is not simply affected by overt nutrient deficien
the sciences of biochemistry, physiology, chemistry, and cies, but both the elaboration of the multi tissue immune
medicine together to define in molecular terms the essential system through life and the mounting ofa n aggressive immune
nutrients for humans. This triumph of scientific discovery response place specific metabolic demands on the organism,
was primarily completed before 1950 when most vitamins many of which are directly related to increased needs for
and essential minerals and major diseases associated with specific dietary nutrients. The last 20 years have seen an
their respective nutritional deficiencies had been described. explosion in research, expanding on the molecular require
A valuable outcome of this chemical approach was the ments of the immune system. From the role of minerals and
capability to produce vitamins synthetically, which made it cofactors in transcriptional regulation of immune matura
possible to implement a true solution to the problem of tion, through the specific protein, vitamin, and lipid needs of
nutrient deficiency in the Western world and, in particular, immune responses, to the increased demand for antioxidant
the United States, through aggressive food fortification. In protection and tissue repair created by the consequences of
terestingly, this "first" nutritional revolution addressed only immune activation, these fields of the molecular nutrition of
those nutrients that were essential for growth and reproduc the immune system are the focus of multiple chapters in the
tion. This perspective failed to address either optimal nutri text.
tion or the speci fic requirements of particular tissues during By defining only nutrient essentiality as the subject for
aging, including the varying and specific needs of the grow public health, the role of nutrient imbalances, especially as
ing and functioning immune system. Some of the reasons for they relate to the gradual development of chronic and degen
not addressing immunology directly lay in the relative state erative diseases in maturity, was largely ignored in the first
of knowledge of molecular immunology, but were also in revolution of nutrition research. Thus, in modern Western
part a consequence of the decision to limit the definitions of societies, the successful elimination of nutritional deficien
nutrient requirements to normal development, neglecting cies through nutrient fortification has not eliminated the diet
the increased nutrient needs attributable to stress and the as a contributor to disease, but rather delayed the conse
increased demands of a stimulated immune response. Over quences of suboptimal diets to the diseases that develop dur-
IX
x PREFACE
ing adulthood. More insidiously, by solving nutrient ota!. It is possible to redesign the food supply because of the
deficiencies by fortification, the food supply has evolved in technological advances of genetic manipulation. If this
the second half ofthe century without sound nutritional inter manipulation is to improve long-term health, the specific
vention, but rather under soft, educational guidance. Ironi nutritional needs ofthe immune system, throughout life and
cally, the first nutritional revolution that eliminated nutrient importantly, during immunologic challenge, must be defined
deficiencies and promoted a significantly greater fraction of in molecular terms. With this improved food supply in mind,
the population into old age also allowed an evolution of the Nutrition and Immunology should serve as a strong blueprint
food supply toward lower nutritional density (1,2). This for that design.
lower nutrient density of diets permitted nutritional imbal
M. Eric Gershwin, MD
ances that are now emerging epidemiologically as a greater
J. Bruce German, PhD
risk of chronic and degenerative disease during aging (3).
Equally ironic, although the fortification offoods was imple Carl L. Keen, PhD
mented as a public health program in the United States with REFERENCES
genuinely spectacular benefits to public health, the impor
1. Steven, A.M. and Sieber, G.M. Trends in individual
tant nutritional improvements warranted by chronic disease
fat consumption in the UK 1900--1985. Brit J Nutr 1994; 71.
prevention (i.e., cholesterol reduction) have been left largely
2. Drewnowski, A. and Popkin, B.M. 1997. The Nutrition
to individual discretionary choice (4). The strategy to improve
Transition: New Trends in the Global Diet. Nutr Rev 55 (2):
nutritional status beyond simple essentiality has been to 31-44.
implement diet change via individual education (5), which 3. Shetty, P.S. Diet, lifestyle and chronic disease:
has led to competition within the food marketplace in, as one lessons from contrasting worlds. In: Diet, Nutrition and
example, targeted cholesterol-lowering foods, and the emer Chronic Disease: Lessons from Contrasting Worlds. Shetty
gence of a large food supplement industry. An obvious con P.S. and McPherson, K., eds. John Wiley and Sons,
sequence of recruiting such vested interests as the food and NY, 1997.
4. James WPT. Where do we go from here in public health? In:
supplement industries into the nutritional educational pro
Diet Nutrition and Chronic Disease: Lessons from Con
cess is a substantial disaffection of the public with nutrition
trasting Worlds. Shetty, P.S. and McPherson, K., eds.,
education in general and the credibility of the science under
John Wiley and Sons, NY, 1997.
lying it as well. Additionally, the focus of attention has
5. Foerster, S.B., Heimendinger, 1., DiSogra, L.K. and Pivonka,
shifted from molecules and scientific mechanisms to spe
E. 1997. The national 5 a day for better health program: an
cific commodities or products as purportedly superior in a American nutrition and cancer prevention initiative. In:
competitive marketplace. A valuable asset of Nutrition and Implementing Dietary Guidelines for Healthy Eating.
Immunology: Principles and Practice is an effort to refocus Wheelock, v., ed. Chapman & Hall, London, 1997.
this attention on the science issues and to provide clear, 6. Gombs, G.F. Should intakes with beneficial actions
understandable summaries of the state of science at the often requiring supplementation be considered for RDA' s?
Am J Clin Nutr 1996; 126:2373S-2376S.
present time nutritional immunologic.
7. Hambidge, K.M. Overview and purpose of the work
The now recognized role of diet in health has led to a
shop on new approaches, endpoints and paradigms for
nutritional revolution in the second half of the century
RDA's of mineral elements. Am J Clin Nutr 1996;
addressing the larger role of diet in optimal health and dis
126:2301 S-2303S.
ease prevention (6-8). Within this context, the role of diet in 8. Metz W. Food fortification in the United States. Nutr Rev
immunological status has emerged as important, if not piv- 1997; 55(2):44--9.
Contents
FOREWORD V 10 Dietary n-3 Polyunsaturated Fatty Acids
Modulate T-Lymphocyte Activation:
PREFACE IX
Clinical Relevance in Treating Diseases
CONTRIBUTORS XIII of Chronic Inflammation 121
Robert S. Chapkin, David N. McMurray,
I. NUTRITIONAL ASSESSMENT and Christopher A. Jolly
Application and Interpretation of Commonly 11 Nucleotides 135
Used Nutritional Assessment Techniques 3 George K. Grimble and Olwyn M. R. Westwood
Kenneth H. Brown
III. NUTRIENT-IMMUNE INTERACTIONS
2 Evaluating Malnutrition: What Should
the Physician Look For? 15 12 Impact of Nutritional Status on Immune
Integrity 147
Charles H. Halsted
Pam Fraker
3 Evaluation of the Immune System
in the Nutritionally At-Risk Host 21 13 Nutritional Modulation of Inflammation by
Jonathan Powell, Andrea T. Borchers, Steven Polyunsaturated Fatty Acids/Eicosanoids 157
Yoshida, and M. Eric Gershwin Vincent A. Ziboh
II. SPECIFIC NUTRIENT REQUIREMENTS IV. CLINICAL ISSUES
(NORMAL POPULATIONS; POPULATIONS WITH 14 Immunological Considerations
low INTAKES, INCLUDING TEENS, FEMALES, of Breast Milk 171
ELDERL Y ••• ) Bo Lonnerdal
4 Caloric Intake: Sources, Deficiencies, 15 Clinical Issues: Childhood Illnesses,
and Excess - An Overview 35 Vaccinations, and Nutritional Status 181
Dean A. Troyer and Gabriel Fernandes Noel W. Solomons and Gerald T. Keusch
5 Protein and Amino Acids 49 16 Protein-Energy Malnutrition and Infectious
Vernon R. Young Disease: Synergistic Interactions 195
6 Specific Nutrient Requirements: Christopher A. Jolly and Gabriel Fernandes
Trace Elements 65 17 Lipids, Inflammatory Cytokines,
Janet C. King and Endothelial Cell Injury 203
7 Vitamins: Overview and Metabolic Bernhard Hennig, Michal Toborek,
Functions 75 and Gilbert A. Boissonneault
Robert Rucker
18 Nutrition and Allergy 221
8 a-Lipoic Acid: The Metabolic Christopher Chang and M. Eric Gershwin
Antioxidant 97
19 Adverse Reactions to Foods 233
John K. Lodge and Lester Packer
Francesco Giuseppe Foschi, Lorenzo Marsigli,
9 Defining the Role of Dietary Phytochemicals
Francesco Chiappelli, Michelle A. Kung,
in Modulating Human Immune Function 107 Mauro Bernardi,
Harold Schmitz and Kati Chevaux and Giuseppe Francesco Stefanini
xi
