Symposium: Nutrition and Infection,

Prologue and Progress Since 1968

Diarrhea and Malnutrition1
Kenneth H. Brown 2
Program in International Nutrition and Department of Nutrition, University of California, Davis, CA
ABSTRACT Publication of the WHO monograph, Interactions of Nutrition and Infection, in 1968 by Scrimshaw,
Taylor and Gordon stimulated many scientists to pursue further research on these issues. With regard to the
relationships between diarrhea and malnutrition, the research conducted since 1968 can be categorized in one of
three major areas: 1) the impact of diarrhea on nutritional status, particularly in young children; 2) nutritional risk
factors for diarrhea; and 3) appropriate dietary therapy for patients during and after enteric infections. The results
of these studies have prompted a number of changes in the clinical treatment of patients with diarrhea and in public
health policies regarding its prevention. J. Nutr. 133: 328S332S, 2003.

diarrhea

malnutrition

infection

It is personally very gratifying to be able to contribute to

this symposium, which revisits the 1968 treatise by Scrimshaw,
Taylor and Gordon entitled, Interactions of Nutrition and
Infection (1), because this publication had a major impact on
my own thinking and career development. For individuals like
me who were U.S. university students at the time, the year
1968 was notable for the growing distrust of the military
industrial complex, the widespread resistance to the war in
Vietnam, and the reawakened social concern for disenfranchised peoples, both in the United States and elsewhere. At
the same time, Timothy Leary was counseling students and
other members of the love generation to turn on, tune in, and
drop out (2); and the hippie movement was reaching its peak.
As a graduating senior confronting these competing claims on
my attention, and as the recipient of a lottery number from the
U.S. Selective Service Board that all but ensured my inscription into the U.S. Army immediately after graduation unless
other options were pursued, I chose instead to enroll in medical school until I could decide what I really wanted to do with
my life. Because I had originally hoped to join the Peace Corps
after finishing my undergraduate studies, once in medical
school I began to explore opportunities for practicing medicine
and/or conducting biomedical research in the developing
world; and I soon discovered the series of publications by
Scrimshaw, Gordon and colleagues on weanling diarrhea (3)
and the interactions between infection and nutrition (4,5).

dietary intake

breastfeeding

Thus began my personal and professional odyssey in quest of

greater knowledge on these topics.
The comprehensive monograph Interactions of Nutrition and Infection stimulated many scientists to pursue
further research on these issues, and in this presentation I
will highlight some of the resulting studies on diarrhea and
nutrition. In general, the research conducted on this topic
since 1968 can be categorized in one of three major areas:
1) the impact of diarrhea on nutritional status, particularly
in young children; 2) nutritional risk factors for diarrhea;
and 3) appropriate dietary therapy for patients during and
after enteric infections. Notably, the results of these studies
prompted a number of changes in the clinical management
of patients with diarrhea and in public health policies
regarding its prevention. For lack of time, and because of
my own personal interests and experience, my comments
will focus primarily on epidemiological and clinical studies
that were conducted in humans. I will not attempt to
provide a comprehensive treatment of the literature; rather,
I will highlight those studies that I believe have exerted the
greatest influence on current thinking.

Overview of diarrhea and nutrition

As articulated by Scrimshaw, Taylor and Gordon in their
1968 review, the relationship between infection and malnutrition is bidirectional (Fig. 1). Infection adversely affects
nutritional status through reductions in dietary intake and
intestinal absorption, increased catabolism and sequestration
of nutrients that are required for tissue synthesis and growth.
On the other hand, malnutrition can predispose to infection
because of its negative impact on the barrier protection afforded by the skin and mucous membranes and by inducing
alterations in host immune function.

1
Presented as part of the symposium Nutrition and Infection, Prologue and
Progress Since 1968 given at the 2002 Experimental Biology meeting on April 23,
2002, New Orleans, LA. The symposium was sponsored by The American Society
for Nutritional Sciences. The proceedings are published as a supplement to The
Journal of Nutrition. Guest editors were Nevin S. Scrimshaw, Massachusetts
Institute of Technology, Cambridge, MA, and Food and Nutrition Programme,
United Nations University, Tokyo, Japan, and William R. Beisel, Department of
Microbiology and Immunology, Johns Hopkins School of Hygiene and Public
Health, Baltimore, MD.
2
To whom correspondence should be addressed.
E-mail: khbrown@ucdavis.edu.

0022-3166/03 $3.00 2003 American Society for Nutritional Sciences.

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KEY WORDS:

DIARRHEA AND MALNUTRITION

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The most recent phase of research on this theme has begun

to examine the effect of diarrhea on micronutrient balance
and assessment of micronutrient status. For example, CastilloDuran et al. (15) assessed trace element balance during and
after acute diarrhea, noting a negative balance of zinc during
the early phase of illness.
Nutritional risk factors for diarrhea

FIGURE 1

Relationship between nutrition and infection.

Nutritional impact of diarrhea

FIGURE 2 Summary of research on the nutritional impact of diarrhea.

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A time line showing each of the major lines of research

concerning the nutritional impact of diarrhea is provided in
Figure 2. As indicated, a number of field studies conducted
during the 1970s and 1980s attempted to quantify the nutritional impact of diarrhea on childrens growth. Leonardo Mata
and colleagues at the Institute of Nutrition of Central America
and Panama produced a series of graphic presentations illustrating the temporal relationships between individual episodes
of infection and periods of growth faltering (6), an example of
which is presented in Figure 3. Subsequently, Martorell et al.
in Guatemala (7), Rowland et al. in West Africa (8) and Black
et al. in Bangladesh (9) developed statistical models to estimate the proportion of the total growth deficit that could be
attributed to diarrhea, and they concluded that an important
component of the observed growth failureperhaps as much
as one-fourth to one-thirdwas attributable to enteric infections.
The groups in Guatemala and Bangladesh proceeded to
explore the mechanisms whereby diarrhea causes growth failure, focusing on dietary intake and intestinal malabsorption.
Martorell et al. (10) reported that fully weaned Guatemalan
children reduced their energy intake by 30% during acute
infections, whereas Brown et al. (11) found that Bangladeshi
children who were still breastfeeding reduced their intakes by
only about 7%, suggesting that breastfeeding may protect
against diarrhea-induced reductions in intake. During a subsequent study in Peru (12), intakes of breast milk energy and
nonbreast milk food sources were examined separately; and
this analysis of disaggregated data confirmed the foregoing
hypothesis. Whereas intake of nonbreast milk energy declined
by about 30% during illness, there were no changes in breast
milk consumption. Thus, the overall impact of illness on
energy intake was partially mitigated by breastfeeding.
Beginning in the 1980s, researchers started to explore factors that might modify the nutritional impact of diarrhea.
Rowland et al. (13) discovered that the previously observed
diarrhea-induced growth deficit was absent in fully breastfed
infants in an urban field site in West Africa, and they concluded that exclusive breastfeeding prevents the adverse nutritional consequences of diarrhea. Lutter et al. (14) found that
the usual diet also influenced the growth response to diarrhea
in older children. Whereas the Colombian children in these
studies who lived in control villages displayed the expected
negative relationship between diarrheal prevalence and height
at 3 y of age, there was no effect of diarrhea on the height of
those children who lived in villages where food supplements
were being distributed.

Nutritional risk factors for diarrhea can be grouped as

anthropometric risk factors, infant and child feeding practices
and micronutrient status. Measures of resulting morbidity from
diarrhea include both incidence rates and the duration and
severity of illness. Research on these issues is summarized in
the time line presented in Figure 4.
Studies by James et al. in 1972 (16) and Sepulveda et al. in
1988 (17) span the period when investigators confirmed a
relationship between preexisting anthropometric status and
diarrheal incidence. Although most investigators accept the
conclusion that malnutrition increases the risk of diarrhea, it
must be recognized that the design of these descriptive epidemiological studies does not permit elimination of the possibility that confounding factors may explain as least some of the
observed results. For example, researchers have noted the
possibility that children with some underlying predisposition
to enteric infection, such as environmental exposures or immunodysfunction, may have become undernourished because
of earlier illnesses. Thus, baseline malnutrition, as defined by
anthropometric indicators, may have been a result of these
prior illnesses rather than a cause of subsequent ones. Disentanglement of the causal sequence of these events has remained problematic.
During this same period of time, investigators also described
associations between anthropometric indicators of nutritional
status and the duration of illness (18), the severity of fecal
purging (19) and, most important, the case-fatality rates (20).
In each case, preexisting malnutrition was associated with an
increased severity of diarrheal disease.
Infant feeding practices is another nutrition-related risk
factor that received heightened attention during the period
after 1968. Two important studies published from Latin America and Asia at the end of the 1980s found that exclusively
breastfed infants had considerably reduced risks of diarrhea

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FIGURE 3 Example of the temporal

relationship between infection and growth
of an individual child. [Data from Mata et
al. 1976 (6).]

FIGURE 4
diarrhea.

Summary of the research on nutritional risk factors for

covered that clinic visits and hospital admissions for diarrhea

were decreased in vitamin Asupplemented children, even
though diarrheal incidence rates remained unchanged (27).
Thus, it appeared that vitamin A reduced the severity of
illness without affecting the overall attack rate.
More recently, several groups of investigators have pursued
studies of the effect of zinc supplementation on the risk of
diarrhea (28,29). These and other studies, which have been
summarized in a recently published pooled analysis (30), demonstrate an impressive reduction in diarrheal incidence of
nearly 20% among zinc-supplemented children.
Dietary management of patients with diarrhea
In response to the growing recognition that diarrhea undermines nutritional status, a number of investigators began to
reexamine the prevailing approaches to the dietary management of these patients, as summarized in Figure 5. As early as
1924, Parks stated that, The habit of starving an infant just
because he has frequent stools is fallacious and gives rise to
disastrous results. In 1948 Chung and Viscorova found that
children who were fed continuously during diarrhea gained
weight more rapidly and did not differ with regard to diarrheal
duration or treatment failure rates compared with those who
were starved during the first 24 48 h of hospital-based treatment (31). Despite these observations, pediatrics textbooks
published during the 1960s and 1970s continued to advise
bowel rest for 12 48 h followed by several days of gradual
refeeding (32,33), and in 1979 the 3rd edition of the Pediatric
Nutrition Handbook of the American Academy of Pediatrics
remained silent on the issue of appropriate dietary therapy
during acute diarrhea (34).
In 1988 researchers from Peru published the results of a
randomized, clinical trial to assess the optimal approach for
the initial dietary management of children with acute diarrhea
and dehydration (35). Immediately after several hours of rehydration therapy, the patients were assigned to receive one of
four different dietary regimens for 48 h: 1) a nutritionally

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(and other infections) compared with infants who either received other foods or liquids along with breast milk or were
fully weaned from the breast (21,22); and similar results have
been published more recently from more industrialized settings
(23).
During the 1980s and 1990s researchers began to question
whether deficiencies of specific micronutrients might also affect the risk of diarrhea. Studies were beginning to emerge that
indicated that the risk of mortality was reduced in children
who had received large doses of vitamin A (24). Because most
childhood deaths in low income settings are attributable to
infection, it was reasonable to assume that this effect of vitamin A might be attributable to a reduced incidence of infections. Despite the apparent logic of this assumption, most
studies of this relationship found no effect of vitamin A
supplementation on the incidence of diarrhea (25,26). However, researchers in Ghana clarified this issue when they dis-

DIARRHEA AND MALNUTRITION

FIGURE 6 Overall summary of research on diarrhea and nutrition.

least as well with mixed diets as they did with more highly
processed formulas, and dietary fiber was found to reduce the
duration of the period of liquid stool excretion (42). With
regard to micronutrients, studies were conducted to determine
the impact of vitamin A and zinc. Little benefit of vitamin A
was detected, except in nonbreastfed infants, in whom vitamin
A reduced slightly the number of bowel movements and the
duration of illness (43). By contrast with this limited impact of
vitamin A, all of the published studies of zinc supplementation
during both acute and persistent diarrhea found significant
reductions of about 20% in diarrheal duration (44). More
studies are currently under way to assess different combinations and dosages of multiple micronutrients on outcomes of
diarrhea.
In summary, applied research published since 1968 has
confirmed the deleterious effect of diarrhea on childrens nutritional status and has produced new evidence in support of
revised approaches to prevent and treat these illnesses (Fig. 6).
In particular, promotion of breastfeeding to prevent diarrhea
and reduce its nutritional complications, continued feeding
during illness and supplementation with selected micronutrients, both to prevent enteric infections and to reduce their
severity, are all important nutritional aspects in the control of
diarrheal diseases and their associated nutritional complications.
LITERATURE CITED

FIGURE 5
rhea.

Summary of research on dietary management of diar-

1. Scrimshaw, N. S., Taylor, C. E. & Gordon, A.J.E. (1968) Interactions of

Nutrition and Infection. WHO monograph series no. 57. World Health Organization, Geneva, Switzerland.
2. Leary, T. (1965) The Politics of Ecstasy. Putnam, New York, NY.
3. Gordon, J. E., Chitkara, I. D. & Wyon, J. B. (1963) Weanling diarrhea.
Am. J. Med. Sci. 245: 129 160.
4. Scrimshaw, N. S., Guzman, M. A. & Gordon, J. E. (1967) Nutrition and
infection field study in Guatemalan villages, 1959 1964. I. Study plan and experimental design. Arch. Environ. Health 14: 657 662.
5. Gordon, J. E., Ascoli, W., Mata, L. J., Guzman, M. A. & Scrimshaw, N. S.
(1968) Nutrition and infection field study in Guatemalan villages, 1959 1964. VI.
Acute diarrheal disease and nutritional disorders in general disease incidence.
Arch. Environ. Health 16: 424 437.
6. Mata, L. J., Kronmal, R. A., Garcia, B., Butler, W., Urrutia, J. J. & Murillo,
S. (1976) Breast-feeding, weaning and the diarrhoeal syndrome in a Guatemalan Indian village. Acute diarrhoea in childhood. Ciba Found. Symp. 42: 311
338.
7. Martorell, R., Habicht, J.-P., Yarbrough, C., Lechtig, A., Klein, R. E. &
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complete, lactose-free formula, which provided 110 kcal/kg

body weight d1; 2) the same formula diluted with water to
provide half the amount of daily energy; 3) oral glucoseelectrolyte solution (GES); or 4) intravenous GES. The levels
of intake were progressively advanced during ensuing 48-h
periods, so that all children were receiving the complete diet
by d 5 of hospitalization. There were no differences in treatment failure rates or fecal purging (except for the intravenous
group during the first 2 d), and the children gained weight in
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Pediatric Nutrition Handbook concludes that, It has now
been convincingly and repeatedly demonstrated that children
of all ages who return to normal feedings as soon as appetite
allows after completion of rehydration (4 to 6 hours) fare
much better in the duration and severity of illness (37).
A number of studies were carried out during the period from
1968 to 1993 to determine whether substitution of lactosefree, milk-based diets for ones that contained lactose would
modify the outcome of treatment of acute diarrhea. The results
of these trials were inconsistent, although a meta-analysis that
was conducted to reexamine them indicated that the rates of
treatment failure were nearly twofold greater (22 vs. 12%) in
the groups that received lactose-containing milk feeding (36).
However, the excess rate of treatment failure was confined to
those studies that enrolled children with initial severe dehydration. Among the studies that enrolled children with mild or
no dehydration, there was no difference in the treatment
failure rates. The authors concluded that it is safe to manage
the vast majority of children by using lactose-containing milk,
especially if they have no clinical evidence of dehydration.
Nevertheless, dehydrated children may benefit from reduced
lactose intake and close supervision during the early phase of
therapy.
As reviewed previously (41), a number of studies completed
during the 1980s and 1990s examined the use of mixed diets
based on staple foods, and others assessed the effects of individual food components, such as dietary fiber and micronutrients, on the outcome of diarrhea. In general, children fared at

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