European Journal of Clinical Nutrition (2003) 57, Suppl 1, S66S69

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ORIGINAL COMMUNICATION
Changes in the immune system are conditioned by
nutrition
A Marcos1*, E Nova1 and A Montero1
1

Grupo de Inmunonutricion, Departamento de Metabolismo y Nutricion, Instituto del Frio (CSIC), Madrid, Spain

Undernutrition due to insufficient intake of energy and macronutrients and/or due to deficiencies in specific micronutrients
impairs the immune system, suppressing immune functions that are fundamental to host protection. The most consistent
abnormalities are seen in cell-mediated immunity, complement system, phagocyte function, cytokine production, mucosal
secretory antibody response, and antibody affinity. There is a number of physiological situations such as ageing and
performance of intense physical exercise associated with an impairment of some immune parameters response. Nutrition can
influence the extent of immune alteration in both of them. There are also numerous pathological situations in which nutrition
plays a role as a primary or secondary determinant of some underlying immunological impairments. This includes obesity, eating
disorders (anorexia nervosa and bulimia nervosa), food hypersensitivity and gastrointestinal disorders as some examples. The
implications of nutrition on immune function in these disorders are briefly reviewed.
European Journal of Clinical Nutrition (2003) 57, Suppl 1, S66S69. doi:10.1038/sj.ejcn.1601819
Keywords: malnutrition; immunity; physiological situations; eating disorders

Introduction
The immune system acts to protect the host from infectious
agents that exist in the environment (bacteria, viruses, fungi,
parasites) and from other noxious insults. To this end, it
relies on two functional branches: the innate and the
acquired, both involving a diversity of blood-borne factors
(complement, antibodies, and cytokines) and cells (macrophages, polymorphonuclear cells, and lymphocytes). The
adequate functioning of this defensive system is critically
determined by nutrition, and, as a consequence, so is the risk
of illness. In this sense, undernutrition due to insufficient
intake of energy and macronutrients and/or due to deficiencies in specific micronutrients impairs the immune system,
suppressing immune functions that are fundamental to host
protection. These changes are associated with an increased

*Correspondence: A Marcos, Grupo Inmunonutricion, Departamento de

Metabolismo y Nutricion, Instituto del Fro (CSIC), c/Antonio Novais, 10,
28040 Madrid, Spain.
E-mail: [email protected]
Guarantor: A Marcos.
Contributors: A Marcos has been coordinator and supervisor of
research projects on eating disorders and elite athletes, whose results
are summarized in the manuscript. She has reviewed the manuscript
and elaborated its final version. E Nova has written the text of the
manuscript in collaboration with A Montero, and both have
participated in research projects included in the manuscript.

risk of infections, which, in turn, produce physiological

changes that worsen nutritional status (Chandra & Newberne, 1977; Chandra, 2002).
Based on this close relationship between nutrition and
immunity, for at least the last two decades, immunocompetence assays are being used as sensitive functional indices in
the assessment of the nutritional status.

Effects of nutrients on the immune system

Without adequate nutrition, the immune system is clearly
deprived of the components needed to generate an effective
immune response. Human malnutrition is usually a complex
syndrome of multiple nutrient deficiencies. However, observations in laboratory animals deprived of one dietary
element, as well as findings in those rare patients with a
single nutrient deficiency, have confirmed the crucial role of
several vitamins, minerals and trace elements in the maintenance of immunocompetence. This includes vitamin A,
beta-carotene, folic acid, vitamin B6, vitamin B12, vitamin C,
vitamin E, riboflavin, iron, zinc, and selenium (Grimble,
1997; Chandra, 2002). Antioxidant nutrients, for example,
play a pivotal role in maintaining the antioxidant/oxidant
balance in immune cells and in protecting them from
oxidative stress and preserving their adequate function

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A Marcos et al

S67
(Victor & de la Fuente, 2002). The addition of the deficient
nutrient back to the diet can restore immune function and
resistance to infection. However, excessive amounts of some
nutrients also impair immune function (Calder and Kew,
2002).
As crucial components in the diets, lipids are substances
that exert a profound effect in the modulation of the
immune system. The fatty acid composition of lymphocytes,
and other immune cells, is altered according to the fatty acid
composition of the diet. Therefore, an immunomodulatory
role has been suggested for dietary lipids, which could be
used in the management of some diseases involving
inflammation processes, such as autoimmune diseases (De
Pablo & Alvarez de Cienfuegos, 2000).

more related to oxidative stress such as adherence, free

radical and proinflammatory cytokine production increase
with age (Victor & De la Fuente, 2002). These mechanisms are
associated with the general decline of the immune system
activity. Nutrient supplements, such as vitamin B6, zinc,
vitamin C, vitamin E may be important for health promotion
and prevention of certain diseases. However, the optimum
doses for antioxidant supplementation are still not clear,
since in certain cases potential deleterious effects of oversupplementation have emerged from some clinical trials.

Protein energy malnutrition

Nutritional deprivation, such as protein energy malnutrition
(PEM), often causes immunodeficiency leading to increased
frequency and severity of infection, thymus atrophy and
wasting of peripheral lymphoid tissue (Chandra & Kumari,
1994), with the subsequent impairment of immune responses, especially in the cell-mediated mechanisms. Malnutrition, independent of its origin (protein, mineral, or
vitamin deficient supply), consistently results in changes in
the thymus gland. The organ undergoes a severe atrophy due
to apoptosis-induced thymocyte depletion plus decreased
thymocyte proliferation (Chandra, 1992). Also, a decrease in
thymic hormone production has been repeatedly documented in various types of nutrient deprivation. Recently, a
hypothesis has been put forward that hormonal control of
malnutrition-induced thymocyte depletion could exist:
involving a decrease of leptin and a consequent rise of
serum glucocorticoid hormone levels (Savino, 2002).

Obesity
Limited and often controversial information exists comparing immunocompetence in obese and nonobese subjects as
well as the cellular and molecular mechanisms involved. The
mechanisms responsible for increased risk of infection and
poor antibody response among obese subjects are unknown,
but may be linked to the negative effect that their metabolic
milieu produces on immunity (Lamas et al, 2002). In this
sense, much evidence supports a link between adipose tissue
metabolism and immunocompetent cell functions. This
includes the closely related factors leptin and tumour
necrosis factor-alpha (TNF-a) in adipose tissue.
Different animal models of obesity have shown a decrease
in all T-lymphocyte subsets and the B-cell population
(Kimura et al, 1998), and also lymphocyte responsiveness
to different mitogens is lower in obese animals compared to
lean ones (Tanaka et al, 1998). As occurs in animal models,
most investigations in humans confirm a lower capacity of
lymphocytes to proliferate in response to mitogen activation. However, different and even opposite results have been
found regarding leukocyte and lymphocyte subset counts,
probably due to heterogeneity in the subjects studied.
Moreover, those studies assessing the immune response in
obese patients after weight loss or nutritional deprivation
have also produced variable results.

Ageing
Older individuals tend to have a high prevalence of nutrient
deficiency. Although very often the manifestations of these
deficiencies are only subclinical, the effects upon the
immune system and cognitive function are remarkable. The
clinical outcome of impaired immunity is an increased
incidence of common infections affecting the upper and
lower respiratory, urinary, and genital tracts. According to
human studies, changes in immunity associated with ageing
include decreased delayed-type hypersensitivity (DTH) responses, reduced IL-2 production and proliferation of
lymphocytes, reduction in serum IgA and decreased antibody
titre after vaccination (Chandra, 2002). The number of
circulating T lymphocytes is slightly decreased. The ratio
mature/immature T lymphocyte decreases, as does the ratio
nave/memory T cells, and NK cells are more numerous
(Lesourd & Mazari, 1999). However, those functions that are

Eating disorders
Studies on the impact of eating disorders, such as anorexia
nervosa (AN) or bulimia nervosa (BN), over the immune
system, have produced controversial findings. On the one
hand, patients with AN frequently show a tendency to
leukopenia together with relative lymphocytosis (Marcos
et al, 1993) and a decreased delayed-type hypersensitivity
skin test response (Varela et al, 1988). But, on the other hand,
immune impairments are less severe than would be expected
considering the highly defective nutritional status of the
patients, and also, they seem to be surprisingly free of
infectious complications or even common viral infections
(Marcos, 2000). To understand why these patients are less
prone to infection than subjects with typical malnutrition,
there are several points that are worth noting. Firstly, while
in starvation the diet is deficient in multiple vitamins and
proteins, in AN the primary dietary inadequacy is of

Relationship between physiological and

pathological situations conditioned by
nutrition and the immune system

European Journal of Clinical Nutrition

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carbohydrates and fats. Also, hypothetically, some of the
complex interactions occurring between cytokines and the
endocrine system and the central nervous system could
provide some compensatory mechanisms to adapt to the
limited nutrient supply and possibly result in the perceived
lack of infection symptoms. A dysregulated cytokine production and the altered acute-phase response to infection, as
well as cortisol and leptin, are considered to be potential
factors involved in the adaptation processes occurring in
these syndromes (Nova et al, 2002).

Physical exercise practice

The effect of exercise on immune response is multifaceted,
depending upon the type of exercise and the intensity of
effort relative to the individuals state of training. In general,
it is accepted that while moderate exercise enhances
immune functions, high-intensity physical activity and
periods of heavy training can suppress various immune
response parameters. Considerable evidence indicates that
improper nutrition and psychological stress increase the
negative effect of heavy exertion upon the immune system.
Some sportswomen performing sports that emphasize leanness, as well as weight-classification sports, suffer from these
three conditions, namely, heavy training, inadequate nutrition and competition-related stress. Under this situation,
their immune system has been proved to be affected, even
before their daily routine of exercise. Basal leukocyte,
lymphocyte, and T lymphocyte subset counts from elite
female gymnasts going through long hours of daily training,
have been shown to be lower than those of healthy
sedentary age-matched controls (Lopez-Varela et al, 2000).
Differences have also been found in cytokine production by
in vitro stimulated blood mononuclear cells from female
gymnasts in comparison with controls (Nova et al, 2001).

Immunocompetence, then, can be used as an index of the

seriously compromised nutritional status of some athletes. In
fact, there are some similarities between gymnasts and
patients with eating disorders in their immune abnormalities
that could be explained by some factors shared in common
such as their restrictive dietary habits, continuous activity,
hormone alterations, and the stressful environment.
Food hypersensitivity
Diet during gestation and early childhood has a profound
effect on many physiological functions and on the occurrence of several disorders. In this sense, it is known that
prolonged breast feeding, the use of a partially hydrolysed
formula, and delayed introduction of certain allergenic
foods are associated with reduced occurrence of food
hypersensitivity. This is an adverse reaction to dietary
components with an immunologic mechanism that contributes to the development of eczema, gastroenteropathology, asthma, and hay fever. The preventive measures
mentioned are especially advisable for those children at
higher risk according to family history. Consequently,
breastfeeding should be promoted for other reasons as well.
It reduces the risk of necrotizing enterocolitis, diabetes
mellitus type I and type II, lymphoma, and infections in
general throughout life (Chandra, 2000).
Gastrointestinal disorders
The primary activity of mucosal immune response is to
protect the mucosa by blocking microbial, toxin and antigen
entry through secretion and transport of IgA to the lumen of
the gut, a process mediated by a special type of memory T
cell capable of providing B cell help. These type of cells can
be found in the lamina propia of the intestinal barrier and
can therefore interact and receive signals from endogenous

Table 1 Brief presentation of some physiological and pathological situations in which nutrition acts as a primary or a secondary determinant of immune
function impairment
Physio/pathological situation

Some observed effects on immunity

Nutritional advise

PEM
Ageing

Thymus atrophy, leukopenia, k CD4/CD8

m frequency of infections, k IL-2 production, k
lymphocyte proliferation
Immunosuppression, m frequency of infections,
poor antibody response
Leukopenia, relative lymphocytosis, k DTH response,
altered pattern of cytokine secretion
Leukopenia, lymphopenia, k DTH response,
altered pattern of cytokine secretion.
Hyper-response of immunologic mechanisms
leading to asthma, atopic eczema and other
allergic manifestations.
Those secondary to nutrient deficiencies
Failure of mucosal mechanisms of defence
(altered IgA-mediated protection)
Impairment of the homeostatic response to
limit epithelial inflammation

Reversible with refeeding

Beneficial nutrient supplementation

Obesity
Eating disorders
Sports requiring low
body weight
Food allergy

Gastrointestinal disorders

European Journal of Clinical Nutrition

Rationally controlled weight loss and then weight stability

Nutritional rehabilitation
Nutritional education and correction of dietary habits
Nutritional rehabilitation
Nutritional education and correction of dietary habits
Strict avoidance of allergenic food. Prevention through
breast feeding, hydrolysed milk formulas and delayed
introduction of allergenic foods
Administration of probiotics with adequate bacteria strains

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microbiota of the gut. Commensal bacteria may exert a dual
function: the stimulation of mucosal mechanisms of defence
on one side (for instance, by lactobacilli) and the maintenance of homeostasis of the immune response on the other
(Schiffrin & Blum, 2002). Reduction of normal commensal
bacteria in the context of infection or after antibiotic
treatment may interfere with nutrient availability and
impair beneficial stimulation of gastrointestinal immune
response. In this sense, probiotics have proved helpful in
prevention of infectious diarrhoea and shortening of the
episodes. On the other hand, an impairment of the
homeostatic control by immunomodulatory cytokines,
normally working to downregulate or limit the extent of
an initial proinflammatory event triggered by nonpathogenic bacteria, may underlay the development of inflammatory bowel disease. Thus, the manipulation of the host
microflora to influence underlying immune responses may
represent a new possibility in the prevention or management
of gastrointestinal pathophysiological disorders.
There are more pathological situations with a clear
participation of immune mechanisms that can be modulated
or conditioned by food components and nutrients. This
includes cancer, inflammation processes such as atherosclerosis, rheumatoid arthritis, bronchial asthma, cystic
fibrosis, fibromyalgia; but further studies are needed to
elucidate the underlying mechanisms and how to perform
adequate nutritional intervention. Overall, the exploration
of functional foods seems clearly interesting in the context
of a Western civilization facing up to a progressive increase
in immune-mediated and gut-related health problems.

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