140

Nutrition and immune system in the elderly

Rina K. Kusumaratna
a
Department of Communty Medicine, Medical Faculty, Trisakti University
ABSTRACT
The number of individuals aged 60 years or older is projected to double

as a proportion of the worlds
population and to more

than triple in number over the next 50 years. Aging is often associated with a dysregulation
in immune function, particularly in T-cell responses, even in the healthy elderly. Adequate nutrition is important
for optimal immune function. Specific nutrient deficiencies can aggravate the age-associated dysfunction in immune
function and increase the risk of illness. Several micronutrients such as iron, zinc, and selenium are essential to
specific and non-specific immune function and thus influence the susceptibility of the elderly to infectious diseases.
Free radicals

and oxidative stress have been recognized as important factors

in the biology of aging and of many
age-associated degenerative

diseases. Therefore, dietary components with antioxidant

activity have received
particular attention because of their

potential role in modulating oxidative stress associated with

aging and chronic
conditions. The nutritional deficiency impairs the immune response, exposure to viral pathogens, and will result in
an increase in the severity of diseases. Nutritional deficiency in the elderly must be treated to reduce the risk of
infection and possibly slow the aging process.
Keywords : Nutrition, aging, immunity
Zat gizi dan sistem kekebalan pada lanjut usia
ABSTRAK
Jumlah penduduk berusia 60 tahun keatas diproyeksikan akan menjadi dua kali lipat dan akan menjadi tiga
kali lipat pada 50 tahun mendatang. Proses penuaan seringkali dikaitkan dengan gangguan regulasi dari sistim
kekebalan, khususnya pada respons sel T yang dapat terjadi bahkan pada lanjut usia (lansia) yang sehat. Zat gizi
yang adekuat sangat penting untuk memelihara fungsi kekebalan yang optimal. Defisiensi zat gizi yang spesifik
dapat memperberat gangguan fungsi sistem kekebalan akibat proses penuaan dan meningkatkan risiko terjadinya
penyakit pada lansia. Beberapa zat gizi mikro seperti seng dan selenium sangat penting untuk fungsi kekebalan
dan berpengaruh terhadap kerentanan lansia untuk terkena penyakit infeksi. Radikal bebas dan stress oksidatif
sudah diketahui sebagai faktor risiko penting terhadap penyakit degeneratif yang berkaitan dengan usia. Dengan
demikian asupan makanan yang mengandung bahan antioksidan sangat menarik perhatian karena peranannya
yang potensial untuk mengatur stress yang bersifat oksidatif. Kekurangan zat gizi mengganggu respons kekebalan,
mudah terkena virus patogen, dan mengakibatkan meningkatnya penyakit yang berat. Bila terjadi kekurangan gizi
pada lansia harus diobati untuk menurunkan risiko timbulnya infeksi dan memperlambat terjadinya proses penuaan.
Kata kunci : Zat gizi, penuaan, kekebalan
Korespondensi :
a
Rina K. Kusumaratna
Bagian Kedokteran Komunitas
Fakultas Kedokteran, Universitas Trisakti
Jl. Kyai Tapa No.260, Grogol Jakarta 11440
Tel. 021-5672731 eks. 2504, Fax. 021-5660706
E-Mail : rkusumaratna@yahoo.com
Universa Medicina J uli-September 2006, Vol.25 No.3
141
Universa Medicina Vol.25 No.3
INTRODUCTION
The proportion of age individuals has
rapidly increased in the second half of the
t went i et h cent ury i n bot h West ern and
Devel opi ng Count ri es
( 1)
The number of
individuals aged 60 years or older is projected
t o doubl e

as a proport i on of t he worl ds
population and to more

than triple in number
over the next 50 years. The United Nations
Population Division estimated that this age

group
represented ~10% of the worlds population, or
~600 million

people, in 1999. They project that
by the year 2050, this proportion

will increase
to 20% and will include >2 billion people.
(2)
These

changes will be most dramatic in the
less developed countries, where

the population
age structure will change rapidly from one that
is predominantly young, with few elderly, to one
with more balanced numbers

across age groups.
One of the mayor consequences of this growing
elderly population is the significant increase in
health care expenses due to their susceptibility
to infection. The aging process has been
described to be associated with decreased
immune functions, mainly with important
decreases in cell-mediated immunity (CMI) and
lower effect of non-specific and humoral
immunity. To support the immune system the
body requires nutrients, defined as substances
in food that the body can use to obtain energy,
synt hesi ze t i ssues or perform regul at ory
functions. Our body needs nutrients for normal
growth and development, maintenance of cells
and tissues, providing fuel for physical activity
and metabolic processes, as well as regulation
of daily body processes. There are six classes
of nutrients in food, such as carbohydrates,
lipids, proteins, vitamins, minerals and water.
The six classes of nutrients serve three general
functions: (i) provide energy, (ii) regulate body
processes and (iii) contribute to body structures.
Our body needs l arge quant i t i es of
carbohydrates, proteins and lipids to serve the
general functions, these substances are called
macronutrients; the vitamins and minerals are
called micronutrients, because the body requires
it in relatively small quantities for cellular
metabolic processes.
Nutritional status plays an important role
in the functions of the immune system. Impaired
immune response in aging may be partly due to
underlying nutritional deficiency. The aging
process increases population risk for nutrient
deficiencies because of various physiological,
social and economic factors. Epidemiological
and clinical data suggest that nutritional
deficiency is a risk to immune competence and
increases the risk of infection, especially in the
elderly.
(3)
Nutrition in the elderly
Aging is associated with physiological and
economical changes that compromised nutritional
status. Environmental, pharmacological and
psychological stresses often increase age-related
changes in body composition, sensory abilities,
organ system and immune function. The clinical
outcome of impaired immunity is an increased
incidence of common infections affecting the
upper and lower respiratory, urinary and genital
tracts. Changes in immunity, which is associated
with aging, include decreased delayed-type
hypersensitivity (DTH) responses, reduced IL-
2 production and proliferation of lymphocytes,
reduction in serum IgA as well as decreased
antibody titer after vaccination.
(4)
Human growth hormone stimulates skeletal
and muscle growth, and its production declines
with age. It also contributes to loss of bone,
muscle mass and strength.
(5)
Also declining with
age is the perception of taste. It requires a higher
concentration of a flavor to detect it, and may
contribute to loss of appetite and poor intake.
Changes that occur along the gastro-intestinal
142
(GI) tract affect GI function that could interfere
with food intake, absorption and elimination of
waste products.
(6)
Under-nutrition is common in the elderly
population that indicates poor dietary practices
caused by age-related decline, especially eating
disorders.
(7)
However, the requirement for dietary
energy and most micronutrients (vitamins and
minerals) does not decrease, and a well-balanced
diet is important to prevent an inadequate intake
of macro and mi cronut ri ent s. Human
malnutrition is usually a complex syndrome of
multiple nutrient deficiencies.
(3,8)
A study
included 3,885 people of 65 years of age and
over in the US showed that older people who
reported food insufficiency: lower mean intake
of several nutrients; lower intake of the vegetable
and meat groups; lower dietary variety; lower
mean serum levels of certain nutrients; higher
risk of being underweight, and in poor or fair
health.
(9)
Considering that older people are at risk of
malnutrition, this study indicates that food
insufficient elderly people are an especially
vulnerable population. If all older people are to
maintain or acquire a healthy lifestyle, then
outreach to the food insufficient elderly must be
developed and implemented. Also, gaps in the
safety net must be identified and remedied and
food assistance and nutrition education efforts
improved.
Micronutrients in the elderly
Micronutrients consist of two components
namely vitamins and minerals. Vitamins are
organic substance that the body needs in
minuscule amounts. Two classes of vitamins
exist fat-soluble (A, D, E, and K) and water-
soluble vitamins (B vitamins and vitamin C).
Minerals are inorganic elements, categorized as
major minerals (sodium, calcium, phosphorus,
magnesium, etc.) and trace element (iron, zinc,
selenium, iodine, etc.) are essential minerals that
the body needs in small amounts.
(10)
The function
of minerals is involved in a variety of structural
and regulatory functions.
In t he el derl y, t he bodys defense
mechanisms begin to weaken, thus as a result
the elderly are more susceptible than younger
adults to infections and illness. Moreover,
elderly people are two to 10 times more likely
to die of a variety of infections than younger
adults.
(11)
Several micronutrients are significant
immuno-modulators and thus are critical in
determining the outcome of host microbe
interactions.
(4)
Vitamin A, beta-carotene, folic
acid, vitamin B
6
, vitamin B
12
, vitamin C, vitamin
E, riboflavin, iron, zinc and selenium are some
of the micronutrients that have been shown to
influence host resistance mechanism, thus
al t eri ng t he suscept i bi l i t y t o i nfect i ous
disease.
(12)
Antioxidant nutrients play a central role in
maintaining the antioxidant or oxidant balance
i n i mmune cel l s and i n oxi dat i ve st ress
protection, and preserving adequate function.
Dietary supplements protect the body from
accelerated aging process in various ways. The
supplements enhance metabolic functions, help
to detoxify harmful substances, antioxidant
activity or recycle antioxidants after quenching
free radicals. Some supplements are important
as cofactors for antioxidant enzyme activity.
Immune system in the elderly
The most basic defense mechanism of the
human body is the immune system. There are
two types of immune function, innate and
acquired immunity. Dysregulation of immune
function on humans may contribute to increasing
the incidence of infection, inflammatory and
cancerous diseases in the elderly and prolonged
recovery period of illness. The increase in
disease frequency associated with aging suggests
that immune responsiveness is decreased in the
elderly; aging is associated with higher incidence
Kusumaratna Nutrition and immunesystemin elderly
143
Universa Medicina Vol.25 No.3
of infections and subsequently, a higher mortality
related to infections. Aging is also associated
with other pathologies related to immune
dysfunction, i.e. higher incidence of cancer,
increased monoclonal immuno-globulins and
increased autoantibody levels.
(1)
Numerous studies have investigated the
age-related changes in immune responses. The
ability of stem cells decreases with age; their
ability to mature in lymphoid tissues also
decreases with age, in relation to decreased
thymus function.
(13)
Lesourd
(14)
examined the
effect of aging (healthy elderly) with or without
PEM, found that age-associated with decline in
total-T and T-helper cells occurred only in the
presence of protein energy malnutrition (PEM).
Similar adverse findings on immune function
also were reported for elderly deficient in
vitamins B
6
, B
12
, iron and zinc. Bogden
(15)
also
reported that deficiency of zinc impairs cell-
mediated Immunity by reduced lymphocyte
proliferation response.
Scri mshaw and Gi ovanni
( 16)
showed
evidence of adverse effects on immunity in
several macro and micronutrients deficiencies.
The results suggested that even mild infections
could adversely affect nutritional status and
deficiency of almost any nutrient will impair
immunity and resistance to infection. Thus, it is
not surprising that some aspect of immunity was
strongly influenced by nutritional deficiencies.
Some studies had summarized that under-
nutrition in the elderly appeared as one of the
main factors that could influenced low immune
response in the elderly.
(8)
Cat abol i c response occurs wi t h al l
infections including sub-clinically and not
accompanied by fever. Under the stimulus of
interleukin-1 released by leukocytes, endocrine
changes are initiated that lead to the mobilization
of amino acids from the periphery, primarily
from skeletal muscle. During infection, amino
acids as an anabolic response are diverted from
normal pathways for the synthesis of immuno-
globulins, lymphokines, C-reactive proteins and
a variety of other proteins.
Barringer
(17)
showed that a multivitamin and
mineral supplement reduced the incidence of
participant-reported infection and related
absenteeism in participants with type-2 DM and
high prevalence of sub-clinical micronutrient
deficiency. Nutrition had strong influence on the
immune system of the elderly. Aging induced
dysregulation of the immune system, mainly
changes in cell-mediated immunity that is
associated with changes to the equilibrium of
peripheral T and B lymphocyte subsets. It
decreased the ratios of mature to immature, nave
to memory, T helper 1 subset (TH-1) to TH-2,
and CD5- to CD5+ cells.
Effect of protein-energy malnutrition on
immune responses in the elderly
Infect i ons are more common i n
undernourished than in well-nourished persons.
Both protein energy malnutrition (PEM) and
aging had cumulative effects on immune
responses that induced a sharp decline in
immunity in aged, both animal trials and
humans, with low protein intakes. Increases in
immature CD2+, CD3-, T cell subsets were
observed in both healthy and well-nourished
elderly, although low serum folate concentrations
was found in Lesourd study.
(18)
On the other
hand, malnourished elderly, showed alterations
in T lymphocyte subsets together with lowered
T lymphocyte proliferation and IL-2 release,
compared with healthy elderly without any
nutritional deficiencies. It has been reported that
undernourished elderly subjects are more likely
t o have pul monary i nfect i on. In many
pulmonary-infected elderly individuals, CD4+
concentrations have been reported as low as
those found in patients with AIDS.
(19)
In el derl y subj ect s wi t h PEM, al l
parameters of cell mediated immunity are
144
decreased beyond the levels found with normal
agi ng: T cel l number (CD3+, CD4+),
l ymphocyt e prol i ferat i on, and cyt oki ne
synt hesi s.
( 1)
PEM i nduces not onl y l ow
lymphocyte counts and functions but also low
polymorphonuclear and monocyte function.
Therefore, PEM can modi fy t he cl i ni cal
symptoms of inflammation in undernourished
elderly individuals, for example, there is a low
release of IL-1 in the undernourished during
infection and although these patients are really
infected, but in some no signs of fever are shown.
Antibody response also is lowered in the
undernourished elderly population. Sero-
conversion rates after tetanus toxoid or influenza
vaccine are shown to be lower in elderly people
suffering from malnutrition. After vaccination,
not only are antibody levels lowered in the
elderly suffering from malnutrition, but antibody
affinity is also reduced.
(20-22)
The role of nutrition in immunity in the elderly
Immunological vigor declines with age,
contributing to increase morbidity and mortality
in the elderly. In addition, the elderly are at
greater risk for low intake of several vitamins
and minerals known to influence the immune
response. The fact t hat nut ri ent -nut ri ent
interactions and multiple nutrient deficiencies
often occur in the elderly. Adequate protein
status is important for determining lymphocytes
counts, lymphocyte proliferation, and antibody
response.
(13)
Recent studies have shown that
supplementing the elderly with single nutrients
or mixture of vitamins and minerals at levels
t hat exceed t he Recommended Di et ary
Allowances (RDA) significantly improves
cert ai n i ndi ces of t he i mmune response.
Harshman et al studied
(23)
supplementation with
t race el ement sel eni um act ed bot h as an
antioxidant and anti-inflammatory agent.
Selenium deficiency could impair both cell-
mediated immunity and B cell function, also may
be linked to the transition of harmless viruses to
virulent ones and may have an impact on viral
disease. By acting as scavengers, gluthatione
peroxi dases (sel enoprot ei ns) hi nder t he
propagation of free radicals and reactive oxygen,
diminishing the production of inflammatory
prostaglandin and leukotrien from hydroperoxide
intermediate. Selenium supplementation showed
enhanced proliferation of activated T cell,
enhanced the response to antigen stimulation of
lymphocyte, increased the ability of lymphocytes
to become cytotoxic for tumor cell destruction,
and increased natural killer-cell activity. Another
study used four-leg supplementation, trace
element (Se & Zn) or Vitamin (E, C, !-carotene)
or a combination of both, or placebo.
(20)
Antioxidant levels in the supplementation
were of physiologic doses: 1 to 3 times the
RDAs, and the study was conducted over 2 years
with institutionalized elderly in apparently good
health with a priori life expectancy of 3 years.
Selenium and vitamin deficits were corrected
with supplementation within 6 months, but a
longer period (1 year) was needed to restore zinc
deficit. The supplementation induced decreases
in lipid peroxidation. The group treated with
antioxidant vitamins showed increased monocyte
functions (IL-1 production). In contrast, the
increase in antibody titers after influenza vaccine
was higher in the trace-element group and
reduced the incidence of infection. Meydani
(24)
have conducted several studies using a large
range of vitamin E supplements for several
months. The result showed that in healthy
elderly, vitamin E supplements increased delayed
type hypersensitivity, lymphocyte proliferation
and IL-2 production. The optimal dose level of
vitamin E per-day that caused this immune
response was 200 mg. An epidemiological study
indicate that the antioxidant properties

of vitamin
E and polyphenols present in green tea may
contribute

to reducing the risk of cardiovascular
disease, in part by reducing

the susceptibility of
Kusumaratna Nutrition and immunesystemin elderly
145
Universa Medicina Vol.25 No.3
low density lipoproteins to oxidation,

decreasing
the vascular endothelial cell expression of pro-
inflammatory

cytokines, and decreasing the
expression of adhesion molecules

and monocyte
adhesion.
(25)
Thus, five general concepts have been
advanced that value the effect of micronutrient
on immune responses, namely (i) alterations in
immune responses occur early in the course of
reduced micronutrient intake, (ii) the extent of
immunology impairment depends on the type
of nutrient involved, its interaction with other
essential nutrients, the severity of deficiency,
the presence of concomitant infection, and the
age of t he subj ect , ( i i i ) i mmunol ogy
abnormalities predict outcome, particularly the
risk of infection and mortality, (iv) for many
micronutrients excessive intake is associated
with impaired immune responses, and (v) test
of immuno-competence are useful in assessment
of safe lower and upper limits of micronutrient
intake. However, in elderly individuals, diet is
restricted and the absorption of nutrients is
reduced in metabolic function that might need
supplementation of certain nutrients.
(26)
Without adequate nutrition, the immune
system is clearly deprived of the components
needed t o generat e an effect i ve i mmune
response. Nutrition deprivation, such as protein
energy mal nut ri t i on (PEM), oft en causes
i mmunodef i ci ency l eadi ng t o i ncr eased
frequency and severity to infection. (Table
1).
(22)
Table 1. Physiological and pathological situations in which nutrition acts as a primary or
secondary determinant of immune function impairment
(22)
146
Older and obese individuals tends to have
high prevalence of common infections. The effect
of exercise on immune response is multifaceted,
depending upon the type of exercise and the
intensity of training. In general, it is accepted
that while moderate exercise enhances immune
functions, high-intensity and heavy training can
suppress various immune response parameters.
The primary activity of mucosal immune
response is to protect the mucosa by blocking
microbial, toxin and antigen. Commensal
bact eri a may exert a dual funct i on: t he
stimulation of mucosal mechanisms of defence
and the maintenance of homeostasis of the
immune response. Probiotics have proved
helpful in prevention of infectious diarrhea and
shortening of the episodes.
CONCLUSION
The importance of adequate macronutrient
and micronutrient intake throughout the life
course to maintain health is essential. Under
nutrition strongly influences immune response
in the elderly since many nutrients interact with
immune system. Because the immune response
needs rapidly dividing cells and highly activated
secreting cells to be efficient, all nutrients that
interfere with cell division and metabolism may
influence immune response. The nutritional
deficiency impairs the immune response,
exposure to viral pathogens, and will result in
an increase in the severity of diseases. The
multiple effects of nutritional deficiencies on
immune function also increase the frequency and
severity of infections. This indicates that aging
and the undernourished had cumulative effects
on immune response of the elderly that could be
detectable both in cell-mediated and humeral
immunity. Supplementation with micronutrients,
including minerals such as selenium and zinc,
coul d reduce morbi di t y from respi rat ory
infections among the aged. Therefore, nutritional
deficiency must be treated in the elderly to reduce
risk of infection and possibly slow down the
aging process.
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