dr.-rina

8/13/2019 dr.-Rina

1/8

140

Nutrition and immune system in the elderly

Rina K. Kusumaratnaa

Department of Communty Medicine, Medical Faculty, Trisakti University

ABSTRACT

The number of individuals aged 60 years or older is projected to doubleas a proportion of the worlds

population and to morethan triple in number over the next 50 years.Aging is often associated with a dysregulationin 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 radicalsand oxidative stress have been recognized as important factorsin the biology of agingand of many

age-associated degenerativediseases. Therefore, dietary components with antioxidantactivity have received

particular attention because of theirpotential role in modulating oxidative stress associated withaging 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 gizipada 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. 021-5660706E-Mail : [email protected]

Universa Medicina Juli -September 2006, Vol.25 No.3

8/13/2019 dr.-Rina

2/8

141

Universa Medicina Vol.25 No.3

INTRODUCTION

The proportion of age individuals hasrapidly increased in the second half of the

twentieth century in both Western and

Developing Countries (1 ) 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. The United Nations

Population Division estimated that this agegroup

represented ~10% of the worlds population, or

~600 millionpeople, 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 numbersacross agegroups.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,

synthesize t issues or perform regulatory

functions. Our body needs nutrients for normal

growth and development, maintenance of cells

and tissues, providing fuel for physical activityand 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 large quantit ies of

carbohydrates, proteins and lipids to serve the

general functions, these substances are called

macronutrients; the vitamins and minerals arecalled 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 skeletaland 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

8/13/2019 dr.-Rina

3/8

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 elderlypopulation 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 micronutrients. 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 inminuscule 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 the elderly, the bodys defensemechanisms 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 B6, 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

altering the susceptibil i ty to infectious

disease.(12)

Antioxidant nutrients play a central role in

maintaining the antioxidant or oxidant balance

in immune cells and in oxidative stress

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 immunefunction 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 Nutrit ion and immune system in elderly

8/13/2019 dr.-Rina

4/8

143


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 B6, B

12, iron and zinc. Bogden(15)also

reported that deficiency of zinc impairs cell-

mediated Immunity by reduced lymphocyte

proliferation response.

Scrimshaw and Giovanni (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)

Catabolic response occurs with allinfections 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 andmineral 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

Infections are more common in

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 thatundernourished elderly subjects are more likely

to have pulmonary infection. In many

pulmonary-infected elderly individuals, CD4+

concentrations have been reported as low as

those found in patients with AIDS.(19)

In elderly subjects with PEM, all

parameters of cell mediated immunity are

8/13/2019 dr.-Rina

5/8

144

decreased beyond the levels found with normal

aging: T cell number (CD3+, CD4+),

lymphocyte proliferation, and cytokine

synthesis.(1 )

PEM induces not only lowlymphocyte counts and functions but also low

polymorphonuclear and monocyte function.

Therefore, PEM can modify the clinical

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 that nutrient-nutrient

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

that exceed the Recommended DietaryAllowances (RDA) significantly improves

certain indices of the immune response.

Harshman et al studied(23)supplementation with

trace element selenium acted both 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

peroxidases (selenoproteins) hinder thepropagation 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 priorilife 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 proliferationand 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 propertiesof vitamin

E and polyphenols present in green tea may

contributeto reducing the risk of cardiovascular

disease, in part by reducing the susceptibility of

Kusumaratna Nutri t ion and immune system in elderly

8/13/2019 dr.-Rina

6/8

145


low density lipoproteins to oxidation,decreasing

the vascular endothelial cell expression of pro-

inflammatory cytokines, and decreasing the

expression of adhesion molecules

and monocyteadhesion.(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 the subject , ( i i i ) immunologyabnormalities 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 assessmentof 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 to generate an effective immune

response. Nutrition deprivation, such as protein

energy malnutrition (PEM), often causes

immunodeficiency leading to increasedfrequency 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)

8/13/2019 dr.-Rina

7/8

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 theintensity 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

bacteria may exert a dual funct ion: the

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 agingand 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,

could reduce morbidity from respiratory

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.

Reference

1. Lesourd BM, Mazari L, Ferry M. The role of

nutrition in immunity in the aged. Nutr Rev 1998;

56: 113-25.

2. Tucker KL, Buranap S. Nutrition and aging in

developing countries. J Nutr 2001;131: 2417S-23S.

3. Meydani A, Ahmed T, Meydani SN. Aging,

nutritional status and infection in the developing

world. Nutr Rev 2005; 63: 233-46.

4. Bhaskaram P. Micronutrient malnutrition,

infection, and immunity: an overview. Nutr Rev

2002; 60: S40-S5.5. Kann PH. Clinical effects of growth hormone on

bone: a review. The Aging Male 2004; 7: 290-6.

6. Mulligan C, Moreau K, Brandol ini M,

Livingstone B. Alterations of sensory perceptions

in healthy elderly subjects during fasting and

refeeding. a pilot study. Gerontology 2002; 48: 39-

43

7. Insel P, Turner ER, Ross D. Life cycle: the adult

years. In: Nutrition. Boston: Jones and Bartlett

Publisher; 2002. p. 616-22.

8. Lesourd B, Simon M, Mazari L. Nutrition and

aging of the immune system. In: Nutrition and

immune function. London: CABI Publishing;

2002. p. 357-65.

9. USDA Center for Nutrition Policy and Promotion.

Food insufficiency and the nutritional status of the

elderly population. 2000. Available at: http://

www.usda.gov/cnpp/Insights/Insight18.PDF.

Accessed July 1, 2006.

10. Ahluwalia N. Aging, nutrition and immune

function. J Nutr Health Aging 2004; 8: 2-5.

11. Yoshikawa TT. Perspective aging and infectious

disease: past, presents, and future. J Infect Dis

1997; 176: 1053-7.

12. Grimble RF. Effect of antioxidative vitamins onimmune function with clinical application. Int J

Vit Nutr Res 1997; 67: 312-20.

13. Molls RR, Ahluwalia N, Masro AM, Smiciklas-

Wright H, Handte G. Nutritional status predicts

primary subclasses of T cells and the lymphocyte

proliferation response in healthy older women. J

Nutr 2005; 135: 2644-50.

14. Lesourd B, Mazari L. Nutrition and immunity in

the elderly. Proc Nutr Soc 1999; 58: 685-95.

Kusumaratna Nutri t ion and immune system in elderly

8/13/2019 dr.-Rina

8/8

147


15. Bogden JD. Influence of zinc on immunity in the

elderly. J Nutr Health Aging 2004; 18: 48-52.

16. Scrimshaw NS, Giovanni P. Synergism of nutrition,

infection and immunity. Am J Clin Nutr 1997; 66:

464S-72S.17. Barringer TA, Kirk JK, Santaniello AC, Foley KL,

Michieluitte R. Effect of a multivitamin and

mineral supplement on infection and quality of life:

a randomized controlled trial. Ann Intern Med

2003; 138: 365-71.

18. Lesourd BM. Nutrition: a major factor influencing

immunity in the elderly. J Nutr Health Aging 2004;

8: 28-35.

19. Lesourd BM. Nutrition and immunity in the

elderly: modification of immune responses with

nutritional treatments. Am J Clin Nutr 1997; 66:

478S-84S.

20. Girodon F, Galan P, Monget AL, Boutron-Ruault

MC, Brunet-Leconte P, Periosi P et al. Impact of

trace elements and vitamin supplementation on

immunity and infections in institutionalized elderly

patients: a randomized controlled trial. Arch Intern

Med 1999; 159: 748-54.

21. Graat JM, Scouten EG, Kok FJ. Effect of daily

vitamin E and multivitamin mineral

supplementation on acute respiratory tract

infections in elderly persons: a randomized

controlled trial. J Am Med Assoc 2002; 288: 715-21.

22. Marcos A, Nova E, Montero A. Changes in the

immune system are conditioned by nutrition. Eur

J Clin Nutr 2003; 57: S66-69.

23. Harshman MR, Aldoori W. The relevance of

selenium to immunity, cancer, infectious/

inflammatory diseases. Can J Diet Prac Res 2005:

66: 98-102.

24. Meydani M, Meydani SN, Blumberg JL.. Vitamin

E supplementation and in vivo immune responses

in healthy elderly subjects. J Am Med Assoc 1997;

277: 1380-6.

25. Meydani M. Nutrition interventions in aging and

age-associated disease. Ann NY Acad Sci. 2001;

928: 226-35.

26. Hughes DA. Antioxidants vitamin and immune

function. In: Nutrition and Immune Function. UK:

CABI Publishing; 2002. p. 171-86.

dr.-rina

Documents