Antioxidant effects on Karlheinz

and /3-carotene:

Schmidt

ABSTRACT status Among

vitamins

Adequacy

or deficiency

in the micronutrient

often are

of an individual deeply affects its immunocompetence. the different micronutrients, antioxidative vitamins

f3-carotene

are

particularly

effective

in

modulating

functions and host defense against microorganisms vasive processes. This involves antigen-specific mediated

reactions

inflammatory

ofthe

processes.

cronutrient

status

the micronutrient risk of specific intervention

system

Owing

and

to the

as well

as nonspecific

interactions

between

the

status ofan individual diseases associated with

can help a deficient

eg, infection it should

in a number

or cancer.

be possible

ences. plines.

of

to predict the or suppressed

this

controlled

risk

studies.

Studies relation,

Assessment

detection

of

Nuir

specific

micronutrient

defi-

KEY

WORDS

Vitamin

vitamin

C,

E, /3-carotene,

immu-

etc.

nocompetence

nations

industrial

groups

and

When

be

athletes,

persons

marginal groups of the In addition, a sociodemographic

In the past

decades,

between clinical

mation,

nutrition relevance

cancer,

of”vitamins

and and

Although has

autoimmune

ofthe

American

the present and ofthe

noxes

nutritional

science

knowledge

of the

for scientific

progress

Association

and

and

area

l99l;53:383S-5S.

most

scientists

of nutritive part are Printed

A problem

field

died

performed represents

recent

Also

down

pressure

the pa-

functional

have

ofadequate

and immunological animal models, in USA.

too

are

older

people,

persons

under

immobilized combined,

persons,

it amounts

population:

to

we are not talking

the population

about everyone. intensifies the

and

coupling

micronutrients,

liquid test

that serve for health.

should

vitamins,

in the fact that, in blood exist,

higher

not

minerals,

to demonstrate On grounds

be invasive

the relevance of practicality,

or should

at least

be

accessible biological material. Vitamin A case as it is detectable in blood by high-

chromatography

(HPLC),

is also

with

for example

and

although methods the matching func-

available

but for which

impression

a good important blood,

starting that

contains

a suitable

cytology.

Especially in the preventive sense, it is important first signs of a decline into deficiency. For this,

bution,

on

to recognize the concept

point. To ensure the compartment micronutrients

optimal of distri-

at a normal

of

little

hindrance methods which

the

test on easily a favorable

of storage represents supply, it is not only

review

characterized

a great

concerning

functional

science

more

on, that also on morbidity.

children,

population, but development

overaging

tional tests are missing of the value measured the

concentrates

to multimorbidity.

trace elements, can be seen for detecting these substances

that a definite surwhen the immu-

The

by further leading

has shaped

to strengthen

is the lack

risks

be men-

and

has precisely

nutritional

in this

1970

has temporarily than

the

must

of “great gaps in knowledge” have too little knowledge

of immunology.

for parallel investigation tions. Here, an important Am J C/in Nuir

is restituated.

in speaking immunologists field

Regarding Axetrod

1940

problem

of inter-

ofantibiotics,

rather

have

that becomes points should

2) determination such as inflam-

in recent times is only possible

host

Medical

situation fact that

topic

introduction

to fight

ofthe

name

between

in this

tient, it has been recognized mounting of these ailments nocompetence

immunology

mechanisms

disease. the

work

successful

endeavored

of the

immunity,”

the interest ofthe

and

field of work areas. Two starting

and immunity and ofdifferent symptoms,

tioned, whose scientific this area decisively. because

science

1) comprehension

be emphasized: action ofthe

nutritional

into an interdisciplinary interesting for both

be investigated

vegetarians,

the total

an energy

consequences.

can be counted and therefore

newborn

about

developed increasingly

science

groups

times

that

the

cannot

fed parenterally,

risk

three

and immune comprehensible

to demonstrate this cordiets are hardly found

smokers,

being

all known

approximately

for

therefore

nations,

would

women,

medication,

sci-

are old disciin establishing

clear

is responsible

where marginal deficits on immunocompetence

risk

pregnant

199 l;53:383S-SS.

methods

in nutritional

and immunology have difficulties

countries serve protein deficiency

industrial

here. In western

Such

early

Am J C/in

relevant

it is immediately

deficiency

in third-world since severe

in western

as has been

Here

substrate

in

very

immunological

species

areas.

in its mechanisms. and

risk groups, have effects

the

Especially,

science disciplines

interdisciplinary

ofthe immunocompetence ofan individual by measuring a limited number of key parameters of the immune system can help ciencies.

areas.

different

The correlation between protein malnutrition deficiencies is relatively well documented and

mi-

assessment

for both for the

Both nutritional But often old

new

By the appropriate

to modify

ofcarefully

immune

or other inhumoral or cell-

immunocompetence,

immunocompetence, shown

immune

and

ill suited missing

quesare

© 1991 American

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I From the Department Tuebingen, Germany. 2 Address reprint requests

D-74l3 Society

Gomaringen,

for Clinical

Nutrition

of Experimental to K Schmidt,

Medicine, Aussere

University

Weiler

of

Strasse

12,

Germany. 383S

SCHMIDT

384S level,

but

deficiency usually which ten,

also

that

will

be the emptying

the

difficult to measure are the relevant body

no change

here,

wilt

emptying

ofthe

bone

the

since

one

can

manifest

early

assume

will

munocompetence. ods

allow

on the specific

the

early

mediated systems hydrolytic

results,

cytokin-type,

A vitious nificance

subclinical

infection

for most

or active

different

states

taken

into

systems

mechanisms,

cilia,

micronutrients

introduce

the relatively

for

at least

four

2) sufficient

of the etc.

of the must

be

3) optimal

supply. At all stages, immunology decisions. Here, one will have

new term

of immunotoxicology,

area that is developing rapidly and will permit ment of every intervention. To illustrate on another example, deficiency

to

a special

a sensitive

judge-

in the

element zinc will lead to characteristic immunological consequences upon malnutrition, such as atrophy oftymphatic tissues, leukopenia, reduced antibody responses, reduced production and release

of cytokines,

impaired

cytotoxicity

of immune

cells,

de-

dined levels ofthymic hormones etc. When increasing the supply of zinc up to the level of overoptimal supply, negative effects can

be detected,

such

as blocking

hibition

ofcytoskeletal

function,

changes

in membrane

fluidity

offunctional fore be optimal

parameters possible supply

approach

ever,

by the

example upon

not

and supplementation infections under not

immune

lead

the areas overoptimal animal,

of the

a wide it should

range there-

of sufficient and supply. In this and

element

iron,

This

deficiency

infection.

to an

increased

of iron does these conditions. lead

system,

in-

transport,

in vitro

studies

each other to acquire the evidences needed. can be in the case ofa single micronutrient

in blood does

receptors,

ofcalcium

By measuring

epidemiological,

should complement How difficult this reduced

etc.

to clearly delimit from deficiency and

clinical,

is shown

ofthe

of membrane inhibition

to infections

susceptibility not improve Iron overload, but

which

is usually

of iron,

the liability to on the other

hand,

does

with

failure cohort single

ofheart and liver function. It has been shown in extensive studies that were carried out in third-world countries that micronutrients are excellent predictive parameters with

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Similar

be shown

ofthe

that

of the

natural

A in vitro.

Another

between

decreased

nutrition

at old

age.

that

munity

situation

point

this

supply

of

of view, factor

and have

age

been

reduces

performed w.here more

that

that

ensure

can

function

as

functions

per

the

an

persons

can

by /3-carotene, have

think

that

studies

are being

yond

doubt

New

data

also

example,

show

by the

of vitamin

E. Similar

chickens.

deduced

from

antibodies to IgG

showing

antiinflammatory oxygen

results humoral

also

exist.

is Here,

the connection effects

that

be-

for vitamin

E.

of E co/i from

clearance

reduced were

also

of rate

on application

under

supplementation

shown

for other

immunity that

vitamin

is also

show

of

species,

effected

increased

E supplementation.

to combine

can

be

production A shift

the antioxidant

relatively effect

compounds

metabolism

But,

evidence

from

of 1gM

described.

It is justified a group

should

and

tumors clarify

of radiaone

radiation.

go further

mortality

clearly

investigations

under is also

that

was

That

Here,

can be improved at a highly significant of vitamin E is optimal. A similar result fact

germs

Especially

be compensated effects

immunostimulant be shown

blood after infection level when the supply pathogenic

but of this

protective

years.

ultraviolet

will

that to dis-

top

further

few

time.

against

that

im-

few years.

it could

is presented

on

can

for some

effects

next

of the

immunosuppressant

performed

in the

has

ofradiation

of fl-carotene

preventive

be considered

toxicologically,

past

at excessive

effects

that as is a

be achieved.

A. That,

of the

known

labialis

preventive

increasing

the

been

of Herpes

It can

usually

fl-carotene

effects

whereas

already

mal-

be noted

fact is surely of importance a micronutrient stands

se is knowledge deleterious

of the

and

improvement

of vitamin A,

is that

unnecessary

unquestionable

supply

provitamin

the long-term

and

as

by addition

it should

at old age.

is completely

as well

be raised question

this,

measures

of old

A is concerned,

immunocompetence

is as unnatural

by dietetic

position

can

important

In discussing vitamin A, the with the provitamin /3-carotene

the

this

ofvitamin

cells

of immunocompetence

proven

eg,

that

the

of lymphocytes

Concerning

at old

reduction

effect

killer

connection

For

group

antiinfectious

studies

blastogenesis

ofvitamin

how-

to infections,

to hemochromatosis

an essential

shown

immunocompetence

of infections.

activity

the

of this

when

at from

of

as a sign

half.

tion

essential

mortality A have

Looked

collective

detectable

infectious diseases, eg, measles in Tanzania, could be reduced from 1 3% to 6%, which means

malnutrition

often dein of mi-

steps

supply,

for other mortality

were

by 30-50%

stabilizes

of Indonesia is raised by a

supplied

spots

vitamin

be considered and

the beginning

the

and

up a scale

A can

it could

is also of sig-

diseases the taking

with

be lowered

As far as the mechanism

by malnutrition,

putting

supply,

1) deficiency,

supply, and 4) overoptimal can be an important help

oxidative

Bitot

A is normalized.

than

antigenor T-cell

mediator

When

of nutritional

account:

suppression

the different effector such as chemo-

is reduced

further.

or meth-

may concern production

studies can

connection, importance.

in populations that mortality

vitamin A deficit the by a factor of 6.6.

Intervention

increases

In this

are ofmajor

to a normally

When

of a considerable was even increased rate

a population.

observed A deficit

vitamin

population.

vitamin

im-

it has been

of 2.7 in comparison

that

of the

opsonization, defense

surely

in such

immunocompetence

a marginal

mortality

measurement,

detection

of deficits

immunocompetence

is reduced

present

mortality with

For example, with factor

cal-

susceptibility

in immunological

tissue

valid

to the

the same

blood

may

for

because of which infectious gastrointestinal velop that lead to malabsorption, so that cronutrients

of Of-

for vitamin the liver res-

by disturbances

ofdecomposition,

cycle

since

the

immunology

be preceded

complement,

mucous

interactions

think

may

accessible

registration

reactions

regard

is

should

while

or humoral level. This in the sense of antibody

phagocytosis,

of

This

to a continuous

is similar when

immunity, but also may concern that can react antigen-independently,

taxis,

sign

vitamin

Advances

cellular reactions

One

leads

measurements

reactions

that

infections

first

future.

functional

to make

The

reservoirs.

ofcalcium,

turnover

for the

Concerning be suited

which

be raised. This show differences

Here,

possibilities

up.

body’s

in the blood.

reservoir even only

are emptied.

filled

and in many cases the question reservoirs remains unanswered.

of osteoporosis,

cium level often may A where blood levels ervoirs

are of the

be detectable

for example,

new

reservoirs

uniform as a result

would of arachidonic

of arachidonic acid process and represent motaxis, phagocytosis,

are

effect

micronutrients spectra.

of interactions

belong,

but also acid.

To with

into this,

the interference

Especially

the

the

activated with

metabolites

major mediators in the inflammatory a number of single functions, eg, cheand intracellular killing. Also, processes

ANTIOXIDANT such as the which opens Paradox with a low whereas

degranulation of granulocytes the way to allergies. reactions are concentration

high

synergistic

between

change the

different vitamins and trace rather coupled redox-reactions several

redox-systems,

can

into

antioxidant

elements must

inhibition.

ascorbate,

already mentioned, zinc, or selenium-belong

ofthese

considerations the

becomes risk

group

most

likely some to this. The particularly

of persons

Despite the

being

glutathion,

area to optimize Besides the vitrace elementsclinical relevance

evident, fed

& IMMUNOCOMPETENCE

3855

whose state of supply of micronutrients is only improved in the fewest cases. One is not rarely

cannot replace each other, be counted on, in which

eg, a-tocopherol,

tamins copper,

regarding

influenced,

micronutrients,

etc. are involved. It is therefore important in this the state of supply for all essential components.

on

be

not uncommon for these regulations, leading to stimulation, for instance,

concentrations

effects

VITAMINS

for instance, parenterally,

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intensive

care

tibiotica

cover,

units

is badly

compromised.

patient

is not

Especially in the overdose field, clinical ciplinary

under

cases

these

to rather

is tolerable research, initial

occurs,

Usually,

the

either,

since,

especially

in most

cases.

requires surely

will

patient

for the

cellular

much

seems than

Progress get

in this experimental by without

that

important

to do too

particularly

specific not

of the

is available

conditions, too

of an-

of the

immunocompetence

of micronutrients,

primarily which stages.

marginal do a little

and in the

in spite

immunocompetence

no flow-through-cytometer assessment.

supplementation however,

a pneumonia the

surveyed

immune functions, would enable quick in these

when

because

monitored surprised

little as an

important and interdisU