The antioxidant

nutrients

and disease

prevention-what

do

we know and what do we need to find out?1’2 William

A Pryor

This has been not only because reflecting but

the

also

a spectacularly ofthe quality

very

because

real ofthe

successful conference. ofthe papers that were

advances

in our

unusual

I say that presented,

knowledge

breadth

ofthe

in this

subjects

Professor

LDL

area,

offatty

covered.

Esterbauer

particle,

for

streaks

Chemistry The

symposium

and

explained

stand

free

started the

radical

are important widespread

with

mechanistic

several

lectures

background

reactions,

and

especially

in free radical biology. nature of radical-mediated

stress. speakers

biological

those

and

from that

systems.

we

must

and

The

and also systems

they

cannot

its “footprints.”

newer

ofan

elusive

Although

tioxidant this

species, of

that

are

more

difficult.

smokers

For

in chronic

example,

have

blood

ofthiobarbaturic

ical involvement to the

Several

must lung

speakers

smokers

plasma

acid

be targeted

when

reactive

do not

gives

materials

does

have

do have lavage

very

provided

man blood disappears

nutrients Professor

insights

protect model Niki presented

serum, showing very much faster

cell membrane. is an interesting

Am J C/in Nuir

that than

sensitive

oxidative into

stress the

rates

in model systems, blood serum and of the mechanisms

(TBARS),

to, oxidative vi-

in USA.

reactive

in

damage

studies in some

oxygen

both

in vitro

solution,

on

the

in vivo.

an-

There

fl-carotene has but the evidence

fl-carotene

at low oxygen

tensions

in aqueous

as an antioxidant

and

The

to its anHowever,

of studies

showing that model systems,

concentrations

ascribed

or by implication. paucity

effect

for fl-carotene.

is often

at all (7).

anis

is most

ef-

(6).

In contrast,

micelles

fl-carotene

Studies

on the

an-

properties of fl-carotene in an aqueous system at low tensions have not been reported; these studies should be (and most are in vitro

mosphere of air. To probe whether

fl-carotene

compound

of its antioxidant

because to know

the

acts

as an antioxidant.

that

is produced

products

behaves that

If a marker

when

fl-carotene

for in cell culture

tumors) solutions

are oxygenated at exposed to an at-

as an anticarcinogenic properties,

are

formed

molecule

it would when

could

traps

radicals,

or animal

studies

displays anticarcinogenic properties. Several speakers also stressed the large more than 600 have been characterized

be identified

this species where

be

fl-carotene could

fl-carotene

number of carotenoids; (8). Virtually nothing

For of hu-

vitamin E in the LDL particle does vitamin E in the red blood

Printed

the

offi-carotene

behave

be searched

ranging from the LDL parby which an-

While reasons for this can be hypothesized, observation that is worthy of further work.

199l;53:39lS-3S.

(5).

can

implicated

to exist

explicitly out

since many organs lower levels than

useful

in smokers.

systems against oxidation. data on the oxidation

either

In chlorobenzene

not

done much

nearly

at which

most

(HNE)

for an anticarcinogen

appears

of fl-carotene

as an antioxidant

tioxidant oxygen

evidence

brought

properties

fective

disease

but they pulmonary

that

to, and

probing

tamins E and C are oxidized simple phospholipids to human tide. More studies are needed tioxidant example,

properties,

at normal involvement

effect

incomplete.

sen-

specific. radical

be

acids

compounds

nutrients

are several published tioxidant properties

in biological samples both to validate those

methods

fatty ofaldehydes,

in the cell than

may

the strongest

conference

tioxidant

but smokers exhale elevated amounts ofethane and pentane (4). Thus, cigarette smoke puts the greatest oxidative burden on the lung, as seems reasonable. Therefore, methods for detecting raddamage

related

anticarcinogenic in

a number

number

farther

therefore

and

At present,

Free

observed

has shown,

4-hydroxy-2-nonenal

diffuse

HNE

/9-Carotene

a given

processes.

level of vitamin E in blood plasma, lower level of vitamin E in their values

the in

the role against

that

be directly

we are on the trail

of proving

(3). Also,

and

group

to LDL.

that

stressed processes

free radical-mediated

to develop

is often

a reduced a strikingly normal

for

and

more

conditions

fluid

Thus,

look

task

reactions

in proving

that mark free radical activity reported (1, 2), there is a need

we have

sitive

the difficulty

results

footprints have been that

addressed

are so reactive

biological

radicals,

can

of the

in the development

polyunsaturated ofa

and

for the antioxidant

effect

radicals

outlined

of

to the production

aldehydes

of the oxidation

Esterbauer’s

oxidation

malonaldehyde

These

to under-

These lectures oxidative

normal biochemistry as well as in pathology ofantioxidant nutrients in protecting biological oxidative Some

that

necessary

that

leads

notably

studies

that may be involved

in atherosclerosis.

example,

(PUFAs)

presented

a process

© 1991 American

Downloaded from https://academic.oup.com/ajcn/article-abstract/53/1/391S/4691409 by Queen Mary University of London user on 25 March 2018

From

I

it

Society

the Biodynamics

Rouge, LA. 2 Address

reprint

isiana

University,

State

for Clinical

Institute,

requests

Nutrition

Baton

Louisiana

to WA Pryor, Rouge,

State

Biodynamics

University, Institute,

Baton Lou-

LA 70803-1800.

3915

PRYOR

392S is known

about

enoids. WF

the

antioxidant

of the

other

carot-

Richard onto

Malone

pointed

out

currently

lists over

of testing

for anticarcinogenic

the

properties

antioxidant

1000

that

the

National

compounds

ofall

effects.

properties

Cancer

types

that

Eventually

of many

of these

Institute

human Max

are worthy data

relating

compounds

with

Diseases

H Garewal:

involve

A remarkable

number

to be partly

data and

injury

through

free

on the potential were presented.

continues

Extensive

data

disease were improvements tioxidant

radical

Antioxidants It must

also

and be stressed

as a reducing

an antioxidant is the inhibitory was reviewed likely nitrite

due and

any

In this reaction,

shorter

for

research,

on rheu-

and

radicals caused

and mucosa

discussions

of free

establishing

by

in aging dietary

the

and an-

ofthese

nutrients

necessarily

can

behaving

play

either

a as

scavenger. An example of this C against stomach cancer that This inhibitory effect is most a nitrosating

agent

ofamines

as a reducing

derived

from

to nitrosamines. agent

by becoming

component

[vi-

that

diet,

taking

might

vitamin

be beneficial.

getting level

even

and

trials

National

vitamin

US

Recommended

ofthese

sponsored

Institutes

Dietary

nutrients.

by the of Health

micronutrients intakes that

deficiency

Further-

National that

Cancer

are

currently

that are considerably only be conveniently

can

fl-carotene,

These

the general of magnitude

appear

(the

RDA)

may

be less

C, and

to have

vitamin

no toxic

E, was

dis-

effects

for

side

even at levels that are at least one order than the RDA. One exception is that very

ofvitamin

E should

on anti-coagulant

Different to prevent

vitamin

nutrients population, higher

levels

diseases

provide protection against cancer or heart the very tow toxicity of these nutrients,

might regard,

especially

cussed.

high

the

(9) ofsome

data and

by taking supplements. Thus, an implicit assumption that the amount ofa nutrient necessary to prevent well-

not be recommended

for persons

therapy.

intakes of a nutrient different pathological

that

to point

spoke

between

at this conference

the intake

ofa

stressed

particular

that

nutrient

may be necessary conditions

can

the

hypothesis

the hypothesis

the epidemiologicat

ofa

health

be taken evidence

effect

from

seriously.

Using

for a health

benefit

appears to be strongest for the inverse relationship takes of fl-carotene and the risk of getting lung

between incancer (8). In

discussed

different

of nutrient (10).

hypothetical

protects

humans

achieved.

than

from

nutrient,

pathologies

amount results

finally,

the

amount

in fact, maximize

all respond

even

levels

protection

condition

effect

as can

B requires

an intake only slightly less than the greater pathology of type B. And

of pathological

condition

C that

can

coming years. I was particularly

study panel

made

during

lectures

or from the floor regarding the overall impact of the epidemiotogical data already in hand. The following remarks, quoted as nearly verbatim as my note-taking allows, illustrate the sentiment of the group:

Downloaded from https://academic.oup.com/ajcn/article-abstract/53/1/391S/4691409 by Queen Mary University of London user on 25 March 2018

of vitamin A; ie, rats

(ie, an RDA-like) vitamin E provide red blood a baseline

be

the full

tected continues to decrease as the amount of the vitamin creases, even up to levels very much higher than the RDA. This description may seem vague and theoretical, but quite real. For example, Bendich et al (1 1) have shown

by comments

A

some-

addition there are one or more reports of positive correlations between high levels of vitamin E and vitamin C and protection against certain cancers and/or ischemic heart disease. Clearly much more work in this area will be done and reported in the struck

to

condition completely

the protective

as much

pathological

ofprotection; in a measurably

that

Pathological ofthis vitamin

condition; already

providing

In contrast,

RDA RDA

this

the RDA

intakes and disease 1 shows the situation

Figure

the presence of a vitamin or nutrient. responds in such a way that the RDA

to this

support

out a feature

is not generally

due

guidelines,

to suggest a healthy

underway use levels ofthese higher than the RDA, daily

all) ofthe these

dietary

cancer.”

controversial

intervention

tower

nutrient

a simple

gastric

to eating

of the

what

a particular

have

not

and a beneficial health outcome requires several studies by several independent groups. Only when a majority (but not necessarily studies

are very

compound.

who

a linkage

carotenoids

cancer.”

(RDA)

Institute

evidence

epidemiologists

prevent

Nu-

against

are

for three The

may

can

be of

and

Allowance

I want Epidemiological

Food

elsewhere, more

Parkinson’s

nitrosated, but radicals are not involved. Similarly, above, fl-carotene may or may not possess antioxradical scavenging properties in systems in which

as an anticarcinogenic

on the

ofour speakers (eg, Gladys Block) presented substantial population groups, in America

one

C acts

may

prevention

Yet a number showing that

achieved is made

the nitrosation

vitamin

field

recognized

trapping

preventing

“We

very

than that which disease. In this

or a free-radical effect of vitamin at this conference.

served

on all the evidence, oral

as opposed

agents

without

to ascorbate

sacrificially as discussed idant and/or it acts

that agent

we

[in the

of vitamins

It remains pills,

discussed.

reducing

intake

Im-

ofoxidized LDL of ischemia/reper-

hemorrhage.

were

appear

to gastrointestinal

and

presented. The role in immunocompetence

that

intermediates.

involvement The area

intraventricular

nutrients

discussed

to be an active

on cataracts

arthritis,

Daily

here

of us who

“Based

that

to fl-carotene,

processes were

involving postischemic injury heart tissue were presented.

matoid

role

ofdiseases

mediated

pressive new data in atherosclerosis fusion

radicat-mediated

C]

regard important

National Research Council had a bias but we are changing our view.”

in preventing

tamin

with

.

“Those

C Schorah:

that

.

Board ofthe supplements,

active

activity.

“.

extremely

cancer]” Horwitt:

trition vitamin

their anticarcinogenic potential will allow a test ofthe hypothesis that antioxidant properties are a useful predictor of anticarcinogenic

Peto:

something

E in rats that are protected

myopathy responds against myopathy

amount of vitamin E and no additional protection.

cell hemolysis follows pattern level do not provide complete

be deinit is in a

as shown in by a baseline

further amounts of On the other hand,

B: levels protection.

much below Most strik-

393S

SUMMARY cronutrients

t

A

Fr ______ 1000 intake

of vitamin

(mg /day)

-*

the coming

response to a micronutrient is shown for three different pathological conditions. The micronutrient provides the maximum protection it can afford against condition A at an intake either at, or even slightly below, the RDA (9). For condition B, the RDA provides complete protection, but amounts slightly less are not sufficient. For condition C, however, the protection afforded by the micronutrient against this pathology continues to increase as long as the intake of the nutrient is increased, so that more than RDA-like amounts are of increased benefit. Conditions probably vary in their response to micronutrients in this way, as shown, eg, by the study of rats and vitamin E by Bendich et at (1 1).

improvements

Increasingly

in immune

higher

doses

higher than responsiveness. the

range,

serum

from

follow

E, even

of vitamin

E over

pattern

up to levels

a baseline amount, continue In fact, immunocompetence levels

0.04

competence

of vitamin

C.

very

to improve imcorrelates

an

enormously

away

with

wide

( 1 1).

to 1 8 zg/mL

Conclusions The

participants

timistic

in the

feeling.

The

congress

disease

flects the fact that the classic of our citizens in 1900 have of Americans cancer

die

free radical-mediated diseases, as well nutrients the

of heart

( 12). Evidence

such

incidences

The overall a watershed

was

went

pattern

in developed

a very countries

infectious diseases that almost been eradicated. and

blood

vessel

presented

that

along

with

suggests

that

injury plays a role in the etiology as others such as cataract formation.

as vitamins of these

tone ofthis with

regard

E and

re-

killed most Now 75%

diseases strongly

op-

C and fl-carotene

of these Micro-

may reduce

diseases.

conference to our

suggests attitude

that we have passed

toward

the

use

of mi-

Downloaded from https://academic.oup.com/ajcn/article-abstract/53/1/391S/4691409 by Queen Mary University of London user on 25 March 2018

life span,

not

vitamins.

be many

with

one

A number

years

daily

before

intake

to prevent known vitamin higher value recommended properties

for considerable

incidences

FIG 1 . The differing

with

is broadened,

son

Increasing

much mune

the

RDA

it may

ease-preventing

Hoo RDA

ingly,

the antioxidant

that

recommended a substantially

I I

and

suggested

ofthe

most

decades, and

ofthese

hopefulness life-limiting with

well-being

ofthe

the consequent of our

ofa

citizens.

concept

nutrient

of being

deficiency diseases and to optimize the dis-

nutrients. about

of speakers

the

our

Thus, ability

chronic improvement

there

is rea-

to reduce diseases

the

within in health,

U

References 1. Pryor WA. On the detection of lipid hydroperoxides in biological samples. Free Radic Biol Med 1989;7: 177-8. 2. Colowick SP, Kaplan NO, Packer L, eds. Methods in enzymology. Oxygen radicals in biological systems. Vol 105. Orlando, FL: Academic Press, 1984. 3. Pacht ER, Kaseki H, Mohammed JR, Cornwelt DG, Davis WB. Deficiency of vitamin E in the alveolar fluid of cigarette smokers. J Clin Invest l986;77:789-96. 4. Lemoyne M, Van Gossum A, Kurian R, Ostro M, Axter I, Jeejeebhoy KN. Breath pentane analysis as an index of lipid peroxidation: a functional test of vitamin E status. Am J Clin Nutr 1987;46:26772.

5. Esterbauer H. Aldehydic products oflipid peroxidation. In: McBrien DCH, Stater TF, eds. Free radicals, lipid peroxidation and cancer. New York: Academic Press, 1982:101-28. 6. Burton GW, Ingold KU. Beta-carotene: an unusual type of lipid antioxidant. Science l984;224:569-73. 7. Pryor WA, Strickland T, Church DF. A comparison ofthe efficiencies of several natural and synthetic antioxidants in aqueous sodium dodecyl sulfate micelle solutions. I Am Chem Soc 1988; 1 10: 2224-9. 8. Bendich A, Olson JA. Biological actions of carotenoids. FASEB I 1989;3: 1927-32. 9. The Surgeon General’s Report on Nutrition and Health. Washington, DC: US Government Printing Office, 1988. [DHHS publication

(PHS) 88-502 10.] to. Pryor WA. Can vitamin

E protect us against the pathological effects of ozone in smog? Am I Clin Nutr (in press). 1 1. Bendich A, Gabriel E, MachIm LI. Dietary vitamin E requirement for optimum immune responses in the rat. I Nutr 1986;l 16:67581. 12. Leaf A. The aging process: lessons from observations in man. Nutr Rev t988;46:40-4.