Differences exist in the relationships between dietary ...

Differences exist in the relationships between dietary linoleic and a-linolenic acids and their respective long-chain metabolites13 Evangeline

Mantzioris,

ABSTRACT

Increased

entaenoic coronary

acid

(EPA)

ders.

heart Successful

EPA

concentrations

between

concentrations

have

been

require

acid

(LA),

eicosap-

on the

of

and

of

dietary conver-

sion to EPA. A dietary intervention study with healthy human volunteers that incorporated a-LA-rich vegetable oil (flaxseed oil),

against

a background

examine

these

between

dietary

cellular observed

diet

relationships. a-LA

low

Linear

and

EPA

in

LA,

allowed

relationships in plasma

phospholipids. By contrast between dietary LA and

there tissue

us

were

to

found

fractions

G Cleland

ratio

of n-6

to n-3

n-6

to n-3

eicosanoids

orders

amounts

of a-LA

Leslie

lular concentrations in coronary heart

relationships

EPA,

an antagonist

in

disorcellular

and dietary

a precursor

acid

and

to be beneficial

and inflammatory for increasing

of EPA

(a-LA),

A Gibson,

of cellular

shown

information

concentrations

of linoleic

Robert

and

in

was no relationship concentrations of its

by

(2).

precursor

nuclear

cells,

and platelets.

dietary

a-LA

will

dictable manner. ning of practical of EPA 320-4

elevate

The

results

tissue

EPA

This insight will dietary strategies

concentrations

WORDS

acid,

flaxseed

oil,

sapentaenoic

acid,

Am J Clin

a-linolenic

plasma

fatty

that

increasing

in a pre-

facilitate the rational planfor the long-term elevation

in tissues.

Dietary

KEY

indicate

concentrations

acids,

docosahexaenoic

acid,

1995;61:

dietary

cellular acid,

Nutr

fatty

arachidonic

eico-

acid

Once

(AA,

ingested,

acid) can

dietary

linoleic

and a-linolenic be desaturated

a 20-carbon

n

-

acid and 6 fatty

acid

period

320

formation

which

allowed

acid

group

of fatty

acid

metabolites

pathways to form and thromboxane), a involved

those ratio

that

are derived

of n -6

to n

-

from 3 fatty

EPA acids,

(1). which

in many

ho-

AA are potent by comparison

Western

diets

is reflected Am

J Clin

1

altering

elevated EPA-rich

remains

of these

the

relationships long-term

the cellular

ratios

the effect

exogenous

EPA

polyunsaturated in a domestic

both

groups

ingested

a-LA

tissue

and

EPA

group

di-

of n -6

on endoge-

incorporation

cooking setting.

continued

the same

of

oils for flaxThe study was

EPA

the

EPA

and

of Paediatrics

and Child

Bedford Park, 2 Supported

South Australia. by the National

Health

Health, and

This

the

dietary

Hospital, Flinders

Medical

from

either high or group had with

second

Unit, Royal Adelaide

the Department

oil.

formation

incorporation

compared

first

respective

of fish

background diets that the flaxseed-oil

concentrations

in both

their

amount

of endogenous

exogenous

From the Rheumatology

sun-

periods

Adelaide Medical

Research

and

Centre,

Council

of

Australia.. 3

Reprints

not available. Unit,

Australia,

Australia,

5000. 1 1, 1994.

have

Received

April

Accepted

for

1995;61:320-4.

Printed

Royal

Address

matology

in the Nutr

oil

of successful

the investigation

dietary

acid)

meostatic functions. Eicosanoids derived from proinflammatory and proaggregatory agonists a high

for favorably

during

flower-oil

eicosapentaenoic

fish

understanding

development

and in addition

elevated

respectively. The AA and can then be metabolized

was with

into two periods: 1) a 4-wk period during which one of volunteers used flaxseed oil and spread and another used sunflower oil and spread, and 2) a further 4-wk

n-6

via the lipoxygenase and cyclooxygenase eicosanoids (leukotrienes, prostaglandins,

with

Greater the

substituting high n-6 seed oil (high in a-LA)

fatty acid

or

an 18-carbon

of eel-

tissue EPA concentrations. on EPA concentrations has

(5) we described

(a-LA, an 18-carbon n-3 elongated to arachidonic

fatty acid), membranes

(LA,

EPA diet

Nevertheless,

fish-oil capsules given against low in a-LA. We observed

(EPA, a 20-carbon n-3 EPA present in cellular

diverse

(5-10).

and

from

Introduction

cellular

nous

diets

increased

shown to be beneficial and inflammatory dis-

Western

to n-3 fatty acids. In a previous report EPA

and the ratio

the mathematical relationships between din-6 and n-3 fatty acids and tissue concenrespective cellular 20-carbon metabolites have

for

strategies

design

fatty acid)

usual

acids

(1, 3, 4). Tissue concentrations of EPA have to increase in varying degrees when the diet with flaxseed oil, which is high in a-LA, the

reported.

is important

divided group group

linoleic

acids,

studies,

of the

to EPA

been documented, etary 18-carbon trations of their

etary

mono-

Importantly,

most efficient means of increasing Although the effect of dietary a-LA

centrations

neutrophils,

fatty

produced.

In experimental

fish-oil capsules also been shown is supplemented

not been

of plasma,

membrane

of EPA have been disease, hypertension,

supplementation

metabolite, arachidonic acid (AA). There was an inverse relationship between dietary a-LA and docosahexaenoic acid conin the phospholipids

cell

Adelaide

publication

in USA.

correspondence Hospital,

August

© 1995

North

to E Mantzioris, Terrace,

Adelaide,

RheuSouth

8, 1994.

American

Society

for Clinical

Nutrition

Downloaded from www.ajcn.org by guest on July 15, 2011

a-linolenic

J James,

disease, hypertension, long-term strategies

cellular

amounts

Michael

DIFFERENCES (5).

Subsequently,

and

tissue

this

study.

acid

These

tionships

fatty

we

fatty

metabolites

the

individual

concentrations

data

between

now

and fatty

from

allow

a-LA) acids

METABOLISM

dietary

the

period

of n-6

of

AND

a-LA

relationships.

321

Fatty

supplementation

acid

were

of the 20-carbon

and

The

mean

daily

reduced

by

>50%

resulting

in a range

groups,

diet

as did

there Thirty

healthy

male

volunteers

were

randomly

allocated

two dietary treatment groups. The experimental was instructed to maintain a high n-3 (a-LA) cold-pressed

flaxseed

flaxseed

oil

ratio

acids.

The

a high

suitable keeping

high n-3

and

a flaxseed-oil

and

by

control n-6

group

diet

(n

foods 15)

=

(reflective

group diet

to

in n-6

instructed

of Western

n-6 fatty acid cooking oils (a-LA) fatty acid consumption

15) using

diets)

to

intake

of

relative

groups

two

distinct

subjects

to a maximum dietary

periods

maintained

second

period

of two

their

both

in

meals this

groups

and spreads while as low as possi-

plasma

fractions

per week. In

their

There

the

were

first diets.

allocated

4 wk In

diet

the

and

in

mononuclear

different

However,

Plasma

and

was

cellularfatty

Peripheral

fasting

acid blood

reported

previously

(5).]

samples

there

(20 mL)

were

taken

before

ously

(5).

TABLE

1

and

was

The

rather

that than

were

2).

of the

significantly

es-

Similarly, in the

neutrophils,

(Figure

1 and

correlated

with

and in the phoscells, erythrocytes,

Dietary a-LA concentrations

in the phospholipids

of the neutro-

decrease

in the

plasma fractions consumption in

intakes in the

3 and Table

(Figure

concentrations

with frac-

mean

or in the as reported

the

plasma

3). con-

cellular previfractions

the trial began, after the 4 wk of the respective prescribed diets, and after fish-oil supplementation. The blood was separated into

plasma,

neutrophils,

mononuclear

cells,

erythrocytes,

and

platelets by using standard cell-separation techniques as described elsewhere (5). The plasma and cellular lipid fractions were separated by thin-layer chromatography and then analyzed

by

using

elsewhere

capillary

gas

chromatography

Anthropometric nutrients

Age

(y)

BMI

(kg/m2)

Energy

analyses

and estimated and control

Flaxseed

as described

(1 1, 12).

Dietary

measurements

in the flaxseed-oil

intake

(MJ/d)

oil

daily

dietary

intakes

of

groups’ (n =

Control

15)

(n =

15)

36.1

± 6.2

(25-44)

34.5

± 5.2

(25-44)

25.6

± 3.3

(20.7-35.1)

25.1

± 4.4

(16.4-35.9)

±

(6.3-12.7)

9.2 ± 2.1

(6.0-13.7)

9.6

1.8

Protein

All

subjects

were

records

for

3 d/wk

using

standard

instructed

by a dietitian

throughout

metric

the trial

household

days comprised two weekdays diet diaries were analyzed for the

1 program

Diet

(Xyris

to maintain

by weighing

measurements. and 1 d from LA and a-LA

Software

Pty

dietary foods

The

and

recorded

the weekend. The intakes by using Ltd,

Highgate

Hill,

Queensland, Australia), which uses the Australian nutrient database Nuttab 91-92 (13). The database was modified to include LA and a-LA contents of food items ingested during the trial. Because tween

the

plasma and

we and

were

dietary tissue

docosahexaenoic

interested

only

18-carbon

fatty

concentrations acid

(DHA),

in the acids of the

(LA LA,

relationships and a-LA,

estimated

be-

a-LA) AA,

and EPA,

individual

dietary intakes of LA and a-LA, and the fatty acid tissue concentrations from these individuals in both groups during the first 4 wk of the trial were combined and used to assess

(g/d) (% of energy)

105

±

19.4

(67-144)

18.9 ± 3.4

(14-25)

19.0

±

2.2

(15-24)

72.9

± 24.8

(42-128)

73.7

± 20.4(53-123)

29.6

± 5.3

(18-38)

29.1

± 6.3

(23-44)

269

± 72.9

(136-395)

286

± 73.5

(173-445)

47.2

± 6.3

(37-57)

47.9

± 6.2

(36-58)

98.7

±

17.2

(68-127)

Fat

(g/d) (% of energy) Carbohydrate

(g/d) (% of energy) Alcohol

(g/d) (% of energy) a-Linolenic

I

± 16.7 (0-62) ± 5.4

(0-20)

± 6.3

12.6 3.9

± 14.3 (0-40) ± 4.6

(0-14)

13.0

(3.6-22.0)

1.1 ± 0.6

(0.3-2.5)

5.3 ± 1.7

(2.3-7.1)

0.4 ± 0.2

(0.1-1.0)

8.2 ± 3.4

(2.9-15.6)

3.3

(1.8-4.6)

acid

(g/d) (% of energy) ,

4.1

acid

(g/d) (% of energy) Linoleic

13.0

±

SD;

range

±

0.8

in parentheses.

a

mononuclear

platelets

and platelets

in the a-LA

AA

indicating

concentrations

and

no significant

DI-LA after

fat,

Table

a-LA

phospholipids

(g/d)

cells,

to

and cholesterol

1 and with

erythrocytes,

phospholipids mononuclear

1), 2.9

of these the two

fats,

of the neutrophils,

in the

intakes

centration of phospholipids

composition

of

and platelets (Figure 2 and Table 3). were inversely correlated with DHA phils,

from

The total intake similar between dietary

was

(Table

groups

EPA concentrations in the plasma fractions pholipids of the neutrophils, mononuclear

plasma

backgrounds

two

type

(Figure

cells,

group

group

triglycerides,

correlated and

Table 3). Dietary a-LA

addition consumed nine fish-oil capsules. [The effect of uniform fish-oil intake in the second period against the two dietary

erythrocytes (g/d)

flaxseed

in the diet.

phospholipids,

a-LA

prescribed

continued

(plasma

and in the phospholipids

dietary

trial.

respective

fish-oil

(g/d) were significantly correlated of total fatty acids) in the plasma

ters)

and

in the

the

fat intake

tions cells,

the control

of total of

Dietary LA intakes concentrations (%

LA

in

the

g a-LAId. remained

intake

exchange

in total

LA to

of intakes

the

an

by using

ble. Both dietary groups were given guidelines to avoid monounsaturated and saturated fats. Fish meals were limited in both

was

difference

=

(butter rich

was

into

(n by

spread

avoiding

after (5).

20.5

± 8.6

7.8 ± 2.3

(9.9-41.4) (4.1-12.8)

Downloaded from www.ajcn.org by guest on July 15, 2011

maintain

oil

of 2:1)

observed

previously

Results

41.4 g LA/d and 0.3 to 22.0 two fatty acids (LA + a-LA)

Subjects

changes

published

18-carbon

and tissue concentrations and of their respective

Methods

fatty

LA

of the rela-

or n-3

and EPA).

(AA

OF the

intakes

initial

an examination

amounts

dietary

acids (LA 18-carbon

same

analyzed

IN

at

322

MANTZIORIS

r= .

Ea

I

20

Correlations

in tissue

1.5

i.o

I

of total

fatty

Tissue

fraction

and n

Plasma

phospholipids

a-Linolenic

I

0

10

20

D_

30

40

5

l’s

.5 ___________________________ ;5 10

.0.5

LA (gld)

DIta,y

a-LA

1.0 14

I

I

12

2;

5

(gld)

r=0.85

0.8

r_0.58>

I

I

a-linolenic

fatty

acid

acid

fatty

acids

Correlation

coefficients

0.4

II

02

I

0

10

20

Docosahexaenoic

acid

cholesteryl

50

.5

0

5

panels.

10

of dietary

linoleic

and neutrophil of total

fatty

r, correlation

acids.

Note

(PL) content