Effects of diets rich in monounsaturated

fatty acids on
plasma lipoproteins-the
Jerusalem Nutrition Study:
high MUFAs vs high PUFAs13
Elliot
Nathan

M Berry,
Shlomo
Eisenberg,
A Kaufmann,
and Yechezkiel
Twenty-six

ABSTRACT
assigned

acid

to a 24-wk

(MUFA)

12-wk

Yeshiva

crossover

32%

periods.

fat,

Total

were

fatty

fatty

acid (PUFA)

fed alternately

cholesterol

(TC)

diets

(50%

during

two

decreased

cholesterol

(LDL-C)

decreased

groups

an additional
significant
effect between
periods.
Concentrations
of high-density-lipoprotein
cholesterol
did not change
significantly.
LDL-receptor
status in fresh monocytes,
affinity
ofLDL
towards
the LDL receptor
in cultured
fibroblasts,
zonalprofiles,

significantly
higher

different

tendency

and

lipoprotein

between

toward

composition

the diets.

lipid

There

were

on

the

by more thiobarbituric
acid-reactive-substances
on that diet. Dietary
PUFA
results in somewhat
lower
LDL-C
concentrations
whereas
with MUFA
the sus-

TC and

ceptibility
of LDL to oxidative
Nutr 1991;53:899-907.

KEY WORDS
fatty

acids,

Dietary

unsaturated

stress

is lower.

Am

ischemic

fats,

fatty

lipids
constituent
of other

fatty

acids,

acids,

it still remains

major

obstacles

free-living

lipoproteins,

adherence.

environment
associated

the Har-Etzion
campus
where
during

type

lipid

peroxi-

effects

of high

MUFAs

over
We

after nearly

with

40 y of

been

able

studies.

One

of natural

period

on lipoprotein
and

low

fatty

acids

Subjects

and

methods

ofteaching

they

ate diets

l991;53:899-907.

and

and

polyunsaturated

and
and

PUFAs,

cholesterol

and
is

by changes

in the

which
function

fatty

high

of MUFAs
quantity
adherence

acids

keeping

was to
of a diet
(PUFAs)

total

fat,

constant.

to establish

at least
Through

an

in part,
the

ofdiffering

fatty

Printed

in USA.

food
was,

study
and

them

to attend

from

the outside

therefore,

an ideal

with

free-living
ofthe

is very limited.
setting

from

is served
to buy

The ye-

for performing

subjects.

of the academic

the purpose

the college

evening.
All food
and the opportunity

study,

year,
details

all students
ofits

were

as-

performance,

in
I From
the Lipid Research
Laboratory,
Department
of Medicine
B,
Hadassah
University
Hospital,
and the Departments
ofSocial
Medicine
and Nutrition,
School
of Public Health and Community
Medicine,
Hebrew University-Hadassah
Medical School, Jerusalem.
2 Supported
by grant HL-39302
from the National Institutes of Health.
3 Address
reprint requests to NA Kaufmann,
Department
of Nutrition,
Hebrew
University-Hadassah
Medical
School,
POB
1 172, Jerusalem
91010, Israel.
Received
December
13, 1989.
Accepted
for publication
May 30, 1990.

experi-

the prob-

cooperation

acid

situation

requires

to late in the
ofthe
yeshiva

ensuring

of

on the
diet pecontent.

Each student
acted as his own control
in this crossover
study.
Oleic acid has been considered
neutral with regard to its effect
on blood lipid concentrations
( 1 , 2). However,
recent
work sugAm J C/in Nutr

Nutrition

of monounsaturated

or low amounts

structure

(SFAs),

that

At the beginning
sembled

of the

foods

while

Yeshiva,
we set up a metabolic
kitchen
male students
participated
in two l2-wk
which

Jerusalem

while keeping
the
constant.
Dietary
analysis

a diet of low MUFAs

metabolic

investigation

in its proof.
time

overcomes,

such

high

of the diet
constituents

saturated

shiva

fat is preferable.

of the effect
a long

have

that

dietary
be related

on lipoprotein
structure
and function
over
protocols
are planned
to determine
the effects

of substituting

or eat additional

alter plasma
lipid
research
and dis-

ofdietary

inherent

is the studying

mental

riods

difficulties

populations

dietary
lems

which

a hypothesis

to the

may

The study was performed

on healthy
normal
male students
ofthe Yeshiva (Talmudic
College) Har Etzion outside
Jerusalem.
A yeshiva is a college in which students
study mainly the Talmud
(a basic compilation
of Jewish law and tradition)
in a unique

monounsaturated

The hypothesis
that diet can predictably
concentrations
continues
to generate
much

is testimony

The

the effects

by food-composition

compare

system

That

between

(3), which

(4).

in detail

early in the morning

by the central
kitchen

about

effect

to investigate

for one
quality

association

disease

Subjects

Introduction

particularly

inverse

heart

J C/in

dation

cussion

be an

hypolipidemic

plans

on blood

with

diet,

as ascertained
formation

may

and

fatty acid content

of erythrocyte
membranes.
We wish to report the first years experiment,

not

PUFA

there

acid

monitored

was a significantly

peroxidation

that

oleic

fatty acids (MUFAs)

a 4-y period.
Yearly

with

centrifugation

Norman,

gests

Study

diets,
Low-

in both

Yehudit

to a possible

signif-

10% and
16% on the MUFA
and PUFA
Plasma
triglyceride
response
was variable.

density-lipoprotein

Friedlander,

randomly

of monounsaturated

18% protein)
plasma

Yechiel

1991 American

Society

for Clinical

Nutrition

899

Downloaded from ajcn.nutrition.org by guest on March 25, 2015

icantly by
respectively.

students

study

vs polyunsaturated

carbohydrate,

Dror Haratz,
Stein

BERRY

900

and requirements
by the

on the part ofthe

investigators

and

participants

the directors

ofthe

were explained
yeshiva.

Thirty

for the study. Each of the volunteers

undermedical
examination
and routine
biochemical
lipids were examined
twice after an overnight
interval
and served as the baseline
values for

randomization.

Subjects

high

such
blood

with

as diabetes
lipid

were excluded.
of the dietary

endocrine

mellitus,

concentrations,

or any

Twenty-six
subjects
study and completed

22 participants

remained

or

metabolic

hypothyroidism,

distur-

obesity,

other

chronic

or

disease

were included
as participants
the first dietary period, and

in the study

until

the end

ofthe

second

period.

was undertaken

of Health

Protection
consent

and

the

of Human

after

approval

Hadassah
Subjects,

Medical
and

from

the Israel

Center

Board

all subjects

gave

Mm-

items

prepared

Before

each

diet,

the

volunteers

were

stratified

by blood

trays

and

period

(period

1) followed

prepared

subjects
period

MUFA
period

by 4 wk of the

or delivered

were

given

by us). After

diets

in reverse

regular

this

order

yeshiva

wash-out

for

a second

1 2-wk

(period 2). One-halfofthe

students
(group 1) began with
diet during period
1 and were given PUFA diet during
2. This

order

was

reversed

in the other

halfofthe

of Official

Analytical

day.

Thus,

diet

the same

meat

the MUFA

fat was

whereas

added

diet

vegetables

diets.

of olive

However,

oil,

avocado,

was supplemented

of saffioweroil,

12 daily

PUFA

in form

the PUFA

amounts

or the same

and

soy

oil,

and

with

walnuts.

For

of similar composition
but of varied
items
were prepared
and used in rotation.
After the food was
cooked,
portions
were weighed
and put on individual
trays for
each participant.
Subjects
were asked to eat all food on their

menus

to report

was consumed.

all leftovers.

To allow

choice,

several

subjects

could

Usually

all the

the participants

equivalent

items

offered.
kinds

between

various

kinds

of dairy

products

food

a certain

were

choose

cr5 or various

distributed

degree

Thus,
ofbread

of equal

of free

for breakfast
and

crack-

fat and

caloric

content.
Snacks of composition
equal to the daily menu were
prepared
and subjects
could eat them ad libitum
provided
that
the total portion
was eaten and the number
ofsnacks
consumed
was reported.
In this way the participants
could adjust their total
food intake
to their caloric
needs without
changing
the composition

of the diet.

All planning

diet

period,

Association

and

calculations

and the food was prepared

in a special kitchen.
Isolation

and

labeling

Very-low-density

students

were

and

done

by a qualified

cooked

under

(VLDL)

and

dietitian

her supervision

of lipoproteins
lipoprotein

low-density

lipo-

(group 2). During both experimental

periods participants
spent
their time in the yeshiva and, therefore,
received
all their meals
and food from our staff. Every second or third weekend
(half of
Friday and Saturday)
the students
visited their families. On these

protein
(LDL) were isolated,
by ultracentrifugation,
and 1.019-1 .063 kg/L, respectively,
from human

Zonal ultracentrifugation
of lipoproteins
was performed
according
to the techniques
of Patsch et al (7) as modified
by Eisenberg
et al (8). Intermediate-density
lipoprotein
(IDL) and
LDL were separated
from 20 mL plasma by zonal centrifugation.
The amounts
of LDL protein (4-10 mg) were sufficient
for further characterization
whereas
with IDL it was sometimes
nec-

occasions

they

were

given

strict

at their

homes,

and

they

were

providing

most

of the

or walnuts,
which
blood
for plasma
At the end ofeach
studies

specific

instructions

about

what

required

to consume

fats,

as olive

such

to eat

the items
oil,

almonds,

were provided
in take-away
packages.
Fasting
lipid determination
was drawn
periodically.
period, blood was also taken for more detailed

of lipoprotein

structure

and

functions.

aminations
were performed
in 1 2 subjects
lected at random
from all the participants.
every 2 wk throughout
the study.

from

Subjects

equal
d-96
hydrate

acids,

cholesterol,

protein,

and

There

was

300

mg

latter

cx-

essary

se-

on the same

were weighed

carbohydrates,

cholesterol

tubes,

group

were

in both diets. Each diet was planned

to provide 2800 kcal/
g fat (33.5%),
100 g protein
( 15.5%), and 325 g carbo(5 1%).

1 g Na2EDTA/L.
plastic

each

The MUFA diet was rich in MUFAs

whereas
the PUFA diet
was rich in PUFAs.
All other components,
ie, total fat and satfatty

into

These

Diet

urated

taming

in each

into

kept

LDL
under

preparations

and

HDL3

from

nitrogen

from

diet. High-density

HDL2

was sterile

two

lipoprotein
lO-mL

plasma

filtrated,

portioned

at 4 #{176}C.

or even

three

(HDL)

subjects

was separated

samples.

LDL

from

normolipemic
subjects
not participating
in the study was pmpared by ultracentrifugation
as described
above. After dialysis
and concentration,
a sample
of this normal
LDL was radioiodinated
to a specific activity of 3.4-10.2
&iJg
protein
by using
the iodine
labeling

monochloride

Freshly

from

(9) as modified

for lipoprotein

l09/L)

and culture

prepared

30-40

procedures
x

method

(10).

Cell isolation

diet.

The diets consisted

ofnatural
and common
food items and were
prepared
and cooked
in customary
ways. About 50 food items
(the major ingredients
ofthe two diets) were analyzed
according

to combine

The

and

at d 1.006
plasma
con-

circulating

mononuclear

cells

were

isolated

mL blood collected
under sterile conditions
by the
of Boyum (1 1) and Bilheimer
et al (12). The cells (6
were suspended
in RPMI
1640 (Gibco,
Paisley, Scot-

Downloaded from ajcn.nutrition.org by guest on March 25, 2015

cholesterol
concentrations
and divided
randomly
into two
groups. After randomization,
subjects were given all food (main
meals and snacks) by the study staff. No other food was allowed.
During the first 4 wk the participants
were given the regular food
ofthe yeshiva including
in-between
meals and snacks. On several
occasions
they were asked to record their 24-h food intake, which
enabled
us to calculate
the individual
energy requirements
of
each participant
and plan his personal
diet accordingly.
At the end ofthis run-in period, the dietary experiment
started.
Two diets, MUFA
or PUFA,
were administered
for a 12-wk

of the

for both

almonds

written

design
the experiment

and

each

MUFA

equivalent

to participate.

Experimental

(not

food

were

for the

their

methods

Chemists
(AOAC)
(5). Duplicate
samples
of the different
diets
were collected
at random
on three occasions
during each period,
the samples
were blended,
and a 5% portion
of each diet was
kept frozen. At the end of each period these subsamples
were
combined
and analyzed.
Fatty acid composition
was determined
by gas-liquid
chromatography
(GLC). The composition
of the
minor
food items was derived
from standard
food tables (6). On
the basis of these data, special food tables for the study were
compiled.
The two experimental
diets contained
the same basic

in the

The study
istry

AL

to standard

stu-

dents volunteered
went a thorough
screening.
Blood
fast at a 3-10-d
bances,

ET

DIETARY
land,

UK)

and

medium

supplemented

5 g protein/L

ie, RPMI

1640-5%

lymphocytes

by

LPDS).

Monocytes

1-h adherence

volunteers

penicillin,

lipoprotein-deficient

Cell viability
was estimated
Human
skin fibroblasts
normal

with

human

and

by trypan-blue
were cultured

used

between

then

Petri

trypsinization,

described
(Biological
100 mL

LDL

3-5

the

5th

and

15th

previously
Industries,

and subcultured
Kibbutz,
Bet

of

passage.

fetal bovine

serum/L

receptor-specific

after

containing
20 mg/L of 251-LDL
in the RPMI
1640-5%
LPDS

LDL

with

by mono-

from a normal-lipidemic
medium.
Degradation

subject
products

tion

nonspecific

of control

Competitive

and

displacement

by experimental

values.

of251-labeled

control

The affinity
LDL receptor
lated cultured

of MUFAand PUFA-derived
LDL towards
the
was determined
by a competition
assay in upregufibroblasts
grown for 48 h in 5% LPDS. Ten mi-

crograms

milliliter

ofcontrol

25I-LDL

protein

was

internalization,

25ILDL
OC

were

by

and

following

proteolytic

proteolytic

determined

degradation

at the end

established

degradation

were

acid-reactive

Conditioning

was carried

simultaneously.

in 1 mL

ofLee

(16).

medium,

data

at 37
of the

out

by incubation

of 50 mg

(Gibco)
without
serum
cultures
of bovine aortic
control dishes were pro-

Thereafter,

(TBARS)

substances

cedure

The

substances

of LDL

LDL protein/L
in Ham F-10 medium
for 24 h in the presence
of confluent
SMC and/or
2.5 mol Cu2/L.
No-cell
cessed

(14).

control

to construct
competition
without
added unlabeled

used

curves in which values for incubations

LDL were taken as 100% activity.
Thiobarbituric

of the

of 3-h incubation

procedures

were
Briefly,
0.5

mL

thiobarbituric
acid-reactive
determined
(1 5) by the modified
pro-

to 1 mL
of 350

plasma

or 50 ig LDL

g tricarboxylic

plasma

or

were
and

procedure

Dieren,

The

Netherlands).

trations

were

determined

lipoproteins
was obtained
tion

collected

triglycerides

in a batch

after

a 12-h

were

determined

analyzer

(Vitalab,

HDL-cholesterol
after

precipitation

with phosphotungstic
by subtraction,

using

overnight

fast.

by an en-

Vital

Scientific,

(HDL-C)

concen-

ofapo

B-containing

acid. LDL-C
(including
IDL)
the Friedewald
et al equa-

(18).

To determine

the composition

procedures

cholesterol,

and

cholesteryl

esters

were

of VLDL,

used

to measure

phospholipids.

LDL,

Unesterified

were

Erythrocytes

separated

from

HDL3,

triglycerides,
cholesterol

were determined
by specific
kit (Boehringer-Mannheim,

with a commercial

and

protein,

and

enzymatic
Mannheim,

methods
FRG).

EDTA-containing

blood

samples
Total
washed

and hemolyzed
by the method
of Dodge
et al (19,
lipids
were
extracted
with
chloroform-methanol
to remove
proteins.
Fatty
acid methyl
esters were

pared

by

transesterification

with

methanolic

nium
hydroxide
(Meth
Prep II, Applied
(2 1). During
the separation
procedures,

(BHT;

5 g/l00

methyl

esters

L) was

Tracor

565 GLC

were

used

column

trimethylammo-

Science,
Deerfield,
2,6-ditert-butyl-9-cresol

as an antioxidant.

separated

and

(1.85

20).
and
pre-

The

quantified

by

m X 4 mm

IL)

fatty

GLC

acid

using

id, 10% SP-2330

on

acid

dards.
Statistical analysis

included

in the incubation
medium
without
or with different
concentrations (5, 10, 20, and 40 mg/L) of unlabeled
LDL preparations,
derived
from subjects
consuming
MUFA or PUFA diets. Binding,

MDA/L

100/ 120 chromosorb

in WAW
1- 185 1 ; Supelco,
Bellefonte,
PA).
Temperature
programming
was used from 185-220
#{176}C.
Peaks
were identified
by comparing
retention
times with known
stan-

LDL

LDL

per

(imol

Statistical
analysis
included
t tests
for the comparison
of
changes in lipid concentrations
in response
to dietary treatment
and time period for this basic two-period,
crossover
design according
to Fleiss (22). For subjects commencing
with the MUFA
diet

in period

measures
2. This value
DMP

1 and

changing

to the

PUFA

diet

in the

the change
in response
from period
includes
a measure
of the difference

period

2,

1 to period
between
the

two treatments
regardless
of the period, plus the time trend regardless
ofthe treatments.
Similarly,
DPM
represents
the change
in response
for subjects
in group 2 who followed
the same procedure
in the reverse
order.
The hypothesis
of equal efficacy
of
the two diets was tested
by means
ofa t test comparing
the two
averages,

DMP

standard

error

The

possible

and

DPM

was

used

interaction

(22).

The

to test

sum
the

between

of

plus

existence

the dietary

was also tested by means ofa

as mean SD or mean SEM.
riod

t test

DM

and

of a period
treatments

(22).

Values

its

effect.
and

pe-

are expressed

protein
(TCA)/L

was added; the solution

was vortex mixed;
1 mL of 5 g TBA/L
was added, vortex mixed, and incubated
for 90 mm at 60 #{176}C
in
a shaking
waterbath.
After incubation,
1 mL of 700 g TCA/L
and 2 mL chloroform
were added
and the tubes were centrifuged
for 20 mm at 1 100 X g. A standard
curve was prepared
by using
malondialdehyde,
and the intensity
of fluorescence
was determined at excitation
of 5 1 5 nm and emission
of 553 nm as employed by Yagis method
(17). The results were expressed
as

Results
The baseline

characteristics

ofthe

students

entering

the study

are shown
in Table
1. During each 12-wk period some students
were unavailable
for blood
tests.
The experimental
crossover
design

required

analysis

were data at the beginning

data

sets were

available

of those

participants

and end ofeach

for 9 students

on

period.

in each

group

whom

there

Such complete
and

therefore

Downloaded from ajcn.nutrition.org by guest on March 25, 2015

culture
medium
as described
( 1 3). Nonspedetermined
in the presence of25-fold
excess
No-cell
control
dishes were processed
sicells were washed
in protein-free
medium
in 0.5 mol NaOH/L
for protein
determidegradation
was calculated
after substrac-

cific degradation

samples

cholesterol

zymatic

2 mL medium

in
was
of unlabeled
LDL.
multaneously.
The
and were dissolved
nation.
LDL-specific

were determined

Plasma

containing

monocytes

of 25I-labeled

8 h incubation

content

protein).

methods

standard

in fresh

degradation

was determined

medium

Israel)

(13).

degradation

Receptor-specific
cytes

in Dulbecco-Vogt

LDL

All blood

seeded

Haemeq,

equivalent

MDA/g

Analytical

in 35-mm dishes
with 2 mL medium
containing
100 mL fetal calfserum/L.
Cells
were fed three times weekly with the same medium.
Bovine
aortic smooth
muscle
cells (SMC) were prepared
as
After

901

PUFA

from
dishes.

exclusion.
from skin biopsies

X 10 cells were

zmol

(LPDS;

separated

(35-mm)

VS

malondialdehyde

streptomycin,

serum

were

to plastic

MUFA

BERRY

902
TABLE

Baseline

characteristics

of participants

ET AL
TABLE 2
Composition

in study

dietary
Group
1
(n=l2)
Body mass index (kg/rn2)
Number
of smokers
Number of subjects born in Israel
Plasma cholesterol
(mmol/L)
Plasma triglycerides
(mmol/L)
Plasma HDL cholesterol
(mmol/L)

23.3

Group 2
(n=l2)

2.4

21.6

3.8 1
1.02
1.09

0.77
0.22
0.25

3.8 1
0.92
1. 1 1

and house

vs from

Diet

SFAs

Period
0.78
0.27
0.17

diets during

the two

analysis5

MUFAs

PUFAs

Fat

Protein

CHO

35.1
31.4

15.2
19.2

49.7
49.4

% of kca/

SD.

planned

2.2

of the experimental

periods:

MUFA
Planned
From analysis

PUFA
Planned
From
Period 2

analysis

8.5
8.1

17.7
14.9

6.3
6.7

8.1

7.1

17.6

35.2

14.7

50.1

7.2

5.9

14.7

29.6

19.4

51.0

8.9

16.5

6.3

33.8

16.7

49.5

7.8

16.9

8.3

34.9

18.4

46.7

MUFA

carbohydrate

being

nearly

identical.

During

period

1 the amounts

ofboth
MUFAs and PUFAs as percent total calories were slightly
less than planned;
during period 2 the discrepancy
disappeared.
The house diet of the Yeshiva
is shown for comparison.
Adherence
to the diet was monitored
by comparing
changes
in
erythrocyte

membrane

fatty

acid

composition,

in particular

the

ratio between
18: 1 (oleic acid) and 18:2 (linoleic
acid). In both
periods on the MUFA
diet, the ratio increased
(more in period
2), and
3).

on the PUFA

During

period

diet

the ratio

1 the

average

from both groups was

< 1.0 kg.
The changes
in total

<

determinations

the

0.5

decreased
weight

kg; during

change
period

of the

was

plasma

beginning

ofthe

experiment

(3-10

apart; baseline)
and two determinations
at the end (weeks
10
and 12). After period
1 for both diets there was a significant
decrease
(1 1%) in total cholesterol;
after period 2 this decrease
was more prominent
on the PUFA diet (20%) and less so on
the MUFA diet (8.5%), but both were significant
when compared
with the baseline
values. The data of the crossover
study were
analyzed

to distinguish

between

effects

on plasma

lipids

due

greater

and

a decrease

of 31%

was

observed,

17.1

33.8

16.8

49.5

6.4

17.2

32.3

16.3

51.4

House,

from analysis

10.5

1 1.5

15.8

40.6

15.7

43.7

S SFAs, saturated
fatty acids; MUFAs,
monounsaturated
PUFAs, polyunsaturated
fatty acids; CHO, carbohydrate.

fatty acids;

ducing
a significant
seasonality
effect (P < 0.01). The overall
effect of PUFAs
on LDL-C
concentrations
was significantly
greater
than that of MUFAs
(P < 0.05).
There were no significant
differences
in lipoprotein
compoanalysis

during

either

period

ofthe

diet

study

or between

(Table 6). The profiles of IDL plus LDL and of

HDL on zonal ultracentrifugation
were also similar (Fig 1).
25I-labeled
LDL degradation
in fresh monocytes
ranged between
80 and 180
LDL protein
g cell protein
h and was
not changed
by the different
diets. Mean values were similar on
the MUFA
and PUFA diets (137 31 and 133 32 g LDL
protein#{149}gcell protein.
8 h, I SD; n
11; n
8 studied
twice on each diet). Competition
studies in cultured
human
skin
fibroblasts
between
normal
LDL and LDL obtained
from subjects on either of the diets produced
identical
curves (Fig 2,

Table 7). There

was,

therefore,

no evidence

for any

change

in

lipoprotein
structure
or function
in response
to the different
diets.
The effect of dietary
MUFAs
and PUFAs
on the tendency
toward
oxidative
stress was assessed
by TBARS
production
in

to

the diet intervention

and those that relate to the timing (seasonality) ofthe experimental
period. Our results for cholesterol
indicated that the overall effect ofthe PUFA diet was significantly
greater than that of the MUFA
diet (P < 0.02). There
was no
seasonality
effect. Plasma triglyceride
concentrations
decreased
significantly
on both diets in period 1, but after period 2 a slight
increase
was observed
after the PUFA diet. Statistical
analysis
showed a significant
effect for the period (seasonality;
P < 0.01)
but not for the diet manipulation.
There were no significant
changes in plasma HDL-C concentrations
as a result of the two
diets or the different
time periods.
LDL-C concentrations
decreased
significantly
on both diets and over both time periods
of study. The reduction
after period 2 on the PUFA diet was
significantly

6.4

7.0

cholesterol,
triglycerides,
HDLC, and LDL-C at the beginning
and end ofthe two study periods
are shown in Table 4. Statistical
analysis
of the overall effects
of diet and season
on plasma
lipids is shown in Table 5. The
plasma lipid values reported
represent
the mean oftwo separate
before

8.4

analysis

From

the two diets

students

2 the change

From analysis
PUFA
Planned

sition

(Table

significantly

Planned

pro-

TABLE

Ratio

of oleic acid to linoleic

MUFA and PUFA diets
Diet
Period

Baseline

Paired

ti

from

End of study

period

subjects

on

P5

MUFA
PUFA
Period 2
MUFA
PUFA
S

acid in erythrocytes

0.023t
0.027

1.069
0.801

0.955 0.029
0.981 0.031

1.066
0.885

1.040

0.980

test.

SEM.

0.027
0.026

0.072
<0.001

0.035
0.019

0.033
0.023

Downloaded from ajcn.nutrition.org by guest on March 25, 2015

plasma lipid concentrations

relate to these 18 students.
Special
studies were performed
on subgroups
of participants
at the end
of each diet period.
The composition
of the planned
experimental
diets is shown
in Table 2. Both diets comprised
2800 kcal with -34% of the
calories
from fat. About
17% of the total calories
came from
either MUFAs
or PUFAs,
the quantities
of SFAs, protein
and

DIETARY
TABLE

MUFA

VS

903

PUFA

4
lipid concentrations

Plasma

by study

period

and diet5
Period

Lipid

Period

End of period

Baselinet

End of period

Baseline

mmol/L
Total

2
P

mmo//L

cholesterol

MUFA
PUFA

3.83
3.89

MUFA
PUFA
HDL-C
MUFA

2.30
2.30

1.06

PUFA
Triglycerides

1.10

1.03
0.92

0.31
0.32

3.42 0.24
3.44 0.27

0.008
0.003

3.96 0.32
4.04 0.32

3.62
3.22

0.26
0.25

0.037
<0.00 1

0.28
0.30

1.98
2.05

0.22
0.26

0.015
0.025

2.51
2.58

0.32
0.30

2.18 0.23
1.78 0.22

0.042
<0.00 1

0.07
0.07

1.06
1.08

0.05
0.06

0.898
0.713

1.09
1.09

0.07
0.09

1.08
1.02

0.08
0.1 1

0.85
0.69

0.09
0.08

0.014
0.007

0.79
0.82

0.07
0.10

0.79
0.90

1 .68

LDL-CII

MUFA
PUFA

Paired Students I test.

II Calculated
by using the Friedewald-Levy

native

and

conditioned

8). There

after

was

incubation

subjects

LDL

a significant

with

on the

under

SMC

PUFA

diet

various

conditions

or copper
compared

(Table

in native

ions
with

LDL

alone

Chol

(mg/dL)

from

subjects

diet. Because
a priori the tendency
toward
oxidative
stress was thought
to be greater
for PUFA than for MUFA,
a
one-tail
significance
test was used. TBARS
production
was
greater
also in whole plasma samples from subjects on the PUFA
diet than from those on the MUFA
diet (0. 174 0.008
vs 0.164
0.007 imol/L,
respectively).

nutritional

SFA,

MUFA,

and PUFA

intakes

of fatty

testing

ofthe

acids

to the regression

study

is part

of an

ongoing

experiment

to

Chol
any

tion

but

dietary

taneously
applicable

2.74

SFA

from

cholesterol

ofcholesterol
diet,

nipulation

to

Previously,

suggested

a beneficial

12 wk,

and

MUFAs

on plasma

used

were

effect

entirely

of a Mediterranean-

on the pioneer

y ago

In this

MUFAs.

ofcalories
investigated,

initiated

(1)

dietary

in the percent
calories.

Further

ofseveral

variables

revised

equation:

- I .3 1 X PUFA
Hegsted

(2)

et al (2) studied

from

in fat content

fat for 2-9

wk (usually

three
for the

men

differing

of which

sets of comparisons
equation

by Ancel

were
change

were

analyzed

in plasma

by Keys (29).
It is ofinterest
to compare
predicted

TABLE

et al 30

were

studied

as was

also

done

simul-

from
fatty

the results

ofour

2. Both

diets

equation

but varied
acid

experiments
contained

with
similar

in fatty acid composition.

composition

as percent

oftotal

On
calories

Statistical

analysis

of overall

effects

Diet: MUFA
vs PUFA

thesis

Keys

added,

These
equations
were found
to be
population
in the 1960s as shown

recently

in their

(1, 2). This

12-27

was

items.

to be neutral

experiment,

of two to six diets

food

concentrations

work

classic

natural

considered

cholesterol

was based

following

the change

contribution

by Keys et al (28).
to the Israeli
male

the house

Forty-one

X LPUFA

led to the following

contribution

amounts

data

diet (rich in olive oil) on heart disease but could not prove
a causal relationship
(3). Several studies have recently
investigated the effects ofMUFAs
on plasma lipid concentrations.
They
employed
either liquid formula
(24) or solid food (25-27)
for
periods
of 6 wk. We have extended
the time of dietary
ma-

were

0.902
0.193

-1.35

oftotal

ofthe

(mg/dL)

miologic
type

of9-44%

represented

analysis

those

diets

0.1 1
0.09

X LSFA

X LMUFA

as percent

significance

the effects ofMUFAs

on plasma lipid concentrations
and lipoprotein
structure
and function.
The nutritional
consequences
ofoleic acid have aroused considerable
interest recently
because
of findings
that suggest that oleic acid-rich
oils may
lower LDL without
lowering
HDL (4, 23-25).
Further,
epidedetermine

on each

0.808
0.203

the response
ofplasma
cholesterol
to diet and arrived at a similar
equation.
They also did not include dietary MUFAs
in the equa-

Discussion

(1).

+ 2.76

+ 0.05

without

influence

0.05
0.07

on the

MUFA

This

(18).

in TBARS

alone
when

10 and 12.
equation

increase

Lipid

of diet

and

season

Season:
period 1 vs
period 2
1

Interaction:
diet vs period
t

over a range
4 wk).

rich

and

Sixteen

in MUFAs.

yielded

cholesterol:

the

Total

cholesterol

2.9 1

<0.02

1.68

NS

1.58

NS

LDL-C

2.26

<0.05

2.98

<0.01

2.13

<0.025

HDL-C

1.08
0.22

NS
NS

1.19
3.69

NS
<0.01

0.32
1 . 13

NS
NS

Triglycerides

Downloaded from ajcn.nutrition.org by guest on March 25, 2015

51SEM.
t Mean of two blood samples, 3-10 d apart.
t Mean ofblood samples at the end ofweeks

904

BERRY

TABLE

ET AL

Composition

oflipoproteins

at the

end

Diet and period

of the

dietary

periods5

Protein

FC

TGs

CE

PLs

VLDL
MUFA,
MUFA,
PUFA,
PUFA,
LDL
MUFA,
MUFA,
PUFA,
PUFA,
HDL3
MUFA,
MUFA,
PUFA,
PUFA,

6)
7)
5)
4)

12.0
13.2
12.0
13.2

0.6
1.7
0.7
1.4

5 1.2
40.3
54.8
48.4

21.8 2.1
24.6 1.5
22.7 2.8

4.6
4.5
5.1

6)
7)
5)

4)

24.0

4.0

4)
4)
4)
4)

51.0 1.9
54.1 2.7
55.7 1.5
54.8 1.1

=
=

1 (n

(n

1 (n
2 (n
1 (n
2 (n

=
=

1 (n
2 (n

=
=

1 (n

2 (n

SD. TG, triglycerides;

lipoprotein

L, observed

in periods

MUFA-rich

diet

dicted

the

in MUFA,
change

3.2
3.4
3.0
3.0

1.0
1.1
0.8
1.0

3.7 2.0
3.0 0.3
4.4 1.8
3.1 0.7

1.6

FC, free cholesterol;

CE, cholesteryl

0.2
0.4
0.3
0.2

0.9
1.1
0.9
1.7

26.9 3.0
26.6 3.7
24.5 1.9
27.7 4.5

8.9 0.5
8.3 0.9
9.4 1.0
8.3 0.5

37.4 2.3
36.2 3.7
38.5 2.2
38.1 1.6

26.4 0.8
26.3 3.0
24.4 1.4
25.6 2.1

1.7 0.2
1.4 0.1
1.5 0.2
1.5 0.2

14.8 1.2
15.4 1.6
14.5 2.6
14.5 1.1

28.8 1.4
26.1 1.1
23.9 2.0
26.2 1.7

esters; PLs, phospholipids.

SFAs:MUFAs:PUFAs.
The PUFA-rich
by average
changes
of -3.4%
in SFA,
+0.2% in PUFA. The predicted
change
using Keys equation
2 would be -0.25
compared
with -0.45 and -0.83 mmol/
I and

2, respectively

relevant

and

changes

-8.3%

in cholesterol

of0.10
mmol/L
mmol/L,
which

2.4
3.4
2.2
5.3

6.8
7.5
5.8
7.8

Values

are percent

contribution

ofindividual

components

mass.

was 10.5: 1 1 .5: 1 5.8 for

diet was accompanied
-5.4%
in MUFA,
and
in plasma
cholesterol
mmol/L
(-9.6 mg/dL)

+4.4%

(Table

are

in PUFA.
would

4). For

in -2.6%

Accordingly,

be an increase

the

question

that

workers

is why

equations

the

United States. Such

the measurement
of
of the most reliable
ofa population
(30,

pre-

-0.34
The

IDL.+ LDL

arises

were

devised

of these

is such

results

and

a discrepancy

results

between

the

was

from

tissue

risen

to 16% in the United

Israel

(34).

The

10%

<

in the

comparable
1950s,

over

body

in

the

years

a manner

on

subjects

living

in the

l950s

changes
affect

(32).

By

1980

it had

(33) and to close to 25% in

for oleic acid in adipose tissue

in 1980(US),

may

that

late

States
figures

46%

It may well be that these

tion

studies

a change was indeed demonstrated

through
adipose-tissue
fatty acid composition,
one
methods
of following
the dietary fat intake
3 1). The percentage
oflinoleic
acid in adi-

pose

are 52% in the

in light

there

observed
and predicted
changes
in cholesterol
concentrations
after changing
dietary
MUFAs.
There is no clear answer,
but a
possible
explanation
may be found in the changes
in dietary
habits that have occurred
over the past 30 y since the original

in SFA,

in cholesterol

(3.7 mg/dL)
compared
with -0.41
and
was found in periods
I and 2, respectively.

obvious
by other

and

in dietary
cholesterol

41%

in I 986 (Israel).

fatty acid consumphomeostasis

has yet to be clearly

defined.

in the

In other

TABLE

7
Competition
of 251-labeled LDL degradation
in cultured
fibroblasts
by LDL isolated from subjects on the MUFA
diets at the end ofthe dietary period5

c%J
4-

Concentration
Diet

5 mg/L

of unlabeled
10 mg/L

human
and PUFA

LDL protein

20 mg/L

40 mg/L

100
Zonal

FIG

1. Zonal

in plasma
(-

- -)

300

Rotor Effluent

ultracentrifugation

HDL (bottom)
of the MUFA

200

obtained

and PUFA

(-)

400

500

(ml)

profile of IDL plus LDL (top) and

from a subject at the end of 12 wk
diets.

Control

(n

MUFA
PUFA

(n
(n

=
=
=

5)
12)
13)

67
66
66

I l.1
10.5
8.6

S1
51
51

10.8
9.0
8.4

42
39
37

9.1
8.6
8.5

26
22
25

8.1
5.7
8.1

S
SD. Results are expressed as percent ofdegradation
in the presence oflabeled
LDL only. Eleven subjects were studied twice at the end
of each diet period. One subject was studied only on the MFA and two
were studied only on the PFA diet.

Downloaded from ajcn.nutrition.org by guest on March 25, 2015

to total

1 (n
2 (n

DIETARY

MUFA

905

VS PUFA

-I

I
400510
Unlabeled

LDL

(pg/mI)

FIG 2. Competition
of 25I-Iabeled
LDL metabolism
in cultured
control subjects (healthy
normal humans)
and with LDL obtained
The 25I-labeled
LDL was prepared
from control subjects.

words,

it may be necessary
for the nutritional

ofthe

major

PUFAs

study

ofthis

ofthe

and redefine
population

shows

or MUFAs

cholesterol

MUFA

l990s.

One

investigations

with

on the biological

similar

amounts

of either

a significant
decrease
of plasma
16% and 10% on the PUFA and
during
the two periods)
without

(-

of HDL-C.

of Mensink

study

diets

respectively,

levels

to those

that

produced

concentrations

diets,

changing

ongoing

the Keys equain the

effects
ofMUFAs
is to collect data sufficient
for addressing
this problem.
The principal
differences
between
this nutritional
study and
other investigations
are that it was carried
out in a free-living
population
eating normal
food (not formula)
over two 12-wk
periods.
The population
studied
was homogenous,
was nonsmoking,
and consumed
negligible
amounts
of alcohol.
This
crossover

aims

to repeat

state

These

and Katan

in a free-living

results

are

in general

(27), who also carried

population.

The

fact that

interesting

questions

regarding

MUFAs
on plasma cholesterol
arise,
The amount
of MUFAs
in the diet
light

ofrecent

diets

may

findings
cause

On the other
tains

an average

a study

27%

dose

animals

that

of cholesterol

from

MUFAs,

Crete
failed

to show

in the concentrations

understood.
The baseline
values
4) were considerably
lower than

liver

March.

Con-

and

to the baseline
values for
and thereafter
increased
by
July. The effects
of season
on plasma
choconcentrations
in this previous
study were
the differences
found in the present
experi-

until

time

that

dietary

manipulation

as linoleic

acid)

(38),

not clear

it was

also

by changes
in erythrocyte
it has been recognized
for a

will alter
whether

be detected.
membrane

with

Our

essential

erythrocyte
diet

composition

fatty

membrane

acids

compo-

enrichment

with

(Table

3) suggest

findings
may

be altered

MUFAs

that

by MUFAs

(mainly
oleic acid). In both groups the high-MUFA
diet led to
an increase
in 18: 1-1 8:2 ratio whereas
the high-PUFA
diet produced converse
changes.
Oleic acid is the most abundant
fatty
acid

of stored

from

dietary

estingly,

adipose-tissue

sources

stearic

acid

appear

to elevate

TABLE

Thiobarbituric

is unique
plasma

dietary

among

cholesterol

acid-reactive

LDL from subjects

second

triglyceride

(30).

or by desaturation

substances

on MUFA

It is derived

of stearic
SFAs

Interit does not

in that

concentrations

in native

both

acid.

(28,

39).

and conditioned

and PUFA diets at the end of the

period5

Smooth-

(35).

favorable

of period 2 (Table
in period
1 This may be due
to confounding
dietary factors related to the 1-mo wash-out
period which included
the Passover
holidays.
We (37) investigated
.

November

between

(such

erythrocyte

are not clearly

at the start

mmol

found

the diet con-

a more

oftriglycerides

mmol/L

we found

serum lipoprotein
pattern
in young boys when compared
with
boys from a more westernized
society.
The response
of plasma triglycerides
was variable with a seasonality effect between the two experimental
periods. The effects
ofseasonality

in Israel

of0.07

lesterol and LDL-C

much smaller than
ment.
Adherence
to diet was monitored
membrane
composition.
Although
long

concentrations

high-MUFA

in the

(36), where

lipid

men a decrease

in

period
0.24

was

on plasma

In middle-aged

April (corresponding
2 in our study) were lowest

centrations

would

of

study.

triglycerides/L

sition

response

ofseasonality

in a previous

similar

to be studied in the future.

is of major importance
in

in experimental

accumulation

hand,

the

the effect

out their

a somewhat
larger decrease
of total and LDL-C on the PUFA
than on the MUFA diet whereas
Mensink
and Katan (27) did
not may be due to differences
in the design of the diets and the
duration
of the experiment.
The percent decrease in total cholesterol
we observed compares
with the 13% observed
by Mattson
and Grundy
(4), who used
diets of between
27% and 33% MUFAs,
and with the - 12.8%
found by Mensink
and Katan (27), who used a diet of 15.1%
MUFAs.
The concentration
of MUFAs
in our diets was 17%
and although
the control
diets in these experiments
were not
similar,

human skin fibroblasts

with unlabeled
LDL from
at the end of 12 wk of the MUFA or PUFA diets.

Diet

Native

Smoothmuscle cells

muscle
+

nmo/

MDA/mg

LDL

cells

Cu2

Cu2

protein

MUFA

(n

5)

1.05

0.03

15.70

4.00

47.00

2.00

7.20

2.00

6)

1.16

0.04t

24.40

2.00

49.80

2.60

18.60

l.40t

I test):

tP

PUFA

(n

SEM. MDA, malondialdehyde

tt Significantly different from MUFA
S

<0.0025.

equivalents

(one-tail

<

0.05,

jP

Downloaded from ajcn.nutrition.org by guest on March 25, 2015

tion

20

906

BERRY

These

indices

of diet

odological
aim
validity
ofresults

adherence

suggest

that

of the study
was achieved
for a free-living
population.

the major

meth-

and strengthens
the
Whether
the results

are applicable
to other populations
and also to females in light
ofthe findings of differing
responses
between
the sexes (27, 40)
requires
further investigation.
Another
point concerns
the issue
ofwhether
the lipid concentrations
would be maintained
or drift
back to the initial values over a longer time period.
There were no differences
in lipoprotein
structure
as shown
by compositional
analysis
or profiles on zonal ultracentrifugation. LDL-receptor
activity
of monocytes
also remained
unchanged
as was the ability ofdiet
LDL to displace
control
LDL
at the fibroblast
receptor.
However,
when the tendency
toward
oxidative
stress was measured,
LDL from the PUFA diet promoted significantly
more TBARS
formation
than did LDL isolated after the MUFA-rich
diet. Recent work showed that unesterified fatty acids may inhibit iron-dependent
lipid peroxidation
(41).

The

effect

of oleic

acid

was

significantly

greater

than

that

because

free

radicals

to be important
atherosclerosis

to the concept
in optimizing

modification

of LDL

factors

In conclusion,

our observations

that

MUFAs

serve

diet

may

lipid

may

considered
lend

as a substitute

concentrations

reduce

are

in the development

(42).
plasma

MUFA-rich
dative

and

pathoetiological

and,

the susceptibility

for SFAs

in addition,

of LDL

of

support
an

to oxi-

stress.

We thank the heads and teachers

ofthe

Har Etzion Yeshiva

for their

enthusiastic
help, the administrative
staffofthe
Yeshiva, and especially
the personnel
involved
in preparation
ofthe special diets. We thank and
appreciate
the student
volunteers
for their devoted
cooperation.

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