Comparison on plasma Margo
of effects of lauric acid lipids and lipoproteins13
A Denke
and
ABSTRACT lipids
Scott
lipoproteins
of laurie
acid (C 16:0) and oleic acid 14 men by using liquid-formula order.
Lauric
acid
palmitic acid rich sunflower
was
acid
compared
were
(C12:0)
with
on
the effects
(C 18: 1 ) in a metabolic-diet diets fed for 3 wk each
supplied
in a synthetic
plasma
cholesterol-raising
to compare the effects oflauric acid lipid and lipoprotein concentrations,
oil,
and hut
total
concentrations
LDL
cholesterol
as much
(4.94
± 0.75
palm
concentrations
as potent
cholesterol
J (Yin Nuir
.ln Laurie
acid,
were acid
noted raises
with
oleic
concentrations
1992;56:895-8.
cholesterol-raising
fatty
Saturated fatty acids plasma concentrations (1).
acid,
an
lesterol
I 8-carbon
and
concentrations
fatty
acid
(Cl 8:0)
(4-8).
hand,
effects
medium-chain seemingly have 3). Likewise,
(2,
does
not
In contrast,
that palmitic acid (C16:0) and serum cholesterol concentrations
the other
constituents that raise and LDL cholesterol fatty acids share this
For example, length 8-10,
cholesterol
concentrations mon saturated laurie other
property. of carbon
concentrations
dicates crease On
are major dietary of total cholesterol not all saturated
However,
cholesterol-raising rated fatty acids on serum
of laurie
raise
acid
(C12:0)
oil
also
are
rich
these
fats. and
Laurie therefore
concentrations. However, to laurie and ;llfl
could
would
Fourteen on the
behave
like
not be expected
in-
(C14:0) in(4, 5, 8, 9).
on cholesterol
in myristic
com45%
acid, whereas coconut oil
acid
(1 7%)
to increase
and
the role action
a medium-chain
acid
.\ii!r
et al (4) assigned
of of
fatty cholesterol
equal
to that
et al (5) 1992:56:895-8.
reported
a cholesterol-raising
of palmitic that Printed
acid laurie
in USA.
and
acid (C
has I992
potential
Upon
kg/m2)
averaged
testinal
tract,
aged
44-7
ward
ofthe
and
was designed
and palmitic acid on plasma both relative to oleic acid, potential.
admission, 25.5
acid,
only
a mild Society
1 y (63
their ± 2.5.
kidneys,
Affairs
mean
(±SE)
None
had
or endocrine
decompensation. disease and
and
throughout
nitroglycerin
± 5, 1 ± SD)
Veterans’
of cardiovascular of coronary heart
body
index
ofthe
study
or a recent
without
history
any
a history blockers change
taking /-adrenergic blocking agents. and continued to smoke during the
The research protocol Board and informed
was approved consent was
(in
gastroin-
Five patients had took calcium channel the
studied Center,
mass
diseases
system,
were
Medical
in
Seven inves-
by the Institutional obtained from each
subject. Diet.c This
study
was an inpatient,
ing
a liquid-formula
fat,
40%
based
diet.
metabolic-ward The
as carbohydrates
protein.
mended
diet
A multivitamin
dietary
allowance
providing (RDA;
intake
‘
From
Medicine,
was
the Center
for Human
Biochemistry,
and
100%
20%
as
as soy-
of the
recom-
vitamins
was
all the daily energy. During to walk around the hospital form of strenuous physical
adjusted
so that
Nutrition,
Clinical
us-
of energy
and
10) for essential
activity.
energy
40%
glucose),
diet provided were allowed engage in any
The
investigation
supplied
(primarily
also given. The liquid the study, the subjects grounds, but did not
each
Departments
Nutrition,
subject
of Internal
University
of
Texas
Southwestern Medical Center, Dallas, and the Veterans’ Affairs Medical Center, Dallas. 2 Supported in part by the Southwestern Medical Foundation and the Moss Heart Foundation, Dallas, and by grants from the Veterans’ Affairs and the National Heart, Lung, and Blood Institute(HL29252). MA Denke 3
myristic
American
men
metabolic
Dallas.
is the
Keys
l-legsted J (liii
acid
cho-
fourth most oil contains
acid and palm-kernel oil contains 47% laurie oils contain only minimal amounts. Because palm-kernel
stearic
evidence
myristic acid in humans
are unclear. Laurie acid is the fatty acid in the diet. Coconut
satulittle
plasma
strong
palmitic acid (8%), it has been difficult to determine laurie acid in contributing to the cholesterol-raising acid
ofpalmitic
study
Subjects
tigation. Review
effect
that
present
cholesterol-raising
dosage. None were men were smokers
acid
Introduction
humans
no serum
The
Methods
mmol/
oil (5. 17 ± 0.65
compared
increasing
for
acid.
KEY WORDS
as did
respectively). No differences or HDL cholesterol. Laurie
cholesterol
is not
as is palmitic
in
has
acids.
recipient Reprints
ofan not
Received
March
Accepted
for
for Clinical
NIH-NHLBI
Clinical
Investigator
Award.
available.
6, 1992.
publication
Nutrition
May
19,
l992.
895
Downloaded from www.ajcn.org by on February 26, 2007
of plasma
and 3.93 0.5 1 mmol/L, in plasma triglycerides acid,
which
of myristic
one-third
study of in random
high-laurie
that
ie, only
one-fourth
L [I ± SE]) and LDL cholesterol (3.70 ± 0.57 mmol/L) when compared with high-oleic sunflower oil (4.44 ± 0.54 and 3.31 ± 0.44 mmol/L, respectively), but did not raise total and LDL
total
action,
of palmitic
was provided by palm oil and oleic acid in oleicseed oil. The high-laurie oil resulted in higher
concentrations
cholesterol
acid
M Grundv
The effects
and
and palmitic
896
DENKE
TABLE I Fatty acid composition Fatty
acid
of the three
AND
diets5
High oleic
High
laurie
High
5
1
0.1 0.1 4.7 2.2 75.8 15.6
palmitic
SD; n = 3
±
maintained
± 0.40
0.3
0.1
± 0.05
1.0 ± 0.05
0.05
2.5
±
2.2
± 0.05
4.3
0.50 0.05
40.1 9.9
± 0.05 ± 0.15
44.4
0.05
±
0.05
±
6.2
±
of methanol:benzene were
then
the fatty
200
acid
(4: 1 , by vol)
tranesterified L
by heating
acetyl
composition
chloride
± 0.05
43.4
illary
0.50
±
had
0.05 0.10
± ±
samples
been
was determined
added.
by gas-liquid with a flameCA) and cap-
column.
Statistical
± 0.05
solution.
the
To
analysis
compare
the
analysis
of variance
verified
by the
three
dietary
was
periods,
carried
out
Wilcox-Shapiro
a repeated-measures
after
normality
normality
test
of data
was
(1 7). When
the
analysis of variance indicated that the results of the diets were different, paired I tests, with Bonferroni correction for multiple measurements, were used. When results are stated to be statis-
weight
throughout
subject
varied
for each
acids
fatty
Finally,
measurements.
a constant
requirements per
43.9
±
volumes
The
chromatography (model 5880 gas chromatograph ionization detector; Hewlett-Packard, Palo Alto,
± 0.05
± 0.05
in 2-mL
at 100 #{176}C for 1 h, after
% C12:0 C14:0 C16:0 C18:0 C18:l C18:2
GRUNDY
the study.
The
energy
within
833
ki (200
keal)
periods,
each
lasting
3 wk.
tically significant, the 3, or 0.01 7. All t tests
p value for that were two-tailed.
comparison
was
0.05/
<
period. There
were
three
diets
fat used.
three
different
dietary
period was separated by went home and resumed were
fed
In one
in random
period
fat. In another sole fat. And
fat made by base oil and trilaurin
catalyzed (Proctor
Ronald
Jandacek)
sitions
ofeach
and
was
fat were
are detailed
Lipid Blood
was
metabolic
have
shown
used
that
differed
high-oleic
period finally,
as the
determined
only
ofhigh-oleic Cincinnati; fat.
Fatty
by gas-liquid
from and
state
each
after
a new
sample
acid
fast
chromatography
on days
inpatient,
steady
heparin
the
time
was analyzed
(HDL)
poprotein precipitation
with
of blood
regard
assay
2 1 of studies
to plasma
sampling.
for total according
cholesterol
The
cholesterol,
lipid the diet were in plasma
triglycerides,
to procedures
was measured containing
To measure
the HDL
ofthe
Lipid
from
enzymatically apolipoprotein
the
after B with
low-density-lipoprotein
cholesterol
was substrated
The at the Lepage
fatty
value
determined
the cholesterol
content
pattern
in plasma
triglycerides
silica-gel ether:aeetie triglyceride
were
separated
by thin-layer
G plates (25O-Mm thick) acid (80: 19: 1, by vol) band
in the were
the
high-laurie
high-palmitic
and
lipoprotein
periods
are
of total
cholesterol
period.
significantly
lower
acid
eantly different LDL-eholesterol
oflipids dietary
concentrations
period
Total
in the
they
from those concentrations
were
in
were
concentraperiod,
intermediate
and
and
in each of the other paralleled changes
in the high-oleic to raise total-
concenpresented
cholesterol
high-oleic
highest LDL-eholesterol period, intermediate
two periods. in total cho-
concentrations in the high-laurie
period. Overall, and LDL-cholesterol
in
signifi-
found pe-
the high-laurie concentra-
tions about two-thirds as much as did high-palmitic feeding. The fatty composition ofplasma triglycerides during each period is presented in Table 3. Total saturated fatty acids (C: 12:0 + C:l4:0 + C16:0 + Cl8:0) were highest during the high-palmitie period, during
intermediate the high-oleic
caused
a small
of plasma
during period
but
the
(P
definite
(P
triglycerides
was
scraped
into
high-laurie 0.001).
increase
in the
0.001),
<
period, and The high-laurie
<
and
laurie
although
acid
lowest diet content
triglycerides
ofthe
2
and lipoprotein
Total cholesterol Triglycerides VLDLcholesterol LDL cholesterol HDL cholesterol
infrana-
to the method were extracted chromatography
tubes
Lipid
concentrations
and
resuspended
on the three
oleic
High
diets5
laurie
High
palmitic
mmo//L
by a separate
of and on
with use of hexane:diethyl as the solvent system. The glass
TABLE
High
was determined
end of each dietary period, according and Roy (16). Fasting plasma lipids
triglycerides
found tions
highest
three
(d
acid anal.vsis acid
2. The
of the
(LDL)
(VLDL) cholesterol plasma by ultracentrifu-
tant.
fatty
Table
concentrations
each
(13), except that cholesterol and triglycwere measured by enzymatic assay, which to yield LRC values (14, 1 5). High-density li-
manganese.
Plasma
serum on
(LRC)
of lipoproteins
and
Mean trations
lesterol, with the in the high-palmitic
16 through
metabolic-ward
state
cholesterol, very-low-density-lipoprotein < I .006 kg/L) was removed from gation,
compo-
Results
riod, and lowest feeding appeared
a 14-h
cholesterol,
Research Clinic eride measurements has been shown
palm oil diet, a
1.
Previous
during
lipoprotein
oil was
sunflower courtesy of
concentrations is reached within 2 wk after changing (9, 1 1, 12); therefore, it was assumed that the patients a steady
in the
sunflower
(high-palmitic), for the high-laurie
sole
time The
analyses
drawn diet.
and
rearrangement and Gamble,
in Table
and lipoprotein
the
order,
(high-oleic),
used as the sole was used as the
1 wk during which their usual activities.
1±
4.94
± 0.75t
5.17
± 0.65
1.06
± 0.19
1.06
± 0.19
0.31
±0.15
0.31 ± 0.13
3.70
± 0.57t
3.93
± 0.5 1
0.96
± 0.21
0.90
± 0.21
SE.
t Significantly with Bonferroni Significantly Bonferroni
different from high palmitic, correction). different from high laurie, P
P <
<
0.0167
0.0167
(P
<
0.05
(P
<
0.05
with
(P
<
0.05
with
correction).
§ Significantly Bonferroni
4.44 ± 0.54tt 1.05 ± 0.20 0.29±0.10 3.3 1 ± 0.44tj 0.83 ± 0.18
different
correction).
from
high oleic,
P
< 0.0167
Downloaded from www.ajcn.org by on February 26, 2007
Each dietary the subjects
LIPID TABLE Plasma
3 triglyceride
Fatty
acid
on the three
High oleic
C12:0 C14:0 CI6:0 C18:0 Total saturates Cl6:l Cl8:l C18:2 Total unsaturates
0.1 ± 1.0 ± 21.7 ± 3.6 ± 26.4 ± 3.0 ± 54.7 ± 16.2±0.7 73.9 ±
diets5
LAURIC
ACID
High laurie
0.1 0.0 1.1 0.3
3.4 1.9 23.2 3.9
1.1
32.4
High
± ± ±
Let
palmitic
± 0.8t
± 0.3
37.9
± 0.6f
2.4
± 0.3
± ± ±
t Significantly 0.0 167. j: Significantly
is the
potentiate lesterol
3.1 ± 0.3
44.7 ± 0.5
of allowing
14.6±0.7
15.3 ±0.7
the synthesis
67.9
62.4
hepatie
from
both
high oleic and high palmitic,
different
from
high oleic,
P
P
<
site ofaction
fatty
and Cl6:O 0.005), the
<
appeared increments
to increase somewhat were relatively small.
in this
period
anee
production acid.
of laurie
investigations have not given a clear indication of acid affects plasma cholesterol concentrations. (4, 5). study was conducted to compare the relative actions acid,
trations
palmitie
of total
testing oils that relative
enriched to oleic
concentrations LDL-cholesterol two-thirds must
that
has
the
that
C12:
acid
and
laurie
fatty
does
acid
acid.
acids
1 fatty
acid
exerts
Thus,
(C8:0
laurie
and
(2, 3). Laurie acid properties of colaurie
acid,
a saturated
fatty
saturated
acid,
shortly acid,
after
concentration ( 1 9). Laurie substrate for the desaturase in plasma
its status
its cholesterol-raising
fatty
as a saturated
property
as a result.
ask
ways: to how
metabolism
1) effects the
fatty
or via chylomierons),
specific acid
ofeholesterol to the fatty was
presented
or 3) effects
and acid
alone,
to the specific
lipoproteins liver
2) effects (via
route
The
acid,
potency
cholesterol
also
extent
depend
of Mensink
serum
of its shorter
chain
lipoprotein
in fatty
depend
length
to triglyceride acid and thus
and/or
difference
clear-
on the rigidity
fatty acids, which LDL-cholesterol
cholesterol
the
do un-
both
is the report
because
whether
stimulate
than
for affecting may
on hepatic
triglycerides
(27, acid
by this
LDL-cholesterol whereas laurie
28),
on how
fatty
acid
effects
the saturated
Could
the
relative
is it possible
acid
that
the
the
acids
in VLDL
content provide
of VLDLs yet another
difference
acid in (20),
trations. (29-31),
Support which
acids.
lomicron
triglycerides
that LDL-cho-
acid
than
did
palm-oil was fatty
then this would in LDL concenstudies of ehy-
chylomicrons
are
en-
presumably
could
be
The
true for VLDL triglycerides. Thus, rates of hydrolysis of VLDL triglycerides could have been slowest on the high-palmitic diet, intermediate on the high-laurie diet, and most rapid on the highdiet.
Further,
inhibit
specific
their
conversion
vein of
ofVLDLs diet,
the
direct
to LDL.
to LDLs
an intermediate
rate
hepatic would
same
seen acid
riched
could
The
ob-
palmitic
comes from previous intravascular lipolysis when
acids.
and
fatty acids in saturated
metabolism, for differences
is retarded fatty
con-
near
fatty
oleic
in saturated
ehylomi-
composition of VLDL a lower percentage of
triglycerides
for this hypothesis suggest that the
with
between acid
ofsaturated difference
alters VLDL mechanism
ex-
raised
LDL-cholesterol
by laurie
and the lowest content the high-oleic diet. Ifthe
acid be
acid
a value
in the result of the different triglyceride particles? Laurie acid feeding produced
cho-
ofO.62 mmol/L, by only 0.39
is absorbed
mmol/L,
imparted
raise
of laurie
palmitic
by an average the concentration
by 0.43
concentrations
fatty
effects
study,
hypothesis,
rise
through
do not
concentrations
In this
of laurie
to this
absorbed
acids
LDL-cholesterol
70%
should
served. Finally,
these
concentrations acid increased
according
centrations
on
are 95%
and
mechanism?
If only
crons,
in three portal
to the composition
to
cho-
to suppress
may
to a greater
concentrations
which
current study did not examine mechanisms for the differences in cholesterol raising oflauric vs palmitic acids, but it may provide some insight into this question. Fatty acids may effect the intrahepatic
acid
monounsaturated rigidity, also raise
Medium-chain
plained
feeding, during
is that
LDL
cholesterol
Palmitic
for this concept
less influence
palmitic
lesterol as
by dietary
raises
trans
concentrations.
saturated
to oleic
observed
portal
stearic
concentrations
retains
26).
the
cholesterol for stearic
is desaturated
was
(25,
mmol/L.
ClO:
on raising
fatty acids are presented to the liver. Available evidence indicates that 25-30% of dietary laurie acid is absorbed via the portal route, whereas < 5% ofpalmitic acid is absorbed by this pathway
and
therefore
acids
point, may impart less rigidity molecules than does palmitie
we can
lesterol
Still, the rise in diet was about
long-chain
acid
it presumably
by
concentration in our laboratory
cholesterol stearie
concen-
in humans
the LDL-cholesterol acid? Previous work
does not raise the cholesterol contrast is probably a poor no
and
fatty
oil. is why
another
raising
Therefore,
plasma
like oleic acid and does not raise serum (8, 1 8). The presumed mechanism
its absorption,
and
diet,
cholesterol concentrations to the cholesterol-raising
acid, not increase as does palmitic
not
on
fatty acids. The data indicate acid does not raise cholesterol
medium-chain
oil and palm-kernel interesting question
shown
acid
cholesterol
a cholesterol-raising
from
acid, behaves concentrations acid
these laurie
on the high-palmitic
0) that do not raise must then contribute
fatty much
oleic LDL
as much as does palmitic acid. concentrations on the high-laurie
differs
conut An
and and
with acid,
be designated
acid
acid,
cholesterol
(23).
Support
on LDL-cholesterol Previous how laurie The present
have
fatty acids appear
acid
oflipoproteins
lower melting phospholipid
Next
Discussion
fatty
hepatocellular
Laurie
may have metabolism.
acid
of hydrolysis uptake Ifso, have
conversion
of VLDL
ofVLDL
the highest occurred with
remnants fractional with
the
the
high-laurie
triglycerides and
favor
conversion high-palmitie diet,
and
Downloaded from www.ajcn.org by on February 26, 2007
C14:0
palmitie
activity
palmitic
receptors.
acids
concentrations.
(P
and
Saturated
oflipoproteins
saturated
and and
affect
of cholesterol and lipofatty acids suggest that the
ofsaturated
Although
ofLDL
fatty
differently
in humans, even when on a cholesterol-free diet, study (8, 9), it may do so by a similar mechanism
synthesis
ofthe
acid
of LDL-receptor
and Katan (24) that have a saturated-like
0.0 167.
<
laurie
endogenous
and
might
metabolism with dietary
concentrations.
(2 1 , 22).
concentrations as used in this
± 0.7
liver
suppression
50.0 ± 0.9t
different
whether
major
1.1
± 0.9t
ask
LDL cholesterol
0.0 0.6f 0.3t
compositions metabolism).
actions on Investigations
0.3
1.2
(ie, different
us first
liver
0.4 1.0 32.1 4.4
897
lipoprotein
different proteins.
WI
0.8t 0.3t 0.9t 0.3
±
acid
nonhepatic
SE.
±
.
OF
the fatty fatty acid composition
% by
5
EFFECTS
898
DENKE
the least
conversion
with
the high-oleic
of VLDL
converted
centrations,
the
triglycerides LDL-cholesterol
in the three diets concentrations.
difference
In summary, for raising terol
to LDL should
laurie
acid
might
acid is not as potent of total
The
precise
oils
(coconut
for
acid
replaces
palmitic
creasing
potential
slightly,
the benefit
would
be too
study
indicates
palmitic
acid.
tojustify
that
acid
laurie
acid
LDL
choles-
difference
oil)
the
less cholesterol
must
the expense acid
and
should
as a cholesterol-raising
be
raising
reduced probably
effort.
Finally,
this
be classified
along
with
saturated
fatty
determination
total
serum
cholesterol.
Clin
Chem
1974;20:
Z, West CE, et al. Determination
DR, Kruijswijk
triglycerides
by
an
accurate
method
enzymic
not affected
1965; 106:480-94. 20.
Brett
Cheryl
21.
acids desaturases the conversion of saturated to monoenoic Arch Biochem Biophys 197 l;143:535-47. Spady DK, Dietsehy IM. Interaction of dietary cholesterol
of the
Veterans’
Affairs
Medical
Center,
Dallas.
D, Howling
glycerides
References
22.
1. Grundy proteins. 2. Furman lipids.
5, Denke M. Dietary influences on serum lipids and lipoI Lipid Res 1990;3 1: I 149-72. RH. Effects of medium chain length triglycerides on serum In: Senior
University
IR,
ed.
of Pennsylvania
Medium
chain
Press,
triglycerides.
1968.
3. Hashim SA, Arteaga A, Van Itallie TB. Effect ofa saturated mediumchain triglyceride on serum-lipids in man. Lancet l960;l:l 105-8. 4. Keys A, Anderson IT, Grande F. Serum cholesterol response to changes in the diet. IV. Particular saturated fatty acids in the diet. Metabolism I 965; 14:776-87. 5. Hegsted DM, MeGandy RB, Myers ML, Stare Fl. Quantitative effects ofdietary fat on serum cholesterol in man. Am I CIin Nutr 1965;l7: 28 1-95. 6. Horlick L, Craig BM. Effect oflong-chain polyunsaturated and saturated fatty acids on the serum lipids of man. Lancet 1957;2: 566-9. 7. Grande
F, Anderson
and stearic Nutr
IT,
Keys
A. Comparison
acids in the diet on serum
cholesterol
ofeffects
Grundy
24.
25.
Am J Clin
28.
l970;23:1 184-93.
SM,
Ahrens
EH
on absorption
excretion,
in man.
Invest
I Clin
Jr. The
effects
synthesis, 1970;49:l
of unsaturated
and distribution
135-52.
dietary
fats
of cholesterol
Tak
29.
regulation
LI,
lames
AT.
of hepatic
low
Specificity
density
of the
fatty
acids. and tri-
lipoprotein
trans-
1951;166:451-5. Yee
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We thank Kathy Schutt and Anh T Nguyen for their technical support and assistance. We also acknowledge the assistance provided by the Nursing Service and Dietetic Services, specifically Kathleen Gray and Davis,
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13
acid.
of
470-5.
15. Sullivan
cholesterol-in-
might
13. Lipid Research Clinics Program Manual of Laboratory Operations. Lipid and lipoprotein analysis. Washington, DC: National Heart, Lung and Blood Institute, 1974. Vol 1. [DHEW Publication no. (NIH) 75-628.] 1974. 14. Allain CC, Poon IS, Chan CS, Richmond W, Fu PC. Enzymatic
is not
certainly
serum fats
GRUNDY
is
oleic acid, laurie acid fatty acid and laurie
formulated
ofone-third
small
and this
in
fats. Little would be gained ofdietary fats in which laurie
Although
of such
of VLDL
as palmitic
palm-kernel
be classified as cholesterol-raising by the synthesis and manufacture
con-
to differences
cholesterol
reason
oil and
the fraction
composition
contribute
apparent. Nonetheless, compared with must be designated as a cholesterol-raising acid-rich
Because
affect LDL-cholesterol
in fatty
concentrations
in humans.
diet.
AND
