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Comparison of monounsaturated fatty acids and

carbohydrates for reducing raised levels of


plasma cholesterol in man13
Scott M Grundy, MD, PhD; Lea Florentin, RN; Dana Nix, RD; and Marjorie F Whelan, RN

ABSTRACT To compare monounsaturated fauy acids and carbohydrates for actions on


lipid and lipoprotein levels from solid-food diets, 10 men were studied on three diets. One diet
was high in saturated fatty acids and very high in cholesterol (High Sat+Chol), a second was
high in monounsaturates but low in cholesterol (High Mono), and a third was low in fat, high
in carbohydrates, and low in cholesterol (Low Fat). All diets were consumed for 6 wk. Com-

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pared with the High Sat+Chol diet, the High Mono and Low Fat diets significantly and sim-
ilarly reduced plasma cholesterol and LDL cholesterol. In contrast, the Low Fat diet signifi-
cantly lowered HDL cholesterol whereas the High Mono diet did not. Therefore, a solid-food
diet rich in monounsaturated fatty acids is equivalent to a low-fat, high-carbohydrate diet for
cholesterol lowering but does not reduce the HDL-cholesterol level. Am J Clin Nuir
1988;47:965-9.

KEY WORDS Monounsaturated fatty acids, carbohydrates, saturated fatty acids, dietary
cholesterol, plasma cholesterol

Introduction caused comparable lowering of plasma cholesterol as


compared with a diet high in saturated fatty acids. How-
Two dietary factors that raise the plasma cholesterol ever, the applicability ofthis finding to the general popu-
concentrations are saturated fatty acids and cholesterol. lation has been questioned because the study was carried
A rise in plasma cholesterol during the feeding of diets out for a relatively short period with liquid-formula diets
high in saturated fatty acids occurs in almost all individu- and carbohydrates consisted entirely of simple sugars.
als (1-5). The response to dietary cholesterol is more var- For this reason our purpose was to carry out a similar
ied although carefully controlled studies revealed that investigation that was longer in duration and that made
most people demonstrate some increase in cholesterol use ofmixed, solid-food diets.
levels on high-cholesterol diets (3, 6, 7). It further was
reported that saturated fatty acids and cholesterol are ad-
Subjects and Methods
ditive in their action to raise the cholesterol level(8). The
relatively high intakes ofsaturated fatty acids and choles- Subjects
terol by Americans are considered by many investigators
to be a significant factor in the high prevalence of coro- Ten men were investigated in the domiciliary-care unit of
the Sam Rayburn Memorial Veterans Administration Medical
nary heart disease (CHD) in the United States (9).
In other regions of the world where dietary habits are
different from those of most Americans, rates of CHD I From the Sam Rayburn Memorial Veterans Administration Medi-
are lower. For example, in China, Japan, and other coun- cal Center, Bonham; the Veterans Administration Medical Center,
tries of the orient, intakes of total fat are relatively low Dallas; and the Center for Human Nutrition, University of Texas
and so are rates of CHD (10). Further, in Greece, Crete, Southwestern Medical Center, Dallas, TX.
2 Supported in part by the Veterans Administration, by grant HL-
southern Italy, and other Mediterranean countries, the
29252 from the National Institutes of Health, and by the Moss Heart
traditional diet is rich in olive oil and total fat intakes can
Foundation, Dallas.
be relatively high but, even so, rates of CHD are rela-
3 Address reprint requests to Scott M Grundy, MD, PhD, University
tively low (10). Olive oil contains large amounts of oleic of Texas Southwestern Medical Center at Dallas, Center for Human
acid, a monounsaturated fatty acid. A recent study from Nutrition, 5323 Harry Hines Boulevard, Dallas, TX 75235.
our laboratory (1 1) demonstrated that a diet low in total Received March 25, 1987.
fat and another high in monounsaturated fatty acids Accepted for publication August 4, 1987.

Am J C/in Nuir l988;47:965-9. Printed in USA. © 1988 American Society for Clinical Nutrition 965
966 GRUNDY ET AL

Center, Bonham, TX. This facility provides medical and pay- bles, fruits, meat, whole eggs, egg whites, milk, fats, and oil).
chiatric care, rehabilitation assessments, and other therapeutic The High Sat+Chol diet was rich in products containing butter
measures to ambulatory eligible veterans. Many ofthe patients fat and it included two eggs per day. The High Mono diet was
in the domiciliary-care unit reside for long-term care. The pa- enriched in high-oleic safflower oil and unhydrogenated peanut
tients were selected by the following criteria: 1) they were men- butter. Butter and safflower oil were added to salads, vegetables,
tally competent and willing to volunteer for a dietary study, 2) bread, and toast. The order ofthe dietary periods was random-
they did not have recent history of alcohol or drug abuse; 3) ized. The patients were weighed twice weekly and caloric intake
they were generally healthy and did not have liver or kidney was adjusted to maintain a constant weight throughout the
dysfunction, diabetes mellitus or other endocrine diseases, hy- study. Patients maintained their normal activity level and no
pertension, or congestive heart failure; 4) they were not taking special exercise regimen was employed.
cardiac medications; and 5) they were not markedly over-
weight. Lipid and lipoprozein
The patients ranged in age from 61 to 70 y (mean ± SD, 64 After allowing 1 mo for equilibration on each new diet, the
± 2 y). Their body mass indices ranged from 20.8 to 30.5 patients were sampled three times per week for the last 2 wk of
(mean, 25.9 ± 3.4). At the time ofadmission to the study, aver- the 6-wk period. Blood samples were drawn after a 14-h fast
age lipids and lipoproteins for the group were total cholesterol, and plasma was obtained by centrifugation at 1232 X g for 30
227 ± I 2 (SEM) mg/dL(5.87 ± 0.3 mmol/L); triglycerides, 127 mm. Each plasma sample was analyzed by Lipid Research
± 21 mg/dL (1.43 ± 0.24 mmol/L), low-density-lipoprotein Ginics procedures (13) for levels oftotal cholesterol, triglycer-
(LDL) cholesterol 143 ± 5 mg/dL (3.70 ± 0. 13 mmol/L), and ides, and lipoprotein cholesterol; plasma total cholesterol and
high-density-lipoprotein (HDL) cholesterol 5 1 ± 3 mg/dL (1.3 triglycerides were measured enzymatically (14, 15). The HDL-

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± 0.08 mmol/L). Several patients carried a diagnosis of athero- cholesterol level was determined enzymatically after precipita-
sclerotic disease, either coronary heart disease or peripheral tion oflipoproteins containing apolipoprotein B with heparin-
vascular disease. Six of the 10 patients smoked cigarettes manganese (13). Through the appropriate use of blanks and
throughout the study. All patients gave informed consent for standards in the enzymatic reaction, this method was shown to
the study. give the same values for HDL cholesterol whether cholesterol
in HDL was estimated enzymatically or by gas-liquid chroma-
Diets tography (16). To obtain the concentration ofLDL cholesterol,
the very-low-density-lipoprotein (VLDL)cholesterol of density
At entrance into the study, the patients were being fed from < 1.006 g/mL was removed by ultracentrifugation (13) after
the domiciliary kitchen. The food served in this kitchen typi- cholesterol was determined in the infranatant, the level of LDL
cally is high in total fat, saturated fatty acids, and cholesterol. cholesterol was calculated as infranatant cholesterol minus the
Meat usually is offered twice daily and eggs always are offered HDL cholesterol.
for breakfast. At entry none ofthe patients was receiving a spe-
cial diet. For this investigation three different solid-food diets St azistical analysis
were fed from the same kitchen but the diets were prepared and
For comparison of means among the three dietary periods,
served under the close supervision ofone ofthe authors (DN). a repeated-measures analysis of variance was carried out (16,
Each dietary period lasted 6 wk. The diets were prepared from
I 7). Mean values for the six measurements ofeach period were
mixed foods. The composition ofeach diet was estimated from
used for the analysis. When the analysis indicated that the re-
a standard handbook (12). For each diet 2-wk menus were pre-
sults for the three periods were different, paired t tests were used
pared and they were rotated three times in each period. The
to compare individuals diet periods with Bonferroni adjust-
participants ate at a special table and their adherence to the diet
ments to control the overall a level (17, 18).
was monitored either by a dietitian or a food-service attendant.
The patients were urged not to eat extra food and they had no
access to alcohol. Results
One diet was designated High Sat+Chol; it was rich in satu-
rated fatty acids and cholesterol. It contained 40% of calories The data for individual patients are given in Figure 1
as fat, 45% as carbohydrate, and 15% as protein. Fatty acid cal- and for the group are given in Table 1 . On average the
ories were distributed as follows: 19% saturated fatty acids, 15% plasma total cholesterol was 1 3% lower on both High
monounsaturated fatty acids, and 6% polyunsaturated fatty Mono and Low Fat diets than on the High Sat+Chol diet
acids. The saturated fatty acids in this diet were calculated to
(p < 0.001). There were no significant differences for
have the following composition: 2.2% of calories had a chain
plasma triglycerides among any ofthe groups. LDL-cho-
length of 4-10 carbon atoms; 13.0% of calories had a chain
length of 12-16 (lauric, myristic, and palmitic acids), and 3.8% lesterol levels were 19% lower on both High Mono and
of calories had a chain length of 18 (stearic acid). Cholesterol Low Fat diets. In contrast HDL-cholesterol levels were
intake in this diet averaged 900 mg/d. The second diet was significantly lower on the Low Fat diet than on both
called High Mono; it contained 40% fat, (7% saturated, 27% High Mono and High Sat+Chol diets (p < 0.02) but
monounsaturated, and 6% polyunsaturated fatty acids), 45% there was no difference between the latter two diets. As
carbohydrate, and 1 5% protein. Cholesterol intake averaged shown in Figure 1, the trends noted for group means
200 mg/d. The third diet was designated Low Fat; it contained were fairly uniform for individual patients.
20% fat (7% saturated, 7% monounsaturated, and 6% polyun-
saturated fatty acids), 65% carbohydrate, and 15% protein.
Cholesterol intake was averaged to be 200 mg/d. In the High Discussion
Mono and Low Fat diets most saturated fatty acids had a C
chain length of 14 and 16 (myristic and palmitic acids). All This study was designed to compare a low-fat, high-
diets were composed of mixed foods (cereals, breads, vegeta- carbohydrate (Low Fat) diet with a diet high in monoun-
DIETARY MONOUNSATURATES VS CARBOHYDRATES 967

Total Cholesterol Triglycerides low intake of saturated fatty acids and cholesterol but
300 200 total fat intakes were twice as high.
According to several reports (6, 20, 2 1), intakes of di-
. etary cholesterol > 500 mg/d produce a diminishing in-
250 - 150 crement in the cholesterol concentration beyond the 500

‘O
:\. mg level. For example,
al (6) for dietary
consider
cholesterol:
the equation of Keys et

200 100
C,
-

. 1 y = l.5(X205 - X105) (1)


E
where y is the change in serum cholesterol in mg/dL and
150 50 x2 and are the cholesterol content of the two diets
expressed as mg/l000 kcal. Raising dietary cholesterol
from 200 to 500 mg/d for an individual consuming 2500
I I I
kcal/d should increase plasma total cholesterol by 8
‘J High High Low High High Low
Sat + Mono Fat Sat + Mono Fat mg/dL (0.21 mmol/L). A further increment in dietary
Chol Chol cholesterol to 900 mg/d should produce an additional
rise in total cholesterol of7 mg/dL (0. 18 mmol/L). Thus,
the increment in dietary cholesterol from 200 to 900 mg/

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LDL Cholesterol HDL Cholesterol
d, as used in our study, should have raised the cholesterol
250- 80
level by 15 mg/dL (0.39 mmol/L). A significant por-
tion ofthe reduction in plasma total cholesterol on High
Mono and Low Fat diets therefore could have been the
200 - 60

.
result ofa decreased intake of cholesterol.
On the High Sat+Chol diet, intakes of saturated fatty
acids averaged 19% of total calories. According to the
150-#{149} 40
C, data ofKeys et al (22) and Hegsted et al (3), all saturated
E
fatty acids do not raise the cholesterol level to the same
extent. Both these reports (3, 22) indicated that the C18
100- 20 .-..-.-.
stearic acid does not raise the total cholesterol level com-
pared with oleic acid. A preliminary study (23) from our
I I I
laboratory in humans confirmed this finding, and several
High High Low High High Low studies in animals are in accord with this response (24-
Sat+ Mono Fat Sat+ Mono Fat 26). Further, several reports (27-29) suggest that medi-
Chol Chol um-chain saturated fatty acids (chain length 4-10) do
FIG 1. Plasmalevels oftotal, LDL, and HDL cholesteroland triglyc- not raise the plasma cholesterol levels. Therefore, if we
erides in 10 patientson High Sat+Chol, High Mono, and Low Fat diets. subtract fatty acids of chain lengths 4, 6, 8, 10, and 18
Each point represents the mean ofsix determinations done during the from the total saturates, the High Sat+Chol diet con-
last 2 wk of6-wk periods. (To convert values forcholesterol and triglyc- tamed only 13% of cholesterol-raising saturated fatty
erides to mmol/L, multiply by 0.02586 and 0.01 129, respectively.)
acids (chain lengths 12, 14, and 16). Keys et al (22) mdi-
cated that these latter saturated fatty acids raise the
saturated fatty acids (High Mono) in which calories were plasma cholesterol by 2.7 mg/dL (0.07 mmol/L) for ev-
consumed mainly as solid foods. These two diets in turn ery 1% ofcalories. Thus for the High Sat+Chol diet com-
were compared to a diet high in both saturated fatty acids pared with the High Mono diet for cholesterol-raising
and cholesterol(High Sat+Chol). The latter diet was em- saturates, the High Mono diet should have caused a
ployed to obtain maximally high levels of cholesterol in mean reduction in plasma cholesterol of 16.2 mg/dL
total plasma and in LDL and HDL subfractions. On the (0.42 mmol/L). This decrease combined with the 1 5 mg/
High Sat+Chol diet, intakes ofboth saturated fatty acids dL (0.39 mmol/L) decrease predicted for the lower cho-
(19% ofcalones) and cholesterol (-9#{174} mg/d) exceeded lesterol intake should have reduced the plasma total cho-
current American intakes, and this cholesterol-raising lesterollevel by 3 1 mg/dL(0.80 mmol/L). This predicted
diet should have provided a plasma cholesterol ceiling by reduction closely approximated the observed mean re-
which the two cholesterol-lowering diets could be com- duction of32 mg/dL (0.83 mmol/L).
pared. In other words, the experimental design not only Both Keys et al (2) and Hegsted et al (3) reported that
facilitated comparison of two cholesterol-lowering diets carbohydrates have approximately the same effect as
but also allowed us to determine the maximal degree of monounsaturated fatty acids on plasma total cholesterol
cholesterol reduction that can be obtained by therapeutic levels. A similar relationship was noted previously in a
diets that are low in both saturated fatty acids and choles- study from ourlaboratory (1 1). The current results are in
terol. The Low Fat diet was equivalent to the American complete accord. On average the plasma total cholesterol
Heart Association Phase III diet for treatment of hyper- fell to the same extent on both High Mono and Low Fat
cholesterolemia (19); the High Mono diet had the same diets. Likewise, the LDL-cholesterol concentration de-
968 GRUNDYETAL

TABLE 1
Plasma lipids and lipoproteins in the three diet periods

Total Total LDL HDL


Diet cholesterol triglycerides cholesterol cholesterol

mg/dL (mmol/L)

HighSat+Chol 240±11 113±11 172±9 52±4


(6.20 ± 0.28) ( 1.27 ± 0. 12) (4.45 ± 0.23) ( 1.34 ± 0.10)
High Mono 208 ± lOt 104 ± 9 140 ± 8t 0±4
(5.37 ±0.26) (1.17 ±0.10) (3.62 ±0.21) (1.29 ± 0.10)
LowFat 208± 7t 113±8 139±5f 46±44
(5.37 ± 0. 18) ( 1.27 ± 0.09) (3.59 ± 0. 13) ( I . 19 ± 0.10)

i±SEM;n= 10.
t High Mono and Low Fat significantly different from High Sat+Chol atp < 0.0010.
High Mono and Low Fat significantly different from High Sat+Chol at p < 0.0002.
§ Low Fat significantly different from High Sat+Chol and High Mono atp < 0.0182.

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dined identically on the two diets. These results suggest nificantly reduce HDL-cholesterol levels whereas diets
that there is nothing gained by way of LDL-cholesterol high in monounsaturates do not. Thus, data obtained on
reduction merely by lowering intakes of total fat. A diet solid-food diets indicate diets high in monounsaturated
high in monounsaturated fatty acids but low in saturates fatty acids induce changes in lipoprotein-cholesterol 1ev-
appears just as effective for lowering of plasma LDL- els that are at least as beneficial from the viewpoint of
cholesterol as a diet low in total fat. The converse of coronary risk as a diet low in fat and high in carbohy-
course also is true. drates. This finding may allow for a greater flexibility in
In a previous report from this laboratory (1 1) in which choice ofdietary constituents for achieving reduced 1ev-
liquid-formula diets were used, a low-fat diet caused a els ofcholesterol for the American population. 13
reduction in levels of HDL cholesterol compared with a
We express appreciation to Carolyn Croy, Peggy Ann Loessberg,
diet high in saturated fatty acids whereas a diet high in Rosemary Abate, and Ray Wheatley for their excellent assistance with
monounsaturates did not. The same result was obtained this project.
in this study. The HDL-cholesterol concentration on the
current Low Fat diet was significantly lower than the
High Sat+Chol diet by an average of 6 mg/dL (0.16 References
mmol/L). In contrast, the High Mono diet did not cause
1. Ahrens EH Jr. Hirsch J, Insull W Jr. Tsaltas Ti’, Blomstrand R,
a significant reduction in HDL cholesterol. Thus the Peterson TK. The influence ofdietary fats on serum lipid levels in
HDL-lowering effect of a low-fat diet apparently occurs man. Lancet 1957; 1:943-53.
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4. Vega GL, Groszek E, WolfR, Grundy SM. Influence of polyunsat-
A high-carbohydrate diet was reported to cause an in-
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DIETARY MONOUNSATURATES VS CARBOHYDRATES 969

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