Effect of diets high in butter, corn oil, or high-oleic acid

sunflower oil on serum lipids and apolipoproteins in men13

Gordon M Wardlaw andfean TSnook

ABSTRACT This randomized blind crossover study com- tween low HDL-cholesterol concentrations and an increased
pared serum lipid and apolipoprotein concentrations in 20 risk for coronary heart disease (14).
men consuming 37-43% of energy as fat from diets based on Replacing saturated fatty acids with monounsaturated fatty
corn oil, high-oleic acid sunflower oil, and butter. Each phase acids does not appear to reduce serum HDL-cholesterol con-
of the crossover design included 2 wk of butter-based diet fol- centrations(3, 4, 6-8, 15). In addition, people in the Mediterra-
bowed by 5 wk ofdesignated vegetable-oil-based diet with a 7- nean area of the world who consume monounsaturated fatty
wk washout period between phases. Compared with values for acids as a primary fat source suffer neither ill health nor an
the butter-based diet, the vegetable-oil-based diets reduced se- increased risk ofheart disease from this practice (16). Thus, the
rum total
cholesterol by 16-21% (p < 0.001), LDL cholesterol best way to compensate for a reduction in saturated-fatty-acid
by 2 1-26% (p < 0.001), triglycerides by 10-21% (p < 0.01 for intake may be a replacement with monounsaturated fatty ac-
the higher figure), and apolipoprotein B-l00 by 22-29% (p ids(l7).
< 0.001). When values fell, they fell further on the corn-oil- One objective of this study was to reexamine the effect of
based diet. There were no significant changes in serum HDL polyunsaturated fatty acids vs monounsaturated fatty acids on
cholesterol or apolipoprotein A-l These data suggest . that serum HDL-cholesterol concentrations. We wanted to deter-
when men on diets high in saturated fatty acids reduce their mine ifa diet oftypical American foods with corn oil (and thus
saturated fatty acid intake but not their total fat intake, many polyunsaturated fatty acids) as the major source of fat would
can still experience a significant lowering in serum total lower serum HDL-cholesterol concentrations. A lowering of
cholesterol. Am J Clin Nuir 1990;5 I :815-21. serum HDL-cholesterol concentrations was reported when a
diet containing 28% of energy as polyunsaturated fatty acids
from safflower oil was fed (7). However, studies show that a diet
KEY WORDS Serum cholesterol, HDL cholesterol, apoli-
containing 19% of energy from polyunsaturated
‘. fatty acids
poproteins, monounsaturated fatty acids, polyunsaturated
can either decrease (5), increase (9), or have no effect (3, 18)
fatty acids, saturated fatty acids, phospholipid fatty acids
on serum HDL-cholesterol concentrations. A second objective
was to document the effects on serum lipids of high-obeic acid
Introduction sunflower oil. Previous studies evaluating the effect of mono-
unsaturated fatty acids on serum lipids used olive oil (3, 4, 6,
One goal of the National Cholesterol Education Program is 8, 1 5) or high-oleic acid safflower oil (6, 7).
for adults 20 y to have serum total cholesterol concentrations
< 5. 18 mmob/L and bow-density-lipoprotein (LDL) cholesterol
Subjects and methods
concentrations < 3.37 mmol/L (1). Diet modification is advo-
cated (1), especially a reduction in the intake ofsaturated fatty Design
acids with a chain length of 16 carbons (2) for individuals
The study protocol and procedure for informed consent was
with serum lipoprotein concentrations exceeding these recom-
approved by the Ohio State University Biomedical Review
mendations.
Committee. We utilized a two-phase randomized crossover de-
When the saturated-fatty-acid content ofa diet is decreased,
sign. Each phase began with a 2-wk period in which 85% of the
that energy source is usually replaced by a mixture of polyun-
dietary fat was from butter. Then the butter was replaced by
saturated fatty acids, monounsaturated fatty acids, and carbo-
corn oil (Poly diet) (Pocahontas Foods, Richmond, VA) or
hydrate. Many studies support the replacement of saturated
fatty acids by any of those options as an effective way to bower
I From the Division ofMedical Dieteticsand the Department ofHu-
serum total cholesterol (3- 13). However, in some short-term
man Nutrition and Food Management, Ohio State University, Colum-
studies (4-8, 10-12) high carbohydrate intakes and to a lesser
bus, OH.
extent high polyunsaturated-fatty-acid intakes were associated 2 Supported by SVO Enterprises, Inc. Wickliffe, OH.
with a reduction in both serum total and high-density-lipopro- 3 Address reprint requests to GM Wardlaw, Division ofMedical Di-
tein (HDL)-cholesterob concentrations. A reduction in serum etetics, 1583 Perry Street, Columbus, OH 43210.
HDL-cholesterol concentrations is not advantageous if it per- ReceivedFebruary 15, 1989.
sists because epidemiobogical studies show a strong link be- Accepted for publication June 21, 1989.

Am J C/in Nutr l990;5 1:8 15-2 1. Printed in USA. © 1990 American Society for Clinical Nutrition 815

Downloaded from https://academic.oup.com/ajcn/article-abstract/51/5/815/4695361

by Washington University in St. Louis user
on 08 June 2018
 816 WARDLAW AND SNOOK

high-oleic acid sunflower oil (Mono diet)(Trisun-80, SVO En- salad with dressing, meat, starch, vegetable, cake, and milk. See
terprises, Inc, Wickliffe, OH), which was fed for 5 wk. A 7-wk Table I for a description ofthe diet composition. The basic diet
washout period was then followed by a repeat of the entire se- was formulated to provide 40% of food energy (40 en%) as fat.
quence except that the vegetable-oil assignments were reversed The actual range varied from 37 to 43 en% because we allowed
for the second phase of the crossover. The butter-based diet the subjects a certain amount of latitude when selecting study
was used for three reasons: It allowed the subjects to adapt to a foods (for example, cookies instead ofcake for dessert). To help
regular and standardized three meals per day. It prevented the maintain compliance on this 4-mo study, subjects were allowed
effects ofthe adaptation to the general dietary regimen imposed modest amounts of alcohol per week but were cautioned, if
by the study protocol (possible changes in total fat intake, di- they chose to consume alcohol, to maintain a constant weekly
etary fiber intake, etc) from confounding the effects ofthe vege- intake. Fourteen subjects averaged < 2 g/d, five subjects aver-
table-oil-based diets. Finally, it helped reestablish a baseline aged < 7 g/d, and one subject averaged 10 g/d. All ofthese in-
total serum cholesterol concentration similar to phase I after takes are below the threshold (30-60 g/d) for influencing serum
the 7-wk washout period. This washout period included No- HDL-cholesterol concentrations (19).
vember 24 to January 1, a time for much festive eating. The subjects were encouraged to maintain a constant body
Subjects were not informed oftheir response to the diets un- weight and were weighed daily. The basic menu provided 1 1.5
til the study was completed. One principal investigator (GM W) MJ/d. Subjects requiring more food energy to maintain a stable
and his staffsupervised the feeding aspect ofthe study and were weight were given extra sandwiches, cookies, and cakes because
blinded to the changes in serum chemistry values. The other these foods had a protein-carbohydrate-fat ratio similar to the
principal investigator (JTS) and her staffsupervised all labora- overall diet. Serving sizes were reduced for subjects needing less
tory analyses and were blinded to the dietary assignments. food energy. Weight change over the entire 150 d of the cross-
One important feature ofthis study was substituting vegeta- over study was 0.3 ± 0.6% (i± SEM, range -7.6 to +4.1%).
ble oils for butter while keeping all other diet constituents con- Only one subject gained or lost > 3 kg in weight during the
stant. This necessarily resulted in a lowering ofthe daily choles- entire study, and a similar amount of weight was lost during
terol intake for the subjects from a mean of480 to 190 mg. To each ofthe two study phases.
assess this independent effect on the changes in serum lipids All food was provided for the subjects as three meals per day
seen after a reduction in saturated fatty acid intake, all but three and was prepared in our laboratory or by a local bakery. On
of the subjects continued on their respective vegetable-oil- weekdays subjects consumed breakfast and dinner at the study
based diets for an additional 2 wk at the end ofthe second cross- site and were given a sack lunch. On weekends they consumed
over phase. During this period cholesterol was given (as eggs) to breakfast at the study site and were given a carryout lunch and
raise the total cholesterol intake for each subject to the amount dinner. Subjects used check lists to keep daily records of all
consumed on the butter-based diet. food eaten, including any occasional extramural food con-
sumption. A staff member regularly verified with the subject
Subjects that these records were complete and accurate. The daily
checklists were combined to yield a week’s intake and analyzed
A total of 86 male subjects aged 25 y volunteered for the
for nutrient content with Food Processor I Software (ESHA
study after seeing advertisements in a student newspaper and
Research, Salem, OR) to which values for monounsaturated
notices posted on campus. After signing the consent form, sub-
and polyunsaturated fatty acids were added according to
jects were screened initially on the basis of serum total choles-
Pennington and Church (20). Seven-day rotating menus were
terol concentration. Subjects with values > 4.66 mmol/L (n
used in which most of the dietary lipid was incorporated into
= 39) were further screened by physical examination and a de-
cakes, cookies, and bread. In this way the overall composition
tailed blood-chemistry analysis (Diagnostic Multi-Chem,
ofthe diet stayed constant in the two crossover phases; only the
Roche Biomedical Laboratories, Columbus, OH). On the basis
type oflipid used in food preparation was changed.
of these examinations, a physician recommended 37 subjects
for inclusion in the study. Ofthese, the 22 men with the highest Serum lipid and apolipoprotein analyses
serum cholesterol concentrations were enrolled. Age was 34.7
Blood samples for serum lipid analyses were obtained after
± 1.5 y (1 ± SEM, range 27-47 y) and weight
was 84.5 ± 3.6
an overnight fast before breakfast by venipuncture seven times
kg (range 70-1 16 kg). For randomization, subjects were
(days 1, 13, 15, 21, 35, 45, and 50) during each phase of the
grouped into intervals ofbody mass index [wt (kg)/ht2 (m2)] of
study. Values from days 13 and 15 (end of the butter-based
20-22.9, 23-24.9, and 25 and then assigned in equal num-
diet) as well as those from days 45 and 50 (end ofthe vegetable-
bers from these groups to the Poly or Mono diet for the first
oil-based diets) were averaged to dampen the effect of day-to-
phase of the study. Two subjects (one on each vegetable-oil-
day variation in serum lipid concentrations. Depending on re-
based diet) resigned from the study after the first phase. This
quirements of the analytical procedure, serum samples ob-
report includes data from the 20 subjects who completed both
tamed by centrifugation were analyzed fresh or were frozen at
crossover phases as well as data for the 17 subjects who com-
-70 #{176}C
for lipid analysis at a later time.
pleted the final higher cholesterol, low-saturated-fatty-acid diet
Serum total cholesterol was analyzed in previously frozen
period.
serum by using an enzymatic assay (procedure 352, Sigma
Chemical Company, St Louis, MO). Serum HDL cholesterol
Diets
was determined by first precipitating non-HDL serum lipopro-
Breakfast comprised fruit juice; eggs and toast, cereal and teins with dextran sulfate (Stanbio Laboratory, Inc, Houston,
toast, french toast, or pancakes; and milk. Lunch comprised TX). Then HDL cholesterol was determined in the supernatant
meat sandwich, cookies, fruit, and diet soda. Dinner comprised by using an enzymatic method as before. Serum triglycerides

Downloaded from https://academic.oup.com/ajcn/article-abstract/51/5/815/4695361

by Washington University in St. Louis user
on 08 June 2018
 DIET AND SERUM LIPIDS 817

TABLE I
Composition ofthe diets5

Butter-based diet Mono diet Poly diet

Energy (Mi) I 2.0 ± 0.6 (80- 15.7) 12.3 ± 0.6 (8.95- 16.0) 12. 1 ± 0.6(9.0-15.4)
Carbohydrate (en%)t 50 ± 1 (47-53) 49 ± 1 (46-5 1) 50 ± I (46-52)
Protein(en%) 13± 1 (10-15) 12± 1 (11-14) 13± 1 (11-14)
Fat(en%) 40± 1 (37-42) 41 ± 1 (37-43) 41 ± I (37-43)
Saturated fatty acids (en%) 21± 1 ( 19-22) 7 ± 1 (5-9) 8 ± 1 (7-9)
Monounsaturated fattyacids(en%) 14 ± I (13-16) 28 ± 1 (26-30) 14 ± 1 (12-15)
Polyunsaturated fatty acids (en%) 5 ± 1 (3-5) 6 ± I (6-7) 19 ± I ( I 8-20)
Cholesterol(mg) 480±20 (345-658) 190± 10 (157-253) 185± 10 (131-261)

5 i± SEM; n = 20. Range isgiven in parentheses.

t En% refers to the percentage ofdiet energy.

were measured enzymatically (procedure 338, Sigma Chemical Deerfield, IL). Samples of fish oil were taken throughout the
Company). Values for serum LDL cholesterol were calculated procedure to check for oxidation of polyunsaturated fatty
as follows: acids. Fatty acids were identified by comparison oftheir reten-
tion times with authentic standards obtained from Sigma
LDL cholesterol = total cholesterol
Chemical Company and Supelco, Inc (Beblefonte, PA).
- HDL cholesterol - triglycerides X 0.16
Data analysis
Portions of a previously frozen serum sample were analyzed Phase I and II serum lipid and apobipoprotein concentrations
along with the standards in most runs. The run-to-run preci- were compared for both the starting and butter-based diet by
sion (coefficient ofvariation) for the various serum lipid analy- using paired I tests to examine if subjects returned to phase I
ses were as follows: total cholesterol, 2.2%; HDL cholesterol, values (SAS, SAS Institute, Cary, NC). For each ofthe vegeta-
2.8%; and triglycerides, 4.3%. The accuracy ofthe serum total ble-oil-based diets, percent changes in serum lipid and apolipo-
cholesterol determination was assessed by using cholesterol protein concentrations from both the prestudy and butter-
standards from the American College ofPathobogy (Skokie, IL) based diets and the last week on the vegetable-oil-based diet
providing 5.39, 6.82, and 9.30 mmol/L. Our values (tested on were again analyzed by using paired t tests (Minitab, Minitab,
one occasion) for these standards were 5.39, 6.88, and 9.17 Inc, State College, PA). Differences between the Poly and
mmol/L, respectively. Mono diets were analyzed with repeated-measures analysis of
Fresh serum samples on days 15, 21, and 50 of both phases variance (ANOVA) for crossover designs (BMDP, BMDP Sta-
were analyzed for apolipoproteins A-b (apo A-b) and B-bOO tistical Software, Los Angeles, CA) (23). In this design possible
(apo B-lOO) by radial immunodiffusion (Tago, Inc, Burlin- fixed sources ofvariation include the overall mean, differential
game, CA). Three levels of reference sera were run with each carry-over, period, and diet effects. Because there were repeated
determination, and serum apolipoprotein concentrations were measurements taken of the serum concentrations over time
calculated from a standard curve using the square ofthe precip- (weeks), additional sources ofvariation include week as well as
itin-ring diameter and antigen concentration. the interaction ofweek with the other factors(differential carry-
On days 13 and 50 ofeach phase ofthe study, serum samples over, period, and diet effect). The analysis showed an absence
were taken for phospholipid fatty acid analysis. Fresh serum of differential carry-over effects. This means that any possible
was extracted with chloroform-methanol (2: 1) and then fib- carry-over from phase I to phase II did not affect the response
tered. Saline was added to the filtrate, creating two layers. This to the diets in phase II more in one group than in the other
mixture was centrifuged and then the saline-methanol layer group. Thus we are able to combine data from both crossover
was removed. A small amount of chloroform-methanol-saline phases of the study. However, some carry-over effects were
(3:47:48) was added to the chloroform-lipid layers and the sa- present for serum total cholesterol and LDL cholesterol when
line-methanol was again removed (21). The chloroform-lipid both butter-based-diet periods were compared (p < 0.02). In
extract was then stored at -20 #{176}C
under nitrogen until assayed. the absence of significant differential carry-over effects for all
After evaporation ofthe chloroform layer, serum phospholipid analyses, it was then necessary to analyze all serum lipid and
fatty acids were isolated by thin-layer chromatography (TLC) apolipoprotein data in terms ofchanges from phase I prestudy
using glass plates coated with Silica Gel G (Analtech, Inc, New- and butter-based-diet serum concentrations (24). The mea-
ark, DE). The solvent system was n-hexane-diethyl ether-ace- surements taken at the start of phase I are the only bonafide
tic acid (80:20: 1, vol:vol:vol). The phospholipid band was starting and baseline values, for it is only then that all the sub-
scraped from the plate for esterification. Fatty acid methyl es- jects are comparable (aside from random differences) in their
ters were prepared by using BF3-methanol (22) and purified by values. At the start of phase II, the subjects have already re-
TLC as before. Fatty acid methyl esters were then separated ceived the treatment diets, and so there may be some carry-over
and quantitated by using a gas chromatograph (model 417, effect onto the butter-based phase II values, possibly because
Packard Beckman, Downers Grove, IL) equipped with a flame of a change in food-consumption patterns during the washout
ionization detector and two glass columns packed with 20% period that contrasted with the self-selected-diet phase that
Silar 1OC on 100/120 mesh Anakrom Q (Altec Associates, preceded the study.

Downloaded from https://academic.oup.com/ajcn/article-abstract/51/5/815/4695361

by Washington University in St. Louis user
on 08 June 2018
 818 WARDLAW AND SNOOK

s-- i- l-_$. fl-I confidence interval (CI) for the difference between the effect of
7.0- the Poly diet vs the Mono diet was 0.2 1 ± 0. 18 mmol/L (p
Told cholsstsrol < 0.03) for changes from the phase I butter-based-diet concen-
trations.
The extent of change in serum total cholesterol concentra-
tions on the vegetable-oil-based diets were correlated to the
6L0
phase I butter-based-diet concentrations for the Mono diet (r
= 0.79, p < 0.0 1) and the Poly diet (r = 0.6 1 , p < 0.0 1). For
55-
serum total cholesterol the range of responses to the vegetable-
I’ oil-based
varied
diets from phase I butter-based-diet
from an increase of 0. 15 mmob/L
concentrations
to a decrease of 2.18
mmol/L on the Mono diet and from a decrease ofO.47 to 2.41
4.5-
f t
mmol/L on the Poly diet.
Mean calculated serum LDL-cholesterol concentrations
were 8% lower than prestudy concentrations (NS) and 21%
2.25-
4 Triglycerides 4 lower than phase I butter-based-diet concentrations (p < 0.001)
after 5 wk on the Mono diet. For the Poly diet mean serum
_I Mo LDL-cholesterol concentrations were 1 3% 0.05) lower (p <
aoo#{149}
than prestudy concentrations and 26% lower (p < 0.001) than
pioseI Poly phase I butter-based-diet concentrations (Table 2). The 95%
- 1.75- wIl Mono CI for the difference between the effect of the Poly diet vs the
Mono diet was 0. 18 ± 0. 17 mmol/L (p < 0.04) for changes
E from phase I butter-based diet concentrations.
Mean serum apo B- 100 concentrations fell dramatically dur-
ing the first week ofthe vegetable-oil-based diets in both phase
I and II (Fig 2). When data from both phases were combined,
1.25-
mean serum apo B- 100 concentrations after 5 wks were 23%
lower (p < 0.001) on the Mono diet and 28% lower(p < 0.001)

1.o on the Poly diet when compared with phase I butter-based-diet

concentrations (Table 2). There was a significant diet-by-time
interaction (p < 0.05), meaning that over time the Poly diet
1.51 HDL-CMSI$SVOI lowered apo B-bOO at a greater rate than did the Mono diet.
Mean serum HDL-cholesterol concentrations did not
change significantly on any of the diets (Table 2 and Fig 1).
There were also no significant changes in mean serum apo A-i
concentrations associated with the Mono diet or the Poly diet
(Table 2 and Fig 2). However, in both cases there was a signifi-
out, t_
Io
cant diet-by-time interaction
time the Poly diet lowered
(p < 0.05), meaning
serum HDL-cholesterol
that over
and apo A-
0 25 &o is
i#{243}o is 1 concentrations at a greater rate than did the Mono diet al-
DAYS ON STUDY
though neither total change was significant.
FIG 1 Changes
. in serum total cholesterol, HDL cholesterol, and Mean serum triglyceride concentrations fell dramatically
triglycerides associated with the butter-based diet (days 1-14 and 100- from prestudy concentrations when subjects consumed both
1 14) and the vegetable-oil-based diets on both phases ofthe crossover the butter-based diet and the vegetable-oil-based diets in phase
study. I ± SEM, n = 20. Poly refers to the corn-oil-based diet and I (Fig 1). When data from both phases were combined, mean
Mono refers to the diet based on high-oleic acid sunflower oil. Arrows serum triglyceride concentrations after 5 wk on the Mono diet
show the start ofthe vegetable-oil-based diets. were 23% lower (p < 0.05) than prestudy concentrations and
10% lower (NS) than phase I butter-based-diet concentrations.
On the Poly diet mean serum triglyceride concentrations were
Results 33% lower (p < 0.001) than prestudy concentrations and 21%
lower (p < 0.01) than phase I butter-based-diet concentrations
Serum lipids and apo/ipoproteins (Table 2). The 95% CI for the difference between the effect of
Serum cholesterol concentrations fell dramatically during the Poly diet vs the Mono diet on serum triglycerides was 0.11
the first week of the vegetable-oil-based diet in both phases I ± 0. 12 mmol/L (NS) for changes from phase I butter-based-
and II (Fig 1). After 5 wk ofthe Mono diet, mean serum total diet concentrations.
cholesterol concentrations were 9% lower (p < 0.05) than pre- Day-to-dayvariations for serum lipid concentrations of sub-
study concentrations and 16% (p < 0.001) lower than phase I jects on a constant diet (butter based or vegetable oil based)
butter-based-diet concentrations. For the Poly diet mean se- when sampling occurred twice within 3-5 d were as follows (1
rum total cholesterol concentrations were 14% lower (p < 0.01) ± SEM, n = 40): serum total cholesterol, 0.28 ± 0.01 mmol/L;
than prestudy concentrations and 2 1% lower (p < 0.001) than HDL cholesterol, 0.05 ± 0.01 mmol/L; and triglycerides, 0.22
phase I butter-based-diet concentrations (Table 2). The 95% ± 0.01 mmol/L. The maximum day-to-day variation seen in

Downloaded from https://academic.oup.com/ajcn/article-abstract/51/5/815/4695361

by Washington University in St. Louis user
on 08 June 2018
 DIET AND SERUM LIPIDS 819

TABLE 2
Concentration ofserum lipids and apobipoproteins for the prestudy, the phase I butter-based diet, and the combined data from both the Poly and
Mono diet intervals5

Prestudy valuet Butter-based diet Poly diet Mono diet

Total cholesterol (mmol/L) 5.78 ± 0.16 6.30 ± 0.16 4.95 ± 0.l6t 5.26 ± 0.l6II
LDL cholesterol (mmol/L) 3.93 ± 0. 13 4.58 ± 0. 16 3.41 ± 0. 13lI 3.62 ± 0. l6
HDL cholesterol (mmol/L) 1.09 ± 0.05 1 . 12 ± 0.05 1.09 ± 0.05 1 . I 2 ± 0.05
Triglycerides(mmol/L) 1.95 ± 0.20 1.65 ± 0. 14 1.30 ± 0. 1 l11 1 .49 ± .1011
ApoA-l(mg/L) - 1320±60 1200±50 1260±40
Apo B- 100 (mg/L) - 1 1 10 ± 50 790 ± 50 860 ± 50

51±SEM;n = 20.
t Before phase I.
11th Significantly different from prestudy value ll < 0.05, fp < 0.01, #{182}p
< 0.001.
55 Significantly different from butter-based diet values 55p < 0.01, §p <0.001.

any subject was serum total cholesterol, 0.80 mmol/L; HDL calculated LDL-cholesterol, HDL-cholesterol, triglycerides,
cholesterol, 0.21 mmol/L; and triglycerides, 1.03 mmol/L. apo A-i, or apo B-lOO concentrations (Table 4).

Serum phospholipidfatty acids

Discussion
Compared with the phase I butter-based-diet values, after
5 wk the Poly diet had reduced C160 (pabmitic acid) in serum This study found that when following a diet both low in satu-
phospholipid fatty acids by 3.3% (p < 0.001) and increased C18: rated fatty acids and high in either polyunsaturated or mono-
2 (linoleic acid) by 3.9% (p < 0.001) (Table 3). After 5 wks the unsaturated fatty acids, 13 ofthe 16 men with an initial serum
Mono diet had reduced C160 by 3.2% (p < 0.001) and increased cholesterol concentration > 5. 18 mmol/L experienced a rapid
C181 (oleic acid) by 4.8% (p < 0.001). Thus, overall there was a decrease and ended the study below this concentration. They
replacement of palmitic acid by unsaturated fatty acids in se- also showed similar decreases in LDL-cholesterol and apo B-
rum phospholipid fatty acids because of the vegetable-oil- 100 concentrations. Apo B-lOO is the major apobipoprotein in
based diets with the specific replacement fatty acid determined the LDL particle, and the drop could be important because it
by the major form present in the diet. also may be predictive offuture heart-disease risk (25). In addi-
tion, our correlation data also suggest that decreases in serum
Effect ofadded cholesterol
total and LDL cholesterol induced by a partial replacement of
After phase II of the crossover study was completed, 1 7 of saturated fatty acids with monounsaturated and polyunsatu-
the 20 subjects continued on the same vegetable-oil-based diet rated fatty acids will be greater if the person has a high total
for an additional 2 wk while cholesterol intake was increased serum cholesterol concentration initially. The magnitude of
to match their butter-based-diet intake (average increase from the change in this study was rebated to the concentrations es-
190 to 500 mg/d). This increase in dietary cholesterol intake
led to no significant change in mean serum total cholesterol,
TABLE 3
Final concentrations ofserum phospholipid fatty acids(percent of
I-phose I-1 1-phase II-1 total) on the butter-based diet (first phase ofthe crossover), the Poly
diet, and the Mono diet5
I.50-
Apo A-I Fatty acid Butter-based diet
methyl ester (phase I) Poly diet Mono diet
1.25-
%t
‘
:z 1.00- 14:0 0.5±0.1
a, Apo B-I00 0.4±0.1 0.4 ±0.1
16:0 3 1.4 ± 0.6 28. 1 ± 0.4 27.6 ± 0.7
18:0 15.4±0.5 16.2±0.3 15.6±0.6
0.75-
phase I Mono phase I Poly
-‘I 18: ln-9 12.9 ± 0.2 1 1.2 ± 0.7 16.9 ± 0.5f
-- phasefl Poly phase fl Mono l8:2n-6 16.7 ± 0.6 21.3 ± 0.6 17.4 ± 0.5
l8:3n-3 0.2±0.1 0.2±0.1 0.3±0.1
o.50J 4
20:4n-6
a 25 50 75 i#{243}o125 150 (+20:3n-3) 6. 1 ± 0.3 6.9 ± 0.3 6.6 ± 0.3
DAYS ON STUDY
20:5n-3 0.4 ± 0. 1 0.3 ± 0. 1 0.4 ± 0.1
FIG 2. Changes in serum apo A-l and apo B-lOO values from butter-
based-diet values because of the vegetable-oil-based diets in both 51±SEM;n= 18-20.
phases ofthe crossover study. i ± SEM, n = 20. Poly refers to the corn- t Percent oftotal fatty acids as methyl esters.
oil-based diet and Mono refers to the diet based on high-oleic acid :1:Significantly different from butter-based diet, p <0.001.
sunflower oil. Arrows show the start ofthe vegetable-oil-based diets. § Significantly different from Mono diet, p <0.001.

Downloaded from https://academic.oup.com/ajcn/article-abstract/51/5/815/4695361

by Washington University in St. Louis user
on 08 June 2018
 820 WARDLAW AND SNOOK

TABLE 4 so variable that an individual evaluation, as recommended by

Changes in serum lipid and apolipoprotein values after 2 wk because McNamara et al (3 1), is the more desirable approach.
ofan increase in the average cholesterol content ofthe vegetable-oil- In conclusion, our results support the view that the first line
based diets from 190 to 500 mg/d5
of treatment for men with high serum concentrations of total
Poly diet Mono diet cholesterol on Western diets should be a reduction in intake of
saturated fatty acids. This diet modification can often cause
Total cholesterol (mmol/L) -0. 13 0. 10
± -0. 13 ± 0.08 a clinically significant reduction in elevated concentrations of
LDLcholesterol (mmol/L) -0.10 0.10
± -0.10 ± 0.13 potentially atherogenic serum lipids and apolipoproteins. Re-
HDL cholesterol (mmol/L) 0.0 1 ± 0.03 0.0 1 ± 0.03 cent work by Anderson and Gustafson (36) shows that a reduc-
ApoA-l(mg/L) 100±60 110±40
tion in lipid concentrations can be maintained for 2 y if di-
ApoB-lOO(mg/L) 10±30 20± 30
etary compliance, in their case with a low-fat, high-fiber diet, is
Triglycerides(mmol/L) -0.09 ± 0.10 -0.03 ± 0.12
maintained.
5i±SEM:n = 8-9. When intake of saturated fatty acids is reduced, either poly-
unsaturated or monounsaturated fatty acids are an appropriate
replacement, although the total drop because of a substitution
tablished on the butter-based diet. A similar result was also with polyunsaturated fatty acids may be more consistent and!
shown in the multiple risk factor intervention trial (MRFIT) or greater. That added benefit may be offset, however, by the
study (26). known safety ofdiets high in monounsaturated fatty acids (16).
We saw no change in mean serum HDL-cholesterol concen- Our data suggest that the type of fat a person consumes is very
trations when either monounsaturated or polyunsaturated important. Both the American Heart Association (37) and the
fatty acids were substituted for saturated fatty acids. We did not National Cholesterol Education Program (1) promote the re-
expect a change with the monounsaturated-fatty-acid substitu- duction oftotal fat intake for people with high concentrations
tion (3-8, 1 5), but some studies showed that diets high in poly- ofserum total cholesterol. Our data with men suggest that this
unsaturated fatty acids can lower serum HDL-cholesterob con- may not be absolutely necessary for those who are willing to
centrations (5, 7, 10, 1 1). The discrepancy between our results simply lower their intake of saturated fatty acids but not their
and those of others could be because fewer polyunsaturated total fat intake. Even a diet containing 40 en% from fat can
fatty acids were fed in this study (28 vs 19 en%) (7) or because allow for a substantial reduction in blood lipids ifintake of sat-
the effect of polyunsaturated fatty acids on HDL-cholesterol urated fatty acids is minimized. B
concentrations may not be consistent (9, 15, 18, 19). This issue
may need further study because there was a trend over time We thank Colleen McCarthy and Joan Sentipal for excellent work
on the diet study, Jong Sook Lee and Mark Slivka for the laboratory
for the Poly diet to lower serum HDL-cholesterol and apo A-
analysis, Chris Demas for the physical examinations, and Melvin
1 concentrations more than the Mono diet did (diet-by-time
Moeschberger, Judy Anderson, and Jim Ashton for statistical advice
interaction p < 0.05). and help with the analysis. Finally, we thank Lorie Wardlaw and
However, it is entirely possible that the current evidence of Juanita Williams for help with the diet record analysis.
a reduction in HDL-cholesterol concentrations by a high in-
take of polyunsaturated fatty acids (5, 7, 1 1) is actually a phar-
macobogical effect. No study has shown that the intake polyun- References
saturated fatty acids close to that of the average American, 7
en% (27), lowers HDL-cholesterol concentrations. Instead, the 1 . National Cholesterol Education Program Expert Panel. Report on
literature suggests that a diet containing 35 en% from fat and detection, evaluation, and treatment of high blood cholesterol in
P-S ratio 1 .5 is not likely to significantly lower serum HDL- adults. Arch Intern Med 1988; 148:36-69.
cholesterol concentrations (28-3 1 ). Pietinen and Huttunen 2. Bonanome A, Grundy SM. Effect ofdietary stearic acid on plasma
( 1 9) came to the same conclusion in a recent review. cholesterol and lipoprotein levels. N Engl J Med 1988: 318:
When the average cholesterol content of the vegetable-oil- 1244-8.
3. Becker N, Illingworth DR. Alaupovic P. Connor WE, Sundberg
based diets was increased from 190 to 500 mg/d, there was no
EE. Effects of saturated, monounsaturated, and u,-6 polyunsatu-
significant increase in mean serum total cholesterol, LDL-cho-
rated fatty acids on plasma lipids, lipoproteins, and apoproteins in
lesterol, or apo B- 100 concentrations. If sustained over time,
humans. Am J Clin Nutr 1983; 37:355-60.
this finding would reinforce observations ofothers (3 1-33) and 4. Garg A, Bonanome A, Grundy SM, Zhang Z, Unger RH. Compar-
the thrust of the National Cholesterol Education Program (1) ison ofa high carbohydrate diet with a high monounsaturated-fat
that reducing saturated fatty acids in the diet should be the ma- diet in patients with non-insulin-dependent diabetes mellitus. N
jor emphasis when lowering serum lipids. Reducing dietary EnglJ Med 1988;3l9:829-34.
cholesterol, when consumed at average American amounts 5. Grundy SM, Nix D, Whelan MF, Franklin L. Comparison of three
(27), can be of secondary importance for most people if a diet cholesterol-lowering diets in normolipidemic men. JAMA
low in saturated fatty acids is consumed. Only 4 of 17 subjects l986;256:235 1-5.
6. Grundy SM. Comparison of monounsaturated fatty acids and car-
in this study showed an increase in serum total cholesterol con-
bohydrates for lowering plasma cholesterol. N Engl J Med
centrations when dietary cholesterol intake was increased, the
1986;3 14:745-8.
largest increase being 0.31 mmol/L.
7. Mattson FH, Grundy SM. Comparison of effects of dietary satu-
The effect of cholesterol in the diet within the ranges we fed rated, monounsaturated, and polyunsaturated fatty acids on
may be greater on serum lipids if the diet is high in saturated plasma lipids and lipoproteins in man. J Lipid Res l985;26:194-
fatty acids (3 1 33),
, but even that statement is in question (34, 202.
35). Overall, the response to cholesterol in the diet is probably 8. Mensink RP, Katan MB. Effect of monounsaturated fatty acids

Downloaded from https://academic.oup.com/ajcn/article-abstract/51/5/815/4695361

by Washington University in St. Louis user
on 08 June 2018
 DIET AND SERUM LIPIDS 821

versus complex carbohydrates on high-density lipoproteins in and dimethyl acetals from lipids with boron fluoride-methanol. J
healthy men and women. Lancet 1987; 1:122-6. Lipid Res l964;5:600-8.
9. Phillipson BE, Rothrock DW, Conner WE, Hams WS, Illingworth 23. Wallenstein S. Fisher AC. The analysis ofthe two-period repeated
DR. Reduction ofplasma lipids, lipoproteins, and apoproteins by measurements crossover design with application to clinical trails.
dietary fish oils in patients with hypertriglyceridemia. N EngI J Biometrics 1977;33:261-9.
Med 1985;312:1210-6. 24. Fleiss JL. The design and analysis of clinical experiments. New
York: John Wiley & Sons, 1986.
10. Schaefer EJ, Levy RI, Ernst ND, Van Saint FD, Brewer HB Jr.
25. Freedman DS, Srinivasan SR. ShearCL, Franklin FA, Webber LS,
The effects oflow cholesterol, high polyunsaturated fat, and low fat
Berenson OS. The relation ofapoproteins A-I and B in children to
diets on plasma lipid and lipoprotein cholesterol levels in normal
parental myocardial infarction. N EngI J Med l986;3l5:72l-6.
and hypercholesterolemic subjects. Am J Clin Nutr 1981;34:
26. Dolecek TA, Milas NC, van Horn LV, et al. A long-term nutrition
1758-63.
intervention experience; lipid responsesand dietary adherence pat-
I I . Shepherd J, Packard CJ, Patsch JR. Gotto AM, Taunton OD. terns in the multiple risk factor intervention trial. J Am Diet Assoc
Effects ofdietary polyunsaturated and saturated fat on the proper- 1986;86:752-8.
ties of high density lipoproteins and the metabolism of apolipo- 27. Human Nutrition Information Service, Nutrition Monitoring Di-
protein A-I. J Clin Invest 1978;6l:1582-92. vision. Continuing survey of food intakes by individuals. Hyatts-
12. Snook iT, DeLany JP, Vivian VM. Effect ofmoderate to very low ville, MD: US Dept of Agriculture, 1985. (NFCS, CSF II report
fat defined formula diets on serum lipids in healthy subjects. Lipids 85-1.)
I985:20:808-16. 28. Blaton V, De Buyzere M, Declerq B, et al. Effect of polyunsatu-
I 3. Thuesen L, Henriksen LB. Engby B. One-year experience with a rated isocaloric fat diets on plasmalipids, apolipoproteins and fatty
low-fat, low-cholesterol diet in patients with coronary heart dis- acids. Atherosclerosis l984;53:9-20.
ease. Am J Clin Nutr l986;44:2l2-9. 29. Brown GD, Whyte L, Gee MI, et al. Effects oftwo “lipid-lowering”
14. Castelli WP, Garrison Ri, Wilson PWF, Abbott RD, Kabousdian diets on plasma lipid levels ofpatients with peripheral vascular dis-
5, Kannel WB. Incidence ofcoronary heart disease and lipoprotein ease. J Am Diet Assoc l984;84:546-50.
cholesterol levels. JAMA 1986:256:2835-8. 30. Weisweiber P, Drosner M, Janetschek P. Schwandt P. Influence of
polyunsaturated fats and fat restriction on serum lipoproteins in
15. Sirtori CR, Tremoli E, Gatti E, et al. Controlled evaluation of fat
humans. Metabolism 1985;34:83-7.
intake in the Mediterranean diet: comparative activities ofolive oil
31. McNamara DJ, Kolb R, Parker TS, et al. Heterogeneity of choles-
and corn oil on plasma lipids and platelets in high-risk patients.
terol homeostasis in man: response to changes in dietary fat quality
Am J Clin Nutr l986;44:635-42.
and cholesterol quantity. J Clin Invest l987;79:l729-39.
16. Keys A. Seven countries: a multivariate analysis ofdeath and coro- 32. Flaim E, Ferreri LF, Thye FW, Hill JE, Ritchey Si. Plasma lipid
nary heart disease. Cambridge, MA: Harvard University Press, and lipoprotein cholesterol concentrations in adult males consum-
1980. ing normal and high cholesterol diets under controlled conditions.
17. Grundy SM. Dietary therapy for different forms of hyperlipopro- AmJClinNutr 198l;34:1l03-8.
teinemia. Circulation l987;76:523-8. 33. Bronsgeest-Schoute DC, Hermus RJJ, Dallinga-Thie GM, Hout-
18. Kromhout D, Arntzenius AC, Kempen-Voogd N, et al. Long-term vast JGAJ. Effects ofdietary cholesterol in a linoleic acid-poor diet.
effects ofa linoleic acid-enriched diet, changes in body weight and Am J Clin Nutr 1979;32:2193-7.
alcohol consumption on serum total and HDL-cholesterol. Ath- 34. Bronsgeest-Schoute DC, Hautvast JGAJ, Hermus RJJ. Depen-
erosclerosis l987;66:99-l05. dence ofthe effects ofdietary cholesterol and experimental condi-
tions on serum lipids in man. I Effects of dietary cholesterol in a
19. Pietinen P. Huttunen JK. Dietary determinants of plasma high-
linoleic acid-rich diet. Am J Clin Nutr l979;32:2 183-7.
density lipoprotein cholesterol. Am Heart J 1987; 1 13:620-5.
35. Edington J, Geekic M, Carter R, et al. Effect ofdietary cholesterol
20. Penninton JAT, Church HN. Food values of portions commonly
on plasma cholesterol concentration in subjects following reduced
used. Philadelphia: JB Lippincott, 1985.
fat, high fiberdiet. Br Med J l987;294:333-6.
21 . Folch J, Lees M, Stanley GHS. A simple method for the isolation 36. Anderson JW, Gustafson NJ. Hypocholesterolemic effects of oat
and purification of total lipids from animal tissue. J Biol Chem and bean products. Am J Clin Nutr l988;48(suppl):749-53.
I957:226:497-509. 37. American Heart Association. Dietary guidelines for healthy adult
22. Morrison WR, Smith LM. Preparation of fatty acid methyl esters Americans. Circulation l988;77:721A-4A.

Downloaded from https://academic.oup.com/ajcn/article-abstract/51/5/815/4695361

by Washington University in St. Louis user
on 08 June 2018