The effect of a high cholesterol and saturated

fat diet on serum high-density lipoprotein-

cholesterol, apoprotein A-I, and apoprotein E
levels in normolipidemic humans1
Meng H. Tan,2 M.D., Mary A. Dickinson,3 P.Dt., John J. Albers,4 Ph.D.,

Richard J. Havel,5 M.D., Marian C. Cheung,6 Ph.D., and Jean-Louis Vigne,7 M.D.

ABSTRACT The effects of a high cholesterol, high saturated fat diet on serum high density
hipoprotein cholesterol, apo A-I, and apo E levels were studied in six normohipidemic subjects. The
study was done on an outpatient basis and mixed natural foods normally consumed by humans

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were used. When compared with a low cholesterol (98 mg/day) high polyunsaturated fat (P/S ratio
1.6) diet, the high cholesterol (1021 mg/day), high saturated fat (P/S ratio 0.4) diet increased serum
cholesterol (23%) by raising the cholesterol concentration in very low-density hipoproteins (59%),
low-density hipoproteins (15%), and high-density hipoproteins (30%). The low-density hipoprotcin-
cholesterol/high-density hipoprotein-cholesterol ratio fell significantly from 1.78 to 1.58. The
increased high-density hipoprotein-cholesterol was associated with an elevation of serum apo A-I
but not apo E. Serum triglycerides did not change significantly. Am. J. C/in. Nuir. 33: 2559-
2565, 1980.

The strong correlation between elevated terol by increasing LDL cholesterol (7, 8).
plasma cholesterol levels and coronary heart Recent reports show that both the prevalence
disease has led to several metabolic studies and incidence of coronary heart disease are
that have related plasma cholesterol levels in inversely correlated with HDL cholesterol (9,
adult humans to dietary cholesterol and type 10). As elevation of plasma cholesterol may
of dietary fat. In general, increasing dietary be the result of an increase in HDL-choles-
cholesterol from about 200 to 1000 mg/day terol the hypercholesterolemic effect of die-
will produce a 15 to 30% elevation of plasma tary cholesterol and saturated fat could be in
cholesterol (1, 2). Increments in saturated part produced by an increase in HDL-choles-
fatty acids in the diet elevate plasma choles-
terol levels and polyunsaturated fatty acid
Supported in part by a grant from the Nova Scotia
tend to lower them (3, 4). The response of
Heart Foundation, United States Public Health Service
plasma cholesterol to dietary cholesterol and Grant HL-14237 (Arteriosclerosis SCOR) HLHV
fat varies considerably among individuals (5, l2157A, and HL 22285 from the Lipid Metabolism
6). Branch, NHLBI.
2 Associate Professor, Department of Medicine, Dal-
Changes in serum lipids induced by high
housie University, 5849 University Avenue, Halifax,
cholesterol and saturated fat diets are usually Nova Scotia, Canada, B3H 4H7. Author to whom reprint
measured in terms of serum total cholesterol requests should be addressed. Nutritionist, Diabetes
and triglycerides. Since the serum total cho- Day Care Centre, Victoria General Hospital,
lesterol reflects the cholesterol derived from Halifax. Research Associate Professor, Department
of Medicine and Laboratory Director, Northwest Lipid
low-density lipoprotein (LDL), very low-den-
Research Clinic, University of Washington, Seattle,
sity lipoprotein (VLDL), and high-density Washington. J. J. A. is an Established Investigator of the
lipoprotein (HDL), changes in the distribu- American Heart Association. Director, Cardiovas-
tion of cholesterol in these lipoprotein classes cular Research Institute and Professor, Department of
Medicine, University of California, San Francisco, Cal-
are not evident when only total cholesterol is
ifornia. 6 Research Instructor, Northwest Lipid Re-
used as the index of change. However, it is search Clinic, University of Washington, Seattle, Wash-
generally accepted that dietary cholesterol ington. Post Doctoral Fellow, Cardiovascular Re-
and saturated fat elevate total plasma choles- search Institute, San Francisco, California.

The American Journal of Clinical Nutrition 33: DECEMBER 1980, pp. 2559-2565. Printed in U.S.A. 2559
2560 TAN ET AL.

terol. The effect of dietary cholesterol on Methods

HDL-cholesterol varies among mammalian
Subjects (Table 1)
species. Cholesterol feeding reduced HDL-
Six healthy adults, two males and four females, par-
cholesterol in the rat (11) and Rhesus monkey
ticipated in the study. They were young (mean age =
(12), produces no significant change in the 31.2 years) and nonobese (mean percentage ideal weight
chimpanzee (13), swine (14), and dogs (15), = 92.3%, Metropolitan Life Insurance Company Tables,
and increases it in the squirrel monkey (13). 1959). None had clinical or biochemical evidence of
In man, little information is available on the cardiac, hepatic, renal, or endocrine disease. No medi-
cations were given during the study period. The subjects
effect of a diet high in cholesterol and satu-
were nonsmokers. All subjects were normolipidemic (se-
rated fat on serum HDL-cholesterol. The rum cholesterol = 168.5 13.0 mg/dl, serum triglyceride
present study is designed to show the effect = 67.5 7.5 mg/dl (mean SEM)). Informed consent
of such a diet in humans on serum HDL- was obtained from each subject.
cholesterol and apo A-I, the major apoprotein
of HDL. Diets and design of study (Table 2)

Cholesterol feeding in miniature swine The study was conducted over a 5-week period and
(14), dogs (15), rabbits (16), and monkeys done on an outpatient basis with each subject continuing
his/her regular activity.
Before beginning the study each
(17) resulted in a hypercholesterolemia with

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subjects caloric intake
was assessed by a 7-day dietary
a distinctive hyperlipoproteinemia and the record. Two isocaloric
diets were then designed for each
subsequent development of atherosclerosis. subject. One diet had a low cholesterol and high poly-
Among the plasma lipoproteins induced by unsaturated fat content whereas the other had a high
cholesterol feeding are fl-migrating VLDL cholesterol, high saturated fat content. The composition
(percentage protein, fat, and carbohydrate) was other-
and a lipoprotein of a-mobility which is re- wise similar. The subjects maintained their regular diet
ferred to as HDLC. Both of these fractions during the 1st week and then consumed the prescribed
contain large amounts of the arginine-rich low cholesterol, high polyunsaturated fat diet during the
apoprotein (apo E) but only the $-VLDL 2nd week. During the next 3 weeks they consumed the
contain the B-apoprotein (apoB). The present prescribed high cholesterol, high saturated fat diet.
Throughout the study the subjects were weighed weekly.
study also examines the effect of a high cho- Subjects were selected on the basis of their under-
lesterol and saturated fat diet on serum apo standing of the dietary principles and their motivation to
E levels in humans. adhere to the prescribed diets. Each subject was individ-

TABLE 1
General characteristics of subjects

Subject Sex Age Percentage ideal wt Seru m cholesterol Serum triglycerides

yr nig/dt mg/dt

A M 34 86 214 98
B F 35 91 186 55
C F 26 92 154 59
D F 33 88 179 50
E M 33 99 157 81
F F 26 98 121 62

TABLE 2
Composition of diets (mean SEM)

Percentage of total cal

Diet Total cal P/S Cholesterol
Protein Fat Carbohydrate
mg/day

Regular 1945 103 15.8 1.0 32.5 1.4 51.7 1.7 0.53 0.06 232.5 32.1

Low cholesterol
Actual 1897 45 16.3 0.2 37.7 0.3 46.0 0.3 1.60 0.01 97.5 1.5
Prescribed 1981 16 39 45 1.6 100

High cholesterol
Actual 2036 16 16.8 0.2 39.5 0.2 43.7 0.2 0.14 0.01 1021.0 2.3
Prescribed 2063 17 40 43 0.14 1028
 HIGH CHOLESTEROL ON HDL-CHOLESTEROL 2561

ually counselled by the dietitian who was available at all for apo E in VLDL by this radioimmunoassay technique
times for consultation. In addition the dietitian discussed and that obtained by the method of Kane et al. (23).
dietary details with each subject at weekly intervals. Statistical analysis of the data was by paired t analysis
Food scales were provided and each subject weighed with each subject serving as his/her own control. Two
his/her food portions. Mixed natural foods were used comparisons were made. The effect of the low choles-
and a list of necessary groceries (with brand names) were terol, high polyunsaturated fat diet was evaluated using
provided. Mixed dishes were not permitted as it would the serum lipid and apoprotein levels at the end of the
then by difficult to estimate their carbohydrate, protein, regular diet period as control. The effect of the high
fat, and cholesterol content. Although all subjects con- cholesterol, high saturated fat diet was evaluated using
sumed little alcohol in their daily life, alcohol was not the serum lipid and apoprotein levels at the end of the
permitted during the study period. The actual menu for low cholesterol, high polyunsaturated fat diet period as
each meal of each day of the week for the low cholesterol, control.
high polyunsaturated fat diet and high cholesterol, high
saturated fat diet periods was provided. The subjects
Results
were instructed and kept a dietary diary of each meal
during the entire study. Dietary composition of food
ingested for each period was calculated using the ex- Dietary compliance (Table 2)
change system of food assessment; standard food tables All subjects adhered closely to their pre-
(18) were used to calculate the average cholesterol con-
scribed diets, as evidenced by the closeness of
tent of the diets. Adherence to the prescribed diet was
their actual food intake and their prescribed

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assessed by comparing the data of the actual food intake
(as recorded in the dietary diary) with those of the diet. The two prescribed diets were similar in
prescribed diet. total calories and the percentage composition
of protein, fat, and carbohydrate. The major
Laboratory procedures
differences were the P/S fatty acid ratio and
Blood samples for lipoprotein fractionation and lipid
the daily cholesterol intake. The increase in
and apoprotein measurements were obtained after the
subjects had fasted overnight (12 to 14 hr) after 1 week cholesterol content was provided mainly by
of the regular diet, I week of the low cholesterol diet, eggs. During the study period there was no
and after 2 and 3 weeks of the high cholesterol diet. significant change in the weight of the group
Cholesterol and triglyceride in serum and cholesterol
(127.0 6.1 lbs (mean SEM) at the begin-
in each hipoprotein fraction were assayed by the Tech-
nicon Auto Analyzer method (19). HDL-cholesterol was
ning of the low cholesterol diet period and
measured in the supernatant serum after precipitating 127.3 6.2 lb at the end of the high choles-
hipoproteins containing apo B with heparin and man- terol diet period).
ganese as outlined by the Lipid Research Clinics Manual
of Laboratory Operations (19). This method may also Total serum lipids and lipoproteins (Tables 3
precipitate some HDLC that might have been formed.
and 4)
Serum hipoprotein fractionation was by preparative ul-
tracentrifugation at a background density of 1.006 g/ml Serum cholesterol decreased in four sub-
(20). Recovery of hipoproteins as estimated from the sum jects and increased slightly in two subjects
of the cholesterol concentrations of the top and bottom
during the week of the low cholesterol, high
fractions was 98.7 1.0% (mean SEM, n = 24). Serum
apo A-I was measured by the method of Albers et al
polyunsaturated fat diet. Serum cholesterol
(21). Serum apo E was measured by a modification of increased in all six subjects during the 3 weeks
the method of Fainaru et al. (22). Human apo E was of high cholesterol and saturated fat diet. The
purified from the VLDL of patients with dysbetalipopro- increases in the 2nd (21.5%) and 3rd (23.3%)
teinemia. Antibodies to purified apo E was raised in
weeks were significant. Total serum triglyc-
rabbits. The antiserum did not react with any other
known apoproteins in VLDL and HDL. There was erides did not change significantly.
excellent agreement obtained (r> 0.9) between the value At the end of 1 week of low cholesterol,

TABLE 3
Effect of dietary cholesterol and fat saturation on serum cholesterol and
triglyceride levels (values in mg/dl, mean SEM)

Type of diet

Regular Low High High

Serumcholesterol 168.5 13.0 153.2 11.1 185.8 15.7 192.515.7

Serum triglycerides 67.5 7.5 49.5 5.2 47.3 6.1 53.3 8.2

P < 0.05 compared with regular diet. Ii P < 0.005 compared with low cholesterol diet. P < 0.0025
compared with low cholesterol diet.
2562 TAN ET AL.

high polyunsaturated fat diet there was no cantly different from that at the end of the
significant change in LDL-cholesterol and regular diet period (1.70 0.3). The ratio
HDL-cholesterol. However, VLDL-choles- after 2 and 3 weeks of high cholesterol and
terol fell significantly. Increases in LDL-cho- saturated fat diet was 1.69 0.35 and 1.58
lesterol and HDL-cholesterol were significant 0.33, respectively. The latter was signifi-
after the 2nd and 3rd week of the high cho- cantly reduced (P < 0.05) when compared
lesterol and saturated fat diet. The increases with the initial value.
in LDL-cholesterol and HDL-cholesterol
after the 3rd week were 15.0 5.3% (mean Serum apo A-I and apo E (Table 5)
SEM) and 29.9 7.8%, respectively. The Serum apo A-I increased in five of the six
increase in VLDL-cholesterol (59.7 19.1%) subjects after 2 and 3 weeks of the high
was significant only after the 3rd week. cholesterol, saturated fat diet. The increase
At the end of 1 week of low cholesterol, was significant only after the 3rd week of the
high polyunsaturated fat diet the LDL-cho- high cholesterol, saturated fat diet. The serum
lesterol/HDL-cholesterol ratio for the group HDL-cholesterol/apo A-I molar ratio in-
was 1.78 0.34 (mean SEM), not signifi- creased from 31.6 2.5 (mean SEM) when

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TABLE 4
Effect of dietary cholesterol and fat saturation on
serum lipoprotein cholesterol levels

LDL-cholesterol HDL-cholesterol vLDL-cholmterol

Subject
Reg Low High High Reg Low High High Reg Low High High

mg/dt mg/dt mg/dt

A 135 136 169 165 50 42 53 53 26 9 18 19

B 98 92 120 113 64 44 65 70 15 7 12 15
C 94 89 99 82 49 57 59 70 12 13 18 22
D 107 83 91 106 59 52 61 76 14 17 14 20
E 81 87 88 94 53 59 70 64 23 13 13 13
F 45 44 47 52 64 60 73 70 18 13 7 20

Mean 93.3 88.5 102.3 102.0 56.5 52.3 63.5 67.2 18.0 12.0 13.7 17.8
SEM 12.2 11.9 16.5 15.4 2.8 3.2 3.0 3.2 2.2 1.4 1.7 1.5

P <0.05 <0.05 <0.005 <0.005 <0.05 <0.01

After 1 week of low cholesterol, high polyunsaturated fat diet. Comparison with regular diet. After 2
weeks of high cholesterol, saturated fat diet. Comparison with low cholesterol, high polyunsaturated fat diet. After
3 weeks of high cholesterol, saturated fat diet. Comparison with low cholesterol, high polyunsaturated fat diet.

TABLE 5
Effect of dietary cholesterol and fat saturation on
serum apo E and apo A-I levels

Se rum apo E Se rum apo A-I

Subject
Reg Low High High Reg Low High High

mg/dI mg/dt

A 7.2 4.1 5.3 6.2 118 124 126 138

B 3.0 3.2 3.5 3.0 126 124 135 145
C 1.7 1.6 1.6 1.7 138 130 122 138
D 6.3 3.1 4.1 4.1 127 124 127 123
E 3.0 3.3 3.3 4.0 89 103 127 134
F 5.1 5.3 7.2 4.6 126 131 139 133

Mean 4.4 3.4 4.2 3.9 120.7 122.7 129.3 135.2

SEM 0.9 0.5 0.8 0.6 6.9 4.1 2.6 3.0

P <0.05
a After 2 weeks of high cholesterol, saturated fat diet. b After 3 weeks of high cholesterol, saturated fat
diet. Statistical analysis as in Table 3.
 HIGH CHOLESTEROL ON HDL-CHOLESTEROL 2563

the subjects were on the low cholesterol, high to show a concomitant decrease in HDL-cho-
polyunsaturated fat diet to 36.0 1.3 and lesterol (28, 29), whereas other have found
36.6 2.3 after 2 and 3 weeks of high cho- that a reduction of HDL-cholesterol contrib-
lesterol, saturated fat diet. The increase after utes to this lowering of serum cholesterol (30,
2 weeks was significant (P < 0.025) whereas 31). Recently, Shepherd et al. (31) showed
that after 3 weeks was not by paired t test. that when compared with the saturated fat
There was no significant change in the diet (P/S ratio = 0.25), a polyunsaturated fat
serum apo E levels. After 2 weeks of the high diet (P/S ratio = 4.0) reduced plasma choles-
cholesterol, saturated fat diet serum apo E terol by affecting the cholesterol in HDL
increased in four subjects and did not change (33%), LDL (20%), and VLDL (25%).
in two subjects. After the 3rd week, the level Only a few studies of the effect of a dietary
increased in four and fell in two subjects. cholesterol and P/S fatty acid ratio on serum
apoprotein levels are available. The present
Discussion study shows that a high cholesterol, saturated
fat diet increases serum apo A-I together with
In this study the serum cholesterol levels of HDL-cholesterol. Shepherd et al. (31) showed
normolipidemic subjects were increased both that a high polyunsaturated fat diet decreased

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as the consequence of increasing the choles- serum apo A-I together with HDL-choles-
terol content of the diet and decreasing the terol. However, Applebaum-Bowden et al.
P/S fatty acid ratio. The elevation of serum (25) showed that a high cholesterol diet (with
cholesterol was the result of an increase in P/S ratio constant) did not increase serum
cholesterol in all the major lipoprotein classes apo A-I and HDL-cholesterol. The differ-
(VLDL = 59.7%, LDL = 15.0%, and HDL ences between the design of their study and
= 29.9%). Our findings are comparable to the present one have been discussed above.
those recently reported by Mistry et al. (24), Other dietary factors affect serum apo A-I
namely the most marked relative percentage levels. A high carbohydrate, fat-free diet (80%
change was seen in the VLDL whereas the carbohydrate and 20% protein) also decreases
LDL-cholesterol and HDL-cholesterol serum apo A-I levels (32).
changed by 14 and 19%, respectively. How- In animals cholesterol feeding induces an
ever, Mistry et al. did not state whether the increase in apo E in fl-VLDL and HDLC (14,
P/S fatty acid ratio of their diet was altered 15). In the present study a high cholesterol,
in addition to the increase in daily cholesterol saturated fat diet caused no significant
intake. Recently Applebaum-Bowden et al. change in serum apo E. Others have reported
(25) reported that cholesterol feeding in three that increasing the cholesterol content of a
normolipidemic subjects resulted in a hyper- liquid formula diet did not affect the serum
cholesterolemia due primarily to an increase apo E level (25). However, increasing the
in LDL-cholesterol, with little change in cholesterol content of a natural diet appeared
HDL-cholesterol and VLDL-cholesterol. to increase the apo E content in VLDL (24).
Their study differed from the present one in The lack of change in apo E in the present
that a liquid formula diet was used, the daily study may be partly due to measurement of
cholesterol intake was extreme (5000 mg/ apo E in whole serum, thereby failing to
day) and the P/S fatty acid ratio was kept detect changes in apo E in specific lipoprotein
constant at 0.5. Mahley et al. (26) recently (VLDL or HDL) fractions. However, it ap-
reported cholesterol feeding produced no pears that humans do not respond to choles-
consistent change in total HDL-cholesterol. terol feeding with large increases in serum
However, there was an increased ability to apo E levels.
displace 25I-LDL from the LDL receptor The present study was designed to use
(26). mixed natural foods normally consumed by
It is well known that the substitution of humans and to study the handling of com-
polyunsaturated fat for saturated fat in the monly eaten amounts of cholesterol. This
diet lowers serum cholesterol. The choles- necessitated the simultaneous change of at
terol-lowering effect has been shown to result least two variables-dietary cholesterol con-
mainly from a decrease in serum LDL-cho- tent and the P/S fatty acid ratio of the diet.
lesterol (27). Some investigators have failed Whether dietary cholesterol intake alone in
 2564 TAN ET AL.

natural foods affects HDL-cholesterol re- References

mains to be established. Other dietary factors
1. CONNOR, W. E., R. E. HODGES AND R. E. BLEILER.
are known to affect HDL-cholesterol. A high The serum lipids in men receiving high cholesterol
carbohydrate diet has been shown to decrease and cholesterol-free diets. J. Clin. Invest. 40: 894,
HDL-cholesterol (32, 33). The carbohydrate 1961.
content of our two diets was closely similar. 2. MATTSON, F. H., B. A. ERICKSON AND A. M. KLING-
MAN. Effect of dietary cholesterol on serum choles-
Moderate alcohol intake, increased physical
terol in man. Am. J. Chin. Nutr. 25: 589, 1972.
activity, and weight loss (in obese hyperlipi- 3. KEYS, A., J. T. ANDERSON AND F. GRANDE. Serum
demic subjects) raise serum HDL-cholesterol cholesterol response to changes in diet. I. Iodine
(34, 36). In the present study these are not value of dietary fat verses 2S-P. Metabolism 14: 747,
important factors as our nonobese subjects 1965.
4. HEGSTED, D. M., R. B. MCGRANDY, M. L. MYERS
did not consume alcohol, increase their phys-
AND F. T. STARE. Quantitative effects of dietary fat
ical activity, or lose weight during the study on serum cholesterol in man. Am. J. Chin. Nutr. 17:
period. Finally four of these subjects were 281, 1965.
females. When they were on the high choles- 5. QUINTAO, E., S. M. GRUNDY AND E. H. AHRENS, JR.
Effects of dietary cholesterol on the regulation of
terol, saturated fat diet their LDL-cholesterol
total body cholesterol in man. J. Lipid Res. 12: 233,
and HDL-cholesterol increased after the 2nd

Downloaded from ajcn.nutrition.org by guest on June 26, 2015

1971.
and 3rd week. These changes could not be 6. NESTEL, P. J., AND A. POYSER. Changes in cholesterol
accounted for by the concomitant changes of synthesis and excretion when cholesterol intake is
lipoproteins with various phases of the men- increased. Metabolism 25: 1591, 1971.
7. BRONTE-STEWART, B., A. ANTONIS, L. EALES AND J.
strual cycle as described by Kim and Kalk-
F. BROCK. Effects of feeding different fats on serum-
hoff(37). cholesterol level. Lancet 1: 521, 1956.
It has been pointed out that the use of 8. NESTEL, P. J., N. HAVENSTEIN, Y. HOMMA, T. W.
polyunsaturated fats to reduce serum choles- SCorr AND L. J. CooK. Increased sterol excretion
with polyunsaturated-fat, high cholesterol diets. Me-
terol must take the reduction of HDL-choles-
tabolism 24: 189, 1975.
terol into consideration (31). The present 9. GORDON, T., W. P. CASTELLI, M. C. HJORTLAND, W.
study shows that a high cholesterol, saturated B. KANNEL AND T. R. DAWBER. High density hipo-
fat diet raises HDL-cholesterol. However, it protein as a protective factor against coronary heart
is important to note that both LDL-choles- disease. The Framingham study. Am. J. Med. 62:
707, 1977.
terol and VLDL-cholesterol are also in-
10. MILLER, N. E., 0. H. F#{216}RDE, D. S. THELLE AND 0.
creased as a result of the diet. Other studies D. Mi#{248}s.The Troms#{248} heart study. High density
have demonstrated that such a diet increases lipoprotein and coronary heart-disease: a prospective
apo B which is believed to be atherogenic case-control study. Lancet 2: 965, 1977.
(25). Although the LDL-cholesterol/HDL- 11. LASSER, N. L., P. S. ROHEIM, D. EDELSTEIN AND H.
A. EDER. Serum hipoproteins of normal and choles-
cholesterol ratio decreased, the change is terol-fed rats. J. Lipid Res. 14: 1, 1973.
small. Both values are within the normal 12. KUEHL, K. S., P. S. ROHEIM, H. WOLINSKY AND H.
range and its significance is not known. A. EDER. Serum hipoproteins in normal and choles-
Our data are preliminary. Further studies terol fed monkeys. Circulation 50: III 94, 1974.
13. SRINIVASAN, S. R., B. RADHAKRISNAMURTHY, C. C.
are needed in larger groups of individuals
SMITH, R. H. WOLF AND G. S. GERENSON. Serum
whose initial serum lipoprotein levels vary lipid and hipoprotein responses of six human primate
over a wide range and also to determine species to dietary changes in cholesterol levels. J.
whether the changes described in this study Nutr. 106: 1757, 1976.
will occur just as rapidly if a longer control 14. MAHLEY, R. W., K. H. WEISGRABER, T. INNERARITY,
H. B. BREWER, JR. AND 0. ASSMANN. Swine lipopro-
period of low cholesterol, low saturated fat
teins and atherosclerosis. Changes in the plasma
diet is used. It will also be important to hipoproteins and apoproteins induced by cholesterol
establish whether the effects of a high choles- feeding. Biochemistry 14: 2817, 1975.
terol and saturated fat diet observed in this 15. MAHLEY, R. W., K. H. WEISGRABER AND T. INNER-
ARITY. Canine hipoproteins and atherosclerosis. II.
study are maintained over longer periods of
Characterization of the plasma hipoproteins associ-
time and are reversible when the diets are ated with atherogenic and nonatherogenic hyperhip-
reversed. U idemia. Cir. Res. 35: 722, 1974.
16. SHORE, V. 0., R. SHORE AND R. 0. HART. Changes
in apolipoproteins and properties of rabbit very low
The authors thank Donna Hutchison and Wayne density lipoproteins on induction of cholesterolemia.
MacIntosh for expert technical assistance. Biochemistry 13: 1579, 1974.
 HIGH CHOLESTEROL ON HDL-CHOLESTEROL 2565

17. EDELSTEIN, C., 0. FLESS, R. WISLER AND R. SCANU. ANGELINETrA, P. EMIsarr AND S. FURNISS. The
Isolation and properties of a 33,000 dalton polypep- effect of a low-cholesterol, high-polyunsaturate diet
tide from hyperlipemic sera of rhesus monkey: ar- on serum lipid levels, apolipoprotein B levels and
ginine-rich peptide or not? Circulation 50: III 113, triglyceride fatty acid composition. Atherosclerosis
1974. 27: 465, 1977.
18. FEELEY, R. M., P. E. GRINER AND B. K. WATT. 28. SPRITZ, N., AND M. A. MI5HIutL. Effects of dietary
Cholesterol content of foods. J. Am. Dietet. Assoc. fats on plasma lipids and lipoproteins: a hypothesis
61: 134, 1972. for the lipid-lowering effect of unsaturated fatty
19. Lipid Research Clinics Program Manual of Labo- acids. J. Chin. Invest. 48: 78, 1969.
ratory Operations. Washington, D.C.: Department 29. FARQUHAR, J. W., AND M. SOKOLOW. Response of
of Health, Education, and Welfare Publication N1H serum lipids and lipoproteins of man to beta-sitos-
75-628, 1974. terol and safflower oil. Circulation 27: 890, 1958.
20. HAVEL, R. J., H. A. EDER AND J. H. BRAGDON. The 30. NICHAMAN, M. Z., C. C. SWEELEY AND R. E. OLSON.
distribution and chemical composition of ultracen- Plasma fatty acids in normolipemic and hyperhipi-
trifugally separated hipoproteins in human serum. J. demic subjects during fasting and after linoleate
Chin. Invest. 34: 1345, 1955. feeding. Am. J. Chin. Nutr. 20: 1057, 1967.
21. ALBERS, J. J., P. W. WAHL, V. 0. CABANA, W. R. 31. SHEPHERD, J., C. J. PACKARD, J. R. PATSCH, A. M.
HAZZARD AND J. J. HoovltR. Quantitation of apo- Gorro, JR. AND 0. D. TAUNTON. Effects of dietary
hipoprotein A-I of human plasma high density hipo- polyunsaturated and saturated fat on the properties
protein. Metabolism 25: 633, 1976. of high density hipoproteins and the metabolism of

Downloaded from ajcn.nutrition.org by guest on June 26, 2015

22. FAINARU, M., R. J. HAVEL AND K. IMAIZUNI. Ra- apolipoprotein A-I. J. Clin. Invest. 62: 1582, 1978.
dioimmunoassay of arginine-rich apohipoproteins of 32. SCHONFELD, 0., S. W. WEIDMAN, J. L. WITZTUM
fat serum. Biochim. Biophys. Acta 490: 144, 1977. AND R. M. BOWEN. Alterations in levels and inter-
23. KANE, J. P., T. SATA, R. L. HAMILTON AND R. J. relations of plasma apolipoproteins induced by diet.
HAVEL. Apoprotein composition of very low density Metabolism 25: 261, 1976.
hipoproteins of human serum. J. Clin. Invest. 56: 33. LEVY, R. I., R. S. LEES AND D. S. FREDRICKSON. The
1622, 1975. nature of pre-beta (very how density) hipoproteins. J.
24. MISTRY, P., A. NICOLL, C. NIEHAUS., I. CHRYSTIE, Chin. Invest. 45: 63, 1966.
E. JANUS, H. STRAIN AND B. LEWIS. Effects of dietary 34. MISHKEL, M. A. Alcohol and alpha-hipoprotein cho-
cholesterol on serum lipoproteins in man. Protides lesterol. Ann. Internal Med. 81: 564, 1974.
Biol. Fluids 25: 349, 1977. 35. WooD, P. D., W. HASKF.LL, H. KLEIN, S. LEWIS, M.
25. APPLEBAUM-BOWDEN, D., W. HAZZARD, J. CAIN, M. P. STERN AND J. W. FARQUHAR. The distribution of
CHEUNG, R. KUSHWAHA AND J. ALBERS. Short-term plasma hipoproteins in middle-aged male runners.
egg yolk feeding in humans. Increase in apohipopro- Metabolism 25: 1249, 1976.
tein B and low density hipoprotein cholesterol. Ath- 36. WILSON, D. E., AND R. S. Lans. Metabolic relation-
erosclerosis 33: 385, 1979. ships among the plasma hipoproteins. Reciprocal
26. MARLEY, R. W., T. L. INNERARITY, T. P. BERSOT, A. changes in the concentrations of very low and low
LIPSON AND S. MARGOLIS. Alteration in human high density hipoproteins in man. J. Clin. Invest. 51:1051,
density hipoproteins, with or without increased 1972.
plasma cholesterol, induced by diets high in choles- 37. KIM, H. J., AND R. K. KALKHOFF. Changes in lipo-
terol. Lancet 2: 807, 1978. protein composition during the menstrual cycle. Me-
27. DURRINGTON, P. N., C. H. BOLTON, M. HARTOG, R. tabolism 28: 663, 1979.