plasma cholesterol-predictive equations demonstrate that ... · urated fatty acids (mufas) had no...

Am J Clin Nutr 1995;61:1129-39. Printed in USA. © 1995 American Society for Clinical Nutrition 1129

Plasma cholesterol-predictive equations demonstrate thatstearic acid is neutral and monounsaturated fatty acids arehypocholesterolem ic1 �

Shaomei Yu, Janice Derr, Terry D Etherton, and PM Kris-Etherton

ABSTRACT In the present study we used regression anal-yses to evaluate the effects of stearic acid (18:0) on total

cholesterol (IC), low-density-lipoprotein-cholesterol (LDL-C),

and high-density-lipoprotein-cholesterol (HDL-C) concentra-tions (rnrnol/L). Using data from 18 articles, we developed thefollowing predictive equations (monounsaturated fatty acids,MUFAs; polyunsaturated fatty acids, PUFAs): �TC =

0.0522�12:0-16:0 - 0.0008M8:0 - 0.0124 �MUFA -

0.0248 i�PUFA; t�LDL-C = 0.0378z�12:0-16:0 +

0.0018M8:0 - 0.0178z�MUFA - 0.0248z�PUFA; �HDL-C= 0.0160M2:0-16:0 - 0.0016M8:0 + 0.0101�MUFA +

0.0062L�PUFA. Our analyses revealed that unlike the otherlong-chain saturated fatty acids (SFAs), steanic acid had no

effect on IC and lipoprotein cholesterol concentrations in men

and women. MUFAS elicited an independent hypocholester-

olemic effect that we believe is due to the small amount of

12:0-16:0 in the experimental diets evaluated. The observation

that steanic acid has unique effects on IC, LDL-C, and HDL-C

provides additional compelling evidence that it be distin-

guished from the other major SFAS in blood cholesterol pre-

dictive equations. Am J Clin Nutrl99S;61:1 129-39.

KEY WORDS Saturated fatty acids, polyunsaturated fattyacids, monounsaturated fatty acids, steanic acid, plasma totalcholesterol, high-density-lipoprotein cholesterol, low-density-

lipoprotein cholesterol

Introduction

The quantitative responsiveness of plasma lipids to dietary

fat and cholesterol was first reported by Keys et al (1, 2) andHegsted et al (3) “�‘30 y ago. Both groups developed predictive

equations using regression analysis of data collected from

feeding experiments conducted mostly with middle-aged men.The effects of diet on different lipoprotein classes [eg, low-

density-lipoprotein-cholesterol (LDL-C) and high-density-li-

poprotein-cholesterol (HDL-C) concentrations] were not as-sessed in early studies, nor were sex effects examined.

Recently, Mensink and Katan (4) and Hegsted et al (5) devel-

oped regression equations to predict dietary responsiveness of

total cholesterol, LDL-C, and HDL-C in both men and women.

Because all of the major long-chain saturated fatty acids(SFAs) in the diet were grouped together in the latter studies,

it is not possible to examine the specific effects of stearic acid

on total and lipoprotein cholesterol concentrations. The early

investigations, however, reported that steanic acid (18:0) was

not hypercholesterolemic compared with the other long-chain

SFAs. More recently we suggested (based on a limited data set)that steanic acid has a cholesterolernic effect that is cleanly

different from that of other long-chain SFAs (6). Despite the

consistent findings over the years that steanic acid is a unique

long-chain SFA, it is still frequently grouped with other SFAs

in both individual diet studies, as well as in studies designed to

develop serum cholesterol predictive equations.

Earlier meta-analysis equations suggested that monounsat-urated fatty acids (MUFAs) had no effect on plasma cholesterol

concentrations (1-3). However, clinical studies consistently

showed that diets rich in MUFAs (and low in SFAs) decreased

plasma total cholesterol and LDL-C as much as did diets rich

in polyunsaturated fatty acids (PUFAs) or low-fat, high-canbo-

hydrate diets (7-12). The reason for the discrepancy between

clinical studies and meta-analyses is not clear.

The present study was conducted to more comprehensively

examine the effects of steanic acid, MUFAS, and other fattyacids on total and lipoprotein cholesterol concentrations in both

men and women. We conducted an exhaustive literature searchof controlled feeding studies published between 1970 and 1993in which the effects of dietary fatty acid manipulations on

plasma lipids and lipoproteins were reported. Eighteen studies

were selected that met our inclusion criteria (that data for

dietary steanic acid and other fatty acid classes be reported).

Using these data, we developed new regression equations to

predict the responsiveness of serum lipids and lipoproteins to

individual dietary fatty acids in both men and women.

Methods

Selection of studies

By searching MEDLINE and the references in the papers we

identified, we selected 18 articles published between 1970 and

1 From the Departments of Nutrition, Statistics, and Dairy and Animal

Science, and The Graduate Program in Nutrition, The Pennsylvania State

University, University Park.

2 Supported in part by The Pennsylvania Agricultural Experiment

Station.

3 Address reprint requests to PM Kris-Etherton, Nutrition Department,

The Pennsylvania State University, 5-126 Henderson Building, University

Park, PA 16802.

Received September 12, 1994.

Accepted for publication January 5, 1995.

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1130 YU El AL

where IC is total cholesterol.

1993 that reported the quantity of individual SFAs or steanic

acid (18:0) and the sum of launic (12:0), myristic (14:0), and

palmitic (16:0) acids, and MUFAs and PUFAS of the expeni-

mental diets (10-27). Dietary fat accounted for 30-40% ofenergy intake in all studies, which is representative of the fat

intake in the United States. The following exclusion criteriawere used to select data for analysis: 1) liquid-formula diets

used as experimental diets (28), 2) diets that were specificallyenriched in trans isomers of unsaturated fatty acids because

this was not our principle focus, 3) diets that were enriched in

very-long-chain (n- 3) polyunsaturated fatty acids (fish oil),

and 4) subjects with familial hypercholesterolemia because ofevidence demonstrating that they may respond differently to

diet (16).

Table 1 summarizes the 18 studies used in our analysis.

Briefly, subjects in the studies analyzed were between the ages

of 19 and 65 y (men) and 18 and 55 y (women). They were

healthy and normocholesterolemic (most had baseline plasma

cholesterol concentrations < 5.17 mmol/L, or 200 mg/dL).They were fed controlled, whole-food diets during the exper-imental periods. The 18 studies yielded 67 data points.

Statistical methods

To predict changes in serum total cholesterol, LDL-C, and

HDL-C concentrations in response to changes in fatty acid

intake (as a percentage of total daily energy intake), we devel-oped equations using multiple-regression analysis. Each data

point (total of 67) represented the difference in the composition

of two particular diets and the difference in the mean serum

total cholesterol, LDL-C, and HDL-C concentrations in sub-

jects on each test diet. For example, a parallel design with a

common baseline diet followed by two test diets yielded two

data points (eg, the differences between the baseline diet andeach test diet). When the diet comparisons were made in arandom order and crossover design study with three test dietsthe study yielded three, six, or nine data points depending onsubject classes (men, women, and/or total). When a study with

three test diets provided mean serum cholesterol concentrations

for all subjects, or of only one sex, the study yielded three datapoints that represented the difference between any two groups.

If the study provided mean serum cholesterol concentrations

for both sexes, the study yielded six data points that repre-sented three data points for each sex. If the study provided

mean serum cholesterol concentrations for all subjects (ie, bothsexes) the study yielded nine data points. The data points

(dependent variable data) in the studies represented the changein mean plasma total and lipoprotein cholesterol concentrationsbetween adjacent dietary periods. The change in the fatty acid

composition of the experimental diets was used as diet data

points (independent variable data). Our set of predictor van-

ables was the difference between dietary periods in the corn-

position of 12:0-16:0, 18:0, MUFAs, and PUFAS. The pre-dicted change in serum and lipoprotein cholesterol was

estimated by using the following equation:

z�TC(z�LDL-C, z�HDL-C) = az�12:0-16:0 + bM8:0

+ c�MUFA + dL�PUFA

The coefficients (a, b, c, and 6) were estimated by least-

squares regression. Analysis of residuals was performed to

check the appropriateness of the regression model used.

Three studies (10, 11, 27) provided the quantities of total

SFAS and the sum of 12:0-16:0. Steanic acid was calculated bysubtracting 12:0-16:0 from total SFAs. If studies provided thequantity of individual fatty acids as gram weight units, we

converted the values to percent of energy. We did not includechange in cholesterol intake in our equations because dailycholesterol intakes in each study were similar among treatmentgroups. Some studies did not report LDL-C concentrations (11,

27). In these studies, we estimated LDL-C from the concen-

tration of total cholesterol, HDL-C, and triglyceride by using

the equation of Fniedewald et al (29). All statistical analyses

were carried out by using the SAS software program (30).

Results

Total cholesterol, LDL-C, and HDL-C in all subjects

Table 1 shows the summary of 18 studies (10-27) used in the

present investigation. Seventeen of the studies reported total

cholesterol and yielded 55 data points. Sixteen studies reported

HDL-C and yielded 49 data points. For 17 studies, LDL-Cvalues were reported or could be calculated, which yielded 61

data points. The regression equations developed for predicting

the relationship between total cholesterol, LDL-C, HDL-C, and

fatty acid intake are as follows:

�TC (mmolIL) = 0.0522*M2:0_16:0 - 0.0008M 8:0

- 0.0124**�MUFA - 0.0248*z�PUFA (R2 = 0.90) (1)

[SIC (rng/dL) = 2.02*z�12:0_16:0 � 0.03M8:0

- 0.48**z�MUFA _0.96*��PUFA]

�LDL-C (mmol/L) = 0.0378*M2:0_16:0 + 0.0018z�18:0

- 0.0178*z�MUFA _ 0.0248*z�PUFA (R2 = 0.90) (2)

[L�LDL-C (mg/dL) = 1.46*M2:0_16:0 + 0.0Th18:0

- 0.69*z�MUFA _0.96*z�PUFA]

AHDL-C (mmol/L) = 0.0160*z�12:0_16:0 - 0.0016M8:0

+ 0.0101*z�MUFA + 0.0062*�PUFA(R2 = 0.59) (3)

[L�HDL-C (mg/dL) = 0.62*M2:0_16:0 � 0.06�18:0

+ 0.39*z�MUFA + 0.24*L�PUFA]

*,* *Regression coefficients are significantly different from 0:

*P < 0.05, **� < �

The equations predict the mean change (�) in a particular

lipid or lipoprotein (mmol/L) in response to changes in daily

dietary energy intake of fatty acids. For example, when other

fatty acids remain constant, for every 1 % increase in energy

from 12:0-16:0 fatty acids, total cholesterol is expected toincrease 0.0522 mmol/L, whereas a 1% increase in PUFA

lowers total cholesterol by 0.0248 mmol/L.

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TABLE 1

Summary of well-controlled studies used in the present investigation’

Reference Men Women Age

Study

design TC Test diets

Dietary composition

12:0-16:0 12:0 14:0 16:0 18:0 MUFA PUFA Other

n n y mmol/L % of energy

6 6 21-56 x

8 - 19-32 x

15 34 19-52 x

36 - 22-32 �

4 1 28-67

26 - 27-57

26 30 18-49

21 - 20-65

Premenopausal

0.0

0.4

2.6

1.5

1.5

x 4.68 Palm oil

Olive oil

Sunflower oil

12.3 3.1 13.5

6.3 2.5 21.4

5.8 2.6 12.4

Young � 4.99 Control

Olive oil

Sunflower oil

Young x 4.76 SFA

Oleate

26 30 Young x 5.04 Stearate

Linoleate

17 24 ./ 4.76 American diet

15 24 Step 1 diet

16 26 FA

20 13 22-41 x <5.69 Coconut oil

Palm oil

Olive oil

27 - 30-63 x 4.55-7.32 Habitual

Oleic acid

Palmitic acid

33 26 x 3.10-5.30 Olive oil

Cocoa butter

Soybean oil

Butter

30 27 x Milk chocolate

Cocoa butter

Mix

Butter

18 21-43 x 5.12 Step 1 diet

Walnuts

30 40-65 x

- 0.01 0.1

- 0.01 0.2

- 0.01 0.1

- 0.8 3.5

- 0.4 0.7

- 0.02 0.2

- 0.2 0.7

- 0.8 3.3

- 0.3 0.8

- 0.1 0.2

4.5 1.4 27.2

9.3 11.4 13.2

4.5 1.7 10.1

9.3 4.5 10.1

9.2 10.3 12.1

9.4 11.4 13.3

9.2 10.3 12.3

9.5 4.7 10.4

5.5 2.2 8.8

3.8 1.6 7.4

8.8

9.2

4.8

14.7

x, a crossover study design; TC, total cholesterol; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid;

CHOLESTEROLEMIC EFFECFS OF 18:0 AND MUFA 1131

Harris et al (13; 1983)

McDonald et al (14; 1989)

Mensink and Katan (15;

1990)

Ginsberg et al (12; 1990)

Friday et al ( 16; 1991)

Nestel et al (17; 1992)

Zock and Katan (18; 1992)

Mata et al (19; 1992)

Mensink et al (20; 1992)

Experiment 1

Experiment 2

Experiment 3

Barr et al (21; 1992)

Ng et al (22; 1992)

Nestel Ct al (23; 1992)

Kris-Etherton (24; 1993)

Study 1

Study 2

Sabate et al (25; 1993)

Grande et al (26; 1970)

I ,, parallel study design;

SFA, saturated fatty acid.

27 31

14 15

13 16

25 34

4.97 Control

Vegetable oil

4.42 Mixed fat

Canola oil

Sunflower oil

4.76 Oleic acid

SFA

- American diet

Step I diet

MUFA diet

4.84 Butter

Safflower oil

4.99-7.50 Control 1

Control 2

Blend 1

Blend 2

4.84 Linoleate

Stearate

Cocoa butter

Mixture

Palm oil

Mixture

- - - 7.9 7.1 17.1

- - - 5.0 1.3 11.3

- - 1.3 8.2 4.2 15.0

- - 0.4 3.1 1.1 20.0

- - 0.4 3.9 2.2 7.0

- 0.5 0.5 4.7 3.0 24.1

- 3.4 2.7 8.1 3.5 14.7

- 3.9 2.6 6.9 3.1 11.7

- 0.7 0.9 4.9 2.4 11.0

- 0.8 0.9 5.2 2.3 17.9

- - 3.2 9.3 4.7 10.2

- - 0.1 2.6 1.0 4.5

- 0.1 0.3 14.4 2.8 15.0

- 0.1 0.3 13.8 2.6 15.0

- 0.1 0.2 7.9 4.3 16.0

- 0.0 0.1 6.5 4.9 16.0

- 0.7 0.9 5.8 2.8 15.8

- 0.5 1.0 5.7 11.8 16.6

- 1.2 3.2 9.3 4.1 11.5

- 0.7 1.4 6.8 3.2 15.1

- 0.9 1.3 6.2 3.4 10.8

- 3.4 2.7 8.1 3.5 14.7

- 0.5 0.5 4.7 3.0 24.1

- 0.5 1.0 5.7 11.8 16.6

- 0.7 0.9 5.8 2.8 15.8

- 1.3 1.8 7.4 3.2 14.5

- 0.5 0.9 5.1 2.2 13.2

- 1.0 1.6 6.1 2.8 10.8

- 12.5 5.4 4.9 1.4 3.9

- 0.3 0.5 13.4 1.8 14.0

- 0.1 0.2 6.3 1.9 21.8

- 0.6 2.3 8.4 3.8 11.9

- 0.2 0.6 5.2 2.3 19.0

- 0.3 0.9 9.8 2.3 14.0

- - - 10.1 11.5

- - - 9.9 11.4

- - - 12.8 12.5

- - - 2.4 12.1

7.9

22.9

7.0

10.0

22.0

4.6

3.4

9.7

10.4

10.5

1.6

25.0

6.0

6.0

10.0

11.0

12.5

4.3

3.2

3.3

12.5

4.6

7.9

12.7

3.4

4.6

4.3

12.5

8.0

7.8

6.5

0.9

3.7

2.9

4.0

7.0

8.0

2.3

2.1

17.8

1.7

1.8

2.1

1.7

1.6

9.5

16.5

2.7

2.8

3.6

3.8

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Observed Change In TC (mmoIIL)

1132 YU El AL

TABLE 1 continued

Reference Men Women Age

Study

design TC Test diets

Dietary composition

12:0-16:0 12:0 14:0 16:0 18:0 MUFA PUFA Other

F, n y mmoLfL % of energy

Brussaard et al (27; 1982) 23 12 19-30 / 4.63 Low-fat diet

Medium fat diet

10.0

6.0

-

-

- - 5.0 12.0

- - 2.0 11.0

5.0

11.0

-

-

Mensink and Katan

(11; 1987) 24 24 18-59 / 5.07 Control

Low-fat diet

Olive oil

13.9

4.1

6.8

-

-

-

- - 6.1 12.4

- - 2.6 9.3

- - 3.0 24.0

4.1

5.2

5.1

-

-

-

Mensink and Katan

(10; 1989) 27 31 20-48 / 4.81 Control

Olive oil

Sunflower oil

13.7

8.9

8.4

-

-

-

- - 5.6 11.6

- - 4.0 15.1

- - 4.2 10.8

4.6

7.9

12.7

-

-

-

Based on our equations, SFAS (12:0, 14:0, and 16:0) signif-icantly increased total cholesterol, LDL-C, and HDL-C con-

centrations. Both MUFAs and PUFAS significantly decreased

total cholesterol and LDL-C, whereas both significantly in-

creased HDL-C. 18:0 had no significant effect on any lipid or

lipoprotein concentration.

Figures 1, 2, and 3 show the association between the ob-

served and the predicted changes in total cholesterol, LDL-C,

and HDL-C for equations 1 (data points, n = 55), 2 (n = 61),

and 3 (n = 49), respectively. There was a strong correlation

between the observed and predicted change in plasma total

cholesterol (r = 0.81), LDL-C (r = 0.78) and HDL-C (r =

0.69) when using the equations we generated.

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FIGURE 1. Correlation between the observed and predicted change in

serum total cholesterol (TC) (n = 55 observations). Each point refers to a

specific test diet for one of the studies in Table 1. Predicted values were

calculated for each particular diet from equation 1: L�TC = 0.0522M2:O-

16:0 - 0.0008M8:0 - 0.0124�MUFA - 0.0248�PUFA, where LVFC is

the predicted change in serum TC concentration (mmol/L) as a function of

changes in the percent of energy from dietary fatty acids. The Pearson

correlation coefficient between observed and predicted values (r) is 0.81

(the coefficient of multiple correlation for the equation R = 0.95).

In 14 studies (12-25) the major individual fatty acids in the

experimental diets were reported. These studies yielded 47 data

points that were used to calculate the cholesterolernic effect of

individual fatty acids. One study did not report the total cho-lesterol concentration and two studies did not report theHDL-C concentration. The predictive equations derived for

both sexes are as follows:

A�TC (mmol/L) = 0.0248M2:0 + 0.1443*�14:0

+ 0.0277**M6:0 + 0.01442M8:0 - 0.0044�MUFA

- 0.0171 **�PUFA(R2 = 0.95) (4)

[z�IC (mg/dL) = 0.96�12:0 + 5.58*iM4:0 + 1.07**M6:0

+ 0.55M8:0 - 0.1ThMUFA - 0.66**z�PUFA]

�HDL-C (mmol/L) = 0.0186**z�12:0 + 0.0036z�14:0

+ 0.0072**L\16:0 _0.0039M8:0 + 0.0075**L\MUFA

+ 0.0028**zWUFA(R2 = 0.68) (5)

[z�HDL-C (mg/dL) = 0.72**z�12:0 + 0.14M4:0

+ 0.28**M6:0 _ 0.15�18:0 + 0.29**�MUFA

+ 0.11z�PUFA]

*,* *Regression coefficients are significantly different from 0:

*P < 0.05, **� < �

For the change in total cholesterol, the regression coeffi-

cients of M4:0, M6:0, and L�PUFA were significantly differ-

ent from zero; for �HDL-C, the regression coefficients of

M2:0, M6:0, and �MUFA were significantly different from

zero. The predictive equation for LDL-C was similar to that for

total cholesterol (equation not shown).

Effects offatty acids on total cholesterol, LDL-C, and HDL-

C in men and women

Table 2 presents the linear-regression equations for men andwomen that predict changes in total cholesterol, LDL-C, and

HDL-C in response to changes in fatty acid intake.

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-0.2 0.0 0.2 0.4 0.6 0.8 1.0

Observed Change In LDL-C (mmol/L)

Observed Change In HDL-C (mmolIL)

CHOLESTEROLEMIC EFFED’S OF 18:0 AND MUFA 1133

TABLE 2

Estimated regression coefficients of equations for predicting mean

changes (�) in total cholesterol (TC), LDL, and HDL cholesterol for

men and women

Cholesterol

and sex

CoefficientsData

points

Number

of

studiesM2:0-16:0 M8:0 �MUFA �PUFA

n nL�TC

Men 0.0489’ -0.0018 -0.0137 -0.0274’ 35 13

Women 0.04812 -0.0109 -0.0197 -0.0253 1 1 6

L�LDL

Men 0.0318’ 0.0034 -0.0181’ -0.030’ 33 13

Women 0.03572 -0.0023 -0.0253 -0.0220 15 7

�HDL

Men 0.0142’ -0.0010 0.0091 ‘ 0.0()722 29 12

Women 0.0142’ -0.0083� 0.0080 -0.0021’ 1 1 6

1.2 Significantly different from zero: ‘ P < 0.01, 2 p < 0.05.

3 Significantly different from men for HDL cholesterol, P < 0.01.


serum LDL-cholesterol response (n = 61 observations). The predicted

responses were calculated by using equation 2: �LDL-C = 0.0378M2:0-

16:0 + 0.0018�18:0 - 0.0178 L�MUFA - 0.0248�PUFA. The Pearson



Total cholesterol. Based on the regression equations developed,

12:0-16:0 significantly increased total cholesterol in both men and

women. The regression coefficients of 18:0 for L�TC were not

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serum HDL-cholesterol concentrations (n = 49 observations). The pre-

dicted values were calculated by using equation 3: �HDL-C = 0.0160M2:

0-16:0 - 0.0016M8:0 + 0.0101 L�MUFA + 0.0062L�PUFA. The Pearson



significantly different from zero in both sexes, thus, 18:0 had a

neutral effect on total cholesterol. PUFA decreased total choles-

terol in both men and women, but the regression coefficient wassignificantly different from zero only in men. There was no sig-

nificant sex difference. MUFA decreased total cholesterol in both

men and women; however, the decrease was not statistically sig-

nificant.

LDL-C. The changes in LDL-C were similar to the changes in

total cholesterol. 12:0-16:0 significantly increased LDL-C concen-

trations in both men and women. 18:0 elicited a neutral effect in

both sexes. Both MUFAs and PUFAs decreased LDL-C in both

men and women; however, the decrease was significant only in

men. The LDL-C response to all fatty acid classes between men

and women, however, was not significantly different.

HDL-C. 12:0-16:0 significantly increased HDL-C concentra-

tions in both men and women. MUFA increased HDL-C concen-

trations in both sexes, but the increase was only significant for

men. When 18:0 and PUFAs were dropped from the equation for

women (the regression coefficients for both of them were not

significantly different from zero), the equation for predicting the

changes in HDL-C was as follows:

�HDL-C (mmollL) = 0.0142*M2:0_16:0 + 0.0083**z�MUFA

[L�HDL-C (mg/dL) = 0.55*�12:0_16:0 + 0.32**z�MUFA]

(6)

In this equation, the regression coefficient for MUFAs for

HDL-C was significantly different from zero. PUFAs increased

HDL-C concentrations in men compared with women. The sex

difference was significant (P < 0.001).

Figures 4, 5, and 6 show the mean changes in total choles-

terol, LDL-C, and HDL-C in response to changes in fatty acid

intake (expressed as a percentage of daily dietary energy in-

take) for men and women. In Figure 4, a 1% increase in PUFA

(with other fatty acids remaining constant) lowered total cho-

lestenol by 0.0274 mmol/L in men and 0.0253 mmolfL in

women; in Figure 6, a 1% increase in PUFA raised HDL-C by

0.0072 rnrnol/L, whereas it lowered HDL-C by 0.0021 mmol/L

in women. This sex effect was significant for HDL-C in ne-sponse to PUFA (P < 0.01).

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0C0SSS

01S

0

I-.

�1

S

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A C12-C16 is cii �s MUFA

Fatty AcidsFatty Acids

Discussion

The present study provides additional evidence to support

the position that steanic acid is a unique long-chain SFA. The

primary objective of our study was to evaluate the effects of

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0-JC-J.�

Fatty Acids

1134 YU El AL

FIGURE 4. Comparison of the predicted change in total cholesterol

(TC) response to the change in the percent of energy from fatty acids for

men and women, the equations used were as follows: for men, �TC

0.0489M2:0-16:0 - 0.0018M8:0 - 0.O13ThMUFA - 0.0274�PUFA;

for women, L�TC = 0.0481�12:0-16:0 - 0.0109M8:0 - 0.O19ThMUFA

- 0.O253L�PUFA. No sex effects were observed.

FIGURE 5. Comparison of the predicted change in LDL-C with the

change in the percent of energy from fatty acids for men and women. The

equations used were as follows: for men, �LDL-C = 0.0318M2:O-16:0 +

0.0034M8:0 - 0.0181i�MUFA - 0.030 �XPUFA; for women, i�LDL-C

0.0357M2:0-16:0 - 0.0023M8:0 - 0.0253�MUFA - 0.0220L�PUFA.

Sex effects were not significant.

FIGURE 6. Comparison ofthe predicted change in HDL-C in men with

that in women. The equations used were as follows: for men, �HDL-C =

0.0142M2:0-16:0 - 0.O010�18:O + 0.0O9l�MUFA + 0.0072�PUFA;

for women, L�HDL = 0.0142 �12:0-16:0 - 0.0O83�18:O +

0.0080�MUFA - 0.O021�PUFA. Sex differences were significant for the

responsiveness of serum HDL-C to the change in dietary 18:0 and PUFAs

(* p < o.oi women compared with men).

stearic acid on total and lipoprotein cholesterol concentrations

in women and men. A distinguishing feature of our approach

was that we included only those studies for which we were able

to determine the intake of the principle fatty acid of interest, ie,

steanic acid. As expected, we found that the other long-chain

SFAS (ie, 12:0-16:0) are hypercholesterolemic. Thus, because

stearic acid is cleanly different, we propose that it be distin-

guished from the other long-chain SFAs and not be grouped

with them when estimating the plasma cholesterol response to

changes in dietary SFAs. Whereas Keys et al (1) excluded

steanic acid from their predictive equations, the fact that we

only found 18 studies that separated steanic acid from the other

long-chain SFAS indicates that, for the most part, many scien-

tists have not recognized the importance of considering steanic

acid separately. In addition, although steanic acid had a neutral

effect on total cholesterol and LDL-C and HDL-C in men, our

study suggests that it may lower HDL-C in women. This

observation is significant because it is based on data from 13

studies.

Another point of interest is that MUFAs may have a greater

cholesterol-lowering effect in both men and women than pre-

viously thought. This is based on our observation that the

regression coefficients for total cholesterol and LDL-C were

significantly negative (equations 1 and 2); the magnitude of the

response was half that reported for PUFAs. Furthermore, the

sex effect of PUFAs on HDL-C provides further support for the

hypothesis that there are significant differences between sexes

with respect to the cholesterolemic effects of individual fatty

acids. It will be important to verify these observations withwell-controlled feeding studies.

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CHOLESTEROLEMIC EFFECTS OF 18:0 AND MUFA 1135

Stearic acid

The early evidence (1-3) suggesting that steanic acid does

not raise plasma total cholesterol concentrations was confirmed

in the present study. The regression coefficients for steanic acid

in the present study are not significantly different from zero (P

= 0.3-0.9). When steanic acid is deleted from equations 1, 2,

and 3, the regression coefficients for the nest of the fatty acid

classes do not change as shown below:

�TC (mmolIL) = 0.0522*z�12:0_16:0 - 0.0122**�MUFA

(R2 0.90)

- 0.0243*z�PUFA (7)

[�TC (mg/dL) = 2.03*z�12:0_16:0 � 0.47**�MUFA

�LDL-C (mmol/L) = 0.0372*�12:0_16:0

(R2 0.89)

- 0.94*z�PUFA]

- 0.0184*�MUFA _ 0.0256*z�PUFA (8)

[L�LDL-C (mg/dL) = 1.44*�12:0_16:0 � 0.71*�MUFA

�HDL-C (mmol/L) = 0.0163*M2:0_16:0

(R2 0.59)

- 0.99*zWUFA

+ 0.0101*L�MUFA + 0.0062*�PUFA (9)

[L�HDL-C (mg/dL) 0.63*�12:0_16:0 + 0.39*z�MUFA

+ 0.24*�PUFA]

Our results also agree with the predictive equations of Den

et al (6) that showed that steanic acid is not a hypercholester-

olemic SFA. Interestingly, the latter study reported a signifi-

cantly negative regression coefficient for steanic acid (-0.0181

for mmolfL, or -0.7 for mg/dL) for total cholesterol, which was

similar to that reported by Hegsted et al (3) in 1965 (ie,

-0.0129 for mrnol/L, or -0.5 for rng/dL) yet less than that

reported for PUFAs. It is clear that steanic acid does not

increase plasma total cholesterol and LDL-C concentrations

compared with other SFAs. However, it is not entirely clean

whether steanic acid truly has a neutral effect or whether, in

fact, it may lower cholesterol concentrations, but less so than

do unsaturated fatty acids. It is possible that the significant

cholesterol-lowering effect of steanic acid in the equations of

Denr et al (6) is due to its high quantity in the test diets.

Well-controlled feeding studies and mechanistic investigations

are needed to resolve the actual cholestenolemic effect of

steanic acid. Irrespective of whether steanic acid is neutral or

lowers cholesterol concentrations, sufficient evidence has ac-

cumulated (including that reported herein) to recommend that

it be distinguished from the other long-chain SFAs in blood

cholesterol predictive equations.

Early studies suggested that steanic acid might have a neutral

effect or slightly lower HDL-C. The present study shows that

the effect of steanic acid on HDL-C is affected by sex. The

regression coefficient (which is negative) for 18:0 for HDL-C

is larger for women than for men. Steanic acid appears to have

a neutral effect on HDL-C in men, whereas it appears to lower

HDL-C in women. A lowering effect of steanic acid on HDL-C

was also supported by Denke and Grundy (31) and Bonanome

and Grundy (32), who reported that a liquid-formula diet high

in steanic acid tended to lower HDL-C by 0.06 mmol/L (2.3

mg/dL) compared with a formula diet high in palmitic acid and

by 0.1 mrnol/L (3.9 mg/dL) compared with a formula diet high

in oleic acid (NS). Likewise, Becker et al (33) reported that a

steanate-nich saturated fat diet increased total cholesterol and

LDL-C, whereas it decreased HDL-C when compared withdiets high in MUFAs and PUFAs. In addition, Zock and Katan

(18) found that a stearate-nich diet lowered HDL-C relative to

a linoleate-nich diet (by 0.06 mmol/L, or 2.3 mg/dL, P <

0.001). These results agree with the regression equation re-

ported herein and suggest that relative to other SFAs, and

MUFA and PUFA, steanic acid may lower HDL-C.

Monounsaturated fatty acids

The present study shows that MUFAs significantly decrease

serum total cholesterol and LDL-C and increase HDL-C con-

centrations. As noted, MUFAs were not included in Keys et

al’s equation because they were thought to be a neutral fatty

acid class. We found that MUFAs decreased total cholesterol

and LDL-C, in part, because most of the test diets in the present

study were high in MUFAs. In the studies of Keys et al (2) and

Hegsted et al (3), about one-half of the groups consumed

< 10% of energy as MUFAs (Figure 7). In addition, the test

diets in the present study were significantly higher in steanic

acid and lower in 12:0-16:0 (P < 0.05) (� ± SD: 4.35 ±

3.15% and 9.17 ± 3.83% of energy, respectively) when com-

pared with those reported by Hegsted et al (3) (3.23 ± 2.32%

and 12.38 ± 8.52% of energy, respectively), although the total

quantity of SFAs in both studies was similar (Figure 8).

Based on our results we speculate that the effect of MUFAs

on serum total cholesterol and LDL-C is dependent on the

amount of SFA (and specifically the amount of hypencholes-

terolemic SFA) in the diet. Based on this line of reasoning,

when 12:0-16:0 SFAs in the diet are low, the independent

cholesterol-lowering effect of MUFAs is observed. In contrast,

when 12:0-16:0 SFAs are high, the cholesterol-lowering effect

of MUFAs is obscured, and MUFAs appear to have a neutral

cholesterolernic effect. It must be appreciated that the amount

of SFA in the diet should be viewed in the context of individual

fatty acids. Thus, we believe that it is the amount of 12:0-16:0

SFA in the diet that plays a key role in detenmining thecholesterolernic effect observed for MUFAs. Accordingly, al-

though the amount of steanic acid affects the total amount of

SFA in the diet, because it is not hypencholesterolemic, it doesnot obscure the hypocholesterolemic response to MUFAs.

Thus, we believe that two important conclusions can be drawn

from these findings. First, MUFAs are hypocholesterolernic

(but less so than are PUFAs), as also described by Mensink and

Katan (see below; 4). Second, our results provide further evi-dence to support the argument that steanic acid should not be

grouped with other long-chain SFAs. In agreement with our

findings, animal studies have shown that oleic acid decreases

plasma cholesterol concentrations by increasing hepatic LDL

receptor activity and that stearic acid is neutral (34, 35).

The neutral response to MUFAs reported by the early inves-

tigatons also could be due to the amount of cholesterol in the

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3O� b.K.ysetai (2)UiC

a

C,

I

20

10#{149}

. i�rn . .

4 6 8 10 12 14 16 18 20 22 24 26 28

Percentage of Energy as MUFA in Test Diets

0

I-

iiC

IL

Fatty Acids

1136 YU El AL

FIGURE 7. Relative frequency histograms for the distribution of per-

centage of energy as MUFAS in diets in three studies (counting percentage

of test groups).

FIGURE 8. Comparison of the mean percentage of energy from fatty

acids in the test diets of the present study with that in the test diets of the

study of Hegsted et al (3). In the present study, the test diets are higher in

18:0 and lower in 12:0-16:0 when compared with the study of Hegsted et

al (*P < 0.05).

experimental diets. Hegsted et al (3) reported that olive oil,

coconut oil, and safflower oil were cholesterol-raising when

dietary cholesterol intake was > 300 mg/d. In fact, there was a

linear relationship between serum cholesterol and the dietary

cholesterol concentration with these three fats. In the studies of

both Keys et al (2) and Hegsted et al (3), one-half of the

treatment groups consumed > 400 mg cholesterol/d; the aver-

age cholesterol intake was 520 mg/d (range 280-1 1 10 mg/d)

and 390 mg/d (range 116-686 mg/d), respectively. Thus, di-etary cholesterol was a significant variable in their equations.

The change in cholesterol intake was not included in our

predictive equations because daily cholesterol intake was sim-

ilar among treatment groups in each study. The mean choles-

terol intake in the present study (300 mg/d) was lower than that

in the studies of Keys et al (2) and Hegsted et al (3).In support of our findings, Mensink and Katan (4) also

reported that MUFAs lower total cholesterol as noted by the

following equation: L�TC (mmol/L) = 0.056�S’ - 0.003i�M

- 0.0151�P), where 5’ is the sum of launic plus mynistic plus

palmitic acids, M is monounsaturated fatty acids, and P is

polyunsaturated fatty acids. The observation that inclusion of

MUFAs improves equations for predicting serum cholesterolchanges is supported by the study of Berry et al (7). These

investigations found a discrepancy between the observed

changes and predicted changes in cholesterol concentration

when the Keys et al equation is used after changing the amount

of dietary MUFAs. MUFAs significantly decreased total cho-

lesterol and LDL-C concentrations, although not as much as

PUFAS did. Other studies have reported that MUFAs are aseffective as PUFAs in decreasing the plasma cholesterol con-

centration (36-38).

The present study suggests that MUFAs not only decrease

total cholesterol and LDL-C, but also increase HDL-C in both

men and women. Compared with PUFA-rich or low-fat diets,

MUFA-rich diets have been shown to increase HDL-C (9, 11,

19). Other studies, however, suggest that MUFAs do notchange HDL-C concentrations (7, 12). Thus, with respect to

HDL-C, MUFAs appear to be either neutral or have a slight

raising effect.

Otherfatty acids

Lauric, myristic, and palmitic acids. The present study suggests

that collectively, launic, myristic, and palmitic acids significantly

increase total cholesterol, LDL-C, and HDL-C concentrations.

Furthermore, these SFAS increase total cholesterol twice as much

as PUFAS decrease it, which agrees with the early equations of

Keys et al (1, 2) and Hegsted et al (3) as well as those published

more recently by Mensink and Katan (4) and Hegsted et al (5).

It is important to point out, however, that SFAs are not equally

hypercholesterolemic. For example, previous studies have shown

that medium-chain SFAS of carbon length 8-10 and stearic acid do

not raise plasma cholesterol concentrations (1-3, 32, 39), whereas

lauric, mynistic, and palmitic acids are hypercholesterolemic (39,

40). Results of the present study suggest that myristic acid is five

to six times more hypercholesterolemic than either launic acid or

palmitic acid (Eq 4), which agrees with the studies of Hegsted et

al (3) and Mensink and Katan (4), and that 12:0 may be less

hypercholesterolemic than palmitic acid (26).

Some investigators suggested that the effects of palmitic acid on

serum cholesterol may vary depending on the experimental design

used (22, 41). In hypercholesterolemic subjects (> 5.82 mmol/L)

and especially those consuming diets providing > 400 mg choles-

terol/d, dietary 16:0 may expand the plasma pool, but not innormocholesterolemic subjects consuming diets containing < 300

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mg cholesterol/d (41). However, in the recent study of Zock et al

(42), the cholesterol-raising effect of palmitic acid in the subjects

consuming 350 mg cholesterol/d in the lowest tertile of initial

cholesterol concentration (3.78 mmol/L) was similar to that of

subjects in the highest tertile (5.97 mmol/L). In the present study,

subjects in most studies consumed 300-400 mg cholesterol/d, and

the results show that 16:0 increases total cholesterol, LDL-C, and

HDL-C concentrations. Although the data that suggest that

palmitic acid is not a potent hypercholesterolemic SFA are scant,

this issue nonetheless should be addressed experimentally within

the context of all other major fatty acids in the diet. Additional,

well-controlled clinical studies need to be conducted to evaluate

the cholesterolemic effects of individual fatty acids.

Mensink and Katan (4) and Hegsted et al (5) reported that SFAS

increase HDL-C concentrations which has been confirmed in the

present study. However, the effects of individual SFAs on the

distribution of cholesterol among the various lipoproteins, espe-

cially on HDL-C, are largely unknown. The present study shows

that 12:0 and 16:0 increased HDL-C; 14:0 had no effect. These

findings were supported by other clinical studies (22, 24, 40). Zock

et al (42), however, recently reported that feeding large concen-

trations of myristic acid (53% of total fat) increased HDL-C by 9%when compared with palmitic acid and oleic acid. In this study,

myristic acid concentrations were considerably higher than those

typically provided in experimental diets because synthetic fats

were fed. Thus, because of limited evidence the specific effects of

individual SFAs on HDL-C remain to be established.

Polyunsaturated fatty acids. In the present study we found a

significant negative correlation between PUFAs and total choles-

terol that is similar to that reported by Keys et al (1) and Hegsted

et al (3). The slightly lower regression coefficient reported herein

for PUFAs is explained by two factors: 1) the inclusion of studies

that provided diets higher in MUFAs than those used by the early

investigators, and 2) the inclusion of MUFAs in the regression

equations (which clearly was indicated because of its significant

cholesterolemic effect).

As noted by Mensink and Katan (4), the specific effects of

PUFAs on total and lipoprotein cholesterol concentrations actually

may be slightly less than was previously thought. Taken together

with the data reported for stearic acid, it is clear that the predictive

equations developed are not only dependent on the experimental

diets fed (and the quantities of specific fatty acids fed), but also on

the inclusion of specific fatty acids in the predictive equations.

Despite this, it is still clear that PUFAs lower total cholesterol and

LDL-C concentrations.

In the equations we developed, there was a positive correlation

between PUFAs and the HDL-C concentration for all subjects

(men and women) and men (the equation for women suggested a

neutral effect of PUFAs on HDL-C). This result agrees with the

equations reported by Hegsted et al (5) and Mensink and Katan (4).

Although the regression coefficients for PUFAs are statistically

significant and positive, they are lower than the regression coef-

ficient for 12:0-16:0, indicating a less potent effect. Some studies

reported (36, 43-45) that PUFAs decreased HDL-C concentra-

tions, however, in those studies, the intake of polyunsaturated fat

was very high, and the ratio of polyunsaturated to saturated fatty

acids (P:S) ranged from 2.0 to 6.5. Erickson et al (46) indicated

that with a cholesterol-free formula diet the plasma cholesterol

concentration is unaffected by changes in the P:S of the diet from

0.1 to 1.6. Another study showed that there is no change in the

HDL-C concentration when subjects are shifted from a diet with a

P:S of 0.7 to a diet with a P:S of 1.3 (47). In most of the studies

reviewed herein, the P:S was < 2.0. The present study suggests

that PUFAs do not decrease HDL-C (and may increase it) despite

significantly decreasing total cholesterol and LDL-C.

Sex effects

The results of the present study suggest that the total and

LDL-C response to diet for women and men is quite similar;

however, there appears to be a difference in the HDL choles-

tenol response to diet between women and men. Specifically,

the relationship between z�PUFAs in the diet and �HDL-C is

significantly positive in men, but not in women. These findings

suggest that PUFAs may increase HDL-C concentrations in

men, but not in women. Moreover, 18:0 has an apparent

HDL-C-lowening effect in women when compared with men.

Because of the limited data available, the findings of the effects

of sex on plasma cholesterol and lipoproteins should be inter-

preted cautiously.

Recently, the question about diet responsiveness in men

compared with women was addressed by several different

investigators. Clifton and Nestel (48) suggested that men and

women differ significantly in their response to dietary fat and

cholesterol; women experienced a greater increase in HDL�,

whereas men had a greater LDL response to changes in diet.

Similar results were reported in a 3-wk residential, lifestyle-

modification study, in which male subjects had a greater de-

crease in total cholesterol (24.4% vs 20.8%) and LDL-C (25%

vs 19.4%) concentrations compared with female subjects,

whereas female subjects had a greater decrease in HDL-C than

did male subjects (19.4% vs 11.6%) in response to a high-

complex-carbohydrate, high-fiber, low-fat, and low-cholesterol

diet (49). Jenkins et al (50) also reported that men were more

responsive than women to a diet high in soluble fiber compared

with a diet high in insoluble fiber (both diets were low in

saturated fat); men had a significantly greater reduction in total

cholesterol (7.5% vs 3.4%) and LDL-C (9.6% vs 2.2%). Like-

wise, Zock and Katan (18) found that a diet high in steanic acid

resulted in a larger decrease in total cholesterol and LDL-C in

men than in women. Taken together, all of these studies sug-

gested that total cholesterol and LDL-C are more responsive to

diet in men whereas HDL-C appears to be more responsive in

women. In contrast, Mensink and Katan (10, 1 1) reported a

greater change in HDL in men than in women when SFAS were

removed from the diet.

The apparent sex differences in dietary responsiveness are

intriguing. It is important to note that few investigations have

been conducted to specifically examine dietary responsiveness

in women and men. Nonetheless, although some consistent

differences have been observed between sexes, it is premature

to define the actual diet-sex effects (and differences) on lipids

and lipoproteins. Clearly, although the results of the present

investigation indicate similar effects of diet on total cholesterol

and LDL-C in women and men, further studies are needed to

corroborate these findings, especially because of the inconsis-

tencies reported among other studies. Moreover, because of the

importance of HDL-C as a risk factor for coronary heart

disease for both women and men (51, 52), additional studies

are needed to understand how diet and sex affect HDL-C

concentrations and metabolism.

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1138 YU El AL

32. Bonanome A, Grundy SM. Effect of dietary stearic acid on plasma

cholesterol and lipoprotein levels. N Engl I Med 1988;318:124’4-8.

Summary

In summary, the blood cholesterol predictive equations pre-

sented herein indicate that SFAS (specifically 12:0, 14:0, and

16:0) significantly increase total cholesterol, LDL-C, and

HDL-C concentrations. Steanic acid, in contrast, is a unique

long-chain SFA and does not increase plasma total cholesterol

and LDL-cholestenol concentrations. Because of this we pro-

pose that it be distinguished from the other long-chain SFAS in

plasma cholesterol predictive equations. We believe this isparticularly important given that many investigations group all

of the long-chain SFAs together. Further studies are needed tocorroborate the observation that steanic acid may decrease

HDL-C concentrations in women. PUFAS and MUFAs signif-

icantly decrease total cholesterol and LDL-C concentrations;

PUFAs do not decrease HDL-C concentrations whereas MU-

FAs may increase them. MUFAs elicit less potent cholesterol-

lowering effects compared with PUFAS. We propose that the

variable cholesterolemic effects observed for MUFAs previ-

ously are explained by the relatively high amount of 12:0-16:0

SFAs in the diet, which appears to obscure the MUFA re-

sponse. The predictive equations for men and women indicate

that the total cholesterol and LDL-C responses to diet are

similar for both sexes. Of potential significance is the evidence

that suggests there is a sex difference in responsiveness of

HDL-C to diet. U

References

1 . Keys A, Anderson IT, Grande F. Serum cholesterol response to

changes in the diet: IV. Particular saturated fatty acids in the diet.

Metabolism 1965; 14:776-87.

2. Keys A, Anderson IT, Grande F. Prediction of serum-cholesterol

responses of man to changes in fats in the diet. Lancet 1957;2:959-66.

3. Hegsted DM, McGandy RB, Myers ML, Stare Fl. Quantitative effects

of dietary fat on serum cholesterol in man. Am I Clin Nutr 1965;17:

281-95.

4. Mensink RP, Katan MB. Effect of dietary fatty acids on serum lipids

and lipoproteins: a meta-analysis of 27 trials. Arterioscler Thromb

1992;12:91 1-9.

5. Hegsted DM, Ausman LM, Johnson IA, Dallal GE. Dietary fat and

serum lipids: an evaluation of the experimental data. Am I Clin Nutr

1993;57:875-83.

6. Derr I, Kris-Etherton PM, Pearson TA, Seligson FH. The role of fatty

acid saturation on plasma lipids, lipoproteins, and apolipoproteins: II.

The plasma total and low-density lipoprotein cholesterol response of

individual fatty acids. Metabolism 1993;42:130-4.

7. Berry EM, Eisenberg 5, Haratz D, et al. Effects of diets rich in

monounsaturated fatty acids on plasma lipoproteins-the Jerusalem

Nutrition Study: high MUFA.S vs high PUFAS. Am I Clin Nutr

1991;53:899-907.

8. Grundy SM. Comparison of monounsaturated fatty acids and carbo-

hydrates for lowering plasma cholesterol. N Engl I Med 1986;314:

745-8.

9. Grundy SM, Florentin L, Nix D, Whelan MF. Comparison of monoun-

saturated fatty acids and carbohydrates for reducing raised levels of

plasma cholesterol in man. Am I Clin Nutr 1988;47:965-9.

10. Mensink RP, Katan MB. Effect of a diet enriched with monounsat-

urated or polyunsaturated fatty acids on levels of low-density and

high-density lipoprotein cholesterol in heathy men and women. N Engl

I Med 1989;321:436-41.

I I . Mensink RP, Katan MB. Effect of monounsaturated fatty acids versus

complex carbohydrates on high-density lipoproteins in healthy men

and women. Lancet 1987;1:122-5.

12. Ginsberg HN, Barr SL, Gilbert A, et al. Reduction of plasma choles-

terol levels in normal men on an American Heart Association step 1

diet or a step 1 diet with added monounsaturated fat. N Engl I Med

1990;322:574-9.

13. Harris WS, Connor WE, McMurry MP. The comparative reductions of

the plasma lipids and lipoproteins by dietary polyunsaturated fats:

salmon oil versus vegetable oils. Metabolism l983;32:179-84.

14. McDonald BE, Gerrard IM, Bruce VM, Corner U. Comparison of the

effect of canola oil and sunflower oil on plasma lipids and lipoproteins

and on in vivo thromboxane A, and prostacyclin production in healthy

young men. Am I Clin Nutr 1989;50:1382-8.

15. Mensink RP, Katan MB. Effect of dietary trans fatty acids on high-

density and low-density lipoprotein cholesterol levels in healthy sub-

jects. N Engl I Med 1990;323:439-45.

16. Friday KE, Failor RA, Childs MT. Bierman EL. Effects of n-3 and

n-6 fatty acid-enriched diets on plasma lipoproteins and apolipopro-

teins in heterozygous familial hypercholesterolemia. Arterioscler

Thromb 1991;! 1:47-54.

17. Nestel P, Noakes M, Belling GB, McArthur R, Clifton PM, Abbey M.

Plasma cholesterol-lowering potential of edible-oil blends suitable for

commercial use. Am I Clin Nutr 1992;55:46-50.

18. Zock PL, Katan MB. Hydrogenation alternative: effects of trans fatty

acids and stearic acid versus linoleic acid on serum lipids and lipopro-

teins in humans. I Lipid Res 1992;33:399-410.

19. Mata P, Garrido IA, Ordovas IM, et al. Effect of dietary monounsat-

urated fatty acids on plasma lipoproteins and apolipoproteins in

women. Am I Clin Nutr 1992;56:77-83.

20. Mensink RP, Zock PL, Katan MB, Hornstra G. Effect of dietary cis

and trans fatty acids on serum lipoprotein[a] levels in humans. I Lipid

Res 1992;33: 1493-501.

21. Barr SL, Ramakrishnan R, Johnson C, Holleran, Dell RB, Ginsberg

HN. Reducing total dietary fat without reducing saturated fatty acids

does not significantly lower total plasma cholesterol concentrations in

normal males. Am I Clin Nutr 1992;55:675-81.

22. Ng TKW, Hayes KC, DeWitt GF, et al. Dietary palmitic and oleic

acids exert similar effects on serum cholesterol and lipoprotein profiles

in normocholesterolemic men and women. I Am Coll Nutr 1992;l 1:

383-90.23. Nestel P, Noakes M, Belling B, et al. Plasma lipoprotein lipid and

Lp[a] changes with substitution of elaidic acid for oleic acid in the diet.

I Lipid Res 1992;33:1029-36.

24. Kris-Etherton PM, Derr I, Mitchell DC, et al. The effect of fatty acid

saturation on plasma lipids, lipoproteins, and apolipoproteins: I. effects

of whole-food diets high in cocoa butter, olive oil, soybean oil, dairy

butter, and milk chocolate on the plasma lipids of young men. Metab-

olism 1993;42:121-9.

25. Sabat#{233}I, Fraser GE, Burke K, Knutsen SF, Bennett H, Lindsted KD.

Effects of walnuts on serum lipid levels and blood pressure in normal

men. N Engl I Med 1993;328:603-7.

26. Grande F, Anderson IT, Keys A. Comparison of effects of palmitic

acid and stearic acid in the diet on serum cholesterol in men. Am I Clin

Nutr 1970;23:1 184-93.

27. Brussaard IH, Katan MB, Groot PHE, Havekes LM, Hautvast 1GM.

Serum lipoprotein of healthy persons fed a low-fat diet or a polyun-

saturated fat diet for three months. Atherosclerosis 1982;42:205-19.

28. Hegsted DM, Nicolosi RI. Do formula diets attenuate the serum

cholesterol response to dietary fats? I Vasc Med Biol 1990;2:69-73.

29. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concen-

tration of low-density lipoprotein in plasma, without use of the pre-

parative ultracentrifuge. Clin Chem 1972;18:499-502.

30. SAS Institute. SAS user’s guide: basics. Version 5. Cary, NC: SAS

Institute Inc.

31. Denke MA, Grundy SM. Effects of fats high in stearic acid on lipid

and lipoprotein concentrations in men. Am I Clin Nutr 1991;54: 1036-

40.

at PE

NN

SY

LVA

NIA

ST

AT

E U

NIV

PA

TE

RN

O LIB

RA

RY


ajcn.nutrition.orgD

ownloaded from



33. Becker N, Illingworth DR. Alaupovic P, Connor WE, Sundberg EE.

Effects of saturated, monounsaturated, and w-6 polyunsaturated fatty

acids on plasma lipids, lipoproteins, and apoproteins in humans. Am I

Clin Nutr 1983;37:355-60.

34. Spady DK, Woollett LA, Dietschy JM. Regulation of plasma LDL-

cholesterol levels by dietary cholesterol and fatty acids. Annu Rev

Nutr 1993;13:355-81.

35. Dietschy IM, Woollett LA, Spady DK. The interaction of dietary

cholesterol and specific fatty acids in the regulation of LDL receptor

activity and plasma LDL-cholesterol concentrations. Ann N Y Acad

Sci l993;676:l 1-26.

36. Mattson FH, Grundy SM. Comparison of effects of dietary saturated,

monounsaturated, and polyunsaturated fatty acids on plasma lipids and

lipoproteins in man. I Lipid Res 1985;26:194-202.

37. Gustafsson lB. Vessby B, Nydahl M. Effects of lipid-lowering diets

enriched with monounsaturated and polyunsaturated fatty acids on

serum lipoprotein composition in patients with hyperlipoproteinaemia.

Atherosclerosis 1992;96: 109-18.

38. Mata P, Alvare-Sala LA, Rubio Ml, Nu#{241}o1, Oya MD. Effects of

long-term monounsaturated- vs polyunsaturated- enriched diets on

lipoproteins in healthy men and women. Am I Clin Nutr 1992;55:846-

50.

39. Hashim SA, Arteaga A, Van Itallie TB. Effect of a saturated medium-

chain triglyceride on serum-lipids in man. Lancet 1960;1:1105-8.

40. Denke MA, Grundy SM. Comparison of effects of lauric acid and

palmitic acid on plasma lipids and lipoproteins. Am I Clin Nutr

1992;56:895-8.

41. Hayes KC, Khosla P. Dietary fatty acid thresholds and cholesterol-

emia. FASEB I 1992;6:2600-7.

42. Zock PL, Vries JHM, Katan MB. Impact of myristic acid versus

palmitic acid on serum lipid and lipoprotein levels in healthy women

and men. Arterioscler Thromb 1994;14:567-75.

43. Vega GL, Groszek E, Wolf R, Grundy SM. Influence of polyunsatu-

rated fats on composition of plasma lipoproteins and apolipoproteins.

I Lipid Res 1982;23:81 1-22.

44. Schaefer El, Levy RI, Ernst ND, Van Sant FD, Brewer HB Jr. The

effects of low cholesterol, high polyunsaturated fat, and low fat diets

on plasma lipid and lipoprotein cholesterol levels in normal and

hypercholesterolemic subjects. Am I Clin Nutr 1981;34:1758-63.

45. Shepherd I, Packard Ci, Grundy SM, Yeshurun D, Gotto AM Ir,

Taunton OD. Effects of saturated and polyunsaturated fat diets on the

chemical composition and metabolism of low density lipoproteins in

man. I Lipid Res 1980;21:91-9.

46. Erickson BA, Coots RH, Mattson FH, Kiigman AM. The effect of

partial hydrogenation of dietary fats, of the ratio of polyunsaturated to

saturated fatty acids, and of dietary cholesterol upon plasma lipids in

man. I Clin Invest l964;43:20l7-25.

47. Gustafsson IB, Vessby B, Karlstrom B, Boberg I, Boberg M, Lithell H.

Effects on the serum lipoprotein concentrations by lipid-lowering diets

with different fatty acid compositions. I Am Coil Nutr 1985;4:241-8.

48. Clifton PM, Nestel P1. Influence of gender, body mass index, and age

on response of plasma lipids to dietary fat plus cholesterol. Arterio-

scler Thromb 1992;12:955-62.

49. Barnard Ri. Effects of life-style modification on serum lipids. Arch

Intern Med 1991;151:1389-94.

50. Jenkins DIA, Wolever TMS, Rao AV, et al. Effect on blood lipids of

very high intakes of fiber in diets low in saturated fat and cholesterol.

N EngI I Med 1993;329:21-6.

51. Jacobs DR Jr, Mebane IL, Bangdiwala SI, Criqui MH, Tyroler HA.

High density lipoprotein cholesterol as a predictor of cardiovascular

disease mortality in men and women: the follow-up study of the lipid

research clinics prevalence study. Am I Epidemiol 1990;131:32-47.

52. Castelli WP, Doyle IT, Gordon T, Ct al. HDL cholesterol and other

lipids in coronary heart disease. Circulation 1977;55:767-72.

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plasma cholesterol-predictive equations demonstrate that ... · urated fatty acids (mufas) had no...

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