APPLIED NUTRITIONAL INVESTIGATION

Comparison Between the Effects of Soy Milk and

Non-Fat Cow Milk on Lipid Profile and Lipid
Peroxidation in Patients With Primary
Hypercholesterolemia
Liliana P. Bricarello, ND, MSc, Nelson Kasinski, MD, PhD, Marcelo C. Bertolami, MD, PhD,
Andre Faludi, MD, PhD, Leonor A. Pinto, MSc, Waldir G. M. Relvas, MD,
Maria C. O. Izar, MD, PhD, Silvia S. M. Ihara, PhD, Sergio Tufik, MD, PhD, and
Francisco A. H. Fonseca, MD, PhD
From the Cardiology Division, Federal University of São Paulo, São Paulo, Brazil; and the
Division of Dyslipidemia, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil

OBJECTIVE: This study assessed whether the consumption of soy milk could add significantly to the lipid
profile and lipid peroxidation in comparison with non-fat milk.
METHODS: A double-blind, randomized, crossover study was conducted on 60 outpatients with primary
hypercholesterolemia following a lipid-lowering diet for at least 6 wk. Lipid profile was obtained at
baseline and at 6 and 12 wk, with the patients randomly assigned to receive initially 1 L/d of soy milk
or non-fat cow milk for 6 wk. Lipid peroxidation was estimated by plasma thiobarbituric reactive
substances. Apolipoprotein E genotypes were examined by polymerase chain reaction restriction fragment
length polymorphism.
RESULTS: The soy milk diet was associated with low-density lipoprotein cholesterol reduction (baseline
⫽ 157 ⫾ 5 mg/dL; soy milk ⫽ 148 ⫾ 4 mg/dL; non-fat cow milk ⫽ 158 ⫾ 4 mg/dL; P ⬍ 0.05, soy milk
versus other treatments) and with high-density lipoprotein cholesterol increase (baseline ⫽ 58 ⫾ 2 mg/dL;
soy milk ⫽ 62 ⫾ 2 mg/dL; non-fat cow milk ⫽ 57 ⫾ 2 mg/dL; P ⬍ 0.05, soy milk versus other
treatments). In addition, plasma thiobarbituric reactive substances were reduced by the soy milk diet
(baseline ⫽ 1.82 ⫾ 0.12 nM/L; soy milk ⫽ 1.49 ⫾ 0.09 nM/L; non-fat cow milk ⫽ 1.91 ⫾ 0.11 nM/mL;
P ⬍ 0.05, soy milk versus non-fat cow milk). Changes in lipid profile were not influenced by APOE
genotypes.
CONCLUSIONS: These results indicate that soy milk as part of a lipid-lowering diet has beneficial effects
in improving lipid profile and reducing lipid peroxidation. Nutrition 2004;20:200 –204. ©Elsevier Inc.
2004

KEY WORDS: soy milk, lipoproteins, lipid peroxidation

INTRODUCTION occur naturally, such as isoflavones, saponins, and fibers. Depend-

There is increasing evidence that consumption of soy protein and
isoflavones in place of casein lowers low-density lipoprotein
(LDL) cholesterol and may provide other cardiovascular bene-
fits,1,2 such as antioxidant properties.3,4 However, even after a
meta-analysis of 38 controlled clinical studies5 suggesting its po-
tential role in the reduction of total and LDL cholesterol, no
recommendation was made to include soy protein in the American
Heart Association dietary guidelines.6,7
Soy protein is an edible component of soybeans and contains
all the essential amino acids in sufficient amounts to be considered
a complete protein.8,9 In addition to protein, other components
Lilliana P. Bricarello, ND, MSc, was supported by a grant from CAPES (a
Brazilian research foundation).
Correspondence to: Francisco A. H. Fonseca, MD, PhD, Lı́pides, Atero-
sclerose e Biologia Vascular, Disciplina de Cardiologia, Universidade
Federal de São Paulo, Rua Pedro de Toledo 458, São Paulo, Brazil,
04039-001. E-mail: lipids.dmed@unifesp.epm.br
ing on the particular process used to obtain the final product, soy
protein may differ considerably regarding these components.10
Many attempts have been made to elucidate the mechanisms
involved in the multiple beneficial effects when following soy
diets. These studies have suggested an inhibition of cholesterol
absorption at the small intestine by soy protein,10 a reduced rate of
saponin-mediated bile salt absorption,11 and an antioxidant effect
on lipids3,10 associated with soy protein with or without isofla-
vones.11 The higher increase of high-density lipoprotein (HDL)
cholesterol serum levels appears to be associated with the presence
of isoflavones in the soy protein.12 In addition, an activation of
peroxisome proliferator-activated receptors (PPARs) was recently
reported, which may explain these interesting effects of soy protein
on lipid metabolism.13
Considering the large use of milk in modern societies and the
potential benefit of soy protein, this study examined the effects of
soy milk on patients with primary hypercholesterolemia, in addi-
tion to the Adult Treatment Panel of the Third Report of the
National Cholesterol Education Program Therapeutic Lifestyle
Changes (TLC) diet.14 We also verified whether the apolipoprotein

Nutrition 20:200 –204, 2004 0899-9007/04/$30.00

©Elsevier Inc., 2004. Printed in the United States. All rights reserved. doi:10.1016/j.nut.2003.10.005
Nutrition Volume 20, Number 2, 2004 Effects of Soy Milk on Lipids and Lipid Peroxidation 201

E polymorphisms affect the lipid profile responses due to the TABLE I.

treatment.
COMPOSITION OF THE SOY MILK AND NON-FAT COW
MILK DIETS*
MATERIALS AND METHODS
Soy milk Non-fat cow milk
Patients (per 200 mL) (per 200 mL)

Sixty subjects were recruited at two centers in Sao Paulo from the Total calories (kcal) 60.0 56.4
Lipids, Atherosclerosis and Vascular Biology Laboratory of Car- Carbohydrate (g) 1.0 8.6
diology Division of the Federal University of Sao Paulo and from Protein (g) 5.0 5.5
the Section of Dyslipidemia of the Dante Pazzanese Institute of Total fat (g) 3.5 ⬍0.01
Cardiology. Men (n ⫽ 15) and women (n ⫽ 45), with an age range Saturated fat (g) 0.5 0.0
of 20 to 70 y, total cholesterol concentrations of 200 to 350 mg/dL, Monounsaturated fat (g) 0.5 0.0
and triacylglycerol concentrations below 400 mg/dL, were eligible Polyunsaturated fat (g) 2.0 0.0
to participate in the study. The exclusion criteria were the presence Cholesterol (mg) 0.0 ⬍1.0
of coronary artery disease and other significant cardiovascular Fiber (g) 0.25 ⬍0.01
diseases and renal, hepatic, gastrointestinal, mental, and endocrine Calcium (mg) 18.2 178.6
disorders, including diabetes mellitus and obesity (body mass Iron (mg) 0.6 ⬍0.1
index [BMI] ⱖ 30 kg/m2). No subjects had taken hypolipidemic Vitamin A (␮g) 120 ⬍1.5
drugs in the previous 8 wk. The ethics committees of both insti- Sodium (mg) 85.0 56.6
tutions approved the protocol, and all patients signed informed Genistein (mg) 9.96 0.00
consent to participate in the study. Daidzein (mg) 6.68 0.00
Glycetein (mg) 0.94 0.00
Study Design
* Estimated composition based on two independent analyses. Daily in-
The study was a double-blind, randomized, and crossover trial. take of each milk was 1L.
Initially, all subjects were asked to follow the TLC diet for a
minimum of 6 wk. The TLC diet with respect to total calories
consists of 15% proteins, 50% to 60% carbohydrates, less than 7% performed with a Spectronic Genesys 2 spectrophotometer
saturated fat, no more than 10% polyunsaturated fat, no more than (Rochester, NY, USA) with readings at 535 nm.
20% monounsaturated fat, less than 200 mg/d of cholesterol and 20
to 30 g/d of viscous (soluble) fiber.14 At this time, baseline blood
samples were collected after a 12- to 14-h fast, and the patients
were randomly assigned to one of the two treatments (1 L/d of soy APOE Genotyping
milk or non-fat cow milk) for 6 wk. After this 6-wk period, the
DNA was obtained from peripheral leukocytes with an extraction
treatments were switched: those receiving soy milk were changed
set (GFX Genomics Blood Purification Kit, Amersham Bio-
to non-fat cow milk and vice versa. After each 6-wk period, second
science, Buckinghamshire, UK) and the APOE genotype was
and third blood samples were drawn. To maintain optimal com-
determined as previously described.21
pliance, patients were carefully monitored with regard to diet and
milk consumption and were asked to bring the label with a code
written at the top of each 1000 mL of tetra-pack milk. These milk
packages were identical, and the code was not known by the Statistical Analysis
investigators or the patients. Both milks were flavored with vanilla
to mask the original flavor or soy taste. Dietary records were All data are presented as mean ⫾ standard error of the mean.
collected during the last 3 d15–17 (including 1 d of the weekend) of Unpaired Student’s t test was used for comparisons between
each treatment period (at 0, 6, and 12 wk) and were analyzed for groups at baseline. Comparisons during the study were made by
nutrient intake by using the Virtual Nutri software.18 At each visit, using analysis of variance for repeated measurements followed by
the randomly assigned milk was delivered to the patient’s home. Tukey’s test. The level of significance was set at P ⬍ 0.05 for all
Milk compositions are detailed in Table I and were determined by analyses.
two independent laboratories (Labor 3, São Paulo, SP, Brazil;
Unilever Bestfoods, Valinhos, SP, Brazil). BMI (weight/height2)
and waist circumference were determined at 0, 6, and 12 wk.
RESULTS
Demographic characteristics, BMI, and baseline lipid profile are
Lipids and Lipoproteins shown in Table II. Middle-age hypercholesterolemic women with
Determinations of total serum cholesterol (CHOD-PAP, Diapack, normal BMI values predominantly formed the studied population.
Helsinki, Finland), HDL cholesterol (COD-ANA, Labtest Diag- Analysis of dietary questionnaires showed good overall com-
nóstica, Lagoa Santa, MG, Brazil), and triacylglycerols (SERA- pliance with the recommended diets, and Table III shows that no
PAK, Bayer, Tarrytown, NY, USA) in fasting blood samples were differences regarding daily intake of total calories were found
made with an automated colorimetric method (Opera, Bayer), and between baseline, soy milk, and non-fat cow milk treatment peri-
LDL cholesterol was calculated by the Friedewald equation.19 ods. However, higher fiber and fat content (predominantly unsat-
urated) and lower carbohydrate and cholesterol content were ob-
served with soy milk.
Lipid Peroxidation During the entire study, patients reported no marked changes in
lifestyle or physical activity based on data collected at each clinical
Lipid peroxidation was estimated on the basis of plasma thiobar- visit (at 0, 6, and 12 wk), and no significant variations in BMI were
bituric acid-reactive substances (TBARs).20 Measurements were observed.
202 Bricarello et al. Nutrition Volume 20, Number 2, 2004

TABLE II. Apolipoprotein E Genotyping

CHARACTERISTICS OF THE STUDY POPULATION Table IV shows the allelic frequencies for apolipoprotein E. A
AT BASELINE* subgroup analysis of patients without the E4 allele (n ⫽ 48)
showed the same benefit of soy milk to the lipid profile as that
Variable Subjects observed in the entire population. In this particular population,
LDL cholesterol was reduced by soy milk (baseline ⫽ 153 ⫾ 5
mg/dL; soy milk ⫽ 146 ⫾ 4 mg/dL; non-fat cow milk ⫽ 156 ⫾ 4
Age (y) 56 ⫾ 1
mg/dL; P ⬍ 0.05, soy milk versus non-fat cow milk, analysis of
Male (%) 15 (25)
variance, Tukey’s test). In addition, soy milk promoted an increase
Weight (kg) 65 ⫾ 1
in plasma HDL cholesterol levels (baseline ⫽ 57 ⫾ 2 mg/dL; soy
BMI (kg/m2) 24.9 ⫾ 0.3
milk ⫽ 61 ⫾ 3 mg/dL; non-fat cow milk ⫽ 56 ⫾ 2 mg/dL; P ⬍
Waist circumference (cm) 88 ⫾ 1
0.05, soy milk versus baseline and non-fat cow milk, analysis of
Total cholesterol (mg/dL) 241 ⫾ 5
variance, Tukey’s test).
LDL cholesterol (mg/dL) 157 ⫾ 4
HDL cholesterol (mg/dL) 58 ⫾ 2
Triacylglycerols (mg/dL) 136 ⫾ 9
DISCUSSION
* Data presented as mean ⫾ standard error of the mean.
Our study focused on the effects of soy milk in comparison with
BMI, body mass index; HDL, high-density lipoprotein; LDL, low-
non-fat cow milk on lipid profile and lipid peroxidation. Although
density lipoprotein
previous studies have shown a hypocholesterolemic effect of soy
protein,1,2,5,7,22,23 a substantial increase in HDL cholesterol and a
reduced lipid peroxidation are less well shown. In fact, there were
Effects of Soy Milk on Lipid Profile different results with the soy protein diet, which can be attributed
to variations in soy components such as the protein content and the
There was no significant effect of soy milk in comparison with amounts of isoflavones,12 saponin,24 and fiber.25,26 Interestingly,
baseline and non-fat cow milk on total cholesterol and triacylglyc- on the basis of the meta-analysis reported by Anderson et al.,5
erol plasma levels. Conversely, soy milk diet promoted a reduction hypercholesterolemic patients appeared to have the highest benefit
in LDL cholesterol plasma levels and an increase in HDL choles- after the use of soy protein. However, this finding was not con-
terol in comparison with baseline and non-fat cow milk (Figure 1). firmed by another study.23
Soy milk did not change plasma apolipoprotein E levels when After comparing the effects of soy milk with those of cow milk
compared with baseline and non-fat cow milk (baseline ⫽ 4.38 ⫾ in severe hypercholesterolemic patients, Sirtori et al.27 found a
0.24 mg/dL; soy milk ⫽ 4.43 ⫾ 0.23 mg/dL; and non-fat cow milk significant reduction in total and LDL cholesterol levels, thus
⫽ 4.80 ⫾ 0.31 mg/dL). confirming the benefits of soy milk even in patients with substan-
tially elevated plasma cholesterol and only partly replacing the
animal protein in the diet.
In our study we found a significant reduction in LDL choles-
Effects of Soy Milk on Lipid Peroxidation terol in patients with cholesterol levels above ideal values (total
cholesterol ⱖ 200 mg/dL). Many attempts have been made to
Lipid peroxidation estimated by TBARs was significantly reduced explain the mechanisms by which soy protein alters the plasma
by the soy milk diet in comparison with the cow milk diet (baseline concentration of LDL cholesterol in comparison with casein. Kho-
⫽ 1.82 ⫾ 0.12 nM/mL; soy milk ⫽ 1.49 ⫾ 0.09 nM/mL; non-fat sla et al.28 reported decreased expression of the LDL receptor
cow milk ⫽ 1.91 ⫾ 0.11 nM/mL; P ⬍ 0.05, soy milk versus induced by casein leading to an increase in plasma cholesterol. It
non-fat cow milk, analysis of variance, Tukey’s test). is interesting to note that amino acids can differ in their effects on
plasma cholesterol levels and on apolipoprotein B synthesis.29
Saponins are steroid glycosides, which occur in many vegetables
including soybeans. It was reported that these substances may
TABLE III.
interact with bile acids, leading to the formation of large mixed
micelles impairing cholesterol absorption and influencing its me-
MAIN FOOD COMPONENTS DURING THE STUDY, ACCORDING
tabolism.23 In our study the fiber content in soy milk was too small
TO FOOD RECORDS*
to explain the observed reduction in LDL cholesterol.
Recently, a new mechanism by which soy protein may produce
Non-fat multiple benefits to the lipid profile was reported. Mezei et al.13
Food components Baseline Soy milk cow milk found an increase in the expression of PPARs related to the content
of isoflavones in the diet. In that study, isoflavones doubled PPAR-
Total calories (kcal) 1538 ⫾ 57 1580 ⫾ 48 1578 ⫾ 51 ␣– directed gene expression but increased PPAR-␥– directed gene
Total fat (%) 30 ⫾ 1 34 ⫾ 1† 25 ⫾ 1‡ expression by 200% to 400%. Therefore, together these studies
Unsaturated fat (g) 25 ⫾ 1 39 ⫾ 1† 24 ⫾ 1 indicate that reduction in LDL cholesterol as related to a soy milk
Saturated fat (g) 28 ⫾ 2 20 ⫾ 1‡ 20 ⫾ 1‡ diet appears to be explained by multiple mechanisms, but they
Carbohydrate (%) 50.8 ⫾ 1.2 45.0 ⫾ 1.1† 53.7 ⫾ 0.9‡ reinforce the need for isoflavones in addition to soy protein to
Protein (%) 19.4 ⫾ 0.7 20.7 ⫾ 0.6 20.9 ⫾ 0.5‡ obtain better results.
Cholesterol (mg) 158 ⫾ 12 113 ⫾ 8† 142 ⫾ 11 These mechanisms related to PPARs might explain the results
Fiber (g) 13 ⫾ 1 16 ⫾ 1† 13 ⫾ 1 obtained in our study concerning the substantial increase in plasma
HDL cholesterol levels. In fact, augmentation of apolipoproteins
* Data presented as mean ⫾ standard error of the mean. A-I and A-II and adenosine triphosphate binding cassette A1 by
† P ⬍ 0.05, soy milk versus baseline and non-fat cow milk (analysis of PPARs can facilitate cholesterol removal from peripheral tissues,
variance, Tukey’s test). thus improving HDL cholesterol plasma levels.30,31
‡ P ⬍ 0.05, soy milk and non-fat cow milk versus baseline (analysis of There is considerable agreement about the important role of
variance, Tukey’s test). oxidative modifications of LDL in atherosclerosis. In this regard,
Nutrition Volume 20, Number 2, 2004 Effects of Soy Milk on Lipids and Lipid Peroxidation 203

FIG. 1. Changes in lipid profile induced by the treatment. *P ⬍ 0.05 soy milk versus baseline and non-fat cow milk (analysis of variance, Tukey’s test).
B, baseline; CM, non-fat cow milk; SM, soy milk.

Damasceno et al.11 tested the capacity of soy protein isolate in with those observed in the entire population. However, the high
reducing the oxidizability of LDL in the diet-induced model of proportion of women in our study may have attenuated genetic
atherosclerosis in rabbits. In comparison with casein-fed rabbits, influences of this polymorphism on the basis of a recent publica-
they found a decrease in oxidizability of LDL in the animals fed tion showing that women are less susceptible to the influence of
the soy protein. The soy protein used was obtained by a hydroal- APOE genotypes on plasma lipid changes.35
coholic extraction process, which removes the major isoflavones. In summary, the addition of soy milk as opposed to non-fat cow
Therefore, the possible explanation for these results was the vari- milk in hypercholesterolemic patients following the TLC diet
ation in LDL cholesterol levels. Increased plasma LDL cholesterol improved the lipid profile and reduced lipid peroxidation. These
levels in the animals treated with casein may be associated with benefits were present even in non-⑀4 allele carriers. These results
reduction in lipoprotein clearance and increased susceptibility of suggest a potential role for soy milk and its derivatives in the
these particles to oxidation.11 In our study, we also observed a prevention of cardiovascular disease.
reduction in lipid peroxidation as estimated by TBARs. The pres-
ence of isoflavones in soy milk and the favorable effect on HDL
particles could explain our findings. However, plasma TBARs
reduction reflects only an indirect estimation of lipid peroxidation, ACKNOWLEDGMENTS
and this finding should be confirmed by other techniques using The authors are grateful to Unilever Bestfoods of Brazil for sup-
direct assessment of lipid peroxidation.32,33 plying the soy milk and non-fat cow milk.
Due to the potential influence of the apolipoprotein E genotype
on dietary changes (⑀4 allele carriers are the most responsive
subjects),34 we examined lipid responses among patients not car-
rying the ⑀4 allele. We verified similar changes in lipid profile REFERENCES
induced by the soy milk among these individuals when compared
1. Sirtori CR, Lovatti MR, Manzoni C, et al. Soy and cholesterol reduction: clinical
experience. J Nutr 1995;125:598S
2. Nagata C, Takatsuka N, Kurisu Y, et al. Decreased serum total cholesterol
TABLE IV.
concentration is associated with high intake of soy products in Japanese men and
women. J Nutr 1998;128:209
DISTRIBUTION OF APOE GENOTYPES AND 3. Kapiotis S, Hermann M, Held I, et al. Genistein, the dietary-derived angiogenesis
ALLELIC FREQUENCIES inhibitor, prevents LDL-oxidation and protects endothelial cells from damage by
atherogenic LDL. Arterioscl Thromb Vasc Biol 1997;17:2868
Allelic 4. Exner M, Hermann M, Hofbauer R, et al. Genistein prevents the glucose autox-
Genotype Population (n) Genotypes (%) frequencies idation mediated atherogenic modification of low-density lipoprotein. Free Radic
Res 2001;34:101
5. Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of the effects of
E2E2 2 3.4 ␧2, 0.25 soy protein intake on serum lipids. N Engl J Med 1995;333:276
E2E3 21 35.5 6. Krauss RM, Deckelbaum RJ, Ernst N, et al. Dietary guidelines for healthy
E3E3 25 42.4 ␧3, 0.66 Americans adults. Circulation 1996;94:1795
E3E4 7 11.9 7. Erdman JW Jr, for the AHA Nutrition Committee. Soy protein and cardiovascular
E2E4 4 6.8 ␧4, 0.09 disease. A statement for healthcare professionals from the nutrition committee of
the AHA. Circulation 2000;102:2555
204 Bricarello et al.
8. Food and Drug Administration. Food labeling, health claims, soy protein, and
coronary heart disease. Fed Reg 1999;57:699
9. Protein Technologies International. Soy protein and health: discovering a role for
soy protein in the fight against coronary heart disease. Houston, TX: Marimac
Communications, 1996
10. Huff MW, Carroll KK. Effects of dietary protein on turnover, oxidation, and
absorption of cholesterol, and on steroid excretion in rabbits. J Lipid Res
1980;21:546
11. Damasceno DRT, Goto H, Rodrigues FMD, et al. Soy protein isolate reduces the
oxidizability of LDL and the generation of oxidized LDL autoantibodies in
rabbits with diet-induced atherosclerosis. J Nutr 2000;130:2641
12. Anthony MS, Clarkson TB, Williams JK. Effects of soy isoflavones on athero-
sclerosis: potential mechanisms. Am J Clin Nutr 1998;68:1390S
13. Mezei O, Banz WJ, Steger RW, et al. Soy isoflavones exert antidiabetic and
hypolipidemic effects through the PPAR pathways in obese Zucker rats and
murin RAW 264.7 cells. J Nutr 2003;133:1238
14. Executive Summary of the Third Report of the National Cholesterol Education
Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High
Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486
15. Karvetti RL, Knuts JR. Validity of the 24-hour dietary recall. J Am Diet Assoc
1985;85:1437
16. Karkeck JM. Improving the use of dietary survey methodology. J Am Diet Assoc
1987;87:869
17. Basiots PP. Number of days of food intake records required to estimate individual
and group nutrient intakes with defined confidence. J Nutr 1987;117:1138
18. Philippi ST, Szarfac SC, Laterza CR. Virtual Nutri: sistema de análise nutricio-
nal [computer program]. Version 1.0. São Paulo, 1996
19. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of
low-density lipoprotein cholesterol in plasma without use of the preparative
ultracentrifuge. Clin Chem 1972;18:499
20. Okhawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by
thiobarbituric acid reaction. Anal Biochem 1979;95:351
21. Hixson J, Vernier D. Restriction isotyping of human apolipoprotein E by gene
amplification and cleavage with Hhal. J Lipid Res 1990;31:545
22. Carrol KK, Kurowska EM. Soy consumption and cholesterol reduction: review of
animal and human studies. J Nutr 1995;125:594S
Nutrition Volume 20, Number 2, 2004
23. Wong WW, Smith EO, Stuff JE, et al. Cholesterol-lowering effect of soy protein
in normocholesterolemic and hypercholesterolemic men. Am J Clin Nutr 1998;
68:1385S
24. Sidhu GS, Oakenfull DG. A mechanism for the hypocholesterolaemic activity of
saponins. Br J Nutr 1986;55:643
25. Potter SM, Bakhit RM, Essex-Sorlie D, et al. Depression of plasma cholesterol in
men by consumption of baked products containing soy protein. Am J Clin Nutr
1993;58:501
26. Potter SM. Overview of proposed mechanisms for the hypocholesterolemic effect
of soy. J Nutr 1995;125:606S
27. Sirtori CR, Pazzucconi F, Colombo L, et al. Double-blind study of the addition
of high-protein soya milk v. cows’ milk to the diet of patients with severe
hypercholesterolaemia and resistance to or intolerance of statins. Br J Nutr
1999;82:91
28. Khosla P, Samman S, Carroll KK. Decrease receptor-mediated LDL catabolism
in casein-fed rabbits precedes the increase in plasma cholesterol levels. J Nutr
Biochem 1991;2:203
29. Zhang ZJ, Sniderman AD, Kalant D, et al. The role of amino acids in apoB100
synthesis and catabolism in human HepG2 cells. J Biol Chem 1993;268:26920
30. Chinetti G, Gbaguidi FG, Griglio S, et al. CLA-1/SR-B1 is expressed in athero-
sclerotic lesion macrophages and regulated by activators of peroxisome
proliferator-activated receptors. Circulation 2000;101:2411
31. Chinetti G, Lestavel S, Bocher V, et al. PPAR-alpha and PPAR-gamma activators
induce cholesterol removal from human macrophage foam cells through stimu-
lation of the ABCA 1 pathway. Nat Med 2001;7:53
32. McDowell A, Young IS, Wisdon GB. Autoantibodies to malondialdehyde-
modified low-density lipoprotein in patients with angiographically confirmed
coronary artery disease. J Pharm Pharmacol 2002;54:1651
33. Tornvall P, Waeg G, Nilsson J, Hamsten A, Regnstrom J. Autoantibodies against
modified low-density lipoproteins in coronary artery disease. Atherosclerosis
2003;167:347
34. Ordovas JM. The genetics of serum lipid responsiveness to dietary interventions.
Proc Nutr Soc 1999;58:171
35. Pedro-Botet J, Schaefer EJ, Bakker-Arkema RG, et al. Apolipoprotein E geno-
type affects plasma lipid response to atorvastatin in a gender specific manner.
Atherosclerosis 2001;158:183