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REVIEW ARTICLE
Cardiovascular Benefits of Soy Supplements
Jörg Grünwald, PhD; Lars M. Høie, MD; Heike Stier, PhD
Abstract
Cardiovascular disease (CVD) is the most frequent cause
of death in Western industrialized nations. The probability of
CVD is directly related to blood cholesterol levels, among sev-
eral other factors such as hypertension, smoking, malnutri-
tion, obesity, and stress. It is well known that changes in life-
style, including physical activity and dietary changes such as
reduction in the consumption of saturated fat, can reduce
blood cholesterol levels. In such cases, dietary soy-protein
supplementation, for which cholesterol-lowering properties
have been shown in many clinical studies, is useful to postpone
the need for cholesterol-lowering medication such as statins.
In this review, we will summarize numerous clinical
studies conducted with soy-protein supplementation in vari-
Jörg Grünwald, PhD, is founder and president of analyze & realize AG, Berlin,
Germany, a research and consulting company specializing in natural products that
has conducted more than 150 clinical trials. Dr Grünwald has published more than
250 scientific articles and has been an author or coauthor of 13 books, including
PDR for Herbal Medicines (Medical Economics Company, 2nd edition, 2000) and
Plant-based Ingredients for Functional Foods (Food Trade Press Ltd, 2003). He has
worked as an advisor to the US Food and Drug Administration Office of Dietary
Supplements, is on the International Advisory Board of the Research Council of
Complementary Medicine, and is a member of the Ad Hoc Group on Botanicals for
the United States Pharmacopoeia. Lars M. Høie, MD, is the director of research and
development as well as a member of the scientific advisory board for Nutri Pharma
ASA, Oslo, Norway, a manufacturing company focused on soy technology for treat-
ment and prevention of life style–related diseases. He is cofounder of the Norwegian
Medical Center & Center for Heart Medicine, Oslo, and founder of Domus Medicus,
a healthcare and research center at the former National Hospital, Oslo. He has
published 15 peer-reviewed papers. Heike Stier, PhD, studied biology at the
University of Hohenheim, Stuttgart, Germany, and works for analyze & realize AG.
She has published 9 peer-reviewed papers.
Disclosure: Lars M. Høie, MD, is cofounder of Nutri Pharma ASA,
which sponsored the studies presented in this review using the
company’s soy-protein supplements Nutri 5, Abalon, and Abacor.
Jörg Gruenwald, PhD, and Heike Stier, PhD, have no financial ties
with Nutri Pharma or the products used.
Background
Cardiovascular disease (CVD) is the most frequent cause of
death in the European Union1 and the United States,2 and will
become the leading cause of death in developing countries by
2010, according to the World Health Organization.3 In Europe,
it accounts for more than 4.3 million deaths per year (48.5% of
all deaths), 54% of deaths in women, and 43% of deaths in men.
The chance of dying from major CVD is more than twice as high
as that of dying from cancer. It is estimated that CVD costs the
European Union economy €192 billion per year.1 CVD is not a
single disease, but rather a class of diseases including ischemic
30 Integrative Medicine • Vol. 8, No. 4 • Aug/Sep 2009
ous formulations that exhibit clear low-density lipoprotein
(LDL) cholesterol-lowering effects. To get more homogeneous
results, we summarized only clinical studies conducted with
soy-protein supplements containing the same isolated soy
proteins, cotyledon fibers, and phospholipids: Nutri 5, Abalon,
and Abacor (all by Nutri Pharma ASA, Norway), which have
shown clear cholesterol-lowering efficacy. Furthermore, these
studies demonstrate that homocysteine, an independent CVD
risk factor, is also reduced by soy-protein supplementation.
Differences between studies showing clear LDL-lowering
effects for soy protein and those that do not are discussed, as
well as possible mechanisms of action for soy-protein supple-
mentation on blood cholesterol levels.
(coronary) heart disease, hypertensive disease, rheumatic heart
disease, and cerebrovascular disease (stroke).
In recent years, eating habits in developed countries have
changed considerably. The average consumption of fruit and
vegetables has decreased while intake of saturated fat, salt, and
refined carbohydrates has increased.3,4 An increase in consump-
tion of snacks and fast food, typically containing a high percent-
age of fat, has also been seen in recent years.
It is very well documented that lipid disorders are strongly
associated with increased risk of coronary heart disease (CHD)
and peripheral arterial disease. According to The World Health
Report 2002, more than 60% of CHD and approximately 40% of
ischemic strokes in industrialized countries are due to total
blood cholesterol levels above the theoretical minimum (3.8
mmol/L).5 Results of a survey called the European Action on
Secondary Prevention through Intervention to Reduce Events
(EUROASPIRE), conducted by the European Society of
Cardiology, estimate that the prevalence of high total cholesterol
(≥ 5.01 mmol/L) in patients with established CVD is 58.8%.6
Most forms of CVD are associated with changes in the blood
vessels. The changes are characterized by local thickening of the
arterial wall by plaque, leading to atherosclerosis. Excess choles-
terol contributes to accumulation of plaque on blood-vessel walls.
This plaque can reduce blood flow, but, even more dramatically, it
can be partially dislodged from the blood-vessel wall, creating a
surface on which blood tends to clot. These clots can partially or
totally block blood flow, resulting in heart attack or stroke.
High blood low-density lipoprotein (LDL) cholesterol level
is especially regarded as a high-risk factor for cardiovascular
disease while increased high-density lipoprotein (HDL) choles-
terol is commonly assumed to reduce the risk of CHD.7,8 A 10%
reduction in total cholesterol lowers the risk of cardiovascular
events by up to 50% for older subjects with mild-to-moderate
hypercholesterolemia.9
Grünwald et al—Cardiovascular Benefits of Soy
 Since the early 1940s, scientists have examined the effect of
soybeans on blood-cholesterol levels. The cholesterol-lowering
effect of soy in humans was first documented in 1967.10 Since
then, numerous articles have been published on this topic.
Numerous in vitro and in vivo studies on soy have shown a
clear LDL- and total cholesterol-lowering effect. A meta-analysis
of 38 clinical studies on the effect of soy protein on serum lipids
in humans gave an average reduction in total and LDL choles-
terol concentration of approximately 9.3% and 12.9%, respec-
tively.11 Based on all these positive results, the US Food and Drug
Administration approved a health claim for reduced risk of heart
disease from consumption of at least 25 g of soy protein per
day.12 Another meta-analysis, conducted on studies from 1995
to 2002, showed that the intake of soy protein containing isofla-
vones was associated with a reduction of total cholesterol, LDL
cholesterol, and triacylglycerols of 3.77%, 5.25%, and 7.27%,
respectively, and also showed a significant increase of HDL cho-
lesterol of 3.02%.13
However, a newer meta-analysis conducted by Sacks et al
(2006)14 puts this into perspective. According to the Sacks
meta-analysis, the average LDL-lowering effect of soy protein
with isoflavones was only about 3% and for isolated isoflavones
there was no effect. They advised substituting some of the daily
protein intake from animal sources with soy products but not
soy isoflavones. In most cases, it was not possible to give rea-
sons for the different effects on cholesterol levels seen in the
different studies.
These differences might be related to the different original
plant material used or different methods of soybean (protein)
processing leading to different concentration, or chemical and
structural alteration, of isoflavones, soybean fibers, fats, sugars,
phytic acid, saponins, or other chemical components important
for lowering cholesterol but not yet identified.
To get more homogeneous results, we summarized only
clinical studies conducted with soy-protein supplements con-
taining the same isolated soy proteins (ISPs), cotyledon fibers,
and phospholipids: Nutri 5, Abalon, and Abacor—newly devel-
oped soy-based dietary supplements that have shown clear cho-
lesterol-lowering efficacy (see Tables 1 and 2). In most of these
studies, the plasma concentration of homocysteine, a cholester-
ol-independent CVD factor, is also measured.
Clinical Studies on Cholesterol-lowering Effects
of Soy-Protein Supplementation
Characteristics of the Studies
The soy-protein supplements Nutri 5, Abalon, and Abacor
were tested in different concentrations and on different subject
populations. Of these 8 selected clinical trials, 6 were random-

Table 1. Characteristics of the Studies Included in This Review

Study Reference Number Subject Number Subject Characteristics Study Design†
(Cited in References) (Inclusion Criteria)*
15 Enrolled: 25 Type 2 diabetic (mean age 63.6±7.5; Controlled, double-blind
Completed: 20 treated with diet alone or crossover study
(14 men, 6 women) receiving diabetes medication)
16 Enrolled: 159 TC: 5.8-7.9 mmol/L: Men (age: Randomized, bicentric,
Completed: 130 30-70 years) and postmenopausal placebo-controlled study
(108 men, 22 women) women (age: 45-70 years)
17 Enrolled: 60 TC: 7.0-9.9: Men (age: 18-70 years) Randomized, placebo-controlled,
Completed: 24 soy group and 28 and postmenopausal women double-blind, parallel-group,
placebo (31 men, 21 female) (age: 45-70 years) single-center study
18 Enrolled: 146 TC: 6.7-9.9 mmol/L: Men (age: Randomized, placebo-controlled,
Completed: 69 soy group and 74 18-75 years) and postmenopausal double-blind, parallel-group,
placebo (67 men, 76 women) women (age: 45-70 years) single-center study
19 Enrolled: 53 Statin-treated hypercholesterolemic Prospective, open-label, single-center,
Completed: 49 men and women cohort study with 6 study visits
(34 men, 15 women) (age: 43-79 years; mean age 59±1);
LDL with statin treatment >3.0
mmol/L and <4.5 mmol/L
20 Enrolled: 121 TC: 5.8-7.9 mmol/L Randomized, placebo-controlled,
Completed: 116 LDL >3.4 mmol/L: Men and triple-armed study
(62 women, 54 men) women (age: 31-70 years)
21 Enrolled 133 TC: 5.8-7.9 mmol/L Randomized, placebo-controlled trial
Completed: 117 LDL >3.4 mmol/L: Men and
(63 men, 54 women) women (age: 31-70 years)
22 Enrolled: 80 TC: 5.2-7.8 mmol/L: Men and Randomized, double-blind, 4-armed,
Completed: 80 (51 women, 29 men) women (age: 30-70 years) placebo-controlled study
*TC=total cholesterol; LDL=low-density lipoprotein
†Supplements were taken for at least 4 weeks or as long as 16 weeks.

Grünwald et al—Cardiovascular Benefits of Soy Integrative Medicine • Vol. 8, No. 4 • Aug/Sep 2009 31
 Table 2. Soy-Protein Supplement Formulation and Effects on LDL, HDL, and Total Cholesterol Levels
Study Subjects’ Soy Protein Soy Fiber Soy Isoflavone Duration of Effect on LDL Effect on HDL Effect on Total
(Ref ) status Concentration/d Concentration/ Concentration/ the Treatment (mmol/L) (mmol/L) Cholesterol
d d (mmol/L)
15 Type 2 diabet- 50 g isolated soy 20 g soy > 165 mg 6 weeks Baseline: 3.63 Baseline: 1.31 Baseline: 5.68
ic protein (ISP) cotyledon fiber 6 weeks: 3.01 6 weeks: 1.38 ns 6 weeks: 5.11
16 TC: 5.8 - 7.9, Active 1: Active 1: Active 1: 16 weeks Active 1: Active 1: Active 1:
men and post- 30 g ISP 10 g soy 111 mg Baseline: 4.81 Baseline: 1.48 Baseline: 6.86
menopausal Active 2: cotyledon fiber Active 2: 4 weeks: 4.26 4 weeks: 1.57 4 weeks: 6.37
women 50 g ISP Active 2: 185 mg 8 weeks: 4.31 8 weeks: 1.58 8 weeks: 6.38
16.6 g soy 12 weeks: 4.19 12 weeks: 1.55 12 weeks: 6.24
cotyledon fiber 16 weeks: 3.94 16 weeks: 1.56 ns 16 weeks: 6.00
Active 2: Active 2: Active 2:
Baseline: 4.58 Baseline: 1.35 Baseline: 6.52
4 weeks: 4.08 4 weeks: 1.44 4 weeks: 6.12
8 weeks: 4.01 8 weeks: 1.46 8 weeks: 6.00
12 weeks: 3.91 12 weeks: 1.47 12 weeks: 5.90
16 weeks: 3.63 16 weeks: 1.47 ns 16 weeks: 5.61
17 TC: 7.0 - 9.9, 52 g ISP 15.5 g soy 192 mg 6 weeks Baseline: 5.13 Baseline: 1.58 Baseline: 7.5
men and post- cotyledon fiber 6 weeks: 4.45 6 weeks: 1.67 ns 6 weeks: 6.86
menopausal
women
18 TC: 6.7 - 9.9, 41.4 g ISP 9 g soy 153.18 mg (in 8 weeks Baseline: 5.11 Baseline: 1.67 Baseline: 7.53
men and post- (in yoghurt) cotyledon fiber yoghurt) 8 weeks: 4.71 8 weeks: 1.72 ns 8 weeks: 6.86
menopausal (in yoghurt)
women
19 Statin-treated 30 g ISP 9.63 g (with 76% 102 mg 8 weeks’ statin Baseline statin: 3.6 Baseline statin: 1.6 Baseline statin:
hypercholes- cotyledon fiber) 6 weeks’ statin 6 weeks: 3.1 (in 6 weeks: 1.5 ns (in 5.9
terolemic + soy-protein men), 3.3 (total men) 1.6 ns (in 6 weeks: 5.3
patients; supplement population) total (in men),
LDL with sta- 6 weeks’ statin mean after 6 population) 5.5 (in total
tin treatment weeks statin population)
>3.0 mmol/L alone (phase I
and III): 3.6
20 TC: 5.8 - 7.9, Active 1: Active 1: Active 1: 8 weeks Active 1: Active 1: Active 1:
LDL >3.4; 25 g ISP 3.2 g soy 96.6 mg Baseline: 4.36 Baseline: 1.51 Baseline: 6.97
men and Active 2: cotyledon fiber Active 2: 4 weeks: 4.19 4 weeks: 1.42 ns 4 weeks: 6.44
women 25 g ISP Active 2: 96.4 mg 6 weeks: 4.19 6 weeks: 1.4 ns 6 weeks: 6.44
0g 8 weeks: 3.94 8 weeks: 1.42 ns 8 weeks: 6.41
Active 2: Active 2: Active 2:
Baseline: 4.41 Baseline: 1.51 Baseline: 7.03
4 weeks: 4.27 4 weeks: 1.48 ns 4 weeks: 6.61
6 weeks: 4.28 6 weeks: 1.51 ns 6 weeks: 6.74
8 weeks: 4.17 8 weeks: 1.49 ns 8 weeks: 6.79
21 TC: 5.8 - 7.9, Active 1: Active 1: Active 1: 8 weeks Active 1: Active 1: Active 1:
LDL >3.4; 25 g ISP 3.2 g soy 96.6 mg Baseline: 4.31 Baseline: 1.46 Baseline: 6.88
men and Active 2: cotyledon fiber Active 2: 4 weeks: 4.50 4 weeks: 1.52 4 weeks: 6.79
women 15 g ISP Active 2: 58 mg 6 weeks: 4.27 6 weeks: 1.48 6 weeks: 6.81
1.92 g soy 8 weeks: 4.06 8 weeks: 1.48 8 weeks: 6.58
cotyledon fiber Active 2: Active 2: Active 2:
Baseline: 4.10 Baseline: 1.44 Baseline: 6.58
4 weeks: 4.31 4 weeks: 1.47 4 weeks: 6.46
6 weeks: 4.24 6 weeks: 1.48 6 weeks: 6.66
8 weeks: 4.06 8 weeks: 1.50 8 weeks: 6.57
22 TC: 5.2 - 7.8, Active 1: Active 1: Active 1: 4 weeks Active 1: Active 1: Active 1:
men and 1 L ultra heat-treated 4.7 g soy 82.8 mg Baseline: 3.468 Baseline: 1.571 Baseline: 6.25
women chocolate-flavored cotyledon fiber Active 2: 2 weeks: 3.977 2 weeks: 1.565 ns 2 weeks: 6.13 ns
milk with 24.4 g soy Active 2: 41.4 mg 4 weeks: 4.112 4 weeks: 1.571 ns 4 weeks: 6.227 ns
protein added 2.35 g soy Active 2: Active 2: Active 2:
Active 2: cotyledon fiber Baseline: 3.915 Baseline: 1.516 Baseline: 6.77
0.5 L ultra heat-treated 2 weeks: 4.427 2 weeks: 1.555 ns 2 weeks: 6.54 ns
chocolate-flavored 4 weeks: 4.598 4 weeks: 1.542 ns 4 weeks: 6.56 ns
milk with 12.2 g soy
protein added
HDL=high-density lipoprotein; ISP=isolated soy protein; LDL=low-density lipoprotein; ns=not significant; TC=total cholesterol

32 Integrative Medicine • Vol. 8, No. 4 • Aug/Sep 2009 Grünwald et al—Cardiovascular Benefits of Soy
ized, placebo-controlled studies, 1 was a controlled, double-
blind, crossover study, and 1 was an open-label, single-center,
cohort study (see Table 1). The placebo-controlled studies used
equal amounts of casein protein and cellulose fibers instead of
the soy equivalent. One study included only type 2 diabetics
with mild hypercholesterol levels (nearly normocholesterolic),
1 study included only hypercholesterolic subjects with addi-
tional statin medication, 4 studies included subjects with mild
hypercholesterolemia (5.8-7.8 or 7.9 mmol/L total cholesterol),
and 2 were studies on subjects with higher (6.7 or 7.0-9.9
mmol/L total cholesterol) cholesterol levels. The mean age of
the subjects in all studies was over 50.
As active treatment, subjects in all studies received at least 25
g isolated soy protein per day with a high isoflavone content of at
least 3.4 mg/g soy protein, and a significant amount of soy cotyle-
don fibers (see Table 2). Cotyledon soy fiber is defined as dehulled
and defatted cell wall structures from the soy bean. Supplements
were taken for at least 4 weeks or as long as 16 weeks.
Results of the Individual Studies on Serum Lipid
Concentration
Hermansen et al (2001)15: In the study by Hermansen et
al, the objective was to evaluate the effects of a dietary soy-pro-
tein supplement containing isolated soy protein (50 g/d), iso-
flavones, and 20 g cotyledon soy fiber on cardiovascular risk
markers, blood glucose, and insulin levels in type 2 diabetic
subjects. In this placebo-controlled, double-blind, crossover
study, soy-protein supplementation resulted in a significantly
lower mean LDL-cholesterol value (10%), a lower mean
LDL/HDL ratio (12%), and a nonsignificant reduction in the
mean concentration of total cholesterol of 8%. Furthermore, the
apo B100 content was decreased by 30%. No changes occurred
in HDL cholesterol, apo B100/apo A1 ratio, plasminogen acti-
vator inhibitor1, factor VIIc, von Willebrand factor, fibrinogen,
lipoprotein (a), glucose, HbA1c, or 24-hour blood pressure. The
mean value of the cholesterol-independent CVD risk factor
homocysteine was significantly reduced by 14% (P<.01 com-
pared with changes in the placebo group). This study showed a
clear cholesterol-lowering effect on type 2 diabetic subjects with
nearly normal plasma cholesterol levels.
Tonstad et al (2002)16: In this trial, researchers performed
a dosage-finding study on hypercholesterolic subjects. Subjects
were treated with either 30 g or 50 g soy protein with 10 g or 16.6
g cotyledon fibers and 3.7 mg isoflavonoids/g protein. After 16
weeks of treatment, LDL-cholesterol values decreased signifi-
cantly from baseline by 0.87 mmol/L and 0.95 mmol/L in the
30-g/d and 50-g/d protein groups, respectively. The reduction
of total cholesterol from baseline was 0.86 mmol/L and
0.91 mmol/L, respectively. The HDL-cholesterol concentration
slightly increased by 0.07 mmol/L (30-g/d group) and 0.05
mmol/L (50-g/d group). However, there were no significant dif-
ferences between the 2 active treatment groups in changes of
LDL, HDL, or total cholesterol levels.
In this study, even the subjects of the control group (treated
with equivalent amounts of casein and cellulose fibers) showed a
significant reduction in LDL-cholesterol levels.16 However, the
Grünwald et al—Cardiovascular Benefits of Soy
reduction in total and LDL cholesterol was less in the control
group than in the soy protein–treated groups. These differences
were statistically significant. The cholesterol-lowering effect seen
in the control group was probably related to the dietary changes
(a cholesterol-lowering diet from the American Heart Association)
that the subjects were asked to make previously (for at least 4
weeks) and during the observation period to minimize baseline
variability among the subjects.
The decrease of plasma homocysteine levels in this study is
noteworthy.16 In both treatment groups, after 16 weeks the
homocysteine concentration was significantly reduced (P=.005
for the interaction between treatment and time) by 0.2 μmol/L
compared to baseline (corresponding to ≈2%), whereas homo-
cysteine levels increased in the placebo group treated with casein
and cellulose fibers.
Puska et al (2002)17: A similar reduction in LDL-cholesterol
content was shown in the study performed by Puska et al, in
which subjects with elevated total cholesterol levels (TC: 7.0-9.9
mmol/L) took a soy-protein supplement containing 52 g protein
(with standardized high isoflavone content of 3.7 mg/g soy pro-
tein) and cotyledon fibers for 6 weeks followed by a follow-up
period of 4 weeks without medication. The mean reduction of
LDL in the treatment group, compared to baseline, was 13.2%
(significance between the control and active treatments was
P=.014). Total-cholesterol concentration in the treatment group
was reduced by 8.5% (significance between the control and
active treatments was P=.049). There was also a slight, but non-
significant, increase in HDL in the treatment group. However,
the placebo medication used in this study, casein with cellulose
fiber, also exhibited a lipid-lowering action. The lipid-lowering
effect was significantly greater in the soy group compared to the
placebo group.
As in Tonstad et al, this 2002 Puska et al study also clearly
showed a statistically significant (even though there was only a
small reduction) homocysteine-lowering effect for the soy-
protein supplement of 0.32 μmol/L (3%).17 After the 4-week
follow-up period without treatment, total cholesterol as well as
LDL-cholesterol values returned to baseline.
Puska et al (2004)18: Another double-blind, placebo-
controlled study, conducted by Puska et al, investigated the effect
of yoghurt that contained isolated soy proteins with high levels of
isoflavones, phospholipids, and cotyledon soy fibers, on hyper-
cholesterolic subjects. After an 8-week, open, dietary run-in phase
(consuming a cholesterol-lowering diet, to reduce the variation in
subjects’ cholesterol-value baselines), subjects were treated twice a
day with a yoghurt formulation containing 20.7 g soy protein,
76.59 mg isoflavones, 4.5 g cotyledon fibers, and 1.76 g soy leci-
thin. The control group received cow’s milk yoghurt with an
equivalent amount of milk protein and cellulose fibers. After 8
weeks of the soy-yoghurt formulation, the LDL-cholesterol level in
the treated subjects was significantly reduced by 7.8%, as were
non-HDL-cholesterol levels (6.1%) and the total:HDL-cholesterol
ratio (2.4%). Compared to placebo, there were no differences in
the effect on HDL-cholesterol triacylglycerols or homocysteine.
Clausen et al (2004)19: The primary objective of the study
by Clausen et al was to test whether a soy-protein supplement
Integrative Medicine • Vol. 8, No. 4 • Aug/Sep 2009 33
 further reduces plasma cholesterol concentrations when given
to statin-treated, hypercholesterolemic patients. This study was
divided into 3 phases. During phase I, patients were treated for
6 weeks (+ 2 weeks run-in phase) with statin alone. In phase II,
patients received a combination therapy of statin and the soy-
protein supplement for 6 weeks, followed by phase III where the
patients were again treated with statin alone for 6 weeks. The
plasma concentrations of total cholesterol and LDL cholesterol
were significantly lower, after 6 weeks of combination treatment
(total cholesterol: 5.5 mmol/L; LDL: 3.3 mmol/L), than the
mean value of the concentrations after 6 weeks of statin mono-
therapy (mean value of the end of phase I and end of phase III:
total cholesterol was 5.9 mmol/L; LDL was 3.6 mmol/L). After
only 1 week of combinational therapy, total cholesterol and LDL
cholesterol levels were significantly reduced (5.6 vs 5.9 mmol/L
and 3.3 vs 3.6 mmol/L, respectively) in the subjects treated with
the soy-protein supplement.
No significant differences in plasma HDL cholesterol and
triglyceride concentrations were found between the statin mono-
therapy and statin + soy protein combination-therapy periods.19
Analysis of the differences in plasma concentrations of total
and LDL cholesterol suggests that the effect of the soy-protein
supplement was greater in males (LDL 3.1 mmol/L after 6
weeks) than in the total study population (LDL 3.3 mmol/L); in
fact, no significant effect was detectable in women.19 The soy-
protein supplement further decreased cholesterol levels already
lowered by statin.
Høie et al (2005)20: In a study by Høie et al, the effect of soy
fibers and phospholipids in a soy-protein preparation was inves-
tigated. Two different soy-protein preparations were compared:
1 with soy fiber and phospholipids and 1 without soy fiber and
phospholipids that had proteins derived from caseinate and
skimmed milk powder.
After 8 weeks of treatment, total cholesterol levels decreased
by 0.56 ± 0.67 mmol/L (P<.001) in the soy fiber/phospholipids
group and by 0.24 ± 0.58 mmol/L (P=.065) in the non-soy fiber/
phospholipids group, while a slight rise of 0.07 ± 0.82 mmol/L
was observed in the placebo group.20 In direct comparison, the
differences in decrease of total cholesterol observed between the
2 soy treatments were statistically significant (P=.025). In addi-
tion, the LDL-cholesterol value also decreased in the soy fiber/
phospholipids-treated group. At the end of the 8-week trial, LDL
values were reduced by 0.42 ± 0.51 mmol/L in the soy fiber/
phospholipids group and by 0.24 ± 0.51 mmol/L in the non-soy
fiber/phospholipids group. LDL-cholesterol changes within
both soy-treatment groups differed significantly from the place-
bo values (differences from placebo were P<.001 and P=.033,
respectively). In the placebo group, a minor increase in LDL
values of 0.04 ± 0.58 mmol/L was observed.
Even though the difference in lipid-lowering effects between
the 2 soy supplementations were not statistically significant
(P=.12), subjects treated with the fiber- and phospholipids-
containing preparation showed a 2-fold reduction in total choles-
terol and LDL-cholesterol levels.20 From this study, there seems
to be a greater lipid-lowering effect for soy fibers and phospholip-
ids together with soy protein than with this particular soy pro-
34 Integrative Medicine • Vol. 8, No. 4 • Aug/Sep 2009
tein alone; whether or not this could be generalized to all soy
protein alone needs to be further investigated.
Høie et al (2005)21: The lipid-lowering effect of 2 dosages
of a soy-protein supplement was tested on hypercholesterolemia
patients in another 2005 study by Høie et al. Subjects were
treated for 8 weeks with a soy-protein supplementation of either
15 g or 25 g per day or placebo.
By week 8, LDL-cholesterol levels had fallen by 0.26 ± 0.47
mmol/L in the 25-g group, corresponding to a decline of 5.9%
compared with baseline and 9.5% compared with placebo.21 In
the 15-g group, LDL cholesterol decreased by 0.05 ± 0.66 mmol/
L—a decline of 1.1% compared with baseline and 4.7% com-
pared with placebo. In the placebo group, an increase in LDL
cholesterol of 0.15 ± 0.59 mmol/L was observed. LDL-cholesterol
changes in each active-treatment group versus the placebo
group were statistically significant (25 g vs placebo, P=.002; 15 g
vs placebo, P=.011).
A reduction of the total-cholesterol level was seen only in
the 25-g group.21 By week 8, those values in the 25-g group had
decreased by 0.30 ± 0.58 mmol/L (4.6% reduction compared
with baseline and a 7.4% reduction compared with placebo). In
the 15-g group, total-cholesterol levels remained virtually
unchanged, with only a small decline of 0.01 ± 0.75 mmol/L.
These results indicate that the consumption of only 15 g of soy
protein daily for 8 weeks is not sufficient to significantly lower
total and LDL-cholesterol levels. Twenty-five grams of soy pro-
tein over 8 weeks significantly reduced these levels, an effect that
was previously shown in the dosage-finding study performed by
Tonstad et al16 in which 50 g of soy protein daily had no addi-
tional effect on lowering these values compared to 30 g/d.
Høie et al (2006)22: The chemical nature of the soy prepa-
ration is important to achieve effects on blood-lipid levels. In a
third study, this time in 2006, Høie et al investigated ultra-
heated soy-protein supplement in milk. This treatment negated
the lipid-lowering effect of soy-protein supplementation shown
in many other studies. Unexpectedly, at the end of the study,
the LDL-cholesterol concentration was significantly increased
compared with baseline in all study groups.
Conclusions From These Studies
The studies listed above clearly show an improvement in
cholesterol levels with sufficient daily amounts of soy-protein
supplement (with soy fibers and phospholipids) in subjects with
mild-to-moderately elevated plasma-lipid levels, as well as in
subjects with type 2 diabetes with nearly normal cholesterol
levels. Plasma total- and LDL-cholesterol levels were signifi-
cantly reduced by these preparations (Nutri 5, Abalon,
Abacor).15-22 Furthermore, HDL cholesterol was slightly elevat-
ed in most of the studies by soy-protein supplementation (even
though the increases were not significant in any of the stud-
ies).17-18,21,22 In most cases, the cholesterol-lowering effects were
seen after 1 week of soy-protein supplementation.
Concentrations of soy protein higher than 30 g/d had no
additional effect on lowering LDL cholesterol.16-18 Preparations
with 15 g or fewer per day showed only a small cholesterol-
lowering effect.21 These data support the FDA recommendation
Grünwald et al—Cardiovascular Benefits of Soy
of consuming 25 grams of soy protein per day. In addition, sub-
jects who consumed 50 g of soy protein/day were more likely to
withdraw because of intolerance.16
It seems that preparations containing fibers and phospholip-
ids decrease cholesterol levels more effectively than preparations
containing only soy protein without additional fibers and phos-
pholipids.20 Ultra-heat treatment of soy-protein preparations
negates the lipid-lowering properties of soy preparations.22
The soy-protein supplement studied further decreased
cholesterol levels already lowered by statins.19 Therefore, it
could be an attractive alternative to increasing statin dosage or
for patients who do not achieve satisfactory cholesterol-lowering
results from statin drugs due to resistance or intolerance.
The independent indicator of atherosclerotic-vascular risk,
homocysteine, was also sometimes decreased in subjects treated
with these soy-protein supplements.
Safety, Adverse Events, and Interaction of Soy-
Protein Supplements
In all studies performed with soy-protein supplements
containing high amounts of isoflavones and cotyledon fibers,
the test products were well tolerated and no serious adverse
events were reported (see Table 2 and Figure 1).
Even though soybeans and various soybean products have
been consumed as staple foods for more than 5000 years, con-
tact with or consumption of soybeans or soybean products
could lead, as with many other foods, to allergic reactions. Soy
is listed by the Food and Agriculture Organization of the United
20
15
Percent Changes of LDL Cholesterol From Baseline
10
5 15g ISP
0
0 2
-5
-10
-15
-20
-25
* ISP=isolated soy protein
Figure 1. The cholesterol-lowering effect of soy-protein supplementation shown in different studies as a percentage referring to baseline.
Grünwald et al—Cardiovascular Benefits of Soy
Nations as 1 of the 8 most significant food allergens along with
milk, eggs, fish, crustaceans, wheat, peanuts, and tree nuts.23
The allergic potential of soy was compared to some of the major
food allergens by Cordle.23 Although it is listed together with
these major food allergens, the amount of protein needed to
initiate an allergic reaction (12.94 mg) in 1% of a population is
more than 40 times higher than that of cow’s milk (0.279 mg)
and 500 times higher than that of eggs (0.023 mg), indicating a
lower allergic reactivity. These values were determined by dose-
response distribution. It has been also shown that 400 mg of
soy protein is safe for 90% of allergic patients, whereas only 0.1
mg of peanut, 1 mg of hazelnut, or 3 mg of egg or milk is safe
for 90% of allergic patients.23 The severity of the allergic reac-
tion to soy is less than has been observed for eggs, milk, wheat,
and peanuts.
In the studies listed in Table 1, no serious adverse events
were reported related to the consumption of the soy supple-
ments Nutri 5, Abalon, and Abacor. In the study by Puska et al
(2002),17 a slight increase in serum uric-acid values was seen but
was not considered to be of any clinical relevance. In the later-
mentioned study by Puska et al (2004)18 where the soy supple-
ment was given in a yoghurt formulation, a significant portion of
subjects dropped out of the study due to “refusal to take more of
the investigational product” or “adverse events,” such as nausea,
vomiting, stomach pain, and feeling of stomach swelling. These
adverse events were mild and transient. In the study by Clausen
et al,19 there were more gastrointestinal complaints from sub-
jects treated with statins and soy supplements than for those
50g ISP; type II diabetes
30g ISP
50g ISP
52g ISP
41.4g ISP in yogurt
30g ISP + statin
25g ISP + fiber
25g ISP – fiber
25g ISP
25g ISP ultra heat treated
12.5g ISP ultra heat treated
4 6 8 10 12 14 16
Time in Weeks
Integrative Medicine • Vol. 8, No. 4 • Aug/Sep 2009 35
 treated with statins alone. For 9 subjects of the treatment group
of the study by Høie et al (2005),21 observed adverse events were
eczema, sensation of fullness, heartburn, nausea, constipation,
flatulence, diarrhea, and impaired sexual function. However,
none were classified as serious adverse events. In general, the soy
supplements were well tolerated.
Soy isoflavones may adversely affect thyroid function. The
goitrogenic potential of soy has been shown in children fed with
soy formula (for review, see Chen and Rogan24). Thyroid-
hormone biosynthesis may be affected by inhibiting thyroid
peroxidase and tyrosine proteinkinase.25-27 Due to this concern,
many clinical trials have been undertaken. In a recent publica-
tion, Messina and Redmond28 reviewed 14 trials with the con-
clusion that, with only 1 exception, a soy-rich diet has only a
mild hormonal effect. However, there is a clear correlation
between some thyroid parameters and isoflavone levels.29
Role and Mechanisms of Different Components
of Soy-Protein Supplements in Lowering
Cholesterol Levels
Soybeans contain a multitude of biologically active sub-
stances such as proteins, peptides, isoflavones, phospholipids,
fibers, saponins, and fatty acids, all of which are included in vari-
ous concentrations in different soy-protein preparations. It is still
not completely understood which of the chemical constituents or
their metabolites are responsible for the lipid-lowering effects of
soybeans. Possible mechanisms for the hypocholesterolemic
effect of soy protein have been described in many reviews.30-35
Based on multiple in vitro and in vivo studies on animal and
humans, several mechanisms are suggested, including increased
LDL-receptor activity, increased synthesis and fecal excretion of
bile acids, increased plasma-thyroxin concentrations, and sup-
pression of cholesterol absorption.32-34 Furthermore, the modu-
latory activity of different components of soy-protein prepara-
tions on transcription factors, changing the downstream gene
expression involved in lipogenesis or lipolysis, is discussed (for
review, see Xiao, Mei, and Wood34).
We believe that the lipid-lowering effect of soy-protein sup-
plements is a synergistic action of all of its different components.
They all contribute to various extents to cholesterol-lowering
effects. We will attempt to explain the different effects of the dif-
ferent constituents.
Soy Protein/Peptides
Trials with soy-protein preparations always include other
components to a minor extent. It is therefore not easy to attri-
bute the cholesterol-lowering effect of soy protein simply to the
protein itself.
One explanation for soy protein acting as a cholesterol-
lowering substance is simply its amino acid composition. Lysine
and methionine, in general, show moderate hypercholester-
olemic properties. In contrast, arginine lowers the cholesterol
concentration. Soy protein contains more arginine than lysine
and methionine, which could account for at least a small amount
of the lipid-lowering properties of soy protein.36-38
Recent studies have identified the soybean 7S globulin, also
36 Integrative Medicine • Vol. 8, No. 4 • Aug/Sep 2009
called β-conglycinin, as a major cholesterol-lowering peptide. It is
a heterotrimer consisting of α’, α, and β subunits. The cholester-
ol-lowering effect of this component has been demonstrated in
animal, as well as human, studies.39-41 Recent studies on human
Hep G2 cells and in vivo experiments on rats have demonstrated
that the α’ subunit from soybean 7S globulin clearly lowers plas-
ma cholesterol concentration.42,43 Experiments with the isolated
α’ chain clearly demonstrate that this single unit has plasma lip-
id-lowering and β-VLDL-receptor upregulating properties.42
With detection of this mechanism, 1 important component
of the cholesterol-lowering effect of soy protein was found.
Isoflavones
Of all of the active components of soy, isoflavones have
received the most attention in recent years. Isoflavones are pres-
ent in various amounts in different soy-protein preparations.
Dried soybeans from various plants, soy flour, and isolated soy
protein provide up to 4.2 mg of isoflavones per gram.44 It has
been thought for many years that the lipid-lowering function of
soy supplements is linked to isoflavones.
Soybeans contain 2 major isoflavones, genistein and daid-
zein, and a minor one, glycitein. Isoflavones have structures
similar to mammalian estrogens and can bind to the estrogen
receptors (ER) ER-α and ER-β. It is well known that estrogen
modulates the blood-lipid profile by promoting a decrease of
LDL and an increase of HDL.
The effect of isoflavones on serum-cholesterol levels is,
however, controversial. Several studies have reported a choles-
terol-lowering effect for soy isoflavones while others have not.
In a recent study, female golden Syrian hamsters were fed
pure synthetic daidzein, genistein, or glycitein for 4 weeks.45
Hamsters fed glycetein had significantly lower plasma total (by
15%) and non-HDL (by 24%) cholesterol levels compared with
controls, while those fed daidzein and genistein did not show
such effects. Another study in which male rabbits were fed an
atherogenic diet (27% casein) supplemented with isoflavones
(0.73 or 7.3 mg of isoflavones/kg/d) for 180 days, soy isoflavones
produced hypolipidemic effects and decreased the pro-inflam-
matory LDL subfraction in the blood plasma and aortas of
hypercholesterolemic rabbits.46 Hsu et al47 found, in a clinical
study, that soy-germ isoflavone extract may significantly improve
the serum lipid profile of postmenopausal women who receive
hormone therapy.
However, other studies found no effect for isoflavones on
plasma lipid levels.48
Because the lipid-lowering effect of isoflavones in clinical
studies is not always equivalent, meta-analyses integrating vari-
ous studies are helpful to find correlations and effects. A recent
meta-analysis of 8 randomized trial on human subjects indicated
that there is an LDL-cholesterol–lowering effect for isoflavones
independent of soy proteins.49 Another meta-analysis of 11 ran-
domized controlled trials evaluated the precise effects of soy
isoflavones on lipid profiles.50 The researchers also examined
the effects of soy protein that contained enriched and depleted
isoflavones. In the 11 studies that they included in their meta-
analysis, soy isoflavones significantly decreased serum total
Grünwald et al—Cardiovascular Benefits of Soy
cholesterol by 0.10 mmol/L (3.9 mg/dL or 1.77%; P=.02) and
LDL cholesterol by 0.13 mmol/L (5.0 mg/dL or 3.58%;
P<.0001). However, no significant changes in HDL cholesterol
were found. The decrease in LDL cholesterol was more pro-
nounced with soy protein that contained enriched isoflavones
than in the preparation without. As in many other studies, the
reduction in LDL cholesterol was larger in the hypercholester-
olemic subjects than in the normocholesterolemics. However,
there was not a significant linear correlation between reduction
in LDL cholesterol and soy-protein ingestion or isoflavone intake.
Hence, the discussion as to what extent isoflavones are responsi-
ble for the lipid-lowering effect of soy protein is ongoing.
Cotyledon Fibers
The cell wall of the soybean cotyledon is a great source of
soluble and insoluble soy fibers. There is evidence that both
purified viscous soluble fiber and soluble fiber in foods reduce
serum cholesterol. Dietary fibers are not digested by human
gastrointestinal enzymes but may be partially degraded by
colonic bacteria.51
Studies in animals suggest that some soluble fibers can
bind bile acids or cholesterol during the intraluminal formation
of micelles, leading to a greater excretion of cholesterol as bile
acid.33 However, greater bile excretion with soluble fibers was
not observed in humans. The effect of soy cotyledon fibers was
tested in a double-blind, crossover study.52 It was found that soy
cotyledon-fiber supplementation did not produce visible intol-
erance and significantly lowered plasma total and LDL choles-
terol in subjects with mildly elevated plasma cholesterol levels.
One suggested mechanism for lower plasma total and
LDL cholesterol reported is that the soluble fiber of soybeans
is fermented in the colon and generates short-chain fatty acids
such as acetate, butyrate, or propionate, which inhibit hepatic
lipid synthesis.53
Anderson et al32 suggested several other mechanisms by
which soy fibers influence serum-cholesterol concentrations.
Dietary fibers may alter gastric empting, which could change the
rate of lipid absorption, intestinal transit time, and intestine
motility, thereby changing the rates of lipid absorption and
lipoprotein assembly in the intestine, modifying pancreatic
secretion or enzyme activity, changing transport barriers, modi-
fying lymphatic flow rates, and influencing secretion rates of
insulin or other pancreatic or intestinal hormones.
However, in many cases, different soy-protein components
show a synergistic effect. One example of this is cotyledon fibers
and isoflavones. The soluble and insoluble components of soy
fibers appear to improve the microbial flora in the intestine and
gastrointestinal function. Bacteria in the intestine cleaves the
isoflavone glycosides from the biologically active components
genistein and daidzein.54 Therefore, an intact healthy microbial
flora influences the bioavailability of soy isoflavones.
Phospholipids
Phospholipids are primarily found in soybean oil; howev-
er, these components are also present, in smaller amounts, in
soy protein.55 Phosphatidylcholine, a major component of leci-
Grünwald et al—Cardiovascular Benefits of Soy
thin, is, at 73% to 76%, the main component of soy phospholip-
ids.56 A cholesterol-lowering effect has been reported for puri-
fied phospholipids.57,58 The high molecular-weight fraction of
the soy-protein hydrolyzate contains approximately 10% of
phospholipids, which might have some additional lipid-lowering
effects.59 Hori et al60 hypothesized that the binding of phospho-
lipids to soy-protein hydrolyzate in large quantities may have
stronger cholesterol-lowering effects. One mechanism of phos-
pholipids or soybean on cholesterol levels is that the activation
of reversed cholesterol transport, including the activation of
lecithin-cholesterol-acetyltransferase, has been shown to
increase cholesterol uptake by HDL and increased biliary excre-
tion of cholesterol.61-65
Saponins
Soy saponins, another class of chemical constituent of the
soybean, have been reported to reduce serum cholesterol.66-68
At least 2 modes of actions are discussed for this effect. Because
of their particular defined structure, soy saponins form insoluble
complexes with cholesterol. Therefore, saponins in the intestinal
system inhibit the intestinal absorption of endogenous and
exogenous cholesterol.67,68 Furthermore, saponins can form
mixed micelles with bile acids. In this manner the resorption of
bile acid is blocked, leading to increased bile acid excretion.66-68
Phytosterols
Sterol is an important constituent of cell membranes.
Cholesterol is the sterol of mammalian cells, while phytosterols are
derived from plants. Plant sterols are structurally related to human
cholesterol, with a different side-chain configuration. The main
source of phytosterols is fat-rich plant parts such as sunflower
seeds, wheat germ, soy beans, and pumpkin seeds. They are
absorbed less and excreted faster by bile than is cholesterol. It has
been shown that phytosterols inhibit cholesterol absorption by
displacing intestinal cholesterol from the micelles and thereby
reducing intestinal cholesterol absorption. This competitive
absorption also results in a compensatory increase in endogenous
cholesterol synthesis, leading to a lower cholesterol level (for
reviews, see Kerckhoffs et al31 and Chagan et al69).
Variation in Cholesterol-lowering Results in
Different Studies
The LDL-cholesterol lowering effect of soy protein has been
shown in this study as well as many previous studies.67,68 The
cholesterol-lowering effect, and the magnitude of effect, is vari-
able from study to study. A broad variety of factors could cause
these differences.
As an example, a soy-protein-rich diet, mainly based on soy
products from the supermarket, including baked soybeans,
toasted soy flakes, or soy flour cookies, when consumed over 6
weeks had no cholesterol-lowering effect.70 In the same experi-
ment, a diet rich in unprocessed soymilk and tofu resulted in
LDL-cholesterol reduction. One explanation for the discrepancy
could be that extensive processing, as occurs in processed super-
market foods, causes denaturing of proteins, peptides, isofla-
vones, and other ingredients. If so, the structure of biologically
Integrative Medicine • Vol. 8, No. 4 • Aug/Sep 2009 37
 active components has been changed, and they are therefore no
longer able to bind to specific receptors or transcription factors
to mediate their functions. Høie et al (2006)22 obtained a similar
result by ultra-heat treatment of a soy-protein preparation. In his
study, as previously mentioned, an ultra-heat-treated soy-milk
preparation did not decrease cholesterol levels.
The soy-protein preparations used in various studies differ
markedly in both macro (protein, fat, and carbohydrate) and
micro (isoflavones, saponins, phytic acid, phospholipids, vita-
mins, and minerals) components.44 Different sources of soy-
beans and storage conditions could cause these differences.
Various extraction techniques may remove specific, and possi-
bly not yet identified, important components. Alcohol extrac-
tion is often used to concentrate the protein content of supple-
ment preparations. However, this procedure removes the sug-
ars, oligosaccharides, saponins, and most of the isoflavones
from the soy.71 It is also known that ethanol treatment could
alter the protein conformation. Using 2-dimensional gel elec-
trophoresis, Gianazza et al72 have shown that after ethanol
treatment the 7S globulin was degraded into various smaller
peptides in different isolates.
Furthermore, the amount of components in these studies is
often not clearly indicated. In many studies, it is not indicated if
the amount of isoflavones is measured as aglycones or in glyco-
side form, which has a much higher molecular weight. In addi-
tion, the ratio of the different isoflavones may not be stated.
Women with different estrogen levels react differently
to phytoestrogens. Women with low blood estradiol levels
(<184 pmol/L [<50 pg/mL]) have higher phytoestrogen uptake
from the diet containing phytoestrogens, and react with lower
LDL and higher HDL levels.73
Women with a specific, single nucleotide polymorphism in
the estrogen receptor betacx Tsp509I (genotype AA) react to
isoflavone-enriched diets with increased HDL levels.74
Finally, human subjects differ tremendously in their ability
to metabolize isoflavones. The bioavailability of isoflavones
depends upon the relative ability of gut microflora to degrade
these components.54 Only 30% to 50% of humans can produce
equol from daidzein. Equol has been suggested to have more
estrogenic activity than the other phytoestrogens.75-77
All these differences lead to different, often opposing, results
in the lipid-lowering action of soy protein preparation. Therefore,
it is important to perform future studies on the effects of soy pro-
tein in as standardized a manner as possible.
Other Benefits of Soy Protein on Decreasing CVD risk
Effects on blood pressure: CVD is not only associated with
high cholesterol levels; hypertension is known to be another
important CVD risk factor. Reduction of systolic blood pressure
by only 2 to 5 mmHg reduces the risk of stroke and CHD by 6%
to 14% and 4% to 9%, respectively78 (see Table 3). It is well known
that nutrition has an impact on blood pressure. In hypertensive
female rats, an 8-week diet containing isolated soy protein
resulted in a decreased mean arterial pressure when compared
to controls.79 In a recent study, it was shown that the daily con-
sumption of 1 L of soy milk (Calcimel, Santivery s.a., Barcelona,
38 Integrative Medicine • Vol. 8, No. 4 • Aug/Sep 2009
Table 3. Effects and Assumed Potential Mechanisms of
Lowering CVD Risk by Supplementing With Soy Protein:
Conclusions From This Study
Decrease of plasma cholesterol levels
• Increase of the bile acid excretion
• Increase of the LDL receptor activity
• Upregulation of LDL receptors by increased LDL receptor
mRNA level
• Reduction of cholesterol absorption
• Increased thyroxin and thyroid-stimulating hormone
• Inhibition of endogenous cholesterol synthesis
Reduced homocysteine levels
Enhanced blood vessel function
• Reduced atherosclerosis by reduced LDL oxidation
• Increased arterial compliance
• Inhibition of monocyte adhesion to endothelial cells by
isoflavones
Reduced blood pressure
Estrogenic activity of soy isoflavones
Effects on obesity
• Limits or reduces body fat accumulation
• Improves insulin resistance
Spain) over a period of 3 months leads to a reduction of systolic
blood pressure of 18 mmHg, in comparison to the consumption
of 1 L of cow milk over the same interval.80 A recent study found
that substituting soy nuts for non-soy protein improves blood
pressure and LDL cholesterol levels in hypertensive women and
blood-pressure-normotensive postmenopausal women.81
Genistein, one of the soy phytoestrogens, upregulates the
endothelial nitric oxide synthase and thereby lowers blood pres-
sure in hypertensive rats.82 However, not all studies have
reported the same result of blood-pressure–lowering effect for
soy proteins.83
Effects on LDL oxidation: LDL cholesterol in its oxidized
form is more pathogenic than unoxidized LDL cholesterol.
Oxidized cholesterol is taken up in macrophages by scavenger-
cell receptors, leading to atherosclerotic plaque. It has been
shown that a soy-protein preparation rich in isoflavones reduc-
es LDL oxidation.84,85 Phospholipids may also protect against
atherosclerosis. Unsaturated lecithin, for example, protects
LDL against oxidation and peroxidation.86
Arterial effects: Arterial compliance and flow-mediated
dilatation are related to the ability of middle-sized arteries to
dilate. This function is also affected in patients with atheroscle-
rosis. Systemic arterial compliance was significantly improved
in perimenopausal and menopausal women taking soy isofla-
vones, to about the same extent as is achieved with conven-
tional hormone-replacement therapy.87
Effects on cerebral and myocardial infarction: In a
recently conducted cohort study, the impact of dietary intake of
soy protein and isoflavones by soy food on cerebral and myocar-
dial infarction was investigated on 40 462 Japanese subjects.88
The conclusion of that study is that regular intake of high
amounts of isoflavones was associated with a significantly
reduced risk of cerebral and myocardial infarction and mortal-
ity in postmenopausal women but not in men.
Grünwald et al—Cardiovascular Benefits of Soy
 Homocysteine effects: Soy-protein supplements have an
impact on homocysteine levels. Moderately elevated homo-
cysteine levels are common in industrialized nations and are
associated with an elevated risk of CVD.89-91 It has been shown
in several studies that soy protein or its components may pro-
tect against homocysteine elevations.92,93 Hanson et al found
that soy protein with native phytate significantly reduces total
homocysteine levels.94
Summary
All of the cited research leads to the conclusion that soy-
protein supplements reduce the risk of CVD. This positive effect
has been shown in several nonclinical and clinical studies
despite the fact that the biologically active components of soy
and their modes of action are still not completely understood.
It has been shown, however, that soy-protein supplements
lower cholesterol levels by regulating the endogenous synthesis
of cholesterol and increasing its catabolism and excretion, as
well as by different mechanisms, inhibiting the uptake of exog-
enous cholesterol. Furthermore, soy and its active components
protect the vascular system by inhibiting cholesterol oxidation,
reducing blood pressure, and lowering homocysteine levels.
Further studies must be performed to completely understand
all these mechanisms.
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40 Integrative Medicine • Vol. 8, No. 4 • Aug/Sep 2009 Grünwald et al—Cardiovascular Benefits of Soy