Content uploaded by Joerg Gruenwald
Author content
All content in this area was uploaded by Joerg Gruenwald
Content may be subject to copyright.
Eur J Nutr (2005) 44 :65 –71
DOI 10.1007/s00394-004-0492-0
Received: 20 May 2003
Accepted: 13 January 2004
Published online: 5 April 2004
L. Høie ()
Nutri Pharma ASA
Kronprincesse Marthas Plass 1
Vika, 0116 Oslo, Norway
E. C. A.Morgenstern · J.Gruenwald
Nutri Pharma GmbH, Berlin, Germany
H.-J.Graubaum · R.Busch
Phytopharm Research
Berlin, Germany
W. Lüder · H.-J. F.Zunft
German Institute of Human Nutrition
Bergholz-Rehbrücke, Germany
H.-J. F. Zunft
Institute for Nutritional Science
University of Potsdam
Potsdam, Germany
■Summary Background Soy pro-
tein is effective in lowering plasma
cholesterol, LDL cholesterol and
triglyceride concentrations.It has
not been conclusively answered,
whether and to what extent other
soy constituents may also con-
tribute to this effect. Objective To
investigate the change in blood
lipid levels after application of two
soy-based supplements containing
soy protein either without
(SuproSoy®) or with (Abacor®) soy
fiber and phospholipids in a ran-
domized placebo-controlled triple-
armed study.Methods 121 hyper-
cholesterolemic adults (66 females,
55 males) were recruited and ran-
domly assigned to one of three
treatments.Over 8 weeks they re-
ceived daily either 25 g soy protein
(as a component of the supple-
ments Abacor® or SuproSoy®) or
25 g milk protein (as a component
of placebo). Serum lipids were
measured at baseline and after 4,6
and 8 weeks. Results After 8 weeks
of supplementation total choles-
terol levels were reduced by
8.0± 9.6% (Abacor®) and
3.4± 8.3% (SuproSoy®);LDL cho-
lesterol levels by 9.7±11.7 % (Aba-
cor®) and 5.4± 11.6%
(SuproSoy®); and Apolipoprotein B
levels by 6.9± 14.6 % (Abacor®)
and 4.0± 12.4% (SuproSoy®).
Serum levels of HDL cholesterol
and triglycerides remained un-
changed. Conclusions A prepara-
tion combining isolated soy protein
with soy fibers and phospholipids
showed twice the lipid-lowering ef-
fect of a preparation containing
isolated soy protein alone.There-
fore, such soy-based supplements
can be useful in reducing the car-
diovascular risk.
■Key words blood cholesterol –
cardiovascular disease – soy
protein – soy phospholipids –
nutritional supplements
ORIGINAL CONTRIBUTION
Lars H. Høie
Eve C. A. Morgenstern
Joerg Gruenwald
Hans-Joachim Graubaum
Regina Busch
Wolf g an g Lüd er
Hans-Joachim F. Zunft
A double-blind placebo-controlled
clinical trial compares the cholesterol-
lowering effects of two different
soy protein preparations in
hypercholesterolemic subjects
Introduction
Cardiovascular diseases cause almost 40% of all deaths
in industrialized countries. Control of this major public
health problem includes early recognition of the related
risk factors. It is widely accepted that dyslipidemia, in
particular hypercholesterolemia, is one of the leading
risk factors for atherosclerosis and coronary heart dis-
ease [1]. Along with hypertension and tobacco con-
sumption,increased cholesterol levels account for ap-
proximately 50% of all coronary heart diseases [2].
In view of the central role that elevated levels of blood
lipids, especially LDL cholesterol, play in the genesis of
atherosclerosis, therapeutic and dietary approaches to
their treatment and prevention are highly relevant. Es-
tablished lipid-lowering drugs, although effective, may
be accompanied by serious adverse reactions [3, 4].As
alternative, early dietary interventions are recom-
mended, such as the restriction of saturated fatty acids
EJN 492
66 European Journal of Nutrition (2005) Vol. 44, Number 2
© Steinkopff Verlag 2004
[3], increased intake of dietary fibers [5, 6] and of pro-
tein-rich legumes, preferably soy [7].
The mechanism by which soy products exert a lipid-
lowering effect is yet unknown. The following possibili-
ties are under discussion: activation of the LDL receptor
by essential amino acids from soy protein [8]; stimula-
tion of fecal bile acid excretion by soy fiber [9]; inhibi-
tion of endogenous cholesterol synthesis [10]. Nume-
rous clinical studies have been performed to demonstrate
that soy protein could cause significant decreases in the
serum levels of total and LDL cholesterol and triglyc-
erides [11–20]. The published results, however, remain
controversial, which can be attributed either to different
study designs or to cofactors in the soy preparations
used. Different treatment durations were used, e. g. 5
[13], 6 [17],16 [20] or 24 [12] weeks, as well as different
daily soy protein intake levels, ranging from 17 to 124 g
[11]. The dosage-response relationship has been investi-
gated in recent studies [17,20]. Otherwise, soy products
differ considerably in their composition, containing
proteins, isoflavones and other soy ingredients of vari-
ous structures and in varying quantities. Isoflavone con-
tent of isolated soy protein is closely linked to their lipid-
lowering action [21, 22]. Various clinical trials have
shown that the decrease in plasma cholesterol levels
achieved with soy protein supplementation is dosage
dependent for the isoflavone concentration [14–16, 23].
Independent cholesterol-lowering and antiatherogenic
effects have been observed for soy components such as
cotyledon fibers [24, 25] or phospholipids [26–29].
There is, however, a lack of data about cooperative ef-
fects of soy constituents in respect to their efficacy as
cholesterol-lowering agents.
This randomized, double blind triple-armed study
was intended to compare the cholesterol-lowering ef-
fects of a soy protein commercial preparation
(SuproSoy®) and a soy protein commercial preparation
enriched with fiber and phospholipids (Abacor®).
Methods
This study enrolled 121 adults (66 women and 55 men),
who met the following inclusion criteria: total serum
cholesterol concentration of 5.8–7.9 mmol/l; serum
LDL cholesterol ≥3.4 mmol/l; serum triglycerides
<4.5mmol/l; ages 30–70; and written informed consent.
The exclusion criteria were severe cardiovascular, gas-
trointestinal, hepatic, renal or endocrine diseases; hy-
pertension (> 160/100mmHg); myocardial infarction or
apoplexy; familiar hypercholesterolemia; diabetes mel-
litus type-1 and type-2 under drug therapy; severe obe-
sity (BMI ≥ 35 kg/m2); use of lipid-lowering drugs in the
4 weeks previous to the trial; adverse reactions to milk
proteins or other components of the verum and placebo
preparation; drug or alcohol abuse; HIV infection or
clinically manifest AIDS; plans to reduce weight during
the study period; pregnancy or breast-feeding; partici-
pation in a clinical trial within 4 weeks previous to the
trial; or potential compliance problems due to insuffi-
cient knowledge of the German language. Concomitant
medications,which could not be expected to notably in-
fluence the study results, were permitted.
The study complied with the good clinical practice
recommendations of the European Union as approved
by the Ethics Committee of the Humboldt University,
Medical School (Charité), Berlin, and was conducted be-
tween July and December 2001.The trial was performed
as a randomized, placebo-controlled, double blind
study. For an individual trial period of 8 weeks and by
means of a block randomization procedure,participants
were assigned to one of three groups,receiving daily ei-
ther 77.5 g Abacor® (containing 25 g soy protein),71.9 g
SuproSoy® (containing 25 g soy protein), or 76.4 g
placebo (containing 25 g protein derived from caseinate
and skimmed milk powder).The respective protein sup-
plements (for a list of ingredients see Table1) were dis-
tributed at the regular examinations. Participants re-
ceived their daily supply in 2 separate sachets, which
they were advised to suspend in cold water and ingest
with the morning and evening meals, respectively. At
each assessment, compliance with the treatment sched-
ule was checked by counting the returned sachets.
Assessments took place at baseline and after 4,6, and
8 weeks and involved evaluation of the general clinical
condition and blood sampling to determine serum lev-
els of total, LDL and HDL cholesterol, triglycerides, and
apolipoprotein B.All blood analyses were performed by
the laboratory “Quadriga”, Berlin, Germany, which is
certified by the national Institute for Standardization
and Documentation in Medical Laboratories and fulfills
the guidelines of the German Federal Medical Associa-
tion.Serum lipid profiles including measurement of to-
tal cholesterol and triglyceride concentrations were an-
alyzed by Olympus AU2700 (Olympus, Ireland). The
coefficient of variation (CV) is 3.0% and 2.6 %, respec-
tively.LDL and HDL cholesterol concentrations were an-
alyzed by Olympus AU600 (Olympus, Ireland).The CV
is 2.7% and 3.4 %,respectively.Serum concentrations of
apolipoprotein B were measured by Beckman Image
(Beckman Coulter, Fullerton, California, USA). The CV
is 2.6%.
To e ns ur e tole ra nce,basic clinical data and safety pa-
rameters were determined at the initial and final evalu-
ation and the general physical condition and occurrence
of undesirable effects were recorded during each assess-
ment. Data were recorded on dBase IV® (Borland;
Scottsvalley, Calif) by double data entry and evaluated
with SPSS® for Windows™ (Chicago, Ill) according to
the full-analysis procedure. In addition to variance
analysis and the F-test, the t-test for coupled observa-
tions was applied.
L. H. Høie et al. 67
A double-blind placebo-controlled clinical trial
Results
Of the 121 subjects initially enrolled, 3 subjects experi-
enced a total of 7 non-serious adverse events that were
unrelated to treatment with the study preparations.Two
of these terminated the trial prematurely by their own
choice but did undergo a final examination; 5 others
were excluded without final examination due to insuffi-
cient compliance. Table 2 summarizes the baseline char-
acteristics of the 116 participants included in the analy-
sis. From these, as well as from further clinical data and
life-style assessments, the three study groups appear to
have sufficiently homogenous baseline values.
The development of total cholesterol levels within the
three study groups during the trial is shown in Table 3
and Fig. 1. After 8 weeks of treatment, total cholesterol
levels decreased by 0.56±0.67 mmol/l in the Abacor®
group and by 0.24±0.58 mmol/l in the SuproSoy®
group, while a slight rise of 0.07± 0.82 mmol/l was ob-
served in the placebo group. This means that a decline
by 8% compared to baseline (9 % compared to placebo)
was achieved upon treatment with Abacor® and a de-
cline by 3.4% compared to baseline (4.4% compared to
placebo) resulted from treatment with SuproSoy®. The
total cholesterol-lowering effect was significantly diffe-
rent from placebo for treatment with Abacor® (p<10–3),
but not with SuproSoy® (p=0.065). In direct compari-
son,the differences observed between the two soy treat-
ments were also statistically significant (p=0.025).
In accordance with the total cholesterol values,serum
concentrations of LDL cholesterol also decreased under
soy protein treatment (Table3; Fig. 2). At the end of the
8-week-trial, values were reduced by 0.42± 0.51 mmol/l
in the Abacor® group and by 0.24±0.51 mmol/l in the
SuproSoy® group. In the placebo group, a minor in-
crease of 0.04 ± 0.58 mmol/l was observed. In percen-
tages, declines compared to baseline amounted to 9.7%
and 5.4% for the Abacor® and SuproSoy® regimens, re-
spectively. LDL cholesterol changes within both soy
treatment groups differed significantly from the placebo
values (p<0.001 and p=0.033,respectively).Differences
between the two treatment groups, however, were not
statistically significant (p=0.12). Of the other efficacy
parameters,serum levels of HDL cholesterol and triglyc-
erides were not significantly different between treat-
Table 2 Baseline characteristics of participants (values are given as means ± SD)
Group Sex (f/m) Age Height (cm) Weight (kg)
Abacor® 22/17 53.0± 11.4 169.9 ±8.6 76.1± 15.1
SuproSoy® 23/16 56.3± 10.3 170.0 ±8.3 77.2± 11.5
Placebo 17/21 55.8± 8.0 171.4± 9.4 77.1 ±13.1
P Value* 0.41 0.31 0.64 0.91
* Differences between all treatment groups by analysis of variance
Abacor®* SuproSoy®** Placebo
Ingredient Per 100 g Per sachet Per 100 g Per sachet Per 100 g Per sachet
Total, g 100 38.8 100 35.9 100 38.2
Energy, kcal 352 136.5 387 138.7 345 132.0
Energy, kJ 1473 571.1 1618 580.3 1443 552.3
Total carbohydrate, g 30.7 11.9 43.7 15.7 46.8 17.9
Lactose, g 4.1 1.6 – – 17.0 6.5
Fructose, g 21.4 8.3 20.9 7.5 17.0 6.5
Maltodextrin, g 2.6 1.0 18.9 6.8 9.7 3.7
Fat, g 10.3 4.0 7.0 2.5 2.6 1.0
Total protein, g 36.3 14.1 39.8 14.3 36.7 14.0
Caseinate, g – – – – 22.7 8.7
Soy protein, g 32.2 12.5 34.8 12.5 – –
Protein, g, from:
Skimmed milk powder 2.8 1.1 – – 12.1 4.6
Cream powder – – 3.6 1.3 0.3 0.1
Cocoa powder 1.3 0.5 1.4 0.5 1.7 0.7
Total fiber, g 13.1 5.1 2.5 0.9 2.6 1.0
Soy fiber, g 8.3 3.2 – – – –
Isoflavonoids, mg 124.3 48.3 134.3 48.2 – –
Total phospholipids, g 5.2 2.0 – – – –
Phosphatidylcholine, g 2.6 1.0 – – – –
Sodium, g 0.13 0.05 0.08 0.03 0.24 0.09
* Registered trademark of NutriPharma A/S, Copenhagen, Denmark
** Registered trademark of Protein Technology International Inc., St Louis, MO, USA
Table 1 Composition of the study preparations
(daily dosage = 2 sachets)
68 European Journal of Nutrition (2005) Vol. 44, Number 2
© Steinkopff Verlag 2004
ment groups (Table 4). Concentrations of apolipopro-
tein B, on the other hand, fell by 0.09± 0.02 g/l and
0.05 ±0.16 g/l in the Abacor® and SuproSoy® groups,re-
spectively,while they rose by 0.04± 0.21 g/l in the
placebo group (Table 4). Decreases obtained with both
active treatment regimens were statistically significant
as compared with placebo (p=0.007 for Abacor® and
p=0.044 for SuproSoy®).
The clinical data such as body weight, heart rate,
blood pressure, body temperature, or hematological
profiles did not undergo any changes during the trial pe-
riod,nor did they significantly differ between study
groups.
Discussion
The serum cholesterol concentration is influenced by
several variables. It changes with increasing cholesterol
content in the diet,the efficiency of its absorption in the
Table 3 Blood lipid levels (values are given as means ± SD)
Abacor® SuproSoy® Placebo P Value*
Total cholesterol [mmol/l]
Baseline 6.97±0.60 7.03 ±0.55 6.85±0.47 0.33
Changes:
4 Weeks –0.53 ±0.79 –0.42 ±0.64 –0.27± 0.63 0.29
6 Weeks –0.53 ±0.66 –0.29 ±0.59 –0.08± 0.75 0.016
8 Weeks ** –0.56± 0.67 –0.24± 0.58 +0.07± 0.82 < 0.001
** P values from paired group comparisons: Abacor®/SuproSoy® = 0.025
Abacor®/placebo < 0.001
SuproSoy®/placebo = 0.065
LDL cholesterol [mmol/l]
Baseline 4.36±0.55 4.41 ±0.47 4.26±0.43 0.41
Changes:
4 Weeks –0.17 ±0.68 –0.14 ±0.75 +0.06 ±0.63 0.29
6 Weeks –0.17 ±0.64 –0.13 ±0.53 +0.11 ±0.75 0.12
8 Weeks ** –0.42± 0.51 –0.24± 0.51 +0.04± 0.58 0.001
** P values from paired group comparisons: Abacor®/SuproSoy® = 0.12
Abacor®/placebo < 0.001
SuproSoy®/placebo = 0.033
HDL cholesterol [mmol/l]
Baseline 1.51±0.35 1.51 ±0.28 1.47±0.28 0.83
Changes:
4 Weeks –0.09 ±0.17 –0.03 ±0.14 –0.10± 0.14 0.10
6 Weeks –0.11 ±0.19 0.0 ±0.14 –0.04± 0.14 0.01
8 Weeks –0.09 ±0.23 –0.02 ±0.12 –0.03± 0.17 0.21
Triglycerides [mmol/l]
Baseline 1.77±0.95 1.83 ±0.76 1.85±0.84 0.91
Changes:
4 Weeks –0.11 ±0.75 +0.07 ±0.60 +0.11 ±0.76 0.36
6 Weeks +0.02 ±0.87 +0.09± 0.58 +0.08± 0.85 0.92
8 Weeks –0.09 ±0.72 –0.01 ±0.47 +0.09± 0.82 0.53
Apolipoprotein B [g/l]
Baseline 1.35±0.20 1.36 ±0.22 1.32±0.14 0.61
Changes:
4 Weeks –0.11 ±0.19 –0.09 ±0.21 –0.03± 0.18 0.18
6 Weeks –0.14 ±0.19 –0.11 ±0.18 –0.04± 0.17 0.037
8 Weeks** –0.09 ±0.20 –0.05 ±0.17 +0.04± 0.22 0.013
** P values from paired group comparisons: Abacor®/SuproSoy® = 0.34
Abacor®/placebo = 0.007
SuproSoy®/placebo = 0.044
* Differences between all treatments by analysis of variance
Fig. 1 Changes of serum total cholesterol levels over the eight-week trial period
(values are given as means ± SEM)
Fig. 2 Changes of serum LDL cholesterol levels over the eight-week trial period
(values are given as means ± SEM)
Table 4
weeks Abacor SuproSoy Placebo
0 100 0 100 0 100 0
4 92.1 2.2 94.1 1.6 96.2 1.5
6922.1 95.9 1.7 98.8 1.5
8 91.9 2.1 96.6 1.7 101 1.8
0 100 0 100 0 100 0
4 95.7 2.7 96.8 2.5 101.7 2.0
6 95.6 2.8 96.9 2.0 102.9 2.1
8 90.4 2.5 94.6 1.9 100.9 1.9
L. H. Høie et al. 69
A double-blind placebo-controlled clinical trial
small intestine, endogenous cholesterol synthesis, and
the release of free cholesterol from peripheral tissues
[33]. It seems reasonable to attempt lowering cholesterol
levels by controlling dietary cholesterol intake. However,
a meta-analysis of large international nutrition studies
revealed a mean decrease of cholesterol values of only
2% with this approach [34]. Supplementation with di-
etary fiber or other food ingredients proved to be more
successful. Therefore,a meta-analysis of 38 trials on the
efficacy of soy protein showed that total and LDL cho-
lesterol levels declined on average by 9.3 and 12.9%, re-
spectively [11]. However, the trials included were of
varying duration, involved daily soy protein dosages be-
tween 17 and 124 g and, moreover, soy products of dif-
ferent protein, isoflavone and fiber content.Although, in
those studies a clear dosage-response relationship was
missing, the cholesterol reduction achieved significantly
diminishes the risk of cardiovascular diseases. A 10 %
decrease of cholesterol in 35 to 44 year old men has been
found to reduce the heart attack risk by half [35].This is
important in all affluent societies. In Germany,60–70 %
of the adult population exceeds a blood cholesterol level
of 5.2mmol/l [36], although values of <5.0 mmol/l for
total cholesterol and <3.0 mmol/l for LDL-cholesterol
are currently recommended [37].
Participants in this study had average baseline values
of 7.08mmol/l for total cholesterol and 4.38mmol/l for
LDL cholesterol, which are substantially above the
threshold for hypercholesterolemia. Apolipoprotein B,
the major apoprotein of LDL, was slightly elevated with
a mean value of 1.34 g/l. Serum concentrations of HDL
cholesterol and triglycerides were within the normal
range. After randomization, the three study groups did
not differ significantly with respect to anamnesis and
life-style.
The trial results reveal a distinct beneficial effect
from active treatment with soy protein preparation re-
garding three risk factors for coronary heart disease: to-
tal cholesterol, LDL cholesterol, and apolipoprotein B,
which is supposed to have the same impact on cardio-
vascular health as LDL cholesterol [38]. The slight in-
crease in cholesterol levels in the placebo group may be
attributable to the composition of the placebo prepara-
tion,which contained a large proportion of casein. Ca-
sein, which is a frequently used control substance in
clinical trials on protein supplements and their effect on
blood cholesterol, has been shown to increase choles-
terol and triglyceride concentrations in some cases [39].
However, this moderate “reverse placebo effect” can
hardly account for the substantial cholesterol reductions
in both verum groups compared to baseline,nor does it
affect the observed differences between the two verum
treatments.The combination of soy constituents present
in Abacor® proved to be approximately twice as efficient
as the alternative treatment with SuproSoy®, which had
also achieved only moderate effects in a previous clini-
cal study [14]. Both soy-derived fibers and phospho-
lipids have been proved to exert lipid-lowering effects as
individual substances. Phosphatidylcholine, in particu-
lar,is assumed to activate reversed cholesterol transport
by increasing the cholesterol uptake of HDL molecules
and the biliary cholesterol excretion [30–32]. Although
some clinical trials failed to show a lipid-lowering effect
[40], several others did result in cholesterol reduction
during the treatment with phosphatidylcholine [26–29]
employing dosages that correspond to the 2 g that are
provided daily by Abacor®. The Commission E of the
German Drug Authority recommends soy lecithin and
lecithin-enriched soy phospholipids for the treatment of
“moderate disturbances of fat metabolism, especially
hypercholesterolemia” in dosages corresponding to
1.2–3.5 g phosphatidylcholine daily [41].
Both trial preparations are complex mixtures of in-
gredients and neither contains pure soy protein. It is
therefore not possible to conclude if the additional ef-
fects of the mixture present in Abacor® are due to its
content of phospholipids or fibers or both. An explana-
tion involving protein quality or structure of the two
products can be excluded since both products have been
manufactured using SuproSoy® isolated soy protein as
their basis. This, however, appeared to be highly frag-
mented in its protein constituents in a recent proteomic
investigation [42], and we have in the meantime per-
formed a clinical trial employing a new isolated soy pro-
tein preparation [43], the results of which will be fully
published in due course.
None of the safety parameters showed significant dif-
ferences compared to the baseline values.Tolerability of
the study preparations was very good; no adverse effects
were observed.
In summary, supplemental intake of 25 g soy protein
daily resulted in significant decreases in serum concen-
trations of total and LDL cholesterol and apolipoprotein
B.The use of soy protein as a nutritional supplement was
shown to be likely to diminish the risk of coronary heart
disease. The efficacy of Abacor® was approximately
twice that of SuproSoy®.
70 European Journal of Nutrition (2005) Vol. 44, Number 2
© Steinkopff Verlag 2004
1. Riesen WF (1998) Fettstoffwechsel. In:
Thomas L (ed) Labor und Diagnose.
TH-Books Verlagsgesellschaft mbH,
Frankfurt/Main, pp 171–190
2. Brönstrup A, Pietrzik K (1996) Bedeu-
tung von Homocystein bei der Entste-
hung von Atherosklerose – ist eine Sup-
plementierung von Vitaminen sinnvoll?
Ernährungsumschau 43:80–87
3. Müller-Bohn T (1996) Atherosklerose-
prophylaxe – Bericht zum Fortbil-
dungskongress in Malente. DAZ 136:
2453–2458
4. Shepherd J, Cobbe SM, Ford I, etal.
(1996) Prävention der KHK durch
Pravastatin bei Männern mit Hyper-
cholesterinämie. Münch Med Wschr
138:21–28
5. Glore SR, an Treeck D, Knehans AW,
Guild M (1994) Soluble fiber and serum
lipids: A literature review. J Am Diet As-
soc 94:425–436
6. Peters P, Peters KM, Saborowski F, etal.
(1990) Lipidsenkung mit Ballaststoffen.
Akt Ernähr-Med 15:119–122
7. Messena M, Erdman JW Jr (eds) (1995)
First international symposium on the
role of soy in preventing and treating
chronic disease. J Nutr 125(Suppl):
567s–808s
8. Sirtori CR, Lovati MR, Manzoni C, etal.
(1998) Reductions of serum cholesterol
by soy proteins: clinical experience and
potential molecular mechanism. Nutr
Metab Cardiovasc Dis 8:334–340
9. Tsai AC, Mott EL, Owen GM, Bennick
MR, Lo GS,Steinke FH (1983) Effects of
soy polysaccharide on gastrointestinal
functions, nutrient balance, steroid
excretions, glucose tolerance, serum
lipids, and other parameters in hu-
mans.Am J Clin Nutr 38:504–511
10. Tham DM, Gardner CD, Haskell WL
(1998) Potential health benefits of di-
etary phytoestrogens: a review of the
clinical, epidemiological and mecha-
nistic evidence. J Clin Endocrinol
Metab 83:2223–2235
11. Anderson JW, Johnstone BM, Cook-
Newell ME (1995) Meta-analysis of the
effects of soy protein intake on serum
lipids. N Engl J Med 333:276–282
12. Baum JA, Teng H, Erdman JW, et al.
(1998) Long-term intake of soy protein
improves blood lipid profiles and in-
creases mononuclear cell low-density
lipoprotein receptor messenger RNA in
hypercholesterolemic, postmenopausal
women.Am J Clin Nutr 68:545–551
13. Wong WW, Smith EOB, Stuff JE, Hachey
DL,Heird WC, Pownell HJ (1998) Cho-
lesterol-lowering effect of soy protein
in normocholesterolemic and hyper-
cholesterolemic men. Am J Clin Nutr
68(Suppl):1385S–1389S
14. Crouse JR, Morgan T, Terry JG, Ellis J,
Vitolins M, Burke GL (1999) A random-
ized trial comparing the effect of casein
with that of soy protein containing
varying amounts of isoflavones on
plasma concentrations of lipids and
lipoproteins. Arch Intern Med 159:
2070–2076
15. Washburn S, Burke GL, Morgan T, An-
thony M (1999) Effects of soy protein
supplementation on serum lipopro-
teins, blood pressure, and menopausal
symptoms in perimenopausal women.
Menopause 6:7–13
16. Merz-Demlow BE, Duncan AM, Wan-
gen KE, etal. (2000) Soy isoflavones im-
prove plasma lipids in normocholes-
terolemic, premenopausal women. Am
J Clin Nutr 71:1462–1469
17. Teixeira SR, Potter SM, Weigel R, Han-
num S, Erdman JW, Hassler CM (2000)
Effects of feeding 4 levels of soy protein
for 3 and 6 wk on blood lipids and
apolipoproteins in moderately hyper-
cholesterolemic men. Am J Clin Nutr
71:1077–1084
18. Hermansen K, Sondergaard M, Hoie L,
Carstensen M, Brock B (2001) Benefi-
cial effects of a soy-based dietary sup-
plement on lipid levels and cardiovas-
cular risk markers in type 2 diabetic
subjects. Diabetes Care 24:228–233
19. Puska P, Korpelainen V, Hoie LH,
Sksovlund E,L ahti E, Smerud KT (2002)
Soy in hypercholesterolaemia: a dou-
ble-blind, placebo-controlled trial. Eur
J Clin Nutr 56:352–357
20. Tonstad S,Smerud KT,Hoie L (2002) A
comparison of the effects of 2 doses of
soy protein or casein on serum lipids,
serum lipoproteins, and plasma total
homocysteine in hypercholesterolemic
subjects. Am J Clin Nutr 76:78–84
21. Greaves KA, Parks JS,Williams KJ,Wag-
ner JD (1999) Intact dietary soy protein,
but not adding an isoflavone-rich soy
extract to casein, improves plasma
lipids in ovariectomized cynomolgus
monkeys.J Nutr 129:1585–1592
22. Ni W,Yoshida S, Tsuda Y, Nagao K,Sato
M, Imaizumi K (1999) Ethanol-ex-
tracted soy protein isolate results in
elevation of serum cholesterol in exog-
enously hypercholesterolemic rats.
Lipids 34:713–716
23. Wangen KE, Duncan AM, Xu X,Kurzer
MS (2000) Soy isoflavones improve
plasma lipids in normocholesterolemic
and mildly hypercholesterolemic post-
menopausal women. Am J Clin Nutr
73:225–231
24. Lo GS, Goldberg AP, Lim A, Grund-
hauser JJ, Anderson C, Schonfeld G
(1986) Soy fiber improves lipid and car-
bohydrate metabolism in primary hy-
perlipidemic subjects. Atherosclerosis
62:239–248
25. Brown L, Rosner B, Willet WW, Sacks
FM (1999) Cholesterol-lowering effects
of dietary fiber: a meta-analysis. Am J
Clin Nutr 69:30–42
26. Dewailley P,Moulin S,Rouget JP, Sezille
G, Jaillard J (1985) Effects of poly-
enylphosphatidyl choline on lipopro-
teins in patients with hypercholes-
terolemia. Med Welt 36:367–369
27. Ovesen L, Ebbesen K, Olesen ES (1985)
The effects of oral soybean phospho-
lipid on serum total cholesterol,plasma
triglyceride, and serum high-density
lipoprotein cholesterol concentrations
in hyperlipidemia. J Parenter Enteral
Nutr 9:716–719
28. Sirtori CR, Zucchi-Dentone C, Sirtori
M, etal. (1985) Cholesterol-lowering
and HDL-raising properties of lecithi-
nated soy proteins in type II hyperlipi-
demic patients. Ann Nutr Metab 29:
348–357
29. Kirsten R, Heintz B, Nelson K, etal.
(1994) Polyenylphosphatidylcholine
improves the lipoprotein profile in
diabetic patients. Int J Clin Pharmacol
Ther 32:53–56
30. Polichetti E, Diaconescu N, de la Porte
PL, etal. (1996) Cholesterol-lowering
effect of soybean lecithin in normolipi-
demic rats by stimulation of biliary
lipid secretion. Br J Nutr 75:471–481
31. LeBlanc MJ, Gavino V, Perea A, Yousef
IM, Lévy E,Tuchweber B (1998) The role
of dietary choline in the beneficial ef-
fects of lecithin on the secretion of bil-
iary lipids in rats. Biochim Biophys Acta
1393:223–234
32. Polichetti E, Janisson A, Lechène de la
Porte P, etal. (2000) Dietary poly-
enylphosphatidylcholine decreases
cholesterolemia in hypercholesterol-
emic rabbits – role of the hepato-biliary
axis. Life Sci 67:2563–2576
33. Leopold F,Noack R (1993) Einfluss von
Ballaststoffen auf den Lipidstoffwech-
sel. In: Schulze J, Bock W (eds) Aktuelle
Aspekte der Ballaststoffforschung.
Behr’s-Verlag, Hamburg, pp 147–155
34. Ramsay IE, Yeo WW, Jackson PR (1991)
Dietary reduction of serum cholesterol
concentration: time to think again.BMJ
303:953–957
35. Law MR, Wald MJ, Thompson SG (1994)
By how much and how quickly does re-
duction in serum cholesterol concen-
tration lower the risk of ischaemic
heart disease? Brit Med J 308:367–373
References
L. H. Høie et al. 71
A double-blind placebo-controlled clinical trial
36. Forschungsverband DHP (ed, 1998) Die
Deutsche Herz-Kreislauf-Präventions-
studie.Verlag Hans Huber,Bern
37. Wood D, de Backer G, Faergeman O,
Graham I, Mancia G, Pyörälä K (1998)
Prevention of coronary heart disease in
clinical practice. Summary of Recom-
mendations of the Second Task Force
of European and other Societies on
Coronary Prevention. Eur Heart J 19:
1434–1503
38. Wald NJ, Law M, Watt HC, etal. (1994)
Apolipoproteins and ischemic heart
disease: implications for screening.
Lancet 343:75–79
39. Damasceno NR, Gidlund MA, Goto H,
Dias CT, Okawabata FS, Abdalla DS
(2001) Casein and soy protein isolate in
experimental atherosclerosis: influence
on hyperlipidemia and lipoprotein oxi-
dation.Ann Nutr Metab 45:38–46
40. Kesaniemi YA, Grundy SM (1986) Ef-
fects of dietary polyenylphosphatidyl-
choline on metabolism of cholesterol
and triglycerides in hypertriglyceri-
demic patients. Am J Clin Nutr 43:
98–107
41. Blumenthal M (ed, 1998) The complete
German Commission E monographs.
American Botanical Council, Austin,
Texas, pp 210–213
42. Gianazza E, Eberini I, Arnoldi A,Wait R,
Sirtori CR (2003) A proteomic investi-
gation of isolated soy proteins with
variable effects in experimental and
clinical studies. J Nutr 133:9–14
43. Hoie LH, Gruenwald J, Graubaum HJ,
etal. (2003) A new isolated soy protein
product with high levels of non-denat-
urated protein shows twice the lipid-
lowering effect of a conventional soy
protein product. 5th International Sym-
posium on the Role of Soy in Preventing
and Treating Chronic Disease, Septem-
ber 21–24:2003, Orlando,Florida, USA
Reproducedwith permission ofthe copyrightowner. Further reproductionprohibited withoutpermission.
