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Nutrition, Metabolism & Cardiovascular Diseases (2012) 22, 712e719

available at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/nmcd

The effects of isoflavones combined with soy


protein on lipid profiles, C-reactive protein and
cardiovascular risk among postmenopausal Chinese
women
Z.-M. Liu a,b, S.C. Ho a,b,*, Y.-M. Chen a,b,c, Y.P. Ho d

a
Department of Community and Family Medicine, The Chinese University of Hong Kong, Hong Kong SAR
b
Center of Research, and Promotion of Women’s Health, School of Public Health, and Primary Care, The Chinese University
of Hong Kong, Hong Kong SAR
c
Department of Medical Statistics & Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, PR China
d
School of Pharmacy, The Chinese University of Hong Kong, Hong Kong SAR

Received 17 June 2010; received in revised form 5 November 2010; accepted 5 November 2010

KEYWORDS Abstract Background & Aims: Observational studies note that regular dietary soy protein
Soy protein; intake (6e11 g day1) has a significant association with lower blood lipids; however, these
Isoflavones; observations have not been confirmed by clinical trials. This study aimed to ascertain the
Lipid profiles; effects of moderate intake of soy protein (15 g) with isoflavones or isoflavones alone on serum
C-reactive protein; lipid profiles, inflammatory markers (C-reactive protein and uric acid) and composite cardio-
Uric acid vascular risk in Chinese postmenopausal, prediabetic women.
Methods and Results: A double-blind randomised, placebo-controlled trial was conducted
among 180 postmenopausal Chinese women with prediabetes or early untreated diabetes,
aged 46e70 years and, on average, 6.0 years since menopause. Participants were randomly as-
signed to one of the three arms to receive 15-g soy protein and 100-mg isoflavone (Soy group),
or 15-g milk protein and 100 mg isoflavone (Iso group) or 15-g milk protein (placebo group) on
a daily basis for 6 months. The results showed that no significant difference was observed in
serum high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-
C), total cholesterol (TC), triaclyglycerol (TG), high sensitive C-reactive protein and
a composite 10-year cardiovascular risk between the three groups at both 3 and 6 months.
Serum uric acid marginally increased by 1.22% in the Soy group and decreased by 4.28% and
4.82% in the Iso and placebo groups at 3 months (P Z 0.087), but no difference was observed
at 6 months (P Z 0.264).

* Corresponding author. 4/F School of Public Health and Primary Care, Prince of Wales Hospital, Shatin, N.T, Hong Kong SAR. Tel.: þ852
2252 8775; fax: þ852 2602 6986.
E-mail address: suzanneho@cuhk.edu.hk (S.C. Ho).

0939-4753/$ - see front matter ª 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.numecd.2010.11.002
Effects of soy protein and isoflavones on cardiovascular risks 713

Conclusion: Soy protein with isoflavones or isoflavones alone at the provided dosage showed no
significantly beneficial effects on measured cardiovascular risk factors in postmenopausal
Chinese women with early hyperglycaemia.
ª 2010 Elsevier B.V. All rights reserved.

Ageing and menopause-related atherogenic alterations in extract alone in an isocaloric setting on cardiovascular risks
lipid profiles and inflammatory markers may contribute among Chinese menopausal women with early untreated
significantly to the increased risk of development of cardio- hyperglycaemia, and to ascertain whether this relative low
vascular disease (CVD) [1]. The attenuation of such processes but practically achievable dosage of 15 g soy protein had
via dietary intervention has significant public health impli- any beneficial effect on cardiovascular health.
cations. In recent decades, soy food and its constituent
protein and isoflavones have received widespread attention Methods
for their potential role in CVD risk improvement [2].
Several meta-analyses [3e5] have examined the effect
Participant recruitment
of soy and supported the role of soy protein in the reduction
of elevated cholesterol. Most of the previous studies used
a relatively large quantity of soy protein (36e50 g), Potential participants were recruited from the local
whereas studies examining the health effects of modest, community. A total of 180 postmenopausal women with
achievable doses of soy protein were limited. Three studies prediabetes (fasting glucose (FG) level 5.6e7.0 mmol l1 or
[6e8] using composite soy products containing 8e17 g soy 2-h postprandial glucose (PG) level 7.8e11.0 mmol l1) and
protein, and one study [9] using 20 g soy protein have found early untreated diabetes were recruited to participate in
favourable effects of soy on lipids; however, studies using a 6-month randomised controlled trial (RCT) designed to
lower dosage of purified soy protein are scant. examine the effect of soy protein and isoflavones on gly-
In 1999, the US Food and Drug Administration (FDA) caemic control and cardiovascular risks. The study design
approved the health claim that the inclusion of 25 g day1 soy and participant recruitment have been reported previously
protein along with a healthy diet can help reduce the risk of in detail [21]. Subjects were Hong Kong Chinese meno-
heart disease. Twenty-five grams is approximately twice the pausal women aged 48e70 years without menstrual cycle
soy protein intake of average Hong Kong adults [10]. It has for at least 1 year (if not natural menopause, age 55
been suggested that 25 g soy protein should not be inter- years). Women were not eligible if they had a history of
preted as a threshold for an effect on blood cholesterol [11]. breast, uterine or ovarian cancer, or stroke, coronary heart
Some studies also suggested that an intake of more than disease or thyroid disease in the previous 5 years, were
20e30 g soy protein daily is not feasible as a long-term currently or in proceeding 3 months on drug treatment for
practice [9]. Furthermore, a dose-response relationship is weight, glucose or lipids reduction, hormone or antibiotic
not observed either in most of the pooled data [3,5,12] or therapy or had a known allergy to soy or milk. The Ethical
within one study [9]. Recent results from two cross-sectional Committee of the Chinese University of Hong Kong
studies noted that even fairly low dietary soy protein intake approved the study protocol, and all participants gave
(6e11 g) had a significant association with lower blood written informed consent prior to the enrolment.
cholesterol level [10,13]; however, these observations have
not been confirmed by clinical trials. Therefore, there is Study design
a need to establish whether a lower intake of soy protein is
efficacious in cholesterol reduction. The study was a 6-month double-blind, randomised,
In addition to dyslipidaemia, CVD is typified by low- placebo-controlled trial with three intervention arms.
grade chronic inflammation. Elevated levels of inflamma- Before admission to the study, subjects were administered
tory markers, that is, C-reactive protein (CRP) and uric acid a placebo product (15 g milk protein, Pacific Dairy Ingre-
(UA), have been shown to predict all-cause and cardiovas- dients Co., Ltd., Shanghai) for 2 weeks as a run-in to
cular mortality [14e16]. Previous data on soy consumption familiarise them with the study procedure. Subjects with
and inflammatory markers are far from conclusive. Some good compliance and without any side effects during the
studies support the effectiveness of soy food consumption run-in phase were then randomly assigned to one of the
on the modulation of pro-inflammatory cytokine [17,18], three arms: 15-g milk protein group (placebo group), 15-g
while others do not [19,20]. There have been no long-term milk protein þ 100-mg isoflavones group (Iso group) and 15-
studies that examined the effects of soy protein on UA. In g soy protein þ 100-mg isoflavones group (Soy group). Soy
addition, up until now, few studies have evaluated the protein (Solpro 931) and isoflavones (Solgen 40/s) were
effects of soy on CVD risk factors among prediabetic provided by Solbar Industries Ltd., Israel. The three kinds of
patients. Most studies investigating the effects of soy on preparation were formulated into an isocaloric powder with
serum lipids were conducted among hypercholesterolaemic similar colour; odour and nutrients profile. Each 100 mg
subjects. To better characterise the cardioprotective isoflavones (in aglycone form) contained 35 mg daidzin,
benefit of soy intake, it is also important to study the effect 59 mg genistin and 4 mg glycitin, with 98.5% in conjugated
in other at-risk sub-populations. form. Supplements were suggested to be mixed with 300 ml
The current trial was performed to examine the 6-month of water or any other liquid of the subject’s choice and
effects of soy protein with isoflavones and isoflavones delivered to subjects at intervals of 1, 2 and 3 months after
714 Z.-M. Liu et al.

randomisation. The major assessment of compliance was by Composition Table 2004. Fasting (10e12 h) blood samples
counting the empty and remaining sachets at each face-to- were collected at baseline, 3- and 6-month follow-ups. Blood
face interview to estimate what percentage of the provided taking for participants with acute inflammation (i.e., fever
supplements had been consumed. Subjects were asked not and cold) or taking anti-inflammation drugs (i.e., aspirin or
to take other supplements containing phytoestrogen or antibiotics) was postponed until recovery. All samples were
extracts known to affect outcome measures (such as red divided into aliquots and stored at 85  C until assay. After
clover extracts, flaxseed and lignan- or flavonoid-contain- completion of the protocol, samples from each subject were
ing supplements). Participants were advised to maintain analysed in the same batch to minimise laboratory variability.
their usual dietary habits and physical activity throughout
the study. During the course of intervention, dietary intake Anthropometric and biochemical measures
was measured by 3-day food records at 0, 3 and 6 months.
Randomisation was performed in blocks of 15 partici- Body weight and height and waist and hip circumferences
pants. A list of randomisation numbers was computer were measured according to standard protocols [22]. Fasting
generated. Personnel not involved in subjects recruitment, serum TC, triacylglycerol (TG) and UA were measured by
data collection and analysis undertook the randomisation standardised enzymatic colourimetric methods (Human,
procedure and labelling work. Participants, investigators Germany). Serum high-density lipoprotein-cholesterol (HDL-
and laboratory technicians were blinded to the treatment C) and LDL-C were measured by enzymatic clearance assay
assignment until the conclusion of the trial. The planned (Daiichi Pure Chemicals Co., Ltd., Tokyo, Japan). High
number of subjects was 180, 60 in each intervention arm. sensitivity-CRP (Hs-CRP) was analysed by the particle-
Based on a conventional two-tailed a Z 0.05 and assuming enhanced immunoturbidimetry method (Orion Diagnostica
a withdrawal rate of 10%, we would have 80% power to Oy, Finland). All analysis were performed on the Hitachi 917
demonstrate a reduction of 7% in low-density lipoprotein- automated analyser (Japan) at a certified clinical laboratory.
cholesterol (LDL-C) and 5% in total cholesterol (TC). Coefficients of intra- and inter-assay variation of the above
bio-parameters were 2.3% and 4.5% for TC, 2.1% and 4.2% for
Data collection TG, 2.9% and 3.2% for HDL-C, 2.6% and 3.7% for LDL-C, 3.3%
and 4.6% for hs-CRP and 3.1% and 4.2% for UA. Individual 10-
Individual information was collected by trained interviewers year CVD risk was calculated based on a recalibrated Fra-
through face-to-face interview based on a structured ques- mingham risk prediction equation [23].
tionnaire on socio-demographic data, medical history,
medication treatment, dietary habits and physical activities. Statistical analysis
Three-day dietary records were completed by subjects
before each follow-up visit at 0, 3 and 6 months. Dietary Statistical analysis was performed with the use of Statistical
nutrients intake was calculated based on the China Food Package for Social Sciences (SPSS) 13.0 software. Skewed

Eligible subjects with untreated hyperglycemia: n = 198

18 give up or excluded during 2-week run-in

Randomized: n = 180

Soy group: n = 60 Iso group: n = 60 Placebo group: n = 60


(15 g SPI+100 mg Iso) (15g MP+100mg Iso) (15g MP)

Valid completers: n=57 Valid completers: n=57 Valid completers: n=50


Dropouts: n=3 Dropouts: n=2; Dropouts: n=9;
Poor complier: n=0 Poor complier: n=1 Poor complier: n=1;

Reasons for withdrawal Reasons for withdrawal Reasons for withdrawal


Weight loss: 1 Too busy: 1 GI discomfort: 5
Skin allergy: 1 Develop certain disease: 1 Too busy: 1
Menstrual recurrence: 1 Feel hot: 1
Develop certain disease: 1
Glucose-lowering drug: 1

Included in final Included in final Included in final


analysis: n=60 analysis: n=60 analysis: n=60

Figure 1 Participants flow diagram. SPI, soy protein isolate; Iso, isoflavones; MP, milk protein; GI, gastro-intestinal.
Effects of soy protein and isoflavones on cardiovascular risks 715

variables (hs-CRP and TG) were treated as log-transformed withdrew from the study were also invited for follow-up
and reported as the geometric means. All results were visits. A total of 176 subjects attended the mid-term visit and
considered significant if the two-tailed P-value was <0.05. 175 attended the final-term visit. Fourteen women (7.8%)
Baseline characteristics, dietary intake and physical activity withdrew during the study after randomisation. The most
level were compared among the three study groups by important reason was gastrointestinal (GI) tract discomfort
analysis of variance (ANOVA). Data were analysed according (n Z 5). Detailed reasons for the withdrawal are indicated in
to an intention-to-treat principle, including all 180 subjects, Fig. 1. Relatively more dropouts were observed in the
who were randomised. The non-compliant subjects were placebo group (n Z 9) than in the Soy (n Z 3) and Iso (n Z 2)
compared with the compliant subjects in baseline charac- groups, but the proportion of valid completers was not
teristics by chi-square or unpaired t-test. significantly different among the three groups. Adherence
Repeated-measures ANOVA was used to determine the was good in all the three groups with more than 90% subjects
effects of supplementation over time (0, 3 and 6 months) on having used 96% of the supplements (data not shown).
outcome variables, and the effects of treatment and their
interactions. ANOVA was used to compare the change Baseline characteristics
percentage at 3 and 6 months from baseline among the three
study groups. Percent changes in outcome measures were
Baseline characteristics indicated that the women in the
calculated as (follow-up value  baseline value) * 100%/
three groups were comparable in terms of age, years since
baseline value. The Least Significant Difference (LSD) test
menopause, medical history, body weight, body mass index
was used for post hoc multiple comparisons.
(BMI) and waist circumstance (Table 1). Women lost to
follow-up had similar baseline characteristics as women
Results retained in the study (data not shown). Baseline dietary
intake and physical activity levels were not significantly
From November 2007 to April 2008, a total of 180 eligible different among the three groups, and the differences
subjects, who had successfully completed the 2-week run-in, across follow-ups compared with baseline were not signifi-
were randomised into the three arms. Subjects who cant. However, baseline TC and LDL-C levels were higher in

Table 1 Baseline characteristics of 180 study participants by 3 treatment arms.*


Soy group (n Z 60) Iso group (n Z 60) Placebo group (n Z 60) p
Mean (SD) Mean (SD) Mean (SD)
Age (year) 56.4 (4.7) 56.0 (4.4) 55.9 (3.8) 0.816
YSM (year) 6.0 (5.1) 6.2 (5.4) 5.7 (4.5) 0.858
Body weight (kg) 58.6 (10.2) 60.2 (10.3) 60.0 (9.3) 0.611
BMI (kg/m2) 24.1 (3.8) 24.7 (3.8) 24.6 (3.4) 0.602
WC (cm) 83.0 (9.0) 83.8 (9.8) 83.1 (8.5) 0.853
Baseline FG (mmol/l) 6.4 (0.74) 6.4 (1.20) 6.3 (0.89) 0.797
Ever use of HRT 13 (21.6%) 12 (20.0%) 11 (18.3%) 0.881
Passive smoking 12 (20.0%) 13 (21.7%) 16 (26.7%) 0.686
Physical activity (PA) level (mets-min/d)
Total PA at baseline 1216.6 (513.7) 1107.0 (590.5) 1109.3 (527.9) 0.460
Total PA at follow-ups 1125.5 (456.1) 1089.0 (514.9) 1096.9 (488.3) 0.385
in average
Dietary nutrients intake at baseline
Total energy (kcal/d) 2202.5 (778.7) 2247.7 (652.7) 2025.3 (762.1) 0.217
Protein (g/d) 95.55 (53.88) 96.87 (32.19) 87.18 (29.59) 0.358
Total fat (g/d) 69.81 (31.16) 74.14 (32.39) 64.93 (53.25) 0.457
% kcal from fat 28.33 (7.42) 29.20 (7.52) 27.38 (9.04) 0.466
Soy protein (g/d) 12.31 (16.80) 12.40 (9.66) 12.55 (11.81) 0.996
Isoflavones (mg/d) 15.65 (27.36) 15.31 (12.14) 15.60 (13.69) 0.996
Dietary intake at follow-ups in average
Total energy (kcal/d) 2211.0 (681.9) 2222.5 (517.0) 1976.3 (418.6) 0.112
Protein (g/d) 95.3 (35.7) 96.9(25.0) 85.3 (17.7) 0.059
Total fat (g/d) 71.5 (28.4) 71.6 (22.6) 67.1 (19.3) 0.311
% kcal from fat 28.5 (5.1) 28.7 (5.0) 27.4 (6.1) 0.413
Soy protein (g/d) 12.5 (11.4) 11.7 (6.1) 12.4 (6.8) 0.631
Isoflavones (mg/d) 16.8 (15.2) 16.4 (7.8) 17.2 (8.0) 0.491
*Data are presented as mean (SD) for continuous variable, or number (%) for categorical variable. ANOVA for continuous variables and
chi-square test for categorical variables.
HRT, hormone replacement treatment; YSM, years since menopause; BMI, body mass index; WC, waist circumference; BP, blood
pressure; FG, fasting glucose; PA, physical activity.
716 Z.-M. Liu et al.

the Soy group than in the Iso group (P Z 0.02 and 0.03, be due to the synergistic effects of various soy ingredients
respectively). No significant differences were found in (unsaturated fatty acid, soy fibre, saponins, sterol, or phytic
other baseline serum parameters. acid, etc.) other than soy protein alone. Soybean processing
can alter the content of many naturally occurring compo-
Effects of soy protein and isoflavones on UA, hs-CRP nents [25]. It has been suggested by the American Heart
and lipids profile Association (AHA) that soy products, in general, are benefi-
cial because of their overall nutrient profile [12].
ANOVA for repeated analysis showed no significant inter- The effect size of soy on lipid profiles may be attribut-
actions between time and treatment in these biomarkers able to the dosage of supplements. The amount of soy
(Table 2). No significant differences were observed in serum protein in the present study was 15 g day1. This amount is
HDL-C, LDL-C, TC and TG levels at both 3- and 6-month equivalent to the daily intake of 30e50 g soybean or
change percentage among the three arms by ANOVA. We equivalent soy products (10e17 g soy protein) recom-
repeated the analysis with baseline TC and LDL as cova- mended by the Chinese Nutrition Society. Higher amounts
riates to adjust for the baseline differences, but the results of soy protein might produce better results for cardiovas-
did not change significantly (data not shown). cular health. However, large dosage may also lead to an
A marginally significant difference between groups was unbalanced daily protein intake and may strongly modify
found in serum UA level at 3-month percent change with an the nutritional habits of participants. Furthermore, several
increase of 1.22% in the Soy group, and a decrease of 4.28% observational studies have noted that even a far lower
and 4.82% in the Iso and placebo groups, respectively amount of soy protein (6e11 g) than in the current study
(P Z 0.087). However, the differences were attenuated was associated with lower blood cholesterol level [10,13].
after further 3-month treatment with non-significance at 6- Thus, it seems unlikely the soy protein dosage is the key
month percent change among the three study groups. Both issue regarding the effect size of soy.
3- and 6-month percent change in hs-CRP did not reach The prediabetic features of our participants may have
statistical significance. We excluded the subjects with hs- contributed to the non-significant findings of our study.
CRP level >10 mg l1 in a sensitivity analysis, but this made Previous meta-analyses suggested that the beneficial effects
little change to the results. Ten-year CVD risks evaluated by of soy on lipids are more remarkable in subjects with hyper-
a Framingham equation recalibrated using Asian data [23] cholesterolaemia [3,5]. Women with prediabetes have a higher
were unaffected by any of the three treatments, although cardiovascular risk profile than the healthy population.
there was a trend of risk reduction by Soy protein However, the relatively mild increase of lipids and inflamma-
treatment. tion seen in prediabetic women may be less susceptible to soy
treatment than in diabetic or hypercholesterolaemia patients.
Blinding effectiveness The habitual soy foods intake in our study population
(12 g day1) may have overshadowed the effect of soy. Asia
women have traditionally higher soy foods consumption than
To assess the efficacy of blinding, the participants were
North American women. To obtain a good compliance in this
asked which intervention group they had been assigned to.
trial with a relatively long-term, participants were not
The proportion of participants who thought they had
required to strictly restrict their regular soy intake. We
received either one of the three treatments did not
tested this effect modification by adding an interaction term
significantly differ among the three groups, indicating the
between treatment and baseline soy levels to the general
blinding was effective (data not shown).
linear model with CVD risk factors as dependent variables;
and no significant interactions were found in all the analyses.
Discussion A further stratification analysis by baseline soy amount (soy
protein >12 g day1 and 12 g day1) indicated that the
This 6-month randomised controlled trial among post- change percentages of CVD risks at both 3 and 6 months
menopausal Chinese women with early hyperglycaemia did remained non-significant in both subgroups, suggesting that
not support the hypothesis that a daily intake of 15 g soy soy intake in habitual form may not be the key contributor to
protein with 100 mg isoflavones, or 100 mg isoflavones the null effect of soy on cardiovascular risks.
extract had significant improvement on cardiovascular In this study, a marginal increase of UA level with soy
risks. The strengths of this trial lie in the relatively large protein intake was observed after a 3-month treatment but
sample size, low dropout rate (<8%) and effective blinding. the effects were attenuated after 6 months. To our
A recent review [24] on the inclusion of an average 25 g soy knowledge, this is the first trial examining the long-term
protein in the diet reported a significant reduction of 6% on effect of soy protein on UA change in human adults. Soy
LDL-C among adults with normal or mild hyperlipidemia. protein contains high levels of purine ribonucleotides,
However, the review has not separated the effect of isolated which are derived from RNA native to the protein isolate
soy protein from soy protein contained in soya food/soy [26]. Previous acute or short-term studies [26,27] had
products, and the placebo groups also included non-protein shown that increased purine intake not only leads to an
controls. In contrast to our null findings, three clinical trials, increase in serum UA level but also concomitantly promotes
with duration ranging from 40 days to 6 months, using soy UA elimination and clearance. Evidence has also shown that
products containing low dosage of soy protein (8e17 g) milk protein can lower serum UA through the uricisuric
(soymilk [8], soy-rich diet [6] or soy protein added with b- effect [28]. These mechanisms may account for the
sitosterol [7]), reported beneficial effects of soy on lipids, marginal and transient effect of soy on the increase of
suggesting that the hypocholesterolaemic effect of soy might serum UA level observed in our study. Further research is
Effects of soy protein and isoflavones on cardiovascular risks 717

Table 2 Serum lipid profiles, hs-CRP, UA, CVD risk and their change% at follow-ups from baseline among 180 intention-to-treat
women.*
ITT Soy group (n Z 60) Iso group (n Z 60) Milk group (n Z 60) p
Mean (SD) Mean (SD) Mean (SD)
TC (mmol/l) 0.617c
b a
Baseline 5.83 (0.94) 5.38 (0.73) 5.63 (0.93) 0.020
Month 3 5.58 (0.84) 5.24 (0.89) 5.33 (0.87) 0.084
Month 6 5.67 (0.87) 5.36 (0.82) 5.43 (0.92) 0.120
Change% (0e3 months) 3.49 (10.38) 2.32 (11.28) 4.54 (12.16) 0.559
Change% (0e6 months) 1.93 (10.85) 0.06 (10.79) 2.55 (13.86) 0.459
TG (mmol/l) 0.928c
Baseline 1.35 (0.79) 1.27 (1.19) 1.30 (0.70) 0.824
Month 3 1.34 (0.79) 1.26 (0.90) 1.24 (0.66) 0.646
Month 6 1.39 (1.02) 1.30 (0.96) 1.28 (0.74) 0.464
Change% (0e3 months) 4.37 (33.22) 6.05 (37.06) 1.54 (26.22) 0.407
Change% (0e6 months) 10.18 (43.35) 8.00 (39.77) 3.36 (33.51) 0.735
HDL (mmol/l) 0.636c
Baseline 1.66 (0.37) 1.60 (0.31) 1.65 (0.30) 0.571
Month 3 1.63 (0.37) 1.54 (0.29) 1.57 (0.31) 0.314
Month 6 1.64 (0.37) 1.55 (0.26) 1.58 (0.30) 0.286
Change% (0e3 months) 0.62 (15.04) 3.03 (10.30) 4.43 (11.96) 0.248
Change% (0e6 months) 0.25 (15.43) 2.40 (10.97) 3.80 (11.86) 0.321
LDL (mmol/l) 0.315c
Baseline 3.94 (0.90)b 3.55 (0.67) a 3.81 (0.88) 0.031
Month 3 3.77 (0.77) 3.50 (0.84) 3.62 (0.76) 0.183
Month 6 3.82 (0.85) 3.62 (0.71) 3.68 (0.82) 0.361
Change% (0e3 months) 2.80 (14.78) 0.76 (16.01) 3.68 (15.08) 0.569
Change% (0e6 months) 1.81 (14.83) 3.16 (15.79) 1.84 (16.61) 0.139
LDL/HDL 0.395c
Baseline 2.50 (0.82) 2.28 (0.55) 2.39 (0.74) 0.241
Month 3 2.43 (0.72) 2.33 (0.61) 2.40 (0.70) 0.683
Month 6 2.47 (0.85) 2.39 (0.56) 2.42 (0.71) 0.808
Change% (0e3 months) 0.74 (18.16) 2.93 (16.80) 1.82 (16.94) 0.494
Change% (0e6 months) 0.44 (15.60)b 6.20 (15.27) 2.80 (18.76) 0.094
UA (umol/l) 0.553c
Baseline 32 (86.83) 324 (89.83) 322 (79.47) 0.983
Month 3 319 (87.59) 305 (81.62) 303 (69.47) 0.498
Month 6 316 (79.78) 307 (78.34) 307 (63.91) 0.729
Change% (0e3 months) 1.22 (18.88)ab 4.28 (16.74) 4.82 (13.34) 0.087
Change% (0e6 months) 0.57 (17.45) 3.71 (13.14) 3.06 (15.14) 0.264
Hs-CRP (mg/l) 0.301c
Baseline 1.01 (2.06) 1.14 (2.38) 1.24 (3.11) 0.624
Month 3 1.16 (2.54) 1.09 (2.68) 1.08 (2.42) 0.929
Month 6 0.91 (1.48) 1.15 (2.40) 1.11 (3.32) 0.551
Change% (0e3 months) 108.17 (325.87) 65.39 (330.34) 35.12 (157.46) 0.242
Change% (0e6 months) 30.95 (171.38) 53.20 (231.20) 50.55 (234.97) 0.834
Recalibrated Framingham risk probability (%)
Baseline 8.50 (4.83) 7.05 (2.96) 7.40 (3.46) 0.099
Month 6 8.05 (4.81) 6.97 (2.86) 7.47 (4.12) 0.388
Change% (0e6 months) 3.80 (18.15) 0.26 (16.51) 0.86 (23.35) 0.367
* All the mean and %changes values presented in the table were unadjusted.
TC, total cholesterol; TG, triglyceride; Hs-CRP, high sensitivity C-reactive protein; UA, uric acid.
a
represents p < 0.05 by comparing with placebo group.
b
represents p < 0.05 by comparing with Iso group by ANOVA.
c
p value for interaction between time and treatment by repeated measure ANOVA. The p-value for a, b are from LSD, post hoc multiple
comparison tests.

necessary before claims can be made regarding the effects may increase the probability of false statistical signifi-
of soy intake on urate metabolism and CVD risk. However, cance. The single marginal significant result in changes of
using the cut-off of P < 0.05 for several hypothesis testing UA level needs to be treated with caution.
718 Z.-M. Liu et al.

Circulating CRP concentration has been shown to increase Industries Ltd. (Israel) for supplying the raw materials of
after oral oestrogen treatment [29] or hormone replacement isoflavones and isolated soy protein for this study. Neither the
therapy [30]. In this study, although the level of hs-CRP funding agency nor Solbar played any role in the study design,
increased more in the Soy group, the overall results did not implementation, data analysis and article preparation.
show statistical significance at either 3- or 6-month Dr. Liu zhao-min was responsible for the data collection
percentage change. Controlling for other covariates had and analysis and the draft of the article. Prof. Suzanne C.
minimal effects on the results. The lack of effect may be Ho and Prof. Chen Yu-ming designed the study, applied for
partially related to the fact that circulating CRP levels in our the grant and supervised data collection and critical revi-
subjects are relatively low, with only 18.3% subjects showing sion and comments on the article. Prof. Ying Ping Ho was
elevated level (hs-CRP >3 mg l1) at baseline. In view of the responsible for randomisation, supplement labelling and
large individual variability of response in this marker, it is isoflavones analysis. We are indebted to all the participants
possible that our study may be underpowered to detect for their outstanding commitment and co-operation and to
a positive effect on CRP, if it exists. Furthermore, due to the the research staff of the Center of Research and Promotion
limited funds, we have studied only CRP among a large number of Women’s Health for their unfailing assistance.
of inflammatory markers. Further assessment of the impact of
soy on other inflammatory markers seems warranted. References
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