Suravaya Soy&Healthwatanabe
Transcript of Suravaya Soy&Healthwatanabe
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Soy and Health
Isoflavone Contents in
FoodsShaw Watanabe, M.D.,Ph.D.
Representative, Soy Nutrition Institute Japan
President, Life Science Promotion Foundation
Director-General emeritus, National Institute of
Health and Nutrition
Surabaya, Indonesia
8-2-2010
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years ago inSakenomiba archeologicsite
Fossil of soy cultivation
Topics of Soy & IFResearch
1. Cancer prevention2.Cardiovascular
disease
3. Osteoporosis4. Menopause
5. Cognitive function
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Comparison of Cancer Incidence
USA
Finland
JapanProstate
Breast
Ovary
Uterinebody
Colon(M
)
0
2
4
6
8
10
12
Cumulati
veIncidenc
e
Ra
te(%)
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1
PhIPHCl (85 mg/kg body wight)
Basic diet
Soy germ Soy germ
Soy germ+ mature garlic powder
0 2 4 28
week
1
Soy germ
Soy germ
n= 6
n=23
n=22
n=25
n=27
n= 6
n= 6
Prevention of PHIP induced Breast Cancer
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Soy germ atinitiation41%
Soy germ at
promotion24%
Soy germ &
garlic 15%Control 0%
PHIP induced Breast Caner
Week
0
IncidenceRate(%)
5 10 2815 20
20
40
60
PHIP only 65 %
80
Watanabe & Haba, 1998
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Correlation coefficient between IFs, hydroperoxides,
and 8-OH-dG in various tissues
PCOOH (RBC) 0.183 0.183 0.242 0.204 0.085
PEOOH (RBC) 0.033 0.033 0.017 0.000 -0.016PCOOH (liver) -0.453** -0.453** -0.396* -0.424** -0.403*
PEOOH (kidney) -0.210 -0.290 -0.147 -0.245 -0.104
8-OH-dG (liver) -0.009i -0.009 -0.038 0.039 -0.066
8-OH-dG (kidney) -0.291 -0.291 -0.271 -0.273 -0.336 *8-OH-dG (urine) 0.469** 0.469 ** 0.343 * 0.395 * 0.332 *
nmol / day intake nmol / day urine
Genistein Daidzein Genistein Daidzein Equol
: Pearsons Correlation Coefficient p
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Promotion
Progression
Anti-vascular
proliferationAnti-estrogenic effect
Aromatase inhibition
Induction of SHBG
Protein tyrosine
kinase inhibition
Anti-oxidation
Effects of isoflavones in the process of
breast cancer
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Odds Ratio/Relat ive Risk
.1 .2 .5 1 2 5
Combined
Lee (pr e-*), 1992Y ama moto, 2003
Witte, 1997
Shu, 2001
D ai, 2001
Wu, 2002
H irose (post-*), 20 03
H irose (pre-*), 2003
Wu, 1996
Y uan, 1995
H orn-Ross, 2001
H orn-Ross, 2002
K ey, 1999
Lee (post-*), 1992
Pooled Risk Estimate = 0.78 (95% CI= 0.68-0.91)
Soy Consumption and Breast Cancer in Women
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Odds Ratio/Relative Risk
.1 .2 .5 1 2 5 10
Combined
Yamamoto, 2003
Wu, 2002
Shu, 2001
Hirose, 2003
Wu, 1996
Lee, 1992
Pooled Risk Estimate = 0.64 (95% CI= 0.47-0.88)
Soy Consumption and Breast Cancer in Postmenopausal Women
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Odds Ratio/Relative Risk
.1 .2 .5 1 2 5 10
Combined
Jacobsen, 1998
Severson, 1989
Lee, 2003
Kolonel, 2000
Strom, 1999
Villeneuve, 1999
Pooled Risk Estimate = 0.66 (0.54-0.81)
Soy Consumption and Prostate Cancer in Men
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Blood Pressure and Isoflavone Supplement in Climacteric
Women**
High Blood PressureN=26
Normal Blood
PressureN=27
200
150
100
50
SBP Baseline
SBP Isoflavone
DBP Baseline
DBP Isoflavone
**
mmHg
** p
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1
1.001.06
0.81
0.71
0
1
0-2 3-4 5-
(
J-PHC Study: multipurpose cohort study in 4
areas40,000 residents, ages 40-59, followed up from 1990 to 2002.
Cerebral infaction 578, cardiac infarction 308.
1.19
0.90
1.15
0.31*
0
1
0-2 3-4 5-
Circulation 116: 2553-2562, 2007
Incidence Mortality
Male Female
Day of Soy Intake per Week Day of Soy Intake per Week
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3 (
1.00
0.69
0.39*
0.60*
0.46*
0
0.2
0.4
0.6
0.8
1
1.2
Q1() Q2 Q3 Q4 Q5()
IF 11.1 187 267 347 452 mg/day
Isoflavone Intake and Risk of Vascular Diseases
J-PHC Study: multipurpose cohort study in 4
areas40,000 residents, ages 40-59, followed up from 1990 to 2002.
Cerebral infaction 578, cardiac infarction 308.
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Decreased E2 and Climacteric Symptomes
Is Isoflavone Supplement effective?
0
50
100
150
30 40 50 60 70 80
Age (yrs)
Estroge
nConcentration
(pg/ml)
Atrophy of vaginal mucosaSkin lesion
OsteoporosisCardiovascular Risk
Vascular neuromoter symptomsDysmenorrhoea
Psychologic sympotoms
Climacterium
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Different Response of Climacteric Symptoms to
Isoflavone Supplement
Year Participants Diet(Isoflavone dose)
Effect in menopausal
symptoms
Albertazzi 1998 104
Postmenpausal
Soy powder(76mg)
12wk
Number of hot flash
Quella 2000 177 Soy tablet(150mg)4wk
No effectin hot flash
Upmalis 2000 177
Postmenpausal
Soy tablet(50mg)
12wkSeverity and number
of flushs
Van Patten 2002 123
Postmenpausal
Soy beverage(90mg)
12wk
No effect
in hot flash and hotflash score
Ishiwata
Watanabe
2004 111
Post and pre
menopausal
Soy IF tablet
(40mg&80mg)
24wk
pre-menopausal
symptom score
M t b li P th f D id i
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O
O
O
O
O
O
O
HO
OH
HO
OH
OH
HO
OH
OH
HO
HO
OH
Daidzein
Dihydrodaidzein Intermediate E
EquolO-desmethylangolensin
Metabolic Pathway for Daidzein
Intestinal
Bacteria
Alercreuz, 2000
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Different rates of Equol Producers by
PopulationYear Target Participants
number
Age Equol
producer
Arai 2000 Population 106 58.01- 50%Lampe 2000 Population 74 32.1 32%
Setchell 2002 Climacteric women 10 46.79.3 30%
Watanabe 2002 Pharmacokinetics 25 20.90.6 48%Uesugi 2003 Climacterium 58 58.07.0 62%
Watanabe 2003 PMS 34 21.10.6 35%Ishiwata 2003 PMS 60 19.60.6 20%Lampe 2004 Plasma hormone 89 50-75 25%
Hall 2006 Metabolic biomarkers 117 57.55.4 28%
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Equol supplement is made by
fermentation of soy germ using selected
Lactococcus. Sp.
The equol supplement is a granular type, and
contains 6.5 mg equol, 0.6 mg daidzein, 0.6
mg genistein and 3.2 mg glycitein per gram.
More than 90% are aglycones. One tablet contains 10.9 mg equol, 66.7%
are fermented material, and 33.3% is
erythrytol.
Production of Equol Supplement
Watanabe et al, 2008
nM/mlnM/ml
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1 2
nM/mlnM/ml
Equol suppl.
10 mgEquol suppl.
30 mg
Equol suppl.
10 mg x 3 times
Men Women
nM/ml01 2 3 4 5 6 12 24 36 1 2 3 4 5 6 12 24 36
0 1 3 5 7 9 11 13 24 36 48
Plasma equol concentration after suppl.
intake
0 1 3 5 7 9 11 13 24
200
400
600
800
200
400
600
800
1000
2000
3000
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Baseline After 3mos
272825 272925n =
EQ non-producer
EQ30EQ10Placebo
EQ
mole/24
hrurine
250200
150100500
161218 161218n =
EQ producer
EQ30EQ10Placebo
250200
150100500
Changes of Urinary Equol Excretion by Equol Supplement
Ishiwata & Watanabe, 2008
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Climacteric Symptoms at Baseline by Equol Producibility
Total Physical
symptom
Mental
symptom
Equol
Equol
0
5
10
15
20
25
Total Physical
symptom
Mental
symptom
Equol
Equol
Climacteric Menopause
Clima
ctericsymptomsc
ore
** p
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Changes of Climacteric Symptom Score by Equol Supplement
Climacteric
EQ nonproducer
Pre Post
EQ producer
BL Post
Menopause
*p
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Feeling Score by POMS in relation to Equol Producibility
* **p
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Equol Supplement is effective for
Hypercholesterolemia (>240 mg/dl) in premenopausal women
220
230
240
250
260
270
Placebo EQ10 EQ30
Totalcholesterol(mg/dl)
n= 4 10 7
**
Before intervention After 12 wks
* Significant difference by paired t- test (p
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Effect on Osseous Metabolic Markers
Baseline
14
12
10
8
6
4
2
0
1 M 4 M Baseline 1 M 4 M
Deoxypyridinoline Osteocalcin
nM/mM Cr
14
12
10
8
6
4
2
0
ng/ml
*
** **
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-10
-5
0
5
10
15
0 6M 12M
ChangeofBMD
control
Isoflavone only
Walking only
IF+walking
*
*
*
-001
-4
Effect of IF Supplement and Walking
Ischimi et ak. J Bone Miner Res. 21:780-789, 2006
Femur
1 year RCT
Isoflavone 75 mg
Walking
6km/h45min/3/W4METs x 3/4 h x 39METhr/W
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Protein A proteinCholesterolemia A A protein 30g soy proteinLDL cholesterol isoflavone
TGInfant diarrhea B soy fiber formulaHot flash at menopause B A isoflavone 50-75mg IFMigrain at menopause C BBreast cancer prevention C A isoflavoneProstate cancer prevention C A isoflavoneColon cancer prevention C isoflavoneCardiovascular disease C A isoflavone 40-80 mgIFNephrosis C
Osteoporosis C A isoflavone 60-80 mgIFObesity, weight control C soy foodsType 2 diabetes mellitus C 7g soy fiberDementia, C isoflavone ?impaired recognition peptide?
Natural Standard
2005, USAOur results
Health Effects of Soy Bean
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Analysis of Isoflavone Contents in foreign Foods
Thailand (3 items)Yuba, Tofu, deeply fried tofuChina (5 items)powder, soy bean cake, soy milkUSA (5 items)supplements
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Concentration of the Isoflavones
in the Soybean Foodsmg/100 g wet
Food Name Daidzein Genistein
Soybean 97.6 147.8
Soymilk 7.8 15.7
Natto(Fermented Soybean) 36.6 60.7
Soysouce 0.8 0.5
Tofu (Soybean curd)
Silken type 13.0 20.6
Momen Type 16.6 26.9
Deep fried tofuThick type 14.9 25.7
Thin type 8.4 17.9
Miso(Soybean paste)
Dark yellow type 21.3 29.3
Light yellow type 17.6 3-
MisoLight yellow type
Soybean
Silken tofu
Momen tofu
Deep fried tofu(Thin type)
Soysouce
Natto
Deep fried tofu
(Thick type)
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Name Material Intake amount Label Aglyconfrom labelmgMeasueddosemg)
Rate CV%
Yuba Soy bean 110 g/pack none 34.5 0.6
Tofu Soy bean 220 g/pack none 28.8 2.5
Fryed Tofu Soy bean 110 g/pack none 52.2 8.0
Isoflavone contents in soy foods in Thailand
aglycone eq. mg /pack
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Name Material Intake amount Label Aglyconfrom labelmgMeasueddosemg)
Rate CV%
Soy 40 g/pack none 15.9 0.8 Soy fiber 6 g/stick none 0.3 1.6 powder ca 23 g/pack none 4.0 1.1 powder ca 50 g/pack none 0.1 powder ca 22 g/pack none 3.5 3.6
Isoflavone contents in Chinese Healthy Foods
aglycon eq. mg/pack
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Name SupplementFacts Intake amount IF doseAglyconeq dosefrom labelmg
Measureddosemg)Rate ofamount CV%
menopause
supportPurifiedisoflavones 2 tablets 80mg 50.0 28.6 57.2 5.5
soy careSoyisoflavones 1 capsule 25mg 15.6 12.7 81.5 5.6
Complete
Balance for
menopause
AMSoyisoflavones 1 capsule 25mg 15.6 7.1 45.4 5.3
PMSoyisoflavones 1 capsule 25mg 15.6 7.6 48.6 6.2
Soy BalanceSoyisoflavones 1 tablet 65mg 40.6 32.5 80.0 4.5
Soy isoflavone contents in US supplementsaglycone eq.mg /serving
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Name Material Daidzein Glycytein Genistein Total(%)Yuba Soy bean 23.4 0.6 76.0 100Tofu Soy bean 41.0 8.4 50.5 100
Deep fried tofu Soy bean 24.8 0.9 74.3 100 Soy bean 29.5 6.3 64.2 100 Soy fiber 38.7 7.9 53.4 100 Yellowpowder 32.6 39.8 27.6 100
Yellowpowder 10- - - 100 Yellowpowder 36.6 8.2 55.1 100
Isoflavone componentsweight % in soy foodsfrom Thailand and China
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Name Supple-mentFacts D MD AD SD De Gl MGl AGl SGl Gle G MG AG SG GeTotal(mg)
Menopause
supportPurifiedisoflavones 9.7 0.2 0.3 0.1 3.4 2.2 0.2 - - 0.2 10.3 0.1 0.4 0.1 1.4 28.6
Soy careSoyisoflavones 5.0 0.1 0.1 - - 1.2 - - - - 5.9 0.2 0.1 0.1 0.1 12.7
Complete
Balance for
menopause
A
MSoyisoflavones 3.4 - 0.2 - 0.1 2.0 - 0.1 - 0.3 0.8 - 0.1 0.1 - 7.1
PMSoyisoflavones - - - - - - - - - - - - - - 7.6 7.6
Soy BalanceSoyisoflavones 11.1 0.1 0.2 - 0.3 2.5 - - - 0.1 17.3 - 0.5 - 0.3 32.5
Isoflavone contents in US supplementsaglycone eq.)mg /serving
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Adequate Intake of Soy Products
Soy IF on improvement of bone biomarkerDPD51g (14-114) mg/d10W12mos-18%
Food for Special Health Use (FOSHU)Soy protein7g/d IF 1030 mg/d
Soy protein fortified foodSoy protein 515g/dIF 2040 mg/d
Soy Proteinwith IF
on Lipid improvement49111 mg/dvs. Animal protein 13mos
-0.18 mmol/L (LDL-C)
Metaanalysis Foods
Soy protein & IF on improvement of systolic
blood pressure 80g (25-375) mg/d2 24W-1.92mmHg
Lipid metabBone metabHypertension
1023 g Soy protein50110 mg isoflavone
Healthy food with isoflavonesIF content: 6.338 mg/d
Improvement
DailySoy FoodHealth FoodWith Soy Protein
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9
5
Thank you very much!
Co-workers
Yoshiko Ishimi, PhD
Kyoko Taku, MD, PhD
Naoko Ishiwata, PhDMariko Uehara, PhD
Melissa Melby, PhD