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


7/36Initiation

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

Suravaya Soy&Healthwatanabe

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