Soy Misinformation Nutr Cancer 55: 1, 2006 10 Nutr. Cancer 55: - - PDF document

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Soy Misinformation Nutr Cancer 55: 1, 2006 10 Nutr. Cancer 55: - - PDF document

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4/6/2017 Soyfoods, Soy Isoflavones & Health: Soyfoods, Soy Isoflavones & Health: Where Does the Science Stand? Where Does the Science Stand? Mark Messina, PhD, MS United Soybean Board Soy Nutrition Institute Soyfoods Council

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April 10, 2017

Soyfoods, Soy Isoflavones & Health: Where Does the Science Stand?

Mark Messina, PhD, MS

Soy Nutrition Institute Loma Linda University Nutrition Matters, Inc.

  • United Soybean Board
  • Soyfoods Council
  • Vitasoy
  • Pharmavite
  • Alpro

Consult for: Soyfoods, Soy Isoflavones & Health: Where Does the Science Stand?

  • Perception of soyfoods
  • Asian soy intake
  • Macronutrient composition
  • Health attributes of soy protein
  • Isoflavones
  • Breast cancer
  • Hot flashes
  • Bone health
  • Concerns

Soyfoods, Soy Isoflavones & Health: Where Does the Science Stand? Disconnect between Nutrition Professionals and the Public about the Healthfulness

  • f Specific Foods

Food

(% viewing as healthful)

Professionals Public Granola bars 28 71 Coconut oil 37 72 Frozen yogurt 32 66 Quinoa 89 58 Humus 90 66 Tofu 85 57

Disconnect between Nutrition Professionals and the Public about the Healthfulness of Specific Foods

Poll conducted by Morning Consult for the NYT. July 2016. Nutritionists = ASN members

 43  35  34  31  24  28

Food

(% viewing as healthful)

Professionals Public Tofu 85 57

Disconnect between Nutrition Professionals and the Public about the Healthfulness of Specific Foods

Poll conducted by Morning Consult for the NYT. July 2016. Nutritionists = ASN members

 28

Why does 43% of the public think tofu isn’t healthful?

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Soy Misinformation

10

Nutr Cancer 55: 1, 2006

  • Nutr. Cancer 55: 1-12, 2006

Unfermented Fermented

Traditional Asian Soyfoods

Edamame Tofu Soy milk Tempeh Miso Natto

Rarely used in clinical trials

Location Serv./d2 Type of soyfood Shanghai

1 – 2

Unfermented Singapore

½ – ¾ Unfermented

Hong Kong

½

Unfermented China

½

Unfermented Japan

1 – 2

50% fermented Korea

½ – 1

30% fermented

Asian Soyfood Consumption1

1Among older adults 2Servings: 240 ml milk, 85-100 g tofu

  • Nutr. Cancer 55: 1-12, 2006
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14 Food Chemistry 229: 663, 2017

Soy protein products

Isolate: ~90% protein Concentrate: ~70% protein Flour: ~50% protein

  • Routinely used in clinical studies
  • Widely used by the food industry:
  • Functional purposes
  • Western (second generation) soyfoods

Macronutrient Composition

vs.

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Macronutrient Soybeans Common beans Carbohydrate 27 70 Protein 33 27 Fat 40 3

AJCN 70: 439S, 1999

Macronutrient (% calories) Composition of Soybeans in Comparison to Common Beans

*Mostly oligosaccharides (indigestible) Capable of functioning as prebiotics

*

0.23 0.25 0.40 0.52 0.53 0.57 0.63 0.68 0.73 0.92 1.00 1.00 1.00

Almond Wheat gluten Whole wheat Peanut meal Rice Rolled oats Pinto beans Kidney beans Pea protein Beef Soy Milk (casein) Egg white

Protein Digestibility Corrected AA Scores

Highest score = 1.0 (truncated)

J Agric Food Chem. 59: 12707, 2011

  • United States (1999)
  • Indonesia
  • Japan
  • Korea
  • Chile
  • Turkey
  • Malaysia
  • Philippines
  • Brazil
  • Columbia
  • South Africa
  • Canada (2014)

“25 grams of soy protein per day … may reduce risk of heart disease”

Countries with approved health claims

  • J. Nutr. 138, 1244S, 2008

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration December 6, 2007

Reevaluating evidence in support of the health claim

23

  • Lowers LDL-C ~3% (22 studies)
  • Doesn’t warrant health claim
  • Didn’t conduct a meta-analysis

24

  • Lowers LDL-C 4.3% (22 studies)
  • Lowers LDL-C 5.2% (11 studies)
  • Warrants health claim

. J Nutr. 140, 2302S, 2010.

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Product

  • r group

Subjects (n) Percent

 LDL

Percent

 TG

Percent  HDL

Cont. Soy All1 1687 1679 4.83 4.92 1.40 Sub-analysis At risk2 32 studies 7.47 3.91 1.15 Healthy 18 studies 2.96 5.13 1.96

  • W. soy3

12 studies 11.06 1.03 1.06

LDL (-6.97%) & TG (-9.39%)  more in non-casein/milk control trials (n=22)

Soy products & Serum Lipids: A Meta‐ analysis of 50 Randomized Controlled Trials

1All products and subjects 2Elevated LDL,

hypertensive or diabetic 3Nuts, milk, oil, whole bean flour BJN. 114, 831-843, 2015

Comprehensive approach that dramatically lowers cholesterol

Metabolism 51: 1596, 2002

  • 35
  • 25
  • 15
  • 5

5 15

  • 1 0 1 2 3 4

Weeks on study

Percent Reduction in LDL‐Cholesterol in 13 Hypercholesterolemic Men and Women Consuming the Portfolio Diet

* * * *

Metabolism 51: 1596, 2002

  • Almonds
  • Low saturated fat
  • Soluble fiber
  • Soyfoods
  • Phytosterols
  • Fruits/vegetables

Components of the Portfolio Diet

High quality protein Protein is hypo- cholesterolemic High PUFA Low saturated fat

Ana M. Cartagena; CMAJ 173: 486, 2005

  • Br. J. Nutr. 106: 317, 2011
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Blood pressure mmHg 95% CI Systolic

  • 2.21
  • 4.10, -0.33

Diastolic

  • 1.44
  • 2.56, -0.31

Blinded trials (n=15) Systolic

  • 2.90
  • 5.49, -0.31

Diastolic

  • 1.93
  • 3.53, -0.34

Effects of Soy on Blood Pressure: Meta‐analysis of 27 Clinical Trials*

*Secondary endpoint in most trials

  • Br. J. Nutr. 106: 317, 2011
  • High quality (PDCAAS, 0.9-1.0)

Similar to animal protein

  • Lowers LDL-cholesterol (4-5%)

Health claims in >10 countries

  • May lower blood pressure (~2 mmHg)

All 4 meta-analysis show reductions

  • May favorably affect kidneys

Possibly multiple benefits

AJCN 88:38, 2008; BJN 106:317, 2011; Nutr Metab CVC 22: 463, 2012; J Hypertens. 28: 1971, 2010; World J Nephrol 5: 233, 2016

Attributes of Soy Protein

World J Nephrol 5: 233, 2016

Fatty Acid Composition of Soybean Oil

Fatty acid

Percent Saturated 12 Monounsaturated 29 Omega-6 PUFA (LA)* 53 Omega-3 PUFA (ALA)* 6

  • J. Agric. Food Chem. 2004 52, 5322; 57: 11174, 2009

*Essential fatty acids: LA, linoleic acid; ALA, -linolenic acid

  • 7% of total calories
  • 43% of linoleic acid
  • 44% of -linolenic acid

Contribution of Soybean Oil to US Caloric and Essential Fatty Acid Intake

Am J Clin Nutr 93: 950-62, 2011

Fatty Acid Composition of Soybean Oil

Fatty acid

Percent Saturated 12 Monounsaturated 29 Omega-6 PUFA (LA)* 53 Omega-3 PUFA (ALA)* 6

  • J. Agric. Food Chem. 2004 52, 5322; 57: 11174, 2009

*Essential fatty acids: LA, linoleic acid; ALA, -linolenic acid

9:1

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37

“ … no evidence from randomized, controlled intervention studies … that LA … increases the concentration

  • f inflammatory markers.”

The Controversy

  • ver Dietary Fat

& Coronary Heart Disease

39

.J Am. Coll. Cardiol. 66: 1538, 2015

Nutrient Coronary heart disease risk Refined carbohydrates 2%22 Carbohydrates, whole grains  9%2 Monounsaturated fat  15% Polyunsaturated fat  25%

Effects of Replacing 5% of Calories from Saturated Fat with 5% of Calories from:

Based on 127,536 study participants who were followed for up to 30 years

.J Am. Coll. Cardiol. 66: 1538, 2015

Isoflavones

O OH O R1 R2 OH

7 5 1

A C B

2 4

Naturally-occurring plant chemicals

>20,000 peer-reviewed publications

Mean Daily Isoflavone Intake

30-50 mg

Nutr Cancer 55:1, 2006 Int J Food Sci Nutr 65: 9, 2014

Traditional soyfoods: 3-4 mg/g protein One serving ~25 mg

<3 mg

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Soybean Isoflavone Aglycones

Phytoestrogens

Isoflavone R1 R2 % of total Genistein H OH 50 Daidzein H H 40 Glycitein OCH3 H 10

O OH O R1 R2 OH

7 5 1

A C B

2 4

Genistein Estradiol

Cholesterol

(animal foods)

Phytosterols

(plant foods)

 Blood cholesterol  Blood cholesterol

Isoflavones

  • Found primarily in soybeans
  • Phytoestrogens but different from estrogen
  • Sometimes effects opposite to estrogen
  • Sometimes no effects in estrogen-sensitive

tissues

  • Estrogen-independent effects

O OH O R1 R2 OH

7 5 1

A C B

2 4

Soyfoods and breast cancer prevention

87.0 72.1 60.7 44.7 20.8 19.7 19.1

50 100

USA Basle Sweden Finland India Japan China

Age‐Adjusted Breast Cancer Incidence Rates (per 100,000) for Selected Countries

BCa: Shanghai, Osaka, Madras, Geneva, San Francisco (W).

20 40 60 80

59-61 65-67 73-77 83-87 93-97

Year of diagnosis

  • Int. J. Cancer: 108,

901–906 (2004)

Westernization

Age‐Adjusted Breast Cancer Incidence Rates (per 100,000) for Miyagi Prefecture, Japan, 1959‐97

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49

Asia Pac J Clin Nutr, 22: 118, 2013

Higher soy intake is associated with a

  • ne-third reduction in breast cancer risk

Early Soy (Isoflavone) Intake Decreases Breast Cancer Risk

  • Rodent data
  • Epidemiologic data
  • Proposed mechanisms

Support

Early Soy (Isoflavone) Intake Decreases Breast Cancer Risk

Author/Y Location (N) Risk % 

Statistically Significant?

Shu, 2001 China 3,015 49 Yes Wu, 2009 USA 345 28 Yes Korde, 2009 USA 250 60 Yes Baglia, 2016 China 36,297 44 Not quite

*Premenopausal only Ref.: Shu: CEBP;10:483, 2001; Wu: AJCN 89: 1145, 2009; Korde: CEBP 18: 1050, 2009; Int J Cancer 139: 742, 2016 *(95% CI: 0.31, 1.00)

High vs low soy intake during adolescence

*

Early Soy Intake and BCa Risk: Summary of Retrospective Studies

Young girls should be sure to eat ≥1 serving of soy per day

100 g 240 ml 100 g 100 g 245 g

Can soyfoods be safely consumed by breast cancer patients?

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Why the controversy?

SOY & BREAST CANCER

Estrogen and Breast Cancer

“… the use of estrogen alone results in a small reduction in the risk for developing

  • r dying of invasive breast cancer.”

Ann Intern Med 158: 47, 2013

35 30 37 36 28 23 29 31 50-79 50-59 60-69 70-79

Estrogen* Use and Annual Breast Cancer Incidence in the WHI Trial

Events/10,000 women Age at enrollment (years) Placebo

(n=5,429)

Estrogen

(n=5,310)

Conjugated equine estrogens (0.625 mg/d); mean use, 7.2 y; 13 y follow up. Events=invasive BCa. JAMA 310: 1353, 2013

P=0.02

No clinical trials have evaluated the effects of soyfoods or isoflavones on breast cancer recurrence or mortality

No effects on markers of cancer risk

Trials Involving Soy & Soy Components

Breast cell proliferation

(N=6*)

Mammographic density (N=11*)

Oncology 2013;430:430-37

Hormone levels (N=50*)

*Number of studies

Nipple aspirate fluid

(N=3*)

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Fertility Sterility 95: 1188, 2011; Breast Cancer Res Tx 78: 159, 2003

Combined Hormone Therapy

(estrogen + progestin)

Increases breast cell proliferation 4 to 10-fold

12 weeks

Increases breast cancer risk

Women with breast cancer can safely consume soyfoods

Isoflavones don’t adversely affect breast tissue in postmenopausal women

Consuming soy after a diagnosis of breast cancer is associated with reduced recurrence and increased survival

  • 5 studies (3 Chinese, 2 American)
  • 11,224 women with breast cancer
  • Follow up: 3.9 to 7.3 years
  • 948 breast cancer deaths
  • 1449 recurrences

Exp. Details

High versus low soy intake Outcome Hazard ratio 95% CI Mortality 0.84 0.71, 0.99 Recurrence 0.74 0.64, 0.85 “… consuming a diet high in soy is associated with a 25% decrease in cancer recurrence and a 15% decrease in mortality…”

J Fam Pract 64: 660,2015

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Soy and hot flashes

9.7 30.9 34.8 13.5

Exp Gerontol 29: 307, 1994; Maturitas 2006

% of women with hot flashes

The Hot Flash Hypothesis

Japan Canada USA China

Isoflavones can mitigate the drop in estrogen levels

Herman Adlercreutz, MD, PhD University of Helsinki, Finland

Lancet 339 (8803), 1233

Only trials intervening with extracts derived from soybeans were eligible*

*1 trial used synthetic genistein

Menopause 19: 776, 2012

Soy isoflavones significantly reduce hot flash frequency and severity in comparison to placebo

Decrease in Hot Flash Frequency and Severity: Meta‐analysis Results

Symptom (Studies/N) Group Percent Decrease Frequency (13/1196) Placebo 29.6 Isoflavones 50.2 Net 20.6 Severity (9/988) Placebo 21.4 Isoflavones 47.6 Net 26.2

1 2

1P < 0.00001 2P = 0.001

“The effectiveness of soy isoflavones was superior to sertraline, venlafaxine, paroxetine, gabapentin, and clonidine …”

Eur J Clin Pharmacol 72: 1051, 2016

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Whole soy Soygerm

Isoflavone Profile of Two Commonly Used Soy Supplements

Soybeans Supplements Genistein Daidzein Glycitein

mg/day1 Number

  • f trials

(n) Net % decrease2

≤18.8 7 596 12.47 >18.8 6 600 29.13

Supplements Providing Sufficient Genistein Are More Potent

3

1Median, 18.8 mg 2Beyond placebo effect 3P = 0.03 between groups

(random effects model) Menopause 19: 776, 2012

Isoflavones and the Alleviation

  • f Menopausal Hot Flashes

Expected  50-65%

(≥50 mg total isoflavones) (≥19 mg genistein)

Approximately two servings

  • f traditional soyfoods

J Nutr 140: 2318S-2321S, 2010

Soy and bone health

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  • Inhibits bone loss
  • Reduces fractures

Large, long-term clinical trials involving isoflavone supplements have generally produced disappointing results

Ann Intern Med 146: 839, 2007; AJCN 91: 218, 2010; Arch Intern Med 171: 1363, 2011; Osteoporosis Int 23: 1571, 2012

AJCN 102: 695, 2015

“… the use of soy isoflavones presents minimal to negligible risk to postmenopausal women … and can be used long term for some protection against postmenopausal bone loss.”

Health effects of isoflavones misrepresented

Food Chem 225: 289, 2017

Feminization

60 year

  • ld man

19 year

  • ld vegan

man

360 mg isoflavones

(12-20 servings/day)

360 mg isoflavones

(3 liters soymilk/day)

, Nutrition 27: 859, 2011 Endocrine Pract 14: 415, 2008

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“No significant effects of soy protein or isoflavone intake on testosterone, sex hormone binding globulin, free testosterone

  • r free androgen index …”

Fertil Steril 93: 2095, 2010

“… isoflavones do not exert feminizing effects on men at intake levels equal to and even considerably higher than are typical for Asian males.”

Asian epidemiologic studies show soy intake is protective against prostate cancer

AJCN Nutr 89: 1155, 2009 Andrology 4: 745, 2016

Soy and thyroid function

Thyroid 16: 249, 2006

No effects of soy or isoflavones

  • n thyroid function in people with

normal-functioning thyroids

J Clin Endo Metab 95: 3067, 2016: 249, 2009

No effect of isoflavones on thyroid function in postmenopausal women

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Isoflavones don’t adversely affect thyroid function in postmenopausal women

Soy and hypothyroid patients

Best Pract Res Clin Endocrinol Metab 23: 781, 2009 Clinical Therapeutics 39: 378, 2017

  • Soy protein
  • Calcium carbonate
  • Fiber supplements
  • Iron
  • Protein pump inhibitors
  • Bile acid sequestrants
  • Certain herbs
  • Etc.

J Pediatr 157: 13, 2010

Not contraindicated for hypothyroid patients

Reduces absorption of minerals – calcium, iron, zinc, and magnesium

Phytate

(phytic acid)

  • Naturally occurring compound
  • Found in whole grains & beans

Peanuts Quinoa Rhubarb Almonds Spinach

Oxalate

Naturally-occurring plant chemical that reduces the absorption

  • f minerals such as

calcium

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  • Calcium absorption:
  • Fortified soymilk = cow’s milk
  • Calcium set tofu = cow’s milk
  • Iron absorption:
  • Greatly underestimated?
  • Soy iron present as ferritin

Soybeans are high in phytate & oxalate, but

J Nutr 135: 2379, 2005; J Food Sci 68: 3144, 2002; Am J Clin Nutr 89: 1680S, 2009 J Nutr 145: 1735, 2015

Habitual consumption of a high phytate diet can reduce the inhibitory effect of phytate on iron absorption

Does soy affect puberty?

Population-based studies worldwide have observed secular trends towards earlier pubertal development

Basic & Clinical Pharmacol and Toxicol 102: 168–175, 2008

Country Time period Beginning Ending Holland 1965 2009 13.4 12.6 Japan 1930  1985 13.8 12.6 Korea 1920  1985 16.9 13.8 UK 1910  1993 13.5 12.3 Spain 1925  1962 13.7 12.8 Canada 1933  1988 13.2 12.5 Brazil

(<8 y education)

13.4 11.7 1932  1977

(>8 y education)

12.4 12.2

Change in Menarcheal Age (y)

Early puberty Childhood soy intake Risk

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Basic & Clinical Pharmacol & Toxicol 102: 168–175, 2008

Earlier pubertal development may be due to exposure to hormonally active chemicals in the environment

Nutr J 13: 54, 2014

  • 327 Seventh-day Adventists, age 12-18
  • High-soya-consuming population
  • Mean intake, 12.9 servings/week
  • 21% consumed >4 servings/day
  • Mean age of menarche, 12.5 years
  • Soy unrelated to age of menarche onset

J Allergy Clin Immunol 119: 1504, 2007; Clinical Pediatr (Phila) 2012;51:856; J Allergy Clin Immunol 125: 683, 2010. European Commission Directive 2007/68/EC of 27th November 2007

  • FDA survey of adults
  • 1 out of 2,500
  • Milk 40x > soy

Soy Allergy Prevalence

FDA “Big 8”

  • N=38,465 children
  • ~1 out of 200
  • Milk/peanuts 4-5x >soy
  • 70% outgrow by age 10

“Big 14”

  • Totality of the evidence
  • Study type and quality

Soyfoods promote health

  • Excellent safety profile
  • High quality protein
  • Hypocholesterolemic, possibly hypotensive
  • Healthy fatty acid profile
  • High in PUFA, both essential fats
  • Uniquely-rich source of isoflavones
  • Early intake may prevent breast cancer
  • Reduces hot flashes  May increase BMD

 May decrease prostate cancer risk

Nutritional and Health Attributes of Soy