Soy Protein and Serum Cholesterol Reduction

David J.A. Jenkins

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto;

Clinical Nutrition & Risk Factor Modification CenterSt. Michael’s Hospital

Ontario, Canada

ColleaguesArash Mirrahimi, Korbua Srichaikul, Claire E. Berryman, Li Wang,Amanda Carleton, Shahad Abdulnour, John L. Sievenpiper, Cyril W. C. Kendall,and Penny M. Kris‐Etherton

J. Nutr. 140: 2302S–2311S, 2010Sonia Blanco Mejia, Siying S Li, Effie Viguiliouk, Laura Chiavaroli, John L Sievenpiper, Penny Kris‐Etherton, Mark Messina.

Unpublished

Conflict of Interest

C = Consultancies; H = Honorarium; SAB = Scientific Advisory Boards; G = Grants

• Barilla, Italy – A general food company. Producer of pasta and baked goods. G

• Solae, St. Louis – The major US producer of soy protein isolate. C,G• Unilever, Vlaardigen,Netherlands – Major margarine producers

including Becel and Take Control (plant sterol enriched margarine). G, GP

• Haine Celestial, CA – One of the largest Health Food companies in the US. G

• Loblaws Supermarkets – Canada’s largest supermarket chain.G, SAB

Sanitarium Company, Sydney, Australia – Australia’s largest health food manufacturing company and soy food producer. G, SAB

Epicure – C, H

Conflict of Interest

Herbalife International, Century City, CA – A nutraceutical company with an emphasis on sourcing plant derived components for weight loss. SAB

Nutritional Fundamentals for Health, Montreal, QE – A new nutraceutical company exploring and aiming to market food derived components for health. SAB

Pacific Health Laboratories INC, Matawan, NJ – a nutrition technology company with functional food and nutraceutical products researched and commercialized for sports performance weight loss and type 2 diabetics which can be marketed without prior approval of the FDA. SAB, Stock

Metagenics/MetaProteomics, Gig Harbor WA – a company assessing natural products from hops which will positively impact individuals with specific genetic susceptibilities for chronic disease. SAB

C = Consultancies; H = Honorarium; SAB = Scientific Advisory Boards; G = Grants

Conflict of Interest

Bayer Consumer Care, Springfield NJ – Marketing of nutritional supplements/nutraceuticals. SAB

Oldways Preservation Trust, Boston, MA – A not for profit organization promoting traditionally “healthy” ways of eating (eg. Mediterranean Diet, etc.) H

Almond Board of California, Modesto, CA – A branch of the USDA (therefore “not for Profit”) to promote the use of almonds. C,H,G

The California Strawberry Commission, Watsonville, CA – Another USDA not for profit group to explore possible health benefits and to promote the use of strawberries. SAB

Orafti, Tienen, Belgium Development of prebiotics for modification of colonic microflora. SAB, G

C = Consultancies; H = Honorarium; SAB = Scientific Advisory Boards; G = Grants

Conflict of Interest

Unilever ‐ Canada – Guidelines for the management of hyperlipidemia. G,C,H

Agriculture and Agrifoods Canada (AAFC) – SAB Canadian Agriculyure Policy Institute (CAPI) – SAB White wave‐ Dean Foods, Colorado – SAB, C, H Orafti, Tienen, Belgium Development of prebiotics for modification of colonic microflora. SAB, G

Wife and is a Director of Glycemic Index Laboratories, Toronto, CA –Financial relationship of a spouse

Kellogg’s, Canada – C, H, SAB Quaker Oats, Canada‐C, H, SAB The Coco Cola sugar Advisory Board . C, H,SAB Griffin Hospital, New Haven‐ For the development of the Nuval System. C, H, SAB

C = Consultancies; H = Honorarium; SAB = Scientific Advisory Boards; G = Grants

Conflict of Interest

• Abbott Laboratories, Algorithms for Diabetes Management. C, H, SAB

• The Canola & Flax Councils of Canada. C, H,SAB

• Pulse Canada ‐ SAB

• Saskatchewan Pulse Growers – SAB

• Canadian Institute of Health Research (CIHR) – G

• Canadian Foundation for Innovation (CFI) –G

• Ontario Research Fund (ORF) – G

• Advanced Foods and material Network (AFMNet) – G

• International Tree Nut Council Nutrition Research and Education Foundation and the Peanut Institute – G, H

• Alpro Soy Foundation – H

• Vegan for last 10year (Vegetarian since 12y, B12deficient?)C = Consultancies; H = Honorarium; SAB = Scientific Advisory Boards; G = Grants

Soy History

1. Anderson et al NEJM 19951.5‐2.0g soy protein/d=↓ LDL‐C 12.5%

2. FDA Soy Health Claim 19993. AHA Soy Advisory 2006 = ↓ LDL‐C 3‐4% (intrinsic)4. FDA proposal to revoke Soy Health Claims 2017

The Evidence

Neither the AHA or FDA based their concerns on meta analyses of RCTs

They arrived at their conclusions by stating that most individual studies (often small numbers) did not reach significance

Hence we believe meta analyses are REQUIRED 

AHA Advisory Soy Studies

J. Nutr. 140: 2302S–2311S, 2010

AHA advisory ~ 4.3% LDL‐C reduction (p<.0001)

~ 3.2% LDL‐C reduction STILL (p<.0001)

Same Meta analysis approach with 46 FDA 2017  trials 

Other FDA Health Claims:

• Nuts 40g ~ ↓4% LDL‐C• β-glucans oats

• 3.5g ~↓5% LDL-C

= Similar order of magnitude

BUT

Add Meat and Dairy SFA displacement valueWhen Soy foods are used

LDL‐C Change

J. Nutr. 140: 2302S–2311S, 2010

% LDL reduction

Soy substitution for Animal Protein Foods LDL‐C reduction bar graph

J. Nutr. 140: 2302S–2311S, 2010FIGURE 2 Change in LDL‐C due to dietary displacement by soy protein at the average fatty acid intake reported in the NHANES III population assessment

Soy Effect

Endogenous LDL‐C reduction =3.2% *+

Displacement LDL‐ C reduction =3.6%‐6.0%

Total LDL‐C reduction = 6.8‐9.2%

How do we use soy as a part of a combination –a Dietary Portfolio

% LDL reduction

NCEP step 2: 10 %

Portfolio Diet: viscous fiber 5 %soy & legumes proteins 5 %plant sterols 5 %almonds 5 %

TOTAL 30 % LDL reduction

= 1st generation Statin

What happens if you combine these cholesterol‐lowering components (Portfolio Diet)?

Jenkins DJ, Kendall CW, et al.Curr Opin Lipidol 2000

after

Key Mechanisms of Action

1. Viscous fibers = Bile acid losses

2. Soy Protein = Cholesterol synthesis LDL receptor uptake

3. Phytosterols = Cholesterol absorption

4. Almonds + multiple mechanisms

Dietary PortfolioStudy Foods: Readily available in supermarkets.

Nuts: ~30 g/dalmonds

Viscous Fiber: ~20 g/doats, barley, psyllium, legumes, eggplant, okra

Vegetable Protein: ~80 g/d (50% soy)soy, beans, chick peas, lentils

Plant Sterols: ~2 g/d plant sterol margarine

Jenkins DJ, Kendall CW et al. Metabolism 2002

Dietary Portfolio: Changes in LDL‐C

-40

-35

-30

-25

-20

-15

-10

-5

0

5

10 LDL Cholesterol

Control

PortfolioStatin

Wk 0 Wk 2 Wk 4

% C

hang

e Fr

om B

asel

ine

Jenkins DJ, Kendall CW et al. JAMA 2003

Dietary PortfolioChanges in C‐Reactive Protein

% C

hang

e Fr

om B

asel

ine

Wk 0 Wk 2 Wk 4

-40

-35

-30

-25

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-15

-10

-5

0

5

10 C-reactive Protein

Control

Statin

Portfolio

Jenkins DJ, Kendall CW et al. JAMA 2003

Portfolio dietary pattern on cardiometabolic outcomes

Chiavaroli L et. al. Prog Cardiovasc Dis. 2018 May ‐ Jun;61(1):43‐53

INFLAMMATIONForest plot of our randomized controlled trials on the effect plant based (no meat) low saturated fat low cholesterol diets (Dietary 

Portfolio) on CRP (n=439)

JAMAJAMA

CMAJCMAJ

JAMAMetabolism

Metabolism

Chiavaroli L et. al. Prog Cardiovasc Dis. 2018 May ‐ Jun;61(1):43‐53

Recent Evolution of More Plant based Dietary Guidelines for the public

1. Sweden (2009) – first to incorporate environmental concerns into dietary guidelines

2. Netherlands(2015) – no more than 2 servings of meat per week

3. USA (2016) – vegetarian diet (1 of 3 healthy diets) 4. China (2016) – reduce all meat consumption by 50%5. UK(2016) – eat more beans and pulses, eat less red and

processed meat 6. Belgium (2017) – make foods derived from plants the basis

of every meal, limit your intake of animal products7. Canada ? Going in Same Direction

74

Soy in Portfolio in Guidelines

Soy has been included in numerous clinical practice guidelines for CVD risk reduction 1. National Cholesterol Education Program [NCEP] Adult Treatment 

Panel [ATP] III update 20042. Heart UK 3. European Atherosclerosis Society [EAS] Statin‐associated muscle 

symptoms [SAMS] advisory4. Canadian Cardiovascular Society [CCS]) 

Summary

1. Soy lowers serum LDL‐C by intrinsic mechanisms by ~3.2% (p<.0001)

2. Soy likely lowers LDL‐C by other food displacement by an additional 3‐6%

3. Soy is likely to have an overall reduction of LDL‐C of 6%‐9%4. Soy forms part of dietary recommendations to lower LDL‐C 

internationally e.g. dietary portfolio 5. Perhaps some of the resistance to soy food consumption 

comes from the fact that soy protein is one of the few plant protein sources that can substitute for meat and dairy to address the international dietary guidelines requirement to eat more plant protein and less animal protein foods