The Science of Plant Stanol Ester. Contents Background Plant stanol ester and LDL-cholesterol lowering Dose-response of plant stanol ester with high daily.

The Science of Plant Stanol Ester

Contents• Background• Plant stanol ester and LDL-cholesterol lowering• Dose-response of plant stanol ester with

high daily intake• Plant stanol ester is widely recommended for

cholesterol lowering as a part of a healthy diet

2

Why lower LDL cholesterol?Lowering LDL cholesterol is the primary target in dyslipidemia management and cardiovascular disease prevention.

Diet and other lifestyle changes always form the basis for the treatment.

3British Heart Foundation. 2000. Coronary Heart Disease Statistics. British Heart Foundation Statistics Database 2000.

Plant stanol ester reduces LDL cholesterol

Plant stanol ester• Reduces total and LDL cholesterol on average by 10%• Does not affect HDL cholesterol

4

2 G OF PLANT STANOLS PER DAY REDUCES LDL-CHOLESTEROL BY 10%

Recognized effect• Plant stanol ester has been granted strong health claims by the

• EU commission• US FDA

• Several official guidelines aiming at reducing the risk of CHD recommend consumption of functional foods with plant stanols as part of the diet

5

Proven efficacyThe cholesterol lowering efficacy of Plant stanol ester has been proven in over 60 clinical studies:

• Healthy women, men and children • Normocholesterolemic subjects• Subjects with modestly elevated and high cholesterol levels• Type 1 and 2 diabetics• Subjects with metabolic syndrome• CAD patients• As a part of normal western diet• As a part of strict cholesterol lowering diet• With statin medication• In different populations all over the world

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Molecular structures:Cholesterol, plant stanols and sterols

7

Mechanism of action

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WITH PLANT STANOL~20% of cholesterol is absorbed

WITHOUT PLANT STANOL~50% of cholesterol is absorbed

Cholesterol Plant stanol ester

Plant stanol ester reduces cholesterol absorption in small intestine.

Adapted from Gylling et al. Circulation 1997; 96: 4226-4231.

Reduced cholesterol absorptionPlant stanol ester reduces the absorption of both dietary and biliary cholesterol.

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Biliary cholesterol absorbed

Dietary cholesterol absorbed

Normal diet Normal diet + plant stanol ester

Abs

orpti

on (m

g/d)

PLANT STANOL ESTER REDUCES ABSORPTION OF DIETARY AND BILIARY CHOLESTEROL

Plant stanol ester and LDL-cholesterol lowering

11Athyros et al. Nutr Metab Cardiovasc Dis 2011; 21(3): 213-221.

Control spread

Mediterranean diet

Plant stanol ester spread (2 g plant stanol/d)

CHANGE IN LDL CHOLESTEROL

*

*

Months

** *

*p <0.01 vs. control

Fast lowering of LDL cholesterolFast and efficient LDL cholesterol reduction with plant stanol ester.

Miettinen et al. New Engl J Med 1995; 333: 1308-1312. 12

The LDL cholesterol lowering effect of plant stanol ester is sustained with daily use.

Sustainable efficacy with daily use

Plant stanol ester spread(1.8 g plant stanol/d)

Control spread

Plant stanol ester spread(2.6 g plant stanol/d)

CHANGE IN SERUM TOTAL CHOLESTEROL LEVELS

**

Chol

este

rol (

mg/

dl)

Months*p<0.05 vs. control

***

*

Plat et al. Eur J Clin Nutr 2000; 54: 671-677.

PLANT STANOL ESTER IS AS EFFECTIVE IF DIVIDED OVER SEVERAL MEALS OR TAKEN ONCE A DAY

Control period Plant stanol ester spread 1 x Day

Plant stanol ester spread 3 x Day

*p<0.001 vs. control

LDL-

chol

este

rol (

mm

ol/l)

*

Once a day is enough

13

*

The efficacy of plant stanol ester is independent of consumption frequency.

Blair et al. Am J Cardiol 2000; 86: 46-52.

Control spread

***

INCREMENTAL LDL-CHOLESTEROL LOWERING OF PLANT STANOL ESTER IN STATIN USERS

Plant stanol ester spread (3 g plant stanol/d)

Chan

ge in

LDL

cho

lest

erol

(%)

Weeks

10 %plant stanol ester specific effect

Additive to statinsPlant stanol ester adds to the cholesterol-lowering effect of statins.

14

*p<0.001 vs. control

Hallikainen and Uusitupa. Am J Clin Nutr 1999; 69: 403-410.

Additive to a healthy dietPlant stanol ester adds to the cholesterol-lowering effect of a healthy diet.

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Cholesterol-lowering diet

Cholesterol-lowering diet + plant stanol ester (2.3 g plant stanol/d)

Chan

ge %

in L

DL

chol

este

rol

EFFECTIVE AS PART OF A STRICT CHOLESTEROL-LOWERING DIET

*Plant stanol ester specific effecta= p<0.01 vs. baselineb= p<0.001 vs. baseline and p<0.01 vs. control

LDL cholesterol

a

b

Athyros et al. Nutr Metab Cardiovasc Dis 2011; 21(3): 213-221.

EFFECTIVE REDUCTION IN THE ESTIMATED RISK OF CORONARY ARTERY DISEASE (CAD)

Control spread

Mediterranean diet

Plant stanol ester spread(2 g plant stanols/d)

Months*p<0.05 vs. control

As effective as Mediterranean dietPlant stanol ester is as effective on lowering the estimated coronary artery disease risk as adopting Mediterranean diet.

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* **

**

*

*

Dose-response of plant stanol ester with high daily intake

Gylling et al. Clin Nutr 2010; 29: 112-118.

Chan

ge (%

)

Control (n=24)Plant Stanol Ester

(8.8 g/d plant stanols)

CHANGE IN LDL CHOLESTEROL DURING THE 10-WEEK STUDY

LDL Cholesterol

**p<0.01 vs. control

Better efficacy with a higher doseAdditional cholesterol reduction with 8.8 g plant stanols a day.

18

Mensink et al. Am J Clin Nutr 2010; 92: 24-33.

Dose-dependent reductionLDL cholesterol reduction is dose-dependent with high intake of plant stanol ester.

19

Chan

ge in

LDL

cho

lest

erol

(mm

ol/l)

com

pare

d to

the

base

line

Plant stanol intake (g/day)

*p<0.01 vs. control

*

*

*

DOSE-DEPENDENT REDUCTION IN LDL CHOLESTEROL WITH PLANT STANOL ESTER

Musa-Veloso et al. Prostaglandins Leukot Essent Fatty Acids 2011; 85: 9-28.

Better maximal efficacySignificantly better maximal efficacy with plant stanol ester.

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LDL

chol

este

rol r

educ

tion

(%)

Plant sterol ester

Plant stanol ester

Plant stanols/sterols (g/day)

Plant stanol ester is widely recommended for cholesterol lowering as a part of a healthy diet

International Atherosclerosis Society, 2013American Diabetes Association, 2013European Atherosclerosis Society, 2013European Society of Cardiology, 2012National Heart, Lung, and Blood Institute & National Institutes of Health & American Academy of Pediatrics, 2011European Society of Cardiology & European Atherosclerosis Society, 2011The Australian Heart Foundation, 2009American Academy of Pediatrics, 2008American Diabetes Association & American College of Cardiology, 2008American Heart Association & American College of Cardiology, 2006Joint British Societies, 2005International Atherosclerosis Society, 2005Joint WHO/FAO Expert Consultation, 2003International Lipid Information Bureau, 2003National Cholesterol Education Program & National Institute of Health, 2002

Expert bodies recommend the use of plant stanols

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ESC/EAS Guidelines for the management of dyslipidemias

The magnitude of the effect of functional foods enriched with phytosterols is graded ’+++’ (=highest possible) and the level of evidence is of class ’A’

’Based on the available evidence, foods enriched with phytosterols (1-2 g/day) may be considered for individuals with elevated TC and LDL-C values in whom the total CV risk assessment does not justify the use of cholesterol-lowering drugs.’ ’Functional food containing phytosterols additionally reduce LDL-C levels by up to 5-10% in patients taking stable dose of a statin, and this combination is also well tolerated and safe.’

ESC/EAS, 2011

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European Guidelines on cardiovascular disease prevention in clinical practice

‘Functional foods containing phytosterols (plant sterols and stanols) are effective in lowering LDL cholesterol levels by on average 10%, when consumed in amounts of 2 g/day. The cholesterol-lowering effect is additional to that obtained with a low-fat diet or use of statins. Some recent research indicates that, especially for stanols, further cholesterol reduction can be obtained with higher doses.’

ESC, 2012

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An International Atherosclerosis Society Position Paper: Global Recommendations for the Management of Dyslipidemia

‘Consider using plant sterols/stanols (2 g/day) as a dietary adjunct [--] to further lower LDL-C levels. Several nations place limits on amounts of plant sterols/stanols that are allowed as nutritional supplements (because of questions about potential benefits vs. possible side effects). However, if plant sterols/stanols are available, they are a useful adjunct to lowering of LDL-C by dietary means.‘

IAS, 2013

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Important step before medicationUsage of plant stanol ester is recommended before starting medication.

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Plant stanol esterIf LDL goal not reached in 6 weeks, add

PharmaceuticalsMonitor adherence to TLC diet after 4-6 months

Therapeutic Lifestyle ChangesIf LDL goal not reached with TLC in 6 weeks, add

NCEP ATPIII, 2002.

Proven efficacy when combined with statinsFor patients already on statins, combining plant stanol ester provides additional 10% effect in LDL reduction.

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Therapeutic Lifestyle Changes

Pharmaceuticals

Plant stanol ester

Blair et al. Am J Cardiol 2000; 86: 46-52.De Jong et al. Br J Nutr 2008; 100: 937-941.

The most effective dietary way to lower cholesterol

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LDL

chol

este

rol r

educ

tion

(%)