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
1
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.
British Heart Foundation. 2000. Coronary Heart Disease Statistics.
British Heart Foundation Statistics Database 2000.
2
Plant stanol ester reduces
LDL cholesterol
2 G OF PLANT STANOLS PER DAY REDUCES
LDL-CHOLESTEROL BY 10%
Plant stanol ester
• Reduces total and LDL
cholesterol on average by 10%
• Does not affect HDL cholesterol
3
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
4
Proven efficacy
The cholesterol lowering efficacy of Plant stanol ester
has been proven in over 60 clinical studies:
•
•
•
•
•
•
•
•
•
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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
5
Molecular structures:
Cholesterol, plant stanols and sterols
6
Mechanism of action
Plant stanol ester reduces cholesterol absorption
in small intestine.
WITHOUT PLANT STANOL
WITH PLANT STANOL
~50% of cholesterol is absorbed
~20% of cholesterol is absorbed
Cholesterol
Plant stanol ester
7
Reduced cholesterol absorption
Plant stanol ester reduces the absorption of both
dietary and biliary cholesterol.
PLANT STANOL ESTER REDUCES ABSORPTION OF
DIETARY AND BILIARY CHOLESTEROL
Biliary cholesterol absorbed
Absorption (mg/d)
Dietary cholesterol absorbed
Normal diet
Normal diet +
plant stanol ester
Adapted from Gylling et al. Circulation 1997; 96: 4226-4231.
8
Plant stanol ester
and LDL-cholesterol lowering
Fast lowering of LDL cholesterol
Fast and efficient LDL cholesterol reduction with
plant stanol ester.
CHANGE IN LDL CHOLESTEROL
Control spread
Months
LDL reduction (%)
Mediterranean diet
Plant stanol ester spread
(2 g plant stanol/d)
*
*
*
*
*
*p <0.01 vs. control
Athyros et al. Nutr Metab Cardiovasc Dis 2011; 21(3): 213-221.
10
Sustainable efficacy with daily use
The LDL cholesterol lowering effect of
plant stanol ester is sustained with daily use.
CHANGE IN SERUM TOTAL CHOLESTEROL LEVELS
Control spread
Cholesterol (mg/dl)
Plant stanol ester spread
(1.8 g plant stanol/d)
Plant stanol ester spread
(2.6 g plant stanol/d)
*
*
*
*
*
*
Months
*p<0.05 vs. control
Miettinen et al. New Engl J Med 1995; 333: 1308-1312.
11
Once a day is enough
The efficacy of plant stanol ester is independent
of consumption frequency.
LDL-cholesterol (mmol/l)
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
Plat et al. Eur J Clin Nutr 2000; 54: 671-677.
12
Additive to statins
Plant stanol ester adds to the
cholesterol-lowering effect of statins.
INCREMENTAL LDL-CHOLESTEROL LOWERING OF PLANT
STANOL ESTER IN STATIN USERS
Change in LDL cholesterol (%)
Control spread
Plant stanol ester spread
(3 g plant stanol/d)
10 %
plant stanol
ester specific
effect
*
*
*
Weeks
*p<0.001 vs. control
Blair et al. Am J Cardiol 2000; 86: 46-52.
13
Additive to a healthy diet
Plant stanol ester adds to the cholesterollowering effect of a healthy diet.
EFFECTIVE AS PART OF A STRICT
CHOLESTEROL-LOWERING DIET
LDL cholesterol
Cholesterol-lowering diet
Change % in LDL cholesterol
Cholesterol-lowering diet +
plant stanol ester (2.3 g plant stanol/d)
a
b
*Plant stanol ester specific effect
a= p<0.01 vs. baseline
b= p<0.001 vs. baseline and p<0.01 vs. control
Hallikainen and Uusitupa. Am J Clin Nutr 1999; 69: 403-410.
14
As effective as Mediterranean diet
Plant stanol ester is as effective on lowering the estimated
coronary artery disease risk as adopting Mediterranean diet.
EFFECTIVE REDUCTION IN THE ESTIMATED RISK OF CORONARY ARTERY DISEASE (CAD)
Change (%) in 10-year estimated
CAD risk (Framingham risk engine)
Control spread
Mediterranean diet
Plant stanol ester spread
(2 g plant stanols/d)
*
*
*
*
*
*
*
Months
*p<0.05 vs. control
Athyros et al. Nutr Metab Cardiovasc Dis 2011; 21(3): 213-221.
15
Dose-response of plant stanol
ester with high daily intake
Better efficacy with a higher dose
Additional cholesterol reduction with 8.8 g plant
stanols a day.
CHANGE IN LDL CHOLESTEROL
DURING THE 10-WEEK STUDY
Plant Stanol Ester
(8.8 g/d plant stanols)
LDL Cholesterol
Change (%)
Control (n=24)
*
*p<0.01 vs. control
Gylling et al. Clin Nutr 2010; 29: 112-118.
17
Dose-dependent reduction
LDL cholesterol reduction is dose-dependent
with high intake of plant stanol ester.
Change in LDL cholesterol (mmol/l)
compared to the baseline
DOSE-DEPENDENT REDUCTION IN LDL CHOLESTEROL
WITH PLANT STANOL ESTER
*
*
*
Plant stanol intake (g/day)
*p<0.01 vs. control
Mensink et al. Am J Clin Nutr 2010; 92: 24-33.
18
Better maximal efficacy
Significantly better maximal efficacy with
plant stanol ester.
Plant stanols/sterols (g/day)
Plant sterol ester
LDL cholesterol reduction (%)
Plant stanol ester
Musa-Veloso et al. Prostaglandins Leukot Essent Fatty Acids 2011; 85: 9-28.
19
Plant stanol ester is widely
recommended for cholesterol
lowering as a part of a healthy diet
Expert bodies recommend the use
of plant stanols
International Atherosclerosis Society, 2013
American Diabetes Association, 2013
European Atherosclerosis Society, 2013
European Society of Cardiology, 2012
National Heart, Lung, and Blood Institute & National Institutes of Health & American Academy of Pediatrics, 2011
European Society of Cardiology & European Atherosclerosis Society, 2011
The Australian Heart Foundation, 2009
American Academy of Pediatrics, 2008
American Diabetes Association & American College of Cardiology, 2008
American Heart Association & American College of Cardiology, 2006
Joint British Societies, 2005
International Atherosclerosis Society, 2005
Joint WHO/FAO Expert Consultation, 2003
International Lipid Information Bureau, 2003
National Cholesterol Education Program & National Institute of Health, 2002
21
ESC/EAS, 2011
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.’
22
ESC, 2012
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.’
23
IAS, 2013
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.‘
24
Important step before medication
Usage of plant stanol ester is recommended before starting medication.
Therapeutic Lifestyle Changes
If LDL goal not reached with TLC in 6 weeks, add
Plant stanol ester
If LDL goal not reached in 6 weeks, add
Pharmaceuticals
Monitor adherence to TLC diet after 4-6 months
NCEP ATPIII, 2002.
25
Proven efficacy when combined
with statins
For patients already on statins, combining plant stanol ester provides additional
10% effect in LDL reduction.
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.
26
LDL cholesterol reduction (%)
The most effective dietary way
to lower cholesterol
27