Eicosapentaenoic acid ethyl ester, Docosahexaenoic acid ethyl ester
The Science of Plant Stanol Ester. Contents Background Plant stanol ester and LDL-cholesterol...
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Transcript of The Science of Plant Stanol Ester. Contents Background Plant stanol ester and LDL-cholesterol...
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
6
Mechanism of action
8
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.
9
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
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.
15
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.
16
* **
**
*
*
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.
20
LDL
chol
este
rol r
educ
tion
(%)
Plant sterol ester
Plant stanol ester
Plant stanols/sterols (g/day)
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
22
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
23
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
24
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
25
Important step before medicationUsage of plant stanol ester is recommended before starting medication.
26
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.
27
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.