1. Plant Sterols – a product case study
Jacqui Morrell
Unilever nutritionist

3. Cardiovascular disease (CVD) is the leading cause of mortality worldwide
16.7 million deaths worldwide from CVD in 20021
7.2 million deaths from coronary heart disease
3.8 million men
3.4 million women
5.5 million deaths from stroke
2.5 million men
3 million women
According to World Health Organization estimates, 16.7 million people worldwide die each year of cardiovascular disease (CVD). Women account for a large proportion of deaths, and many are not aware of their risk.
Mackay and Mensah, The atlas of heart disease and stroke, WHO 2004

4. Coronary heart disease (CHD) mortality rates in Europe
CHD is the main cause of death in Europe
Deaths
per 100,000
83–151
152–210
211–296
297–507
508–839
There is a distinct trend across Europe that mortality from coronary heart disease increases as you move north and east.
Mortality rates in Eastern Europe are five times higher than Western Europe.
European cardiovascular disease statistics, 2005: Age-standardised death rates for men aged 35–74, latest year

5. Major risk factors for coronary heart disease
Modifiable risk factors
Abnormal blood lipid levels
high total cholesterol
high LDL cholesterol
low HDL cholesterol
high triglycerides
High blood pressure
Lifestyle factors smoking, physical inactivity, obesity, unhealthy diet
Non-modifiable risk factors
Increased age
Gender
Family history
Ethnicity or race
Some of the risk factors that predispose an individual to coronary heart disease (CHD) are outlined on the slide. Age, gender, family history and ethnicity influence an individual’s likelihood of being affected by CHD, but nothing that can be done to alter these factors.
There are still many changes that can reduce CHD risk substantially. The most powerful steps are to stop smoking, keep a healthy body weight and consume a balanced diet. Regular physical activity is another important part of a healthy lifestyle, and all these features taken together reduce risk of developing CHD.
Lifestyle and pharmaceutical interventions that aim to reduce the effect of risk factors such as blood pressure and blood lipids can help people who have elevated levels of these modifiable risk factors experience a healthier future.

6. Lower cholesterol levels associated with lower risk for coronary heart disease (CHD)20 15
(age-adjusted per 1000 men in 6-years)1
CHD mortality 10 5
The link between high cholesterol and coronary heart disease (CHD) is well established and high cholesterol accounts for a large number of deaths worldwide.
Several studies like the Multiple Risk Factor intervention trial (which includes 356,222 men aged 35–57) shows just how imperative it is to keep blood cholesterol within the healthy range.
This graph shows that the chance of dying from heart disease in the next six years increases as the amount of cholesterol in the person’s blood increases. To indicate the role that cholesterol plays in heart disease, the data has been analysed in such a way that the effects of age have been removed.
As cholesterol rises from the desirable values between 3.8 and 5.2 mmol/l, there is a steady increase in the age-adjusted six-year heart disease mortality.
3.8 [147]
5.2 [201]
6.5 [251]
7.6 [294]
Total serum cholesterol (mmol/l, [mg/dl])
Martin et al. Lancet 1986

7. Contribution of selected risk factors to coronary heart disease: high cholesterol a major factor
22%
31%
49%
56% 10 20 30 40 50 60
Of four key contributors to coronary heart disease, high blood cholesterol stands out as the one with greatest impact. These risk factors are modifiable.
High blood cholesterol
Low fruit & vegetable intake
Suboptimal blood pressure
systolic BP >115 mmHg
Physical inactivity
Mackay and Mensah, The atlas of heart disease and stroke, WHO 2004

9. Prevalence of elevated blood cholesterol globally
Switzerland
Germany
Czech
Republic
Sweden
France UK
Belgium
Denmark
Italy
Canada
Poland
Spain
Russia
USA
China 10 20 30 40 50 60 70 80 90
100
Prevalence of high cholesterol (%)1
Given the heart disease risk associated with increased cholesterol, it is concerning that so many people around the world have elevated blood cholesterol.
This graph considers elevated cholesterol as any serum level over the desirable concentration of 5.0 mmol/l for men and women aged 35–64 years. Data are from the multinational World Health Organization MONICA project.
The prevalence of high cholesterol in this large data set ranges from about 22% in China to about 88% in Switzerland. Many people are not even aware of having elevated blood cholesterol concentrations.
MONICA data: age-standardised, estimated from average men and women: Total cholesterol >5.0 mmol/l Tolonen et al. Int J Epidemiol 2005

10. Guidelines for desirable blood lipid levels
European Guidelines1
NCEP Guidelines2
Total cholesterol
<5.0 mmol/l (190 mg/dl)
<200 mg/dl
LDL cholesterol
<3.0 mmol/l (115 mg/dl)
<100 mg/dl
HDL cholesterol
>1.0 mmol/l (40 mg/dl) male
>1.2 mmol/l (46 mg/dl) female
>40 mg/dl
Triglycerides
<1.7 mmol/l (150 mg/dl)
<150 mg/dl
The European guidelines and the USA’s National Cholesterol Education Program’s (NCEP) guidelines for blood lipids recommend similar levels for adults where high cholesterol is the only CHD risk factor.
Guidelines for individual’s with more than one risk factor, such as for people with diabetes are stricter than the figures shown in the table.
Third European Joint Task Force, De Backer Eur J Cardio Prev Rehab 2003
National Cholesterol Education Program Expert Panel, JAMA 2001

11. Cholesterol, plant sterols and stanols have similar structures
Campesterol
Cholesterol
There is a high degree of molecular structural similarity among sterols (including cholesterol), with the majority of the differences being in the side chain. Plant stanols are the saturated form of plant sterols and lack the double bond in the ring structure. HO
Plant sterol-
b-Sitosterol HO
Plant stanol-
b-Sitostanol

12. Plant sterols are natural components of the human diet
Average daily intake of adults
mg/day
(higher in vegetarians)

13. Plant sterols… Old-timers
Reduction of Blood Cholesterol in Man
By O.J.POLLAK, M.D., Ph.D.
Dietary-cholesterol contributes to the development and maintenance of hypercholesterolemia in man. Intake of sitosterol prevents cholesterol resorption. This results in lowering of blood cholesterols to a basal endogenous levels. Upon cessation of sitosterol intake hemocholesterols return to the original level. Excess supply of plant sterol was required in clinical experiments because the material used contained but 75 to 80 per cent of sitosterol and because of the large amount of endogenous cholesterol which has to be inactivated by the sitosterol, besides exogenous cholesterol.
Circulation Volume VII. May 1953
Researchers first recognised the potential of plant sterols or phytosterols to lower cholesterol back in the 1950’s.

14. Plant sterol-enriched food products: why use plant sterol esters?
Esterification of plant sterols with fatty acids increases their solubility in food products
sterol
fatty acid
esterification HO
Recommendations for LDL cholesterol-lowering are for people to consume approximately 2 g of plant sterols a day. The challenge is to incorporate 2 g of plant sterols into a normal daily intake of every day food products so that people don’t have to drastically change their existing habits. However, plant sterols are poorly soluble. A way to increase solubility is to esterify plant sterols with dietary fatty acids to create plant sterol esters. These plant sterol esters are then much more readily incorporated into regular food products.
sterol ester O C O

15. Overview of clinical trials assessing efficacy of plant sterols
plant sterols (g/d)
0.5 1
1.5 2
2.5 3
3.5
2–2.5 g of plant sterols daily significantly reduces LDL cholesterol by ~10% -4 -8
LDL cholesterol (% change)
-12
Many studies have shown that plant sterols substantially lower LDL cholesterol levels, and in this graph is the dose response relationship.
Numerous Unilever initiated independent studies at various sites around the world have been undertaken using plant sterol-enriched foods. The LDL cholesterol results compared to plant sterol dose of these studies are shown with the orange dots. A recent meta-analysis of the data from 41 clinical trials of plant sterols and stanols was also performed. The LDL cholesterol confidence intervals effect compared to plant sterol dose are shown in green bars on the graph.
The extent of the reduction in LDL cholesterol is dose-dependent up to a daily plant sterol intake of 2–2.5 g where the curve reaches a plateau. Increasing plant sterol intake beyond this achieves little further reduction in LDL cholesterol.
-16
41 trials with plant sterols/stanols: 95% CI from meta-analysis
Katan et al. Mayo Clin Proc 2003
LDL cholesterol from pro.activ sponsored studies

16. Substantial impact of plant sterol consumption on heart health
Scientific evidence is sufficient to promote use of plant sterols for lowering LDL cholesterol levels in persons at increased risk for coronary heart disease
Reduction in LDL cholesterol levels of about 10% could be expected to reduce the incidence of coronary heart disease by about 12–20% over 5 years
Longer-term risk reduction would be about 20%
These are the conclusions from an expert workshop on plant sterol efficacy and safety in the management of blood cholesterol.
Expert Workshop: Katan et al. Mayo Clin Proc 2003

17. Dietary recommendations for prevention of coronary heart disease
Saturated fat: <7% of total energy
Trans fatty acids: low
n-3 fatty acids: >1% of total energy (2–3 g/day)
Dietary cholesterol: <200 mg/day
Viscous fibre: ~10 g/day
Fruits and vegetables: 5 servings daily
Folic acid: 400–1000 µg/day
Alcohol: <20–30 ml/day (men) and 10–20 ml/day (women)
Consider plant stanol/sterol: 2 g/day
Dietary changes can positively influence cholesterol levels and can help in the prevention of coronary heart disease (CHD) as shown in a number of international guidelines. Dietary recommendations from the International Atherosclerosis Society are shown. Plant sterols/stanols are included in the list for consideration. Other organisations worldwide have similar dietary guidelines for improving and promoting heart health.
Clinical Guidelines, International Atherosclerosis Society, 2003

18. Therapeutic Lifestyle Changes (TLC) according to NCEP ATP III guidelines
Main features of the TLC:
Weight reduction
Increase physical activity
Total fat intake: 25–35% total energy
Reduce saturated fat and cholesterol intake:
saturated fat <7% total energy
cholesterol <200 mg/day
Option for enhancing LDL lowering:
plant sterols/stanols 2 g/day
increased viscous, soluble fibre intake to 10–25 g/day
Recommendations for adult cholesterol management from the US National Cholesterol Education Program (NCEP) are shown. Plant sterols are included in the list of dietary changes that aim to enhance lowering of LDL cholesterol concentrations.
National Cholesterol Education Program Expert Panel, JAMA 2001

19. Cholesterol-lowering effect of plant sterols is additive to a healthy diet and to lipid-lowering medication (statins)
healthy diet*
healthy diet
healthy diet
plant sterol-enriched foods **
-10
Statin treatment***
% LDL cholesterol-lowering
-20
-30
The additive cholesterol-lowering effect of plant sterol-enriched foods (based on 2 g/day plant sterols) to a healthy diet (low in saturated fat and cholesterol) and to lipid lowering medication (statins) is evident in this graph.
plant sterol-enriched foods
-40
* low in saturated fat and cholesterol
** 2g/day
*** based on average statin effects
Based on: Katan et al. Mayo Clin Proc 2003; 78: 965–978
Edwards & Moore BMC Family Practice 2003; 4–18

20. Cholesterol-lowering with plant sterol-enriched foods
Reproducible, robust effects
Sustained with longer-term use
Independent of the background diet (typical Western or low-fat)
Proven compliance and efficacy in free-living populations (adults and familial hypercholesterolemia children)
Additive effect to low saturated fat, low cholesterol lipid-lowering diet
Additive effect to lipid-lowering medication (statins and fibrates)
No adverse effect on HDL cholesterol

21. pro.activ product range
The Becel/Flora pro.activ range consists of spreads, a milk drink, a range of yoghurts and yoghurt mini drinks.
Not all countries have the full range yet. Unilever offers a choice of healthy cholesterol-lowering foods enriched with plant sterols. Their every day use makes it easier to incorporate into a healthy diet for optimal cholesterol-lowering effect.

22. pro.activ spread 35% low-fat spread
Enriched with plant sterols proven to reduce cholesterol
Per 10 g serving:
33 calories
0.75 g of sterols
Made from vegetable oils
High in polyunsaturated fatty acids and low in saturated fatty acids
Can be used like any other low-fat spread
Virtually free from trans fatty acids

23. pro.activ milk drink Milk drink: enriched with plant sterols
semi-skimmed milk drink (1.8% fat)
Can be used like any other semi-skimmed milk
Per 250 ml serving:
125 calories
0.75 g of plant sterols

24. pro.activ yoghurts Yoghurts: Per 125 g pot:
enriched with plant sterols
low-fat (0.5% fat)
range of flavours
Per 125 g pot:
97–101 calories (depending on flavour)
0.75 g of plant sterols

25. pro.activ yoghurt mini drinks
Enriched with plant sterols
Semi-skimmed yoghurt drink
Contains probiotic Bifidobacterium lactis Bb12
A range of flavours
Per bottle:
87 calories
2 g of plant sterols

26. Optimal daily plant sterol intake for cholesterol-lowering: servings or portions
The plant sterols in 3 portions of pro.activ foods (or one yoghurt mini drink) are clinically proven to lower LDL (bad) cholesterol levels significantly
1 mini drink = 2 g plant sterols
3 portions of milk, spread, yoghurts = g plant sterols
The cholesterol-lowering effect of plant sterols in Becel/Flora pro.activ foods has been proven in more than 40 studies.
The optimal amount of plant sterols for lowering cholesterol is 2–2.5 g daily. One could consume this amount by either drinking:
one bottle of the pro.activ yoghurt mini drink daily or
by consuming 3 servings/portions of the other products (spread, milk, yoghurt):
1 serving/portion of milk is a medium (250 ml) glass of milk and it contains 0.75 g of plant sterols
1 serving/portion of yoghurt is a pot of 125 g and it contains 0.75 g of plant sterols
1 serving/portion of spread is around 2 teaspoons and it contains 0.75 g of plant sterols.

28. ‘The most significant advancement in the dietary management of cholesterol in thirty years’
Professor Leon Simons, Head of Lipids Department, St Vincent’s Cholesterol Clinic, Australia, speaking on National TV news

29. Conclusions
Cholesterol-lowering efficacy of plant sterol-enriched foods has been proven in more than 40 clinical studies. The results are reproducible and sustainable in the long-term
The 10% reduction in LDL cholesterol levels can reduce the risk of coronary heart disease by up to 20%
Plant sterol-enriched foods are safe, approved and endorsed internationally
Plant sterols are recommended in dietary guidelines for cholesterol-lowering

30. Flora pro.activ performance
Volume
+50%
Value
+35%
Source: AC Nielsen MAT TO WE vs MAT TO WE

31. The CL market still showing strong growth with Unilever boasting over 58% share of the value.