1. Natural Cholesterol Reduction: Latest Development in Functional Foods Rebecca S. Reeves, DrPH, RD Iowa Dietetic Association Meeting December 5, 2008

2. Topics Heart Disease Statistics Dietary Treatment of Heart Disease Efficacy of Plant Sterols in Lowering Blood Cholesterol Food Sources of Plant Sterols FDA Health Claims for Plant Sterols Commercial Foods containing Plant Sterols

3. A Total CVD B Cancer C Accidents D Chronic Lower Respiratory Diseases E Diabetes Mellitus F Alzheimer’s Disease CVD and other major causes of death for all males and females (United States: 2004). Source: NCHS and NHLBI.

4. Age-adjusted death rates for CHD, stroke, lung and breast for white and black females ( United States: 2004). Source: NCHS and NHLBI.

5. Prevalence of CVD in adults age 20 and older by age and sex (NHANES: 1999-2004). Source: NCHS and NHLBI. These data include coronary heart disease, heart failure, stroke and hypertension.

6. Trends in mean total serum cholesterol among adults age 20 and older, by race/ethnicity and survey (NHANES : 1988-94, 1999-02 and 2003-04). Source: NCHS and NHLBI. NH – non-Hispanic.

7. Annual number of U.S. Adults having diagnosed heart attack by age and sex (ARIC: 1987-2004). Source: NHLBI. Includes MI and fatal CHD but not silent MI’s.

8. Deaths from cardiovascular disease (I00-I99) (United States: 1900–2004). Source: NCHS and NHLBI.

9. Lifestyle changes – the cornerstone of coronary heart disease (CHD) prevention and cholesterol management

10. Therapeutic Lifestyle Changes Nutrient Composition of TLC Diet NutrientRecommended Intake Saturated fatLess than 7% of total calories Polyunsaturated fatUp to 10% of total calories Monounsaturated fat Up to 20% of total calories Total fat25–35% of total calories Carbohydrate50–60% of total calories Fiber20–30 grams per day ProteinApproximately 15% of total calories CholesterolLess than 200 mg/day Total calories (energy)Balance energy intake and expenditure to maintain desirable body weight/ prevent weight gain

11. Therapeutic Lifestyle Changes (TLC) according to NCEP ATP III guidelines Main features of the TLC: Weight reduction Increase regular 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) fiber intake to 10–25 g/day National Cholesterol Education Program Expert Panel, JAMA 2001

12. Therapeutic modifications to reduce the risk of cardiovascular disease Clinical Guidelines, International Atherosclerosis Society, 2003 reduce saturated fats to <7% of total energy keep intakes of trans fatty acids low maintain omega-3 fatty acids intake to at least 1% of total energy (2- 3g/day). reduce dietary cholesterol to <200mg/day consume at least 5 servings of fruits and vegetables daily ensure adequate intake of folic acid (400-1000  g/day) avoid excessive intakes of alcohol. Limit consumption to no more than 2 drinks per day (men) and 1 drink/day (women) Additional options to enhance lowering of LDL-cholesterol levels consider adding plant stanol/sterol (2 g/day) increase viscous (soluble) fiber to 10 g/day

13. Diet plays a key role in cholesterol management

14. Dietary factors reduce LDL cholesterol levels* Dietary componentDietary change Approximate LDL cholesterol reduction (%) Plant sterols2–3 g/day6-15 Saturated fat<7% of energy5–10 Dietary cholesterol<200 mg/day5 Viscous fiber5–10 g/day5 Soy protein25 g/day<3 Body weight maintenanceLose ~10 lb5 Sacks, FM et al. Soy proteins, isoflavones, and cardiovascular health: An American Heart Association science advisory for professionals from the nutrition committee. Circulation 2006; 113. Jenkins et al. Curr Opin Lipidol 2000, Weggemans and Trautwein Eur J Clin Nutr 2003, Katan et al. Mayo Clin Proc 2003. *Percentage claims for plant sterols are based on studies conducted mainly with spreads consumed at least twice a day with meals. Individual experiences tend to vary widely.

15. Dietary Guidelines for Americans for chronic disease risk reduction Consume adequate nutrients within calorie needs Manage body weight Be physically active everyday Consume a variety of fruits and vegetables, whole grains and fat-free or low-fat dairy Keep trans fat as low as possible, saturated fat below 10% of calories, no more than 300 mg of cholesterol daily, and choose polyunsaturated and monounsaturated fats Choose fiber-rich fruits, vegetables and whole grains Reduce sodium intake and emphasize potassium If you consume alcohol, do so in moderation and sensibly Keep food safe

16. Plant sterol or plant stanols Are they equally effective in lowering LDL-cholesterol?

17. What is a plant sterol? Plant sterols, sometimes called phytosterols, are plant compounds which are naturally found in some vegetable oils, nuts, grain products, fruits and vegetables. Plant sterols are naturally present in foods – but in low levels- levels so small which makes it difficult to reach the recommended amounts necessary to reduce cholesterol. Have a similar structure to cholesterol. This helps to reduce cholesterol absorption in the small intestines Typically added to common foods like vegetable oil spreads (soft margarines), mayonnaise, orange juice, fruit and yogurt drinks and snack bars.

18. Cholesterol – Plant Sterol

22. What is a plant stanol ester? Plant stanol esters, are also plant compounds which are naturally found in some vegetable oils, nuts, grain products, fruits and vegetables. Plant stanol esters are also naturally present in foods in very small amounts --- even smaller amounts than plant sterols. Have a similar chemical structure to plant sterols

23. Cholesterol, plant sterols and stanols have similar structures HO Cholesterol Plant sterol-  -Sitosterol Plant sterol- Campesterol Plant stanol-  -Sitostanol

24. Plant sterol-enriched food products: why use plant sterol esters? Esterification of plant sterols with fatty acids increases their solubility in food products sterol sterol ester esterification fatty acid HO O C O

25. Food sources of plant sterols

26. Vegetable oils – a rich source of plant sterols Corn oil (refined) 715–952 mg/100g Rapeseed oil (refined) 250–731 mg/100g Soybean oil (refined) 221–328 mg/100g Olive oil (extra virgin) 144–150 mg/100g Palm oil (refined) 49–61 mg/100g Weihrauch et al. J Am Diet Assoc 1978 and Normen et al. J Food Comp and Analysis 2002

27. Fruits, vegetables, cereals and nuts contain plant sterols at low levels Apple (one small, 100g): 13 mg 1 Orange (one small, 100g): 24 mg 1 Broccoli (one cup chopped, 100g): 39 mg 1 Carrot (one cup chopped, 100g): 16 mg 1 Tomato (one medium, 100g): 4.7 mg 1 Wholemeal bread (3 slices, 100g): 86 mg 2 Peanuts (100g): 119 mg 3 1.Normen et al. Eur J Nutr 1999 2.Normen et al. J Food Comp and Analysis 2002 3.Weihrauch et al. Am Diet Assoc 1978

28. Plant sterol dietary intake levels 1.Morton et al. J Hum Nutr Diet 1995 2.Vuoristo et al. Am J Clin Nutr 1994 3.International Atherosclerosis Society, 2003 4.NCEP III Expert Panel, 2001 In a typical western diet, plant sterol intake is ~0.2–0.4 g/day 1 In a typical vegetarian diet, plant sterol intake is ~0.6 g/day 2 For cholesterol management, dietary recommendations for plant sterol intake is 2 g/day. 3,4

29. 2 grams of plant sterols can be found in: 150 apples (where each weighs 100 g)* 83 oranges (where each weighs 100 g)* 210 carrots (where a carrot weighs 60 g)* 425 tomatoes (where a tomato weighs 100 g)* 11 cups of peanuts* 70 slices of whole grain bread* One serving (3 fl oz bottle) of Promise® SuperShots® for cholesterol Two cups of Active Lifestyle Kroger Skim Milk *Reflect approximate amounts to be consumed to achieve ~ 2 grams

30. Plant sterol or stanol esters Summary Both have similar blood total and LDL cholesterol-lowering Both have similar efficacy in short-term and long-term Both have similar effects on cholesterol absorption Plant sterols are typically used in foods products due to their increased solubility.

31. Plant Sterols Cholesterol-lowering efficacy of plant sterol-enriched foods has been proven in over 160 studies. The results are reproducible and sustainable in the long-term Studies have shown reductions of total cholesterol up to 10% and LDL cholesterol up to 14% Levels of the protective HDL cholesterol are not reduced by the use of plant sterols

32. Plant sterol- and stanol-enriched foods are equally effective in lowering LDL cholesterol Direct comparison short-term studies Weststrate & Meijer 1998 Hallikainen et al. 2000 Nestel et al. 2001 Jones et al. 2000 Noakes et al. 2002 -16 -12 -8 -4 0 LDL cholesterol (% change) -13% -13.2% -6.4% -10.4% -12.7% -13.6% -8.3% -7.7% -9.5% -13% plant sterols; 1.8–2.7 g/d plant stanols; 1.8–3.2 g/d

33. Overview of clinical trials assessing efficacy of plant sterols -16 -12 -8 -4 0 0.511.522.533.5 plant sterols (g/d) LDL cholesterol (% change) 41 trials with plant sterols/stanols: 95% CI from meta-analysis Katan et al. Mayo Clin Proc 2003 LDL cholesterol from Unilever sponsored studies 2–3 g of plant sterols daily significantly reduces LDL cholesterol by ~10% *The percentage claims for plant sterols are based on studies conducted mainly with spreads consumed at least twice a day with meals. Individual experiences tend to vary widely.

34. Studies with plant sterol or stanol-enriched dairy foods -7.9** -6.1** -5.2** -7.1** -9.6** -15.9** -8.6** -13.7** -11.1* (-6.2 # ) % change LDL cholesterol Low-fat milk Low-fat yogurt Low-fat yogurt 2.0 1.8 1.7 Noakes et al. Eur J Nutr 2004 Low-fat milk1.2 1.6 Thomsen et al. Eur J Clin Nutr 2004 Semi-skim milk Low-fat yogurt1.6 Clifton et al. Eur J Clin Nutr 2004 Low-fat yogurt3.0Mensink et al. Atherosclerosis 2002 Low-fat yogurt drink1.0Volpe et al. Br J Nutr 2001 Food formatDose g/d Study *Significantly different compared to baseline #Control treatment adjusted (estimate) **Significantly different from control treatment

35. What is a health claim? Health claims on food labels are claims by manufacturers of food products that their food will reduce the risk of developing a disease or condition. FDA Structure Function This section of the law states that a dietary supplement may bear certain statements on its label or in its labeling if the claim meets certain requirements.

36. Foods and Beverages containing at least 0.4g per serving of plant sterols, when consumed twice a day with meals for a daily total intake of 0.8g as part of a diet low in saturated fat and cholesterol, may reduce the risk of coronary heart disease.

37. Jelly Bean Rule 10% DV of prior to fortification at least one of: vitamin A, Vitamin C, calcium, iron, protein or fiber per ref amt

38. Plant sterols: A natural component of the diet

39. Clinical Evidence For effective cholesterol lowering, plant sterol enriched foods should be consumed twice a day with meals as part of an overall diet low in saturated fat and cholesterol. Plant sterol are included in the National Cholesterol Education Program (NCEP) guidelines for effective cholesterol lowering for adults with elevated cholesterol levels. Plant sterol and plant stanol esters have similar effects on reducing total and LDL-cholesterol. Plant sterol-enriched foods are safe, approved and endorsed internationally *The percentage claims for plant sterols are based on studies conducted mainly with spreads consumed at least twice a day with meals. Individual experiences tend to vary widely.

40. Type of fat eaten impacts blood cholesterol Changes in total blood cholesterol levels (mmol/L) Clarke et al. Br Med J 1997; 314: 112–117 Replacement of dietary saturated fat (5% total energy) by monounsaturated fat Reduction of dietary cholesterol by 200 mg 0 -0.2 -0.4 -0.6 -0.8 Replacement of dietary saturated fat (5% total energy) by polyunsaturated fat Sum of all three dietary changes

41. Potential heart health impact of a 10% LDL cholesterol reduction

42. 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 Plant sterols on average can reduce LDL cholesterol levels by 10% or a range of 6-15% * Epidemiological studies suggest that a 10% reduction in LDL cholesterol is associated with about a 12-20% reduced risk of coronary heart disease over 5 years and a long term risk reduction of as much as 20% Expert Workshop: Katan et al. Mayo Clin Proc 2003 *The percentage claims for plant sterols are based on studies conducted mainly with spreads consumed at least twice a day with meals. Individual experiences tend to vary widely.

43. What it is Benefit it brings How it works Plant compound found naturally in fruits, vegetables, nuts, seeds and vegetable oils.  Reduce total cholesterol  Reduce LDL  FDA approved heart health claim  Structurally similar to cholesterol  Competes for the absorption into the body  Inhibits dietary cholesterol absorption  Lowers LDL cholesterol

44. Consumer Demand for Products Containing Plant Sterols Source: American Heart Association; Invoke Solutions- Cargill primary research Top Products Where Consumers Would Like To See CoroWise™ Source: Cargill Proprietary Marketing Research

47. Super Shots with 2 Grams of Plant Sterols

48. Margarines with Plant Sterols 1 tbsp = serving size

49. CoroWise™ is versatile and can go into many products for variety Oroweat™ Whole Grain & Oat Marketing Manager "This is one of the most popular Oroweat bread introductions throughout the company in many years, with double the demand expectations.“ Oroweat™ Whole Grain & Oat Marketing Manager "This is one of the most popular Oroweat bread introductions throughout the company in many years, with double the demand expectations.“