LOWERING CHOLESTEROL WITH PLANT STANOL ESTER. for Healthcare Professionals

Transcription

1 LOWERING CHOLESTEROL WITH PLANT STANOL ESTER for Healthcare Professionals 1

2 INTRODUCTION CONTENTS Cardiovascular diseases (CVD) are still the most common cause of morbidity and mortality worldwide. The risk of developing CVD is strongly related to blood cholesterol levels, and numerous studies have established a direct relationship between cholesterol and the incidence of CVD. Recent studies indicate that elevated blood lipids are also associated with other diseases, such as dementia, which makes fighting elevated cholesterol levels even more important. Meta-analyses suggest that for every 1 % decrease in total cholesterol, there is a 2 % decrease in CVD. These results have been demonstrated with medical treatments as well as with lifestyle changes. Lifestyle changes are always the cornerstone of the prevention and treatment of CVD, and they are recommended at any risk level. A heart-healthy diet is low in saturated fat and cholesterol, and high in dietary fibre. Foods enriched with plant stanol ester are widely recommended as the second step if a conventional heart-healthy diet alone does not bring enough improvement. Plant stanol ester reduces serum total and LDL cholesterol by up to 1 to 15 %. This effect is additive to those of other dietary changes and cholesterol medication. Lack of motivation is a major barrier to successful long-term cholesterol reduction by dietary means. Importantly, consumption of plant stanol ester can motivate further dietary changes, because the effect of plant stanols is fast, significant and lasting. This brochure provides basic information on plant stanol ester and Benecol products for healthcare professionals. Benecol products were the very first evidence-based, cholesterol-lowering functional foods introduced to the market in the 199s. Today, Benecol products are sold in almost 3 countries, and are backed by more than 5 clinical studies that have confirmed the efficacy and safety of plant stanol ester. The accumulating scientific data convincingly show that Benecol products can be the basis of cholesterol management for all individuals at risk. 2 Introduction 3 Contents 4 Plant sterols and plant stanols in human nutrition 5 Plant stanol ester effectively lowers serum cholesterol 6 2 grams a day.. 7 with daily meals 8 Effective in any diet 9 Effective in conjunction with statin medication 1 Patients with CVD 11 Diabetics 12 Patients with familial hypercholesterolemia 12 Healthy children 13 Fast effect and lasting cholesterol reduction 14 Plant stanol ester mechanism of action 15 Safety 16 Recommended by international expert bodies 17 Literature 18 Benecol products a tasty and convenient way of reducing cholesterol 19 Summary 2 3

3 PLANT STANOLS AND PLANT STEROLS IN HUMAN NUTRITION PLANT STANOL ESTER EFFECTIVELY LOWERS SERUM CHOLESTEROL Gylling et al Katan et al. 23. Ostlund 22. Cholesterol Plant sterol: sitosterol Plant stanol: sitostanol Plant stanols and sterols are cholesterol-like molecules with only minor differences in their molecular structure. The highest concentrations of plant stanols and sterols occur in vegetable oils and cereals. The daily intake of these substances in a typical Western diet varies between 3 to 5 mg/day and 15 to 45 mg/day, respectively, while cholesterol intake varies between 3 to 5 mg/day. Plant stanols and plant sterols have been shown to reduce the absorption of cholesterol from the dietary tract. This reduction applies to both dietary and biliary cholesterol. However, the intake of plant stanols and plant sterols from an ordinary diet is not sufficient to effectively lower blood cholesterol levels. Therefore, plant stanols are added into foods as plant stanol ester, a soluble form of plant stanols, which has been shown to effectively reduce serum LDL levels by up to 15 %. The absorption of cholesterol in humans is effective - approximately 5 % of it is absorbed. Plant sterols, and especially plant stanols, however, are much less readily absorbed from the diet. When foods with added plant sterols or plant stanols are consumed, approximately.5 to 2 % of the plant sterols and only.4 to.2 % of the plant stanols are absorbed. Furthermore, plant stanols are effectively eliminated from the body. EFFECTIVE REDUCTION IN SERUM CHOLESTEROL % change versus control margarine Total cholesterol p<.1 LDL cholesterol The efficacy of plant stanol ester in lowering cholesterol has been shown in more than 5 peer-reviewed clinical studies. A daily intake of approximately 2 g of plant stanols reduces serum LDL cholesterol by up to 15 %. Such significant cholesterol-lowering effects have been shown in: normo- and hypercholesterolemic individuals; women and men, as well as in children; patients with coronary heart disease; patients with type 1 diabetes; patients with type 2 diabetes; conjunction with typical Western diets; conjunction with a strict lipid-lowering diet; conjunction with cholesterol-lowering statin therapy. In most studies, HDL cholesterol and triglyceride levels have remained unchanged. However, the most recent research indicates that plant stanol ester also reduces serum triglycerides in subjects with elevated triglyceride levels. Gylling and Miettinen Miettinen et al Gylling et al Andersson et al Hallikainen and Uusitupa Blair et al. 2. Hallikainen et al.2. Miettinen et al. 2. Tammi et al. 2. Vuorio et al. 2. Mensink et al. 22. Plat et al. 27. Hallikainen et al. 28. Naumann et al. 28. Plant stanol ester Figure 1. Plant stanol ester effectively lowers serum total and LDL cholesterol (Hallikainen et al. 2). 4 5

4 PLANT STANOL ESTER EFFECTIVELY LOWERS SERUM CHOLESTEROL PLANT STANOL ESTER EFFECTIVELY LOWERS SERUM CHOLESTEROL 2 GRAMS A DAY... WITH DAILY MEALS Katan et al. 23. Clinical studies have shown that two grams of plant stanols per day (as plant stanol ester) produce a clinically relevant cholesterol-lowering effect. It is important to aim at this recommended daily intake of plant stanols because a smaller daily amount does not give a full effect. Consumption of larger than recommended amounts of plant stanols has no adverse effects, but may not provide any additional benefit. The optimal daily intake of plant stanols is easily obtained when Benecol products are consumed on a daily basis at normal dietary levels. The cholesterollowering effect has been shown with different types of foods and beverages enriched with plant stanol ester. Most studies have assessed the effects of taking 2 grams of plant stanols in two or more portions per day. However, taking the daily dose of plant stanols in one dose with a main meal is just as effective in lowering serum LDL cholesterol concentrations as splitting the dose over three meals. Consuming Benecol products with daily meals is important for optimum efficacy. This is due to one phase of the mechanism of plant stanols, by which they replace cholesterol in mixed micelles formed in the digestive tract. Micelle formation requires sufficient amounts of fat and other macronutrients ingested in daily meals. Plat and Mensink 2. EXAMPLES OF STUDIES WITH DIFFERENT PLANT-STANOL-ESTER-ENRICHED FOOD PRODUCTS Product Plant stanols (g/day) LDL reduction (%) Reference Margarine 2 13 Hallikainen et al. 2 Low-fat spread 2 15 Ketomäki et al. 25 Yoghurt drink 2 13 Salo and Wester 25 Yoghurt 3 14 Mensink et al. 22 LDL cholesterol (mmol/l) ONCE-A-DAY WITH A MEAL IS ENOUGH p<.1 for change versus control Figure 2. The consumption of 2.5 g of plant stanols (as plant stanol ester) at lunch resulted in a similar LDL cholesterol lowering effect as the consumption of 2.5 g plant stanols divided over three meals (Plat et al. 2). 2. Control Once per day Three times per day 6 7

5 PLANT STANOL ESTER EFFECTIVELY LOWERS SERUM CHOLESTEROL PLANT STANOL ESTER EFFECTIVELY LOWERS SERUM CHOLESTEROL EFFECTIVE IN ANY DIET EFFECTIVE IN CONJUNCTION WITH STATIN MEDICATION Miettinen et al Andersson et al Hallikainen and Uusitupa Plant stanols reduce the absorption of both dietary and biliary cholesterol from the digestive tract. Research shows that plant stanol ester is effective in all kinds of diets. It works in typical Western diets as well as in diets low in saturated fat and cholesterol. For people unwilling or unable to accomplish hearthealthy dietary changes, plant stanol ester can be the first significant dietary step in reducing serum cholesterol. For those who already follow a heart-healthy diet, plant stanol ester gives an additional cholesterollowering effect. Thus, modifying the diet to combine heart-healthy foods with Benecol products may result in sufficient cholesterol reduction through diet alone. According to international guidelines for the treatment of elevated serum cholesterol levels, the fi rst step is to choose a diet low in saturated fat, trans fat and cholesterol, and rich in dietary fibre. These dietary choices are enhanced when plant stanol ester is added to the diet. In specific cases, cholesterol medication may be needed. Statins are the most widely used cholesterollowering medications. They reduce serum cholesterol concentration by inhibiting the synthesis of choles- terol in the liver. The cholesterol-lowering effects of statins and plant stanols are additive because they have different mechanisms of action. Statins inhibit the production of cholesterol while plant stanols partly block the absorption of cholesterol from the digestive tract. Adding plant stanol ester to the diet of subjects already on statin medication further reduces serum LDL cholesterol by up to 1 to 15 %. Blair et al. 2. De Jong et al. 28. De Jong et al. In Press. EFFECTIVE IN A LOW-FAT, LOW-CHOLESTEROL DIET ADDITIONAL LDL REDUCTION WITH PLANT STANOL ESTER Figure 3. Plant stanol ester further reduced serum total and LDL cholesterol when it was included in a recommended NCEP Step II diet (Hallikainen and Uusitupa 1999). Recommended diet Recommended diet + plant stanol ester Change [%] versus home diet Total cholesterol LDL cholesterol LDL change [%] p<.1 for difference in change Weeks Figure 4. Incorporating a plant stanol ester containing vegetable oil spread into the diet of statin users resulted in signifi cant additional 1 % cholesterol reduction (Blair et al. 2). Control spread Plant stanol ester spread 8 9

6 PLANT STANOL ESTER EFFECTIVELY LOWERS SERUM CHOLESTEROL PLANT STANOL ESTER EFFECTIVELY LOWERS SERUM CHOLESTEROL PATIENTS WITH CVD DIABETICS Gylling Gylling et al. 26. Measures taken to reduce the risk or prevent the reoccurrence of a cardiac event in individuals with an existing history of CVD are of outmost importance. Therefore, effective action must address the treatment of elevated cholesterol values. Research has shown that plant stanol ester is an effective means of lowering serum total and LDL cholesterol in individuals with existing cardiovascular disease. The prevalence of diabetes, especially type 2 diabetes, is increasing rapidly worldwide as populations age and as unhealthy lifestyles are adopted. People with diabetes have a multiple risk of developing cardiovascular diseases compared with healthy individuals. This is why it is very important to treat diabetics risk factors as effectively as possible. Plant stanol ester has been shown to effectively reduce serum cholesterol values in type 1 and in type 2 diabetics. Gylling and Miettinen Gylling and Miettinen Gylling and Miettinen De Jong 27. Hallikainen et al. 28. SIGNIFICANT CHOLESTEROL REDUCTION IN PATIENTS WITH CVD CHANGES IN LIPID CONCENTRATION BY DIETARY PLANT STANOLS Figure 5. Plant stanol ester containing margarine effectively reduced serum total and LDL cholesterol in patients with existing CVD (p<.5 from home diet and from control margarine) (Gylling et al. 1997). Control margarine Plant stanol ester margarine Change [%] versus home diet Total cholesterol LDL cholesterol Change [%] Figure 6. Plant stanol ester signifi - cantly reduced serum total and LDL cholesterol and increased serum HDL cholesterol (p<.5) in type 2 diabetic men (Gylling and Miettinen 1994) Total cholesterol LDL cholesterol HDL cholesterol 1 11

7 PLANT STANOL ESTER EFFECTIVELY LOWERS SERUM CHOLESTEROL PLANT STANOL ESTER EFFECTIVELY LOWERS SERUM CHOLESTEROL PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA (FH) FAST EFFECT AND LASTING CHOLESTEROL REDUCTION Gylling et al Vuorio et al. 2. Jakulj et al. 26. Moruisi et al. 26. The efficacy and safety of consuming products enriched with plant stanol ester has been shown in clinical studies with both adult and child subjects with FH. An early study concluded that a partial replacement of normal dietary fat by plant stanol ester margarine appeared to be an effective and safe hypocholesterolemic treatment in children with FH. A significant cholesterol-lowering effect was also seen in a recent study where FH children consumed yoghurt enriched with plant stanol ester. In a study with patients suffering from heterozygous familial hypercholesterolemia, spread containing plant stanol ester lowered serum cholesterol alone and in conjunction with statin medication by 11 to 2 %. And a recent meta-analysis stated that plant stanols may offer an effective adjunct to the cholesterol-lowering treatment strategy of FH patients. The full cholesterol-lowering effect of plant stanol ester can occur in as little as one to two weeks. From a treatment point of view, it is more important that this effect be sustained. The lasting cholesterol lowering effect of plant stanol ester has been shown in two controlled, double-blind studies. One was a 12-month study with mildly hypercholesterolemic subjects. A second was a recent 18-month study with subjects on statin treatment. The lasting effect was also demonstrated in a 5-year study in a free-living population. Miettinen et al Hallikainen et al. 22. Mensink et al. 22. Fransen et al. 27. De Jong 27. De Jong et al. In Press. THE CHOLESTEROL-LOWERING EFFECT OF PLANT STANOL ESTER IS SUSTAINED Williams et al Tammi et al. 2. HEALTHY CHILDREN Atherosclerosis may start to develop early in life. So it is important to follow a heart-healthy diet early in childhood. Research also shows that plant stanol ester is a safe and effective adjunct to a normal healthy diet in children. In these studies, children have easily adhered to a regular dietary regimen including products enriched with plant stanol ester. However, such products are not recommended for children younger than five years due to their special dietary needs. % change in LDL mo 6 mo 12 mo p<.1 for difference in change versus control Figure 7. When incorporated into a Western diet, plant stanol ester effectively and maintained constant effects on serum LDL cholesterol levels over time. (Miettinen et al. 1995). Control margarine Plant stanol ester margarine (2.6 g plant stanols/d) Plant stanol ester margarine (1.8 g plant stanols/d) 12 13

8 PLANT STANOL ESTER MECHANISM OF ACTION SAFETY Ikeda et al Heinemann et al Plat and Mensink 22. Figure 8. Cholesterol Plant stanol Plant stanol ester partially blocks cholesterol absorption from the gut but the exact mechanism of action is not fully understood. In the digestive tract, plant stanol ester is first hydrolysed into plant stanols and fatty acids. Because of the structural similarity of plant stanols and cholesterol (see page 4), plant stanols can partially replace WITHOUT plant stanol ester intake, 25 to 8 % of cholesterol is absorbed cholesterol in so called mixed micelles, which are needed for cholesterol absorption. Thus, cholesterol absorption is significantly reduced. Furthermore, plant stanols may activate still unknown transport proteins in intestinal enterocytes. These transport proteins most likely excrete cholesterol into the gut lumen and, accordingly, out of the body. WITH plant stanol ester from Benecol products, cholesterol absorption is reduced by 5 to 8 % INTESTINE More than 5 published clinical studies, extensive safety evaluation studies and the long experience of Benecol products on the market have shown that plant stanol ester is safe to use, well-tolerated and without adverse effects. Plant stanol ester has obtained Generally Recognised As Safe status (GRAS) in the USA. It has also been evaluated by food authorities in several EU countries prior to introduction in these countries. Food authorities in Europe have evaluated the use of plant stanols in foods and their recommendation is that the daily intake should range from 1 to 3 grams. Plant stanols are virtually unabsorbable, and are effectively eliminated from the body. Levels of plant stanol in blood remain very low even after continuous long-term use of Benecol products. Data from clinical studies show that the lipidstandardized blood concentration of β-carotene may be reduced in connection with plant stanol ester consumption. However, adherence to dietary recommendations including a daily consumption of vegetables and fruit prevents this decrease in carotenoids. Miettinen et al. 2. Noakes et al. 22. De Jong 27. INTESTINAL WALL BLOODSTREAM 14 15

9 RECOMMENDED BY INTERNATIONAL EXPERT BODIES LITERATURE According to all international and national guidelines and recommendations, dietary intervention is always the cornerstone of therapy for dyslipidemia. This is the case even when cholesterol-lowering drug therapies have been initiated because diet may have other beneficial cardiovascular effects beyond its effects on lipid concentrations, such as antithrombotic effects and improved endothelial function. Several international bodies have included the use of foods with added plant stanol ester in their recommendations for cholesterollowering dietary therapies. Examples of these are: US National Cholesterol Education Program NCEP (21) European Union Scientific Committee on Foods (22) International Atherosclerosis Society (23) International Lipid Information Bureau (23) WHO/FAO (23) American Diabetes Association & American College of Cardiology Foundation (28) American Academy of Pediatrics (28) National guidelines, e.g. Finnish Medical Society (24), Finnish Diabetes Association (1999, 28) Benecol products are recommended as part of a diet low in saturated fat and cholesterol and rich in dietary fibre. American Academy of Pediatrics. Pediatrics 28; 122: American Diabetes Association & American College of Cardiology Foundation. J Am Coll Cardiol 28; 51: American Diabetes Association & American College of Cardiology Foundation. Diabetes Care 28; 31: Andersson A, Karlström B, Mohsen R, Vessby B. Eur Heart J Suppl 1999; 1: S8-S9. Blair SN, Capuzzi DM, Gottlieb SO, Nguyen T, Morgan JM, Cater NB. Am J Cardiol 2; 86: European Union Scientifi c Committee on Foods 22. Available at: Fransen HP, de Jong N, Wolfs M, Verhagen H, Verschuren WM, Lütjohann D, von Bergmann K, Plat J, Mensink RP. J Nutr 27; 137: Gylling H, Miettinen T. Diabetologia. 1994; 37: Gylling H, Miettinen TA. Atherosclerosis 1995; 117: Gylling H, Miettinen TA. J Lipid Res 1996; 37: Gylling H, Radhakrishnan R, Miettinen TA. Circulation 1997; 96: Gylling H, Rajaratnam RA, Vartiainen E, Puska P, Miettinen TA. Menopause 26; 13: Gylling H, Siimes M, Miettinen TA. J Lipid Res 1995; 36: Hallikainen M, Lyyra-Laitinen T, Laitinen T, Moilanen L, Miettinen TA, Gylling H. Atherosclerosis 28; 199: Hallikainen MA, Sarkkinen ES, Gylling H, Erkkilä AT, Uusitupa MI. Eur J Clin Nutr 2; 54: Hallikainen MA, Sarkkinen E, Wester I, Uusitupa M. BMC Cardiovascular Disorders 22; 2: 14. Hallikainen MA, Uusitupa MI. Am J Clin Nutr 1999; 69: Heinemann T, Kullak-Ublick GA, Pietruck B, von Bergmann K. Eur J Clin Pharmacol 1991; 4 Suppl 1: S59-S63. Ikeda I, Tanabe Y, Sugano M. J Nutr Sci Vitaminol 1989; 35: International Atherosclerosis Society 23. Available at: org/guidelines. International Lipid Information Bureau 23. In: Gotto AM et al. (eds). Dyslipidemia and Coronary Heart Disease, 3rd edition. Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ. J Pediatr 26; 148: De Jong A. Doctoral Dissertation, Maastricht University 27. De Jong A, Plat J, Bast A, Godschalk RW, Basu S, Mensink RP. Eur J Clin Nutr 28; 62: De Jong A, Plat J, Lütjohann D, Mensink RP. Br J Nutr. In Press. Mensink R, Ebbing S, Lindhout M, Plat J, van Heugten MMA. Atherosclerosis 22; 16: Katan MB, Grundy SM, Jones P et al. Mayo Clinic Proc 23; 78: Ketomäki A, Gylling H, Miettinen TA. Clin Chim Acta 25; 353: Mensink RP, Ebbing S, Lindhout M, Plat J, van Heugten MMA. Atherosclerosis 22; 16: Miettinen TA, Puska P, Gylling H, Vanhanen H, Vartiainen T. N Engl J Med 1995; 333: Miettinen TA, Vuoristo M, Nissinen M, Järvinen HJ, Gylling H. Am J Clin Nutr 2; 71: Moruisi KG, Oosthuizen W, Opperman AM. J Am Coll Nutr 26; 25: Noakes M, Clifton P, Ntanios F, Shrapnel W, Record I, McInerney J. Am J Clin Nutr 22; 75: Ostlund RE Jr. Annu Rev Nutr 22; 22: Plat J, van Onselen ENM, van Heugten MMA, Mensink RP. Eur J Clin Nutr 2; 54: Plat J, Mensink RP. FASEB J 22; 16: Salo P, Wester P. Am J Cardiol 25; 96: Tammi A, Rönnemaa R, Gylling H, Rask-Nissilä L, Viikari J, Tuominen J, Pulkki K, Simell O. J Pediatr 2; 136: US National Cholesterol Education Program NCEP. JAMA 21; 285: Vuorio AF, Gylling H, Turtola H, Kontula K, Ketonen P, Miettinen TA. Arterioscler Thromb Vasc Biol 2; 2: WHO/FAO Expert Consultation. WHO Technical Report Series 23, No TRS 797. Available at: WHO_TRS_916.pdf. Williams CL, Bollella MC, Strobino BA, Boccia L, Campanaro L. J Am Coll Nutr 1999; 18:

10 BENECOL PRODUCTS A TASTY AND CONVENIENT WAY OF REDUCING CHOLESTEROL SUMMARY Plant stanol ester is available for consumers as Benecol products in many countries worldwide. These products have been formulated to fit local cultures, eating habits and attitudes, but the important common feature that links them all is that they contain enough plant stanol ester to significantly reduce cholesterol. The overall nutritional profi le of all Benecol products also fits into current dietary guidelines and recommendations. Examples of Benecol products: Benecol margarines and spreads Benecol milk and soy-based yoghurts Benecol milk and soy-based yoghurt mini drinks Benecol cream cheese style spreads Benecol oatmeal porridge Benecol bread Plant stanol ester, the cholesterol-lowering ingredient in Benecol products, reduces serum total cholesterol by up to 1 % and LDL cholesterol by up to 15 %. Such clinically relevant results are gained from a daily dose of approximately 2 grams of plant stanols in conjunction with meals. The cholesterol-lowering effect is lasting when Benecol products are consumed on a daily basis. Plant stanol ester is recommended by numerous national and international expert bodies and it is considered as efficient and safe. Benecol foods are tasty, and they fit well into a recommended heart-healthy diet. Please visit to find out which Benecol products are available in your country 18 19

11 Raisio Nutrition Ltd / Ingredients Division, P.O. Box Raisio, Finland Tel , benecol@raisio.com, IDBBN FINEPRESS