Marais, A D

Raal, F J

Rajput, M C

Ubbink, J B

Vorster, H H

South African Medical Journal (SAMJ)

SAMJ FORUMIt is estimated that ischaemic heart disease (IHD) will be theleading contributor to the global burden of disease in thefuture, moving from fifth place in 1990 to first in 2020.1Changes in lifestyle such as increased smoking, sedentaryoccupations, adoption of high-fat, high animal protein dietsand increased exposure to stressful urban situations willincrease the risk of IHD and stroke. 2-4 It can be accepted thatcardiovascular disease, already high among whites, colouredsand Indians, will become a major public health problem amongall South Africans in the future. Hypercholesterolaemia is the main risk factor for both IHDand stroke. It is not surprising that all recent guidelines forprevention and treatment of cardiovascular disease5-7emphasise prevention of hypercholesterolaemia throughlifestyle modification and treatment with appropriate lipid-modifying drugs in high-risk patients. There is no doubt thatthe modern  statins and fibrates are effectivehypocholesterolaemic agents and that they reducecardiovascular morbidity and mortality. However, theintroduction of these drugs should be approached with care,considering the expense, possible side-effects and the necessityfor lifetime compliance.5 Behavioural changes are never easy.The low-fat, high-fibre diet prescribed for prevention andtreatment of hypercholesterolaemia is less palatable than thetypical Western diet. Consequently, worldwide compliancewith this diet has been disappointing.8It seems, therefore, that there is a need for palatable andaffordable food products that can effectively and safely lowerblood cholesterol levels, reducing risk of IHD and stroke. Sucha food, a spread (margarine) with added plant sterols, has beendeveloped in Europe and is now available on the South Africanmarket (Pro.active). Plant sterols, b-sitosterol, campesterol andstigmasterol, are structurally related to cholesterol and usualdietary intakes vary from 200 mg to 450 mg/day. In largerquantities, they lower low-density lipoprotein (LDL)cholesterol by inhibiting exogenous (dietary) and endogenous(biliary) cholesterol absorption in the intestine. 9 The questionsmedical professionals need answered before recommendingthis margarine, centre around efficacy, safety, target groups andaffordability.EfficacyExtensive clinical testing9-11 involving hundreds ofhypercholesterolaemic subjects has shown that in a dose-response manner up to 2 g per day of plant sterolsincorporated into food vehicles significantly lowers LDLcholesterol by approximately 10 - 15% without influencinghigh-density lipoprotein (HDL) cholesterol or triglycerideconcentrations. The few studies12 that showed no effect offeredplausible explanations such as giving the sterol in capsuleswhich prevented mixing of the sterol with gut contents andconsequent absorption of cholesterol, as well as the type ofexperimental subjects.12 There is convincing evidence fromrandomised clinical trials that plant sterols, when added to aspread or salad dressing, effectively lower total and LDLcholesterol in adult hypercholesterolaemic men and women,independent of their baseline cholesterol levels or backgrounddiet.9-11Safety issues and target marketThe recommended daily portion of the margarine with addedplant sterols provides approximately 10 times more plant581CLINICAL PRACTICEPhytosterols — a new dietary aid for the treatment ofhypercholesterolaemiaH H Vorster, F J Raal, J B Ubbink, A D Marais, M C RajputProfessor HH Vorster is director of a multidisciplinary groupresearching preventive and therapeutic interventions in theFaculty of Health Sciences, Potchefstroom University, where sheis also Professor in Nutrition and heads the lipid clinic.Derrick Raal is Director of the Carbohydrate and LipidMetabolism Research Unit and Professor and Head of theDivision of Endocrinology and Metabolism, Department ofMedicine, Johannesburg Hospital. His particular interest is lipidsand the lipid disorders, and he supervises the lipid clinic atJohannesburg Hospital.Job Ubbink has a PhD in biochemistry and was Professor ofPathology at the University of Pretoria. He is a world expert onhomocysteine metabolism and specialises in the field of non-communicable diseases.David Marais is a consultant at Groote Schuur Hospital andheads the lipid clinic and laboratory at the University of CapeTown.Chiman Rajput is principal specialist and head of theDepartment of Medicine at R K Khan Hospital, Durban. He runsthe lipid clinic there and is also attached to the Nelson R MandelaSchool of Medicine, University of Natal, as a senior lecturer.August 2003, Vol. 93, No. 8  SAMJAugust 2003, Vol. 93, No. 8  SAMJSAMJ FORUMsterols than normally present in the average Western diet.Because of possible detrimental effects, the safety of this spreadhas been extensively examined in doses of up to 3 g/day forperiods of up to 3 years.13,14 None of these studies found anyevidence that sterol hormone functions, reproductivecharacteristics, gut microflora, short-chain fatty acidproduction or formation of secondary sterol metabolites wereinfluenced. There is some concern about a reduced absorptionof lipid-soluble vitamins and pro-vitamins (a - and b -carotenesand serum lycopenes). Eating more fruit and vegetables shouldcounter this effect.9 However, there may be some individualswith a genetic defect resulting in abnormally high absorptionof these plant sterols — sitosterolaemia should be suspected ina patient who has Achilles tendon as well as cutaneousxanthomata with normal to severe hypercholesterolaemia in anautosomal recessive pattern. It is not known if individualsheterozygous for this condition also absorb higher amounts ofphytosterols. It is advised that homozygous individuals shouldnot use products with added phytosterols. 15 It is also advised15that the target market for these products should be adult, non-pregnant, non-lactating individuals with raised cholesterollevels or an increased risk of IHD. If the spread is consideredfor use in hypercholesterolaemic children, lipid-soluble vitaminstatus should be monitored. Before long-term safety studieshave been completed, routine ingestion by the generalpopulation to lower IHD risk is not advised.15 It isrecommended that post-marketing surveillance should beestablished to determine the long-term safety of phytosterolspreads.Affordability and practical issuesSpreads are used to provide lubrication and taste for theconsumption of bread. Butter contains about 4 g of fat per 5 gportion, chiefly as saturated fat. Margarines simulate this fatcontent but contain plant oils. These may be hydrogenated andconverted to trans-isomers when processed to hard margarinesand are undesirable. The soft margarines have not undergonethese processes and consist mainly of mono- orpolyunsaturated fatty acids. The new spread on the SouthAfrican market contains polyunsaturated fatty acids as well asthe plant sterols.Because of cost and its high water content, the spread shouldnot be used for baking or frying of foods. It can be expectedthat compliance with such a small change in diet, namelyreplacing one spread with another, will be better thancompliance with more dramatic dietary interventions. It can beconcluded from the available evidence that this product can beused to lower total and LDL-cholesterol inhypercholesterolaemic individuals.The addition of plant sterols to a spread does not changetaste, consistency or acceptability of the spread. These productsare, however, expensive compared with other spreads, because2 500 parts of raw material are needed to extract one part ofsterol. But compared with hypolipidaemic drug treatment thespread with plant sterols may be cost-effective when at-risksubjects need to lower plasma cholesterol concentration.Together with a strict lipid-lowering diet, the plant sterolspread may achieve target concentrations in a significantnumber of subjects with moderate hypercholesterolaemia. Insevere hypercholesterolaemia, the LDLcholesterol-loweringpower of the statin drugs is superior, but the combination of astatin and the spread with added plant sterols displays anadditive effect.9 Where a statin dose has to be doubled toachieve a LDLcholesterol target concentration, it may thereforebe cost-effective to use the combination of the statin and theplant sterol-containing spread.1. Murray CJL, Lopez AD. The Global Burden of Disease . Vol. 1. Harvard: Harvard UniversityPress, 1996: 1-990.2. Bradshaw D, Bourne D, Schneider M, Sayed R. Mortality patterns of chronic disease oflifestyle in South Africa. In:Fourie J, Steyn K, eds. Chronic Diseases of Lifestyle in South Africa.MRC Technical Report. Cape Town:Medical Research Council, 1995: 1-32.3. Mollentze WF, Moore AJ, Steyn AF, et al. Coronary heart disease risk factors in a rural andurban Orange Free State black population. S Afr Med J 1995; 85: 90-96.4. Vorster HH. The emergence of cardiovascular disease during urbanisation of Africans. PublicHealth Nutrition 2002; 5: 239-243.5. South African Medical Association and Lipid and Atherosclerosis Society of Southern AfricaWorking Group. Diagnosis, management and prevention of the common dyslipidaemias inSouth Africa — clinical guideline. S Afr Med J 2000; 90: 164-178.6. South African Medical Association-Neurological Association of South African StrokeWorking Group. Stroke therapy clinical guideline. S Afr Med J 2000; 90: 276-306.7. South African Medical Association Dyslipidaemia Nutrition Working Group. Dietarymanagement of dyslipidaemia clinical guideline. S Afr Med J 2000; 90: 179-185.8. Walker AR. Diet in the prevention of cancer: what are the chances of avoidance? J R SocHealth 1996; 116: 360-366.9. Law M. Plant sterol and stanol margarines and health. BMJ 2000; 320: 861-864.10. Moghadasian MH, Frohlich JJ. Effects of dietary phytosterols on cholesterol metabolism andatherosclerosis:clinical and experimental evidence. Am J Med 1999; 107: 588-594.11. Jones PJ, Raeini-Sarjaz M, Ntanios FY, Vanstone CA, Feng JY, Parsons WE. Modulation ofplasma lipid levels and cholesterol kinetics by phytosterol versus phytostanol esters. J LipidRes 2000; 41: 697-705.12. Denke M. Lack of efficacy of low-dose sitostanol therapy as an adjunct to a cholesterol-lowering diet in men with moderate hypercholestrolemia. J Clin Nutr 1995; 61: 392-396.13. Baker VA, Hepburn PA, Kennedy SJ, et al. Safety evaluation of phytosterol stress. Part 1.Assessment of oestrogenicity using a combination of in vivo and in vitro assays. Food ChemToxicol 1999; 37: 13-22.14. Sanders DJ, Minter HJ, Howes D, Hepburn PA. The safety evaluation of phytosterol esters.Part VI. The comparative absorption and tissue distribution of phytosterols in the rat. FoodChem Toxicol 2000; 38: 485-491.15. Lichtenstein AH, Deckelbaum RJ. Stanol/sterol-ester containing foods and blood cholesterollevels. A statement for healthcare professionals from the Council on Nutrition, PhysicalActivity, and Metabolism of the American Heart Association. Circulation 2001; 103: 1177-1179.

Phytosterols - a new dietary aid for the treatment of hypercholesterolaemia

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Phytosterols - a new dietary aid for the treatment of hypercholesterolaemia

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