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Afunctional food is one which has been modi-fied or has had additional food ingredients

added to provide a desired health benefit beyondthe usual nutrients in the food.1 The terms “nu-traceutical or designer food” are also used in thesame context. Recently, there has been a growinginterest in designing functional foods to modifyplasma lipids with the aim of reducing the risk ofcoronary artery disease. Benecol2 and Take Con-trol3 are relatively new nutraceuticals designed tolower total cholesterol and low density lipoprotein(LDL) cholesterol when consumed in the appropri-ate amount and frequency. They are available as amargarine spread (both regular and light versions),snack bars, and salad dressings.

MECHANISM OF ACTION AND CLINICAL TRIAL RESULTSIt has been known for several decades that plantsterols, such as sitosterol and campesterol, arestructurally similar to cholesterol and thus can inhibit cholesterol absorption by competitivemechanisms.4 However, the insolubility of thesecompounds has limited their use as potential cho-lesterol lowering agents. Recently, sitostanol (a de-rivative of sitosterol) has been made fat-soluble byesterification to fatty acids, producing a sitostanolester (SE). Thus, it is now possible to solubilizethese compounds in margarine and other fat-basedfood products marketed as Benecol and Take Con-trol.2,3 The SEs in these foods are virtually unab-sorbed, thereby interfering with the absorption ofdietary and biliary cholesterol and reducing plasmacholesterol levels. A number of controlled clinicalstudies5–11 demonstrate that consumption of mar-garine containing SEs lowers total and LDL choles-terol by 10%–15% in hypercholesterolemicsubjects. These effects are achieved after approxi-

mately 4–8 weeks with a daily dose of 2–3 g ofSEs—the amount provided in approximately 3 Tbsp of the commercial product. The cholesterolreduction is observed in normocholesterolemicsubjects,7 as well as those consuming lower fatdiets.10 SEs appear to have little or no effect uponplasma high density lipoprotein (HDL) cholesterolor triglyceride levels.

PRACTICAL ISSUES AND COSTThere are a variety of methods available to pa-tients to help them reduce their LDL cholesterol,including lifestyle/diet modification, pharmacolog-ic agents and, more recently, the consumption offunctional foods. For each of these, the practicalissues of cost, compliance, side effects, and poten-tial benefits must be considered. Lifestyle changescan achieve similar or superior effects when com-pared with SE-containing nutraceuticals, are lessexpensive, and have added benefits beyond reduc-ing cholesterol levels, such as weight loss and im-proved fitness.

A number of cholesterol-reducing drugs can beused, most notably statins, fibrates, and niacin. The lat-ter two have significant side effects that limit their ac-ceptance by many patients, while the statins arerelatively free of side effects. The SE-containing foodproducts are as potent as most pharmacologic agents,but have been shown to be relatively free of side ef-fects.4 They do not interfere with clotting parametersor steroid hormone levels.9 No gastrointestinal intoler-ance or drug interactions have been reported. Howev-er, regular consumption of the sitostanol-containingmargarines significantly reduced ß carotene levels inthe blood.4,6 Although other lipid-soluble vitaminswere not impacted, further study is needed to deter-mine if other important carotenoids or lipid-solublecompounds are affected. In addition, the safety of SEsin pregnancy has not been established.

Supplementation of the diet with fiber such aspsyllium products may achieve results similar to SEin reducing LDL cholesterol,12 may or may not beless expensive depending upon the product used,and allows dietary supplementation rather than re-placement. The latter consideration is important inpatients who are trying to lose weight. As summa-rized in the Table, these SE-containing products

Functional Foods to Lower Cholesterol Nicholas D. Browning, BS, RD; Deborah Studebaker-Hallman, BS; Dianne A. Hyson, RD, PhD

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From the University of California, Davis, CAAddress for correspondence/reprint requests: Dianne Hyson, RD, PhD, Department of Endocrinology, Clinical Nutrition and Cardiovascular Medicine, TB172, One Peter Shields Avenue, UC-Davis, Davis, CA 95616Manuscript received April 11, 2000; accepted June 21, 2000

SUMMER 2000 PREVENTIVE CARDIOLOGY 141

are not calorie or fat free. The manufacturers ofBenecol and Take Control recommend using anaverage of 2–3 Tbsp per day of their spreads toachieve the cholesterol reductions reported in theirstudies. Consuming the regular spread of Benecolin the recommended amounts provides 42% of thetotal daily fat allowance, while the light spreadgives 23% of the same. For most patients, con-sumption of this product would require efforts tocurtail other sources of fat in the diet to ensurecompliance with <30% of daily calories fromfat.13 This might prove very difficult unless theywere replacing the margarine or oil that they nor-mally eat with Benecol or Take Control. This ismore easily achieved if the light products are used.Considering that many nutrition professionals aretrying to have patients limit or eliminate intake of“discretionary fat” such as margarine, butter, andsour cream, SE-containing products may not be thebest choice for someone who is unable to limitother sources of fat. With careful consultation,however, the light products are a reasonablechoice.

In order to achieve the maximum benefit fromSE-containing products, they need to be consumedwith each meal. Consuming all of the product atonce or periodically would mean that the SEwould not always be present, and thus limit theireffectiveness, as only some meals would be subjectto their interference with cholesterol absorption.In addition, as with other cholesterol loweringagents, the cholesterol lowering effect is onlyachieved with continued use of the product.

The inevitable question regarding nutraceuti-cals, and indeed, everything else in medicine is:“what does it cost?” Using Benecol as an example,the manufacturers recommend three servings ofthe spread throughout the day. Currently, a tub ofBenecol regular or light margarine spreads costs$4.99 (Safeway, Sacramento, CA, telephone com-munication). This tub yields 16 servings, or enoughfor a just over 5 days. To achieve the recommend-ed intake, almost 69 tubs of margarine will need tobe purchased each year at a current cost of $341,or close to $30 each month out of the patient’spocket. Most statins fall in the range of $37–$100per month although most patients with insurancethat includes a drug benefit would not pay the fullprice of statin therapy. While the current choicesof SE-containing food products do allow for other

ways of achieving the recommended intake, thetub of margarine seems to be the most economicalat the current time.

CONCLUSIONIn practical terms, advising a patient to useBenecol or Take Control margarine is akin to pre-scribing a three-times a day medication that theyhave to measure out themselves. Viewed anotherway, advising a patient to use these SE-containingproducts in place of the margarine or butter thatthey normally eat could be a potentially easymethod of lowering LDL and total cholesterol. De-pending on the patient, therefore, this productcould be a boon or a burden. Given a patient whoconsumes margarine or butter with every meal andis able to limit other sources of fat in the diet, this would be a relatively easy, albeit somewhat ex-pensive, method of reducing LDL cholesterol. Alternatively, for a patient who does not normallyconsume fat in this manner but is achieving (or ex-ceeding) the recommended daily fat intake withother foods, the use of these products would re-quire substantial dietary modification.

There is also the issue of potential variability incholesterol lowering effects due to inherent “di-etary responsiveness” of an individual or variationin dietary intake of fat and cholesterol. It seemslikely that hypercholesterolemic subjects with high-er intake of dietary fat and cholesterol wouldachieve the most benefit from consuming SE.9

In summary, SE-containing foods, such asBenecol and Take Control, have potential utility inpatients who consume margarine or butter on aregular basis, would not mind switching to theseproducts, and can afford it. Alternatively, some pa-tients might be amenable to occasional use of theproduct with the understanding that such usewould be associated with diminished cholesterol re-duction. Nutraceuticals enriched with SEs mightalso be useful in patients in whom other therapieshave failed to achieve the desired results. There-fore, we conclude that consumption of these SE-containing products may be a useful approach tocholesterol lowering in selected patients.

REFERENCES1 Position of the American Dietetic Association: Phytochemi-

cals and Functional Foods. J Am Diet Assoc. 1995.

TABLE. COMPARISON OF FAT AND ENERGY COMPOSITION OF SELECTED SITOSTANOL ESTER SPREADS1,2

TYPE OF TAKE CONTROL BENECOL LIGHT BENECOLDIETARY FAT GRAM/SERVING (KCAL=50) GRAM/SERVING (KCAL=80) GRAM/SERVING (KCAL=45)

Total fat 6 9 5Saturated fat 0.5 1 0.5Polyunsaturated fat 2 3 2Monounsaturated fat 2.5 4 2.5

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2 Benecol is a registered trademark of Raisio Group, licensed toMcNeil Consumer Healthcare, division of McNeil-PPC, Inc.

3 www.takecontrol.com4 Gylling H, Puska P, Vartianen E, et al. Retinol, vitamin D,

and α-tocopherol in serum of a moderately hypercholes-terolemic population consuming sitostanol ester margarine.Atherosclerosis. 1999;145:279–285.

5 Nguyen TT. The cholesterol-lowering action of plantstanol esters. J Nutr. 1999;129(12):2109–2112.

6 Gylling H, Puska P, Vartianen E, et al. Serum retinol, α-to-copherol, carotenes and lipid peroxide production duringserum cholesterol lowering by SE margarine in a mildly hy-percholesterolemic population (abstract). Circulation.1996;94:I–578.

7 Nguyen TT, Dale LC, von Bergmann K, et al. Cholesterol-low-ering effect of stanol ester in a U.S. population of mildly hyper-cholesterolemic men and women: A randomized controlledtrial. Mayo Clin Proceed. 1999;74(12):1198–206.

8 Weststrate JA, Meijer GW. Plant sterol enriched mar-garines and reduction of plasma total and LDL cholesterol

concentrations in normocholesterolemic and mildly hyper-cholesterolemic subjects. 1998;52:334–343.

9 Plat J, Mensink RP. Vegetable oil-based vs. wood-basedstanol ester mixtures: Effects on serum lipids and hemosta-tic factors in nonhypercholesterolemic subjects. Atheroscle-rosis. 2000;148(1):101–112.

10 Gylling H, Miettinen TA. Cholesterol reduction by differentplant stanol mixtures and with variable fat intake. Metab: ClinExper. 1999;48(5):575–580.

11 Hallikainen MA, Uusitupa MI. Effects of two low-fat stanolester-containing margarines on serum cholesterol concentra-tions as part of a low-fat diet in hypercholesterolemic subjects.Am J Clin Nutr. 1999;69:403–410.

12 Yarnall SR. The role of soluble fiber in reducing cholesterol levels. Prev Cardiol.1999;2(4):174–176.

13 National Cholesterol Education Program Expert Panel. Secondreport of the National Cholesterol Education Program ExpertPanel on Detection, Evaluation, and Treatment of High BloodCholesterol in Adults (Adult Treatment Panel). Circulation.1994;89:1333–1445.