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(Circulation. 2001;103:1177.)
© 2001 American Heart Association, Inc.
AHA Science Advisory |
Stanol/Sterol Ester–Containing Foods and Blood Cholesterol Levels
A Statement for Healthcare Professionals From the Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association
Abstract
Abstract—Considerable attention in the recent past has focused on the potential benefits or adverse effects of butter versus different types of margarines, usually with respect to their relative content of polyunsaturated, saturated, and trans fatty acids, and the impact of these on low-density lipoprotein (LDL) cholesterol levels. Recently, a new class of margarines and other fat-derived products (eg, salad dressings, mayonnaise) containing plant-derived sterols that are intended for use to lower blood cholesterol levels have been introduced into the food supply. These products are being marketed as adjuncts to low-saturated-fat and low-cholesterol diets to maximize reductions in LDL cholesterol levels achievable by dietary means.
Key Words: AHA Science Advisory • diet • fatty acids • cholesterol • risk factors • coronary disease
Background
In the early 1950s, plant-derived sterols were observed to decrease serum cholesterol levels.1 2 The effective dose in humans was reported to be between 5 and 10 g/d when given in divided doses. The efficacy of plant sterols with regard to lowering blood cholesterol levels was soon confirmed,3 4 5 6 albeit at somewhat lower doses.7 On the basis of these data, plant sterols were briefly used in the reduction of blood cholesterol levels before the introduction of pharmacological agents with higher efficacy and patient acceptance. The resurgence of interest in plant-derived sterols is now coupled with the incorporation of these compounds into fat-containing foods. More recent evidence has shown that esterification of these sterols increases their solubility in fat and their efficacy in lowering low-density lipoprotein (LDL) cholesterol levels.8 9
What Are Plant-Derived Sterols?
Sterols represent a group of compounds that are alcoholic derivatives of cyclopentanoperhydrophenanthrene and are an essential constituent of cell membranes in animals and plants. Cholesterol is the sterol of mammalian cells, whereas multiple sterols, or phytosterols, are produced by plants, with sitosterol, campesterol, and stigmasterol being most common. Plant sterols, although structurally similar to cholesterol, are not synthesized by the human body. They are very poorly absorbed by the human intestine. The specific plant sterols that are currently incorporated into foods intended to lower blood cholesterol levels are extracted from soybean oil or tall (pine tree) oil. Additional sources of plant sterols may be available in the near future. The plant sterols currently incorporated into foods are esterified to unsaturated fatty acids (creating sterol esters) to increase lipid solubility, thus allowing maximal incorporation into a limited amount of fat. Some plant sterols currently available are saturated, to form the stanol derivatives, sitostanol and campestanol, which after esterification form stanol esters.
Effect of Plant Sterol–Containing Fats on Blood Lipid Levels
In the early 1990s, it was reported that
sitostanol ester (3.4 g/d) delivered in the form of rapeseed (canola)
oil–based margarine lowered LDL cholesterol levels by 
10% in
modestly hypercholesterolemic subjects and that individuals with
apolipoprotein (apo) E4 alleles, previously reported to have the
highest efficiency of cholesterol absorption, derived the greatest
benefit from
treatment.8 9
Subsequent work has established that maximal efficacy with respect to
total and LDL cholesterol lowering is achieved at 2 g/d and that
there is little or no effect on high-density lipoprotein (HDL)
cholesterol or triglyceride
levels.10 11 12 13 14 15 16 17 18 19 20 21
In addition, these studies demonstrated that the consumption of fats
containing plant-derived sterol esters is efficacious in both
normolipidemic and dyslipidemic individuals, including those treated
with ß-hydroxy-ß-methylglutaryl–coenzyme A (HMG-CoA) reductase
inhibitors and other lipid-lowering agents. In addition, daily
ingestion of 1.8 to 3 g of plant stanol esters in
hypercholesterolemic children has been reported to reduce LDL
cholesterol levels to an extent similar to that in
adults.22 For the most part,
the consumption of 2 g/d of plant sterol ester has been reported to
decrease LDL cholesterol levels 9% to 20%, with considerable
variability reported among
individuals.10 11 12 13 14 15 16 17 18 19 20 21
There appears to be little difference in efficacy of campestanol ester
and sitostanol ester with respect to cholesterol
lowering.23
The impact of the sterol/stanol ester–containing fats on LDL cholesterol lowering is relatively consistent regardless of whether the background diet is similar to that currently consumed in Western countries or reduced in total fat, saturated fat, and cholesterol, consistent with current guidelines for hypercholesterolemic individuals, and whether the plant sterol ester–containing fats have been incorporated into regular fat or reduced fat products.8 9 10 11 12 13 14 15 16 17 18 19 20 21
Both unsaturated (sterol ester) and saturated (stanol
ester) forms of plant sterols have been used in the above studies.
Comparative investigations of the relative efficacy of these 2
preparations in regular-fat margarine have recently been
reported.15 21
Superimposed on a background diet high in total and saturated fat, 2
to 3 g/d taken in 2 divided doses of both sitostanol ester and
sitosterol ester in margarine resulted in 10% to 13% reductions in
LDL cholesterol and no significant change in HDL cholesterol levels. An
additional study has compared the effect of 2 reduced-fat (40% of fat)
margarines containing stanol esters, the sterol esters derived from
either tall oil or soybean oil, within the context of diets consistent
with the American Heart Association Step 2 diet
criteria.24 The efficacy of
both preparations was similar, with a decrease of 9% in LDL
cholesterol levels.
Mechanisms of Action of Plant Stanol/Sterol Ester–Containing Fats
Sterol balance studies have suggested that decreased blood cholesterol levels are attributable, at least in part, to an inhibition of cholesterol absorption.25 This inhibition has been ascribed to a number of mechanisms, including partitioning in the micellar phase of the intestinal lumen, presence in the unstirred water layer or other mucosa barriers that might limit transmembrane transport, and alteration in rates of cholesterol esterification in the intestinal wall.25 26 27 28 29
Plant sterols differ structurally from cholesterol by a methyl or ethyl group in their side chains and are not synthesized in the human body. These structural differences render them minimally absorbable. Serum campesterol levels and stable isotope–labeled cholesterol can be used to estimate the efficiency of intestinal cholesterol absorption in humans.27 28 29 Such data have confirmed the original observations from sterol balance studies that plant-derived sterols decrease the absorption of both dietary and endogenously derived cholesterol in the intestine. It has been speculated that the full magnitude in the decreased rate of cholesterol absorption (33% to 60%) is not realized in decreased LDL cholesterol levels because of compensatory mechanisms that increase the rate of endogenous cholesterol synthesis.8 9 This speculation has recently been confirmed.30 Lipoprotein kinetic studies have associated the significant decreases in LDL cholesterol levels with a decreased production rate of LDL apoB rather than a change in the LDL apoB fractional catabolic rate.12 The general lack of effect of plant-derived sterols on HDL cholesterol levels was reflected in essentially no change in the kinetic parameters of HDL apoA-I.12
Potential Risks Associated With the Use of Plant Stanol/Sterol Ester–Containing Fats
Few adverse effects related to either the short-term or
long-term consumption of the plant stanol/sterol ester–containing fats
have been reported. However, of concern are some observations of
decreased levels of plasma alpha plus beta carotene, 
-tocopherol,
and/or lycopene as a result of the consumption of foods containing both
stanol esters and sterol
esters.16 17 23 24
In general, with the exception of beta carotene, these decreases often
parallel the decreases in total and LDL cholesterol. Still, at this
time it appears prudent to recommend additional monitoring of the
effect of foods containing plant-derived sterol/stanol esters on
fat-soluble nutrient levels and to recommend that an assessment of the
biological significance of the changes observed be determined. The
activities of alkaline phosphatase, alanine transaminase, aspartate
transaminase, and 
-glutamate transaminase have been reported to be
unaffected by plant sterol consumption within the recommended
range.17 Other technical
data on safety evaluation are now
available.31 32 33 34 35 36 37
Plasma levels of plant sterols/stanols have not been or are only minimally elevated after daily ingestion of sterol/stanol ester–containing foods.12 16 23 24 However, there may be some individuals in the population who have abnormally high absorption of plant sterols. For example, individuals homozygous for sitosterolemia absorb substantial amounts of sitosterol, with resultant hypercholesterolemia and development of xanthomas.38 It is not known whether some individuals heterozygous for this condition could absorb higher amounts of plant sterols than the normal population and whether this would lead to adverse effects. In a study of 2 obligate heterozygotes for sitosterolemia,39 increased sitosterol absorption was balanced by enhanced plant sterol elimination. It is not known what percentage of individuals in a given population would have this condition. Still, in the absence of more data on genetic mutations involved in sitosterolemia, it would be prudent to counsel these individuals against the use of these foods at the present time.
Of concern are the potential adverse effects of lowering beta carotene and perhaps other fat-soluble vitamins over long periods of time in children who would be ingesting plant sterol–containing fats. Likewise, data on the effect of these compounds in pregnant women are lacking. Because food products containing plant sterols are likely to be shared during meals by all family members, the potential for intake by nonhypercholesterolemic individuals is significant. Thus, the American Heart Association recommends that further studies and large-scale monitoring be undertaken to determine the long-term safety of plant sterol/stanol ester–containing foods in both normocholesterolemic and hypercholesterolemic adults, as well as in children.
Who Should Use Stanol/Sterol Ester–Containing Fats?
Until long-term studies are performed to ensure the absence of adverse effects in all individuals ingesting plant sterol esters, these products should be reserved for adults requiring lowering of total and LDL cholesterol levels because of hypercholesterolemia or the need for secondary prevention after an atherosclerotic event. Although their use as a dietary adjunct in moderate to severely hypercholesterolemic children can be considered, fat-soluble vitamin status should be monitored, and again, long-term studies on safety are required. Whether plant sterols should be used in normocholesterolemic individuals with other risk factors for coronary heart disease (eg, low HDL cholesterol levels) remains to be determined. It has been suggested that introduction of plant sterols into the food supply (eg, by fortification of margarines and food oils) might lower coronary heart disease risk for the whole population.20 However, the excess costs of this measure need to be considered, along with population efficacy and safety data. Thus, although foods containing plant sterols are a promising addition to dietary interventions aimed at improving cardiac risk profiles, more information is required before their routine ingestion is recommended in the general population as a step toward dietary prevention of coronary heart disease.
Footnotes
This statement was approved by the American Heart Association Science Advisory and Coordinating Committee in November 2000. A single reprint is available by calling 800-242-8721 (US only) or writing the American Heart Association, Public Information, 7272 Greenville Ave, Dallas, TX 75231-4596. Ask for reprint No. 71-0201.
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