Article Text
Summary
Plant sterol-enriched margarine consumption is known to significantly reduce concentrations of plasma low density lipoprotein (LDL) cholesterol. However, there is no evidence that such margarines may reduce cardiovascular events. This is the first report of a significant increase in the plasma concentration of phytosterols due to plant sterol-enriched margarine consumption leading to extravascular lipid deposits (xanthelasma), in a woman with hypercholesterolaemia. Because increased plasma levels of phytosterols may promote atherosclerosis, the present observation raises concern about potential cardiovascular risk after long-term consumption of these margarines.
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BACKGROUND
Plant sterol-enriched margarines have been available for several years and have been shown to lower concentrations of plasma low density lipoprotein (LDL) cholesterol by reducing intestinal cholesterol absorption.1,2 At the usual recommended intakes of 2 to 2.5 g/day, margarines enriched with plant sterols lower plasma LDL cholesterol concentrations by 10% to 14%.2 Despite this significant reduction, such margarines have not been shown prospectively to reduce cardiovascular events. We report for the first time the case of extravascular lipid deposits (xanthelasma) associated with increased plasma phytosterol levels induced by a regimen of margarine enriched with plant sterols in a woman with hypercholesterolaemia.
CASE PRESENTATION
A 59-year-old woman without a history of coronary disease was referred to our department because of hypercholesterolaemia. The woman had previously experienced myalgia when taking statins (pravastatin, fluvastatin) or fibrates (fenofibrate) and gastrointestinal disorders when taking colestyramine. Because of these side effects, all hypolipidaemic drug therapies had been discontinued. Three months after the woman started a controlled diet, her LDL cholesterol concentration remained elevated (5.75 mmol/l). Because she was intolerant to hypolipidaemic agents, we recommended that she consume a plant sterol-enriched margarine at the recommended dose of 20 g/day (Fruit d’Or Pro-activ margarine, containing 8% phytosterols), corresponding to 1.6 g/day phytosterols. After 18 months of regular consumption of plant sterol-enriched margarine, the patient developed xanthelasma (fig 1), whereas her plasma LDL cholesterol level was 4.49 mmol/l. This rapid development of xanthelasma associated with an only moderately elevated concentration of plasma LDL cholesterol prompted us to measure this patient’s plasma phytosterol concentration (campesterol), which was significantly increased (165 μmol/l; normal <25 μmol/l).
OUTCOME AND FOLLOW-UP
We asked the patient to discontinue her consumption of plant sterol-enriched margarine. Three months later, her plasma campesterol levels were normal (20 μmol/l; normal <25 μmol/l) (fig 2). No mutations of ABCG5/ABCG8 transporters were found in this patient, ruling out a “minor form” of phytosterolaemia (or sitosterolaemia).3
DISCUSSION
We report, for the first time, a significant increase in plasma concentrations of phytosterols due to plant sterol-enriched margarine leading to extravascular lipid deposits (xanthelasma). Although our patient had no sitosterolaemia (she had no ABCG5/ABCG8 mutation, and her plasma campesterol concentrations returned to normal after withdrawal of plant sterol-enriched margarine), she had elevated plasma concentrations of phytosterols. In our patient, the plasma concentration of campesterol was not as high as is usually observed in familial sitosterolaemia but was more than 6 times the upper limit of normal values, which is not negligible. The rise in plasma campesterol observed in our patient was greater than the mean 90% increase usually reported in clinical trials of plant sterol-enriched margarine.4,5 The reasons for this discrepancy are not clear, but several studies in humans have shown a heterogeneous level of increase in plasma campesterol after consumption of plant sterol-enriched margarine.4–6 Several different mechanisms are responsible for plasma campesterol concentrations, which are influenced by other genes beside ABCG5/ABCG8.6 The heterogeneous levels of increase in plasma campesterol after consumption of plant sterol-enriched margarine could be due to genetic diversity in the general population. Thus, some individuals may show a larger increase in plasma campesterol after consumption of plant sterol-enriched margarine than others.
Patients with sitosterolaemia show extravascular lipid deposits and premature severe atherosclerosis.7 Promotion of atherosclerosis in patients with sitosterolaemia has been shown to be related to augmented plasma phytosterol concentrations.8 Thus, the increase in plasma phytosterol concentrations due to plant sterol-enriched margarines could be harmful, and we cannot exclude that long-term consumption of plant sterol-enriched margarines may increase cardiovascular risk. Indeed, although plant sterol-enriched margarines diminish the plasma LDL cholesterol concentration, they have not been shown to reduce cardiovascular risk.8 Our present observation showing a large increase in plasma phytosterols and extravascular lipid deposits (xanthelasma) due to a regimen of plant sterol-enriched margarine raises concern about potential cardiovascular risk after long-term consumption of these margarines.
LEARNING POINTS
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Plant sterol-enriched margarines significantly reduce the concentration of plasma LDL cholesterol but have not been shown to reduce cardiovascular events.
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We report a case of significant increase in plasma phytosterol concentration (campesterol) leading to extravascular lipid deposits (xanthelasma) 18 months after the initiation of treatment with plant sterol-enriched margarines.
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The plasma concentration of campesterol returned to normal after the consumption of plant sterol-enriched margarine was discontinued, showing that the regimen had caused the increase in plasma phytosterol levels.
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Because increased plasma levels of phytosterols may promote atherosclerosis, our observation raises concern about potential cardiovascular risk after long-term consumption of these margarines.
Footnotes
Competing interests: none.
Patient consent: Patient/guardian consent was obtained for publication.