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Phytosterols: to be or not to be toxic; that is the question

Published online by Cambridge University Press:  01 December 2008

Gérard Lizard*
Affiliation:
Centre de Recherche Inserm U866 ‘Lipides, nutrition et cancer’, Université de Bourgogne, Faculté des Sciences Gabriel, 6 Bd Gabriel, 21000Dijon, France
*
*Corresponding author: Dr Gérard Lizard, fax +33 380 39 62 50, email Gerard.Lizard@u_bourgogne.fr
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Abstract

Type
Invited commentary
Copyright
Copyright © The Authors 2008

Plant sterols (phytosterols) are membrane constituents of all plants with a structure analogous to that of cholesterol. Thus, phytosterols have either an additional methyl or ethyl group on the carbon-24 position or an additional double bond in the side chain(Reference Von Bergmann, Sudhop and Lütjohann1). Noteworthy, in patients with the rare inherited disease of phytosterolaemia characterized by a hyperabsorption and diminished biliary secretion of cholesterol and phytosterols as well as by tendon and tuberous xanthoma, elevated plasma concentrations of phytosterols (campesterol, sitosterol) have been shown to constitute a risk factor for premature atherosclerosis(Reference Glueck, Speirs, Tracy, Streicher, Illig and Vandegrift2). However, whether plasma concentrations of campesterol and sitosterol are risk factors for CVD in subjects without phytosterolaemia is not clearly established, and still remains controversial(Reference Sudhop, Gottwald and von Bergmann3). Thus, whereas some benefits are attributed to phytosterols found in fruits, vegetables, vegetable oils, seeds and nuts(Reference Weihrauch and Gardner4), especially their ability in decreasing cholesterol concentrations through various ATP-binding cassette transporters present at the intestinal level(Reference Plat and Mensik5, Reference Sudhop, Lütjohann and von Bergmann6), the potential effects of phytosterols, and of their oxide derivatives(Reference Adcox, Boyd, Oehrl, Allen and Fenner7), on other metabolic processes remain to be elucidated(Reference De Jong, Plat and Mensink8). Therefore, the article by Rubis et al. (Reference Rubis, Paszel, Kaczmarek, Rudzinska, Jelen and Rybczynska9), published in the current issue of the British Journal of Nutrition, concerning the in vitro effects of rape seed oil extract components (a mixture of various phytosterols containing mainly campesterol, sitosterol and stigmasterol derivatives), of β-sitosterol, and of 5α,6α-epoxycholesterol on the proliferation and viability of the human abdominal aorta endothelial cells, HAAE-2, is of great interest. In agreement, with previous investigations(Reference Maguire, Konoplyannikov, Ford, Maguire and O'Brien10), strong cytotoxic effects of β-sitosterol were shown, whereas a low cytotoxicity and no side-effects were observed with 5α,6α-epoxycholesterol and the seed oil extract, respectively. Although absorption of plant sterols is low compared with cholesterol(Reference Heinemann, Axtmann and von Bergmann11), these data show that some phytosterols, in isolation, can have more or less pronounced cytotoxic effects on normal cells. These observations are in agreement with those obtained with high concentrations of β-sitosterol (up to 0·7 mm) on human umbilical vein endothelial cells where cell contraction and increased release of intracellular lactate dehydrogenase in the culture medium was reported(Reference Boberg, Pettersen and Prydz12). Interestingly, these observations suggest that very high concentrations of certain phytosterols (mainly β-sitosterol) in foodstuffs might impair vascular reactivity, and interfere with the vascular tone. As it has been well established (1) that atherosclerosis is associated with abnormalities of vascular function characterized both by an increase in the response to specific vasoconstrictor agents(Reference Heistad, Armstrong, Marcus, Piergors and Mark13), and by a marked attenuation of endothelium-dependent relaxation(Reference Jayakody, Senaratne, Thomson and Kappagoda14), and (2) that alteration of vascular reactivity occurs at an early stage of the atherosclerotic process(Reference Heistad, Armstrong, Marcus, Piergors and Mark13, Reference Celermajer, Sorensen, Bull, Robinson and Deanfield15), it seems very important to identify precisely the effects of certain phytosterols on the endothelium. However, only concentrations of the oil extract that contain high, non-physiological concentrations of β-sitosterols resulted in a significant growth inhibition. Therefore, as previously reported and as well described with oxysterol mixtures(Reference Biasi, Leonarduzzi, Vizio, Zanetti, Sevanian, Sottero, Verde, Zingaro, Chiarpotto and Poli16), these data indicate that some phytosterols may quench the inherent toxic effects of others, and may therefore counteract the proatherogenic signals involved in the initiation and the development of atherosclerotic lesions. Thus, as the involvement of phytosterols in atherogenesis cannot be excluded, a better knowledge of the biological activities of these molecules present in high amounts in various foodstuffs remains an important and essential source of investigation necessary to avoid important side-effects, and to identify adequate phytosterol mixtures capable of bringing benefit to human health.

References

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