September 2006: 385– 402 Lead Article Plasma Concentrations of Plant Sterols: Physiology and Relationship with Coronary Heart Disease Yen-Ming Chan, MSc, Krista A Varady, PhD, Yuguang Lin, PhD, Elke Trautwein, PhD, Ronald P. Mensink, PhD, Jogchum Plat, PhD, and Peter J.H. Jones, PhD Recently, it has been questioned whether elevated levels of circulating plant sterols increase the risk of coronary heart disease (CHD). To date, no definitive conclusions regarding such a relationship have been reached, nor have there been any studies summarizing the factors that contribute to the observed elevations in plant sterol concentrations in plasma. Thus, the purpose of this review is to systematically compare the plant sterol levels of subjects from the general popu- lation and to describe factors that contribute to the variations observed. The question of whether elevated plasma concentrations of plant sterols are associated with an increased risk of CHD was also assessed. Results indicate that the key factors accounting for variations in circulating plant sterol concentrations include: apolipoprotein E phenotypes, ATP-binding cassette transporter polymorphisms, use of statin drugs, presence of metabolic syndrome, dietary intake of plant sterols, gender, and analytical techniques used in the measurement of plant sterols in the plasma. An analysis of the studies examining the relationship between circulating levels of plant sterols and CHD risk in non-sitosterolemic populations re- vealed no clear associations. Furthermore, it was shown that the above-mentioned factors play an im- portant role in determining the levels of plant sterols in plasma. Since these factors may act as potential confounders, they must be controlled for before more solid conclusions can be reached. Key words: blood concentrations, coronary heart dis- ease, cholesterol, plant sterols © 2006 International Life Sciences Institute doi: 10.1301/nr.2006.sept.385– 402 INTRODUCTION Plant sterols are naturally occurring constituents of plants that are structurally similar to cholesterol yet differ in side chain configuration. These compounds are not synthe- sized in mammals, and therefore are derived solely from the diet. It is well established that dietary plant sterols lower plasma cholesterol concentrations by inhibiting intestinal cholesterol absorption. Compared with cholesterol, plant sterol concentrations in the plasma are low due to their limited capacity to be absorbed. Although several epidemi- ological studies have investigated circulating levels of plant sterols in populations consuming habitual diets, this has yet to be systematically compared across populations. In addi- tion, the underlying factors responsible for these differences have not been well established. Furthermore, since some investigators have recently suggested that circulating levels of plant sterols may be linked to an increased risk of coronary heart disease (CHD), 1-5 a comprehensive analysis of the literature in this area is warranted. Thus, in order to address these queries and concerns, the aim of the present review is to systematically compare plant sterol levels of subjects from the general population and to describe the factors that may contribute to the variations observed. An additional objective of this review is to assess whether elevated plasma concentrations of plant sterols are associ- ated with an increased risk of CHD. PLANT STEROL LEVELS IN THE GENERAL POPULATION To determine plant sterol concentrations in the gen- eral population, studies conducted from 1986 to 2005 were analyzed. 6-50 Both population-based studies and clinical trials were included to generate the data pool. For clinical trials, baseline plant sterol concentrations were Drs. Chan, Varady, and Jones are with the School of Dietetics and Human Nutrition, McGill University, Ste. Anne de Bellevue, Que ´ bec, Canada; Drs. Lin and Trautwein are with the Unilever Food and Health Re- search Institute, Unilever R & D, Vlaardingen, The Netherlands; Drs. Mensink and Plat are with the De- partment of Human Biology, Maastricht University, Maastricht, The Netherlands. Please address all correspondence to: Dr. Peter Jones, School of Dietetics and Human Nutrition, McGill University, 21,111 Lakeshore Road, Ste. Anne de Belle- vue, Que ´ bec, Canada H9X 3V9; Phone: 514-398-7547; Fax: 514-398-7739; E-mail: peter.jones@mcgill.ca. 385 Nutrition Reviews, Vol. 64, No. 9