Vascular Effects of Diet Supplementation With Plant Sterols

Weingärtner, Oliver; Lütjohann, Dieter; Ji, Shengbo; Weisshoff, Nicole; List, Franka; Sudhop, Thomas; Bergmann, Klaus von; Gertz, Karen; König, J.; Schäfers, Hans‐Joachim; Endres, Matthias; Böhm, Michael; Laufs, Ulrich

doi:10.1016/j.jacc.2007.09.074

Cited by 176 publications

(153 citation statements)

References 25 publications

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“…5 Finally, deposits of plant sterols have been found in plaques and degenerated aortic valves of patients with atherosclerosis. 4,39 Our findings might have potential public health relevance with regard to the frequent use of phytosterol food supplements because a substantial number of individuals with certain genotypes may respond with relatively high phytosterol serum levels after intake of these additives. 3 In summary, to our knowledge, this genome-wide association study is the first to investigate genetic variability of serum phytosterol levels in the general population.…”

Section: Discussionmentioning

confidence: 87%

“…First, elevated phytosterol levels have been associated with CAD in previously published studies. 4,6,7,38 Second, patients with sitosterolemia, a rare autosomal disease caused by mutations in ABCG5 and ABCG8, display a severe accumulation of phytosterols in serum and tissues and subsequently develop premature atherosclerosis. 5 Finally, deposits of plant sterols have been found in plaques and degenerated aortic valves of patients with atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

“…1 A recent study found that dietary supplementation with phytosterols not only increases serum levels of the respective sterols, but also affects atherogenesis in mice and leads to increased tissue sterol concentrations in sclerotic aortic valves of humans. 4 Evidence for a proatherogenic role of phytosterols also is documented in patients with sitosterolemia, a rare autosomal disease characterized by massive accumulation of phytosterols in serum and tissues, who subsequently develop severe premature atherosclerosis. 5 Moreover, some but not all epidemiological studies found an association of elevated serum phytosterol levels with coronary artery disease (CAD).…”

Section: Clinical Perspective On P 339mentioning

confidence: 99%

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Genetic Regulation of Serum Phytosterol Levels and Risk of Coronary Artery Disease

Teupser¹,

Baber²,

Ceglarek³

et al. 2010

Circ Cardiovasc Genet

151

100

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Background-Phytosterols are plant-derived sterols that are taken up from food and can serve as biomarkers of cholesterol uptake. Serum levels are under tight genetic control. We used a genomic approach to study the molecular regulation of serum phytosterol levels and potential links to coronary artery disease (CAD). Methods and Results-A genome-wide association study for serum phytosterols (campesterol, sitosterol, brassicasterol) was conducted in a population-based sample from KORA (Cooperative Research in the Region of Augsburg) (nϭ1495) with subsequent replication in 2 additional samples (nϭ1157 and nϭ1760). Replicated single-nucleotide polymorphisms (SNPs) were tested for association with premature CAD in a metaanalysis of 11 different samples comprising 13 764 CAD cases and 13 630 healthy controls. Genetic variants in the ATP-binding hemitransporter ABCG8 and at the blood group ABO locus were significantly associated with serum phytosterols. Effects in ABCG8 were independently related to SNPs rs4245791 and rs41360247 (combined Pϭ1.6ϫ10 Ϫ50 and 6.2ϫ10 Ϫ25 , respectively; nϭ4412). Serum campesterol was elevated 12% for each rs4245791 T-allele. The same allele was associated with 40% decreased hepatic ABCG8 mRNA expression (Pϭ0.009). Effects at the ABO locus were related to SNP rs657152 (combined Pϭ9.4ϫ10 Ϫ13 ). Alleles of ABCG8 and ABO associated with elevated phytosterol levels displayed significant associations with increased CAD risk (rs4245791 odds ratio, 1.10; 95% CI, 1.06 to 1.14; Pϭ2.2ϫ10 Ϫ6 ; rs657152 odds ratio, 1.13; 95% CI, 1.07 to 1.19; Pϭ9.4ϫ10 Ϫ6 ), whereas alleles at ABCG8 associated with reduced phytosterol levels were associated with reduced CAD risk (rs41360247 odds ratio, 0.84; 95% CI, 0.78 to 0.91; Pϭ1.3ϫ10 Ϫ5 ). Conclusion-Common variants in ABCG8 and ABO are strongly associated with serum phytosterol levels and show concordant and previously unknown associations with CAD. (Circ Cardiovasc Genet. 2010;3:331-339.)

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Clinical Perspective On P 339mentioning

confidence: 99%

See 1 more Smart Citation

Genetic Regulation of Serum Phytosterol Levels and Risk of Coronary Artery Disease

Teupser¹,

Baber²,

Ceglarek³

et al. 2010

Circ Cardiovasc Genet

151

100

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“…An investigation from the Dallas Heart Study showed no relationship between plasma phytosterols and a surrogate marker for CHD, namely, coronary calcium scores measured by electron beam computed tomography ( 26 ). Miettinen et al ( 27 ) reported an association between raised plasma phytosterol levels and increased phytosterol content of surgically removed carotid plaques, while Weingärtner et al ( 28 ) showed that consumption of phytosterol-enriched margarine correlated with increased plasma concentrations and tissue deposi- An additional factor that infl uences plasma phytosterolto-cholesterol ratios is statin treatment ( 7,36 ), a reason why statin users were excluded from the analyses. Finally, the plasma sitosterol and campesterol ratios to cholesterol were in the same physiological range as reported in previous studies (9)(10)(11)(12)(13)(14)(15)30 ), strengthening the reliability of our data.…”

Section: Characteristics Of Chd Cases and Matched Controlsmentioning

confidence: 99%

Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort

Escurriol

Cofán

Moreno-Iribas

et al. 2010

Journal of Lipid Research

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This article is available online at http://www.jlr.org heart disease in the prospective Spanish EPIC cohort. J. Lipid Res . 2010. 51: 618-624. Supplementary key words plant sterols • sitosterol • campesterol • lathosterol • cholesterol • European Prospective Investigation intoCancer and Nutrition • nested case-control study • cardiometabolic risk • apolipoprotein E Dietary sterols consist of animal-derived cholesterol and plant-derived noncholesterol sterols or phytosterols. Phytosterols are important components of a vegetable-based diet and are particularly abundant in whole grains, nuts, seeds, and oils derived from them. The principal molecular forms are sitosterol and campesterol ( 1 ). These compounds are structurally related to cholesterol but have bulkier and more hydrophobic molecules, which confer them a higher affi nity for intestinal micelles than has cholesterol. Consequently, cholesterol is displaced from micelles, and the amount available for absorption is limited. The phytosterol content of usual diets is similar to that of cholesterol (150 to 450 mg/day), but their intestinal absorption is much less effi cient (see review in Ref.2 ). Because of low absorption and rapid biliary elimination, physiological plasma concentrations of phytosterols are in the order of 10 Ϫ 3 those of cholesterol. Their ratios to cholesterol are accepted as surrogate markers for the effi ciency of cholesterol absorption, while those of the Abstract Phytosterol intake with natural foods, a measure of healthy dietary choices, increases plasma levels, but increased plasma phytosterols are believed to be a coronary heart disease (CHD) risk factor. To address this paradox, we evaluated baseline risk factors, phytosterol intake, and plasma noncholesterol sterol levels in participants of a case control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort who developed CHD (n = 299) and matched controls (n = 584) who remained free of CHD after a 10 year follow-up. Sitosterol-to-cholesterol ratios increased across tertiles of phytosterol intake ( P = 0.026). HDL-cholesterol level increased, and adiposity measures, cholesterol/HDL ratios, and levels of glucose, triglycerides, and lathosterol, a cholesterol synthesis marker, decreased across plasma sitosterol tertiles ( P < 0.02; all). Compared with controls, cases had nonsignifi cantly lower median levels of phytosterol intake and plasma sitosterol. The multivariable-adjusted odds ratio for CHD across the lowest to highest plasma sitosterol tertile was 0.59 (95% confi dence interval, 0.36-0.97). Associations were weaker for plasma campesterol. The apolipoprotein E genotype was unrelated to CHD risk or plasma phytosterols. The data suggest that plasma sitosterol levels are associated with a lower CHD risk while being markers of a lower cardiometabolic risk in the EPIC-Spain cohort, a population with a high phytosterol intake. -Escurriol,

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“…Use of these sterols and stanols as cholesterollowering agents and as biomarkers of cardiovascular disease have been reviewed [103] [104]. Although ezetimibe and plant sterols reduced plasma cholesterol to a similar extent, however, a greater protective effect was shown by ezetimibe on atherosclerotic lesion area [105]. Some studies have raised concerns over the use of plant sterols that accumulate in vascular lesions with increasing supplementation [106].…”

Section: Pharmacological Targeting Of Intestinal Cholesterol Absorptionmentioning

confidence: 99%

Regulation of Intestinal Cholesterol Absorption: A Disease Perspective

Iqbal¹,

Qarni²,

Hawwari³

2017

ABC

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Hypercholesterolemia promotes atherosclerosis and precise regulation of cholesterol homeostasis is essential. Besides risk factor for cardiovascular disease, abnormalities in cholesterol metabolism have been associated with type 2 diabetes. Cholesterol homeostasis in the body is maintained by de novo synthesis. Furthermore, intestinal cholesterol absorption has recently been considered as an important control point in cholesterol homeostasis. Important insights have been gained into the mechanisms of transport of cholesterol from the intestinal lumen into the enterocytes. Several transporter proteins that appear to be key players in the control of the cholesterol absorption from the intestinal lumen have been identified. Here, we review intestinal cholesterol absorption and the mechanisms underlying alterations in cholesterol absorption under physiological conditions and in diseases such as diabetes mellitus.

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Vascular Effects of Diet Supplementation With Plant Sterols

Cited by 176 publications

References 25 publications

Genetic Regulation of Serum Phytosterol Levels and Risk of Coronary Artery Disease

Genetic Regulation of Serum Phytosterol Levels and Risk of Coronary Artery Disease

Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort

Regulation of Intestinal Cholesterol Absorption: A Disease Perspective

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