Phytosterols and Cardiovascular Risk Evaluated against the Background of Phytosterolemia Cases-A German Expert Panel Statement

TY - JOUR

T1 - Phytosterols and Cardiovascular Risk Evaluated against the Background of Phytosterolemia Cases-A German Expert Panel Statement

AU - Windler, Eberhard

AU - Beil, Frank-Ulrich

AU - Berthold, Heiner K

AU - Gouni-Berthold, Ioanna

AU - Kassner, Ursula

AU - Klose, Gerald

AU - Lorkowski, Stefan

AU - März, Winfried

AU - Parhofer, Klaus G

AU - Plat, Jogchum

AU - Silbernagel, Günter

AU - Steinhagen-Thiessen, Elisabeth

AU - Weingärtner, Oliver

AU - Zyriax, Birgit-Christiane

AU - Lütjohann, Dieter

PY - 2023/2/6

Y1 - 2023/2/6

N2 - Phytosterols (PSs) have been proposed as dietary means to lower plasma LDL-C. However, concerns are raised that PSs may exert atherogenic effects, which would offset this benefit. Phytosterolemia was thought to mimic increased plasma PSs observed after the consumption of PS-enriched foods. This expert statement examines the possibility of specific atherogenicity of PSs based on sterol metabolism, experimental, animal, and human data. Observational studies show no evidence that plasma PS concentrations would be associated with an increased risk of atherosclerosis or cardiovascular (CV) events. Since variants of the ABCG5/8 transporter affect the absorption of cholesterol and non-cholesterol sterols, Mendelian randomization studies examining the effects of ABCG5/8 polymorphisms cannot support or refute the potential atherogenic effects of PSs due to pleiotropy. In homozygous patients with phytosterolemia, total PS concentrations are ~4000% higher than under physiological conditions. The prevalence of atherosclerosis in these individuals is variable and may mainly relate to concomitant elevated LDL-C. Consuming PS-enriched foods increases PS concentrations by ~35%. Hence, PSs, on a molar basis, would need to have 20-40 times higher atherogenicity than cholesterol to offset their cholesterol reduction benefit. Based on their LDL-C lowering and absence of adverse safety signals, PSs offer a dietary approach to cholesterol management. However, their clinical benefits have not been established in long-term CV endpoint studies.

AB - Phytosterols (PSs) have been proposed as dietary means to lower plasma LDL-C. However, concerns are raised that PSs may exert atherogenic effects, which would offset this benefit. Phytosterolemia was thought to mimic increased plasma PSs observed after the consumption of PS-enriched foods. This expert statement examines the possibility of specific atherogenicity of PSs based on sterol metabolism, experimental, animal, and human data. Observational studies show no evidence that plasma PS concentrations would be associated with an increased risk of atherosclerosis or cardiovascular (CV) events. Since variants of the ABCG5/8 transporter affect the absorption of cholesterol and non-cholesterol sterols, Mendelian randomization studies examining the effects of ABCG5/8 polymorphisms cannot support or refute the potential atherogenic effects of PSs due to pleiotropy. In homozygous patients with phytosterolemia, total PS concentrations are ~4000% higher than under physiological conditions. The prevalence of atherosclerosis in these individuals is variable and may mainly relate to concomitant elevated LDL-C. Consuming PS-enriched foods increases PS concentrations by ~35%. Hence, PSs, on a molar basis, would need to have 20-40 times higher atherogenicity than cholesterol to offset their cholesterol reduction benefit. Based on their LDL-C lowering and absence of adverse safety signals, PSs offer a dietary approach to cholesterol management. However, their clinical benefits have not been established in long-term CV endpoint studies.

KW - Animals

KW - Humans

KW - Hypercholesterolemia

KW - Cholesterol, LDL

KW - Cardiovascular Diseases/chemically induced

KW - Risk Factors

KW - Phytosterols/pharmacology

KW - Cholesterol

KW - Heart Disease Risk Factors

KW - Atherosclerosis/chemically induced

U2 - 10.3390/nu15040828

DO - 10.3390/nu15040828

M3 - SCORING: Journal article

C2 - 36839186

VL - 15

SP - 828

JO - NUTRIENTS

JF - NUTRIENTS

SN - 2072-6643

IS - 4

ER -