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Dyslipidemia
Published in Gia Merlo, Kathy Berra, Lifestyle Nursing, 2023
Susan Halli-Demeter, Lynne T. Braun
Plant stanols/sterols at 2 g/day can potentially inhibit cholesterol absorption in the intestine and reduce LDL-C by 8–10% (12% at 3 g/day) and triglycerides by 6–9% (Gylling et al., 2014; Trautwein et al., 2018). In a rare genetic disorder called sitosterolemia, plant sterols accumulate in the blood and tissues with decreased biliary excretion. Sitosterolemia has been associated with premature ASCVD in case reports and has led to the hypothesis that plant sterols can increase cardiovascular risk in non-sitosterolemia individuals (Köhler et al., 2017). There are no randomized controlled trials to support the clinical benefit of plant stanols/sterols and consideration should be given when advising these supplements to patients.
Nutrition and Nutritional Supplements in the Management of Dyslipidemia and Dyslipidemia-Induced Cardiovascular Disease
Published in Stephen T. Sinatra, Mark C. Houston, Nutritional and Integrative Strategies in Cardiovascular Medicine, 2022
The plant sterols can interfere with absorption of lipid-soluble compounds such as the fat-soluble vitamins and carotenoids (vitamins A D, E, K, and alpha carotene) [5]. Some studies have shown reduction in atherosclerosis progression, reduced carotid IMT, and decreased plaque progression, but the results have been conflicting [5]. There are no studies on CHD or other CVD outcomes. The recommended dose is about 2–2.5 g/day (average 2.15 g/day). Patients that have the rare homozygote mutations of sitosterolemia and abnormal ATP-binding cassette are hyper-absorbers of sitosterol (absorbing 15%–60% instead of the normal 5%) and will develop premature atherosclerosis. The patients can be identified with genetic testing and should avoid plant sterols.
The Role of Nutrition and Nutritional Supplements in the Treatment of Dyslipidemia
Published in Stephen T. Sinatra, Mark C. Houston, Nutritional and Integrative Strategies in Cardiovascular Medicine, 2015
The plant sterols, which are similar to cholesterol molecules, are naturally occurring sterols of plant origin that include B-sitosterol (the most abundant), campesterol, stigmasterol (4-desmethyl sterols of the cholestane series), and the stanols, which are saturated.5,54,76–78 The plant sterols are much better absorbed than the plant stanols. The daily intake of plant sterols in the United States is about 150–400 mg/day mostly from soybean oil, various nuts, and tall pine tree oil.54 These have a dose-dependent reduction in serum lipids.77 TC is decreased 8%, LDL is decreased 10% (range 6%–15%) with no change in TG and HDL on doses of 2–3 g/day in divided doses with meals.5,50,51,52 A recent meta-analysis of 84 trials showed that an average intake of 2.15 g/day reduced LDL by 8.8% with no improvement with higher doses.77 The mechanism of action is primarily to decrease the incorporation of dietary and biliary cholesterol into micelles due to lower micellar solubility of cholesterol, which reduces cholesterol absorption and increases bile acid secretion. In addition, there is an interaction with enterocyte ATP-binding cassette transport proteins (ABCG8 and ABCG5) that directs cholesterol back into the intestinal lumen.5,54,76 The only difference between cholesterol and sitosterol consists of an additional ethyl group at position C-24 in sitosterol, which is responsible for its poor absorption. The plant sterols have a higher affinity than cholesterol for the micelles. Patients that have the rare homozygote mutations of the ATP-binding cassette are hyperabsorbers of sitosterol (absorb 15%–60% instead of the normal 5%) and will develop premature atherosclerosis.54 This is a rare autosomal recessive disorder termed sitosterolemia. The plant sterols are also anti-inflammatory and decrease the levels of proinflammatory cytokines such as HS-CRP, IL-6, IL1b, TNF alpha, PLA 2, and fibrinogen, but these effects vary among the various phytosterols.78,79 Other potential mechanisms include modulation of signaling pathways, activation of cellular stress responses, growth arrest, reduction of APO-B48 secretion from intestinal and hepatic cells, reduction of cholesterol synthesis with suppression of HMG COA reductase and CYP7A1, interference with sterol regulatory element-binding protein (SREBP), and promotion of reverse cholesterol transport via ATP-binding cassette transporter (ABCA1) and ATP-binding cassette sub-family G member 1 (ABCG1).79 The biological activity of phytosterols is both cell-type and sterol specific.79
Beyond the Usual Suspects: Expanding on Mutations and Detection for Familial Hypercholesterolemia
Published in Expert Review of Molecular Diagnostics, 2021
Shirin Ibrahim, Joep C. Defesche, John J.P. Kastelein
Variants in the genes encoding adenosine triphosphate-binding cassette transporters G5 and G8 (ABCG5 and ABCG8) have also been shown to affect LDL-C levels. ABCG5 and ABCG8 form a heterodimer that is responsible for the transmembrane transport of sterols, in particular, plant sterols [41]. In the intestine, the complex is involved in the transport of sterols from the enterocyte into the intestinal lumen, whereas in the liver it promotes the transport of sterols into the bile. Mutations in ABCG5 and ABCG8 can cause sitosterolemia, an autosomal recessive disorder whereby plant sterols accumulate in blood and tissues. Studies have shown an association between hypercholesterolemia and sitosterolemia in the general population [41]. With the expansion of NGS panels in FH patients, variants in ABCG5 and ABCG8 have been frequently discovered. Patients with sitosterolemia can present with xanthomas and premature CAD, characteristics that closely mimic the clinical FH phenotype [56]. Studies by Tada et al. and Nomura et al. suggest that heterozygous pathogenic variants in the ABCG5/ABCG8 can worsen the clinical expression of FH in terms of additional elevation of LDL-C levels and cardiovascular risk [57,58]. Recently, we have also addressed this issue and could not confirm these findings [41].
ABCG5 and ABCG8 gene variations associated with sitosterolemia and platelet dysfunction
Published in Platelets, 2021
Jose María Bastida, Rocío Benito, José Ramón González-Porras, José Rivera
Caucasians usually carry variants in ABCG8, whereas molecular changes in ABCG5 are more commonly found in Asian and Indian population. Compound heterozygosity conditions (65%) are more prevalent than homozygosity, because consanguinity has been noted only in 35% of the cases [1,8,12]. Some heterozygous subjects exhibit higher than normal PS levels, but these levels still substantially lower than those in homozygous individuals [1,13]. Until now, there is no clear evidence about genotype-phenotype correlation in sitosterolemia. However, most genetic variants in ABCG5 and ABCG8 causing sitosterolemia affect residues that localize within the structural motifs E-helix, NBDs, TMD, and apex of TMHs. In particular, three missense variants, R419P and R419 H in ABCG5 and G574 R in ABCG8, are located near the apices of TMH2 and TMH5, respectively, and both residues are involved in contacts with the ECDs. These mutations would be predicted to interfere with the native positions of the ECD helices, suggesting their importance for sterol exit from the TMDs [5,29].
Alterations of drug-metabolizing enzymes and transporters under diabetic conditions: what is the potential clinical significance?
Published in Drug Metabolism Reviews, 2018
Feng Chen, De-Yi Li, Bo Zhang, Jie-Yu Sun, Fang Sun, Xing Ji, Jin-Chun Qiu, Robert B. Parker, S. Casey Laizure, Jing Xu
Located on the apical membrane of enterocytes and hepatocytes, ABCG5 and ABCG8 limit intestinal absorption and facilitate biliary secretion of cholesterol and phytosterols. This heterodimer transporter is positively regulated by Liver X receptor. Mutated ABCG5/G8 genes could cause sitosterolemia (abnormal accumulation of cholesterol and plant sterols in the circulation), thereby leading to premature cardiovascular disease (Yu et al. 2014). The hepatic mRNA expression of ABCG5/G8 was decreased in SI rats with declined cholesterol output (Bloks et al. 2004), but increased in SI mice (Aleksunes et al. 2013). Both mRNA and protein expression of ABCG5/G8 in jejunum of the SI rats were found to be suppressed, whist campesterol and β-sitosterol concentrations in rat plasma were decreased (Bloks et al. 2004).