-
Critical Reviews in Food Science and... 2022Phytosterols have been shown to lower cholesterol levels and to have antioxidant, anti-inflammatory and other biological activities. However, the high melting point and... (Review)
Review
Phytosterols have been shown to lower cholesterol levels and to have antioxidant, anti-inflammatory and other biological activities. However, the high melting point and poor solubility limit their bioavailability and practical application. It is advantageous to modify phytosterols chemically and physically. This article reviews and discusses the chemical and physical modifications of phytosterols, as well as their effects on the bioavailability and possible toxicity in vivo. The current research on chemical modifications is mainly focused on esterification to increase the oil solubility and water solubility. For physical modifications (mainly microencapsulation), there are biopolymer-based, surfactant-based and lipid-based nanocarriers. Both chemical and physical modifications of phytosterols can effectively increase the absorption and bioavailability. The safety of modified phytosterols is also an important issue. Phytosterol esters are generally considered to be safe. However, phytosterol oxides, which may be produced during the synthesis of phytosterol esters, have shown toxicity in animal models. The toxicity of nanocarriers also needs further studies.
Topics: Animals; Biological Availability; Esterification; Phytosterols; Solubility; Surface-Active Agents
PubMed: 33612007
DOI: 10.1080/10408398.2021.1888692 -
Current Opinion in Endocrinology,... Apr 2023The aim of this study was to assess the potential value of the measurement of plasma xenosterols (or phytosterols) concentrations in clinical practice. (Review)
Review
PURPOSE OF REVIEW
The aim of this study was to assess the potential value of the measurement of plasma xenosterols (or phytosterols) concentrations in clinical practice.
RECENT FINDINGS
Recent genetic studies suggest that individuals with elevated plasma phytosterol concentrations due to monogenic and polygenic variants are at an increased risk of coronary artery disease. This supports early observations that elevated plasma phytosterol concentrations are per se atherogenic.
SUMMARY
Measurement of plasma phytosterols can identify individuals with xenosterolemia (or phytosterolemia). This may be clinically useful in four ways: Establishing a diagnosis and informing management of patients with homozygous phytosterolemia; Providing a comprehensive differential diagnosis for familial hypercholesterolemia; Providing an index of cholesterol absorption that may inform personalized pharmacotherapy; and Informing more precise assessment of risk of cardiovascular disease.
Topics: Humans; Hypercholesterolemia; Lipid Metabolism, Inborn Errors; Phytosterols; Intestinal Diseases
PubMed: 36597814
DOI: 10.1097/MED.0000000000000795 -
Phytotherapy Research : PTR Oct 2022α-Spinasterol is a phytosterol found in various edible and non-edible plant sources. The edible plant materials containing α-spinasterol include spinach leaves,... (Review)
Review
α-Spinasterol is a phytosterol found in various edible and non-edible plant sources. The edible plant materials containing α-spinasterol include spinach leaves, cucumber fruits, seeds of pumpkin and watermelon, argan seed oil, cactus pear seed oil and Amaranthus sp. It is a bioavailable nutraceutical, and it can cross the blood-brain barrier. It possesses several important pharmacological properties such as anti-diabetes mellitus, antiinflammation, hypolipidemic, antiulcer, neuroprotection, anti-pain and antitumour activities. For this review, literature search was made focusing on the pharmacological properties of α-spinasterol using PubMed and Google Scholar data bases. Recent studies show the promising antidiabetic properties of α-spinasterol. Its anti-diabetic mechanisms include enhancement of insulin secretion, reduction in insulin resistance, anti-diabetic nephropathy, increase in glucose uptake in muscle cells and inhibition of glucose absorption from intestine. Besides, it is a safe antiinflammatory agent, and its antiinflammatory mechanisms include inhibition of cyclooxygenases, antagonism of TRPV1 receptor and attenuation of proinflammatory cytokines and mediators. It is a promising and safe nutraceutical molecule for human health care. Food supplements, value-added products and nutraceutical formulations can be developed with α-spinasterol for the management of diabetes, chronic inflammatory diseases and improving general health. This review provides all scattered pharmacological studies on α-spinasterol in one place and highlights its immense value for human health care.
Topics: Anti-Inflammatory Agents; Cytokines; Dietary Supplements; Glucose; Humans; Hypoglycemic Agents; Phytosterols; Plant Oils; Prostaglandin-Endoperoxide Synthases; Stigmasterol
PubMed: 35802356
DOI: 10.1002/ptr.7560 -
Journal of Agricultural and Food... Mar 2022Phytosterols are natural plant-based bioactive compounds that can lower blood cholesterol levels and help prevent cardiovascular diseases. Consequently, they are being... (Review)
Review
Phytosterols are natural plant-based bioactive compounds that can lower blood cholesterol levels and help prevent cardiovascular diseases. Consequently, they are being utilized in functional foods, supplements, and pharmaceutical products designed to improve human health. This paper summarizes different approaches to isolate, purify, and characterize phytosterols. It also discusses the hypolipidemic mechanisms of phytosterols and their impact on cholesterol transportation. Phytosterols have a low water-solubility, poor chemical stability, and limited bioavailability, which limits their utilization and efficacy in functional foods. Strategies are therefore being developed to overcome these shortcomings. Colloidal delivery systems, such as emulsions, oleogels, liposomes, and nanoparticles, have been shown to be effective at improving the water-dispersibility, stability, and bioavailability of phytosterols. These delivery systems can be used to incorporate phytosterols into a broader range of cholesterol-lowering functional foods and beverages. We also discuses several issues that need to be addressed before these phytosterol delivery systems can find widespread commercial utilization.
Topics: Cardiovascular Diseases; Cholesterol; Dietary Supplements; Emulsions; Humans; Phytosterols
PubMed: 35170307
DOI: 10.1021/acs.jafc.1c07390 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Mar 2023Steroids are a class of medicines with important physiological and pharmacological effects. In pharmaceutical industry, steroidal intermediates are mainly prepared... (Review)
Review
Steroids are a class of medicines with important physiological and pharmacological effects. In pharmaceutical industry, steroidal intermediates are mainly prepared through transformation, and then modified chemically or enzymatically into advanced steroidal compounds. Compared with the "diosgenin-dienolone" route, transformation has the advantages of abundant raw materials, cost-effective, short reaction route, high yield and environmental friendliness. Based on genomics and metabolomics, the key enzymes in the phytosterol degradation pathway of and their catalytic mechanisms are further revealed, which makes it possible for to be used as chassis cells. This review summarizes the progress in the discovery of steroid-converting enzymes from different species, the modification of genes and the overexpression of heterologous genes, and the optimization and modification of as chassis cells.
Topics: Mycobacterium; Steroids; Phytosterols; Genomics
PubMed: 36994571
DOI: 10.13345/j.cjb.220548 -
Phytotherapy Research : PTR Feb 2024Despite multiple investigations assessing the impact of phytosterol supplementation on serum lipid levels, there is still a great deal of debate regarding the benefits... (Meta-Analysis)
Meta-Analysis Review
Despite multiple investigations assessing the impact of phytosterol supplementation on serum lipid levels, there is still a great deal of debate regarding the benefits of this intervention in the management of dyslipidemia. Therefore, we aimed at clarifying this dilemma by conducting the present umbrella review of interventional meta-analyses. Scopus, PubMed, Web of Science, and EMBASE were used to search for pertinent publications on the effect of phytosterol supplementation on the lipid profile in humans up to June 2023. To compute the overall effect size (ES) and confidence intervals (CI), the random-effects model was used. The I statistic and Cochrane's Q-test were applied to estimate the heterogeneity among the studies. Seventeen meta-analyses with 23 study arms were included in the umbrella meta-analysis. Data pooled from the 23 eligible arms revealed that phytosterol supplementation reduces low-density lipoprotein cholesterol (LDL-C) (ES = -11.47 mg/dL; 95% CI: -12.76, -10.17, p < 0.001), total cholesterol (TC) (ES = -13.02 mg/dL; 95% CI: -15.68, -10.37, p < 0.001), and triglyceride (TG) (ES = -3.77 mg/dL; 95% CI: -6.04, -1.51, p = 0.001). Subgroup analyses showed that phytosterol administration with dosage ≥2 g/day and duration over 8 weeks and in hypercholesterolemic subjects was more likely to decrease LDL-C, TC, and TG. Phytosterol administration did not significantly modify HDL-C (ES = 0.18 mg/dL; 95% CI: -0.13, -0.51, p = 258) levels when compared to controls. The present umbrella meta-analysis confirms that phytosterol administration significantly reduces LDL-C, TC, and TG, with a greater effect with doses of ≥2 g/day and treatment duration >8 weeks, suggesting its possible application as a complementary therapy for cardiovascular risk reduction. Further studies are needed to determine the efficacy of phytosterols in patients with specific health conditions, as well as to ascertain the adverse effects, the maximum tolerable dose, and the maximum recommended duration of phytosterol administration.
Topics: Humans; Phytosterols; Cholesterol, LDL; Cholesterol, HDL; Triglycerides; Dietary Supplements
PubMed: 37905579
DOI: 10.1002/ptr.8052 -
Diabetes & Metabolic Syndrome 2020Several commercially available phytosterol supplements are promoted for their cholesterol-lowering effects. However, limited information is available about their...
BACKGROUND AND AIMS
Several commercially available phytosterol supplements are promoted for their cholesterol-lowering effects. However, limited information is available about their potential anti-hyperglycaemic effects. This study aimed to evaluate the dipeptidyl peptidase-4 (DPP-4) inhibitory effects of phytosterol supplements in silico and in vitro to determine their potential for anti-diabetic activity.
METHODS
Docking studies were carried out in silico to evaluate the potential for interactions between three major phytosterol compounds (stigmasterol, β-sitosterol, campesterol) and the DPP-4 enzyme, the enzyme that is inhibited by the anti-diabetic gliptins. Gas chromatography-tandem mass spectrometry (GC-MS/MS) was used to analyse three different supplements for phytosterol content. DPP-4 inhibitory activity was tested in vitro for these phytosterol supplements and two major phytosterol standards.
RESULTS
In silico calculations predicted free binding energies for DPP-4 with the phytosterols to be: stigmasterol -8.78 kcal/mol; β-sitosterol -8.70 kcal/mol; campesterol -8.40 kcal/mol. These binding energies indicated a potential for significant DPP-4 inhibition. However, these results were not supported by the in vitro studies. Stigmasterol and β-sitosterol had an IC > 50 mg/ml (maximum tested concentration) and the Thompson's Cholesterol Manager® and Mega Strength Beta Sitosterol® supplements gave an IC > 100 mg/ml (maximum tested concentration). Blackmores Cholesterol Health® gave an IC value of 40 mg/ml which was attributed to β-carotene content.
CONCLUSIONS
Phytosterol supplements do not appear to offer any anti-diabetic activity potential via pathways that involve the inhibition of DPP-4.
Topics: Dietary Supplements; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Humans; In Vitro Techniques; Molecular Docking Simulation; Phytosterols
PubMed: 32771921
DOI: 10.1016/j.dsx.2020.07.019 -
Current Medicinal Chemistry 2019The central nervous system (CNS) is the most cholesterol-rich organ in mammals. Cholesterol homeostasis is essential for proper brain functioning and dysregulation of... (Review)
Review
The central nervous system (CNS) is the most cholesterol-rich organ in mammals. Cholesterol homeostasis is essential for proper brain functioning and dysregulation of cholesterol metabolism can lead to neurological problems. Multiple sclerosis (MS) and Alzheimer's disease (AD) are examples of neurological diseases that are characterized by a disturbed cholesterol metabolism. Phytosterols (PS) are plant-derived components that structurally and functionally resemble cholesterol. PS are known for their cholesterol-lowering properties. Due to their ability to reach the brain, researchers have started to investigate the physiological role of PS in the CNS. In this review, the metabolism and function of PS in the diseased and healthy CNS are discussed.
Topics: Animals; Central Nervous System; Central Nervous System Diseases; Humans; Molecular Structure; Phytosterols
PubMed: 29984647
DOI: 10.2174/0929867325666180706113844 -
Methods in Molecular Biology (Clifton,... 2023The chapter describes the bioconversion of phytosterols into androstenedione (AD) by Mycolicibacterium spp. in shake flasks and fermenters, as well as LC-MS-based...
The chapter describes the bioconversion of phytosterols into androstenedione (AD) by Mycolicibacterium spp. in shake flasks and fermenters, as well as LC-MS-based methods for analysis of phytosterols and steroid products. Phytosterols are derived as by-products of vegetable oil refining and manufacture of wood pulp. They contain the same four-ring nucleus as steroids and may be converted to high-value steroids by removing the sidechain at C17 and minor changes at other sites in the ring structure. Many bacteria, including Mycolicibacterium spp., can degrade phytosterols. Mutants of Mycolicibacterium spp. unable of ring cleavage can, when growing on phytosterols, accumulate the steroid intermediates androstenedione (AD) and androstadienedione (ADD). The practical challenge with microbial conversion of phytosterols to steroids is that both the substrate and the product are virtually insoluble in water. In addition, some steroids, notably ADD, may be toxic for the cells. Two main strategies have been employed to overcome this challenge: the use of two-phase systems and the addition of chemically modified cyclodextrins. The latter method is used here. Defined cultivation and bioconversion media for both shake flask and fermenter are given, as well as hints how to minimize the practical problems due to the water-insoluble phytosterol. Sampling, sample extraction, and quantification of substrates and products using LC-MS analysis are described.
Topics: Humans; Androstenedione; Bioreactors; Cell Nucleus; Phytosterols; Tremor; Water
PubMed: 37642849
DOI: 10.1007/978-1-0716-3385-4_15 -
Journal of Clinical Lipidology 2022Sitosterolemia is a rare autosomal recessive disease characterized by phytosterol accumulation in the blood and tissues. However, the detailed clinical and genetic...
BACKGROUND
Sitosterolemia is a rare autosomal recessive disease characterized by phytosterol accumulation in the blood and tissues. However, the detailed clinical and genetic spectra are lacking.
OBJECTIVE
To describe and compare the clinical, biochemical, genetic, therapeutic, and follow-up characteristics of 55 pediatric and five adult sitosterolemia patients.
METHODS
Clinical, genetic and therapeutic data from 60 patients at Xinhua Hospital from January 2016 to June 2021 were retrospectively collected.
RESULTS
Pediatric patients' manifestations included xanthomas(93%), hematological disorders(30%), arthralgia(24%), splenomegaly(11%), atherosclerosis(10%). Adult patients had symptoms such as atherosclerosis(5/5), xanthomas(4/5), hematological disorders(3/5), arthralgia(3/5), splenomegaly(3/5). Elevated total cholesterol(TC) and low-density lipoprotein cholesterol(LDL-C) were observed in 96% patients (pediatric 98%, adult 3/4), and phytosterol levels in 100% patients. The age of onset was also negatively correlated with blood TC (P < 0.0001, r = -0.5548) and LDL-C (P = 0.0001, r = -0.4859) levels. Targeted treatments resulted in symptomatic remission(pediatric 96%, adult 4/5), and significantly decreased lipid and phytosterol levels(all P<0.05). In the dietary-therapy cohort(n=34), blood lipid levels decreased(all P<0.05). In the 13 pediatric patients from the dietary-therapy cohort who switched from dietary to combination therapy with ezetimibe, dietary therapy decreased TC and LDL-C levels by 54% and 52%, and ezetimibe further decreased them by 18% and 20%, respectively. Further, we identified 15 novel ABCG5/ABCG8 variants.
CONCLUSIONS
This study expands the clinical and genetic spectra of sitosterolemia. The low-phytosterol diet is the cornerstone of sitosterolemia treatment. Ezetimibe can further decrease blood lipid levels and increase daily dietary phytosterol tolerance.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; Adult; Arthralgia; Atherosclerosis; Child; Cholesterol, LDL; Ezetimibe; Genetic Profile; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Phytosterols; Retrospective Studies; Splenomegaly; Xanthomatosis
PubMed: 34969652
DOI: 10.1016/j.jacl.2021.11.015