Compendium of the most significant studies with reference to properties, intake, effects.

Rondanelli M, Giacosa A, Morazzoni P, Guido D, Grassi M, Morandi G, Bologna C, Riva A, Allegrini P, Perna S. MediterrAsian Diet Products That Could Raise HDL-Cholesterol: A Systematic Review. Biomed Res Int. 2016;2016:2025687. doi: 10.1155/2016/2025687. 

Abstract Background. High HDL-cholesterol (HDL-C) values are negatively correlated with cardiovascular diseases. This review analyses the effect of the supplementation with various Mediterranean diet products (artichoke, bergamot, and olive oil) and Asian diet products (red yeast rice) on the HDL-C value in dyslipidemic subjects. Methods. A systematic review has been done involving all the English written studies published from the 1st of January 1958 to the 31st of March 2016. Results. The results of this systematic review indicate that the dietary supplementation with red yeast rice, bergamot, artichoke, and virgin olive oil has promising effects on the increase of HDL-C serum levels. The artichoke leaf extract and virgin olive oil appear to be particularly interesting, while bergamot extract needs further research and the effect of red yeast rice seems to be limited to patients with previous myocardial infarction. Conclusions. Various MediterrAsian diet products or natural extracts may represent a potential intervention treatment to raise HDL-C in dyslipidemic subjects.

Willett WC, Sacks F, Trichopoulou A, Drescher G, Ferro-Luzzi A, Helsing E, Trichopoulos D. Mediterranean diet pyramid: a cultural model for healthy eating. Am J Clin Nutr. 1995 Jun;61(6 Suppl):1402S-1406S. doi: 10.1093/ajcn/61.6.1402S. 

Abstract We present a food pyramid that reflects Mediterranean dietary traditions, which historically have been associated with good health. This Mediterranean diet pyramid is based on food patterns typical of Crete, much of the rest of Greece, and southern Italy in the early 1960s, where adult life expectancy was among the highest in the world and rates of coronary heart disease, certain cancers, and other diet-related chronic diseases were among the lowest. Work in the field or kitchen resulted in a lifestyle that included regular physical activity and was associated with low rates of obesity. The diet is characterized by abundant plant foods (fruit, vegetables, breads, other forms of cereals, potatoes, beans, nuts, and seeds), fresh fruit as the typical daily dessert, olive oil as the principal source of fat, dairy products (principally cheese and yogurt), and fish and poultry consumed in low to moderate amounts, zero to four eggs consumed weekly, red meat consumed in low amounts, and wine consumed in low to moderate amounts, normally with meals. This diet is low in saturated fat (< or = 7-8% of energy), with total fat ranging from < 25% to > 35% of energy throughout the region. The pyramid describes a dietary pattern that is attractive for its famous palatability as well as for its health benefits.

Schade DS, Shey L, Eaton RP. Cholesterol Review: A Metabolically Important Molecule. Endocr Pract. 2020 Dec;26(12):1514-1523. doi: 10.4158/EP-2020-0347. 

Abstract Objective: Cholesterol is an important molecule in humans and both its excess and its deficiency cause disease. Most clinicians appreciate its role in stabilizing cellular plasma membranes but are unaware of its myriad other functions. Methods: This review highlights cholesterol's newly recognized important roles in human physiology and pathophysiology. Results: The basis for cholesterol's ubiquitous presence in eukaryote organisms is its three part structure involving hydrophilic, hydrophobic, and rigid domains. This structure permits cholesterol to regulate multiple cellular processes ranging from membrane fluidity and permeability to gene transcription. Cholesterol not only serves as a molecule of regulation itself, but also forms the backbone of all steroid hormones and vitamin D analogs. Cholesterol is responsible for growth and development throughout life and may be useful as an anticancer facilitator. Because humans have a limited ability to catabolize cholesterol, it readily accumulates in the body when an excess from the diet or a genetic abnormality occurs. This accumulation results in the foremost cause of death and disease (atherosclerosis) in the Western world. Identification of cholesterol's disease-producing capabilities dates back 5,000 years to the Tyrolean iceman and more recently to ancient mummies from many cultures throughout the world. In contrast, a deficiency of cholesterol in the circulation may result in an inability to distribute vitamins K and E to vital organs with serious consequences. Conclusion: Understanding the benefits and hazards of cholesterol in the clinical setting will improve the endocrinologist's ability to control diseases associated with this unique molecule.

Spann NJ, Glass CK. Sterols and oxysterols in immune cell function. Nat Immunol. 2013 Sep;14(9):893-900. doi: 10.1038/ni.2681.

Abstract Intermediates in the cholesterol-biosynthetic pathway and oxysterol derivatives of cholesterol regulate diverse cellular processes. Recent studies have expanded the appreciation of their roles in controlling the functions of cells of the innate and adaptive immune systems. Here we review recent literature reporting on the biological functions of sterol intermediates and oxysterols, acting through transcription factors such as the liver X receptors (LXRs), sterol regulatory element-binding proteins (SREBPs) and the G protein-coupled receptor EBI2, in regulating the differentiation and population expansion of cells of the innate and adaptive immune systems, their responses to inflammatory mediators, their effects on the phagocytic functions of macrophages and their effects on antiviral activities and the migration of immune cells. Such findings have raised many new questions about the production of endogenous bioactive sterols and oxysterols and their mechanisms of action in the immune system.

Zeljković A, Ardalić D, Vekić J, Antonić T, Vladimirov S, Rizzo M, Gojković T, Ivanišević J, Mihajlović M, Vujčić S, Cabunac P, Spasojević-Kalimanovska V, Miković Ž, Stefanović A. Effects of Gestational Diabetes Mellitus on Cholesterol Metabolism in Women with High-Risk Pregnancies: Possible Implications for Neonatal Outcome. Metabolites. 2022 Oct 11;12(10):959. doi: 10.3390/metabo12100959.

Abstract Metabolic disorders in pregnancy, particularly gestational diabetes mellitus (GDM), are associated with an increased risk for adverse pregnancy outcome and long-term cardiometabolic health of mother and child. This study analyzed changes of serum cholesterol synthesis and absorption markers during the course of high-risk pregnancies, with respect to the development of GDM. Possible associations of maternal lipid biomarkers with neonatal characteristics were also investigated. The study included 63 women with high risk for development of pregnancy complications. Size and proportions of small low-density (LDL) and high-density lipoprotein (HDL) particles were assessed across trimesters (T1-T3), as well as concentrations of cholesterol synthesis (lathosterol, desmosterol) and absorption markers (campesterol, β-sitosterol). During the study, 15 women developed GDM, while 48 had no complications (non-GDM). As compared to the non-GDM group, women with GDM had significantly higher triglycerides in each trimester, while having a lower HDL-C level in T3. In addition, they had significantly lower levels of β-sitosterol in T3 (p < 0.05). Cholesterol synthesis markers increased across trimesters in both groups. A decrease in serum β-sitosterol levels during the course of pregnancies affected by GDM was observed. The prevalence of small-sized HDL decreased in non-GDM, while in the GDM group remained unchanged across trimesters. Newborn's size in the non-GDM group was significantly higher (p < 0.01) and inversely associated with proportions of both small, dense LDL and HDL particles (p < 0.05) in maternal plasma in T1. In conclusion, high-risk pregnancies affected by GDM are characterized by altered cholesterol absorption and HDL maturation. Advanced lipid testing may indicate disturbed lipid homeostasis in GDM

Yanagisawa R, He C, Asai A, Hellwig M, Henle T, Toda M. The Impacts of Cholesterol, Oxysterols, and Cholesterol Lowering Dietary Compounds on the Immune System. Int J Mol Sci. 2022 Oct 13;23(20):12236. doi: 10.3390/ijms232012236.

Abstract Cholesterol and its oxidized forms, oxysterols, are ingested from foods and are synthesized de novo. Cholesterol and oxysterols influence molecular and cellular events and subsequent biological responses of immune cells. The amount of dietary cholesterol influence on the levels of LDL cholesterol and blood oxysterols plays a significant role in the induction of pro-inflammatory state in immune cells, leading to inflammatory disorders, including cardiovascular disease. Cholesterol and oxysterols synthesized de novo in immune cells and stroma cells are involved in immune homeostasis, which may also be influenced by an excess intake of dietary cholesterol. Dietary compounds such as β-glucan, plant sterols/stanols, omega-3 lipids, polyphenols, and soy proteins, could lower blood cholesterol levels by interfering with cholesterol absorption and metabolism. Such dietary compounds also have potential to exert immune modulation through diverse mechanisms. This review addresses current knowledge about the impact of dietary-derived and de novo synthesized cholesterol and oxysterols on the immune system. Possible immunomodulatory mechanisms elicited by cholesterol-lowering dietary compounds are also discussed.

Gimpl G, Gehrig-Burger K. Cholesterol reporter molecules. Biosci Rep. 2007 Dec;27(6):335-58. doi: 10.1007/s10540-007-9060-1.

Abstract Cholesterol is a major constituent of the membranes in most eukaryotic cells where it fulfills multiple functions. Cholesterol regulates the physical state of the phospholipid bilayer, affects the activity of several membrane proteins, and is the precursor for steroid hormones and bile acids. Cholesterol plays a crucial role in the formation of membrane microdomains such as "lipid rafts" and caveolae. However, our current understanding on the membrane organization, intracellular distribution and trafficking of cholesterol is rather poor. This is mainly due to inherent difficulties to label and track this small lipid. In this review, we describe different approaches to detect cholesterol in vitro and in vivo. Cholesterol reporter molecules can be classified in two groups: cholesterol binding molecules and cholesterol analogues. The enzyme cholesterol oxidase is used for the determination of cholesterol in serum and food. Susceptibility to cholesterol oxidase can provide information about localization, transfer kinetics, or transbilayer distribution of cholesterol in membranes and cells. The polyene filipin forms a fluorescent complex with cholesterol and is commonly used to visualize the cellular distribution of free cholesterol. Perfringolysin O, a cholesterol binding cytolysin, selectively recognizes cholesterol-rich structures. Photoreactive cholesterol probes are appropriate tools to analyze or to identify cholesterol binding proteins. Among the fluorescent cholesterol analogues one can distinguish probes with intrinsic fluorescence (e.g., dehydroergosterol) from those possessing an attached fluorophore group. We summarize and critically discuss the features of the different cholesterol reporter molecules with a special focus on recent imaging approaches.

Cortes VA, Busso D, Maiz A, Arteaga A, Nervi F, Rigotti A. Physiological and pathological implications of cholesterol. Front Biosci (Landmark Ed). 2014 Jan 1;19(3):416-28. doi: 10.2741/4216. 

Abstract Cholesterol has evolved to fulfill sophisticated biophysical, cell signaling and endocrine requirements of animal systems. At a cellular level, cholesterol is found in membranes, where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signaling functions. At an organismal level, cholesterol is the precursor for all steroid hormones, including gluco- and mineralo-corticoids, sex hormones and vitamin D, all of which regulate carbohydrate, sodium, reproductive and bone homeostasis, respectively. This sterol is also the precursor for bile acids, which are important for intestinal absorption of dietary lipids as well as energy and glucose metabolic regulation. Importantly, complex mechanisms maintain cholesterol within physiological ranges and the disregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these diseases has been demonstrated by diverse genetic and pharmacologic animal models that are commented in this review.

Poznyak AV, Litvinova L, Poggio P, Orekhov AN, Melnichenko AA. Familial Hypercholesterolaemia as a Predisposing Factor for Atherosclerosis. Biomedicines. 2022 Oct 20;10(10):2639. doi: 10.3390/biomedicines10102639. 

Abstract Lipid metabolism alterations are an important component of the pathogenesis of atherosclerosis. However, it is now clear that the atherogenesis process involves more than one mechanism, and more than one condition can predispose this condition. Multiple risk factors contribute to the atherosclerosis initiation and define its course. Familial hypercholesterolaemia is a disorder of lipid metabolism that often leads to atherosclerosis development. As is clear from the disease name, the hallmark is the increased levels of low-density lipoprotein cholesterol (LDL-C) in blood. This creates favourable conditions for atherogenesis. In this review, we briefly described the familial hypercholesterolaemia and summarized data on the relationship between familial hypercholesterolaemia and atherosclerosis.

Koide Y, Miyoshi T, Nishihara T, Nakashima M, Ichikawa K, Miki T, Osawa K, Ito H. The Association of Triglyceride to High-Density Lipoprotein Cholesterol Ratio with High-Risk Coronary Plaque Characteristics Determined by CT Angiography and Its Risk of Coronary Heart Disease. J Cardiovasc Dev Dis. 2022 Sep 28;9(10):329. doi: 10.3390/jcdd9100329.

Abstract The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio is an independent risk index for cardiovascular events. This study aimed to evaluate the association between TG/HDL-C ratio and coronary plaque characteristics as seen on coronary computed tomography angiography (CCTA) and the corresponding increase in the likelihood of cardiovascular events. A total of 935 patients who underwent CCTA for suspected coronary artery disease (CAD) were included. High-risk plaques (HRP) were defined based on three characteristics: positive remodeling, low-density plaques, and spotty calcification. Significant stenosis was defined as luminal narrowing of &gt;70%. Patients with a higher TG/HDL-C ratio showed significantly greater prevalence of HRP and significant stenosis than patients with low TG/HDL-C ratios (p &lt; 0.01). Multivariate logistic analysis demonstrated that the TG/HDL-C ratio was significantly associated with the presence of HRP (p &lt; 0.01) but not with significant coronary stenosis (p = 0.24). During the median follow-up period of 4.1 years, 26 cardiovascular events including cardiovascular death and acute coronary syndrome occurred. The highest TG/HDL-C tertile was associated with cardiovascular events, with the lowest TG/HDL-C tertile as the reference (hazard ratio, 3.75; 95% confidence interval, 1.04-13.50). A high TG/HDL-C ratio is associated with the presence of CCTA-verified HRP, which can lead to cardiovascular events in patients with suspected CAD.

Vyletelová V, Nováková M, Pašková Ľ. Alterations of HDL's to piHDL's Proteome in Patients with Chronic Inflammatory Diseases, and HDL-Targeted Therapies. Pharmaceuticals (Basel). 2022 Oct 18;15(10):1278. doi: 10.3390/ph15101278.

Abstract Chronic inflammatory diseases, such as rheumatoid arthritis, steatohepatitis, periodontitis, chronic kidney disease, and others are associated with an increased risk of atherosclerotic cardiovascular disease, which persists even after accounting for traditional cardiac risk factors. The common factor linking these diseases to accelerated atherosclerosis is chronic systemic low-grade inflammation triggering changes in lipoprotein structure and metabolism. HDL, an independent marker of cardiovascular risk, is a lipoprotein particle with numerous important anti-atherogenic properties. Besides the essential role in reverse cholesterol transport, HDL possesses antioxidative, anti-inflammatory, antiapoptotic, and antithrombotic properties. Inflammation and inflammation-associated pathologies can cause modifications in HDL's proteome and lipidome, transforming HDL from atheroprotective into a pro-atherosclerotic lipoprotein. Therefore, a simple increase in HDL concentration in patients with inflammatory diseases has not led to the desired anti-atherogenic outcome. In this review, the functions of individual protein components of HDL, rendering them either anti-inflammatory or pro-inflammatory are described in detail. Alterations of HDL proteome (such as replacing atheroprotective proteins by pro-inflammatory proteins, or posttranslational modifications) in patients with chronic inflammatory diseases and their impact on cardiovascular health are discussed. Finally, molecular, and clinical aspects of HDL-targeted therapies, including those used in therapeutical practice, drugs in clinical trials, and experimental drugs are comprehensively summarised.

Colesterolo  is one of the most important stabilising molecules distributed widely throughout the human body, a sterol and cholestanoid, a small lipid present in both body tissues and blood plasma, and in particular in the spinal cord, liver (which acts as a primary storage and metabolic function), and brain. It was discovered in 1769 in human gallstones.

Synthesised, it appears as a white powder that is practically insoluble in water, poorly soluble in ethanol and acetone.

Medical

Cholesterol acts as a membrane stabiliser and regulator in the immune response of cells against various types of viruses and in antibiotic drug resistance by preventing structural damage. Despite the variety of roles that cholesterol plays in the human body, to date its mechanisms have not been fully elucidated by science (1), and while the regulation of cholesterol homeostasis and the metabolic pathways involved have been analysed and largely elucidated, some obscurities remain in the knowledge of plasma levels and the regulatory relationship of its synthesis.   Its distribution in the plasma membrane in cells is still unknown (2).

The accumulation of lipids such as cholesterol characterises atherosclerosis, which is mainly responsible for coronary artery disease, and is classified according to its density.

• LDL-cholesterol = low-density lipoprotein
• HDL-cholesterol = high-density lipoprotein

HDL-cholesterol is a biomarker for assessing cardiovascular risk and is responsible for maintaining the arterial wall in good condition as it controls reverse cholesterol transport, anti-inflammatory, antioxidant, vasodilator and antithrombotic effects.

Low-density lipoprotein LDL-cholesterol must remain within safe limits as its increase can lead to cardiovascular disease and is the hallmark of hypercholesterolaemia, which often leads to the development of atherosclerosis.

Food

Cholesterol is ingested through food. The main sources of cholesterol intake come from milk and dairy products, meat, egg yolk, poultry, and seafood.

One of the foods with the highest nutritional content is the egg, in which cholesterol content is present in large quantities. Since there are concerns about the relationship between cholesterol and cardiovascular disease of the atherosclerotic type, a moderate diet of cholesterol-containing foods is recommended.

Cosmetics

Water loss from the skin is responsible for certain aesthetic and functional defects of the stratum corneum such as reduced elasticity, flaking and dryness. To remedy these drawbacks, cosmetic formulations contain emollient ingredients capable of restoring proper skin hydration. Cholesterol is generally extracted from animals and plays the important role of an emollient that is easily absorbed by the skin with medium penetration capacity, so it is non-irritating and non-photosensitising. It has foam-stabilising activity and improves colour fastness. Improves the function of other active agents. In hair dyes it improves colour fastness and nourishes the hair.

Doses: 1.4% in cosmetic formulations

Other uses

• Plasticiser with good compatibility with most synthetic resins and rubbers used in industry.
• Fixative for gas chromatography 
• Feed additive

For further information:

Cholesterol studies

Typical commercial product characteristics Cholesterol CAS 57-88-5

• Molecular Formula     C₂₇H₄₆O
• Molecular Weight     386.7
• Exact Mass     386.354858
• CAS  57-88-5
• UNII    97C5T2UQ7J
• EC Number   200-353-2
• DSSTox Substance ID  DTXSID3022401
• IUPAC  (3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol
• InChl=1S/C27H46O/c1-18(2)7-6-8-19(3)23-11-12-24-22-10-9-20-17-21(28)13-15-26(20,4)25(22)14-16-27(23,24)5/h9,18-19,21-25,28H,6-8,10-17H2,1-5H3/t19-,21+,22+,23-,24+,25+,26+,27-/m1/s1
• InChl Key      HVYWMOMLDIMFJA-DPAQBDIFSA-N
• SMILES   CC(C)CCCC(C)C1CCC2C1(CCC3C2CC=C4C3(CCC(C4)O)C)C
• MDL number  MFCD00003646
• PubChem Substance ID    24892329
• Beilstein     1915888
• eCl@ss     39023139
• NACRES NA.77
• ChEBI  16113
• RTECS  FZ8400000
• RXCUI     2438
• NCI    C369
• ICSC    8798

Synonyms

• 5-Cholesten-3β-ol
• 3β-Hydroxy-5-cholestene
• 20-Dihydro-11-deoxycortisol
• cholesterin

References_____________________________________________________________________

(1) Westover EJ, Covey DF. The enantiomer of cholesterol. J Membr Biol. 2004 Nov;202(2):61-72. doi: 10.1007/s00232-004-0714-7.

(2) Giang H, Schick M. On the puzzling distribution of cholesterol in the plasma membrane. Chem Phys Lipids. 2016 Sep;199:35-38. doi: 10.1016/j.chemphyslip.2015.12.002.