Red Yeast Rice and Statin Therapy in Patients with Hypercholesterolemia and the Comorbidities: A Retrospective Cohort Study on Lipid-Lowering Effects and Cardiovascular Outcomes.

Red yeast rice (RYR) is known for its lipid-lowering effects in patients with hypercholesterolemia; however, its comparative efficacy with statins and risk reduction remains uncertain. This retrospective study analyzed data from 337,104 patients with hyperlipidemia in the Chang Gung Research Database cohort, spanning from January 2016 to December 2021. Exclusion criteria were applied to ensure data completeness and compliance, including an age limit of [Formula: see text] years, absence of RYR or statin treatment, and a treatment duration of [Formula: see text] days. Propensity score matching was employed to minimize bias based on baseline factors, with one patient matching with four patients in the comparison group. The study encompassed a total of 5,984 adult hyperlipidemic patients, with 1,197 in the RYR group and 4,787 in the statin group. The patients were also stratified into statin ([Formula: see text]) or combined use ([Formula: see text]) groups for further comparison. Following one year of treatment, both the RYR and statin groups exhibited reductions in total cholesterol and triglyceride levels. Most biochemical parameters showed no significant differences, except for elevated glutamic oxaloacetic transaminase levels in the RYR group ([Formula: see text]) and increased glycohemoglobin levels in the statin group at the three-month mark ([Formula: see text]). In patients with comorbid diabetes, hypertension, kidney, or liver diseases, RYR and statins demonstrated comparable risks for emergency room (ER) visits, stroke, and myocardial infarction (MI). However, the combination of RYR and statins was associated with reduced stroke-related hospitalizations in patients with diabetes, hypertension, and kidney disease, as well as decreased MI-related hospitalizations in patients with hypertension and kidney disease (all [Formula: see text]). In conclusion, both RYR and statins effectively lower blood lipid levels and mitigate related complications. Combining these therapies may lead to fewer ER visits, reduced stroke frequency, and fewer MI hospitalizations in hypertensive and kidney disease patients, and they decreased all-cause mortality in the kidney disease population. Further research on combined therapy is warranted.

Diosgenin as a substitute for cholesterol alleviates NAFLD by affecting CYP7A1 and NPC1L1-related pathway.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) rapidly becomes the leading cause of end-stage liver disease or liver transplantation. Nowadays, there has no approved drug for NAFLD treatment. Diosgenin as the structural analogue of cholesterol attenuates hypercholesterolemia by inhibiting cholesterol metabolism, which is an important pathogenesis in NAFLD progression. However, there has been no few report concerning its effects on NAFLD so far. METHODS: Using a high-fat diet & 10% fructose-feeding mice, we evaluated the anti-NAFLD effects of diosgenin. Transcriptome sequencing, LC/MS analysis, molecular docking simulation, molecular dynamics simulations and Luci fluorescent reporter gene analysis were used to evaluate pathways related to cholesterol metabolism. RESULTS: Diosgenin treatment ameliorated hepatic dysfunction and inhibited NAFLD formation including lipid accumulation, inflammation aggregation and fibrosis formation through regulating cholesterol metabolism. For the first time, diosgenin was structurally similar to cholesterol, down-regulated expression of CYP7A1 and regulated cholesterol metabolism in the liver (p < 0.01) and further affecting bile acids like CDCA, CA and TCA in the liver and feces. Besides, diosgenin decreased expression of NPC1L1 and suppressed cholesterol transport (p < 0.05). Molecular docking and molecular dynamics further proved that diosgenin was more strongly bound to CYP7A1. Luci fluorescent reporter gene analysis revealed that diosgenin concentration-dependently inhibited the enzymes activity of CYP7A1. CONCLUSION: Our findings demonstrated that diosgenin was identified as a specific regulator of cholesterol metabolism, which pave way for the design of novel clinical therapeutic strategies.

Immature carob pods extract and its fractions prevent lipid metabolism disorders and lipoprotein-rich plasma oxidation in mice: A phytochemical and pharmacological study.

ETHNOPHARMACOLOGICAL RELEVANCE: In Morocco carob fruits are used traditionally to treat hypercholesterolemia, diabetes and related diseases. AIMS: This study was designed to evaluate the hypolipidemic activity of Ceratonia siliqua green pods extract and its fractions in Triton WR-1339 and high fat/cholesterol diet (HFCD) induced hyperlipidemia mice, as well as their ability to prevent lipoproteins oxidation in vitro. MATERIALS AND METHODS: High performance liquid chromatography (HPLC) analysis was used to determine the phenolic composition of the immature carob pods extract (HWCE). Antioxidant activities were evaluated using the DPPH radical scavenging test as well as MDA measurement in oxidized lipoprotein rich plasma. Plasma lipids, glucose and biliary total cholesterol, as well as lipids level in liver and feces, were analyzed. The acute oral toxicity was performed in mice single dosed with the HWCE at 2000 and 5000 mg/kg body weight. RESULTS: HPLC analysis shows that gallic acid is the main phenolic compound in the HWCE. The acute oral toxicity assessment revealed that the HWCE is not toxic (LD50 is greater than 5000 mg/kg body weight). In the acute hypolipidemic study, mice treated with the HWCE and its fractions exhibited a significant (P < 0.001) reduction in plasma total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) levels. Importantly, immature carob aqueous extract was more effective in lowering mice hypercholesterolemia than its fractions. Indeed, mice fed the HFCD for 12 weeks showed a significant raise in plasma TC, TG and LDL-C, as well as in hepatic and fecal TC and TG levels. The HWCE at 100 and 200 mg/kg body weight significantly (P < 0.001) reversed the plasmatic levels of these lipid parameters, increased plasma HDL-C level, reduced hepatic lipids accumulation, but increased cholesterol level in the bile and fecal lipids excretion. The HWCE decreased also the atherogenic index, the LDL-C/HDL-C ratio and plasma glucose level after 12 weeks' experiment. On the other hand, the HWCE was more effective in preventing mice lipoprotein-rich plasma oxidation than its fractions, with a concentration-dependent manner. CONCLUSION: C. siliqua green fruits extract could be effective in preventing atherosclerosis and related cardiovascular complications through the inhibition of lipoprotein oxidation and cholesterol clearance.

Polymethoxyflavones in citrus extract has a beneficial effect on hypercholesterolemia rats by promoting liver cholesterol metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia is characterized by the disorder of lipid metabolism accompanied by oxidative stress damage, and low-grade inflammation, with the pathway of cholesterol and bile acid metabolic are an important triggering mechanism. Polymethoxyflavones (PMFs) are the active constituents of Aurantii Fructus Immaturus, which have many biological effects, including anti-inflammatory, antioxidant activities, anti-obesity, suppressing adipogenesis in adipocytes, and ameliorate type 2 diabetes, with potential roles for regulation of lipid metabolism. However, its associated mechanisms on hyperlipidemia remain unclear. AIM OF THE STUDY: This study aims to identify the anti-hypercholesterolemia effects and mechanisms of PMFs in a hypercholesterolemia model triggered by high-fat compounds in an excessive alcohol diet (HFD). MATERIALS AND METHODS: A hypercholesterolemia rat model was induced by HFD, and PMFs was intragastric administered at 125 and 250 mg/kg daily for 16 weeks. The effects of PMFs on hypercholesterolemia were assessed using serum lipids, inflammatory cytokines, and oxidative stress levels. Hematoxylin & eosin (H&E) and Oil Red O staining were performed to evaluate histopathological changes in the rat liver. The levels of total cholesterol (TC) and total bile acid (TBA) in the liver and feces were determined to evaluate lipid metabolism. RAW264.7 and BRL cells loaded with NBD-cholesterol were used to simulate the reverse cholesterol transport (RCT) process in vitro. The signaling pathway of cholesterol and bile acid metabolic was evaluated by Western Blotting (WB) and qRT-PCR. RESULTS: Lipid metabolism disorders, oxidative stress injury, and low-grade inflammation in model rats were ameliorated by PMFs administration. Numerous vacuoles and lipid droplets in hepatocytes were markedly reduced. In vitro experiments results revealed decreased NBD-cholesterol levels in RAW264.7 cells and increased NBD-cholesterol levels in BRL cells following PMFs intervention. PMFs upregulated the expression of proteins associated with the RCT pathway, such as LXRα, ABCA1, LDLR, and SR-BI, thereby promoting TC entry into the liver. Meanwhile, the expression of proteins associated with cholesterol metabolism and efflux pathways such as CYP7A1, CYP27A1, CYP7B1, ABCG5/8, ABCB1, and BSEP were regulated, thereby promoting cholesterol metabolism. Moreover, PMFs treatment regulated the expression of proteins related to the pathway of enterohepatic circulation of bile acids, such as ASBT, OSTα, NTCP, FXR, FGF15, and FGFR4, thereby maintaining lipid metabolism. CONCLUSIONS: PMFs might ameliorate hypercholesterolemia by promoting the entry of cholesterol into the liver through the RCT pathway, followed by excretion via metabolism pathways of cholesterol and bile acid. These findings provide a promising therapeutic potential for PMFs to treat hypercholesterolemia.

Phytosterol supplementation in capsules or tablets as adjunctive treatment for hypercholesterolemia: A systematic review of randomized controlled trials.

BACKGROUND: The exploration of lipid-lowering resources, such as phytosterols, for the complementary nutritional treatment of hypercholesterolemia is relevant to reduce cardiovascular risk. The use of phytosterols in capsules or tablets can bring advantages in the context of diet therapy, but such format is still less studied when compared to fortified foods. OBJECTIVE: Systematically review randomized clinical trials on the effects of phytosterol supplementation, in capsules or tablets, on the lipid profile and its use in the treatment of hypercholesterolemia in adults. DESIGN: A systematic review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis, with a PROSPERO protocol registered under number CRD42021249539. The process was conducted by two independent reviewers. Only randomized clinical trials with phytosterol supplementation in adult individuals with hypercholesterolemia were included. The terms were searched in the databases: PubMed/MEDLINE, Cochrane Library/CENTRAL, Embase, LILACS and Web of Science, without restriction of time and language. The manual search was also performed through the list of references of articles included in this review. RESULTS: The searches resulted in 977 articles. 22 articles were selected, whose full text was read, and according to the eligibility criteria 10 were incorporated into the review. The studies were separated into groups according to the association of the intervention with changes in lifestyle and the characteristics extracted from the studies were summarized and displayed in tables. Most studies have revealed a positive association between phytosterol supplementation and cholesterol reduction, despite the short duration of interventions. CONCLUSION: The analyzed studies showed that phytosterol supplements can be useful to modulate the lipid profile, helping to reduce the plasma concentration of LDL cholesterol. However, more research with the aforementioned supplementation in such pharmaceutical formats should be encouraged.

Confounding Effects of Tamoxifen: Cautionary and Practical Considerations for the Use of Tamoxifen-Inducible Mouse Models in Atherosclerosis Research-Brief Report.

BACKGROUND: In recent years, fate-mapping lineage studies in mouse models have led to major advances in vascular biology by allowing investigators to track specific cell populations in vivo. One of the most frequently used lineage tracing approaches involves tamoxifen-inducible CreERT-LoxP systems. However, tamoxifen treatment can also promote effects independent of Cre recombinase activation, many of which have not been fully explored. METHODS: To elucidate off-target effects of tamoxifen, male and female mice were either unmanipulated or injected with tamoxifen or corn oil. All mice received PCSK9 (proprotein convertase subtilisin/kexin type 9)-AAV (adeno-associated virus) injections and a modified Western diet to induce hypercholesterolemia. After 2 weeks, serum cholesterol and liver morphology were assessed. To determine the duration of any tamoxifen effects in long-term atherosclerosis experiments, mice received either 12 days of tamoxifen at baseline or 12 days plus 2 sets of 5-day tamoxifen boosters; all mice received PCSK9-AAV injections and a modified Western diet to induce hypercholesterolemia. After 24 weeks, serum cholesterol and aortic sinus plaque burden were measured. RESULTS: After 2 weeks of atherogenic treatment, mice injected with tamoxifen demonstrated significantly reduced serum cholesterol levels compared with uninjected- or corn oil-treated mice. However, there were no differences in PCSK9-mediated knockdown of LDL (low-density lipoprotein) receptors between the groups. Additionally, tamoxifen-treated mice exhibited significantly increased hepatic lipid accumulation compared with the other groups. Finally, the effects of tamoxifen remained for at least 8 weeks after completion of injections, with mice demonstrating persistent decreased serum cholesterol and impaired atherosclerotic plaque formation. CONCLUSIONS: In this study, we establish that tamoxifen administration results in decreased serum cholesterol, decreased plaque formation, and increased hepatic lipid accumulation. These alterations represent significant confounding variables in atherosclerosis research, and we urge future investigators to take these findings into consideration when planning and executing their own atherosclerosis experiments.

Determination of chemical composition and investigation of potential of triphala powder in hypercholesterolemia in men in controlled randomized trial.

Hypercholesterolemia is a condition with elevated cholesterol and lipid profile. It is the leading reason behind myocardial infarction and coronary heart disease. It is observed in young people as well due to a sedentary lifestyle. Triphala powder has a hypolipidemic and anti-hypercholesterolemia effect. This study was designed to investigate the effect of triphala powder against hypercholesterolemia. This study also examined Triphala powder's chemical composition. Total phenolic and flavonoid content were examined. Encapsulated 400 mg and 600 mg Triphala powder were given to treatment groups I and II. Lipid profile parameters were measured and compared at 0 weeks and 10th weeks in all groups. All results were analyzed using ANOVA in IBM SPSS Statistics 20. Results of proximate analyses have shown that Okra pod powder contains moisture 12.27%, ash 11.25%, nitrogen-free extract 45.93%, crude protein 13.37%, crude fat 2.95% and crude fiber 14.23%. Mineral analysis showed that iron and manganese are major minerals in triphala powder. Triphala powder showed a significant reduction in lipid profile parameters in hypercholesterolemia. All results are taken significantly at p<0.05.

Lactobacillus reuteri NCIMB 30242 (LRC) Inhibits Cholesterol Synthesis and Stimulates Cholesterol Excretion in Animal and Cell Models.

In this study, we evaluated the effects of Lactobacillus reuteri NCIMB (LRC™) supplementation on hypercholesterolemia by researching its effects on cellular cholesterol metabolism in hypercholesterolemic rats (KHGASP-22-170) and HepG2 cell line. Rats were separated into six groups after adaptation and were then fed a normal control (NC), a high-cholesterol diet (HC), or a HC supplemented with simvastatin 15 mg/kg body weight (positive control [PC]), LRC 1 × 109 colony-forming units (CFU)/rat/day, LRC 4 × 109 CFU/rat/day, or LRC 1 × 1010 CFU/rat/day (1 × 109, 4 × 109, or 1 × 1010). The rats were dissected to study the effects of LRC on cholesterol metabolism and intestinal excretion at the end of experimental period. We discovered that LRC mainly participated in the restraint of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the uptake of low-density lipoprotein (LDL) cholesterol into tissues, partially in the transport of cholesteryl esters into high density lipoprotein for maturation, and intestinal excretion of cholesterol. These results are supported by the expression of transcription factors and enzymes such as HMG-CoA reductase, SREBP2, CYP7A1, CETP, and LCAT in both messenger RNA (mRNA) and protein levels in serum and hepatic tissue. Furthermore, the LRC treatment in HepG2 significantly reduced the mRNA expression of HMG-CoA reductase, SREBP2, and CEPT and significantly increased the mRNA expression of LDL-receptor, LCAT, and CYP7A1 at all doses. Hence, we suggest that LRC supplementation could alleviate the serum cholesterol level by inhibiting the intracellular cholesterol synthesis, and augmenting excretion of intestinal cholesterol.

Effect of Black Garlic Consumption on Endothelial Function and Lipid Profile: A Before-and-After Study in Hypercholesterolemic and Non-Hypercholesterolemic Subjects.

BACKGROUND: Black garlic is obtained from raw garlic (Allium sativum L.), by a fermentation process, under humidity and heat treatment, showing a high concentration of organosulfur compounds, which have been related to benefits in the prevention or delay of cardiovascular diseases (CVDs). The objective of the research was to evaluate whether long-term consumption of black garlic improves endothelial function and lipid profile in subjects with hypercholesterolemia. METHODS: Single center, controlled clinical trial with two branches: Hypercholesterolemia vs. Healthy condition. Sixty-two subjects of both sexes were distributed in two groups, the hypercholesterolemia group (n = 31) (total cholesterol (TC) range 200-300 mg/dL and low-density lipoprotein (LDL)-cholesterol range 135-175 mg/dL) and the healthy group (n = 31). The intervention consisted of the ingestion of 4 cloves of black garlic (12 g) daily for 12 weeks. RESULTS: significant increases in Apolipoprotein (Apo)A1 occurred in both groups: Hypercholesterolemia (Δ 11.8 mg/dL p < 0.001) vs Healthy (Δ 11.1 mg/dL p < 0.001). Besides, significant reductions for endothelial adhesion molecules monocyte chemoattractant protein-1 (MCP-1) (Δ -121.5 pg/mL p = 0.007 vs. Δ -56.3 pg/mL p = 0.015), intracellular adhesion molecule-1 (ICAM-1) (Δ -39.3 ng/mL p < 0.001 vs. Δ 63.5 ng/mL p < 0.001), and vascular cyto-adhesion molecule-1 (VCAM-1) (Δ -144.4 ng/mL p < 0.001 vs. Δ -83.4 ng/mL p = 0.061) were observed, for hypercholesterolemic and healthy subjects, respectively. CONCLUSIONS: These data show that black garlic consumption could improve some parameters related to endothelial function and lipid profile, which may have a favorable impact on the risk of CVDs, although more long-term studies are necessary to confirm.

Low Dose Monacolin K Combined with Coenzyme Q10, Grape Seed, and Olive Leaf Extracts Lowers LDL Cholesterol in Patients with Mild Dyslipidemia: A Multicenter, Randomized Controlled Trial.

Certain nutraceuticals, mainly containing red yeast rice, might be considered as an alternative therapy to statins in patients with dyslipidemia, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing a low dose of monacolin K combined with coenzyme Q10, grape seed and olive tree leaf extracts in patients with mild hypercholesterolemia. In total, 105 subjects with mild hypercholesterolemia (low-density lipoprotein cholesterol LDL-C levels 140-180 mg/dL) and low CV risk were randomly assigned into three treatment groups: lifestyle modification (LM), LM plus a low dosage of monacolin K (3 mg), and LM plus a high dosage of monacolin K (10 mg) and treated for 8 weeks. The primary endpoint was the reduction of LDL-C and total cholesterol (TC). LDL-C decreased by 26.46% on average (p < 0.001) during treatment with 10 mg of monacolin and by 16.77% on average during treatment with 3 mg of monacolin (p < 0.001). We observed a slight but significant reduction of the triglyceride levels only in the high-dose-treated group (mean -4.25%; 95% CI of mean -11.11 to 2.61). No severe adverse events occurred during the study. Our results confirm the LDL-C-lowering properties of monacolin are clinically meaningful even in lower doses of 3 mg/day.

Prevalence of LDL-hypercholesterolemia and other cardiovascular risk factors in young people with type 1 diabetes.

BACKGROUND: Mortality and morbidity in people with Type 1 diabetes (T1D) is mainly caused by cardiovascular disease (CVD). Early treatment of cardiovascular risk factors (CVRFs) is of great importance. OBJECTIVE: To analyze the prevalence of LDL-hypercholesterolemia and other CVRFs in youth with T1D. METHODS: Clinical and laboratory parameters, and vascular thickness measurement were obtained in youth with T1D (age 6-18 years, T1D duration >1 year) attending a diabetes clinic. LDL-hypercholesterolemia, microalbuminuria and arterial hypertension were defined as CVRFs. RESULTS: A total of 333 youth (48% girls; age: 13.3 years [10.3-15.5], median [interquartile range]) participated in the study. The T1D duration was 5.9 years [3.5-9.4] with HbA1c of 7.4% [6.8-8.0]. Intima media thickness (N=223) was 538.0 µm [470.0-618.0]). LDL-hypercholesterolemia was present in 30 participants (9%; 18 girls; age: 14.3 years [11.2-15.7]). None of the participants had persistent microalbuminuria, although 59 (18.3%) had elevated albumin excretion in a random urine specimen. LDL-hypercholesterolemia was associated with increased blood pressure (p<0.05), insulin requirement (p<0.05), HbA1c (p<0.05), triglyceride (p<0.001) and total cholesterol (p<0.001), and a family history of premature CVD (p<0.001), but negatively correlated with HDL cholesterol levels (p<0.05). Sex, pubertal status, duration of diabetes, type of therapy, and physical activity did not differ between participants with and without LDL- hypercholesterolemia. Arterial hypertension was present in 11 participants (3.3%; 4 girls; age: 14.1 years [11.1-16.1]). CONCLUSION: LDL-hypercholesterolemia affected 9% of youth with T1D in this cohort and was associated with other CVRFs. A holistic therapeutic concept for these young people is essential.

Red Yeast Rice for the Improvement of Lipid Profiles in Mild-to-Moderate Hypercholesterolemia: A Narrative Review.

Reducing low-density lipoprotein cholesterol (LDL-C) levels is a key target for lowering cardiovascular risk and preventing atherosclerotic cardiovascular disease (ASCVD). Red yeast rice (RYR) is a nutraceutical widely used as a lipid-lowering dietary supplement. The main cholesterol-lowering components of RYR are monacolins, particularly monacolin K, which is structurally identical to lovastatin and targets the same key enzyme of cholesterol biosynthesis. RYR supplementation reduces LDL-C levels by approximately 15-34% versus placebo, with a similar effect to low-dose, first-generation statins in subjects with mild-to-moderate dyslipidemia. RYR has also demonstrated beneficial reductions of up to 45% versus placebo in the risk of ASCVD events in secondary prevention studies. RYR at a dose that provides about 3 mg/d of monacolin K is well tolerated, with an adverse event profile similar to that of low-dose statins. RYR is therefore a treatment option for lowering LDL-C levels and ASCVD risk for people with mild-to-moderate hypercholesterolemia who are ineligible for statin therapy, particularly those who are unable to implement lifestyle modifications, and also for people who are eligible for statin therapy but who are unwilling to take a pharmacologic therapy.

Effects of phytosterol supplementation on lipid profiles in patients with hypercholesterolemia: a systematic review and meta-analysis of randomized controlled trials.

Phytosterols (PSs) have been reported to improve blood lipids in patients with hypercholesterolemia for many years. However, meta-analyses of the effects of phytosterols on lipid profiles are limited and incomplete. A systematic search of randomized controlled trials (RCTs) published in PubMed, Embase, Cochrane Library, and Web of Science from inception to March 2022 was conducted according to the 2020 preferred reporting items of the guidelines for systematic reviews and meta-analysis (PRISMA) statement. These included studies of people with hypercholesterolemia, comparing foods or preparations containing PSs with controls. Mean differences with 95% confidence intervals were used to estimate continuous outcomes for individual studies. The results showed that in patients with hypercholesterolemia, taking a diet containing a certain dose of plant sterol significantly reduced total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) (TC: Weight Mean Difference (WMD) [95% CI] = -0.37 [-0.41, -0.34], p < 0.001; LDL-C: WMD [95% CI] = -0.34 [-0.37, -0.30], p < 0.001). In contrast, PSs had no effect on high density lipoprotein cholesterol (HDL-C) or triglycerides (TGs) (HDL-C: WMD [95% CI] = 0.00 [-0.01, 0.02], p = 0.742; TG: WMD [95% CI] = -0.01 [-0.04, 0.01], p = 0.233). Also, a significant effect of supplemental dose on LDL-C levels was observed in a nonlinear dose-response analysis (p-nonlinearity = 0.024). Our findings suggest that dietary phytosterols can help reduce TC and LDL-C concentrations in hypercholesterolemia patients without affecting HDL-C and TG concentrations. And the effect may be affected by the food substrate, dose, esterification, intervention cycle and region. The dose of phytosterol is an important factor affecting the level of LDL-C.

Functional foods and nutraceuticals in the treatment of hypercholesterolemia: Statement of the Spanish Society of Arteriosclerosis 2023. / Alimentos funcionales y nutracéuticos en el tratamiento de la hipercolesterolemia: posicionamiento de la Sociedad Española de Arteriosclerosis 2023.

In the management of hypercholesterolemia, besides advising a healthy, plant-based diet, it may be useful to recommend functional foods or nutraceutical with cholesterol-lowering properties. Given the progressive increase in the number of these products and their rising use by the population, the Spanish Society of Arteriosclerosis (SEA) has considered it appropriate to review the available information, select the results of the scientifically more robust studies and take a position on their usefulness, to recommend to health professionals and the general population their potential utility in terms of efficacy and their possible benefits and limitations. The following clinical scenarios have been identified in which these products could be used and will be analyzed in more detail in this document: (1) Hypolipidemic treatment in subjects with statin intolerance. (2) Hypolipidemic treatment «a la carte¼ in individuals in primary prevention. (3) Long-term cardiovascular prevention in individuals with no indication for lipid-lowering therapy. (4) Patients with optimized lipid-lowering treatment who do not achieve therapeutic objectives.

Hepatoprotective effect of dihydroxy piperlongumine in high cholesterol-induced non-alcoholic fatty liver disease zebrafish via antioxidant activity.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are a growing epidemic and the most common liver diseases. Consumption of a western diet with high fats alters redox status, induces inflammation, and impairs the physiological function of hepatocytes. However, the pharmacological market lacks anti-NAFLD/NASH drugs. Long pepper (Piper longum L) is used in traditional Mongolian medicine for treating hyperlipidemia. Piperlongumine (PL) is a bioactive compound of Piper longum L, which usually possesses anticancer activities due to its ROS elevation property. However, when PL was demethylated they behave as an antioxidant. Previously, we found dihydroxy piperlongumine (DHPL) possesses high antioxidant activity among the hydroxy piperlongumines, which makes us curious to reveal the anti-NAFLD effect. A high-cholesterol diet (HCD) was chosen to induce NAFLD zebrafish model, and the antioxidant and lipid-lowering effects of DHPL were evaluated. Histological alterations of NAFLD were also scored along with gene expression to explore the molecular mechanism. DHPL reduced lipid accumulation in both short-term and long-term feeding trials. DHPL increases antioxidant activity and lipid-lowering gene expression and decreases hepatic triglyceride, oxidative stress, and lipogenic genes. In conclusion, DHPL halted the progression of HCD-induced NAFLD in the zebrafish model.

Nutritional and Therapeutic Properties of Fermented Camel Milk Fortified with Red Chenopodium quinoa Flour on Hypercholesterolemia Rats.

Quinoa is a nutrient-dense food that lowers chronic disease risk. This study evaluated the physicochemical and sensory qualities of fermented camel milk with 1, 2, 3, and 4% quinoa. The results showed that improvement in camel's milk increased the total solids, protein, ash, fiber, phenolic content, and antioxidant activity more effectively. Fermented camel milk with 3% of quinoa flour exhibited the highest sensory characteristics compared to other treatments. Fermented camel milk enriched with 3% red quinoa flour was studied in obese rats. Forty male Wistar rats were separated into five groups: the first group served as a normal control, while groups 2-4 were fed a high-fat, high-cholesterol (HF)-diet and given 2 mL/day of fermented milk and quinoa aqueous extract. Blood glucose, malondialdehyde (MDA), low-density lipoprotein (LDL), cholesterol, triglyceride, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), creatinine, and urea levels decreased dramatically in comparison to the positive control group, while high-density lipoprotein (HDL), albumin, and total protein concentrations increased significantly. Fortified fermented camel milk decreased the number of giant adipocytes while increasing the number of tiny adipocytes in the body. The results showed that the liver and renal functions of hypercholesterolemic rats were enhanced by consuming fermented milk and quinoa. These results demonstrated the ability of quinoa and camel milk to protect rats from oxidative stress and hyperlipidemia. Further studies are needed to clarify the mechanisms behind the metabolic effects of fermented camel milk and quinoa.

Review of recent clinical trials and their impact on the treatment of hypercholesterolemia.

PURPOSE OF REVIEW: Cardiovascular disease is the leading cause of death in the United States with incidence expected to increase in the coming decades. Recent years have produced a variety of new and novel therapeutics aimed at reducing the global burden of cardiovascular disease. This review highlights these recent advancements. RECENT FINDINGS: In addition to more rigorous therapeutic thresholds for traditional LDL lowering agents such as statins, recent studies have developed new pathways of lipid lowering for both typical cardiovascular disease and complex, genetic lipid disorders. This includes inhibition of the cholesterol synthesis enzyme ATP citrate lyase with bempedoic acid, prevention of PCSK9 mRNA translation with inclisiran, inhibition of the lipoprotein lipase inhibitor angiopoetin like 3 protein with evinacumab and the use of anti-sense oligonucleotides to lower lipoprotein(a) levels. Icosapent ethyl, while remaining a topic of debate and controversy, demonstrates efficacy in cardiovascular risk reduction when all available data are examined. Lastly fibrate therapy continues to produce negative results in terms of cardiovascular disease reduction. SUMMARY: Recent years have yielded breadth and depth to cardiovascular treatments. This expanded armamentarium will allow for more effective and more consistent treatment and prevention of cardiovascular disease.

Portulaca oleracea L. Extract Regulates Hepatic Cholesterol Metabolism via the AMPK/MicroRNA-33/34a Pathway in Rats Fed a High-Cholesterol Diet.

This study examined the effect of extruded Portulaca oleracea L. extract (PE) in rats fed a high-cholesterol diet through the AMP-activated protein kinase (AMPK) and microRNA (miR)-33/34a pathway. Sprague-Dawley rats were randomized into three groups and fed either a standard diet (SD), a high-cholesterol diet containing 1% cholesterol and 0.5% cholic acid (HC), or an HC diet containing 0.8% PE for 4 weeks. PE supplementation improved serum, liver, and fecal lipid profiles. PE upregulated the expression of genes involved in cholesterol efflux and bile acids' synthesis such as liver X receptor alpha (LXRα), ATP-binding cassette subfamily G5/G8 (ABCG5/8), and cholesterol 7 alpha-hydroxylase (CYP7A1), and downregulated farnesoid X receptor (FXR) in the liver. In addition, hepatic gene expression levels of apolipoprotein A-l (apoA-1), paraoxonase 1 (PON1), ATP-binding cassette subfamily A1/G1 (ABCA1/G1), lecithin-cholesterol acyltransferase (LCAT), and scavenger receptor class B type 1 (SR-B1), which are related to serum high-density lipoprotein cholesterol metabolism, were upregulated by PE. Furthermore, hepatic AMPK activity in the PE group was higher than in the HC group, and miR-33/34a expression levels were suppressed. These results suggest that PE improves the cholesterol metabolism by modulating AMPK activation and miR-33/34a expression in the liver.