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Complementary Therapies in Medicine Aug 2023Numerous approaches have been assigned to treat dyslipidemia (DLP). Turmeric/curcumin have been widely investigated with this regard. In the current study, we explored... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Numerous approaches have been assigned to treat dyslipidemia (DLP). Turmeric/curcumin have been widely investigated with this regard. In the current study, we explored the effect of curcumin/turmeric supplementation on lipid profile.
METHODS
Online databases were searched up to October 2022. The outcomes included triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), apolipoprotein B (Apo-B), and apolipoprotein A (Apo-A). We used the Cochrane quality assessment tool to evaluate the risk of bias. The effect sizes were estimated as weighted mean difference (WMD) and 95% confidence intervals (CIs).
RESULTS
Out of 4182 articles retrieved from the initial search, 64 randomized clinical trials (RCTs) were included in the study. Between-study heterogeneity was significant. Meta-analysis showed that turmeric/curcumin supplementation exerts statistically significant improvements on blood levels of TC (WMD = -3.99 mg/dL; 95% CI = -5.33, -2.65), TG (WMD = -6.69 mg/dL; 95% CI = -7.93, -5.45), LDL-c (WMD = -4.89 mg/dL; 95% CI = -5.92, -3.87), and HDL-c (WMD = 1.80 mg/dL; 95% CI = 1.43, 2.17). However, turmeric/curcumin supplementation was not associated with improvements in blood levels of Apo-A or Apo-B. The studies did not thoroughly address the issues of potency, purity, or consumption with other foods.
CONCLUSION
Turmeric/curcumin supplementation seems to be effective in improving blood levels of TC, TG, LDL-c, and HDL-c; but may not be capable of improving their pertinent apolipoproteins. Since the evidence was assessed to be low and very low concerning the outcomes, these findings should be dealt with caution.
Topics: Humans; Apolipoproteins A; Cholesterol, HDL; Cholesterol, LDL; Curcuma; Curcumin; Dietary Supplements; Lipids; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 37230418
DOI: 10.1016/j.ctim.2023.102955 -
Current Opinion in Lipidology Apr 2024While biallelic rare APOA5 pathogenic loss-of-function (LOF) variants cause familial chylomicronemia syndrome, heterozygosity for such variants is associated with highly... (Review)
Review
PURPOSE OF REVIEW
While biallelic rare APOA5 pathogenic loss-of-function (LOF) variants cause familial chylomicronemia syndrome, heterozygosity for such variants is associated with highly variable triglyceride phenotypes ranging from normal to severe hypertriglyceridemia, often in the same individual at different time points. Here we provide an updated overview of rare APOA5 variants in hypertriglyceridemia.
RECENT FINDINGS
Currently, most variants in APOA5 that are considered to be pathogenic according to guidelines of the American College of Medical Genetics and Genomics are those resulting in premature termination codons. There are minimal high quality functional data on the impact of most rare APOA5 missense variants; many are considered as variants of unknown or uncertain significance. Furthermore, particular common polymorphisms of APOA5 , such as p.Ser19Trp and p.Gly185Cys in Caucasian and Asian populations, respectively, are statistically overrepresented in hypertriglyceridemia cohorts and are sometimes misattributed as being causal for chylomicronemia, when they are merely risk alleles for hypertriglyceridemia.
SUMMARY
Both biallelic and monoallelic LOF variants in APOA5 are associated with severe hypertriglyceridemia, although the biochemical phenotype in the monoallelic state is highly variable and is often exacerbated by secondary factors. Currently, with few exceptions, the principal definitive mechanism for APOA5 pathogenicity is through premature truncation. The pathogenic mechanisms of most missense variants in APOA5 remain unclear and require additional functional experiments or family studies.
Topics: Humans; Apolipoprotein A-V; Genetic Variation; Heterozygote; Hyperlipoproteinemia Type I; Hypertriglyceridemia; Polymorphism, Genetic; Triglycerides
PubMed: 38117614
DOI: 10.1097/MOL.0000000000000916 -
Atherosclerosis Apr 2024High plasma lipoprotein (a) [Lp(a)] levels are associated with increased atherosclerotic cardiovascular disease (ASCVD), in part attributed to elevated inflammation....
BACKGROUND AND AIMS
High plasma lipoprotein (a) [Lp(a)] levels are associated with increased atherosclerotic cardiovascular disease (ASCVD), in part attributed to elevated inflammation. High plasma Lp(a) levels inversely correlate with apolipoprotein (a) [(APO(a)] isoform size. APO(a) isoform size is negatively associated with APO(a) production rate (PR) and positively associated with APO(a) fractional catabolic rate (FCR). We asked whether APO(a) PR and FCR (kinetics) are associated with plasma levels of interleukin (IL)-6 and IL-18, pro-inflammatory interleukins that promote ASCVD.
METHODS
We used samples from existing data of APO(a) kinetic studies from an ethnically diverse cohort (n = 25: 10 Black, 9 Hispanic, and 6 White subjects) and assessed IL-6 and IL-18 plasma levels. We performed multivariate linear regression analyses to examine the relationships between predictors APO(a) PR or APO(a) FCR, and outcome variables IL-6 or IL-18. In these analyses, we adjusted for parameters known to affect Lp(a) levels and APO(a) PR and FCR, including race/ethnicity and APO(a) isoform size.
RESULTS
APO(a) PR and FCR were positively associated with plasma IL-6, independent of isoform size, and dependent on race/ethnicity. APO(a) PR was positively associated with plasma IL-18, independent of isoform size and race/ethnicity. APO(a) FCR was not associated with plasma IL-18.
CONCLUSIONS
Our studies demonstrate a relationship between APO(a) PR and FCR and plasma IL-6 or IL-18, interleukins that promote ASCVD. These studies provide new insights into Lp(a) pro-inflammatory properties and are especially relevant in view of therapies targeting APO(a) to decrease cardiovascular risk.
Topics: Humans; Apoprotein(a); Interleukin-6; Ethnicity; Interleukin-18; Kinetics; Apolipoproteins A; Lipoprotein(a); Atherosclerosis; Protein Isoforms
PubMed: 38428286
DOI: 10.1016/j.atherosclerosis.2024.117474 -
Frontiers in Endocrinology 2023Research has shown that the disordered serum lipid profile may be associated with the risk of differentiated thyroid cancer (DTC). Whether this association reflect...
BACKGROUND
Research has shown that the disordered serum lipid profile may be associated with the risk of differentiated thyroid cancer (DTC). Whether this association reflect causal effect is still unclear. The aim of this study was to evaluate the causality of circulating lipoprotein lipids on DTC.
METHODS
Mendelian randomization (MR) analysis was conducted to evaluate the relationship between the circulating lipoprotein lipids and DTC risk using single-nucleotide polymorphisms (SNPs) from a genome-wide association (GWA) study containing a high-incidence Italian population of 690 cases samples with DTC and 497 controls.
RESULTS
Univariate and multivariate mendelian randomization analysis demonstrated that 'total cholesterol', 'HDL cholesterol', 'apolipoprotein B' and 'ratio of apolipoprotein B to apolipoprotein A1' were correlated with DTC. According to sensitivity analysis, our results were reliable. Furthermore, multivariate analysis revealed that there is no causative association between DTC and any of the many cause factors when they interact with one another, suggesting that there was a deep interaction between the four factors, which could affect each other. Finally, the mechanism of the related effects each other as well as the target genes with significant SNP regulatory effects in DTC was explored by conducting functional enrichment analysis and constructing the regulatory networks.
CONCLUSIONS
We obtained four exposure factors (total cholesterol, HDL cholesterol, apolipoprotein B and ratio of apolipoprotein B to apolipoprotein A1) closely related to DTC, which laid a theoretical foundation for the treatment of DTC.
Topics: Humans; Apolipoprotein A-I; Genome-Wide Association Study; Mendelian Randomization Analysis; Adenocarcinoma; Apolipoproteins B; Cholesterol, HDL; Lipid Metabolism Disorders; Thyroid Neoplasms
PubMed: 38189054
DOI: 10.3389/fendo.2023.1291445 -
Cellular and Molecular Gastroenterology... 2024Apolipoprotein A-1 (ApoA-1), the main apolipoprotein of high-density lipoprotein, has been well studied in the area of lipid metabolism and cardiovascular diseases. In...
BACKGROUND & AIMS
Apolipoprotein A-1 (ApoA-1), the main apolipoprotein of high-density lipoprotein, has been well studied in the area of lipid metabolism and cardiovascular diseases. In this project, we clarify the function and mechanism of ApoA-1 in liver regeneration.
METHODS
Seventy percent of partial hepatectomy was applied in male ApoA-1 knockout mice and wild-type mice to investigate the effects of ApoA-1 on liver regeneration. D-4F (ApoA-1 mimetic peptide), autophagy activator, and AMPK activator were used to explore the mechanism of ApoA-1 on liver regeneration.
RESULTS
We demonstrated that ApoA-1 levels were highly expressed during the early stage of liver regeneration. ApoA-1 deficiency greatly impaired liver regeneration after hepatectomy. Meanwhile, we found that ApoA-1 deficiency inhibited autophagy during liver regeneration. The activation of autophagy protected against ApoA-1 deficiency in inhibiting liver regeneration. Furthermore, ApoA-1 deficiency impaired autophagy through AMPK-ULK1 pathway, and AMPK activation significantly improved liver regeneration. The administration of D-4F could accelerated liver regeneration after hepatectomy.
CONCLUSIONS
These findings suggested that ApoA-1 played an essential role in liver regeneration through promoting autophagy in hepatocytes via AMPK-ULK1 pathway. Our findings enrich the understanding of the underlying mechanism of liver regeneration and provide a potential therapeutic strategy for liver injury.
Topics: Animals; Male; Mice; AMP-Activated Protein Kinases; Apolipoprotein A-I; Autophagy; Liver; Liver Regeneration
PubMed: 38122985
DOI: 10.1016/j.jcmgh.2023.12.004 -
Cancer Medicine Nov 2023Plasma cell neoplasms are a group of hematologic neoplasms that often develop in the elderly population. The relationship between cholesterol levels and hematologic...
BACKGROUND
Plasma cell neoplasms are a group of hematologic neoplasms that often develop in the elderly population. The relationship between cholesterol levels and hematologic malignancy has been identified in population studies. However, it is still unclear if there is a relationship between cholesterol levels and plasma cell neoplasm in European ancestry.
METHODS
Prospective cohorts included 502,507 individuals from the UK Biobank who were followed up to 2019 and assessed total cholesterol(TC) levels, low-density lipoprotein (LDL) levels, high-density lipoprotein (HDL) levels, apolipoprotein A (ApoA) and apolipoprotein B (ApoB) as risk factors for plasma cell neoplasms with Cox proportional hazard regression and restricted cubic spline model. We also used two-sample Mendelian randomization to determine if the cholesterol level has a causal effect on developing plasma cell neoplasms.
RESULTS
We observed 1819 plasma cell neoplasm cases during 14.2 years of follow-up in the UK Biobank. We found higher blood serum cholesterol levels at baseline were associated with a lower risk of plasma cell neoplasm in our study. All lipid profiles we analyzed in this study were inversely associated with plasma cell neoplasm risk (all p <0.005) but triglycerides did not have such association. However, there was no suggestive association of genetically predicted serum LDL, HDL, and total cholesterol levels with multiple myeloma.
CONCLUSION
Low serum total cholesterol, LDL, HDL, ApoA, and ApoB levels were all associated with increasing the risk of plasma cell neoplasm.
Topics: Humans; Aged; Cohort Studies; Prospective Studies; Multiple Myeloma; Biological Specimen Banks; Cholesterol, HDL; Cholesterol, LDL; Apolipoproteins B; Risk Factors; Triglycerides; Apolipoproteins A
PubMed: 37908181
DOI: 10.1002/cam4.6649 -
BMC Medical Genomics Dec 2023In response to the controversy surrounding observational studies of the association between lipid profiles and the risk of insomnia, the aim of this study was to analyze...
OBJECTIVES
In response to the controversy surrounding observational studies of the association between lipid profiles and the risk of insomnia, the aim of this study was to analyze lipid profiles, including triglycerides (TG), apolipoprotein A-1 (ApoA-1), apolipoprotein B (ApoB) and lipoprotein A (LPA), in a European population to further assess the causal relationship between these lipid types and insomnia.
MATERIALS AND METHODS
This study explores the causal effect of lipid profiles on insomnia based on a genome-wide association study (GWAS)-derived public dataset using two-sample and multivariate Mendelian randomization (MVMR) analysis. The main MR analyses used inverse variance weighting (IVW) odds ratio (OR), and the sensitivity analyses included weighted median (WM) and MR‒Egger.
RESULTS
Both MR and MVMR showed that lowering ApoA-1 and LPA levels had causal effects on the risk of insomnia [MR: per 10 units, ApoA-1: OR: 0.7546, 95% CI: 0.6075-0.9372, P = 0.011; LPA: OR: 0.8392, 95% CI: 0.7202-0.9778, P = 0.025; MVMR: per 10 units, ApoA-1: OR: 0.7600, 95% CI: 0.6362-0.9079, P = 0.002; LPA, OR: 0.903, 95% CI: 0.8283-0.9845, P = 0.021]. There were no causal effects of TG or ApoB on insomnia (all P > 0.05). The MR‒Egger intercept test, funnel plot, and IVW methods all suggested an absence of strong directional pleiotropy, and leave-one-out permutation analysis did not detect any single single-nucleotide polymorphism that had a strong influence on the results.
CONCLUSION
Elevated levels of ApoA-1 and LPA were independently and causally associated with the risk of insomnia, suggesting that elevated ApoA-1 and LPA levels may contribute to a reduced risk of insomnia.
Topics: Humans; Apolipoprotein A-I; Apolipoproteins B; Genome-Wide Association Study; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Sleep Initiation and Maintenance Disorders; Triglycerides
PubMed: 38087303
DOI: 10.1186/s12920-023-01761-y -
International Immunopharmacology Dec 2023Recent clinical studies have shown that serum high-density lipoprotein (HDL) levels are correlated with acute pancreatitis (AP) severity. We aimed to investigate the...
BACKGROUND AND PURPOSE
Recent clinical studies have shown that serum high-density lipoprotein (HDL) levels are correlated with acute pancreatitis (AP) severity. We aimed to investigate the role of HDL in pancreatic necrosis in AP.
EXPERIMENTAL APPROACH
ApoA-I is the main constitution and function component of HDL. The roles of healthy human-derived HDL and apoA-I mimic peptide D4F were demonstrated in AP models in vivo and in vitro. Constitutive Apoa1 genetic inhibition on AP severity, especially pancreatic necrosis was assessed in both caerulein and sodium taurocholate induced mouse AP models. In addition, constitutive (Casp1) and acinar cell conditional (Pdx1Nlrp3 and Pdx1Gsdmd) mice were used to explore the effects of HDL on acinar cell pyroptosis in AP.
KEY RESULTS
Apoa1 knockout dramatically aggravated pancreatic necrosis. Human-derived HDL protected against acinar cell death in vivo and in vitro. We found that mimic peptide D4F also protected against AP very well. Constitutive Casp1 or acinar cell-conditional Nlrp3 and Gsdmd genetic inhibition could counteract the protective effects of HDL, implying HDL may exert beneficial effects on AP through inhibiting acinar cell pyroptosis.
CONCLUSION AND IMPLICATIONS
This work demonstrates the protective role of HDL and apoA-I in AP pathology, potentially driven by the inhibition of NLRP3 inflammasome signaling and acinar cell pyroptosis. Mimic peptides have promise as specific therapies for AP.
Topics: Animals; Humans; Mice; Acinar Cells; Acute Disease; Apolipoprotein A-I; Caspase 1; Ceruletide; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Pancreatitis, Acute Necrotizing; Pyroptosis
PubMed: 37890377
DOI: 10.1016/j.intimp.2023.110950 -
Lipids in Health and Disease Jul 2023Prevention measures for cardiovascular diseases (CVD) have shifted their focus from lipoproteins to the immune system. However, low-grade inflammation and dyslipidemia...
BACKGROUND AND AIMS
Prevention measures for cardiovascular diseases (CVD) have shifted their focus from lipoproteins to the immune system. However, low-grade inflammation and dyslipidemia are tightly entangled. The objective of this study was to assess the relations between a broad panel of inflammatory biomarkers and lipoprotein subclass parameters.
METHODS
We utilized data from the population-based Study of Health in Pomerania (SHIP-TREND, n = 403). Plasma concentrations of 37 inflammatory markers were measured by a bead-based assay. Furthermore, we employed nuclear magnetic resonance spectroscopy to measure total cholesterol, total triglycerides, total phospholipids as well as the fractional concentrations of cholesterol, triglycerides, phospholipids, ApoA1, ApoA2 and ApoB in all major lipoprotein subclasses. Associations between inflammatory biomarkers and lipoprotein subclasses were analyzed by adjusted linear regression models.
RESULTS
APRIL, BAFF, TWEAK, sCD30, Pentraxin-3, sTNFR1, sTNFR2, Osteocalcin, Chitinase 3-like 1, IFN-alpha2, IFN-gamma, IL-11, IL-12p40, IL-29, IL-32, IL-35, TSLP, MMP1 and MMP2 were related with lipoprotein subclass components, forming two distinct clusters. APRIL had inverse relations to HDL-C (total and subclasses) and HDL Apo-A1 and Apo-A2 content. MMP-2 was inversely related to VLDL-C (total and subclasses), IDL-C as well as LDL5/6-C and VLDL-TG, IDL-TG, total triglycerides as well as LDL5/5-TG and HDL4-TG. Additionally, we identified a cluster of cytokines linked to the Th1-immune response, which were associated with an atherogenic lipoprotein profile.
CONCLUSION
Our findings expand the existing knowledge of inflammation-lipoprotein interactions, many of which are suggested to be involved in the pathogeneses of chronic non-communicable diseases. The results of our study support the use of immunomodulatory substances for the treatment and possibly prevention of CVD.
Topics: Humans; Inflammation; Cytokines; Apolipoprotein A-II; Apolipoproteins B; Cardiovascular Diseases
PubMed: 37434164
DOI: 10.1186/s12944-023-01856-6 -
Nutrients May 2024Previous studies have shown encouraging results regarding the efficacy and safety of nutraceuticals, such as "red yeast rice (RYR) extract", on reducing... (Meta-Analysis)
Meta-Analysis Review
Safety and Efficacy of the Consumption of the Nutraceutical "Red Yeast Rice Extract" for the Reduction of Hypercholesterolemia in Humans: A Systematic Review and Meta-Analysis.
Previous studies have shown encouraging results regarding the efficacy and safety of nutraceuticals, such as "red yeast rice (RYR) extract", on reducing hypercholesterolemia in humans. A systematic review and meta-analysis was conducted from January 2012 to May 2022. The search was strictly focused on clinical trials that examined the association between RYR extract consumption and parameters of the lipid profile in humans. Fourteen double-blinded clinical trials were identified. The interventions lasted 4-24 weeks. In most studies, there was one intervention group and one control group. RYR extract consumption statistically significantly reduced total cholesterol (mean absolute reduction: 37.43 mg/dL; 95% confidence interval [CI]: -47.08, -27.79) and low-density lipoprotein cholesterol (LDL-C; mean absolute reduction: 35.82 mg/dL; 95% CI: -43.36, -28.29), but not high-density lipoprotein cholesterol, triglycerides and apolipoproteins A-I and B. As regards the safety, RYR extract was considered a safe choice with neither threatening nor frequent side effects. The consumption of RYR extract by people with hypercholesterolemia was associated with statistically significant reduction in total cholesterol and LDL-C, whereas it was not associated with an increase in life-threatening side effects. Further research on specific subpopulations and outcomes could establish a consensus on determining the clinical benefits and potential risks, if any, of this nutraceutical.
Topics: Adult; Humans; Middle Aged; Anticholesteremic Agents; Biological Products; Cholesterol; Cholesterol, LDL; Dietary Supplements; Hypercholesterolemia; Treatment Outcome; Young Adult; Aged; Aged, 80 and over
PubMed: 38794691
DOI: 10.3390/nu16101453