astaxanthine and Hypercholesterolemia

Statins are at the forefront of strategies to manage dyslipidemia, although they are not always well tolerated. At 6-7 months after the drug was supplied, discontinuation rates averaged 30%. Alternate agents to statins have been studied. Some nutraceuticals demonstrated an efficacy in reducing cholesterol concentrations. However, there are no data regarding the use of nutraceuticals in elderly dyslipidemic patients. The purpose of this study was to examine the efficacy, safety, and tolerability of a nutraceutical-based protocol in elderly hypercholesterolemic patients previously intolerant to statins.. This study was performed as a randomized, prospective, parallel group, single-blind study. Patients were included in the study if they had high total cholesterolemia, high low-density lipoprotein cholesterol (LDL-C), >75 years of age, statin-intolerant, and were refusing other pharmaceutical treatments for hypercholesterolemia. At the baseline visit, eligible patients were randomized to either nutraceutical-combined pill (containing berberine 500 mg, policosanol 10 mg, red yeast rice 200 mg, folic acid 0.2 mg, coenzyme Q10 2.0 mg, and astaxanthin 0.5 mg) or placebo, and the first dose was dispensed. The efficacy, safety, and tolerability of the proposed treatment were fully assessed after 3, 6, and 12 months of treatment.. Out of 106 consecutive patients screened, 80 eligible patients were randomized to receive either nutraceutical-combined pill (40 patients) or placebo (40 patients). No patients were lost and no deaths occurred during the follow-up. There was a statistically significant reduction in total cholesterolemia (-20%), LDL-C (-31%), and insulin resistance (-10%) with nutraceutical treatment. No significant changes were detected for plasma high-density lipoprotein cholesterol (HDL-C). Furthermore, no statistical differences were found between baseline and end-study safety parameters. Medication compliance and tolerability were high.. In this study the authors have demonstrated that combined nutraceuticals significantly reduce cholesterolemia and achieved acceptable plasma LDL-C levels in elderly hypercholesterolemic patients who were previously statin-intolerant. Combined nutraceuticals is also safe and well tolerated in these patients.

Topics: Aged; Aged, 80 and over; Anticholesteremic Agents; Berberine; Biological Products; Blood Glucose; Cholesterol; Dietary Supplements; Fatty Alcohols; Female; Folic Acid; Humans; Hypercholesterolemia; Lipoproteins, LDL; Male; Medication Adherence; Prospective Studies; Single-Blind Method; Ubiquinone; Xanthophylls

Inhibition of HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, the rate rate-determining enzyme for the biogenesis of cholesterol is known to show antineoplastic effects. Therefore, this study investigates the in-silico HMG-CoA reductase (HMGCR)-inhibitory and in-vivo anti-lipidaemic/anticancer effects of carotenoids from Spondias mombin.. Carotenoids from S. mombin leaves were characterized with the aid of liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). The characterized phytochemicals were obtained from PubChem. They were docked into the orthosteric site of human HMGCR (Protein Data Bank code 1HW8) using AutoDock 4.0 suites. DMBA (7,12-dimethylbenz[a]anthracene) model of breast cancer was treated with the carotenoids extract from S. mombin (100 mg/kg and 200 mg/kg doses) to assess its anti-lipidaemic cum anticancer effects.. Carotenoids from S. mombin; beta-carotene-15,15'-epoxide, astaxanthin and 7,7',8,8'-tetrahydro-β-β-carotene demonstrate HMGCR inhibition. They form hydrophobic interactions with key residues within the catalytic domain of HMGCR. The carotenoids extract exhibits anti-lipidaemic/anticancer effects, lowering serum triglyceride, LDL and cholesterol concentration. It increases HDL concentration and downregulates the expression of HMGR, AFP, CEACAM-3, BRCA-1 and HIF-1 mRNAs.. Carotenoids from S. mombin demonstrate HMG-CoA reductase (HMGCR) inhibition, anti-lipidaemic, and anticancer effects. The inhibition of HMGCR by the carotenoids extract further poses it as a potential anti-hypercholesterolaemia compounds.

Topics: Acyl Coenzyme A; Anacardiaceae; Animals; Anticholesteremic Agents; Antineoplastic Agents, Phytogenic; beta Carotene; Breast; Breast Neoplasms; Carotenoids; Down-Regulation; Female; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipidemias; Hypolipidemic Agents; Lipids; Molecular Docking Simulation; Phytotherapy; Plant Extracts; Rats, Wistar; Xanthophylls

Armolipid Plus (AP) is a nutraceutical that contains policosanol, fermented rice with red yeast, berberine, coenzyme Q10, folic acid, and astaxanthin. It has been shown to be effective in reducing plasma LDL cholesterol (LDLc) levels. In the multicenter randomized trial NCT01562080, there was large interindividual variability in the plasma LDLc response to AP supplementation. We hypothesized that the variability in LDLc response to AP supplementation may be linked to LDLR and PCSK9 polymorphisms.. We sequenced the LDLR 3' and 5' untranslated regions (UTR) and the PCSK9 5' UTR of 102 participants with moderate hypercholesterolemia in trial NCT01562080. In this trial, 50 individuals were treated with AP supplementation and the rest with placebo.. Multiple linear regression analysis, using the response of LDLc levels to AP as the dependent variable, revealed that polymorphisms rs2149041 (c.-3383C>G) in the PCSK9 5' UTR and rs14158 (c.*52G>A) in the LDLR 3' UTR explained 14.1% and 6.4%, respectively, of the variability after adjusting for gender, age, and BMI of individuals. Combining polymorphisms rs2149041 and rs14158 explained 20.5% of this variability (p < 0.004).. Three polymorphisms in the 3' UTR region of LDLR, c.*52G>A, c.*504G>A, and c.*773A>G, and two at the 5' UTR region of PCSK9, c.-3383C>G and c.-2063A>G, were associated with response to AP. These results could explain the variability observed in the response to berberine among people with moderate hypercholesterolemia, and they may be useful in identifying patients who could potentially benefit from supplementation with AP.

Topics: Adult; Aged; Alleles; Berberine; Cholesterol, LDL; Fatty Alcohols; Female; Heterozygote; Humans; Hypercholesterolemia; Linear Models; Male; Middle Aged; Polymorphism, Single Nucleotide; Proprotein Convertase 9; Proprotein Convertases; Receptors, LDL; Serine Endopeptidases; Xanthophylls

Three groups of male Wistar rats (130-140 g) were fed 30 days with a synthetic diets containing 0.1% of beta-carotene, canthaxanthin and astaxanthin respectively. Another group was fed with a synthetic diet without carotenoids. The results shows that the beta-carotene does not induce change in plasma cholesterol (49, 7 +/- 3.6 mg/dl), but canthaxanthin and astaxanthin induce a significant increase in cholesterol concentration (92.1 +/- 3.6 and 66.5 +/- 5.1 mg/dl). This increase is noted mainly in the HDL fraction of the lipoproteins. Canthaxanthin has more affinity than astaxanthin for the liver, principal site of lipoproteins catabolism. The hypercholesterolemic effect of these xanthophylls is not related to reported mechanisms of carotenoids in mammalian, because beta-carotene does not induce changes in plasma cholesterol.

Topics: Animals; beta Carotene; Canthaxanthin; Carotenoids; Hypercholesterolemia; Liver; Male; Rats; Rats, Wistar; Tissue Distribution; Xanthophylls