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Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease which increases the lysosomal degradation of low density lipoprotein receptor (LDLR) resulting in elevated serum LDL-cholesterol levels. Elevated LDL-cholesterol is the main risk factor for cardiovascular disease (CVD). Antibodies to PCSK9 decrease LDL-cholesterol. Recent studies have suggested a direct relationship between PCSK9 and inflammation and the potential inhibitory effects of anti-inflammatory agents against this enzyme. Nutraceuticals are natural compounds, which have numerous anti-inflammatory and lipid-lowering effects. In this review we focus on anti-inflammatory substances and nutraceuticals, which are beneficial in treatment of dyslipidemia. We also reviewed the recent findings concerning the role of PCSK9 as the main target for molecular mechanisms of these substances.

Objective: This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to analyze the effects of flaxseed oil supplementation on biomarkers of inflammation and oxidative stress in patients with metabolic syndrome (MetS) and related disorders., Methods: Databases including PubMed, Scopus, EMBASE, Web of Science, and Cochrane Central library were searched until January 31 th , 2019., Results: 14 effect sizes from 12 studies were identified eligible to be included in current meta-analysis. Flaxseed supplementation resulted in a significant reduction in interleukin 6 (IL-6) (WMD: -0.22; 95% CI: -0.43, -0.01) and malondialdehyde (MDA) (WMD: -0.17; 95% CI: -0.31, -0.03) and a significant increase in total antioxidant capacity (TAC) levels (WMD: 137.25; 95% CI: 68.04, 206.47). Flaxseed oil supplementation did not affect other biomarkers of inflammation and oxidative stress., Conclusions: Overall, this meta-analysis demonstrated flaxseed oil supplementation decreased IL-6 and MDA levels, and increased TAC, but did not affect other biomarkers of inflammation and oxidative stress among patients with MetS and related disorders. This suggests that flaxseed oil supplementation may have played an indirect role in improved clinical symptoms in diseases with metabolic disorders., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: This systematic review and meta-analysis aimed to assess the effects of whey protein on serum lipoproteins and glycemic status in patients with metabolic syndrome (MetS) and related disorders., Methods: Online databases, such as Web of Science, Cochrane Library, PubMed and Scopus were systematically searched by two independent authors from inception until 30th April 2020 for English randomized clinical trials investigating the efficacy of whey protein administration in subjects with Mets or related conditions on the parameters of glycemic and lipid control compared to certain control. In order to evaluate the included studies' methodological quality, Cochrane Collaboration risk of bias tool was applied. Using Cochrane's Q test and I-square (I 2 ) statistic, the included trials' heterogeneity was also examined. Using a random-effects model, data were pooled, and weighted mean difference (WMD) was considered as the overall effect size., Results: Twenty-two studies were selected to be included in this meta-analysis. Consumption of whey protein resulted in significant reduction of HbA1c (WMD: -0.15; 95% CI: - 0.29, - 0.01) insulin (WMD: -0.94; 95% CI: - 1.68, - 0.21) and homeostasis model assessment-estimated insulin resistance (HOMA-IR) (WMD: -0.20; 95% CI: - 0.36, - 0.05). A significant reduction in triglycerides levels (WMD: -17.12; 95% CI: - 26.52, - 7.72), total cholesterol (WMD: -10.88; 95% CI -18.60, - 3.17), LDL-cholesterol levels (WMD: -8.47 95% CI: - 16.59, - 0.36) and total cholesterol/HDL-cholesterol ratio (WMD: -0.26; 95% CI: - 0.41, - 0.10) was found as well., Conclusions: This meta-analysis suggests that supplementation with whey protein had beneficial effect on several indicators of glycemic control and lipid parameters in patients with MetS and related conditions.

Background: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM)., Methods: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks., Results: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.003) and total antioxidant capacity (TAC) (β 43.44 mmol/L, 95% CI, 3.39, 83.50; P = 0.03) when compared with placebo. Furthermore, magnesium and zinc significantly reduced the Beck Depression Inventory index (BDI) (β - 1.66; 95% CI, - 3.32, - 0.009; P = 0.04) and Beck Anxiety Inventory (BAI) (β - 1.30; 95% CI, - 2.43, - 0.16; P = 0.02) when compared with the placebo., Conclusions: In patients with T2DM and CHD, the 12-week intake of magnesium plus zinc had beneficial effects on FPG, HDL-cholesterol, CRP, insulin, total nitrite, TAC levels, and BDI and BAI score. This suggests that magnesium and zinc co-supplementation may be beneficial for patients with T2DM and CHD. Further studies on more patients and lasting longer are needed to determine the safety of magnesium and zinc co-supplementation., Trial Registration: Current Controlled Trials http://www.irct.ir: IRCT20130211012438N31 at 11 May 2019 of registration. This study retrospectively registered.

Recently, concerns regarding the safety of red yeast rice (RYR) have been raised after the publication of some case reports claiming toxicity. Since the previous meta-analyses on the effects of RYR were mainly focused on its efficacy to improve lipid profile and other cardiovascular parameters, we carried out a meta-analysis on safety data derived from the available randomized controlled clinical trials (RCTs). Primary outcomes were musculoskeletal disorders (MuD). Secondary outcomes were non-musculoskeletal adverse events (Non-MuD) and serious adverse events (SAE). Subgroups analyses were carried out considering the intervention (RYR alone or in association with other nutraceutical compounds), monacolin K administered daily dose (≤3, 3.1-5 or >5 mg/day), follow-up (>12 or ≤12 weeks), with statin therapy or statin-intolerance and type of control treatment (placebo or statin treatment). Data were pooled from 53 RCTs comprising 112 treatment arms, which included 8535 subjects, with 4437 in the RYR arm and 4303 in the control one. Monacolin K administration was not associated with increased risk of MuD (odds ratio (OR) = 0.94, 95% confidence interval (CI) 0.53,1.65). Moreover, we showed reduced risk of Non-MuD (OR = 0.59, 95%CI 0.50, 0.69) and SAE (OR = 0.54, 95%CI 0.46, 0.64) vs. control. Subgroups analyses confirmed the high tolerability profile of RYR. Furthermore, increasing daily doses of monacolin K were negatively associated with increasing risk of Non-MuD (slope: -0.10; 95%CI: -0.17, -0.03; two-tailed p < 0.01). Based on our data, RYR use as lipid-lowering dietary supplement seems to be overall tolerable and safe in a large kind of moderately hypercolesterolaemic subjects., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Apolipoprotein C-III (apo C-III) is a key regulator of triglycerides metabolism. The aim of this meta-analysis was to assess the effect of fish omega-3 polyunsaturated fatty acids (PUFAs) on apo C-III levels., Methods: Randomized placebo-controlled trials investigating the impact of omega-3 on apo C-III levels were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar. A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate the impact of potential confounders on glycemic parameters., Results: This meta-analysis comprising 2062 subjects showed a significant reduction of apo C-III concentrations following treatment with omega-3 (WMD: -22.18 mg/L, 95% confidence interval: -31.61, -12.75, p < .001; I 2 : 88.24%). Subgroup analysis showed a significant reduction of plasma apo C-III concentrations by eicosapentaenoic acid (EPA) ethyl esters but not omega-3 carboxylic acids or omega-3 ethyl esters. There was a greater apo C-III reduction with only EPA as compared with supplements containing EPA and docosahexaenoic acid (DHA) or only DHA. A positive association between the apo C-III-lowering effect of omega-3 with baseline apo C-III concentrations and treatment duration was found., Conclusions: This meta-analysis has shown that omega-3 PUFAs might significantly decrease apo C-III. Key messages Omega-3 PUFA supplements significantly reduce apo C-III plasma levels, particularly in hypertriglyceridemic patients when applied in appropriate dose (more than 2 g/day) Triglyceride (TG)-lowering effect is achieved via peroxisome proliferator-activated receptors α Further studies should address the effect of omega-3 PUFAs alone or with other lipid-lowering drugs in order to provide a final answer whether apo C-III could be an important target for prevention of cardiovascular disease New apo C-III antisense oligonucleotide drug (Volanesorsen) showed to be promising in decreasing elevated TGs by reducing levels of apo C-III mRNA.

Statins are the most common drugs administered for patients with cardiovascular disease. However, due to statin-associated muscle symptoms, adherence to statin therapy is challenging in clinical practice. Certain nutraceuticals, such as red yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and stanols alone or in combination with each other, as well as with ezetimibe, might be considered as an alternative or add-on therapy to statins, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. These nutraceuticals could exert significant lipid-lowering activity and might present multiple non-lipid-lowering actions, including improvement of endothelial dysfunction and arterial stiffness, as well as anti-inflammatory and antioxidative properties. The aim of this expert opinion paper is to provide the first attempt at recommendation on the management of statin intolerance through the use of nutraceuticals with particular attention on those with effective low-density lipoprotein cholesterol reduction., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

In recent years, there has been growing interest in the possible use of nutraceuticals to improve and optimize dyslipidemia control and therapy. Based on the data from available studies, nutraceuticals might help patients obtain theraputic lipid goals and reduce cardiovascular residual risk. Some nutraceuticals have essential lipid-lowering properties confirmed in studies; some might also have possible positive effects on nonlipid cardiovascular risk factors and have been shown to improve early markers of vascular health such as endothelial function and pulse wave velocity. However, the clinical evidence supporting the use of a single lipid-lowering nutraceutical or a combination of them is largely variable and, for many of the nutraceuticals, the evidence is very limited and, therefore, often debatable. The purpose of this position paper is to provide consensus-based recommendations for the optimal use of lipid-lowering nutraceuticals to manage dyslipidemia in patients who are still not on statin therapy, patients who are on statin or combination therapy but have not achieved lipid goals, and patients with statin intolerance. This statement is intended for physicians and other healthcare professionals engaged in the diagnosis and management of patients with lipid disorders, especially in the primary care setting., (© The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)