There is an increasing number of nutraceutical combinations (NCs) on the market for hypercholesterolemia, although clinical trials to verify their safety and efficacy are scarce. We selected fourteen randomized, placebo-controlled clinical trials (RCTs) on different lipid-lowering NCs in hypercholesterolemic subjects. We described each compound′s mechanism of action and efficacy in the mixtures and summarized the clinical trials settings and NCs safety and efficacy results. Almost all NCs resulted efficient against hypercholesterolemia; only one reported no changes. Interestingly, red yeast rice (RYR) was present in eleven mixtures. It is not clear whether the lipid-lowering efficacy of these combinations derives mainly from the RYR component monacolin K “natural statin” single effect. Up to now, few RCTs have verified the efficacy of every single compound vs. NCs to evaluate possible additive or synergistic effects, probably due to the complexity and the high resources request. In conclusion, to manage the arising nutraceutical tide against hypercholesterolemia, it could be helpful to increase the number and robustness of clinical studies to verify the efficacy and safety of the new NCs.

Background: Elevated cholesterol levels and systemic inflammation are considered relevant risk factors for cardiovascular disease (CVD) development and progression. Increasing evidence suggests that cholesterol-lowering and inflammation-lowering nutraceuticals are useful in the management of moderate hypercholesterolemia. Here, we describe the study protocol of a clinical trial aimed to evaluate the cholesterol and inflammatory lowering effect of an innovative dietary supplement (BruMeChol™, Mivell S.r.l., Italy), composed of a mixture of extracts of bergamot and olive fruits in association with vitamin K2 in subjects with mild hypercholesterolemia. Methods: The study was planned as a randomized, double-blind, placebo-controlled, parallel group clinical trial for 12 weeks at the Cardiology Unit of the IRCCS INRCA of Ancona, Italy. A total of 125 subjects (age ≥ 40 years) with mild hypercholesterolemia (total serum cholesterol levels ≥ 200 and ≤ 250 mg/dl) will be recruited. Intervention arm participants will take one capsule of dietary supplement two times a day, 15 min before the main meal. Control arm participants will receive one capsule of placebo in the same way. The dietary supplement capsule contains the following ingredients: phytosterols, flavonoid-rich extract of bergamot fruit (Citrus bergamia), flavonoid-rich extract of olive fruit (Olea europaea), and vitamin K2. Participants will undergo a medical evaluation and chemical-clinical examinations, which include lipid profile, glycemia, biomarkers of renal, liver and cardiac/muscular functions, interleukins (IL 6, IL-32, IL-37, and IL-38), and innovative mediators of inflammation such as inflamma-miRs (miR-21 and miR-146a), at baseline, and after 6 and 12 weeks of treatment. The decrease in total cholesterol levels and inflammatory biomarkers will be the primary and secondary endpoints of the study. Discussion: This protocol study, planned to verify the effects of BruMeChol™ dietary supplementation in subjects with mild hypercholesterolemia, could also contribute to new study designs for next large-scale multicenter clinical trials. Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12619000170123. Retrospectively registered on 5 February 2019

Background: Nutraceutical combinations (NCs) against hypercholesterolemia are increasing in the marketplace. However, the availability of NCs without monacolin K is scarce even though the statin-intolerant population needs it. Methods: This study is a parallel-group, randomized, placebo-controlled, double-blind trial. We evaluated the effects of the NC containing phytosterols, bergamot, olive fruits, and vitamin K₂ on lipid profile and inflammatory biomarkers in 118 subjects (mean age ± SD, 57.9 ± 8.8 years; 49 men and 69 women) with hypercholesterolemia (mean total cholesterol ± SD, 227.4 ± 20.8 mg/dL) without clinical history of cardiovascular diseases. At baseline and 6 and 12 weeks of treatment, we evaluated lipid profile (total, LDL and HDL cholesterol, and triglycerides), safety (liver, kidney, and muscle parameters), and inflammatory biomarkers such as hs-CRP, leukocytes, interleukin-32, and interleukin-38 and inflammatory-microRNAs (miRs) miR-21, miR-126, and miR-146a. Results: Compared to the placebo, at 6 and 12 weeks, NC did not significantly reduce total cholesterol (p = 0.083), LDL cholesterol (p = 0.150), and triglycerides (p = 0.822). No changes were found in hs-CRP (p = 0.179), interleukin-32 (p = 0.587), interleukin-38 (p = 0.930), miR-21 (p = 0.275), miR-126 (p = 0.718), miR-146a (p = 0.206), myoglobin (p = 0.164), and creatine kinase (p = 0.376). Among the two reported, only one adverse event was probably related to the nutraceutical treatment. Conclusions: The evaluated nutraceutical combination did not change serum lipid profile and inflammatory parameters, at least not with the daily dose applied in the present study.

Disorders of lipoprotein metabolism are among the major risk factors for cardiovascular disease (CVD) development. Single nucleotide polymorphisms (SNPs) have been associated with the individual variability in blood lipid profile and response to lipid-lowering treatments. Here, we genotyped 34 selected SNPs located in coding genes related to lipid metabolism, inflammation, coagulation, and a polymorphism in the MIR499 gene—a microRNA previously linked to CVD—to evaluate the association with lipid trait in subjects with moderate dyslipidemia not on lipid-lowering treatment (Treatment-naïve (TN) cohort, n = 125) and in patients treated with statins (STAT cohort, n = 302). We also explored the association between SNPs and the effect of a novel phytochemical lipid-lowering treatment in the TN cohort. We found that 6 SNPs (in the MIR499, TNFA, CETP, SOD2, and VEGFA genes) were associated with lipid traits in the TN cohort, while no association was found with the response to twelve-week phytochemical treatment. In the STAT cohort, nine SNPs (in the MIR499, CETP, CYP2C9, IL6, ABCC2, PON1, IL10, and VEGFA genes) were associated with lipid traits, three of which were in common with the TN cohort. Interestingly, in both cohorts, the presence of the rs3746444 MIR499 SNP was associated with a more favorable blood lipid profile. Our findings could add information to better understand the individual genetic variability in maintaining a low atherogenic lipid profile and the response to different lipid-lowering therapies.

Introduction: Health-Related Quality of Life (HRQOL) is a key indicator of how chronic conditions such as type 2 diabetes (T2D) affect an individual’s overall well-being. This study explored the relationship between HRQOL and health-related data in older T2D participants. Methods: This retrospective study analyzed data from 987 participants with T2D who underwent checkups at the IRCCS INRCA Hospital, Ancona, Italy. Participants with an EQ-5D-3L index score of 1 were classified as having “no problems” in any dimension, and those with a value less than 1 were categorized as having “any problems”. Results: The mean age was 76.5 years (SD ± 4.5), and 46.5% were male. The “any problems” group (n = 795) was older and had longer diabetes duration, lower educational attainment, higher total cholesterol, higher triglycerides, and a higher Body Mass Index (BMI) with respect to the “no problems” group (n = 195). Multivariate logistic regression identified female sex (OR 2.14, 95% CI: 1.24–3.70), higher BMI (OR 1.07, 95% CI: 1.01–1.14), and depressive symptoms by the 5-item mini-Geriatric Depression Scale (mini GDS 5) (OR 2.43, 95% CI: 1.84–3.21) as significantly associated with lower HRQOL. Conversely, higher scores of the Instrumental Activities of Daily Living (IADL) (OR 0.77, 95% CI: 0.65–0.91) were related to better HRQOL. Conclusions: Female sex, overweight status, depressive symptoms, and lower physical performance are associated with impaired HRQOL in older Italian T2D outpatients. In particular, the EQ-5D-3L index provides a comprehensive index associated with depressive symptoms and low mobility.

Peritoneal dialysis (PD) catheter placement is considered a controversial procedure in patients with a history of abdominal surgeries or peritonitis. In these subjects, video laparoscopic (VLS)-assisted placement under general anesthesia (GA) is the gold standard procedure. However, older multimorbid patients are at high risk for complications in GA. In our opinion, thoracic spinal anesthesia (TSA) instead of GA could also be used in older multimorbid patients undergoing PD. Here, we report five cases of older multimorbid end-stage kidney disease (ESKD) patients aged 79.6 ± 3.5 years with a history of abdominal surgery or peritonitis needing renal replacement therapy. Overall comorbidity was high (Cumulative Illness Rating Scale (CIRS) comorbidity index 4.0 ± 1.2 and CIRS severity index 2.1 ± 0.5). We placed the PD catheter in these patients using the VLS-assisted placement under TSA. All subjects underwent TSA performed at the T9-T10 thoracic level, obtaining optimal pain control and no periprocedural side effects. This is the first attempt to utilize the TSA in PD catheter VLS placement in very old multimorbid patients. Further studies could be useful to confirm whether TSA can be successfully used in VLS-assisted PD catheter placement, especially in subjects ineligible for GA such as older frailty patients.