Effects of a novel nutraceutical combination (BruMeChol™) in subjects with mild hypercholesterolemia: study protocol of a randomized, double-blind, controlled trial

Abstract

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

The Association between Single Nucleotide Polymorphisms, including miR-499a Genetic Variants, and Dyslipidemia in Subjects Treated with Pharmacological or Phytochemical Lipid-Lowering Agents

“…The six SNPs associated with blood lipid profile variables in the TN cohort were then analyzed as predictors of the response to the phytochemical product administered in a randomized clinical trial [ 19 ]. Results of the analysis, performed after adjustment for age and gender, revealed no significant interaction between phytochemical intervention and each SNP on variations in blood lipid parameters observed at the 12-week follow-up visit ( Supplementary Table S2 ).…”

“…20), previously investigated in the framework of lipid metabolism, were significantly associated with lipid traits in the treatment-naïve (TN) cohort. However, no significant effect of these SNPs was found on the response to a twelve-week treatment with a phytochemical administered to these subjects as a potential lipid-lowering supplement in the context of a randomized clinical trial [ 19 ]. Here, we aimed at exploring whether interindividual genetic variations in genes involved in systemic inflammation and lipid metabolism affected the response to the polyphenols and plant sterols contained in the dietary supplements.…”

“…Exclusion criteria included a therapy with statins or food supplements with lipid-reducing effects or with anticoagulants, hypothyroidism, or hyperthyroidism; diabetes; intestinal malabsorption, acute illnesses, neoplastic disease or life expectancy less than one year; statin non-related liver disease; severe chronic renal failure; participation in a clinical trial of intervention for lipid modulations in the previous three months; presence of cognitive disorders and other impediments that do not guarantee the correct adherence to the study treatments; current or presumed pregnancy and pregnancy planning and incapacity; and impossibility or unavailability to sign the written consent. Participants were enrolled for participation in a randomized, double-blind, placebo-controlled, parallel group clinical trial (ACTRN12619000170123) evaluating the lipid-lowering effect of a dietary supplement [ 19 ]. Briefly, subjects were randomized to receive two capsules a day—one capsule taken 15 min before lunch and one capsule 15 min before dinner—of either a placebo or a dietary supplement containing 400 mg phytosterols, 100 mg bergamot fruit, 20 mg olive fruit extract, and 52 mcg vitamin K2.…”

Randomized, Double-Blind, Placebo-Controlled Trial to Test the Effects of a Nutraceutical Combination Monacolin K-Free on the Lipid and Inflammatory Profile of Subjects with Hypercholesterolemia

“…: ACTRN12619000170123). The study protocol was previously described in detail [ 11 ]. Here, we report the summary of the study methods.…”

Nutraceutical Combinations in Hypercholesterolemia: Evidence from Randomized, Placebo-Controlled Clinical Trials

“…RCTs are a gold standard for clinical research to verify the efficacy and safety of a novel NC [ 104 ]. RCTs study designs comprehend four major categories: parallel, crossover, cluster, and fractional [ 105 ].…”