Effect of a Dietary Supplement on Lipid Pattern and Liver Parameters in Hypercholesterolemia

Evaluation of the Effect of a Dietary Supplement on Lipid Pattern and Liver Parameters in Moderately Hypercholesterolemic Subjects: a Double-blind, Placebo-controlled, Randomized, Clinical Trial

The joint ESC/EAS guidelines for the management of dyslipidaemias recommend, for patients at low/moderate CV risk with raised LDL-C, a set of measures collectively defined as "lifestyle interventions", with use of drugs only if the LDL-C levels cannot be controlled with such lifestyle interventions. "Lifestyle interventions" also includes food supplements. The reason is the following: a simple "dietary advice" has been shown (Cochrane review and meta-analysis, Rees et al, 2013) to achieve a modest reduction of total-C and LDL-C. The review reports: Dietary advice reduced total serum cholesterol by 0.15 mmol/L (95% CI 0.06 to 0.23) and LDL cholesterol by 0.16 mmol/L (95% CI 0.08 to 0.24) after 3 to 24 months." An average reduction of LDL-C by 0.16 mmol/L (6.2 mg/dL) is definitely insufficient to control the level of LDL-C in those subjects. Therefore, those subjects would lose motivation to keep dieting. In this context, use of supplements would significantly amplify the result of diet.

A significant proportion of ischemic cardiovascular events are believed to be supported by the coexistence of traditional cardiovascular risk factors such as diabetes, hypertension, dyslipidemia, smoking, and others. The aggregation of these factors is accompanied by a significant increase in the risk of cardiovascular events.

Observational studies shown the existence of a relationship between cholesterolemia and coronary heart disease, clearly showing that subjects with even modestly increased total cholesterol values over time develop both fatal and non-fatal vascular events with a higher frequency compared to subjects with similar characteristics, but with lower basal values of cholesterol.

Numerous controlled intervention studies, on the other hand, have shown that there is a close correlation between cholesterol reduction and cardiovascular risk; in fact, reductions in the plasma concentration of total and LDL-C, obtained through lifestyle modification or specific drugs, result in reductions in the incidence of major coronary events. The effectiveness of these interventions has been demonstrated both in subjects in primary prevention and in patients in secondary prevention.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Other: Placebo; Dietary supplement: Dietary supplement

Detailed Description

The National Cholesterol Education Program (NCEP) has defined in the ATP III report the target values of LDL cholesterol (LDL-C) to be reached with interventions on food and / or pharmacological habits to perform an effective cardiovascular prevention.

Although the atherogenic action of hypercholesterolemia is largely attributable to a direct damage action on the vascular endothelium, recent studies suggest that the activation of a low-grade systemic pro-inflammatory state, typical of the patient with cardiovascular risk factors, in turn would play a role in the determinism of endothelial damage and atheroma degeneration of the arteries. It is believed that the systemic inflammation, documented by the determination of some humoral signs of inflammation (e.g. C-reactive protein, interleukin-6, tumor necrosis factor-alpha), may contribute to increase of cardiovascular risk; it also seems that elevated plasma levels of the aforementioned markers can exert a synergistic pro-atherogenic action with the various cardiovascular risk factors.

The inflammatory state can modulate the atherosclerotic process at various levels, determining endothelial activation, promoting leukocyte chemotaxis in the sub-intimal space of the arterial wall and therefore the formation of an atheromatous plaque rich in inflammatory cells; the latter represents the lesion responsible for the vast majority of the coronary and cerebrovascular events observed in patients with cardiovascular risk factors.

C-reactive protein (hsCRP) has been identified as an indicator of systemic inflammation and a predictor of cardiovascular risk. In the AFCAPS / TexCAPS study, subjects with normal LDL-C levels and low levels of HDL-C were shown to encounter a greater number of coronary ischemic events as baseline hsCRP levels increased. On the contrary, in the Justification for the Use of statins in Prevention-an Intervention Trial Evaluating Rosuvastatin (JUPITER), the treatment with rosuvastatin in subjects with high hsCRP was associated with a significant reduction of CV events even in patients with low LDL-C level.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Arrigo FG Cicero, MD; Phone Number: +39516362224; Email: arrigo.cicero@unibo.it

Study Locations

• Italy
  • BO
    • Bologna, BO, Italy, 40138
      • University of Bologna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subjects agree to participate in the study and having dated and signed the informed consent form.
• Subjects who have the capability to communicate, to make themselves understood, and to comply with the study's requirements.
• Male or female aged ≥ 18 years and ≤ 70 years old.
• LDL-Cholesterol plasma levels >115 mg/dL and < 190 mg/dL.
• TG<400 mg/dL.
• Subjects who, according to the SCORE charts, have a low or moderate cardiovascular risk (defined as a total cardiovascular risk < 5%) and for whom, according to ESC/EAS guidelines 2012, the intervention strategy does not require a pharmacological lipid-lowering intervention.

Exclusion Criteria:

• Subjects already affected by cardiovascular diseases (secondary prevention) or with estimated 10 years cardiovascular disease risk> 5%;
• Obesity (BMI>30 kg/m2) or diabetes mellitus;
• Assumption of lipid lowering drugs or food supplements, or drugs potentially affecting the lipid metabolism;
• Antihypertensive treatment not stabilized since at least 3 months;
• Anticoagulants therapy
• Uncontrolled hypertension (systolic blood pressure> 190 mmHg or diastolic arterial pressure> 100 mmHg);
• Known current thyroid, gastrointestinal or hepatobiliary diseases;
• Any medical or surgical condition that would limit the patient adhesion to the study protocol;
• Abuse of alcohol or drugs (current or previous);
• History of malignant neoplasia in the 5 years prior to enrolment in the study;
• History or clinical evidence of inflammatory disease such as severe arthritis, systemic lupus erythematosus or chronic inflammatory diseases or current therapy with immunosuppressive agents or long-term glucocorticoids;
• History or clinical evidence of any significant concomitant disease that could compromise the safety of the subject or the possibility of completing the study;
• Known previous intolerance to the tested nutraceutical
• Women in fertile age not using consolidated contraceptive methods
• Pregnancy and Breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo comparator; Placebo	Other: Placebo; Oral administration: 1 tablet/day at evening meal
Active Comparator: Active Comparator; Dietary supplement	Dietary supplement: Dietary supplement; Dietary supplement formulated with 400 mg Bergamot d.e. obtained from different parts of the Citrus Bergamot whole fruit (Citrus bergamia Risso et Poiteau, fructus), specifically from fresh fruits collected from November to February (Brumex TM). Oral administration: 1 tablet/day at evening meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LDL-cholesterolemia absolute reduction from baseline and between groups	Absolute reduction of LDL-cholesterolemia after 12 weeks of treatment	12 weeks
LDL-cholesterolemia % reduction from baseline and between groups	% reduction of LDL-cholesterolemia after 12 weeks of treatment	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute reduction from baseline and between groups in other lipid fractions, apolipoproteins and their ratios	Absolute reduction of serum concentrations of total cholesterol, HDL-cholesterol, apolipoprotein B, triglycerides and their ratios after 12 weeks of treatment	12 weeks
% reduction from baseline and between groups in other lipid fractions, apolipoproteins and their ratios	% reduction of of serum concentrations of total cholesterol, HDL-cholesterol, apolipoprotein B, triglycerides and their ratios after 12 weeks of treatment	12 weeks
% reduction from baseline and between groups in blood pressure levels	% reduction of systolic and diastolic blood pressure after 12 weeks of treatment	12 weeks
Absolute reduction from baseline and between groups in blood pressure levels	Absolute reduction of systolic and diastolic blood pressure after 12 weeks of treatment	12 weeks
% reduction from baseline and between groups in creatine phosphokinase (CPK) serum levels	% reduction of creatine phosphokinase (CPK) serum levels after 12 weeks of treatment	12 weeks
Absolute reduction from baseline and between groups in creatine phosphokinase (CPK) serum levels	Absolute reduction of creatine phosphokinase (CPK) serum levels after 12 weeks of treatment	12 weeks
% reduction from baseline and between groups in anthropometric parameters	% reduction of body mass index after 12 weeks of treatment	12 weeks
Absolute reduction from baseline and between groups in anthropometric parameters	Absolute reduction of body mass index after 12 weeks of treatment	12 weeks
Absolute reduction from baseline and between groups in liver parameters	Absolute reduction of GOT, GPT and gamma-GT after 12 weeks of treatment	12 weeks
% reduction from baseline and between groups in liver parameters	% reduction of GOT, GPT and gamma-GT after 12 weeks of treatment	12 weeks

Collaborators and Investigators

• Sponsor: University of Bologna
• Investigators: Principal Investigator: Claudio Borghi, MD, S. Orsola-Malpighi University Hospital

Publications and helpful links

General Publications

• Pierdomenico M, Cicero AFG, Veronesi M, Fogacci F, Riccioni C, Benassi B. Effect of Citrus bergamia extract on lipid profile: A combined in vitro and human study. Phytother Res. 2023 Sep;37(9):4185-4195. doi: 10.1002/ptr.7897. Epub 2023 Jun 13.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2020
• Primary Completion (Actual): October 4, 2021
• Study Completion (Actual): October 4, 2021

Study Registration Dates

• First Submitted: July 21, 2020
• First Submitted That Met QC Criteria: July 21, 2020
• First Posted (Actual): July 24, 2020

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: NUT1-BO-2019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No