Effect of Bergamot Juice on LDL Cholesterol Level in Healthy Subjects

A Randomized Controlled Intervention Study to Assess the Effect of Bergamot Juice on LDL Cholesterol Level in Healthy Subjects

A single-centre, randomized (1:1), open label, controlled study to assess the lipid-lowering effect at 12 weeks of 400 cc/die bergamot juice consumption compared to free diet in healthy subjects

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: Bergamot Juice

Detailed Description

Cardiovascular diseases (CV) are the first cause of morbidity and mortality in industrialized countries. Hypercholesterolemia is the main CV risk factor: high cholesterol values are directly and linearly correlated with CV events and mortality in the absence of a threshold value. Intervention studies show unequivocally how the decrease in cholesterol levels significantly reduces CV risk. Bergamot juice is considered a possible food with nutraceutical activity, especially as regards the control of blood cholesterol levels. It is now known that bergamot juice has chemical components that can positively affect blood cholesterol levels. These compounds are called 3-hydroxy-3-methyl flavonoids (HMG-flavonoids) and are peculiar to some citrus plants and in particular to the Citrus bergamia species. The aim of this study is to provide clinical evidence of the effect of these metabolites on cholesterol levels. Specifically, a single-centre, randomized (1:1), open label, controlled study is conducted in healthy subjects to evaluate the possible lipid-lowering effects at 12 weeks of 400 cc/die of bergamot juice consumption compared to a free diet. Changes in the following parameters: body mass index (BMI kg/m²), waist circumference, glycemia, insulin, glycated hemoglobin (HbA1C), total cholesterol, HDL cholesterol and triglycerides, plasma levels of inflammatory cytokines, C-reactive protein (hsCRP) and Proprotein convertase subtilisin / kexin type 9 (PCSK9) are also investigated at 12 weeks.

• Study Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alessandra Dei Cas, Prof.; Phone Number: +390521033321; Email: alessandra.deicas@unipr.it

Study Locations

• Italy
  • Parma, Italy, 43126
    • Recruiting
    • University of Parma, Department of Medicine and Surgery
    • Contact: Alessandra Dei Cas, Prof; Phone Number: +39 0521033321; Email: alessandra.deicas@unipr.it
    • Contact: Raffaella Aldigeri, Dr; Phone Number: +39 0521033306; Email: raffaella.aldigeri@unipr.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Caucasian persons of both sexes aged ≥18 and ≤75 years
• ability to understand the methods, purposes and implications of the study, and to give free and informed consent

Exclusion Criteria:

• Diabetes mellitus defined according to ADA criteria
• Present or past history of alcohol or drug abuse or organ failure (kidney and liver)
• Tumor pathologies in the last 5 years;
• Past or present cerebro-vascular diseases;
• Subjects taking drugs or supplements active on the lipid profile;
• Pregnancy or breastfeeding
• Presence of severe or monogenic dyslipidemia
• Use of antibiotics in the last three months before enrollment
• Subjects who are on a diet for any reason
• Individuals who have intentionally or unintentionally lost 3 kg or more of body weight in the past 3 months.
• Known allergies to some components of the product
• Subjects who do not like bergamot

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Free diet
Experimental: Bergamot juice; Consumption of 400 cc/die of Bergamot juice (35% in water sweetened with stevia) for 12 weeks	Dietary supplement: Bergamot Juice; Bergamot Juice (35% in water)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low-density lipoprotein (LDL) cholesterol	Changes in LDL cholesterol at 12 weeks in both study arms	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
body mass index (BMI)	Changes in body mass index (BMI) at 12 weeks in both study arms	12 weeks
waist circumference	Changes in waist circumference at 12 weeks in both study arms	12 weeks
fasting plasma glucose (FPG)	Changes in FPG at 12 weeks in both study arms	12 weeks
insulinemia	Changes in insulinemia at 12 weeks in both study arms	12 weeks
glycated hemoglobin	Changes in glycated hemoglobin at 12 weeks in both study arms	12 weeks
total cholesterol	Changes in total cholesterol at 12 weeks in both study arms	12 weeks
high density lipoprotein (HDL) cholesterol	Changes in HDL cholesterol at 12 weeks in both study arms	12 weeks
triglycerides	Changes in triglycerides at 12 weeks in both study arms	12 weeks
plasma levels of inflammatory cytokines	Changes in plasma levels of inflammatory cytokines (IL-1,IL-6,IL-10,hsPCR,TNF-alpha) at 12 weeks in both study arms	12 weeks
Proprotein convertase subtilisin/kexin type 9 (PCSK9)	Changes in PCSK9 at 12 weeks in both study arms	12 weeks

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero-Universitaria di Parma
• Collaborators: University of Parma

Publications and helpful links

General Publications

• Silverman MG, Ference BA, Im K, Wiviott SD, Giugliano RP, Grundy SM, Braunwald E, Sabatine MS. Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis. JAMA. 2016 Sep 27;316(12):1289-97. doi: 10.1001/jama.2016.13985.
• Ballistreri G, Amenta M, Fabroni S, Consoli V, Grosso S, Vanella L, Sorrenti V, Rapisarda P. Evaluation of lipid and cholesterol-lowering effect of bioflavonoids from bergamot extract. Nat Prod Res. 2021 Dec;35(23):5378-5383. doi: 10.1080/14786419.2020.1768085. Epub 2020 May 22.
• Cappello AR, Dolce V, Iacopetta D, Martello M, Fiorillo M, Curcio R, Muto L, Dhanyalayam D. Bergamot (Citrus bergamia Risso) Flavonoids and Their Potential Benefits in Human Hyperlipidemia and Atherosclerosis: an Overview. Mini Rev Med Chem. 2016;16(8):619-29. doi: 10.2174/1389557515666150709110222.
• Di Donna L, De Luca G, Mazzotti F, Napoli A, Salerno R, Taverna D, Sindona G. Statin-like principles of bergamot fruit (Citrus bergamia): isolation of 3-hydroxymethylglutaryl flavonoid glycosides. J Nat Prod. 2009 Jul;72(7):1352-4. doi: 10.1021/np900096w.
• Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, Hegele RA, Krauss RM, Raal FJ, Schunkert H, Watts GF, Boren J, Fazio S, Horton JD, Masana L, Nicholls SJ, Nordestgaard BG, van de Sluis B, Taskinen MR, Tokgozoglu L, Landmesser U, Laufs U, Wiklund O, Stock JK, Chapman MJ, Catapano AL. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017 Aug 21;38(32):2459-2472. doi: 10.1093/eurheartj/ehx144.

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2022
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: October 18, 2022
• First Submitted That Met QC Criteria: October 18, 2022
• First Posted (Actual): October 21, 2022

Study Record Updates

• Last Update Posted (Actual): October 21, 2022
• Last Update Submitted That Met QC Criteria: October 18, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 562/2021/SPER /UNIPR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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