Clinical trial NCT05589636: Effect of Bergamot Juice on LDL Cholesterol Level in Healthy Subjects
Official title: A Randomized Controlled Intervention Study to Assess the Effect of Bergamot Juice on LDL Cholesterol Level in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Healthy
Lead sponsor: Azienda Ospedaliero-Universitaria di Parma
Sponsor class: OTHER
Collaborators: name: University of Parma
First posted: 2022-10-21
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Low-density lipoprotein (LDL) cholesterol
timeFrame: 12 weeks
Secondary outcomes:
measure: body mass index (BMI)
timeFrame: 12 weeks
measure: waist circumference
timeFrame: 12 weeks
measure: fasting plasma glucose (FPG)
timeFrame: 12 weeks
measure: insulinemia
timeFrame: 12 weeks
measure: glycated hemoglobin
timeFrame: 12 weeks
measure: total cholesterol
timeFrame: 12 weeks
measure: high density lipoprotein (HDL) cholesterol
timeFrame: 12 weeks
measure: triglycerides
timeFrame: 12 weeks
measure: plasma levels of inflammatory cytokines
timeFrame: 12 weeks
measure: Proprotein convertase subtilisin/kexin type 9 (PCSK9)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Parma
country: Italy
facility: University of Parma, Department of Medicine and Surgery
Study officials:
References:
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citation: 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.
citation: 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.
citation: 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.
citation: 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.