Grape Polyphenols and Metabolic Syndrome (PolyGrape)

Effects of Polyphenols From a Table Grape on the Lipidomic Profile and Serum LDL Fractions: Possible Implications in the Metabolic Syndrome

Fruits and vegetables are beneficial for patients with metabolic syndrome, a condition characterized by the coexistence of various risk factors (obesity, hypertension, hypercholesterolemia, insulin resistance) that predispose to cardiovascular disease and diabetes. Diets such as the Mediterranean diet, rich in flavonoids and polyphenolic compounds can exert a high anti-inflammatory, antithrombotic and antiproliferative action. Several studies have shown that grape polyphenols exert a crucial protective action against the onset of cardiovascular, neurodegenerative, and cancer diseases. On the other hand, little information is available on the health effects deriving from the consumption of table grapes on cell membranes lipidomic profile. On this basis, the aim of this study is the evaluation of possible changes in lipidomic profile and plasma antioxidant activity induced by a diet enriched with table grape polyphenols.

Study Overview

• Status: Active, not recruiting
• Conditions: Metabolic Syndrome, Protection Against
• Intervention / Treatment: Dietary supplement: Table Grape supplement

Detailed Description

Purified polyphenols extracted by table grape can decrease cell proliferation in vitro and exert anti-atherosclerotic and antithrombotic activities, regulating endothelial function. Literature studies have already evaluated the cytostatic and apoptotic effects produced by table grape extracts from different cultivars, demonstrating a different behavior based on extract composition. The beneficial effects of polyphenols have been attributed exclusively to their direct antioxidant action; however, in recent years it has emerged that polyphenols can interact with intracellular signaling mechanisms, modulating the activity of transcription factors involved in cell lipid metabolism. Lipidomic analysis studies the lipids in a "dynamic" way, monitoring the changes in membrane phospholipids content, caused by inflammation, stress, or malnutrition. These changes can also affect the cellular and plasmatic prothrombotic potential, which results altered in metabolic diseases. Recently, alterations in erythrocytes lipidomic profile have been detected in subjects with steatosis. Moreover, in patients with colorectal cancer patients, the presence of metastases at the time of surgery was associated with an altered profile of fatty acids in the membrane of colonic tissue cells.

Moreover, data in literature show how diet and functional foods can modify serum lipid content, in particular, an important role in the onset of dysmetabolic diseases is undoubtedly played by the different fractions of Low-Density Lipoproteins (LDL). The presence of smaller LDL fractions in the serum, such as fraction 3 and fraction 4, has been associated with the onset of cardiovascular disease and myocardial infarctions. Therefore, understanding the molecular mechanisms underlying the effects of nutraceuticals is essential to develop prevention and intervention strategies on subjects at risk for metabolic syndrome.

On this basis, the aim of this study is the evaluation of possible changes happening in lipidomic profile, plasma antioxidant activity and plasma prothrombotic potential induced by a diet enriched with table grape polyphenols in subjects with metabolic syndrome.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Bari
    • Castellana Grotte, Bari, Italy, 70013
      • Irccs Saverio de Bellis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age > 30 years and <65 years
• overweight.

Exclusion Criteria:

• cardiovascular disease.
• stroke
• treatment with insulin or oral hypoglycemic drugs
• fasting glucose > 126 mg / dl, or casual glycemia > 200 mg / dl
• more than 20 g/day of alcohol intake
• serious medical conditions that may compromise participation in the trial
• subjects following a special diet or involved in a weight-loss program or unable to follow a diet for religious or other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Diet with table grape; Table grape (5g/Kg) administered for four weeks with dietary recommendations. A strict restriction of fruits and the limitation of other foods containing polyphenols will be necessary.	Dietary supplement: Table Grape supplement; 5g/Kg of table grape for four weeks with dietary recommendations along with a strict restriction of fruits and limitation of other foods containing polyphenols.
NO_INTERVENTION: Specific dietary advice; Dietary recommendations (such as limitation of alcohol, caffeine), and low consumption of fruits.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in serum concentrations (mg/dL) of cholesterol, triglycerides, glucose	Blood samples will be taken after at least 12 hours of fasting and the concentrations of cholesterol. triglycerides, and glucose will be assessed according to the standard laboratory methods (commercially available kits).	Before the start of the study (time 0), after four weeks (time 1) and after eight weeks (time 2)
Changes in blood concentration of fatty acids (stearic acid, oleic acid, arachidonic acid, eicosaepentanoic acid) expressed as percentage (%)	All human blood samples are treated with chloroform: methanol (2:1, v/v), and the samples are centrifuged. The lower layer, containing fatty acids, are removed with care, replaced in a new tube and dried by a centrifugal evaporator. The fatty acid methyl ester (FAME) is obtained by adding toluene and BF3. Samples are collected and transferred into a vial and analyzed by gas chromatography.	Before the start of the study (time 0) and after eight weeks (time 2)
Changes in serum concentration of single subfractions of LDL (expressed as mg/dL)	Small dense LDL analysis: Small dense Lipoproteins (sdLDL) are assayed using Lipoprint LDL System (Quantimetrix, USA). Each serum sample is applied on high resolution polyacrylamide gel tube in order to separate LDL fractions and subfractions by electrophoresis. The resolved lipoproteins bands are scanned and analyzed.	Before the start of the study (time 0) and after eight weeks (time 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the concentrations of radical monocation of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) expressed as µM Trolox equivalents/g of dry weight	The ABTS assay will be performed using the commercially available ZENBIO-AOX-1 kit.	Before the start of the study (time 0), after four weeks (time 1) and after eight weeks (time 2)
Changes in plasma prothrombotic potential	The plasma prothrombotic potential will be evaluated using a functional test able to monitor the entire kinetics of thrombin generation, including its inactivation by plasma physiological inhibitors. In these tests, the coagulation will be activated by purified tissue factor.	Before the start of the study (time 0), after four weeks (time 1) and after eight weeks (time 2)
Changes in plasma grape miRNA content	Total serum RNA, including Small RNAs, will be extracted from plasma (200µL) of the subjects involved in the study using the miRNeasy Mini Kit (QIAGEN). After checking the concentration and quality, the effective presence of miRNAs will be verified by retro-transcription with a specific miRNA kit (TaqMan miRNA Reverse Transcription kit - Life Technologies) using Real Time-polymerase chain reaction (PCR) method.	Before the start of the study (time 0) (time 1) and after eight weeks (time 2)

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
• Investigators: Principal Investigator: Maria Notarnicola, ScD, IRCCS "Saverio de Bellis" Castellana Grotte

Publications and helpful links

General Publications

• Li B, Zhang C, Zhan YT. Nonalcoholic Fatty Liver Disease Cirrhosis: A Review of Its Epidemiology, Risk Factors, Clinical Presentation, Diagnosis, Management, and Prognosis. Can J Gastroenterol Hepatol. 2018 Jul 2;2018:2784537. doi: 10.1155/2018/2784537. eCollection 2018.
• Liu YC, Chen WL, Kung WH, Huang HD. Plant miRNAs found in human circulating system provide evidences of cross kingdom RNAi. BMC Genomics. 2017 Mar 14;18(Suppl 2):112. doi: 10.1186/s12864-017-3502-3.
• Mlotshwa S, Pruss GJ, MacArthur JL, Endres MW, Davis C, Hofseth LJ, Pena MM, Vance V. A novel chemopreventive strategy based on therapeutic microRNAs produced in plants. Cell Res. 2015 Apr;25(4):521-4. doi: 10.1038/cr.2015.25. Epub 2015 Feb 27. No abstract available.
• Notarnicola M, Caruso MG, Tutino V, Bonfiglio C, Cozzolongo R, Giannuzzi V, De Nunzio V, De Leonardis G, Abbrescia DI, Franco I, Intini V, Mirizzi A, Osella AR. Significant decrease of saturation index in erythrocytes membrane from subjects with non-alcoholic fatty liver disease (NAFLD). Lipids Health Dis. 2017 Aug 23;16(1):160. doi: 10.1186/s12944-017-0552-0.
• Ammollo CT, Semeraro F, Milella RA, Antonacci D, Semeraro N, Colucci M. Grape intake reduces thrombin generation and enhances plasma fibrinolysis. Potential role of circulating procoagulant microparticles. J Nutr Biochem. 2017 Dec;50:66-73. doi: 10.1016/j.jnutbio.2017.08.012. Epub 2017 Sep 1.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2019
• Primary Completion (ACTUAL): November 1, 2020
• Study Completion (ANTICIPATED): November 1, 2022

Study Registration Dates

• First Submitted: August 6, 2019
• First Submitted That Met QC Criteria: August 9, 2019
• First Posted (ACTUAL): August 12, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 22, 2022
• Last Update Submitted That Met QC Criteria: March 20, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: diet; metabolic syndrome; polyphenols; lipidomics
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Metabolic Syndrome
• Other Study ID Numbers: RC2019019

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