Effects of Dietary Polyphenols and ω-3 Fatty Acids on Cardiovascular Risk Factors in High Risk Subjects (Etherpaths)

Effects of Polyphenols and Omega-3 Fatty Acids on Cardiovascular Rik Factors (Focusing on Postprandial Lipids Metabolism) in Subjects With High Risk for Type 2 Diabetes and Cardiovascular Diseases

The aim of this study is to explore if a 8-weeks dietary intervention with polyphenols and omega 3 fatty acids (alone or combined) may be effective on postprandial lipids metabolism and other cardiovascular risk factors in people at high cardiovascular risk.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Other: Diet rich in omega-3 fatty acids; Other: Diet rich in polyphenols; Other: diet rich in omega-3 and polyphenols; Other: Control diet

Detailed Description

Fish consumption is associated with a lower cardiovascular risk and dietary supplementation with ω-3 fatty acids reduces plasma triglyceride levels. The mechanisms of action of ω-3 fatty acids are currently not completely understood. It has been hypothesized that polyunsaturated ω-3 fatty acids beneficial effects may be mediated through their ability to facilitate plasmalogen replenishment.

Polyphenols are associated with beneficial effects on some cardiovascular risk factors, in particular with a reduced lipid oxidation. Less data are available on their effects on lipid metabolism. Recent data suggest that these effects could be mediated by changes in plasmalogen levels.

The effects on lipid metabolism of combining the two dietary approaches (ω-3 fatty acids and polyphenols) are not known.

While developed populations live for the most part in the postprandial state, much of the information on lipid metabolism refers to fasting condition.

Dietary Intervention Study Design

Eighty people at high cardiovascular risk randomly assigned to one of the four different nutritional 8-week interventions:

(A) Control diet poor in omega-3 fatty acids and polyphenols (B) Diet rich in omega-3 fatty acids (C) Diet rich in polyphenols (D) Diet rich in omega-3 fatty acids and polyphenols

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Naples
    • Napoli, Naples, Italy, 80131
      • Federico II University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• bmi >25<35 kg/m2
• High waist circumference (men >102 cm, women >88 cm) + one the following components of metabolic syndrome :

Fasting plasma triglycerides ≥150 mg/dl Fasting HDL-col <40 mg/dl (men) and <50 mg/dl (women) Fasting plasma glucose 100-125 mg/dl

Exclusion Criteria:

• Fasting plasma triglycerides ≥400 mg/dl and cholesterol >270 mg/dl
• Cardiovascular events (AMI and/or stroke) in the last 6 months
• Diabetes mellitus
• Regular intensive physical activity
• Kidney (serum creatinine >1.7 mg/dl) and liver (transaminases >double)
• Hypolipidemic or antinflammatory drugs
• Anemia (Hb <12 g/dl) or any other chronic disease

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: B group; Diet rich in omega-3 fatty acids	Other: Diet rich in omega-3 fatty acids; fish at least 3 times per week, large leaf vegetables
Experimental: C group; Diet rich in polyphenols	Other: Diet rich in polyphenols; extra virgin olive oil, green tea, berries,fruits rich in polyphenols, dark chocolate, decaffenated coffee
Experimental: D group; Diet rich in polyphenols and in omega-3 fatty acids	Other: diet rich in omega-3 and polyphenols; Fish at least 3 times x week,large leaf vegetables + extra virgin olive oil, green tea, berries,fruits rich in polyphenols, dark chocolate, decaffenated coffee
Placebo Comparator: A group (control group); diet with low content of omega-3 fatty acids and polyphenols	Other: Control diet; low content of omega-3 fatty acids and polyphenols (low intake of fish, nuts and legumes,oil rich in monounsaturated fatty acids, vegetables and fruits poor in polyphenols)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
incremental AUC after a test meal of triglycerides concentration in chylomicrons and VLDL fraction	48 months

Secondary Outcome Measures

Outcome Measure	Time Frame
insulin sensitivity	48 months
plasma and adipose tissue adipokines	48 months
endothelial function	48 months

Collaborators and Investigators

• Sponsor: Federico II University
• Investigators: Study Director: Giovanni Annuzzi, Federico II University

Publications and helpful links

General Publications

• Costabile G, Vetrani C, Bozzetto L, Giacco R, Bresciani L, Del Rio D, Vitale M, Della Pepa G, Brighenti F, Riccardi G, Rivellese AA, Annuzzi G. Plasma TMAO increase after healthy diets: results from 2 randomized controlled trials with dietary fish, polyphenols, and whole-grain cereals. Am J Clin Nutr. 2021 Oct 4;114(4):1342-1350. doi: 10.1093/ajcn/nqab188.
• Della Pepa G, Vetrani C, Vitale M, Bozzetto L, Costabile G, Cipriano P, Mangione A, Patti L, Riccardi G, Rivellese AA, Annuzzi G. Effects of a diet naturally rich in polyphenols on lipid composition of postprandial lipoproteins in high cardiometabolic risk individuals: an ancillary analysis of a randomized controlled trial. Eur J Clin Nutr. 2020 Jan;74(1):183-192. doi: 10.1038/s41430-019-0459-0. Epub 2019 Jun 27.
• Bozzetto L, Annuzzi G, Ragucci M, Di Donato O, Della Pepa G, Della Corte G, Griffo E, Anniballi G, Giacco A, Mancini M, Rivellese AA. Insulin resistance, postprandial GLP-1 and adaptive immunity are the main predictors of NAFLD in a homogeneous population at high cardiovascular risk. Nutr Metab Cardiovasc Dis. 2016 Jul;26(7):623-629. doi: 10.1016/j.numecd.2016.01.011. Epub 2016 Apr 14.
• Bozzetto L, Annuzzi G, Pacini G, Costabile G, Vetrani C, Vitale M, Griffo E, Giacco A, De Natale C, Cocozza S, Della Pepa G, Tura A, Riccardi G, Rivellese AA. Polyphenol-rich diets improve glucose metabolism in people at high cardiometabolic risk: a controlled randomised intervention trial. Diabetologia. 2015 Jul;58(7):1551-60. doi: 10.1007/s00125-015-3592-x. Epub 2015 Apr 24.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: June 14, 2010
• First Submitted That Met QC Criteria: June 30, 2010
• First Posted (Estimate): July 1, 2010

Study Record Updates

• Last Update Posted (Estimate): June 19, 2013
• Last Update Submitted That Met QC Criteria: June 18, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: polyphenols omega-3 postprandial lipemia adipose tissue
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Insulin Resistance; Hyperinsulinism; Metabolic Syndrome
• Other Study ID Numbers: EpWP5