The Role of Gut Microbiome on Cardiovascular Health Benefits of Dietary Lignans (CardioFlax Study).

The Role of Gut Microbiome on Cardiovascular Health Benefits of Dietary Lignans ( CardioFlax Study).

The aim of this study is to investigate the effects of gut microbial metabolism of flaxseed lignans on cardiovascular health. Enterolactone is the main gut microbial metabolite of lignans. The study population will be stratified in low and high enterolactone producers and will investigate whether high producers will have greater benefits than low producers, and whether low producers may become high producers after daily consumption of lignans over 8 weeks. The investigators will evaluate changes in endothelial function, blood pressure, arterial stiffness, insulin resistance, lipid profile and gut microbiome composition after 8 weeks daily consumption of flaxseed lignans.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Dietary supplement: lignan capsules contain 300 mg flaxseed (SDG) extract; Dietary supplement: Placebo treatment matching intervention

Detailed Description

Epidemiological studies have shown inverse relation between enterolactone levels and cardiovascular mortality. Participants will be stratified from first phase (NCT03573414) and then randomly allocated to treatment or placebo. Outcomes are measured at baseline and after 8 weeks post consumption.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 9NH
    • King's College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy women aged 20-70 years
• BMI between 18 and 35 kg/m2
• Subjects are willing to maintain their normal eating/drinking habits and exercise habits to avoid changes in body weight over the duration of the study
• Are able to understand the nature of the study
• Able to give signed written informed consent
• Signed informed consent form

Exclusion Criteria:

• Medical history of cardiovascular disease including coronary artery disease, cerebrovascular disease and peripheral artery disease
• Hypertensive, as defined as SBP superior or equal to 140 mmHg, and CBP superior or equal to 90 mmHg
• Participants with BMI superior to 35 kg/m2, and BMI below 18 kg/m2
• Medical history of diabetes mellitus, metabolic syndrome, terminal renal failure or malignancies
• Abnormal heart rhythm (lower or higher than 60-100 bmp)
• Allergies to flaxseed or other significant food allergy
• Subjects under medication that can affect the cardiovascular system or on vitamin/dietary supplements.
• Subjects who have lost more than 10% of their weight in the past 6 months or are currently in a diet
• Subjects who reported participant in another study within one month before the study start
• Smoker Subjects
• Pregnant women or planning to become pregnant in the next 6 months
• Any reason or condition that in the judgment of the clinical investigator(s) may put the subject at unacceptable risk or that may preclude the subject from understanding or complying with the study's requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High enterolactone producer's (intervention); lignan capsules contain 300 mg flaxseed (SDG) extract	Dietary supplement: lignan capsules contain 300 mg flaxseed (SDG) extract; lignan capsules contain 300 mg flaxseed (SDG) extract
Placebo Comparator: High enterolactone producer's (Control); Placebo treatment matching intervention	Dietary supplement: Placebo treatment matching intervention; Placebo treatment matching intervention
Active Comparator: Low enterolactone producer's (intervention); lignan capsules contain 300 mg flaxseed (SDG) extract	Dietary supplement: lignan capsules contain 300 mg flaxseed (SDG) extract; lignan capsules contain 300 mg flaxseed (SDG) extract
Placebo Comparator: Low enterolactone producer's (Control); Placebo treatment matching intervention	Dietary supplement: Placebo treatment matching intervention; Placebo treatment matching intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in flow-mediated dilation (FMD)	To investigate the effect of daily consumption of 300 mg of flaxseed (SDG) extract vs Placebo for 8 weeks on endothelium-dependent flow mediated dilation (FMD) of the brachial artery (0, 8 weeks)	Baseline vs 8 weeks post-consumption

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in flow-mediated dilation (FMD)	To investigate the acute effect of 300 mg of flaxseed (SDG) extract vs Placebo on endothelium-dependent flow mediated dilation (FMD) of the brachial artery after 24- hour post-consumption.	Day 0, Day1 post-consumption
Change in office blood pressure	To investigate the effect of 300 mg flaxseed lignans (SDG) extract vs Placebo on peripheral systolic and diastolic blood pressure, and heart rate after 8 weeks daily consumption.	Day 0, Day 1 and 8 weeks post-consumption
Change in pulse wave velocity (PWV)	To determine the effect of 300 mg of lignans (SDG) vs Placebo on pulse wave velocity (PWV ) using a Sphygmocor device, after 8 weeks daily consumption	Baseline vs 8 weeks post-consumption
Change in augmentation Index (AIx)	To determine the effect of 300 mg of lignans (SDG) vs Placebo on augmentation index (PWA) using a Sphygmocor device, after 8 weeks daily consumption	Baseline vs 8 weeks post-consumption
Change in Total cholesterol	To investigate the effect of 300 mg Lignans (SDG) extract vs Placebo on blood lipids Total cholesterol after 8 weeks daily consumption	Baseline vs 8 weeks post-consumption
Change in blood inflammatory markers (IL-6)	To investigate the effect of 300 mg lignans (SDG) extract vs Placebo on inflammation markers (IL-6) after 8 weeks daily consumption.	Baseline vs 8 weeks post-consumption
Change in glucose marker	To investigate the effect of 300 mg lignans (SDG) extract vs Placebo on glucose levels (glucose) after 8 weeks daily consumption.	Baseline vs 8 weeks post-consumption
Change in blood lipid (HDL cholesterol ) concentrations	o investigate the effect of 300 mg Lignans (SDG) extract vs Placebo on blood lipids (HDL)after 8 weeks daily consumption	Baseline vs 8 weeks post-consumption
Change in blood lipid (LDL cholesterol )concentrations	o investigate the effect of 300 mg Lignans (SDG) extract vs Placebo on blood lipids( LDL cholesterol) after 8 weeks daily consumption	Baseline vs 8 weeks post-consumption
Change in blood lipid (triglycerides) concentrations	o investigate the effect of 300 mg Lignans (SDG) extract vs Placebo on blood lipids (triglycerides) after 8 weeks daily consumption	Baseline vs 8 weeks post-consumption
Change in blood inflammatory markers (CRP)	To investigate the effect of 300 mg lignans (SDG) extract vs Placebo on inflammation markers ( CRP) after 8 weeks daily consumption.	Baseline vs 8 weeks post-consumption
Change in insulin markers	To investigate the effect of 300 mg lignans (SDG) extract vs Placebo on glucose levels (insulin) after 8 weeks daily consumption.	Baseline vs 8 weeks post-consumption
Change in glucose (HbA1c) markers	To investigate the effect of 300 mg lignans (SDG) extract vs Placebo on glucose levels (HbA1c) after 8 weeks daily consumption.	Baseline vs 8 weeks post-consumption

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in metabolic (poly)phenol metabolite concentrations	To determine the plasma levels of polyphenol metabolites after acute and chronic consumption of flaxseed lignans (SDG).Measured by liquid chromotography-mass spectrometry (LC/MS)	Baseline, 24 hand 8 weeks post-consumption
Change in metabolic (poly)phenol metabolite concentrations	To determine the urine levels of polyphenol metabolites baseline and chronic consumption of flaxseed lignans (SDG). Measured by liquid chromotography-mass spectrometry (LC/MS)	Baseline vs 8 weeks post-consumption
Gut microbiome composition	To investigate changes in gut microbiota composition and diversity after 8 weeks consumption of flaxseed lignans (SDG) extract.	Baseline vs 8 weeks post-consumption
Menopausal symptoms	To investigate the effect of 300 mg flaxseed lignans (SDG) extract vs Placebo on menopausal symptoms using menopausal questionnaire for women over 45 years.	Baseline vs 8 weeks post-consumption
Homeostatic model assessment	To assess insulin resistance (IR) using homeostatic model assessment (HOMA).	Baseline vs 8 weeks post-consumption

Collaborators and Investigators

• Sponsor: King's College London
• Investigators: Principal Investigator: Dr.Ana Rodriguez-Mateos, PhD, King's College London

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2019
• Primary Completion (Actual): July 30, 2021
• Study Completion (Actual): July 30, 2021

Study Registration Dates

• First Submitted: November 21, 2019
• First Submitted That Met QC Criteria: November 25, 2019
• First Posted (Actual): November 27, 2019

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Cardiovascular system Polyphenols
• Other Study ID Numbers: CardioFlax study

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