Effects of Aronia Berries on Vascular Endothelial Function and the Gut Microbiota in Middle-Aged/Older Adults

Sponsor

Colorado State University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03824041

Collaborator

Naturex-Dbs (Industry)

Enrollment

Location

Arms

51.6

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Aging is the primary risk factor for cardiovascular disease (CVD) largely due to vascular endothelial dysfunction, a major initial step in the development of atherosclerosis. Endothelial dysfunction is characterized by impaired endothelium-dependent dilation and is primarily caused by reduced nitric oxide bioavailability secondary to oxidative stress and inflammation. Interventions that improve endothelial dysfunction are important for improving endothelial function and reducing CVD risk in this high-risk population. Aronia melanocarpa, commonly known as aronia berries or chokeberries, are rich in polyphenols such as anthocyanins, proanthocyanidins, and phenolic acids. These compounds, and derivatives resulting from gut microbial and phase II metabolism, have been shown to attenuate oxidative stress and inflammation, and to improve endothelial function. Aronia berries and other berries have been shown in numerous studies to have diverse cardiometabolic health effects including modulation of endothelial function, arterial stiffness, blood pressure, oxidative stress, and inflammation. In addition, berries, dietary fiber, polyphenols have been shown to exert positive effects on the gut microbiota, which may mediate improvements in cardiovascular health. Recently, we have demonstrated that modulation of the gut microbiota is associated with improvements in vascular dysfunction. The primary goal of the currently proposed research is to assess the efficacy and dose-dependent response of an aronia full spectrum dietary supplement to improve endothelial function in middle-aged/older men and postmenopausal women. A secondary goal is to determine whether aronia full spectrum modulation of the gut microbiota is associated with improvements in endothelial function. Other functional and biochemical measures of cardiovascular health, oxidative stress, inflammation, and polyphenol metabolism will be assessed.

Condition or Disease	Intervention/Treatment	Phase
Endothelial Dysfunction Aging	Dietary Supplement: Aronia full spectrum - half dose Dietary Supplement: Aronia full spectrum - full dose Dietary Supplement: Placebo	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

Aronia Berry Supplementation for Improving Vascular Endothelial Dysfunction and Modulating the Gut Microbiota in Middle-Aged/Older Adults

Actual Study Start Date :

Feb 11, 2019

Actual Primary Completion Date :

Jul 26, 2021

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Formulation containing inert artificially colored maltodextrin, two capsules once a day, in a 500 mg capsule regimen (total intake 1000 mg)	Dietary Supplement: Placebo Identical formulation as the treatment consisting of colored maltodextrin using artificial colors.
Experimental: Aronia full spectrum - half dose Formulation containing 50% Aronia full spectrum and 50% placebo, two capsules once a day, in a 500 mg capsule regimen (total intake 1000 mg)	Dietary Supplement: Aronia full spectrum - half dose Powdered whole fruit obtained from aronia berries (Aronia melanocarpa)
Experimental: Aronia full spectrum - full dose Formulation of 100% Aronia full spectrum, two capsules once a day, in a 500 mg capsule regimen (total intake 1000 mg)	Dietary Supplement: Aronia full spectrum - full dose Powdered whole fruit obtained from aronia berries (Aronia melanocarpa)

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Formulation containing inert artificially colored maltodextrin, two capsules once a day, in a 500 mg capsule regimen (total intake 1000 mg)

Dietary Supplement: Placebo

Identical formulation as the treatment consisting of colored maltodextrin using artificial colors.

Experimental: Aronia full spectrum - half dose

Formulation containing 50% Aronia full spectrum and 50% placebo, two capsules once a day, in a 500 mg capsule regimen (total intake 1000 mg)

Dietary Supplement: Aronia full spectrum - half dose

Powdered whole fruit obtained from aronia berries (Aronia melanocarpa)

Experimental: Aronia full spectrum - full dose

Formulation of 100% Aronia full spectrum, two capsules once a day, in a 500 mg capsule regimen (total intake 1000 mg)

Dietary Supplement: Aronia full spectrum - full dose

Powdered whole fruit obtained from aronia berries (Aronia melanocarpa)

Outcome Measures

Primary Outcome Measures

Change from baseline reactive hyperemia index (RHI) after 6 weeks consumption [Baseline and 6 weeks]
Determine the effects on RHI measured by EndoPAT

Secondary Outcome Measures

Gut microbiota analysis [Baseline and 6 weeks]
Determine the effects on stool sample microbial populations
Blood pressure [Baseline and 6 weeks]
Determine the effects on brachial and aortic blood pressure measured by SphygmoCor
Augmentation index [Baseline and 6 weeks]
Determine the effects on augmentation index measured by SphygmoCor
Gastrointestinal health [Baseline and 6 weeks]
Determine the effects on gastrointestinal health using a validated questionnaire
Pulse wave velocity [Baseline and 6 weeks]
Determine the effects on aortic arterial stiffness measured by SphygmoCor
Blood lipids [Baseline and 6 weeks]
Determine the effects on blood lipid profiles (total cholesterol, HDL, LDL, triglycerides)
Blood hemoglobin A1c [Baseline and 6 weeks]
Determine the effects on Hemoglobin A1c
Blood oxidized LDL [Baseline and 6 weeks]
Determine the effects on oxidized LDL
Blood ICAM [Baseline and 6 weeks]
Determine the effects on ICAM
Blood VCAM [Baseline and 6 weeks]
Determine the effects on VCAM

Other Outcome Measures

Plasma polyphenol metabolites [Baseline and 6 weeks]
Determine the effects on plasma polyphenol metabolites
Fecal polyphenol metabolites [Baseline and 6 weeks]
Determine the effects on fecal polyphenol metabolites
Urine polyphenol metabolites [Baseline and 6 weeks]
Determine the effects on urine polyphenol metabolites

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Men and postmenopausal women (> 1 year from cessation of menstruation)
Aged 45-75 years
Baseline endothelial dysfunction (RHI ≤ 1.67)
Hemoglobin A1C ≤ 6.4%
Blood pressure < 129/80 mmHg
Total cholesterol < 240 mg/dL
LDL cholesterol < 190 mg/dL
Triglycerides < 350 mg/dLhttps://register.clinicaltrials.gov/prs/app/template/Home.vm?uid=U00036MD&ts=50&s id=S0008GBU&cx=gvt3fw
Body mass index ≥ 18.5 and < 30 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 and willing to give signed written informed consent
Signed informed consent form

Exclusion Criteria:

Individuals taking antihypertensive, lipid-lowering, and/or hormone replacement medications
Diagnosed hypertension, CVD, diabetes, metabolic syndrome, cancer, kidney, liver, pancreatic disease
Obese participants, defined as BMI superior or equal to 30
Neuropathy, thrombosis, or past arm trauma or surgery
3 days/wk vigorous exercise
Participating in a weight loss program
Weight change > 5% in the past 3 months
Current smokers or history of smoking in the last 12 months
Heavy drinkers (> 7 drinks/wk for women; >14 drinks/wk for men)
Antibiotic use at any point during the study or two months prior to enrollment
Allergies to aronia berries or other study materials
Unwillingness to maintain normal diet and/or physical activity pattern, or to discontinue use of dietary supplements for the duration of the study
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