Aging, Endothelial Dysfunction
Conditions
Keywords
Polyphenols, Anthocyanins, Vascular function, Gut microbiome, Gut health, Berries
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.
Interventions
DIETARY_SUPPLEMENTAronia full spectrum - half dose
Powdered whole fruit obtained from aronia berries (Aronia melanocarpa)
DIETARY_SUPPLEMENTAronia full spectrum - full dose
Powdered whole fruit obtained from aronia berries (Aronia melanocarpa)
DIETARY_SUPPLEMENTPlacebo
Identical formulation as the treatment consisting of colored maltodextrin using artificial colors.
Sponsors
Naturex-Dbs
Colorado State University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
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&sid=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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline reactive hyperemia index (RHI) after 6 weeks consumption | Baseline and 6 weeks | Determine the effects on RHI measured by EndoPAT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pulse wave velocity | Baseline and 6 weeks | Determine the effects on aortic arterial stiffness measured by SphygmoCor |
| 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 |
| 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 |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Urine polyphenol metabolites | Baseline and 6 weeks | Determine the effects on urine polyphenol metabolites |
| Fecal polyphenol metabolites | Baseline and 6 weeks | Determine the effects on fecal polyphenol metabolites |
| Plasma polyphenol metabolites | Baseline and 6 weeks | Determine the effects on plasma polyphenol metabolites |
Countries
United States
Outcome results
None listed