Acetate and Age-associated Arterial Dysfunction

Description

Cardiovascular diseases are the leading cause of morbidity and mortality and contribute most to healthcare costs in the U.S. Age is the strongest cardiovascular disease risk factor, with \>90% of all deaths from cardiovascular disease occurring in adults \>50 years old. The age-associated increased risk of cardiovascular disease is due, in large part, to the development of arterial dysfunction, including endothelial dysfunction and stiffening of the large elastic arteries. Therefore, novel, effective interventions that improve arterial function will have a large public health impact by decreasing the risk of cardiovascular diseases. The short-chain fatty acid acetate is endogenously produced by the gut microbiome from fermentation of dietary soluble fiber. High-fiber diets reduce risk of cardiovascular diseases, but unfortunately, a low percentage of Americans meet guidelines for adequate dietary fiber intake and, despite nationwide efforts to improve this, trends in fiber intake have not improved over the last 20+ years. Thus, directly supplementing acetate may be a more practical and feasible intervention for effectively improving arterial function in older adults and reducing the risk of cardiovascular diseases. The investigators will conduct a study to determine the efficacy of 12 weeks of oral supplementation with acetate for improving arterial function in late middle-aged and older (50+ years) adults. They will also assess the safety and tolerability of acetate supplementation in these adults and perform innovative mechanistic analyses to determine how acetate supplementation improves arterial function. The investigators hypothesize that oral acetate supplementation will improve arterial function by decreasing oxidative stress and increasing nitric oxide bioavailability, and also hypothesize that acetate supplementation will be safe and promote high rates of adherence.

Conditions

Aging, Vascular Stiffness, Vascular Dilation

Study Overview

Study Details

Study overview

Cardiovascular diseases are the leading cause of morbidity and mortality and contribute most to healthcare costs in the U.S. Age is the strongest cardiovascular disease risk factor, with \>90% of all deaths from cardiovascular disease occurring in adults \>50 years old. The age-associated increased risk of cardiovascular disease is due, in large part, to the development of arterial dysfunction, including endothelial dysfunction and stiffening of the large elastic arteries. Therefore, novel, effective interventions that improve arterial function will have a large public health impact by decreasing the risk of cardiovascular diseases. The short-chain fatty acid acetate is endogenously produced by the gut microbiome from fermentation of dietary soluble fiber. High-fiber diets reduce risk of cardiovascular diseases, but unfortunately, a low percentage of Americans meet guidelines for adequate dietary fiber intake and, despite nationwide efforts to improve this, trends in fiber intake have not improved over the last 20+ years. Thus, directly supplementing acetate may be a more practical and feasible intervention for effectively improving arterial function in older adults and reducing the risk of cardiovascular diseases. The investigators will conduct a study to determine the efficacy of 12 weeks of oral supplementation with acetate for improving arterial function in late middle-aged and older (50+ years) adults. They will also assess the safety and tolerability of acetate supplementation in these adults and perform innovative mechanistic analyses to determine how acetate supplementation improves arterial function. The investigators hypothesize that oral acetate supplementation will improve arterial function by decreasing oxidative stress and increasing nitric oxide bioavailability, and also hypothesize that acetate supplementation will be safe and promote high rates of adherence.

The Short-chain Fatty Acid Acetate for Improving Age-associated Arterial Dysfunction

Acetate and Age-associated Arterial Dysfunction

Condition
Aging
Intervention / Treatment

-

Contacts and Locations

Aurora

University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States, 80045

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * Able to provide informed consent;
  • * Age 50+ years;
  • * Serum phosphorus levels \>= 2.5 mg/dl at screening;
  • * Habitual dietary fiber intake \<30 g/day for men or \<21 g/day for women, based on Block Fiber Screener conducted at screening;
  • * Weight-stable in the 3 months prior to enrollment (self-report);
  • * Willing to abstain from dietary supplements for 48 hours and from alcohol, tobacco, and cannabis products for 24 hours before all visits;
  • * History of current serious, chronic clinical disease, e.g., cardiovascular disease, diabetes, liver disease, Alzheimer's disease and related dementias, cancer;
  • * Major changes in health in the past 3 months, e.g., hospitalizations, major surgeries, significant changes in medications;
  • * Currently taking calcium acetate or any other calcium supplementation;
  • * Screening FMDba \> 8%;
  • * Body mass index \> 40 kg/m\^2 at screening;
  • * Regular vigorous/aerobic endurance \>4 bouts/week for \>30 min/bout at a workload of \>6 METS;
  • * Any apparent dependence on or abuse of alcohol, tobacco, and cannabis products;
  • * Pregnancy, breast-feeding, or plans to become pregnant during the duration of the study;
  • * Any finding on the medical history, physical exam, or standard clinical blood labs that, in the opinion of the physician of record, would put the subject at increased risk with calcium supplementation.

Ages Eligible for Study

50 Years to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

Yes

Collaborators and Investigators

University of Colorado, Denver,

Vienna Brunt, PhD, PRINCIPAL_INVESTIGATOR, University of Colorado - Anschutz Medical Campus

Study Record Dates

2025-09-01