Acetate and Age-associated Arterial Dysfunction

Summary

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

Interventions

DRUG

Calcium Acetate Oral Solution

Subjects will be supplemented with calcium acetate (4,000 mg/day), as described in the arm/group descriptions, for 12 weeks.

DRUG

Calcium Carbonate Oral Suspension

Subjects will be supplemented with calcium carbonate (2,500 mg/day), as described in the arm/group descriptions, for 12 weeks.

Sponsors & Collaborators

• University of Colorado, Denver

  lead OTHER

Principal Investigators

• Vienna Brunt, PhD · University of Colorado, Denver

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-09-29

Primary Completion

2025-07-01

Completion

2025-09-01

FDA Drug

Yes

Countries

• United States

Study Locations