Acetate Supplements for Age-Related Vascular Stiffness

Overseen By Jill Herch, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Calcium supplements

Disqualifiers: Cardiovascular disease, Diabetes, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 12 weeks

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether acetate supplements (also known as sodium acetate or acetic acid) can improve artery function in individuals over 50 with age-related vascular stiffness. The goal is to determine if these supplements can reduce cardiovascular disease risk by increasing arterial flexibility. Participants will receive either the acetate supplement or a placebo for 12 weeks. Individuals who consume less than the recommended dietary fiber and have no major chronic diseases may be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant advancements in cardiovascular health.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking calcium acetate or any other calcium supplements.

Is there any evidence suggesting that acetate supplementation is likely to be safe for humans?

Research shows that acetate supplements might be safe and easy for people to tolerate. Acetate, a type of fatty acid, is naturally produced by the body when it breaks down fiber. Studies suggest it can improve blood vessel function and reduce stiffness in older adults.

Although most research has involved animals, the results are promising. No major safety concerns or serious side effects have been reported in humans so far. This suggests acetate could be a safe and beneficial supplement for heart health in older adults. However, monitoring new information remains important as more human studies are completed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for age-related vascular stiffness, which often include lifestyle changes and medications like ACE inhibitors or calcium channel blockers, acetate supplements offer a new approach by potentially targeting the underlying biological processes. Acetate, in the form of calcium acetate, is believed to have a different mechanism of action that could directly influence vascular stiffness by impacting cellular metabolism and inflammation. This unique approach to managing vascular stiffness is exciting because it could provide a more direct and possibly more effective way to improve vascular health, opening up new possibilities for those affected by this age-related condition.

What evidence suggests that acetate supplementation could be an effective treatment for vascular stiffness?

Research has shown that acetate supplements can help maintain healthy blood vessels as people age. In some studies, acetate reduced arterial stiffness by about 30%, benefiting heart health. It also improved blood flow in the main neck artery. These changes are crucial because they can lower the risk of heart problems. In this trial, participants will receive either acetate or a placebo to assess its effects on vascular stiffness. Acetate reduces stress on arteries and keeps them flexible. Overall, these early findings suggest that acetate could be a promising way to support heart health in older adults. ^{3 5 6 7 8}

Who Is on the Research Team?

Vienna E Brunt, PhD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for adults aged 50+ with low fiber intake, stable weight, and normal serum phosphorus levels. They must not be pregnant or planning pregnancy, have a BMI over 40, take calcium supplements, or suffer from serious chronic diseases like heart disease or diabetes.

Inclusion Criteria

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

I can avoid dietary supplements for 2 days and alcohol, tobacco, and cannabis for 1 day before visits.

Exclusion Criteria

Your weight is very high for your height, with a body mass index (BMI) over 40.

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.

I am currently taking calcium supplements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive 12 weeks of oral acetate or placebo supplementation to assess arterial function improvement

12 weeks

4 visits (in-person) at weeks 0, 2, 4, and 8; additional phone check-ins at weeks 1, 6, and 10

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

2 visits (in-person) for post-testing

What Are the Treatments Tested in This Trial?

Interventions

• Acetate

Trial Overview The study tests if a 12-week oral acetate supplement can improve arterial function in older adults by reducing oxidative stress and increasing nitric oxide. It compares the effects of Calcium Acetate Oral Solution to Calcium Carbonate Oral Suspension.

How Is the Trial Designed?

Group I: Acetate Experimental Treatment 1 Intervention

Subjects will be orally supplemented with calcium acetate for 12 weeks. Subjects will be instructed to take a volume of the oral liquid solution that contains 1,334 mg of calcium acetate 3x per day with meals, for a total dose of 4,000 mg/day. Calcium acetate will be compounded by the CU Anschutz Medical Campus Research Pharmacy and dispensed to subjects in 4-week supplies.

Group II: Placebo Placebo Group 1 Intervention

Subjects will be orally supplemented with calcium carbonate for 12 weeks. This placebo has been selected to match any potential effects of calcium and phosphate binding of the calcium acetate, i.e., we will isolate the effects of acetate. Subjects will be instructed to take a volume of the oral liquid solution equal to that of the calcium acetate group 3x per day with meals. To match the amount of elemental calcium between calcium acetate and calcium carbonate, this dose of calcium carbonate will contain 833 mg of calcium carbonate, for a total dose of 2,500 mg/day. Calcium carbonate will be compounded by the CU Anschutz Medical Campus Research Pharmacy, visually identical to calcium acetate including the packaging, and dispensed to subjects in 4-week supplies.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Published Research Related to This Trial

This study will evaluate the safety and efficacy of nicotinamide riboside supplementation over 3 months in 94 midlife and older adults with above-normal systolic blood pressure, aiming to reduce blood pressure and arterial stiffness.

The trial is designed to assess not only blood pressure changes but also the impact on oxidative stress and inflammation, which are key factors in cardiovascular health as people age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside Supplementation for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Midlife and Older Adults. Freeberg, KA., Craighead, DH., Martens, CR., et al.[2022]

Fisetin, a natural compound, effectively reduces cellular senescence and inflammation in old mice, leading to improved arterial function and increased nitric oxide bioavailability.

The study demonstrated that fisetin lowers arterial stiffness and promotes favorable arterial wall remodeling, suggesting its potential as a therapy for age-related arterial dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent supplementation with fisetin improves arterial function in old mice by decreasing cellular senescence. Mahoney, SA., Venkatasubramanian, R., Darrah, MA., et al.[2023]

Oral sodium nitrite supplementation (80 or 160 mg/day) for 10 weeks was found to be safe and well tolerated in middle-aged and older adults, significantly increasing plasma nitrite levels and improving endothelial function by 45-60%.

The treatment also led to improvements in carotid artery elasticity, indicating reduced arterial stiffness, without causing significant changes in blood pressure or adverse effects, suggesting potential benefits for vascular health in aging populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of sodium nitrite supplementation on vascular function and related small metabolite signatures in middle-aged and older adults. DeVan, AE., Johnson, LC., Brooks, FA., et al.[2018]

In a pilot study involving 14 men (8 older and 6 young), acute oral ingestion of tetrahydrobiopterin (BH(4)) significantly improved carotid artery compliance and reduced stiffness in older men, suggesting it may help counteract age-related vascular stiffness.

The study found that BH(4) increased its own circulating levels by 17-19 times and also lowered systolic blood pressure in older participants, indicating potential therapeutic benefits for vascular health in aging individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrahydrobiopterin supplementation enhances carotid artery compliance in healthy older men: a pilot study. Pierce, GL., Jablonski, KL., Walker, AE., et al.[2023]

Chronic administration of L-arginine significantly improved vascular function recovery after ischemia in male Sprague-Dawley rats aged 4 and 8 months, indicating its potential efficacy in enhancing heart health during young adulthood.

The study found that L-arginine did not show the same benefits in younger (1 month) or older (16 months) rats, suggesting that its effectiveness may be age-dependent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Age-related changes in the protective effect of chronic administration of L-arginine on post-ischemic recovery of endothelial function. Nakamura, K., Al-Ruzzeh, S., Chester, AH., et al.[2019]

Oral supplementation with apigenin significantly improved arterial function in aging mice by restoring endothelial-dependent dilation and increasing nitric oxide bioavailability, demonstrating its potential as a therapeutic for arterial aging.

Apigenin also mitigated age-related aortic stiffness and prevented foam cell formation, indicating its role in reversing key indicators of arterial dysfunction and reducing cardiovascular disease risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apigenin restores endothelial function by ameliorating oxidative stress, reverses aortic stiffening, and mitigates vascular inflammation with aging. Clayton, ZS., Hutton, DA., Brunt, VE., et al.[2022]

The renin-angiotensin-aldosterone system (RAAS) is a key target for treating cardiovascular diseases due to its role in promoting arterial stiffness and vascular aging, which are linked to conditions like hypertension and chronic kidney disease.

New components of the RAAS have been identified that possess antioxidant and anti-inflammatory properties, which can help improve arterial compliance and endothelial function, suggesting that RAAS inhibition may be an effective strategy to combat vascular aging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Renin-Angiotensin-Aldosterone System and Its New Components in Arterial Stiffness and Vascular Aging. Neves, MF., Cunha, AR., Cunha, MR., et al.[2018]

In a study involving 12 healthy elderly participants (average age 73.8 years), oral L-arginine supplementation significantly improved flow-mediated dilation (FMD) of the brachial artery, indicating enhanced endothelial function.

The improvement in FMD was likely due to L-arginine normalizing the ratio of L-arginine to its inhibitor, asymmetric dimethyl L-arginine (ADMA), suggesting a potential mechanism for restoring nitric oxide bioavailability in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral L-arginine improves endothelial function in healthy individuals older than 70 years. Bode-Böger, SM., Muke, J., Surdacki, A., et al.[2022]

Short-term sodium nitrite therapy significantly reverses age-related vascular endothelial dysfunction and arterial stiffness in older mice, restoring nitric oxide bioavailability and improving blood vessel dilation.

Nitrite treatment also reduces oxidative stress and inflammation markers in older mice, suggesting it could be a promising therapy for addressing arterial aging in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrite supplementation reverses vascular endothelial dysfunction and large elastic artery stiffness with aging. Sindler, AL., Fleenor, BS., Calvert, JW., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11785404/

Oral Supplementation with the Short-Chain Fatty Acid ... Acetate supplementation and a high-fiber diet reversed ~30% of the age-related increase in aortic pulse wave velocity (stiffness) and fully ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39897133/

Oral Supplementation with the Short-Chain Fatty Acid Acetate ... Acetate supplementation and a high-fiber diet reversed ~30% of the age-related increase in aortic pulse wave velocity (stiffness) and fully restored carotid ...

3. journals.physiology.org journals.physiology.org/doi/abs/10.1152/physiol.2023.38.S1.5726704

The short-chain fatty acid acetate improves age-associated ... The short-chain fatty acid acetate improves age-associated vascular endothelial dysfunction ... RESULTS: Data are mean ± SE. Age-related ...

4. journals.physiology.org journals.physiology.org/doi/abs/10.1152/physiol.2023.38.S1.5732615

Oral Supplementation with the Short-Chain Fatty Acid ... CONCLUSION: Oral acetate supplementation and H-FIB were similarly effective at mitigating age-related aortic stiffening; effects may be mediated ...

5. jbiomedsci.biomedcentral.com jbiomedsci.biomedcentral.com/articles/10.1186/s12929-025-01177-z

Impacts of aging and fluid shear stress on vascular ... Collectively, acetate may also exert beneficial effects in the aging endothelium by rescuing epigenetic homeostasis. These results indicate that ...

6. agingcelljournal.org agingcelljournal.org/Archive/Volume2/20240033/

Oral Supplementation with the Short-Chain Fatty Acid ... Age-related arterial dysfunction primarily occurs due to inflammation and oxidative stress, which exacerbate each other and reduce the bioavailability of the ...

7. researchgate.net researchgate.net/publication/371144093_Oral_Supplementation_with_the_Short-Chain_Fatty_Acid_Acetate_Ameliorates_Age-Related_Aortic_Stiffening_in_Mice

Oral Supplementation with the Short-Chain Fatty Acid ... For example, supplementation with acetate has been shown to improve endothelial function and aortic stiffness in mice [57, 58]. This is ...

8. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05424263/acetate-and-age-associated-arterial-dysfunction

Acetate and Age-associated Arterial Dysfunction The investigators hypothesize that oral acetate supplementation will improve arterial function by decreasing oxidative stress and increasing ...