Nicotinamide Riboside Malate for Vascular Stiffness

(NRM Trial)

Overseen By Jennifer Soderlind

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Must not be taking: Hypertension medication, Nicotinamide riboside

Disqualifiers: Pregnancy, Hypertension, Cancer, others

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

200 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to better understand the effects of nicotinamide riboside supplement in overall cardiovascular health in healthy adults.

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 taking medication for high blood pressure or certain supplements like nicotinamide riboside, quercetin, trans-resveratrol, or betaine anhydrous.

What data supports the effectiveness of the drug Nicotinamide Riboside Malate for reducing vascular stiffness?

Research shows that nicotinamide riboside, a component of Nicotinamide Riboside Malate, can increase NAD+ levels in the body, which may help improve cardiovascular health by reducing blood pressure and arterial stiffness in older adults. Additionally, studies on similar compounds like nicotinamide mononucleotide have shown they can reverse age-related vascular dysfunction and oxidative stress in animal models. ^{1 2 3 4 5}

Is Nicotinamide Riboside Malate safe for human use?

Nicotinamide Riboside, a form of vitamin B3, has been studied in various forms and is generally considered safe for human use. Clinical trials have shown that it is well-tolerated, with no significant differences in adverse events compared to placebo, and no serious side effects reported at various doses. ^{1 5 6 7 8}

How does the drug Nicotinamide Riboside Malate differ from other treatments for vascular stiffness?

Nicotinamide Riboside Malate is unique because it boosts NAD+ levels, a molecule important for energy and cell function, which tends to decline with age. This approach may help improve cardiovascular health by reducing oxidative stress and inflammation, which are key factors in vascular stiffness, making it different from other treatments that may not target these underlying mechanisms. ^{1 2 3 4 5}

Research Team

Brent Bauer, MD

Principal Investigator

Mayo Clinic

Ryan Hurt, MD, PhD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for healthy adults aged 40-60 who are not pregnant, nursing, or trying to conceive. Participants must understand and agree to the study's procedures without any chronic diseases, unstable medical conditions, severe obesity, or recent use of certain natural health products.

Inclusion Criteria

Not pregnant at time of consent

Provides consent to participate in the study

Understands and agrees to follow all study procedures and limitations

Exclusion Criteria

An unstable medical or mental health condition as determined by the physician investigator

BMI less than 30

Pregnant, nursing, or trying to conceive

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 830 mg or 1660 mg of Nicotinamide or a placebo twice a day for 12 weeks

12 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Nicotinamide Riboside Malate

Trial Overview The trial is testing the effects of a supplement called Nicotinamide Riboside Malate on cardiovascular health in comparison with a placebo. The goal is to see if this supplement can improve vascular function in healthy individuals.

Participant Groups

Group I: 830 mg Nicotinamide and Placebo Active Control 2 Interventions

830 mg Nicotinamide supplement capsule and 1 identical Placebo capsule twice a day for 12 weeks

Group II: 1660 mg Nicotinamide Active Control 1 Intervention

1660 mg Nicotinamide supplement; 2 of the 830 mg capsules twice a day for 12 weeks

Group III: Placebo Placebo Group 1 Intervention

2 identical Placebo capsules twice a day for 12 weeks

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

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]

A 12-week randomized, double-blind, placebo-controlled trial showed that chronic supplementation with nicotinamide riboside (NR), a precursor to NAD+, is well tolerated and effectively increases NAD+ levels in healthy middle-aged and older adults.

The study suggests that NR supplementation may have potential benefits for improving cardiovascular health, specifically in reducing blood pressure and arterial stiffness, warranting further investigation in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Martens, CR., Denman, BA., Mazzo, MR., et al.[2021]

In an 8-week clinical trial with overweight but healthy participants, nicotinamide riboside (NR) significantly increased whole blood NAD+ levels in a dose-dependent manner, with increases of 22%, 51%, and 142% for doses of 100, 300, and 1000 mg, respectively.

The study found NR to be safe, with no significant adverse effects reported compared to placebo, and it did not negatively impact cholesterol levels or 1-carbon metabolism, supporting its potential as a dietary supplement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Conze, D., Brenner, C., Kruger, CL.[2023]

Nicotinamide riboside (NR) is a form of vitamin B3 that effectively increases NAD+ levels, which may help counteract age-related declines in this important metabolite.

In a 90-day safety study on Sprague Dawley rats, NR-E showed no significant adverse effects at doses up to 1,200 mg/kg/d, establishing a no-observed-adverse-effect-level (NOAEL) of 500 mg/kg/d for males and 1,200 mg/kg/d for females.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Assessment of High-Purity, Synthetic Nicotinamide Riboside (NR-E) in a 90-Day Repeated Dose Oral Toxicity Study, With a 28-Day Recovery Arm. Marinescu, AG., Chen, J., Holmes, HE., et al.[2021]

Nicotinamide riboside (NR), a form of vitamin B3, was found to be safe in various toxicity studies, including a 90-day rat study, with no genotoxic effects and no mortality at high doses (5000 mg/kg).

The lowest observed adverse effect level for NR was determined to be 1000 mg/kg/day, indicating that while it is generally safe, higher doses may lead to toxicity in organs such as the liver and kidneys.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of nicotinamide riboside, a form of vitamin B3. Conze, DB., Crespo-Barreto, J., Kruger, CL.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside Supplementation for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Midlife and Older Adults. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Role of endothelial NAD+ deficiency in age-related vascular dysfunction. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Reversal of endothelial dysfunction by nicotinamide mononucleotide via extracellular conversion to nicotinamide riboside. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Safety Assessment of High-Purity, Synthetic Nicotinamide Riboside (NR-E) in a 90-Day Repeated Dose Oral Toxicity Study, With a 28-Day Recovery Arm. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Safety assessment of nicotinamide riboside, a form of vitamin B3. [2019]