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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how the supplement nicotinamide riboside malate affects heart and blood vessel health. Participants will take either the supplement in two different doses or a placebo (a pill with no active ingredient) for 12 weeks. The trial seeks healthy adults who do not have high blood pressure, are not taking certain supplements, and have no major health issues. Individuals who have generally been healthy and do not have conditions like cancer or severe obesity may be a good fit. As an unphased trial, this study offers a unique opportunity to contribute to scientific understanding and potentially improve heart health for many.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nicotinamide riboside, a type of vitamin B3, is generally safe for people. Studies have found it to be well-tolerated when used to support blood pressure and heart health. In trials where participants took nicotinamide riboside for several weeks, reports of side effects were few.

One study found that this supplement could help lower blood pressure without causing major problems. Another study showed that participants taking it for six months did not experience significant negative effects. This suggests that the supplement is safe for short-term use in healthy adults.

Overall, existing research provides strong evidence of nicotinamide riboside's safety, making it a promising option for those interested in its heart health benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Nicotinamide Riboside Malate is unique because it targets vascular stiffness by boosting levels of a compound called NAD+ (nicotinamide adenine dinucleotide) in the body. Most treatments for vascular stiffness focus on managing symptoms or related risk factors, like high blood pressure, with medications such as ACE inhibitors or beta-blockers. However, Nicotinamide Riboside Malate works by potentially enhancing cellular energy production and repair, which could directly improve vessel elasticity. Researchers are excited about its novel approach, as it might offer a more direct way to improve vascular health and prevent related cardiovascular issues.

What evidence suggests that nicotinamide riboside malate could be effective for vascular stiffness?

Research has shown that nicotinamide riboside might improve heart and blood vessel health by reducing blood vessel stiffness and lowering systolic blood pressure. Studies have found that this supplement can enhance blood flow and increase the flexibility of the aorta. It also raises levels of NAD+, a molecule that aids cellular function, which might explain these health benefits. For individuals with peripheral artery disease, nicotinamide riboside has helped them walk longer distances. Overall, early evidence suggests this supplement could offer significant benefits for blood vessels. ^{1 3 4 6 7}

Who Is on the Research Team?

Ryan Hurt, MD, PhD

Principal Investigator

Mayo Clinic

Brent Bauer, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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

Provides consent to participate in the study

Not pregnant at time of consent

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9127073/

Nicotinamide Riboside Supplementation for Treating Elevated ... The primary outcome is casual (resting) SBP and secondary outcomes include 24-h SBP and aortic stiffness. Other outcomes include assessment of safety ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04040959

Study Details | NCT04040959 | Nicotinamide Riboside ... We hypothesize that nicotinamide riboside will lower aortic stiffness and SBP and that these improvements will be related to increases in systemic NAD+ ...

3. nature.com nature.com/articles/s41467-024-49092-5

Nicotinamide riboside for peripheral artery disease Here we show that NR meaningfully improves 6-min walk, and resveratrol does not add benefit to NR alone in PAD. Results. Ninety participants ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022356525398204

Effects of NAD+ supplementation with oral nicotinamide ... NR supplementation may offer vascular benefits, such as improved blood pressure and aortic stiffness, although data specific to its effects on cerebrovascular ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35620522/

Nicotinamide Riboside Supplementation for Treating Elevated ... The primary outcome is casual (resting) SBP and secondary outcomes include 24-h SBP and aortic stiffness. Other outcomes include assessment ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02921659

NCT02921659 | Safety & Efficacy of Nicotinamide Riboside ... The purpose of this study is to assess the efficacy of supplementation with the Nicotinamide Adenine Dinucleotide (NAD+) precursor compound, ...

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03821623/nicotinamide-riboside-for-treating-elevated-systolic-blood-pressure-and-arterial-stiffness-in-middle-aged-and-older-adults

Nicotinamide Riboside for Treating Elevated Systolic Blood ... We have recently demonstrated that chronic supplementation with nicotinamide riboside lowers SBP and carotid-femoral pulse wave velocity (CFPWV; ...