Nicotinamide Riboside for High Blood Pressure

Overseen By Daniel H Craighead, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Douglas Seals

Must not be taking: Antihypertensives

Disqualifiers: Diabetes, Chronic kidney disease, Cancer, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 12 weeks

118 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether nicotinamide riboside, a form of vitamin B3, can lower high blood pressure and reduce artery stiffness in middle-aged and older adults. It seeks to provide an alternative to calorie restriction, which can be difficult to maintain and may not be safe for everyone. Participants will receive either nicotinamide riboside or a placebo for three months. The trial seeks individuals with a systolic blood pressure between 120 and 139 mmHg who are not currently on blood pressure medication. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important research.

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 antihypertensive medications.

Is there any evidence suggesting that nicotinamide riboside is likely to be safe for humans?

Research has shown that taking nicotinamide riboside orally is likely safe in doses up to 300 mg per day, with side effects typically mild. Some studies tested higher doses, and side effects remained mild, even for individuals with high blood pressure. One study found that nicotinamide riboside is generally safe and recognized as such by food safety experts.

This treatment is a form of vitamin B3, a natural compound. While caution is always advisable with new treatments, current research suggests that nicotinamide riboside is well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for high blood pressure, like ACE inhibitors, beta-blockers, and diuretics, work by affecting hormones or relaxing blood vessels, but nicotinamide riboside (NR) works differently. NR is a precursor to vitamin B3 and acts by boosting levels of NAD+, a molecule involved in energy metabolism and cellular repair. Researchers are excited about NR because it might offer a novel way to improve blood vessel function and reduce blood pressure from within the cells, potentially offering a gentler alternative with fewer side effects. Plus, as a vitamin derivative, it might be better tolerated in the long term compared to conventional medications.

What evidence suggests that nicotinamide riboside might be an effective treatment for high blood pressure?

Research has shown that nicotinamide riboside, which participants in this trial may receive, can help lower systolic blood pressure, particularly in individuals with slightly elevated levels (120-139 mmHg). In a previous study, taking nicotinamide riboside for six weeks resulted in an average drop of 8 mmHg in blood pressure compared to a placebo. This treatment also reduced arterial stiffness, which is crucial because stiff arteries can lead to heart problems. Nicotinamide riboside increases NAD+ levels, a compound that mimics the effects of calorie restriction, a known method for lowering blood pressure. These findings suggest that nicotinamide riboside could be an effective way to manage blood pressure and support heart health. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for middle-aged and older adults who have slightly elevated blood pressure (120-159 mmHg) and are generally healthy. Participants should not be on blood pressure medication, must have a stable weight, BMI under 40 kg/m2, normal cholesterol and glucose levels, no chronic diseases like diabetes or kidney disease, non-smokers, and not heavy drinkers.

Inclusion Criteria

Ability to provide informed consent

Willing to accept random assignment to condition

Your body mass index is less than 40.

Exclusion Criteria

Your blood pressure doesn't respond normally to exercise, or it goes too high during exercise.

You have a problem with drinking too much alcohol or being dependent on alcohol.

You have a thyroid condition that is not well controlled, or you have changed your thyroid medication in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

2 visits (in-person)

Treatment

Participants receive either nicotinamide riboside or placebo for 3 months

12 weeks

6 visits (in-person, bi-weekly)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Nicotinamide Riboside
• Placebo

Trial Overview

The study tests if Nicotinamide riboside can lower high systolic blood pressure and make arteries less stiff in people as they age. It's compared to a placebo over three months in a double-blind setup where neither the researchers nor participants know who gets the real supplement.

How Is the Trial Designed?

Group I: Nicotinamide riboside Experimental Treatment 1 Intervention

Subjects will take 500 mg of the vitamin B3-precursor, nicotinamide riboside (NIAGEN) twice per day (1,000 mg per day total) for 3 months.

Group II: Placebo Placebo Group 1 Intervention

Subjects will take placebo pills twice a day for 3 months.

Nicotinamide Riboside is already approved in United States, European Union for the following indications:

Approved in United States as Niagen for:

• Dietary supplement for general health and wellness

Approved in European Union as Niagen for:

• Dietary supplement for general health and wellness

Who Is Running the Clinical Trial?

Douglas Seals

Lead Sponsor

Trials

3

Recruited

210+

Published Research Related to This Trial

Nicotinamide riboside (NR) is a promising NAD+ precursor that has shown potential health benefits in treating various conditions, including cardiovascular, neurodegenerative, and metabolic disorders, based on numerous animal and human studies.

Research indicates that NR may also have therapeutic applications against infections, such as SARS-CoV-2, but challenges related to its bioavailability and safety need to be addressed for effective translation into clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Mehmel, M., Jovanović, N., Spitz, U.[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]

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]

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]

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 ...

This study is designed to establish the safety and efficacy of the NAD + boosting compound, nicotinamide riboside, for reducing casual and 24-h SBP and aortic ...

2.

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 of ...

3.

link.springer.com

link.springer.com/article/10.1007/s11357-025-01815-2

Nicotinamide riboside combined with exercise to treat ...

The primary outcome of this study was mean daytime SBP. The secondary outcomes were diastolic BP and arterial stiffness. Additionally, urine ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03821623

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; gold-standard ...

5.

science.org

science.org/doi/10.1126/sciadv.adi4862

What is really known about the effects of nicotinamide ...

It was reported that the steady-state levels of NR and NAD+ in whole blood were increased by oral NR after 8 days of escalating NR doses (250 to ...

6.

webmd.com

webmd.com/vitamins/ai/ingredientmono-1560/nicotinamide-riboside

NICOTINAMIDE RIBOSIDE – Uses, Side Effects, and More

When taken by mouth: Nicotinamide riboside chloride is possibly safe when used in doses up to 300 mg daily. Side effects are usually mild and might include ...

7.

nature.com

nature.com/articles/s41598-019-46120-z

Safety and Metabolism of Long-term Administration ...

NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease ... high blood pressure and were mild ...

8.

fda.gov

fda.gov/files/food/published/GRAS-Notice-000635--Nicotinamide-riboside-chloride.pdf

GRAS Notice 635: Nicotinamide riboside chloride

The intake of Niagen from the intended uses specified above has been shown to be safe and GRAS based on generally available and accepted ...