Nicotinamide Riboside for Acetaminophen Toxicity

Overseen By BENJAMIN CAMPBELL

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of South Alabama

Disqualifiers: Allergy to acetaminophen, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the common pain reliever acetaminophen (such as Tylenol) might affect health, particularly in conditions similar to space. Researchers aim to determine if the dietary supplement nicotinamide riboside (also known as Niagen or NR) can reduce any harmful effects of acetaminophen. Participants will take acetaminophen alone and with the supplement to compare results. Individuals who are not allergic to acetaminophen or nicotinamide riboside and use acetaminophen regularly might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to early-stage medical research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it focuses on the effects of acetaminophen, so you may need to continue taking it as part of the study.

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

Research has shown that nicotinamide riboside (NR), a type of vitamin B3, is generally safe for people. In several studies, including those where participants took 500–1000 mg daily for extended periods, NR was well-tolerated. A few individuals experienced mild side effects like headaches or dizziness, but these were uncommon.

Researchers have also tested NR in animals for 90 days without causing harm, suggesting it is likely safe for humans as well. While it's important to remember that this is early research, past studies have not identified any serious safety concerns with NR. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nicotinamide Riboside is unique because it targets acetaminophen toxicity in a novel way. Unlike standard treatments that primarily focus on detoxifying the liver after damage has occurred, Nicotinamide Riboside is believed to work by boosting cellular energy and enhancing the liver's resilience before extensive damage sets in. Researchers are excited about this treatment because it introduces a proactive approach, potentially minimizing liver damage by fortifying the body's natural defenses, which could lead to safer outcomes for patients experiencing acetaminophen overdose.

What evidence suggests that Nicotinamide Riboside might be an effective treatment for acetaminophen toxicity?

This trial will compare the effects of Tylenol with and without Nicotinamide Riboside. Research has shown that Nicotinamide Riboside can increase NAD+ levels in the body, potentially protecting the liver from damage caused by acetaminophen, the main ingredient in many pain relievers like Tylenol. Studies with mice demonstrated that Nicotinamide Riboside can protect the liver from acetaminophen-induced harm by reducing certain harmful chemicals that acetaminophen can elevate. Although more research on humans is needed, these findings suggest possible benefits for frequent acetaminophen users, such as astronauts. ^{1 2 3 5 6}

Who Is on the Research Team?

marie migaud, PHD

Principal Investigator

University of South Alabama

Are You a Good Fit for This Trial?

This trial is for people who use acetaminophen (like Tylenol) to manage pain and discomfort. It's especially relevant for those in conditions similar to space travel, where such drug use is common. Participants must not be allergic to acetaminophen or the dietary supplement nicotinamide riboside.

Exclusion Criteria

Individual allergic to acetaminophen or nicotinamide riboside

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acetaminophen and acetaminophen with nicotinamide riboside to study their effects under space-like conditions

1 day

Multiple visits for blood and urine collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nicotinamide Riboside

Trial Overview The study tests if a dietary supplement called Nicotinamide Riboside can reduce harmful chemicals produced by taking acetaminophen. Volunteers will take both substances together, and their urine and blood samples will be analyzed under space-like conditions.

How Is the Trial Designed?

Group I: Tylenol and Nicotinamide Riboside Experimental Treatment 2 Interventions

Group II: Tylenol Only Active Control 1 Intervention

Who Is Running the Clinical Trial?

University of South Alabama

Lead Sponsor

Trials

44

Recruited

15,800+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

National Aeronautics and Space Administration (NASA)

Collaborator

Trials

32

Recruited

1,900+

Rutgers University

Collaborator

Trials

127

Recruited

2,814,000+

University of Nevada, Las Vegas

Collaborator

Trials

81

Recruited

14,700+

Published Research Related to This Trial

The synthetic form of β-nicotinamide mononucleotide (NMN-C®) was found to be safe in a study involving acute and subchronic toxicity tests, with no mutagenic or genotoxic effects observed.

In a 90-day study with doses up to 1500 mg/kg/day, NMN-C® did not show any adverse effects, establishing a No-Observable Adverse Effect Level (NOAEL) of ≥1500 mg/kg/day, indicating its potential safety for short to intermediate-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation after acute and sub-chronic oral administration of high purity nicotinamide mononucleotide (NMN-C®) in Sprague-Dawley rats. Cros, C., Cannelle, H., Laganier, L., et al.[2021]

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) 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]

The study found that the enzyme NAD kinase (NADK) is linked to acetaminophen (APAP)-induced acute liver injury (ALI), with higher levels of NADK correlating with increased liver damage in a dose- and time-dependent manner.

Inhibiting NADK with methotrexate (MTX) reduced liver injury and oxidative stress by increasing NAD+ levels, which improved the liver's antioxidant capacity and reduced DNA damage, suggesting a potential therapeutic target for APAP overdose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of NAD kinase elevates the hepatic NAD+ pool and alleviates acetaminophen-induced acute liver injury in mice. Liao, C., Zhang, L., Jiang, R., et al.[2022]

Nicotinamide (NAM) has potential benefits for various health conditions, but high doses can lead to adverse effects, including inhibition of protective enzymes and alterations in cellular metabolism.

While current usage levels of NAM are considered safe, chronic high-dose use may pose risks for epigenetic changes, highlighting the need for further research on its long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible Adverse Effects of High-Dose Nicotinamide: Mechanisms and Safety Assessment. Hwang, ES., Song, SB.[2021]

Dihydronicotinamide riboside (NRH) is a newly synthesized compound that significantly increases NAD+ concentrations in mammalian cells by 2.5-10 times within just 1 hour of administration, outperforming nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) at equivalent doses.

NRH enhances the NAD+/NADH ratio and protects cells from death caused by NAD+-depleting agents without inducing apoptosis or increasing lactate levels, suggesting it acts as a precursor to NAD+ through a novel metabolic pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dihydronicotinamide riboside is a potent NAD+ concentration enhancer in vitro and in vivo. Yang, Y., Mohammed, FS., Zhang, N., 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7277745/

Possible Adverse Effects of High-Dose Nicotinamide Nicotinamide (NAM) at doses far above those recommended for vitamins is suggested to be effective against a wide spectrum of diseases and conditions.

2. withpower.com withpower.com/trial/phase-1-therapeutic-agent-toxicity-2024-45d93

Nicotinamide Riboside for Acetaminophen Toxicity Research shows that increasing NAD+ levels, which Nicotinamide Riboside can do, may help protect the liver from damage caused by acetaminophen overdose. This is ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1567576912002846

Protective effects of nicotinamide against acetaminophen ... ▻ NAM has protective effects against acetaminophen-induced acute liver injury. ▻ The TNF-α, IFN-γ and IL-6 levels were markedly increased after APAP exposure. ▻ ...

4. journals.sagepub.com journals.sagepub.com/doi/10.1177/09603271211014573

Nicotinamide improves NAD + levels to protect against ... Nicotinamide improves NAD+ levels to protect against acetaminophen-induced acute liver injury in mice.

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06214468/protective-effect-of-nicotinamide-riboside-against-acetaminophen-toxicity

Protective Effect of Nicotinamide Riboside Against ... The study seeks to examine whether a dietary supplement, nicotinamide riboside (NR), can reduce some adverse effects of these toxins by reducing their ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2161831323013595

The Safety and Antiaging Effects of Nicotinamide ... Existing human clinical trials suggest that oral NMN administration is generally safe, and although only a limited number of indicators were studied, the ...