NAD Supplementation for Brain Health in Aging

Overseen By Andriy Yabluchanskiy, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Oklahoma

Must not be taking: NAD enhancers

Disqualifiers: CNS disease, Major psychiatric, others

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

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

214 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if taking Nicotinamide Riboside (NR), a form of Vitamin B3, can improve brain health and memory in older adults aged 60-85 by boosting a molecule called NAD that helps with energy and cell health. Nicotinamide Riboside (NR) is a precursor to NAD+, which has been identified as a promising treatment strategy for age-related cognitive decline and other conditions.

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 take other NAD enhancers like Nicotinamide riboside or nicotinamide mononucleotide within 4 weeks before starting the trial.

What data supports the effectiveness of the treatment Nicotinamide riboside for brain health in aging?

Research shows that Nicotinamide riboside (NR) can increase NAD+ levels, which are important for energy metabolism, and improve brain function in some animal models of neurodegeneration. In humans, NR supplementation has been shown to raise NAD+ levels and modify biomarkers related to neurodegenerative diseases, suggesting potential benefits for brain health. ^{1 2 3 4 5}

Is NAD supplementation safe for humans?

Nicotinamide riboside (NR), a form of NAD supplementation, has been shown to be generally safe in humans. Studies have found no significant differences in adverse events between NR and placebo groups, and it is recognized as safe for use in foods and dietary supplements. However, high doses of a related compound, nicotinamide, may pose potential risks for long-term use. ^{2 4 6 7 8}

How does the drug nicotinamide riboside differ from other treatments for brain health in aging?

Nicotinamide riboside is unique because it boosts NAD+ levels, which are important for energy metabolism and brain function, and it has shown potential in improving cognitive function and reducing neurodegenerative markers in aging and Alzheimer's models. Unlike other treatments, it is a precursor to NAD+ and can be taken orally, making it a convenient option for enhancing brain health. ^{1 2 3 4 5}

Research Team

Andriy Yabluchanskiy, MD, PhD

Principal Investigator

University of Oklahoma

Eligibility Criteria

This trial is for people aged 60 to 85 who can read and write in English, have good enough vision and hearing to participate, and can give informed consent. It's not for those with recent severe strokes, major uncontrolled psychiatric conditions, substance abuse issues, active brain diseases or poor kidney function.

Inclusion Criteria

I am between 60 and 85 years old.

I can see and hear well enough to undergo tests.

I understand and can agree to the study's procedures and risks.

Exclusion Criteria

I haven't taken NAD enhancers like nicotinamide riboside or mononucleotide in the last 4 weeks.

You have a serious mental illness, such as severe depression that is not well controlled with medication, or you have a problem with alcohol or drug abuse.

I have not had a stroke, excluding TIA, in the last 60 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Nicotinamide Riboside (NR) or placebo daily for 8 weeks to assess effects on neurovascular coupling and endothelial function

8 weeks

Weekly visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Nicotinamide riboside
• Placebo

Trial Overview The study tests if Nicotinamide Riboside (NR), a form of Vitamin B3, improves brain health and memory in older adults. Participants will take NR daily or a placebo without knowing which one they're getting to compare the effects fairly.

Participant Groups

Group I: NR Experimental Treatment 1 Intervention

Treatment with oral NR (1g/day per os for 8 weeks)

Group II: Control Placebo Group 1 Intervention

Visually identical placebo (daily, per os, for 8 weeks)

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 Tru Niagen for:

• Dietary supplement for general health and wellness

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Elysium Health

Industry Sponsor

Trials

18

Recruited

37,000+

Oklahoma Medical Research Foundation

Collaborator

Trials

24

Recruited

8,400+

Findings from Research

Oral supplementation with nicotinamide riboside has shown potential in improving learning and memory while reducing Alzheimer's disease-related pathology in mouse models, indicating its efficacy in combating age-related cognitive decline.

Nicotinamide riboside is well tolerated in humans with minimal side effects, suggesting it could be a safe therapeutic option for enhancing cognitive function and maintaining brain health as we age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can nicotinamide riboside protect against cognitive impairment? Braidy, N., Liu, Y.[2021]

Nicotinamide riboside (NR) was safely administered to 20 older adults with mild cognitive impairment (MCI) over a 10-week period, resulting in a significant 2.6-fold increase in blood NAD+ levels without any adverse effects reported between the NR and placebo groups.

While NR treatment did not improve cognitive function as measured by the Montreal Cognitive Assessment (MoCA), it did lead to a reduction in cerebral blood flow in specific brain regions, indicating that further research is needed to explore its potential effects on cognition and brain health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment. Orr, ME., Kotkowski, E., Ramirez, P., et al.[2023]

Nicotinamide ribose (NR) supplementation for 3 months improved cognitive functions, such as short-term spatial memory in aged mice and contextual fear memory in Alzheimer's disease (AD) model mice, indicating its potential efficacy in combating cognitive decline.

NR supplementation also reduced harmful effects associated with AD, such as the accumulation of amyloid-beta (Aβ) and the activation of astrocytes, suggesting a mechanism of action that may help prevent the progression of dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide ribose ameliorates cognitive impairment of aged and Alzheimer's disease model mice. Xie, X., Gao, Y., Zeng, M., et al.[2022]

A study involving 22 healthy older adults showed that oral supplementation with nicotinamide riboside (NR) significantly increases NAD+ levels in neuronal extracellular vesicles, which are indicators of brain health.

The NR supplementation also reduced levels of biomarkers associated with neurodegenerative diseases, such as Aβ42 and certain kinases, suggesting a potential therapeutic effect on neuroinflammatory pathways and insulin resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin. Vreones, M., Mustapic, M., Moaddel, R., et al.[2023]

Supplementing with NAD+ precursors shows promise in preserving cognitive ability and may help with age-related cognitive decline and other conditions like diabetes and traumatic brain injury, based on mostly positive findings from animal studies.

Despite the potential benefits, there are some reports of null or adverse effects, highlighting the need for more controlled clinical research to determine the true impact of NAD+ precursor supplementation on human cognitive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supplementation with NAD+ and Its Precursors to Prevent Cognitive Decline across Disease Contexts. Campbell, JM.[2022]

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]

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 (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]

References

1. England pubmed.ncbi.nlm.nih.gov

Can nicotinamide riboside protect against cognitive impairment? [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment. [2023]

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

Nicotinamide ribose ameliorates cognitive impairment of aged and Alzheimer's disease model mice. [2022]

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

Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Supplementation with NAD+ and Its Precursors to Prevent Cognitive Decline across Disease Contexts. [2022]

6. 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]

7. 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]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Possible Adverse Effects of High-Dose Nicotinamide: Mechanisms and Safety Assessment. [2021]