NAD+ Supplement for Brain Function

Recruiting at 1 trial location

Overseen By Geoff Greene, Ph.D.

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: University of Rhode Island

Must not be taking: Hormone medication

Disqualifiers: Pregnant, Breastfeeding, others

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

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the supplement Nicotinamide adenine dinucleotide (NAD+) can improve brain function and affect blood markers related to inflammation and brain health. Researchers will administer NAD+ to some participants and a placebo to others to determine any differences in cognitive abilities and blood test results. The trial seeks Latina women who are healthy, cognitively intact, have experienced three or more difficult childhood events, and have a BMI of 18.5 or above. Participants will complete surveys, take the supplement or placebo for four weeks, and undergo cognitive tests and blood draws before and after the trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on brain health and inflammation.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking hormone medication.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that Nicotinamide adenine dinucleotide (NAD+) is generally safe for people. Studies have found that healthy adults can safely take NAD+ in pill form, even at doses up to 1250 mg per day for four weeks, without serious side effects. This suggests NAD+ is unlikely to be harmful as a short-term supplement. However, as with any supplement, individuals may react differently, so participants should monitor their well-being if they join a trial involving NAD+. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Nicotinamide adenine dinucleotide (NAD+) is unique because it focuses on boosting cellular energy and supporting brain function by increasing NAD+ levels in the body. Unlike many traditional treatments for cognitive decline, which often aim to manage symptoms or modify neurotransmitter activity, NAD+ targets the fundamental energy metabolism within cells, potentially offering a more foundational approach to brain health. Researchers are excited because NAD+ may help improve cognitive performance and protect against neurodegenerative changes, offering hope for maintaining brain function as we age.

What evidence suggests that NAD+ might be an effective treatment for brain function?

This trial will evaluate the effects of Nicotinamide adenine dinucleotide (NAD+) on brain function. Studies have shown that NAD+ can improve brain function by reducing inflammation and cellular stress, protecting the brain from aging and damage. Some research suggests that increasing NAD+ levels might aid thinking and memory. It may also maintain brain cell health by boosting energy production. Although results in older adults have varied, the potential for NAD+ to enhance cognitive function remains promising. Participants in this trial will receive either NAD+ or a placebo to assess its impact on cognitive function. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for Latina women aged 40-80 who are healthy and cognitively intact, have experienced three or more adverse childhood events, and have a BMI of at least 18.5. It's not open to those on hormone medication, or who are pregnant or breastfeeding.

Inclusion Criteria

Identify as Latina, have three or more adverse childhood experiences, and a BMI of 18.5 or above

Exclusion Criteria

Pregnant

Breastfeeding

I am currently taking hormone medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-testing

Participants complete an online questionnaire and visit the lab for cognitive testing and a blood draw before receiving the supplement

1 week

1 visit (in-person)

Treatment

Participants take NAD+ or a placebo every day for 4 weeks

4 weeks

1 visit (in-person) at the end of treatment

Post-testing

Participants visit the lab for cognitive testing and a blood draw after receiving the supplement

1 week

1 visit (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 adenine dinucleotide

Trial Overview Researchers are testing if NAD+ supplements can improve brain function (like planning and decision-making) and reduce markers of inflammation and neurodegeneration in the blood compared to a placebo over four weeks.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

For four weeks, the participant will consume an oral supplement, either Nicotinamide adenine dinucleotide or a placebo.

Group II: Pre-testing prior to intervention Active Control 1 Intervention

Prior to receiving the supplement, either Nicotinamide adenine dinucleotide or the placebo, participants will undergo cognitive testing and a blood draw.

Group III: Post-testing after intervention Active Control 1 Intervention

After receiving the supplement, either Nicotinamide adenine dinucleotide or the placebo, participants will undergo cognitive testing and a blood draw.

Who Is Running the Clinical Trial?

University of Rhode Island

Lead Sponsor

Trials

57

Recruited

22,400+

National Institute of General Medical Sciences (NIGMS)

Collaborator

Trials

315

Recruited

251,000+

Published Research Related to This Trial

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]

A phase I trial involving 20 individuals with Parkinson's disease found that high-dose nicotinamide riboside (NR) therapy (1500 mg twice daily) was well tolerated, with no moderate or severe adverse events reported, indicating a good safety profile for this treatment.

NR therapy significantly increased blood NAD+ levels by up to 5-fold and was associated with clinical improvements in Parkinson's disease symptoms, although these improvements may be influenced by the timing of levodopa administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease. Berven, H., Kverneng, S., Sheard, E., et al.[2023]

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]

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 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) is more effective than NAD+ in protecting against brain damage caused by excitotoxicity, as shown in experiments with cortical neurons and NMDA injections.

The protective effects of NR involve maintaining intracellular NAD+ levels, highlighting its potential as a neuroprotective agent in neurodegenerative conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide riboside, a form of vitamin B3, protects against excitotoxicity-induced axonal degeneration. Vaur, P., Brugg, B., Mericskay, M., et al.[2021]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11877801/

A systematic review of the therapeutic potential of ... Studies have revealed that treatment with NAD + rescues cognitive deficits by inhibiting inflammation, oxidative stress, and apoptosis and improving ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02942888

The Effects of Nicotinamide Adenine Dinucleotide (NAD) ... The purpose of this study is to determine the effects of Niagen (nicotinamide riboside, vitamin B3), on NAD levels, brain function including cognition and blood ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1043276025000700

NAD augmentation as a disease-modifying strategy for ... Restoring brain NAD levels may therefore counteract age-related cellular stress and vulnerabilities and mitigate neurodegeneration. Moreover, ...

4. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.70023

Cognitive and Alzheimer's disease biomarker effects of oral ... Interpretation: Our findings were consistent with previous studies, suggesting that NR is safe but did not alter cognition in older adults with ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6787556/

NAD+ in Brain Aging and Neurodegenerative Disorders - PMC Moreover, NAD+ augmentation restores mitochondrial function and bioenergetics, leading to enhanced neuronal survival and improved cognitive function in ...

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

The Safety and Antiaging Effects of Nicotinamide ... NMN supplementation increases NAD + concentration and could mitigate aging-related disorders such as oxidative stress, DNA damage, neurodegeneration, and ...

7. nature.com nature.com/articles/s41598-022-18272-y

Safety evaluation of β-nicotinamide mononucleotide oral ... Our results indicate that β-NMN is safe and well-tolerated in healthy adult men and women an oral dose of 1250 mg once daily for up to 4 weeks.

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

Possible Adverse Effects of High-Dose Nicotinamide Therefore, NAM supplement helps maintaining serotonin level, and thereby alleviates depression and psychological disorders. NAD+ level is also elevated through ...