Nicotinamide Riboside for Sarcopenia

(NR-VET Trial)

Recruiting at 1 trial location

Overseen By Ayesha Rahman, MS

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Congestive heart failure, COPD, others

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

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

144 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether nicotinamide riboside (NR), a form of vitamin B3, can improve muscle function in older adults. Researchers aim to determine if NR, which boosts a molecule vital for cell health, can enhance muscle performance and reduce frailty. Participants will take either NR supplements or a placebo (a pill with no active ingredient) to compare the effects. The trial seeks individuals aged 65 to 85 who can use an exercise bike and are healthy enough for a muscle biopsy.

As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research on enhancing muscle health in older adults.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that nicotinamide riboside is safe?

Research has shown that nicotinamide riboside (NR), a type of vitamin B3, is generally safe for people. Studies have found that older adults can take NR supplements without serious side effects. In one study, participants took NR for 21 days and experienced no major issues. Another study demonstrated that taking up to 2000 mg of NR daily is safe.

In this trial, participants will take 1000 mg per day, which remains well below the highest safe dose identified in research. This suggests that the treatment is likely safe for most people. While NR helps increase NAD levels in the body, some studies did not find it effective for improving muscle function in older adults. However, the strong safety data make NR a promising option for further study. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for sarcopenia, which often focus on physical therapy and nutritional support, Nicotinamide Riboside (NR) acts on a cellular level by boosting NAD+ levels. This is important because NAD+ is essential for energy production and cellular repair, potentially leading to improved muscle health and function. Researchers are excited about NR because it offers a new mechanism of action that could complement existing therapies, providing a novel way to combat the muscle loss and weakness associated with sarcopenia.

What evidence suggests that nicotinamide riboside might be an effective treatment for sarcopenia?

Research has shown that nicotinamide riboside (NR), a type of vitamin B3, can increase NAD+ levels in the body. This is important because NAD+ is crucial for many cell functions, and its decrease is linked to aging. In humans, NR has improved metabolism and slowed muscle decline. Although some studies suggest only small benefits for muscle issues like sarcopenia, NR has improved artery health and skin condition in other cases. In this trial, participants will receive either NR supplementation or a placebo. Overall, NR supplements appear promising for supporting muscle health, though results can vary. ^{1 2 4 5 6}

Who Is on the Research Team?

Kenneth L Seldeen, PhD

Principal Investigator

Kansas City VA Medical Center, Kansas City, MO

Are You a Good Fit for This Trial?

This trial is for older veterans aged 65-85 who can use an exercise bike and are medically cleared for a muscle biopsy. It's not suitable for individuals with severe illnesses, advanced heart failure or COPD, serious kidney disease, significant cognitive impairment, or those extremely overweight.

Inclusion Criteria

I am either male or female.

I am between 65 and 85 years old.

Any race

Exclusion Criteria

Your VA-SLUMS cognitive screen score is 20 or lower.

I have chronic kidney disease stage 3 or higher.

I have severe COPD.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive NR or placebo supplementation for 3 months, with assessments of frailty, gait speed, and muscle strength at each time point

12 weeks

Regular visits for assessments

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

Trial Overview The study tests if Nicotinamide Riboside (a vitamin B3 form) can improve muscle function and increase NAD+ levels in the body compared to a placebo. Participants will be randomly assigned to either the supplement group or placebo group without knowing which one they're receiving.

How Is the Trial Designed?

Group I: NR Supplementation Experimental Treatment 1 Intervention

Participants in this group will receive NR supplementation at 1000 mg per day (given as 2x250mg capsules morning and 2x250mg at night).

Group II: Placebo supplementation Placebo Group 1 Intervention

Participants in this group will receive placebo given as 2 pills in the morning and 2 pills at night. Placebo pills contain micro cellulose which is likewise found in NR containing capsules.

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?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

University at Buffalo

Collaborator

Trials

139

Recruited

105,000+

Published Research Related to This Trial

Skeletal muscle cells primarily use the enzymes NAMPT, NRK1, and NRK2 to synthesize NAD+ from dietary supplements like nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), which are crucial for maintaining muscle health as we age.

Inhibition of NAMPT reduces NAD+ levels in muscle, but this can be restored by NMN and NR, indicating that both supplements are effective in enhancing NAD+ availability through pathways that depend on NRK1 and NRK2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells. Fletcher, RS., Ratajczak, J., Doig, CL., et al.[2022]

In a 12-week randomized, placebo-controlled trial with 40 middle-aged, obese, insulin-resistant men, nicotinamide riboside (NR) supplementation did not significantly affect mitochondrial function, content, or morphology in skeletal muscle.

Despite a 14% decrease in the protein abundance of NAMPT, an enzyme involved in NAD+ biosynthesis, NR supplementation did not change NAD+ levels or the respiratory capacity of muscle mitochondria, suggesting limited efficacy in improving mitochondrial health in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men. Dollerup, OL., Chubanava, S., Agerholm, M., et al.[2021]

In a mouse model of cancer cachexia, preemptive administration of nicotinamide riboside (NR) significantly reduced weight loss and muscle atrophy by inhibiting key inflammatory factors and muscle-specific proteins associated with muscle degradation.

NR intake also enhanced the production of NAD+ biosynthesis enzymes and inhibited the activity of sirtuin 1, suggesting that NR could be a promising intervention to prevent cachexia in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside Vitamin B3 Mitigated C26 Adenocarcinoma-Induced Cancer Cachexia. Park, JM., Han, YM., Lee, HJ., 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12022230/

The Effect of Nicotinamide Mononucleotide and Riboside ... Despite promising pre‐clinical outcomes, our findings indicate that NMN and NR supplementation offer minimal benefits for sarcopenia and muscle ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6702140/

Nicotinamide Riboside Augments the Aged Human Skeletal ... Its application in vivo has produced impressive results ameliorating metabolic dysfunction and muscle decline (Fang et al., 2017). No data exist ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1568163723002659

NAD+: An old but promising therapeutic agent for skeletal ... Intravenous nicotinamide riboside elevates mouse skeletal muscle NAD(+) without impacting respiratory capacity or insulin sensitivity. iScience, 25 (2022), ...

4. cell.com cell.com/cell-reports/pdf/S2211-1247(19)30940-4.pdf

Nicotinamide Riboside Augments the Aged Human ... The data indicate that oral NR greatly boosts the blood NAD+ metabolome without an increase in NAM, increases muscle NAD+ meta- bolism, and ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/acel.70093

Nicotinamide Riboside Supplementation Benefits in ... Nicotinamide riboside improved arterial stiffness (cardio–ankle vascular index), reduced skin ulcer area, and showed a trend toward ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006291X24001256

The therapeutic perspective of NAD + precursors in age- ... Based on these investigations, the highest safe dose of NR is 2000 mg per day [89], while NMN has been confirmed to be safe at a maximum recorded dose of 1250 ...