NAM + NMN for Healthy Adults

Overseen By Nancy K Latham, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Metro International Biotech, LLC

Must not be taking: Steroids, Opiates, Amphetamines, others

Disqualifiers: Diabetes, Severe kidney disease, Pregnancy, others

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

Compensation: Varies

Number of Visits: 4

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

We are doing this research to learn how healthy younger and older adults use two forms of vitamin B3-called nicotinamide mononucleotide (NMN) and nicotinamide (NAM)-to make NAD+. NAD+ is a natural substance that cells need for energy and other important processes. Our goal is to find out how these NAD precursors are absorbed and metabolized and how they raise NAD+ in different tissues. Who can join? Healthy adults men and women aged 18 to 40 (younger group) or 65 and older (older group) Participants with a body mass index ranging between 19 and 35 No major health issues like diabetes or severe kidney disease What will happen? Participants will take labeled or unlabeled NMN or NAM by mouth every day for 14 days. Researchers will collect blood, urine, and stool samples. Researchers also do a small muscle biopsy (under local numbing) twice to check how these NAD precursors raise NAD+ in muscle. Why is this important? NAD+ levels may drop as people age, and this drop could affect overall health and energy in cells. A better understanding of how NMN and NAM are metabolized in the body to raise NAD+ levels in both younger and older adults may help us optimize dosing and strategies for raising NAD in older people. Possible benefits and risks: Participants may not get any direct health benefit from this study; the main goal is to gather new knowledge. NMN and NAM appear safe in the doses used. A muscle biopsy may cause soreness or bruising. Researchers will monitor participants closely for any side effects throughout the study.

Will I have to stop taking my current medications?

You may need to stop taking certain supplements, especially those containing niacin, nicotinic acid, nicotinamide, or herbal supplements, at least 14 days before starting the trial. If you are using a supplement with NAM, niacin, NMN, or NR, you must stop it at least 2 weeks before joining. Other medications like anabolic steroids, certain performance-enhancing drugs, and some recreational drugs are also prohibited.

Is the combination of NAM and NMN safe for healthy adults?

Research shows that NMN is generally safe for healthy adults when taken orally at doses up to 1250 mg daily for 4 weeks, with no severe side effects reported. However, high doses of NAM may have potential risks, such as changes in DNA and protein methylation, especially with long-term use. ^{1 2 3 4 5}

How does the drug NAM + NMN differ from other treatments for age-related conditions?

The drug NAM + NMN is unique because it combines nicotinamide and nicotinamide mononucleotide, which are precursors to nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme for metabolism. This combination aims to increase NAD+ levels, potentially counteracting age-related changes and improving metabolic health, which is different from other treatments that may not target NAD+ levels directly. ^{1 2 6 7 8}

What data supports the effectiveness of the drug Nicotinamide Mononucleotide (NMN) for healthy adults?

Research shows that NMN, a precursor to NAD+ (a molecule important for energy and cell repair), can increase NAD+ levels in humans, which may help with age-related conditions. In older adults, NMN has been found to improve sleep quality, reduce fatigue, and enhance physical performance. ^{1 2 7 9 10}

Who Is on the Research Team?

Shalender Bhasin, MB, BS

Principal Investigator

Brigham and Women's Hosptial

Are You a Good Fit for This Trial?

Healthy adults aged 18-40 or 65+ with a BMI of 19-35 can join this study. They must not have major health issues like diabetes or severe kidney disease. The trial aims to understand how the body uses vitamin B3 forms (NMN and NAM) to produce NAD+, which is vital for cellular energy.

Inclusion Criteria

Has a body mass index (BMI) between 19 and 35 kg/m2, inclusive

Is free from clinically significant medical problems as determined by the Investigator

Is capable of providing written informed consent

Exclusion Criteria

Has AST or ALT > 2 times the upper limit of normal

Hematocrit < 36% or > 51% for men, or < 35% to > 48% for women

Participation in an investigational trial within the past 3 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

1 visit (in-person)

Intervention

Participants receive daily doses of NMN or NAM for 14 days with detailed sampling on Days 1 and 14

14 days

Multiple visits for blood draws and biopsies on Days 1, 2, 3, 5, 8, 14, and 15

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person) on Days 16 and 43

What Are the Treatments Tested in This Trial?

Interventions

• Nicotinamide
• Nicotinamide Mononucleotide

Trial Overview The trial tests how orally taken Nicotinamide Mononucleotide (NMN) and Nicotinamide (NAM) are metabolized in healthy younger and older adults. Participants will consume these substances daily for two weeks, while researchers monitor their effects on raising NAD+ levels in tissues through blood, urine, stool samples, and muscle biopsies.

How Is the Trial Designed?

Group I: NAM- Nicotinamide Active Control 1 Intervention

This arm will include 16 participants (8 young and 8 older adults) who will receive NAM once daily for 14 consecutive days.

Group II: NMN- Nicotinamide Mononucleotide Active Control 1 Intervention

This arm will include 16 participants (8 young and 8 older adults) who will receive NMN once daily for 14 consecutive days.

Who Is Running the Clinical Trial?

Metro International Biotech, LLC

Lead Sponsor

Trials

5

Recruited

230+

Published Research Related to This Trial

A study involving 31 healthy adults showed that daily oral administration of 1250 mg of β-NMN for 4 weeks is safe and well-tolerated, with no significant adverse effects reported.

The research indicates that β-NMN does not cause harmful changes in various health parameters, suggesting its potential for further exploration in age-related disease prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women. Fukamizu, Y., Uchida, Y., Shigekawa, A., et al.[2022]

A study involving 108 older adults showed that taking nicotinamide mononucleotide (NMN) in the afternoon significantly improved lower limb function and reduced drowsiness after 12 weeks.

The NMN group demonstrated the largest improvements in physical performance, particularly in the 5-times sit-to-stand test, indicating its potential to enhance physical capabilities and combat fatigue in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study. Kim, M., Seol, J., Sato, T., 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]

In a double-blind, placebo-controlled study involving 32 overweight or obese adults aged 55-80, the microcrystalline formulation MIB-626 was found to be safe and well-tolerated, with no significant differences in adverse events compared to placebo.

MIB-626 significantly increased blood levels of nicotinamide mononucleotide (NMN) and nicotinamide adenine dinucleotide (NAD) in a dose-dependent manner, suggesting its potential to enhance NAD metabolism and support healthspan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of β-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-Aged and Older Adults. Pencina, KM., Lavu, S., Dos Santos, M., et al.[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]

Oral supplementation of nicotinamide mononucleotide (NMN) at 250 mg/day for 24 weeks was found to be safe for older male patients with diabetes, with no severe adverse events reported.

Despite the safety of NMN, the study showed no significant improvements in grip strength or walking speed compared to the placebo group, although there were indications of reduced frailty and changes in retinal thickness that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of nicotinamide mononucleotide on older patients with diabetes and impaired physical performance: A prospective, placebo-controlled, double-blind study. Akasaka, H., Nakagami, H., Sugimoto, K., et al.[2023]

Citations

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

Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women. [2022]

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

Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study. [2022]

4. England 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. [2021]

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

MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of β-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-Aged and Older Adults. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety Evaluation for Restorin® NMN, a NAD+ Precursor. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Subacute Toxicity Study of Nicotinamide Mononucleotide via Oral Administration. [2021]

9. Japan pubmed.ncbi.nlm.nih.gov

Effects of nicotinamide mononucleotide on older patients with diabetes and impaired physical performance: A prospective, placebo-controlled, double-blind study. [2023]

10. Egypt pubmed.ncbi.nlm.nih.gov

Nicotinamide mononucleotide (NMN) as an anti-aging health product - Promises and safety concerns. [2022]