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?

This trial aims to understand how healthy adults, both younger and older, process two forms of vitamin B3—nicotinamide (NAM) and nicotinamide mononucleotide (NMN)—to produce NAD+, a vital substance for cell energy. Researchers seek to determine how these vitamins are absorbed and their impact on NAD+ levels in the body. Healthy adults with no major health issues, such as diabetes, and a BMI between 19 and 35, may be eligible to join. Participants will take either NAM or NMN daily for 14 days and provide blood, urine, and stool samples, along with a couple of small muscle biopsies. This study could help improve dosing strategies to boost NAD+ levels, especially in older adults. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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

Research has shown that both nicotinamide (NAM) and nicotinamide mononucleotide (NMN) are safe for use. Studies have found that NMN is well-tolerated by healthy adults, even at doses up to 1250 mg per day for four weeks. One study showed that taking 250 mg of NMN daily increased NAD+ levels without significant side effects.

For nicotinamide, research indicates that taking 1 gram daily is generally safe and can improve metabolic health. However, doses exceeding 3000 mg may cause liver problems, so the amounts used in the study are much lower and should be safe.

Overall, both NAM and NMN are considered safe and well-tolerated, especially in the doses used in this research. Participants will be closely monitored for any side effects to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Nicotinamide (NAM) and Nicotinamide Mononucleotide (NMN) because these compounds target cellular energy and aging processes in a novel way. Unlike standard treatments that might focus on symptoms, NAM and NMN aim to enhance the body's natural energy production and repair mechanisms by boosting NAD+ levels, a crucial molecule in cell metabolism. This could potentially lead to improved vitality and healthspan, especially in older adults. The promise of these treatments lies in their potential to rejuvenate cellular functions, offering a fresh approach to maintaining health and wellness as we age.

What evidence suggests that this trial's treatments could be effective for raising NAD+ levels?

This trial will compare the effects of nicotinamide and nicotinamide mononucleotide (NMN) on NAD+ levels in healthy adults. Research has shown that both nicotinamide, administered to participants in one arm of this trial, and NMN, given to participants in another arm, can effectively increase NAD+ levels in the body. Studies have found that oral nicotinamide can safely boost NAD+ levels for a short time. NMN supplements have raised NAD levels in the blood and are safe and well-tolerated, even at higher doses. These NAD+ boosters may support energy and other vital cell functions, which can decrease with age. While direct evidence of health improvements is not yet available, these NAD precursors show promise for enhancing cellular energy. ^{1 6 7 8 9}

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

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9735188/

The efficacy and safety of β-nicotinamide mononucleotide ... A 12-week RCT with a fixed 250 mg/day oral NMN dose on 42 healthy older men showed that blood NAD concentration was significantly elevated and ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2468501121000055

A single oral supplementation of nicotinamide within the ... This study shows that oral supplementation of nicotinamide within the daily tolerable upper level is an effective way to transiently increase NAD + levels.

3. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-05614-9

Advancements in NMN biotherapy and research updates in ... The results showed that supplementation with NMN for 24 weeks was safe but could not improve grip strength or walking speed [62]. A 12-week ...

4. nature.com nature.com/articles/s41514-022-00084-z

Chronic nicotinamide mononucleotide supplementation ... In this study, we reported that the chronic oral supplementation of 250 mg of NMN per day is safe and a well-tolerated and effective strategy ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/10408398.2024.2387324

Full article: Efficacy of oral nicotinamide mononucleotide ... The objective of the review was to assess the effects of NMN supplementation on fasting glucose, triglycerides, total cholesterol, LDL-C, and HDL-C in adults.

6. 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.

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

The Safety and Antiaging Effects of Nicotinamide ... Supplementing 1 g of NAM daily is a safe and effective way to improve the metabolic abnormalities and quality of life in diabetes patients with nonalcoholic ...

8. aao.org aao.org/eye-health/tips-prevention/vitamin-b3-nicotinamide-glaucoma

Nicotinamide Safety Concerns Nicotinamide can have side effects, especially at high doses (over 3000mg), potentially causing liver damage. Long-term safety is unknown, and ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04910061

Safety and Pharmacokinetics of Nicotinamide ... The purpose of this study is to investigate the safety, pharmacokinetic profile, and effects of nicotinamide mononucleotide (NMN-C) in healthy adults, ...