NMN Studies: The Top 5 Research Studies On NMN (Including Objectives, Testing And Outcomes)

Reviewing the latest NMN research is the smart way to ensure you get the facts about NMN whether you’re increasing your academic knowledge or considering taking NMN.

In this article you’ll find a summary of 5 studies on NMN conducted by highly respected universities, government and private organizations.

We’re providing a summarized version to speed up your consumption of the research as well as providing direct links to each research study for you to investigate further.

Let’s get into it…

Study:  “Long-term administration of nicotinamide mononucleotide (NMN) mitigates age-associated physiological decline in mice.”

Study URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668137/
Authors: Kathryn F. Mills, et al.
Journal/Publisher: PubMed
Year Published: 2016

Research Objective(s):  To determine the influence of NMN on NAD+ levels, both of which are involved in the process of aging.

Testing: The researchers conducted a 12 month-long study to investigate the effects of administering NMN to mice during normal conditions of aging.

Outcomes: The NMN, administered orally was utilized quickly in synthesizing NAD+ in tissues.

The NMN appeared to mitigate age-associated physiological decline in mice without any signs of toxicity or negative effects.

The NMN appeared to enhance energy metabolism, improve physical activity, suppress age-related body weight gain, improve eye function, improve plasma fat profile and improve insulin sensitivity.

The NMN appeared to prevent age-related gene expression changes in important metabolic organs, enhance mitochondrial oxidative metabolism and protein imbalance in skeletal muscle.

Conclusion: These effects of NMN highlight the preventive and therapeutic potential of NAD+ intermediates as effective anti-aging interventions in humans.

Study:  “The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multi-center, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial.”

Study URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9735188/
Authors: Lin Yi et al.
Journal/Publisher: GeroScience
Year Published: 2022

Research Objective(s):

To test the efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation on blood NAD levels in healthy middle-aged adults, as well as test the clinical efficacy, tolerability and safety of NMN.

Testing:  The randomized, parallel, double-blinded, placebo-controlled and dose-dependent study involved multiple centers, using daily oral doses of 300mg, 600mg, and 900mg for 60 days.

Outcomes: The trial revealed NMN supplementation to be safe and well-tolerated at daily doses of up to 900mg.

No adverse effects we identified and there were no dropouts during the study.

Conclusion: During treatment, participants showed significant and dose-dependent increases in blood NAD concentration.

Daily oral doses of NMN of up to 900mg was safe and well-tolerated and NMN had an overall positive effect on physical endurance and general health conditions of healthy adults in the study.

Study: “Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice.”

Study URL:  https://www.sciencedirect.com/science/article/pii/S221323171930240X
Authors:  Stefano Tarantini et al.
Journal/Publisher:  Redox Biology
Year Published:  2019

Research Objective(s):  To test the hypothesis that supplementing NMN can rescue neurovascular coupling responses in aged mice by reducing mitochondrial oxidative stress in cerebro-microvascular endothelial cells.

Testing: 

Several tests were performed to measure various effects of NMN.

Aged mice were treated with NMN for two weeks and tested for:

• Cognitive function
• Motor coordination
• Endothelial function
• Oxidative stress
• Antioxidant defences
• Mitochondrial function
• Behavioral tasks

Outcomes:

• A 14-day treatment with NMN significantly increased CBF (Cerebral Brain Fluid) responsesNMN treatment significantly increased Cerebral Brain Fluid in aged mice
• Treatment of aged mice with NMN significantly improved acetylcholine-induced vasodilation (a widening of blood vessels leading to improved blood flow)

Conclusion:

These findings suggests that NMN significantly improves endothelial function by restoring endothelial Nitrous Oxide mediation in aged vessels.

The effectiveness of NMN was demonstrated through increased vascular NAD+ levels.

Restoration of cerebro-microvascular function in the aged mice supplemented with NMN is linked with improved cognitive function.

Study:  “Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men”

Study URL: https://www.jstage.jst.go.jp/article/endocrj/67/2/67_EJ19-0313/_article
Authors: Junichiro Irie, et al.
Journal/Publisher: Endocrine Journal
Year Published: 2020

Research Objective(s):  A clinical trial to investigate the safety of single NMN administration in 10 healthy Japanese men.

Testing: A single-arm, non-randomized intervention was conducted by researchers. Patients received a single oral administration of NMN in quantities of 100mg, 250mg, and 500mg.

For 5 hours after each intervention, clinical findings and parameters were investigated and recorded.

Ophthalmic (eye) examination and sleep quality assessment were also conducted before and after the intervention.

Outcomes:

The single oral administrations of NMN did not cause any significant clinical symptoms or changes in heart rate, blood pressure, oxygen saturation, and body temperature.

Laboratory analysis results did not show significant changes, except for increases in serum bilirubin levels and decreases in serum creatinine, chloride, and blood glucose levels within the normal ranges, independent of the dose of NMN.

Results of ophthalmic (eye) examination and sleep quality score showed no differences before and after the intervention.

Plasma concentrations of N-methyl-2-pyridone-5-carboxamide (an end product of NAD degradation) was significantly increased dose-dependently by NMN administration.

The single oral administration of NMN was shown to be safe and effectively metabolized in the 10 healthy patients, without causing any significant deleterious effects.

Conclusion:  Oral administration of NMN was found to be feasible which implicates NMN as a potential therapeutic strategy to mitigate aging-related disorders in humans.

Study: “Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study.”

Study URL:  https://www.tandfonline.com/doi/full/10.1186/s12970-021-00442-4
Authors: Yunlong Zhao, et al.
Journal/Publisher: Journal of the International Society of Sports Nutrition
Year Published:  2021

Research Objective(s):  This study investigates the effects of NMN and exercise training on cardiovascular fitness in healthy amateur runners.

Testing: 

The six-week study included 48 young and middle-aged recreationally trained runners.

A randomized, double-blind, placebo-controlled, four-arm clinical trial.

Participants were placed at random into one of four groups:

• Group 1: Low dosage group (300 mg/day NMN)
• Group 2: Medium dosage group (600 mg/day NMN)
• Group 3: High dosage group (1200 mg/day NMN)
• Group 4: Control group (placebo).

Each group consisted of 10 male participants and 2 female participants.

The runners trained 5-6 times weekly, with each training session between 40–60 min.

At 6 weeks, cardiopulmonary exercise testing was performed at baseline and after the intervention to assess the aerobic capacity of the runners.

Outcomes:

Over the 6 week period, the change from baseline revealed increases in the medium and high dosage groups in each of the following areas (versus the control group);

• Oxygen uptake (VO2)
• Percentages of maximum oxygen uptake (VO2max)
• Power at first ventilatory threshold
• Power at second ventilatory threshold.

Conclusion:

NMN increases the aerobic capacity of humans during exercise training, and the improvement is likely the result of enhanced O2 utilization of the skeletal muscle.

The Scientific Community’s Interest In NMN

NMN has gained a lot of interest in the scientific community due to its potential role in slowing the aging process and improving health outcomes, particularly for those aged over 35.

Studies such as the ones listed above that investigate the biological impact of NMN supplementation on cellular health have suggested that it could play a key role in enhancing longevity and overall health.

Pioneering work in this field by people such as Dr David Sinclair of Harvard University has identified NMN’s role in the enhancement of NAD+ levels, a critical coenzyme in cellular metabolism.

This suggests that NMN supplementation could counteract certain age-associated physiological declines.

Clinical trials, such as the first human clinical study for NMN conducted in Japan, have started to evaluate the effectiveness and safety of NMN in humans, aiming to confirm findings from preclinical studies conducted in animal models.

Given the therapeutic promise revealed to date by laboratory studies including improvements in neuronal functions, the outcomes of these NMN clinical trials could reveal exciting insights into how we can slow aging.

NMN researchers are continuing to understand and uncover the pharmacokinetics and bioavailability of NMN as well as how it interacts with various physiological processes.

NMN Fundamentals: How NMN Works

NMN is a nucleotide derived from ribose and nicotinamide.

As a precursor to nicotinamide adenine dinucleotide (NAD+), NMN plays a pivotal role in the biochemistry of mammalian cells.

• NMN Production In The Body:  NMN is naturally produced in the body and is a critical step in the NAD+ biosynthetic pathway.
• NAD+ Role:  NAD+ is essential for energy production, DNA repair, and cellular signalling.

A Cyclical Relationship

The relationship between NMN and NAD+ is cyclical.

NMN is synthesised from nicotinamide (a form of vitamin B3) through the salvage pathway and subsequently transformed into NAD+.

Conversely, as NAD+ is utilized, it breaks down into nicotinamide, thus promoting the production of NMN and continuing the cycle.

NMN’s Impact On Biological Functions:

• Energy Production:  NMN contributes to the creation of ATP, the energy currency of the cell.
• DNA Repair:  NMN supports the body's natural DNA repair mechanisms.
• Metabolic Function:  NMN influences metabolism and age-related metabolic decline.

Supplementation: Studies reveal the potential of quality NMN supplements to boost NAD+ levels, which naturally decline with age.

Dosage and Safety: Research has indicated that NMN is safe providing dosage is within recommended ranges, which for both men and women could range from 250mg to 1200mg per day depending on age, current health status and physical activity levels.

NMN’s role in NAD+ production and metabolism underlines the importance of understanding NMN in the context of health and age-related diseases.

NMN is a foundational compound in the cellular processes sustaining life.

Clinical Trials Overview

Clinical trials of NMN are essential for assessing the efficacy and safety of NMN’s potential impact on health and aging.

Mouse Models

Mouse models serve as an essential preliminary step before human NMN clinical trials.

They provide critical data on the potential benefits and mechanisms of action of substances like NMN.

Numerous preclinical studies on mice have shown promising results, suggesting that NMN supplementation could influence age-related genetic expression and metabolic processes.

These studies pave the way for human trials of NMN by revealing the appropriate dosages for safety and effectiveness that can later be adjusted for human physiology.

Human Clinical Trials With NMN

Randomized, double-blind, placebo-controlled NMN trials are the gold standard in human clinical research and ensure that the results are attributable to NMN, rather than other variables.

A recent study (mentioned above) on NMN supplementation in middle-aged adults was conducted in this manner to assess safety and biological effects.

Daily NMN oral doses of up to 900mg were shown to be safe and well-tolerated.

The study revealed that NMN had an overall positive effect on physical endurance and the general health condition of healthy adults in the study.

Biological Impact of NMN

NMN plays a crucial role in enhancing various biological mechanisms including metabolic pathways, maintaining DNA integrity, promoting cell growth, supporting neurological functions, and bolstering cardiovascular health.

Metabolic Pathways

NMN has been found to be a key player in metabolic pathways, affecting energy production and utilization in the body.

Research has shown that NMN can improve glucose clearance in conditions such as diet-induced obesity.

Metabolism rates can be improved, potentially offering benefits in energy balance and weight management.

DNA Repair and Cell Growth

NMN plays a significant role in DNA repair and cell growth.

By increasing the levels of NAD+, NMN helps to facilitate crucial DNA repair processes and is involved in the promotion of healthy cell function.

These properties are instrumental in mitigating the effects of age-related degeneration.

Neurological Effects

Neurodegeneration is another area where NMN presents potential therapeutic effects.

NMN has been observed to support brain health by participating in pathways that may prevent or slow down the progression of neurological disorders such as Alzheimer’s disease.

The positive impact on cognitive functions highlights the importance of NMN in neuroprotection and neurological resilience.

Cardiovascular Health

NMN has also shown benefits for heart and blood pressure regulation.

Supplementation has been associated with improved cardiovascular function and the potential to counteract some detrimental effects of aging on the cardiovascular system.

This spans from arterial health to the maintenance of healthy blood pressure levels, revealing its significance in heart health maintenance.

NMN and Longevity

NMN has been correlated with positive impacts on aging and longevity, particularly through lifespan extension and healthspan improvement.

Aging Process

The aging process is a complex biological process often characterized by the gradual decline in physiological function.

Research suggests that NMN may play a role in ameliorating these effects.

One study (included above) indicates that NMN pre-clinical studies have demonstrated improved cellular bioenergetics and reduced signs of aging at the cellular level.

Lifespan Extension

Lifespan extension is a key aspect of geroscience, and NMN has been noted for its potential in this area.

For example, in mouse models, NMN was linked to a significant increase in lifespan—about a 29% rise, as outlined in a study mentioned on ScienceDirect.

This extends the understanding of NMN's involvement in anti-aging to practical, measurable outcomes.

Healthspan Improvement

Focusing on healthspan improvement, NMN has shown promise in enhancing overall quality of life by potentially delaying the onset of age-related diseases.

Nature's article on human clinical studies for NMN underway in Japan highlights its potential benefits in reducing complications associated with aging diseases, leading to a potentially better healthspan.

This suggests NMN might support physiological resilience during aging.

Therapeutic Potential and Safety

Recent studies consistently highlight the significant therapeutic potential of NMN in various age-related conditions while also testing its safety and tolerability in humans.

Current Findings

Research indicates that NMN may benefit metabolic activities, with positive implications for age-induced complications.

For instance, administration of NMN was found to have reversing effects on metabolic defects in age-related animal models.

This is linked to NMN's role in enhancing the NAD+ levels in cells, a crucial factor for energy production and cellular health.

In humans, clinical trials are ongoing to assess the efficacy of NMN in improving health markers among middle-aged adults.

These studies will reveal more about its capacity to act as a therapeutic agent.

Adverse Events Of NMN

In parallel with the exploration of NMN's therapeutic effects, the safety of its supplementation is carefully examined.

Clinical studies aim to ascertain the frequency and severity of any adverse events associated with NMN intake.

So far, the tolerability at commonly used dosages appears to be acceptable in the short term.

However, comprehensive long-term safety assessments are needed to fully endorse NMN as a consistently safe health supplement.

Molecular Biology of NMN

Within molecular biology, NMN influences the activity of sirtuins and gene expression, acts as a substrate for enzymes like PARP and CD38, and is fundamental in supporting mitochondrial function.

Sirtuins and Gene Expression

NMN plays a pivotal role in modulating the activity of sirtuins, a family of NAD+-dependent deacetylase enzymes that directly influence gene expression.

Sirtuins can affect the transcription of genes by removing acetyl groups from specific proteins that interact with DNA, thereby impacting cellular processes such as aging, apoptosis and inflammation.

Research highlighted by Cell Metabolism demonstrates how NMN, through its contribution to NAD+ levels, can enhance the function of sirtuins, thereby promoting the maintenance and repair of DNA and other cellular components.

PARP and CD38

Both Poly (ADP-ribose) polymerases (PARP) and CD38 rely on NAD+ to perform their essential cellular roles.

These enzymes use NAD+ as a substrate to transfer ADP-ribose units onto proteins - a process vital for repairing DNA damage in the case of PARP and for calcium signalling in the case of CD38.

Adequate NMN levels ensure a constant supply of NAD+ for these enzymes, supporting their activity in cellular maintenance and homeostasis.

Mitochondrial Function

Mitochondria are often described as the powerhouses of the cell, and NMN significantly impacts their function.

NMN supports mitochondrial function including energy production as the availability of NAD+ is crucial for the electron transport chain – the series of reactions that generate cellular energy in the form of ATP.

Additionally, NAD+ availability has been linked to the promotion of mitophagy, the selective degradation of mitochondria by autophagy, which is crucial for removing damaged mitochondria and maintaining cellular health.

Studies, such as those reported in Frontiers in Pharmacology, suggest that NMN supplementation can result in enhanced mitochondrial biogenesis and improved oxidative metabolism, thus highlighting NMN's importance in mitochondrial maintenance.

Physiological Effects and Health Interactions

Recent studies into NMN have uncovered its significant role in various physiological processes and health interactions, particularly in relation to metabolic diseases, obesity, diabetes and systemic inflammation.

Insulin Sensitivity and Diabetes

Research suggests that NMN may improve insulin sensitivity in individuals, playing a positive role in the management of diabetes.

A study highlighted by Cell Metabolism revealed NMN's potential in stabilizing blood glucose levels and enhancing insulin action, indicating promising therapeutic implications for diabetic patients.

Obesity and Metabolic Health

NMN has been studied for its effects on obesity and overall metabolic health.

Findings in mice have shown that long-term NMN administration can reduce liver fat and mitigate age-associated physiological decline, which is particularly relevant for metabolic diseases often associated with obesity.

These effects, pointed out by studies such as those published in Cell Metabolism, suggest that NMN could support the body in maintaining a healthier metabolism throughout the aging process.

Inflammation and Immune Response

Inflammation is a known factor in the development of chronic diseases, and NMN's impact on immune response and inflammatory processes has been a subject of scientific investigation.

Research indicating that NMN could have anti-inflammatory properties has been significant, cited in journals such as ScienceDirect.

This points to NMN's role in modulating the body's immune response, with potential benefits for inflammatory-related conditions.

By exploring the intricate mechanisms at play, these studies continue to unravel the many ways in which NMN could positively influence human health, particularly in the management of metabolic and inflammatory diseases.

Pharmacokinetics And Bioavailability

Understanding the pharmacokinetics and bioavailability of NMN is essential for its therapeutic application.

Researchers focus on how NMN is absorbed, distributed, metabolized and excreted in the body as well as how its effects vary with dosage.

Dose-Dependent Effects

NMN demonstrates dose-dependent pharmacokinetics, meaning that the substance's behavior in the body changes with the amount administered.

A study noted the increased circulating NAD+ levels after the oral administration of NMN, suggesting a direct relationship between the dose and the extent of systemic exposure to NMN.

Transport And Uptake

The transport and uptake of NMN into cells are pivotal factors in its bioavailability.

NMN is believed to be transported into cells via a specific transporter name SLC12A8.

The effective functioning of this transporter is crucial for the cellular uptake and subsequent utilization of NMN, impacting its potential as a therapeutic agent.

Dietary Sources And Supplements

When exploring options for increasing levels of NMN, one can look toward diet and commercially available supplements.

Both avenues offer means to potentially augment the body's NAD+ levels, a coenzyme essential for many physiological functions.

Natural Occurrences

NMN can be found in a variety of foods such as broccoli and edamame - two natural sources that contain NMN, albeit in low concentrations.

Milk is another dietary source of NMN, providing a natural pathway to boost NAD+ levels in the body.

Although these foods contribute to NAD+ precursors, the amounts may not be sufficient to significantly increase NAD+ levels, underscoring the interest in concentrated NMN supplement forms.

Supplement Forms

Supplements of NMN are available to directly increase NAD+ levels.

There are varieties of NMN supplements, often marketed with anti-aging claims, due to the importance of NAD+ for cellular functions and energy.

Another related compound, nicotinamide riboside (NR), is available in supplement form.

It functions similarly to NMN by acting as a precursor to NAD+.

In a supplement form called nicotinic acid, or niacin, it has been used not only for its potential anti-aging effects but also for its role in supporting metabolic and cardiovascular health.

However, despite their availability, consumers should approach NMN and NR supplements with careful analysis of their purported benefits and existing clinical evidence.

Finding a supplement with high-purity and without fillers, preservatives and heavy metals should be a priority for consumers.

Emerging Research

NMN is a compound of growing interest in the field of aging and metabolic health, and emerging research points toward its potential benefits in various models and conditions.

Preclinical Studies

NMN has gained significant attention in preclinical studies using murine (rodent) models.

Researchers have found that NMN can delay aspects of aging and improve metabolic functions in rodents.

For example, studies suggest that NMN might combat age-related declines in energy metabolism and has the potential to improve outcomes related to Werner syndrome, a condition that accelerates the aging process in humans.

Gut Microbiome and Metabolism

The gut microbiome plays a crucial role in overall health and metabolism, and NMN research is now extending into this arena.

Initial findings indicate that NMN could influence the gut microbiota composition, leading to metabolic improvements.

Studies are exploring how supplementation boosts NAD+ levels, which in turn supports various metabolic pathways modulated by the microbiome.

Neurodegenerative Diseases

When it comes to neurodegenerative diseases, NMN is being observed for its neuroprotective properties.

Evidence from preclinical studies indicates that it may support axonal health, where the over-activation of the enzyme SARM1 plays a part in axon degeneration, which is common in neurodegenerative diseases.

By targeting this pathway, NMN could offer a new approach to managing such diseases.

FAQs

What are natural sources of NMN?

Natural sources of NMN include a variety of foods such as broccoli, cabbage, cucumber, edamame, and avocados.

Regular consumption of these foods can contribute to the levels of NMN within the body but may not be adequate to make a significant impact on NAD+ levels. Supplementing with NMN may be required.

What are the results of recent human trials on NMN?

Recent human trials with NMN have indicated that it can boost NAD+ biomarkers which are important for mitochondrial function and energy metabolism.

More research is needed to establish a comprehensive understanding of NMN's effects in human health.

What benefits can one expect from using NMN supplements?

Supplementing with NMN may support cellular energy production and promote cellular repair mechanisms due to its role as a precursor to NAD+.

It may also improve insulin sensitivity, although individual results can vary.

How does NMN compare to NAD+ in terms of health benefits?

NMN is a precursor to NAD+, meaning it contributes to the biosynthesis of NAD+ in the body.

NAD+ plays a critical role in energy metabolism and cell health.

As such, NMN, by raising NAD+ levels, indirectly supports the same biological processes as NAD+.

Is there scientific proof to support the effectiveness of NMN?

Scientific research is ongoing to determine the effectiveness of NMN.

Early studies have shown promising results indicating NMN may support various aspects of cellular health, though larger, long-term human studies are required to confirm these findings.

Do Doctors prescribe NMN?

At the time of writing, NMN is available in supplement form and not available as a pharmaceutical drug accessible for Doctors to prescribe to patients.

As medical and scientific research into NMN advances, there may come a time when NMN could be available as a medicine by prescription.

Wrapping Up

NMN offers hope in a world obsessed with staying young and aging gracefully.

For NMN researchers such as Dr. David Sinclair, the field of aging offers almost unlimited possibilities for bringing new research to the masses.

This research offers pharmaceutical companies and supplement manufacturers an opportunity to deliver effective products to meet the demand for NMN to support healthy aging.

One such manufacturer is AlphaCell Labs who offer a 99.5% pure NMN supplement complete with third-party test certificate verifying its purity and absence of heavy metals and other contaminants.

Find out more about their high purity 500mg NMN capsules.