Study type: 

Randomised, multicentre, double-blind, placebo-controlled, parallel group, dose-dependent trial

Purpose:

The primary objective was to evaluate blood concentrations of nicotinamide adenine dinucleotide (NAD) with different doses of NMN. NAD is a vital molecule that acts like a helper in the body's cells, participating in important processes like turning food into energy and helping to repair damaged DNA.  The secondary objectives were to assess the safety, tolerability and clinical efficacy of NMN supplementation.

Measurement methods:

Clinical efficacy was evaluated by conducting a subjective general health assessment (survey) and measuring NAD blood concentration, physical performance (six-minute walking test), blood biological age (Aging.Ai 3.0 calculator) and the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). The HOMA-IR calculation involves analysing fasting blood glucose and insulin levels to provide an estimate of insulin resistance. 

NMN dose:

300, 600 or 900 mg/day, or a placebo

Duration:

60 days

Participants:

80 middle-aged healthy adults

Results:

Compared to the placebo, the blood concentration of NAD significantly improved as the NMN dose increased (dose-dependent). An increase in NAD+ may enhance energy metabolism, support cell and tissue repair, and contribute to overall well-being. Research has found that NAD+ levels naturally decline with age. The most beneficial effects in the study, particularly on blood NAD levels and physical performance, were achieved with a daily oral intake of 600 mg.  Oral administration of NMN up to 900 mg/day for 60 days was safe and well tolerated. The 900 mg/day oral dose did not have significantly better efficacy than the 600 mg/day dose. 

In addition, the study found an association between NMN supplementation and improvements in physical endurance and general health conditions, as evidenced by significant improvements in measures such as the six-minute walking test, blood biological age, and general health survey when compared to a placebo. Overall, these findings suggest that NMN supplementation may improve health and physical performance.

Year:

2022

Link:

https://doi.org/10.1007/s11357-022-00705-1

Study type: 

Randomised, double-blind, placebo-controlled, parallel-group trial

Purpose:

To investigate the influence of 12-week NMN supplementation on biochemical and metabolic health parameters.

NMN dose:

250 mg/day (2 x 125 mg/day) or a placebo

Duration:

12 weeks

Participants: 

36 healthy, middle-aged men and women

Results:

The researchers observed that serum nicotinamide (NAD+) levels were significantly higher in the NMN intake group than in the placebo group. Nicotinamide is a form of vitamin B3 and a building block for NAD+, which plays a critical role in cellular energy production and other cellular processes. Low levels of nicotinamide in the blood may indicate a vitamin B3 deficiency, potentially impacting various aspects of health, as NAD+ is involved in many vital processes within the cells. 

NMN supplementation showed potential in reducing arterial stiffness as indicated by a tendency of pulse wave velocity values, a measure of arterial stiffness, to decrease in the NMN group. Stiff arteries hinder blood flow, which can increase the risk of heart-related problems. However, no significant difference was found between the NMN and placebo groups. 

Long-term NMN supplementation at 250 mg/day was well tolerated and did not cause adverse events. NMN safely and effectively elevated NAD+ metabolism in healthy middle-aged adults.  

Year:

2023

Link:

https://doi.org/10.1038/s41598-023-29787-3

Study type: 

Randomised double-blind placebo-controlled trial

Purpose:

To investigate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who are overweight or obese

NMN dose:

250 mg/day or placebo

Duration:

10 weeks

Participants:

25 postmenopausal women with prediabetes

Results:

The study found an association between NMN supplementation and increased muscle insulin signalling, which involves the phosphorylation (activation) of certain proteins such as protein kinase AKT and the targeting of rapamycin (mTOR), compared to the placebo group. These proteins work together and are crucial for maintaining proper blood sugar levels and ensuring the muscles have the energy they need to function effectively. 

In addition, NMN supplementation was associated with increased muscle insulin sensitivity, indicating that the muscles became more responsive to the effects of insulin, a crucial factor for managing blood sugar levels and overall metabolic well-being. This improvement was measured by how quickly glucose was removed per unit of fat-free mass.

Year:

2021

Link:

https://doi.org/10.1126/science.abe9985

Study type: 

Animal study (age-induced and diet-induced diabetic mice)

Purpose:

To investigate whether NMN could help treat diabetes caused by diet and ageing in mice.

Age-related complication:

Age- and diet-induced diabetes

NMN dose:

500 mg/kg body weight/day intraperitoneally for 7–10 days

Results:

Researchers observed several positive effects of NMN in mice with type 2 diabetes. Firstly, NMN improved glucose and lipid metabolism, specifically enhancing insulin secretion, insulin sensitivity, lipid profile, hepatic insulin sensitivity, and glucose tolerance.  Improvements in these factors collectively contribute to maintaining healthy blood sugar levels, efficient energy metabolism, and overall cardiovascular health. When these aspects are functioning optimally, the risk of chronic diseases such as type 2 diabetes and cardiovascular diseases is lowered. 

Secondly, NMN restored NAD+ levels (a molecule involved in energy metabolism) in the liver and body fat. Elevated NAD+ levels are generally associated with improved cellular health, enhanced metabolism, and potential benefits for longevity and overall well-being.

Thirdly, NMN normalised the inflammatory response, circadian rhythm (the body's internal clock that regulates sleep and other functions) and oxidative stress (cell damage caused by harmful molecules) affected by high-fat diets and ageing. These improvements were partly attributed to increased NAD+ levels and the activation of SIRT1, a protein associated with metabolic regulation and longevity.

The results provide evidence that promoting NAD+ biosynthesis by administering NMN may be an effective intervention to treat the pathophysiology of diet- and age-induced type 2 diabetes. 

Year

2011

Link:

https://doi.org/10.1016/j.cmet.2011.08.014 

Study type: 

Animal (rats) and cellular study 

Purpose:

To study the impact of NMN on beta-amyloid oligomer-induced neuronal death and cognitive impairment.  These oligomers are considered to be toxic and are thought to play a significant role in the development and progression of Alzheimer's disease.

Age-related complication:

Alzheimer's disease

NMN dose:

500 mg/kg body weight/day

Duration:

10 days

Results:

NMN improved cognitive function, neuron survival and energy metabolism. These improvements potentially slow down the progression of cognitive decline. NMN restored levels of NAD+ (a key player in energy metabolism, DNA repair, and cell signalling) and ATP (the cell's primary energy currency) and eliminated the accumulation of reactive oxygen species (ROS), which are harmful molecules that can cause damage to cells and DNA This restoration of NAD+ and ATP levels and reduction in ROS accumulation is beneficial because it can potentially support better cellular energy production, protect neurons from oxidative stress, and contribute to the overall health of brain cells. This is particularly important in the context of Alzheimer's disease, where cellular dysfunction and oxidative damage contribute to the disease's progression.

Year

2016

Link:

https://doi.org/10.1016/j.brainres.2016.04.060

Study type: 

Animal study (a mice model of Alzheimer’s disease)

Purpose:

To investigate the effect of NMN on brain mitochondrial impairments. Mitochondria are the energy-producing "powerhouses" of our cells.

Age-related complication under study:

Alzheimer’s disease

NMN dose:

100 mg/kg body weight subcutaneously every other day for 28 days

Duration:

28 days

Results:

Researchers observed improvements in the functioning of mitochondria, the energy-producing “powerhouses” of cells. In Alzheimer’s disease, there are known issues with the functioning of mitochondria. There was also a reduction in mutant amyloid precursor proteins, which may potentially slow down or prevent the progression of Alzheimer's disease.

NMN treatment also increased the levels of SIRT1 and CD38, which are proteins that play important roles in cellular processes that normally decline with age.  

Year

2015

Link:

https://doi.org/10.1186/s12883-015-0272-x 

Study type: 

Animal study (mice) 

Purpose:

To investigate the effects of NMN and its underlying mechanisms in mice with Alzheimer's disease.

Age-related complication:

Alzheimer’s disease

NMN dose:

100 mg/kg body weight/every other day (subcutaneously)

Duration:

28 days

Results:

NMN substantially improved cognitive impairments, neuroinflammation, beta-amyloid pathology and synaptic loss. Both beta-amyloid pathology (plaques) and synaptic loss are key features of Alzheimer's disease and are associated with cognitive decline and memory problems characteristic of the condition.

Year

2017

Link:

https://doi.org/10.1016/j.neulet.2017.03.027

Study type: 

Animal study (aged rats) 

Purpose:

To investigate the effect of NMN on cognitive outcomes in aged rats.

Age-related complication:

Cognitive impairment due to ageing

NMN dose:

100 mg/kg body weight/ every other day

Duration:

28 days

Results:

NMN had neuroprotective effects, reduced cognitive decline and helped improve age-associated memory and learning impairments.

Year

2019

Link:

https://doi.org/10.1016/j.neuroscience.2019.09.037

Study type: 

Randomised double-blind placebo-controlled trial

NMN dose:

There were 3 different dosage groups and a placebo group:

1. 300 mg/day (low dosage group)
2. 600 mg/day (medium dosage group)  
3. 1200 mg/day (high dosage group)

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

Additional interventions:

All participants actively trained during the study period by adhering to an exercise program: 6 weeks of aerobic exercise (running and cycling), with 5–6 sessions per week lasting 40–60 min each. 

Participants:

48 young and middle-aged recreational runners

Duration:

6 weeks

Results:

The researchers observed significant improvements in aerobic capacity (a measure of the body's ability to take in, transport, and utilise oxygen during sustained physical activity) and the endurance of amateur runners during exercise training after NMN supplementation, when compared to the placebo group. These improvements were dose dependent, meaning that the higher the NMN dose, the greater the effect on aerobic capacity and endurance. The authors attribute this improvement to enhanced oxygen utilisation in skeletal muscles. The moderate and higher doses were associated with greater improvements in aerobic capacity than the lower dose. 

Year:

2021

Link:

https://doi.org/10.1186/s12970-021-00442-4 

Study type: 

Randomised double-blind placebo-controlled trial

Purpose:

To investigate the effects of the time-dependent intake of nicotinamide mononucleotide (NMN) on sleep quality, fatigue, and physical performance in older adults.

NMN dosage:

250 mg or a placebo either in the morning or in the evening to compare the effect of intake at different times.

Duration:

12 weeks

Participants: 

108 

Results:

The participants in the study reported reduced drowsiness after NMN supplementation. The study also revealed an association between NMN intake in the afternoon and significant improvements in lower body strength, balance, and functional mobility (the ability to move and perform daily tasks without difficulty). Overall, the authors concluded that NMN may have the potential to improve fatigue and prevent the loss of physical performance.

Year:

2022

Link:

https://doi.org/10.3390/nu14040755

Study type: 

Randomised, double blind, parallel-group trial 

Purpose:

To investigate the safety of orally administered NMN and its efficacy to increase NAD+ levels.

NMN dose:

250 mg/day or a placebo

Duration:

12 weeks

Participants: 

30 healthy subjects 

Results:

Oral supplementation of NMN for 12 weeks caused no abnormalities in physiological and laboratory tests, and no obvious adverse effects were observed. NAD+ levels in whole blood were significantly increased after NMN administration.  NAD+ plays a vital role in multiple cellular processes, and an increase in its levels suggests that the body has additional support for these vital processes, potentially resulting in favourable impacts on overall health and well-being. The authors concluded that oral administration of NMN may be a safe and practical strategy to boost NAD+ levels in humans.

Year:

2022

Link:

https://doi.org/10.3389/fnut.2022.868640

Study type: 

Randomised, double-blind, placebo-controlled, parallel-group trial

Purpose:

To evaluate the safety of 1250mg of β-NMN administered orally once daily. 

NMN dose:

1250 mg/day or a placebo

Duration:

4 weeks

Participants: 

31 healthy adult men and women aged 20-65

Results:

The researchers observed that oral administration of 1250 mg of NMN once daily for 4 weeks did not result in any severe adverse events during the study period. The findings suggest that NMN is safe and well-tolerated in healthy adults.

Year:

2022

Link:

https://doi.org/10.1038/s41598-022-18272-y

Study type: 

Uncontrolled exploratory trial

Purpose:

To verify the safety of NMN administered through human veins.

NMN dose:

300 mg dissolved in 100mL of salt solution

Duration:

12 weeks

Participants: 

5 males and 5 females (aged 20-70)

Results:

The study found an association between intravenous NMN administration and increased blood NAD+, a vital molecule that helps keep proper cell functioning and supports various aspects of overall health, without damaging blood cells.

Researchers also observed that NMN did not affect the participants’ heart's electrical activity, pulse, or blood pressure. It also did not impact metabolic markers in the liver, heart, pancreas, and kidneys. Additionally, the researchers noted a reduction in blood triglyceride (fat) levels after NMN administration. Elevated triglyceride levels have been linked to an increased risk of heart disease and other health issues. Intravenous administration normally carries a higher risk of damaging major organs compared to oral administration. This is because nutrients and drugs administered intravenously circulate directly in the blood without going through the liver, the body's centre for detoxification. 

These findings indicate that intravenous NMN administration is not only safe but also potentially beneficial for humans.

Year:

2022

Link:

https://doi.org/10.7759/cureus.28812

Study type: 

Uncontrolled trial

Purpose:

To investigate the safety of single NMN administration in 10 healthy men

NMN dose:

100, 250, and 500 mg (single administrations)

Duration:

Acute (5 hours)

Results:

The study found an association between NMN administration and a significant increase in the levels of NMN metabolites, the chemical compounds produced as a result of the metabolic processes of NMN. Previous research has already demonstrated a positive correlation between changes in NMN metabolite levels and changes in NAD+, a crucial component in cell functions such as energy production and DNA repair. Therefore, an increase in these NMN metabolites may indicate an elevation in NAD+ levels, potentially benefiting overall health and addressing age-related concerns.

In addition, a single oral administration of NMN up to 500 mg was safe and well-tolerated in healthy men. No significant adverse effects were observed. The authors concluded that oral administration of NMN is feasible and could be used as a potential therapeutic strategy to replenish cellular NAD+ levels to mitigate age-related functional disorders in humans.

Year:

2020

Link:

https://doi.org/10.1507/endocrj.EJ19-0313