NMN (Nicotinamide mononucleotide) is a direct precursor of NAD+ (nicotinamide adenine dinucleotide, also known as Noga factor), and has been regarded as an emerging health ingredient in anti-aging in recent years
Other common NAD+ precursors are: nicotinic acid, Nicotinamide, Nicotinamide riboside
What are the benefits of NMN in empirical medicine? Are there any side effects of NMN? See discussed in the text for details
What is NMN?
NMN (nicotinamide mononucleotide) is one of the derivatives of vitamin B3 (niacin) and an intermediate product of NAD+ biosynthesis, which is a bioactive nucleotide formed by the reaction of phosphate groups and nucleosides containing ribose and nicotinamide
In general, it exists in two synonymous forms, alpha and beta. The beta isomer is the active form with a molecular weight of 334.221 g/mol.
NMN is found in small amounts in a variety of natural foods such as vegetables, fruits, and meat.
Vegetables such as cauliflower, cabbage contains 0.25 to 1.12 and 0 to 0.90 mg of NMN per 100 grams, fruits such as avocados, tomatoes contain 0.36 to 1.6 and 0.26 to 0.3 mg of NMN per 100 grams, and beef contains 0.06 to 0.42 mg of NMN per 100 grams.
What is NAD+ (Noplus factor)?
NAD+ (nicotinamide adenine dinucleotide) is an important coenzyme found in eukaryotic cells and is required for more than 500 enzymatic reactions. It plays a key role in various biological processes, including metabolism, aging, mitochondrial function, DNA repair, and gene expression.
NAD+ deficiency is strongly associated with multiple pathophysiological mechanisms, including type 2 diabetes, obesity, heart failure, Alzheimer’s disease, and cerebral ischemia.
As we age, NAD+ levels in multiple organs gradually decline, which accelerates the development of age-related diseases. Therefore, increasing NAD+ is considered a possible way to cope with disease, which is essential for human health and longevity.
What are the empirical benefits of NMN?
1. Beneficial to the physical function of the elderly
Aging is associated with decreased muscle strength and physical performance, which exacerbates the burden of daily work capacity, increases the risk of falls and poor health outcomes.
By 2030, the elderly population is expected to outnumber the number of children under 10 years of age (1.41 billion, 1.35 billion) According to projections for 2050, the number of people aged 60 and over will exceed the number of adolescents and young people aged 10 to 24 (2.1 billion, 2 billion people)
Performance indicators are useful tools for predicting the risk of functional decline and death, and have become an important component of geriatric assessment.
A randomized, double-blind, placebo-controlled (12-week study of 108 participants over the age of 65) reported that NMN supplementation (250 mg per day) improved lower extremity function and reduced drowsiness. Note 1
*Conclusion: NMN may bring positive help to the physical function of the elderly, but due to the small sample size, more studies are still needed for further verification
2. Improve aerobic endurance
For people of all ages, habitual exercise is an effective factor in weight control, but it can also play many other positive effects, including preventing metabolic and cardiovascular disease and promoting mental health.
A literature analysis (Meta-Analyses in sedentary healthy adults) confirmed that running helps reduce body mass index, body fat, resting heart rate, and triglycerides, and increase maximum oxygen uptake and HDL cholesterol, especially in the context of long-term regular training. Note 1
A randomized, double-blind, placebo-controlled trial (6-week trial of 48 healthy amateur runners) in four groups: low-dose (NMN 300 mg daily), medium-dose (NMN 600 mg), high-dose (NMN 1200 mg), and control. Note 2
The results showed that compared with the control group, the oxygen uptake, maximum oxygen uptake percentage, and first and second ventilation thresholds of the NMN medium and high dose groups had a higher degree of increase.
*Conclusion: Athletic training combined with NMN supplementation is a practical strategy to improve athletes’ endurance performance, and this improvement may be due to increased oxygen utilization in skeletal muscle.
3. Improve the metabolic capacity of skeletal muscle
Skeletal muscle, which makes up 40% of the total body weight, is composed of slow-shrinking and fast-contracting fiber types, which differ in the composition of contractile proteins, oxidizing capacity, and matrix preference for ATP production.
Slow-shrinking fibers exhibit low fatigue, high oxidation capacity, and preference for fatty acids as substrates for ATP production. Fast shrinkage fibers have higher fatigue, higher contraction strength, lower oxidation capacity, and prefer glucose as a substrate to produce ATP by anaerobic glycolysis.
A randomized, placebo-controlled, double-blind trial (10-week trial of overweight or obese women with prediabetes) noted that NMN (250 mg daily) increased muscle insulin sensitivity, muscle insulin signaling, and muscle remodeling. Note 1
*Conclusion: NMN supplementation may have a positive effect on muscle metabolism, repair and remodeling ability, but limited by the small sample size, more studies are needed to further verify
4. Beneficial for liver fibrosis
Liver fibrosis is a reaction caused by chronic liver damage, such as alcohol intake, viral hepatitis (hepatitis B and C), autoimmune hepatitis, nonalcoholic fatty liver disease, and cholestatic liver disease.
The structure of the liver is destroyed by the presence of fibrous scar, which leads to the loss of liver cells and normal liver dysfunction, which eventually leads to liver failure.
Liver fibrosis is a reversible process, and as long as the liver is not in the advanced cirrhosis stage, removing the fibrosis reaction helps fibrosis to resolve.
An animal study pointed out that NMN supplementation can inhibit the activation of mouse liver stellate cells and prevent liver fibrosis, providing new opportunities for the development of liver fibrosis treatment. Note 1
*Conclusion: Animal studies have found that NMN supplementation may have a positive effect on inhibiting liver fibrosis, but human studies are lacking and need to be further verified
5. Anti-aging
Telomeres are specific DNA protein structures found at both ends of each chromosome that protect the genome from nuclear dissolution degradation, unwanted recombination, repair, and interchromosomal fusion.
Telomeres therefore play a vital role in preserving the information in our genome. As a normal cellular process, a small portion of telomic DNA is lost with each cell division.
When telomere length reaches a critical value, cells age or die. Thus, telomere length can serve as a biological clock to determine the lifespan of a cell and an organism.
An animal study pointed out that NAD+ precursor nicotinamide mononucleotide (NMN) can maintain telomere length, inhibit DNA damage response, and improve mitochondrial function. Note 2
Another animal study has shown that NMN specifically increases the activity of the SIRT1 (sirtuin 1) gene. Note 3
*Conclusion: Animal studies have pointed out that NMN may slow down aging or improve disease by stabilizing telomeres and initiating sirtuins, but it needs to be further validated due to the lack of human studies
6. Beneficial for blood sugar control
Diabetes is a common chronic condition characterized by high blood sugar. It has two types, which are summarized as type 1 diabetes and type 1 diabetes.
Type 1 diabetes mellitus is an autoimmune disease with absolute insulin deficiency that occurs in young adults. Type 2 diabetes is characterized by insulin resistance, hyperinsulinemia, and β cell failure.
Diabetes and poor control are associated with microvascular (retinopathy and nephropathy), macrovascular and nonvascular (neuropathy) complications.
An animal study has shown that nicotinamide mononucleotide (NMN) can enhance liver insulin sensitivity by partially activating SIRT1, restore gene expression related to oxidative stress, inflammatory response and circadian rhythm, and help improve glucose tolerance. Note 4
*Conclusion: Animal studies suggest that NMN may have a positive effect on diabetic glycemic control, but there is still a lack of human studies and further verification
7. Beneficial for Alzheimer’s disease
Alzheimer’s disease, the most common form of dementia (affecting tens of millions of people worldwide), is characterized by progressive cognitive impairment caused by synaptic loss and neuronal death in brain regions that are vital for learning, memory, and emotional control.
The accumulation of two autopolymeric proteins, including amyloid plaques and neurofibrillary tangles, is a diagnostic feature of Alzheimer’s disease.
A rat model study of Alzheimer’s disease pointed out that NMN treatment can improve neuronal survival, improve energy metabolism and reduce the accumulation of reactive oxygen species. Note 5
*Conclusion: Animal studies suggest that NMN treatment may have a positive effect on Alzheimer’s disease, but human evidence is lacking and needs to be verified
Are side effects of NMN?
Regarding the oral side effects of NMN, there is still a lack of well-designed clinical studies, and the safety of application in humans is relatively unknown.
A human study showed that a single oral administration of 100mg, 250mg, and 500mg of NMN did not change heart rate, blood pressure, blood oxygen level or body temperature after 5 hours, and no major adverse reactions occurred. Note 6
Oral NMN (doses 375, 750, 1500 mg/kg/day) was shown to be safe in rodents for 90 days, and acute toxicity trials showed that NMN did not cause any death or treatment-related adverse symptoms at an orally restricted dose of 2666 mg/kg. Note 7
In a long-term study of rodents, oral administration of NMN for 1 year (dose 100 or 300 mg/kg/day) did not produce any significant toxicity, serious side effects, or increased mortality. Note 8
In addition, due to the effect of NMN promoting angiogenesis, it may theoretically increase tumor growth rate, but in a study of rodents, it was pointed out that the use of NMN did not affect the proliferation of tumor cells, which needs to be further verified by human studies. Note 9