1. What is NMN?
Nicotinamide mononucleotide (NMN) is a derivative of vitamin B3 (nicotinamide) with a molecular weight of 334221g/mol。
There are two epimers of NMN: type and type.
The study found that only NMN was biologically active. At the molecular level, it is a ribonucleotide that is the basic building block of nucleic acid RNA. Structurally, the molecule consists of nicotinamide groups, ribose and phosphate groups.
2. What are the ** of NMN?
NMN is naturally found in some fruits, vegetables and poultry.
Diagram of NMN content in different foods.
At the same time, NMN is also a naturally occurring substance in the human body, which can be synthesized through endogenous substances in the human body.
3. What are the functions of NMN?
According to the literature obtained from the current search, the efficacy of NMN can be summarized as follows.
Increases NAD+ content.
NAD+ is an important substance for maintaining the operation of the body, exists in all cells, participates in thousands of physiological reaction processes in the body, and requires NAD+ for the action of more than 500 enzymes in the human body.
In 2013, a research team led by Professor D**id Sinclair of Harvard Medical School experimentally demonstrated:
One week after oral administration of NMN in 22-month-old mice increased NAD+ levels in vivo and restored key biochemical markers related to mitochondrial homeostasis and muscle function to the equivalent of young mice at 6 months in size.
The findings were published in Cell.
Activates sirtuins protein.
Nearly 20 years of research have found that sirtuins play a major regulatory role in almost all cellular functions, influencing physiological processes such as inflammation, cell growth, circadian rhythm, energy metabolism, neuronal function, and stress resistance.
Sirtuins are a family of NAD+-dependent deacetylase proteins that include sirtuin 1 through sirtuin 7 (sirt 1-7).
NAD+ is involved in the response of the sirtuins protein family.
In 2019, Professor Kane A E et al. from the Department of Genetics at Harvard Medical School found that:
As an important precursor of NAD+ synthesis in living organisms, NMN plays many beneficial effects (such as improving metabolism and protecting cardiovascular system) by activating sirtuins after it increases the level of NAD+ in cells.
In 2019, Dr. de Picciotto Nee et al., Department of Integrative Physiology, University of Colorado Boulder, found that:
Intraperitoneal injection of NMN can increase arterial sirtuin1 activity and reverse age-related arterial dysfunction and oxidative stress in mice, in addition to activating sirtuin1, nmn can also affect the activity of sirtuin3 in mitochondria, reduce oxidative stress, and enhance physiological function.
Repair DNA damage.
In addition to influencing sirtuins activity, NAD+ levels in vivo are also important substrates for the functioning of the DNA repair enzyme PARPS (polyadenosine diphosphate ribose polymerase).
In 2017, a research team led by Professor D**id Sinclair at Harvard Medical School discovered the mechanism by which NAD+ repairs DNA damage.
As NAD+ levels decline with age, the DNA repair enzyme PARP1 is increasingly bound by DBC1 (breast cancer deletion factor 1) to form the PARP1-DBC1 complex. This complex prevents PARP1 from repairing damaged DNA.
Increasing NAD+ levels interferes with the formation of the PARP1-DBC1 complex, thereby restoring the DNA repair activity of PARP1. A reduction in DNA damage was found after one week of oral administration of NMN to radiated aged mice.
Boosts metabolism.
Metabolism is a collection of life-sustaining chemical reactions in an organism that allow an organism to grow and reproduce, maintain structure, and respond to the environment.
Metabolism is a process in which an organism constantly undergoes the exchange of matter and energy, and once it stops, the life of the organism ends.
In 019, a study by Professor Nina Klimova et al. at the University of Maryland School of Medicine found that:
Intraperitoneal injection of NMN significantly increased the level of mitochondrial NAD+ in the hippocampus of the brain of experimental rats, and increased the level of ATP, an energy molecule in brain tissue, thereby improving the body's bioenergy metabolism.
In 2020, Dr. Jie Xiaoxian of Zhejiang University of Technology and others found that:
Depression mice were alleviated by increasing NAD+ levels, activating sirtuin 3, and improving mitochondrial energy metabolism in the hippocampus and liver cells of the brain of mice.
Promote blood vessel regeneration and maintain blood vessel elasticity.
Blood vessels are indispensable tissues for transporting oxygen and nutrients, processing carbon dioxide and metabolites, and regulating body temperature.
As we age, blood vessels also gradually lose their softness, becoming harder, thicker, and narrower, resulting in "arteriosclerosis".
In 2018, a research team led by Professor D**id Sinclair at Harvard Medical School found:
After 2 months of oral administration of NMN to 18-month-old mice, the number and density of capillaries returned to the level of young mice.
In 2016, Dr. Picciotto Nee et al., from the Department of Integrative Physiology at the University of Colorado Boulder, found that:
Oral administration of NMN restored carotid endothelium-dependent impaired diastolic function (EDD) and nitric oxide NO-mediated EDD in aged mice, decreased aortic pulse conduction rate (APWV), decreased nitrotyrosine, reversed collagen I, increased elastin, and restored vascular SIRT1 activity, thereby maintaining vascular elasticity and maintaining vascular health.
Promotes heart health.
The heart is the most important organ in the human body, and it is essential to maintain its function.
In 2014, Dr. Yamamoto T et al., Medical College of New Jersey, showed that:
Mice are injected intraperitoneally with NMN, which significantly increases the level of NAD+ in the heart and prevents the reduction of NAD+ during ischemia. NMN protects the heart from ischemia and reperfusion injury.
In 2017, research by Dr. Rongli Zhang, et al., Case Western Reserve University School of Medicine, showed that:
Short-term intraperitoneal injection of NMN successfully protected mice from heart failure caused by stress overload.
Promotes brain health.
Neurovascular dysfunction can cause early vascular and neurodegenerative cognitive impairment. Maintaining neurovascular function is important for the prevention of neurodegenerative diseases.
Risk factors such as diabetes, middle-aged hypertension, middle-aged obesity, physical inactivity, and smoking are all associated with vascular dementia and Alzheimer's disease.
In 2019, Dr. Tarantini S et al., University of Oklahoma Health Sciences Center, found that:
Intraperitoneal injection of NMN has a significant protective effect on the brain microvessels of aging mice.
In 2020, a study by Dr. Tamar Kiss et al. at the University of Oklahoma Health Sciences Center also found that:
Restoring cellular NAD+ levels in aging mice by intraperitoneal injection of NMN can rescue neurovascular function, increase cerebral blood flow, and improve cognitive performance.
Improves insulin sensitivity.
Insulin sensitivity is a description of the degree of insulin resistance. The lower the insulin sensitivity, the lower the degree to which sugars are broken down.
Insulin resistance refers to a state in which the target organ of insulin action becomes less sensitive to insulin action, i.e., a state in which normal doses of insulin produce lower than normal biological effects.
The causes of type 2 diabetes are mainly due to low insulin secretion and low insulin sensitivity.
Kelly L., University of Washington School of Medicine, 2016Dr. Stromsdorfer et al.'s findings:
Decreased NAD+ levels in adipose tissue in obese mice and aged mice are associated with severe multi-organ insulin resistance. Feeding mice with NMN to the drinking water of mice where specific enzymes are inactivated leading to insulin resistance can reverse insulin resistance and reduce plasma concentrations of free fatty acids.
In 2012, Dr. Yoshino J et al., Department of Developmental Biology, University of Washington School of Medicine, found:
Intraperitoneal injection of NMN improves glucose tolerance and lipid profile in type 2 diabetic mice by increasing NAD+ levels, enhances hepatic insulin sensitivity and restores expression of genes related to oxidative stress, inflammatory response, and circadian rhythm.
Helps with weight management.
Weight not only affects quality of life and health, but can also be a trigger for other chronic diseases.
Margaret J., Faculty of Medicine, University of New South Wales, 2017The team led by Professor Morris made a series of findings on the role of NMN in weight management:
For hereditarily obese mice, NMN appears to have a stronger effect on hepatic fat catabolism (HADH) and anabolic 15 (FASN) than exercise.
The researchers believe that it may be because the injection of NMN increases NAD+ levels in the body and thus activates the sirtuins protein, increasing the catabolism and anabolism of liver fat.
Improve physiological decline.
Aging is the result of the accumulation of stress and strain, injuries and infections, weakened immune responses, nutritional disorders, metabolic disorders, and other factors.
In 2016, a research team led by Professor Shin-Ichiro Imai at the University of Washington School of Medicine conducted long-term experiments on mice with oral administration of NMN.
Mice that received 12 months of oral administration of NMN compared to mice that did not take NMN for normal aging found that:
Oral administration of NMN quickly converts into NAD+ in tissues and effectively eliminates various aging-related physiological declines: preventing aging-related weight gain, boosting metabolism, increasing physical strength, improving insulin sensitivity and plasma fat indicators, improving vision, improving immune function, preventing loss of bone density, and more.
Moreover, NMN does not have any toxicity and ***
4. The difference between NMN and other NAD+ precursors.
Harvard University NAD+ researcher D**id Sinclair said:
Direct feeding or application of NAD+ to organisms is not a practical option. NAD+ molecules cannot easily cross the cell membrane and enter the cell and cannot positively affect metabolism.
Instead, precursor molecules of NAD+ must be used to increase the bioavailability of NAD+.
This means that NAD+ is not easily absorbed directly. Whereas NAD+ precursors are more easily absorbed than NAD+ and are more effective supplements.
NMN is structurally similar to other NAD+ precursors such as NR (nicotinamide ribose), NA (niacin), and NAM (nicotinamide) in that they all contain a pyridine ring structure.
But niacin (Na) and nicotinamide (NAM) have some drawbacks in terms of application:
Niacinamide (NAM) can cause nausea and flushing, and high doses of niacinamide have been reported to cause liver toxicity. A recent preclinical study showed that nicotinamide (NAM) stays in rats for a shorter period of time compared to NMN.
As an immediate-release preparation, niacin (Na) can cause adverse reactions such as flushing when used, and may cause hepatotoxicity as an extended-release preparation.
Fifth, the safety and security of NMN.
NMN is considered safe in animals, the results are encouraging, and clinical trials in humans have begun.
In 2016, Keio University and the University of Washington jointly conducted a first-in-human clinical trial of NMN to discuss the potential of NMN as a functional food by evaluating metabolism-related parameters.
Report of the first human trial conducted in Japan.
The trial was conducted in healthy men aged 40 to 60 years and was divided into two phases:
Phase I evaluates the safety of a single dose of NMN.
Phase II evaluates the safety of long-term (8 weeks) administration of NMN.
No adverse effects or safety issues have been reported.
In 2017, Fumiko Higashikawa et al. from Hiroshima University in Japan conducted a clinical trial to study the safety and effects of long-term oral administration of NMN on human health.
Clinical trial report.
It is designed as a parallel randomized double-blind trial.
Healthy subjects administered NMN orally at a dose of 100mg D, 200mg D.
For 24 weeks, the parameters in serum plasma were measured, and the number and incidence of adverse reactions were recorded.
No adverse effects or safety issues have been reported.
On March 31, 2020, Japan's Ministry of Health, Labor and Welfare added NMN to the "non-medical list," i.e., allowing it to be used in food production.
In 2021, the University of Washington College of Pharmacy conducted a clinical trial on the metabolic effects of dietary supplement NMN in women, in which subjects were administered daily to NMN capsules at a dose of 250mg D for 8 weeks.
The results of the study showed:
NMN can enhance the insulin sensitivity of muscle tissue in the test population.
6. Summary and outlook.
NMN is a vitamin B derivative and one of the precursors of NAD+, which is mainly involved in the regulation of cellular function by converting to NAD+.
Supplementing with NMN provides the body with raw materials for the synthesis of NAD+, which has the advantage of being more stable and safer than direct supplementation of NAD+.
There are a growing number of in vitro studies proven:
NMN can increase NAD+ levels in the body and improve aging-related indicators, and more and more human clinical studies have confirmed the harmlessness and functionality of NMN to the human body.
In the future, there will be more human trials with larger sample sizes and longer durations to prove the effectiveness of NMN in different populations. The outlook for NMN is promising.