NMN Applications Research

The results of scientific research and clinical trials should be taken as a basis for understanding and evaluating the function and efficacy of NMN; based on the literature currently available, summary as below.


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1.Boost NAD+ level 


NAD+ is an important substance to keep human body functioning. It exists in all cells and participates in thousands of physiological reactions in human body[1].
The experiments conducted by Harvard Medical School in 2013 showed that one week after oral administration of NMN by 22-month-old mice, the NAD+ level in the mice body increased and the key biochemical indexes related to mitochondria stability and muscle function restored to the level equivalent to those of 6-month-old young mice[2].
In 2012, the University of Washington School of Medicine found that intraperitoneal injection of NMN can promote NAD+ biosynthesis in mice and increase insulin sensitivity or insulin secretion so as to improve sugar tolerance, which is an effective intervention measure to prevent development of T2D (Type II diabetes) induced by dietary and age[3].


2.Activate SIRTUINS 


Sirtuins influence physiological processes, such as inflammation development, cell growth, circadian rhythm, energy metabolism, neuron function, stress reaction, and etc.
In 2019, the Harvard Medical School found that NMN, acting as the important precursor for the synthesis of NAD+ in organism, plays many beneficial roles in body function (such as metabolism improvement, protection of cardiovascular system, etc.) through activation of Sirtuins[4].
In 2019, the University of Colorado found that intraperitoneal injection of NMN can enhance the activity of Sirtuin1 in mice's artery and reverses age-related arterial dysfunction and oxidative stress; in additional to activating Sirtuin1, it can also reduce oxidative stress and improves vascular function of aged mice[5].


3.Repair DNA damage


The NAD+ level in body not only influences the activity of Sirtuins, but also plays an important role as a substrate for the normal function of PARPs (Poly ADP ribos polymerase)[6]. PARP, located in the cell nucleus, is a DNA repair enzyme related to DNA repair under stress conditions.
In 2017, the Harvard Medical School found the mechanism through which the NAD+ repairs DNA damage. One week after oral administration of NMN by aged mice which are exposed to radiation, it is discovered that the DNA damage is reduced[7].


4.Promote metabolism and Increase level of energy


Metabolism is the collection of chemical reactions that sustain life in organisms, and a general term of chemical reactions that sustain life in organisms[8].
In 2019, the research results of the University of Maryland Medical school showed that intraperitoneal injection of NMN can significantly increase the level of NAD+ in the mitochondria of the laboratory mouse's hippocampus, and the contents of kinetomeres ATP in the brain tissue also increases, thus improves metabolism of bio-energy of organisms[9] .
In 2020, the research results of Zhejiang University of Technology showed that after oral administration of NMN by mice suffering from depressive disorders, Sirtuin 3 was activated by the increasing of NAD+ level, the metabolism of bio-energy in the mitochondria of the laboratory mouse's hippocampus of the brain and liver cells; in this way the depressed symptom of the mice is relieved[10].


5.Promote Blood vessel repair maintain vascular elasticity, enhance endurance and vitality 


In 2016, the University of Colorado conducted a research and found that oral administration of NMN can repair the damaged EDD of carotid artery endothelium dependent relaxation function of the aged mice, reduce aortic pulse wave velocity (APWV), decrease the content of nitrotyrosine and retroviridae collagen I, increase the content of elastin and recover the activity of SIRT1[11].


6.Help weight management


In 2017, the University of New South Wales found that both NMN and exercise are useful to reduce obesity and improve glucose tolerance and mitochondrial function for mice with hereditary obesity. The injection of NMN can increase the NAD+ level in body, so as to activate Sirtuins protein and boost metabolism of fat in liver[12][13].


7.Promote heart health


In 2014, the New Jersey Medical School conducted a research and found that intraperitoneal injection of NMN can significantly increase the NAD+ level of the mice's heart and prevent decrease of NAD+ during ischemic stage. NMN protects the heart from ischemic/reperfusion injuries[14].
In 2017, the research result of the Case Western Reserve University showed that short-term intrauterine injection of NMN successfully protected mice from heart failure caused by overloading pressure. This is because NMN protected the microscopic structure of the chondriosome, reduced the level of active oxygen and prevent myocardial cells from dying[15].


8.Promote brain health


Diabetes, mid-age hypertension and mid-age obesity, lack of physical activity and smoking are all associated with vascular dementia and Alzheimer's disease[16].
In 2019, the University of Oklahoma found that intraperitoneal injection of NMN provides significant protection to cerebral microvasculature of aged mice. NMN reduces the oxidative stress of the cerebral microvascular endothelium, improves endothelial function and relieves the coupled reaction of neurovascular bundle in aged mice's cortex[17].
In 2020, the University of Oklahoma found that intrauterine injection of NMN can restore NAD+ level of cells for aged mice, save neurovascular function, increase cerebral blood flow and enhance cognitive function[18].


9.Improved insulin sensitivity


In 2016, the University of Washington School of Medicine found that by adding NMN in drinking water and feed mice suffering from insulin resistance caused by certain inactive enzymein, the insulin resistance can be reversed and the free fatty acid concentration in plasma can be reduced[19].
In 2012, the University of Washington School of Medicine found that intrauterine injection of NMN can increase the level of NAD+, so as to improve the glucose tolerance and lipid distribution, increase insulin sensitivity of liver, restore oxidative stress and inflammation reaction, circadian rhythm and other genetic expressions for mice suffering from type 2 diabetes[20].


10.Prevent losing bone mineral density and improve eyesight and immune function


In 2016, the University of Washington School of Medicine conducted a long-term experiment in which the mice were given oral administration of NMN for 12 months. The NMN taken orally soon was transformed into NAD+ and eliminated physiological decline associated with aging. Moreover, there was no any toxicity and side effects with NMN[21].






[2]Gomes A P,Price N L,Ling A J Y,et al.Declining NAD+induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging[J].Cell,2013, 155(7):1624-1638.


[3]Yoshino J,Mills K F,Yoon M J,et al.Nicotinamide mononucleotide,a key NAD+ intermediate,treats the pathophysiology of diet-and age-induced diabetes in mice[J].Cell metabolism,2011,14(4):528-536.


[4]Kane A E,Sinclair D A.Sirtuins and NAD+in the development and treatment of metabolic and cardiovascular diseases[J].Circulation research,2018,123(7):868- 885.


[5]de Picciotto N E,Gano L B,Johnson L C,et al.Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice[J].Aging Cell,2016,15(3):522-530.




[7]Li J,Bonkowski M S,Moniot S,et al.A conserved NAD+binding pocket that regulates protein-protein interactions during aging[J].Science,2017,355(6331): 1312-1317.




[9]Klimova N,Long A,Kristian T.Nicotinamide mononucleotide alters mitochondrial dynamics by SIRT3‐dependent mechanism in male mice[J].Journal of neuroscience research,2019,97(8):975-990.


[10]Xie X,Yu C,Zhou J,et al.Nicotinamide mononucleotide ameliorates the depression-like behaviors and is associated with attenuating the disruption of mitochondrial bioenergetics in depressed mice[J].Journal of Affective Disorders, 2020,263:166-174.


[11]Das A,Huang G X,Bonkowski M S,et al.Impairment of an Endothelial NAD+- H2S Signaling Network Is a Reversible Cause of Vascular Aging[J].Cell,2019,176(4): 944-945.


[12]Uddin G M,Youngson N A,Doyle B M,et al.Nicotinamide mononucleotide (NMN)supplementation ameliorates the impact of maternal obesity in mice: comparison with exercise[J].Scientific reports,2017,7(1):1-11.


[13]Uddin G M,Youngson N A,Sinclair D A,et al.Head to head comparison of short-term treatment with the Nad+precursor nicotinamide mononucleotide (NMN)and 6 weeks of exercise in obese female mice[J].Frontiers in pharmacology, 2016,7:258.


[14]Yamamoto T,Byun J,Zhai P,et al.Nicotinamide mononucleotide,an intermediate of NAD+synthesis,protects the heart from ischemia and reperfusion[J].Plos one,2014,9(6):e98972.


[15]R,Shen Y,Zhou L,et al.Short-term administration of nicotinamide mononucleotide preserves cardiac mitochondrial homeostasis and prevents heart failure[J].Journal of molecular and cellular cardiology,2017,112:64-73.




[17]Tarantini S,Valcarcel-Ares M N,Toth P,et al.Nicotinamide mononucleotide (NMN)supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice[J]. Redox biology,2019,24:101192.


[18]Kiss T,Nyúl-TóthÁ,Balasubramanian P,et al.Nicotinamide mononucleotide (NMN)supplementation promotes neurovascular rejuvenation in aged mice: transcriptional footprint of SIRT1 activation,mitochondrial protection,anti-inflammatory,and anti-apoptotic effects[J].Geroscience,2020:1-20.


[19]https://baike.baidu.com/item/%E8%83%B0%E5%B2%9B%E7%B4%A0%E6%95% 8F%E6%84%9F%E6%80%A7


[20]Stromsdorfer K L,Yamaguchi S,Yoon M J,et al.NAMPT-mediated NAD+ biosynthesis in adipocytes regulates adipose tissue function and multi-organ insulin sensitivity in mice[J].Cell reports,2016,16(7):1851-1860.


[21]Mills K F,Yoshida S,Stein L R,et al.Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice[J].Cell metabolism,2016,24(6):795-806.