About NMN
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NMN
Nicotinamide mononucleotide (abbreviated as "NMN" and "β-NMN") is a nucleotide derived from ribose and nicotinamide.
NMN, like nicotinamide ribose, belongs to the vitamin B group. Humans have an enzyme that uses NMN to produce nicotinamide adenine dinucleotide (NAD+).
It is one of the components found in vitamin B3. It is a substance that exists in humans and all living organisms and is naturally produced in the body, but it is thought that its levels decrease with age, and as a result, people may notice changes in their physical condition.
It is a substance found in various natural foods.
Because it is found in small amounts in natural foods, it is not found in everyday meals.
It is difficult to consume sufficient amounts of NMN.
Recommended daily intake of NMN 100mg
Broccoli 8.9kg / Cabbage 11kg / Beef 23.8kg / Shrimp 45kg
What is NMN?
History of NMN Research Development
Development stage
In 1904, British scientist Arthur Harden revealed the existence of the coenzyme NAD.
In 1920, Hans von Euler-Chelpin of Sweden (who received the Nobel Prize in Chemistry in 1929) and his colleagues discovered a method (enzymatic method) for extracting NAD from yeast, and from the extracted NAD, they discovered the structure of dinucleotides.
In 1930, German officer Otto Heinrich Warburg discovered the material and metabolic roles of NAD and published a paper on the subject.
In 1980, Professor George Birkmayer of the Faculty of Natural Sciences at the University of Graz in Austria was the first to use proto-NAD+ to treat pellagra.
Mammalian research experimental stage
In 2013, David Sinclair, a professor at Harvard Medical School, first published his mouse experiments and results in the journal "Cell."
When NMN was used to administer NAD to 22-month-old mice (equivalent to 60-70 year old humans) for one week, the state of their mitochondria and muscles was similar to that of healthy mice at 6 months old (equivalent to 20-30 year old humans).
In the same year, Shinichiro Imai, a professor at the University of Washington, shocked the scientific community by showing that when he injected mice with β-nicotinamide mononucleotide acid synthase (β-NMN), their internal NAD+ levels increased, and in older mice, not only did their appearance improve, but their overall aging process also improved (their fur became thicker and lighter). Their average lifespan increased from 2 months (equivalent to 6 years in humans) to 4.6 months, a 2.3-fold increase in lifespan.
Furthermore, the Japanese edition of "LIFE SPAN," the culmination of David Sinclair's research, was published on September 23, 2020, and has caused a sensation in society. (In the book, he reveals that he takes 1 gram of NMN every morning.)
Human research and clinical trial stages
2013年、NAD＋が長寿蛋白活性を高めることがわかりました。
2016年、NAD+は人間のDNAを修復することで寿命を延ばすことができることがわかってきました。
2016年、NAD＋はNMNで補充できることがわかりました。
2017年、NAD＋の前駆体NMNを補充することによって、生物時計を調節し、睡眠障害の状態にある人を正常な生活リズムに戻らせることを発見されました。
2013年から2017年にかけての一連の研究によって、NAD＋及びその関連前駆エネルギーは心臓、脳、神経末梢の保護効果とリスニング損傷にも回復作用があることが証明されました。
2017年から2018年にかけて、NMNは脳出血と血管の老化に対して改善作用があることもわかりました。
2019年に、内服NMNが人体NAD＋の転送合成メカニズムを高めることがわかってきました。
2020年1月にNMNが安全に人に使いうることが世界で初めて確認されました。
Commercialization stage
NMN research
Research and results on the effectiveness of NMN in human longevity
In 2013, David Sinclair, a professor at Harvard Medical School, first published his findings in the journal "Cell." Using NMN, he demonstrated that after one week, the function of the glomeruli in the skin of 22-month-old mice (equivalent to 60-70 year old humans) could be restored to the same level as that of 6-month-old mice (equivalent to 20-30 year old humans).
Professor Shin-ichiro Imai of the University of Washington discovered through mouse experiments that injecting β-nicotinamide mononucleotide quickly converts it to NAD in the body. The mice, even in their later years, showed signs of rejuvenation in appearance (thicker, lighter fur). Furthermore, it was found that their average lifespan was extended from 2 months (equivalent to about 6 years for humans) to 4.6 months, shocking the scientific community.
In July 2016, the journal "Cell" published research findings that enhance the longevity protein activity of NAD+. This discovery, made by scientists including Johan Auwerx of the Department of Life Sciences at the Swiss Federal Institute of Technology Lausanne, reveals that NAD+ and the longevity protein Sirtuin have a function in the body that extends human lifespan.
In October 2016, the journal "Cell" published a report stating that NAD+ can extend lifespan by repairing human DNA. According to scientists at the National Center for Biotechnology Information, the human body can replenish NAD+, ultimately extending lifespan and improving health through mitochondrial DNA repair.
Historical research on the safety of NMN for human health
In 2016, Shinichiro Imai's team, in collaboration with Keio University, conducted the world's first clinical trial on NMN. Ten healthy men aged 40 to 60 were given unequal doses of NMN, and the safety and absorption of NMN in the human body were confirmed through physiological and blood tests. The study revealed that a sufficient amount of NMN is metabolized within the body to support its safe application to healthy individuals. This is expected to be useful in the prevention and treatment of age-related diseases in the future.
On January 21, 2020, Keio University School of Medicine became the first in the world to demonstrate that NMN, a candidate substance for anti-aging, can be safely administered to humans.
In 2017, Keio University conducted Phase II clinical trials on oral NMN administration after completing Phase I clinical trials.
NMN: A crucial research project to combat a human disease.
Improvement of Type 2 Diabetes
NMN is key to treating age-related and diet-induced diseases in mice. Type 2 diabetes (T2D) is already an epidemic in modern lifestyles. This may be because high-fat, high-calorie diets are overwhelming our adaptive metabolism. One such pathway is nicotinamide phosphoribosyltransferase (NAMPT), mediated by the restriction rate enzyme and NAD+-dependent protein deacetylase (SIRT1) in mammalian NAD+ biosynthesis. Here, we show that NAMPT-mediated NAD+ biosynthesis is severely impaired by high-fat diets (HFD) in metabolic organelles. Surprisingly, nicotinamide mononucleotide (NMN), the product of the NAMPT reaction and a key NAD+ intermediate, improved glucose tolerance by restoring NAD+ levels in HFD-induced T2D mice. NMN enhances insulin sensitivity in the liver and restores genetic expression related to oxidative stress, inflammatory responses, and diurnal rhythms. These parts are activated by SIRT1. Furthermore, NAD+ and NAMPT levels showed a significant decrease in multiple organs during aging, and NMN improved glucose intolerance and lipid spectrum in age-induced T2D mice. These findings offer important insights into conventional nutritional perspectives and suggest potential countermeasures against T2D, which is deeply related to diet and age. In October 2011, NCBI published the research by Professor Imai and Professor Yoshino of the University of Washington.
NMN is caused by experimental diabetes.
Prevent cognitive impairment and hippocampal neuron loss
NMN supplementation can prevent hippocampal damage caused by diabetes. Its potential mechanism of action involves increasing mitochondrial reserves, improving the energy metabolism of hippocampal cells, and maintaining the youthful vitality of hippocampal cells. (Meanwhile, NMN regulates the deacetylation of SIRT1, an anti-aging protein, in an NAD+-dependent manner. SIRT1 is a histone deacetylase closely related to cell differentiation, aging, and energy metabolism. SIRT1 is a bidirectional regulatory protein, and its activity is NAD+-dependent. Its functional state is affected by NAD+ levels, and the opposite phenomenon may occur. When NAD+ levels decrease, SIRT1 is acetylated, making cells more susceptible to aging and apoptosis. This is thought to be the cause of the decrease in the number of cells in the hippocampus and atrophy of the C1 region. By supplementing with NAD+, SIRT1 is acetylated, preserving SIRT1 enzyme activity, maintaining the metabolism and stability of hippocampal cells, improving hippocampal function, and reducing memory impairment. This research was published in the journal of the European Molecular Biology Organization (EMBO) in June 2014.)
Current research suggests that axonal degeneration is a cause of neurodegenerative diseases (e.g., Parkinson's disease, Alzheimer's disease (AD), and amyotrophic lateral sclerosis). It is hypothesized that symptoms may improve after neuronal injury by inducing many transcripts, including NRK2, which catalyze NAD+ synthesis and increase NAD+ levels. Experiments have demonstrated that supplementing with NAD+ enhances neuroprotection against traumatic brain injury, Parkinson's disease, and amyotrophic lateral sclerosis, and delays memory decline by normalizing neuromuscular function. Alzheimer's disease is characterized by decreased NAMPT and impaired differentiation of neural stem cells. It is believed that significantly increasing NAMPT activity or supplementing with NAD+ reduces the increase in β-amyloid protein levels, leading to improved Alzheimer's disease through PGC-1α-mediated degradation of β-lactase (BACE1) and induction of mitochondrial biosynthesis.
A key mechanism by which NMN improves degenerative diseases such as dementia is that it can directly increase NAD+ concentration in the brain and, in combination with Sirtuins proteins, activate them. Sirtuins are called "longevity proteins" because they can extend the lifespan of many animals. As the brains of older adults age, nerves atrophy and die, and learning ability declines significantly. Before this happens, Sirtuins repair the tactile network, strengthen the neural communication system, and slow the decline of brain function. In elderly people with dementia or Parkinson's disease, a large amount of toxic egg white deposits accumulate in the cerebrum. These severe deposits accelerate nerve death, worsening and reducing the memory and motor skills of these patients compared to people of the same age. Sirtuins can convert these deposits into other substances, further accelerating their breakdown and preventing their accumulation from becoming concentrated.
Another protective function of NMN for nerves is its ability to promote the regeneration of aging cerebral blood vessels. Recent research has confirmed that NMN can promote angiogenesis and improve blood flow to the brain. This is evidence that NMN slows brain aging, and in addition to repairing neural communication systems and removing plaques in the brain, NMN can maintain brain rejuvenation by increasing blood flow to nerves and supplying oxygen.
NMN alleviates ischemic cardiovascular tissue injury.
NMNは虚血性心脳組織損傷を緩和あるいは改善でき、著しい脳血管保護作用を有することがわかりました。2019年6月、研究により、NMN補助剤は老年マウスに著しい脳血管保護作用を有し、老年皮質中のNVC反応とそれによる認知症を改善できたことがわかりました。予防手段としても補助治療としても、NMNは非常に有効な物質であることが確認されました。
循環器系医学博士Zoltan Ungvari氏と彼の研究チームは関連実験研究を行い、彼らの研究成果は2019年6月のRedox Biology誌に発表されました。NAD+は内皮細胞における生存促進経路とミトコンドリア機能の重要な調節因子であり、NMNはNAD+を補う最も有効な前駆物質として、すでに抗老衰領域の各方面で優れていることがわかっており、NMNが高齢患者の神経血管機能障害や認知障害を治療・予防できるかどうかを検証するために行われたものです。
NMN is a neurodegenerative disease.
(Preventing Parkinson's disease, Alzheimer's disease, etc.)
NMN promotes alcohol metabolism,
Improving the human body's tolerance to alcohol
NMN improves depressive behaviors.
Depression is a persistent emotional disorder with physiological effects. NMN and NR are commonly referred to as NAD+ mediators, increasing NAD+ levels in the human body. A study published in the journal "Cell Metabolism" in 2018 provides a good explanation of NMN's role in promoting NAD+. A study published in the "Journal of Affective Disease" at the end of December 2019 showed that NMN can improve the pathology of cortisol (CORT)-induced depressed mice and enhance the activity of the NAD+ synthesis enzyme NAMPT. NMN improved energy metabolism and mitochondrial function in depressed mice and corrected negative behaviors in the mice. At the same time, NMN can increase the activity of the NAMPT enzyme, which can further increase NAD+ levels. A study in June 2019 showed that supplementing the NAMPT enzyme could similarly extend lifespan.
NMN promotes fat breakdown and improves diseases caused by obesity.
Between 2017 and 2020, research institutions in various countries published literature demonstrating that NMN promotes lipolysis and increases exercise endurance. They also revealed that supplementing with NAD+ increases skeletal muscle formation and mitochondrial oxidative metabolism.
NMN reverses the aging process of oocytes,
Benefits for pregnancy
A study published in the journal "Aging Cell" in June 2019 revealed that the enzyme NMNAT 2, which mediates NAD+ biosynthesis, protects and regenerates aged oocytes through the NAD+ biosynthesis it mediates. In the Priss-Handler pathway, nicotinic acid biosynthesizes NAD+ via NMNAT, while in the pathway that complements biosynthesis, NMNAT is the enzyme that directly biosynthesizes NAD+ from NMN. Experimental results showing that supplementing with niacin increases NAD+ content and protects aged oocytes suggest that supplementing with NMN may have a similar effect.
Similar to nicotinic acid, the process of NMN synthesis and NAD+ synthesis is constrained by the NMNAT 2 enzyme. Furthermore, NMN is a safer supplementation method compared to the high side effects of oral nicotinic acid, and further research is expected. In the February 2020 issue of the top academic journal "Cell Reports," it was hypothesized that supplementing with NMN to enhance the NAD+ content in mouse oocytes may be a low-risk and non-invasive method to improve fertility. Recent research findings: β-NMN has been shown to reverse the trend, restoring fertility in women during periods of declining reproductive capacity.
Between 2016 and 2019, scientists discovered that NMN (β-nicotinamide mononucleotide) improves the function of "alcohol-induced hepatitis," increasing NAD+ levels in the liver. This has significant implications for the treatment of alcoholic fatty liver disease, as it can block ethanol-induced increases in ALT and AST through Atf 3 and Erk 1/2 signaling pathways and modify 25% of genes regulated by ethanol metabolism.
From July 2018 to 2020, extensive theorizing and large-scale experiments facilitated the commercialization of NMN. Research findings confirmed its potential to contribute to human health, and experts began commercializing NMN. By the first half of 2020, hundreds of people were continuing to use NMN. Information about its use by global celebrities and the surge in NMN Concept stock listings on the Chinese stock market in July 2020 led to increased public awareness of NMN itself.
Furthermore, as mentioned earlier, the publication of the Japanese edition of "LIFE SPAN," a book that culminates the research of David Sinclair, a pioneer in NMN research, on September 23, 2020, has created an even greater NMN craze in Japan.