Why we need NMN supplements

What is the Nicotinamide Mononucleotide (NMN)?

So, what is the fuss all about Nicotinamide Mononucleotide? Let me explain.

NMN exists in both alpha (α) and beta (β) forms. However, β-NMN is the most active form. This bioactive nucleotide is an intermediate in the biosynthesis of nicotinamide adenine dinucleotide or NAD+.

This compound naturally exists in avocadoes, tomatoes, cucumber, cabbages, broccoli, and raw beef. In the laboratory, it is available as nicotinamide mononucleotide wholesale powder.

In its raw form, it identifies with CAS number, 1094-61-7. The compound comes into being from the reaction between a nucleoside, such as nicotinamide riboside and a phosphate group.

In preclinical studies, Nicotinamide Mononucleotide work on mice has proved to be handy in cellular biochemical activities, management of Alzheimer’s disease, age-related diabetes, complications that arise from obesity, and cardioprotection. Despite all these pharmacological activities associated with Nicotinamide Mononucleotide, the most groundbreaking discovery is its involvement in anti-aging activities.

In the human body, NMN is the principal source of energy within the cells. As you age, cellular energy decreases due to the low levels of nicotinamide mononucleotide and subsequent reduction of NAD+. Administering NMN will reverse the process and compensate for the deficit.

How is NMN mysterious?

These anti-aging drugs travel like lightning from the gut into the blood circulation. In a couple of minutes, they will have been taken up into the bloodstream. For this reason, it becomes clear that there might not be any biochemical reactions taking place in the molecules’ pathway.

The puzzling speed has made researchers to conclude the possibility of a transporter, which facilitates cell fuel delivery. For example, Imai and his associates set out to find an answer through his recent study published on January 7, 2019.

With old age, the body uses up more NAD+ than it can manufacture. However much you use nicotinamide mononucleotide, the process will still be a waste of time for as long as there’s no molecule to aid its transport. Keep scrolling to unravel the mysterious transporter that will solve 90% of the aging complications.

The latest Research of Nicotinamide Mononucleotide Work on Mice There are countless preclinical studies on murine models that bear out the therapeutic benefits of Nicotinamide Mononucleotide.

Let’s focus on a few, which have had a revolutionary effect in biochemistry.

(1) According to Sinclair, NAD+ is a Fountain of Youthfulness Dr. Sinclair and his colleagues have published several pieces of research regarding the potentiality of nicotinamide mononucleotide and NAD+ in reversing aging. According to his 2013 study, Sinclair and the team found out that 22-month old mice taking NMN for six days showed improvements on muscle capacity, metabolism, and endurance.

Later in a 2016 research paper, the group affirmed that NMN had similar benefits as exercising.

Rather than running on a treadmill daily, you can still experience the same effects when you use Nicotinamide Mononucleotide supplements instead.

According to this Harvard Geneticist, the NMN work on human revolves around ameliorating blood flow on the elderly and elite athletes.

(2) Mills Asserts that NMN Alleviates Physiological Decline in Aging Mice In reference to the 2016 study, Mills et al. found that NMN treatment would counter the decline in both physiological and immunological function in old mice. At the end of this NMN supplement research, the rodents registered an increase in the expression of immune cells, lymphocytic proliferation, and shrinkage in neutrophils.

Previously, in 2011, Mills, Yoshino, and Imai had used mice models to confirm the role of NAD+ in the treatment of diet-induced and age-related diabetes. In yet another 2016 study, he joined hands with other researchers who established that NMN supplementation would counteract oxidative stress and vascular dysfunction in aged mice.

(3) NMN Combats Alzheimer’s Disease (AD) in Murine Models In 2015, Long et al. investigated the effect of NMN on brain mitochondrial respiratory deficits on mice with Alzheimer’s disease. The team noted that the NMN treatment was able to treat the etiology of AD, including low OCR (oxygen consumption rates), NAD+ falloff, and mitochondria abnormalities.

In 2016, Wang and his associates published their research, concluding that these anti-aging drugs combat cognitive and neural impairment, which result from β-amyloid (Aβ) oligomer. This Aβ protein is neurotoxic and is responsible for plaque formation in the brain of AD patients. Wang et al. concluded that NMN administration in mice led to a decrease in Aβ oligomers, thereby boosting the cognitive functions.

Following a 2017 study, Hou and his colleagues discovered that NAD+ supplementation decreased the production of β-amyloid oligomers. A year later, Yao and his team established that Nicotinamide Mononucleotide reduces the accumulation of Aβ and synaptic loss in AD-Tg murine models.

(4) NMN and Cardio-protection According to a 2014 publication by Yamamoto and his colleagues, NMN protects the heart against ischemic injury and reperfusion. Before this study, Yamamoto was part of a 2012 team, which found out that NAD+ counters diet-induced obesity in mice.

In 2016, De Picciotto et al. and his fellow biochemists studied the effect of NMN supplementation on the vascular functionality of aging mice. From the inference, nicotinamide mononucleotide proved to be effective in reversing vascular dysfunction, oxidative stress, and decrease in elastin.

(5) The Discovery on a New Route of Cell Fuel Delivery by Shin-Ichiro Imai In recent research, a team of scientists led by Imai discovered and unraveled the mysterious transporter of NMN into the cells.

This NMN supplement research was first available in January 2019 in Nature Metabolism. Imai established that a particular protein, Slc12a8, is responsible for the rapid conversion of NMN to NAD+ and transporting it into the cell. This enzyme is predominant in old folks rather than in young or healthy individuals.

In all the preclinical studies, research scientists would dissolve known measures of nicotinamide mononucleotide in water before administering them to the mice.

What

Benefits

Nicotinamide

can

we

get

Mononucleotide

from (NMN)

supplement?

NMN has numerous therapeutic functions and pharmacological effects on the human body. In less than a decade, scientists have dedicated their time to study all the Nicotinamide Mononucleotide including the mechanisms that explain aging and the age-related ailments.

Let’s delve into the advantages of the compound in the human system.

(1) Lengthening the Cellular Lifespan Up to the onset of the 21st century, scholars had enough reasons to declare aging as an irreversible process. However, this notion has become void thanks to the cutting-edge discovery of anti-aging supplements like Nicotinamide Mononucleotide.

NMN is natural-occurring in the human cells and is responsible for the biosynthesis of NAD+ and production of energy. As you grow old, these two compounds degenerate leading to regression of the stem cells. Remember, these functional units need enough cellular fuel to replicate continually, and therefore, a fall off will cut short the cellular lifespan.

Administering effective anti-aging drugs like NMN will reverse the process and delay the aging mechanism.

(2) Upholding Youthful Cellular Energy Levels The primary origin of the scores of ailments associated with aging is narrowed down to the cellular level. A decrease in the production of energy within the cells is the major contributing factor of the old age symptoms.

Being a precursor of NAD+, NMN has a role to play in maintaining the optimal energy levels of the cell’s mitochondria. Aging will automatically cause a decline in the concentration of NAD+. As a result, the aging process momentarily picks up leading to the development of old age diseases.

A drop in the cellular energy levels within the vital organs such as muscles, blood vessels, kidneys, liver, or pancreas always interferes with physical and cognitive health. It’s for this reason that

diseases such as ischemia, heart conditions, kidney failure, neurodegenerative disorders, and others shoot up.

The perfect solution is by supplementing the body’s Nicotinamide mononucleotide and NAD+ with external NMN treatment. These anti-aging drugs give a new lease of life to the aging cells, which will then put on a youthful look.

(3) Improving Blood Circulation One of the changes that occur during old is the decrease in the quality of the blood vessels within the mammalian body. Therefore, the circulatory system undergoes a lot of strain when carrying nutrients, oxygen, heat, or removing waste from the organs. Since the situation is persistent, it worsens over time leading to the occurrence of long-standing diseases.

Nicotinamide Mononucleotide is indirectly responsible for the production of blood vessels. Allow me to explain. The compound synthesizes NAD+, which in turn activates sirtuin deacetylase (SIRT1) protein.

Conversely, SIRT1 deacetylates lysine residues that aid in the production of oxygen free radicals.

This mechanism fights against possible oxidative stress, reperfusion, or ischemic injuries. In typical cases, the body itself will endogenously counteract ischemia and the related conditions through ischemic preconditioning (IPC). IPC will then act to stimulate the production of SIRT1.

You can either administer NMN before an ischemic event occurs or during its manifestation.

Before the occurrence, the compound offers cardio-protection by boosting ATP production through glycolysis.

In the case of Ischemia, you can still use Nicotinamide Mononucleotide as it will trigger acidosis and cause mitochondrial impermeability; hence, guaranteeing the protection of the cardiac system.

(4) Muscle Endurance What do you expect when the blood flow declines? Well, the state will lead to loss of muscle mass. It’s no doubt you’ll notice the old folks have less performance, low endurance, immobile, and so much tired all the time.

One of the groundbreaking discoveries by Dr. Sinclair was centered on the efficiency of NMN in boosting muscle strength. According to his 2013 and the recent 2018 studies, old mice exposed to a seven-day NMN treatment became physically fit and active like their younger counterparts.

The muscle capacity and the endurance of the oldest mice (30-months old) were the same as those of a five-month-old youngling. These ages are comparable with approximately 70 and 20 years in humans. From the findings, you can infer that NMN work on human is sure as death.

(5) Combating Neurodegenerative Disorders The brain is more like a powerhouse of your system. This aspect might be the reason why medics will always rely on brain functions when declaring the time of death.

A reduction in the levels of NAD+ in the brain interferes with cognitive health among the elderly.

Administration of NMN accelerates NAD+ production, hence, protecting the neural functions.

Scores of studies prove that Nicotinamide Mononucleotide benefits cognition, stroke, and impedes memory loss, which is prevalent with old age. Summarily, this anti-aging supplement is responsible for the maintenance of neurons.

NMN mainly targets the etiology of any given neurological condition. For instance, Alzheimer’s disease occurs due to a decrease in NAD+, a low rate of oxygen consumption in the brain, and mitochondrial abnormalities. Increasing the amount of NMN in the body counters all these effects.

According to a study published in 2012, Nicotinamide Mononucleotide will effectively manage intracerebral damage, which often leads to stroke. Old mice who were under NMN dosage registered significant improvement in the intracerebral NAD+ production. These research models had maximum protection against ischemic stroke, neural death, and neurological inflammation.

(6) Improved Metabolism in Old Age Several researchers have studied and proved that NMN facilitates glucose tolerance while enhancing the metabolism of sugar on aging mice with a poor diet. This study also applied to aged humans who develop diabetes either as a result of high sugar or poor nutrition. Additionally, a diet rich in fat leads to insulin resistance.

Nicotinamide Mononucleotide maintains a peak production of NAD+, which in turn reduces the age-related inflammation while improving the activation of insulin in fatty organs.

(7) Treatment of Diabetes People with type II diabetes always exhibit resistance to insulin. This characteristic is due to a falloff in NAD+. As a result, the cells undergo oxidative stress and inflammation. If you’re still young, the body will rejuvenate itself through some endogenous physiological activities. However, with old age, NAD+ levels decrease in the life-supporting organs like the skeletal muscles, liver, brain, and pancreas.

Another contributing factor to age-related diabetes is a high-fat diet. Abnormal amounts of saturated fats inhibit the biosynthesis of NAD+. In a bid to prove the efficacy of Nicotinamide Mononucleotide in the treatment of age and diet-induced diabetes, Yoshino and his colleagues

used two mice models.

After administering a daily dose of NMN for close to 10 days, the scholars established that the mice, which were subjected to high-fat meals, recorded improved insulin intolerance. On the other hand, the diabetic mice showed significant improvement in hyperlipidemia.

(8) Reversing Aging Chronic health complications always accompany the process of aging. As the body undergoes several physiological changes, some of the cellular functions happen to fall back. Take, for example, the levels of nicotinamide adenine dinucleotide decreases in multiple organs, leading to a decline in energy production by the cell’s mitochondrion.

Aging sets in motion various factors such as damaging of the DNA due to uncharged molecules, vascular oxidative stress, and other cognitive disorders. Do you know what happens? Well, there’s a DNA-repairing protein (PARP1) in the human system. In the case of DNA damage, NAD+ will activate this protein to repair the affected cell.

Several studies have come up with the nicotinamide mononucleotide benefits in aging. For instance, Mills and his colleagues used mice models to investigate the effect of NMN age-induced physiological decline.

In the study, the researchers noted that long-term administration of the treatment led to the upregulation of the compromised genes within the liver, skeletal muscles, and the adipose tissue.

What is more, the findings confirmed an improvement in the immune cell expression, an increase in lymphocytes, and activation of the leukocytes.

Another characteristic of aging is the presence of light-colored spots in the eye fundus. This condition together with bone density depletion and the inability to produce tears have been studied thoroughly on rodents. Scientists observed that mice, which were put on a 12-month NMN treatment, had all the above conditions reversed.

Longevity is the sole reason why people buy Nicotinamide Mononucleotide.

(9) Treatment of Obesity For the elderly, NMN can reduce up to 10% of the initial body weight without finding the middle ground between appetite and growth. The pathological mechanism of obesity and diabetes are correlated. Low NAD+ levels bring about mitochondrial dysfunction; hence, a decrease in the production of ATP. Obesity weighs down the potential of the mitochondria in generating ATP energy for the cells.

Once you administer Nicotinamide Mononucleotide, the drug will improve glucose intolerance and other metabolic functions relating to obesity.

When it comes to improving the blood flow, NMN for obese treatment acts similarly to exercising.

A single pill would be as good as using a treadmill daily. However, the difference comes in the levels of NAD+ content in the body organs. Whereas Nicotinamide Mononucleotide increases NAD+ in both the liver and muscular tissues, exercise only builds up the compound within the muscles.

Does Nicotinamide Mononucleotide (NMN) Really Work On Human?

Well, this might be the current question ringing in your head. In any case, all the research and Preclinical studies centered on Nicotinamide mononucleotide and NAD+ have been targeting the murine models.

If you have reservations about the efficiency of NMN work on human, here’s all you need to know.

Dr. David Sinclair, a top researcher, and geneticist at Harvard University is one of the recipients of NMN. Sinclair confesses that he takes the supplement. So far, the scholar hasn’t recorded any grave nicotinamide mononucleotide side effects. On the contrary, he professes that he feels young with a sharp mind. Hangovers and jet lags are now a past tense to him. He further asserts that his father, who is in his late seventies, also takes the supplement.

Additionally, Dr. Sinclair has used the treatment as an early trial at the Brigham and Women’s Hospital. He has plans for further testing the supplement on healthy elderly folks. Although his phase one study is complete, he is yet to make an official publication. Sinclair began the second phase of this clinical NMN supplement research in 2018.

Summary Research into NMN is ongoing and, so far, it’s showing great potential to slow, if not reverse, the signs of aging. It sounds illogical to assert that NMN prolongs the life span of humans. However, NMN is a safe and effective way to naturally raise the levels of NAD+ within the cells of your body and, with it, all the benefits of optimized NAD+ levels.

Reference: [1] Mills, K.F., Yoshino, J., Yoshida, S., et al. (2016). Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metabolism.

[2] Yoshino, J., Mills, K.F., Imai, S.I., and Yoon, M.J. (2011). Nicotinamide Mononucleotide, a key NAD+ Intermediate, Treats the Pathophysiology of Diet- and Age-Induced Diabetes in Mice. Cell Metabolism.

[3] Yamamoto, T., Byun, J., Zhai P., Ikeda, Y., Oka, S., and Sadoshima, J. (2014). Nicotinamide Mononucleotide, an Intermediate of NAD+ Synthesis, Protects the Heart from Ischemia and Reperfusion.

[4] Sinclair, D.A., Uddin, G.M., Youngson, N.A., and Morris, M.J. (2016). Head to Head Comparison of Short-Term Treatment with NAD+ precursor Nicotinamide Mononucleotide (NMN) and six Weeks of Exercise in Obese Female Mice.

[5] Imai, S., Yoshino, J., Mills, K.F., Grozio, A., et al. (2019) Slc12a8 is a Nicotinamide Mononucleotide Transporter. Nature Metabolism.

[6] De Picciotto, N.E., Mills, K.F., Imai, S., Gano, L.B., et al. (2016). Nicotinamide Mononucleotide Reverses Vascular Dysfunction and Oxidative Stress with Aging Mice.

[7] Yao, Z., Gao, Z., Yang, W., and Jia, P. (2017). Nicotinamide Mononucleotide Inhibits JNK Activation to Reverse Alzheimer Disease.

[8] Hou, Y., Wang, Y., Zhang, Y., Lautrup, S., et al. (2018). NAD+ Supplementation Normalizes Key Alzheimer’s Features and DNA Damage Responses in a New AD Mouse Model with Introduced DNA Repair Deficiency.