What is nicotinamide Mononucleotide (NMN)? NMN is produced from nicotinamide (NAM), a form of water-soluble vitamin B3, and 50-phosphoribosyl-1-pyrophosphate (PRPP) by nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting NAD+ biosynthetic enzyme found in mammals. NMN is also created from nicotinamide riboside (NR) via a phosphorylation reaction mediated by nicotinamide riboside kinase (NRK). The conversion of NMN into NAD+ is facilitated by nicotinamide mononucleotide adenylyltransfereases (NMNATs), rate-limiting enzymes that are present in all organisms. Data from rodent studies has shown that NMN can increase NAD+ biosynthesis in multiple tissues, including the pancreas, liver, adipose tissue, heart, skeletal muscle, kidneys, eyes, and blood vessels. It is still not totally clear if NMN can cross the blood-brain barrier (BBB), as it may be too large to pass through the membrane from the bloodstream into the brain. However, studies show that intraperitoneal injection increases NAD+ in multiple brain regions, including the hippocampus and hypothalamus, within 15 minutes of administration. This strongly suggests that NMN can pass through the BBB and increase NAD+ synthesis in the brain.
What is NAD+? nicotinamide adenine dinucleotide (NAD+), a molecule that participates in a myriad of metabolic and physiological processes, is crucial for our survival. Cellular NAD+ levels decline with age, however, and drive age-related decline and disease. A growing body of evidence suggests that supplementing with NAD+ precursor molecules may be a viable strategy to forestall the effects of aging.
Nicotinamide Mononucleotide benefits what does nicotinamide mononucleotide do? Nicotinamide mononucleotide (NMN) is a precursor of NAD+ (nicotinamide adenine nucleotide) and NADH biosynthesis, delivered in vegetarian capsules and providing anti-aging benefits. This new compound should not, however, be confused with nicotinamide riboside (NR) and other substances already on the market even though they may share certain properties, particularly at a genetic level; NMN is significantly more powerful than NR. Nicotinamide mononucleotide benefits are:
NMN suppresses age-associated body weight gain and enhances energy metabolism
NMN improves insulin sensitivity, eye function, and other features with no toxicity. It enhanced insulin sensitivity in the liver, restored impaired gene expression related to oxidative stress, inflammatory response and the circadian rhythm by activating SIRT1.
NMN prevents age-associated gene expression changes in a tissue-specific manner.
NMN is an effective anti-aging intervention that could be translated to humans.
NMN not only helps prolong life expectancy but has also shown promise in treating type 2 diabetes.
Does Nmn reverse aging? Finding a way of stopping the aging process has been the stuff of dreams for generations. But now it's on the way to becoming reality as Australian and American scientists believe they've found a way of not just pausing the aging process but rewinding it. Cellular NAD+ levels are depleted in aging In light of NAD+'s role in mitigating DNA repair and activating sirtuins, it's not surprising that cellular NAD+ levels are depleted in aging, a consequence of decreased synthesis and increased
consumption and degradation. The ensuing NAD+ deficits are associated with many of the hallmarks of aging and may predispose us to age-related diseases and poor immune function. Tissues such as the brain, heart, and skeletal muscle, which have high metabolic demands (and subsequently high NAD+ use), are hit hardest, increasing our susceptibility to Alzheimer's disease, cardiovascular disease, and sarcopenia – a progressive condition characterized by loss of skeletal muscle mass and strength and a leading cause of functional decline and loss of independence in older adults. Nicotinamide mononucleotide (NMN) is present in the diet and is available in dietary supplement form, it is also an intermediate compound in the NAD+ salvage pathway. Evidence from animal studies suggests that NMN supplementation may be beneficial to health and may delay or prevent the onset of age-related disease. It raises NAD+ levels and have been shown to counteract the effects of an obesogenic diet, promote mitochondrial health, improve markers of cardiovascular health, and slow both physical and mental aging. NMN is expected to work because NMN indirectly enhances sirtuin activity, thereby boosting metabolism. Sirtuins are a family of proteins that use nicotinamide adenine dinucleotide (NAD) for their enzymatic activities. The NAD molecule is a key element of any cell’s fuel supply chain. Past work has shown NAD levels in tissues throughout the body decrease with age. Nicotinamide mononucleotide (NMN), a key NAD+ intermediate.one way cells manufacture NAD begins with NMN. Imai said NMN can boost NAD+ production, enhancing sirtuin activity and“slowing down” aging. Orally administered NMN was quickly utilized to synthesize NAD+ in tissues. Remarkably, NMN effectively mitigates age-associated physiological decline in mice. Without any obvious toxicity or deleterious effects, NMN suppressed age-associated body weight gain, enhanced energy metabolism, promoted physical activity, improved insulin sensitivity and plasma lipid profile, and ameliorated eye function and other pathophysiologies. Consistent with these phenotypes, NMN prevented age-associated gene expression changes in key metabolic organs and enhanced mitochondrial oxidative metabolism and mitonuclear protein imbalance in skeletal muscle. These effects of NMN highlight the preventive and therapeutic potential of NAD+ intermediates as effective anti-aging interventions in humans.
Nicotinamide Mononucleotide(NMN) dosage - How much NMN should I take? There is no official dose of NMN. The trial did not set out to demonstrate efficacy of NMN, and given the small number of trial participants, the single dose, and the short study time, it was never going to do more than establish that the drug is safe for human use.
Although the size of the Phase one clinical trial was small, the study showed that dosages up to 500mg of orally administered NMN is safe in humans, implicating a potential therapeutic strategy. NMN is absorbed extremely quickly and has a short half-life, so to keep NAD+ levels high for as much of the day as possible it’s recommended to take one 125 mg capsule on waking and another in the afternoon if taking 250 mg per day. If taking a higher dose, you would want to take one 125 mg capsule in the morning and continue to take more an additional capsules every 1-3 hours depending on the total dose you’re aiming for.
What are the side effects of NMN? NMN is considered safe in animals, and the results are promising enough that human clinical trials have started. This molecule is largely considered to be safe and not toxic, even at high concentrations in mice and in a human study. Long-term (one-year) oral administration in mice does not have toxic effects. The very first clinical trial in humans was completed and the evidence supports the idea that it is not toxic in single doses. Although one study of Japanese men published in November 2019 noted that subjects had increased levels of bilirubin in their blood following NMN administration, these levels remained within the normal range. Future studies should focus on long-term safety and efficacy of usage. NMN is not associated with any other known side effects.
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Reference: [1] Nicotinamide mononucleotide (NMN) supplementation promotes anti-aging miRNA
expression profile in the aorta of aged mice, predicting epigenetic rejuvenation and anti-atherogenic effects.Tamas Kiss, Cory Giles, Stefano Tarantini, Andriy Yabluchanskiy, Priya Balasubramanian, Tripti Gautam, Tamas Csipo, Eszter Farkas, Ádam Nyúl-Tóth, Agnes Lipecz Csaba Zsabo, Jonathan Wren, Anna Csiszar. First published: 18 April 2020 [2] Vamshi K.C. Nimmagadda, Tapas K. Makar, Krish Chandrasekaran, Avinash Rao Sagi, Jayanta Ray, James W. Russell, Christopher T Bever Jr. SIRT1 and NAD+ precursors: Therapeutic targets in multiple sclerosis a review. J Neuroimmunol, 2017; DOI: 10.1016/j.jneuroim.2016.07.007. [3] Henryk Jęśko, Przemysław Wencel, Robert P. Strosznajder, Joanna B. Strosznajder. Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders. Neurochem Res, 2017; DOI: 10.1007/s11064-016-2110-y. [4] Jun Yoshino, Kathryn F. Mills, Myeong Jin Yoon, Shin-ichiro Imai. Nicotinamide Mononucleotide, a Key NAD+ Intermediate, Treats the Pathophysiology of Diet- and Age-Induced Diabetes in Mice. Cell Metab, 2011; DOI: 10.1016/j.cmet.2011.08.014. [5] Mills KF, Yoshida S, Stein LR, Grozio A, Kubota S, Sasaki Y, Redpath P, Migaud ME, Apte RS, Uchida K, Yoshino J, Imai SI. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab, 2016; DOI: 10.1016/j.cmet.2016.09.013. [6] Irie J, Inagaki E, Fujita M, et al. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men, 2019 Nov 2]. Endocr J. 2019;10.1507/endocrj.EJ19-0313.