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Nicotinamide mononucleotide

Nicotinamide mononucleotide(NMN) is a nucleotide derived from ribose and nicotinamide. Like nicotinamide riboside, NMN is a derivative of niacin, and humans have enzymes that can use NMN to generate Nicotinamide adenine dinucleotide(NAD+).



  • Effectively alleviate and prevent chronic cardiovascular disease

  • Detoxificationliver-protection and vision and hearing improvement

  • DNA reparation

  • Diabetes treatment

  • Stamina enhancement

  • Effectively  prevent Alzheimer’s disease and Parkinson’s disease

  • Memory improvement and anti-aging



Uthever™: The NAD Pre-Cursor for Life

To put it bluntly – nobody likes aging – especially health-conscious supplement consumers. Effepharm can help, with anultra-pure form of NMN that’s tested and approved.

With customers experiencing age-related pain, injury-prone joints, decreased strength, and lower energy levels, supplement formulators are always looking for the next big thing to help them out. It is here right now in the form of Effepharm’s Uthever™.

Although there’s no Fountain of Youth, there may be something out there already that comes very close to approximating one?

Introducing Uthever™ from EffePharm: the NAD Pre-Cursor You’ve Been Looking For

Uthever™ from Effepharm may just have what it takes to get you feeling a little younger again. This incredibly pure, high-quality form of isolated nicotinamide mononucleotide packs a heavy mitochondria-powering punch, and pulls all the right strings into bringing some once-fabled anti-aging effects to reality.

Before getting into the science of NMN, let’s explore why Uthever™ is the only one worth seriously considering:

Uthever™: The True Purity in a Sea of Fake NMN

EffePharm brings supplement formulators and research scientists a lab-tested NMN that can be relied upon for these critically important supplement applications. In a market that’s inundated with fake and adulterated NMN ingredients (some with less than 80% purity, others that are completely fraudulent and 0% pure), it’s time to get a time-tested and trusted brand that’s brought you many great ingredients in the past.

Confirmed by Intertek

Formulating with an NMN ingredient from anyone but EffePharm puts customers at risk. Yes, 200mg of 80% purity is the same as 160mg at 99.9% purity, but what’s in the other 40mg from the competition? Nobody knows, and it’s simply not safe. Only EffePharm supplies authentic NMN with purity that was confirmed by an international third party — Intertek.

An All-Star R&D Team

Effepharm’s R&D team members are extremely experienced, most of whom come from top pharmaceutical companies such as GSK. We strictly control the manufacturing process and follow SOPs to ensure consistency between batches. From batch to batch, you will always get the same high quality NMN from Effepharm.

Added Features: Less Temperature Sensitivity, Higher Bioavailability, and Sustained Release

With Effepharm’s NMN, we’ve made it far less hygroscopic and temperature sensitive, which allows it to be stored at ambient room temperature. To improve its bioavailability, we’ve employed modern pharmaceutical technology to develop controlled-release and sustained-released versions of NMN as well. More innovative forms will be developed very soon, so please contact us for more information.

Safety Testing

To top it off, at Effepharm, animal tests are being conducted and a clinical trial is planned. We’ve launched a project encouraging R&D institutes and nutritionists to get free NMN samples as well as funding from Effepharm — we’re that confident in our purity and efficacy.

Now that we’ve covered the benefits of using Effepharm, it’s time to learn more about what NMN can do for your consumers, and how you may formulate with it:

NMN: The next major breakthrough in supplement formulation

NMN is popular to use on its own, and is often marketed by supplement brands towards anti-aging and general wellness markets. We also believe there are applications for this in energy supplements, work out enhancement, blood sugar control, and even weight loss, but we leave it to you to formulate fantastic products – we simply provide the key to the engine with the best NMN on the market.

In this post, we’ll break down all that goes on within the body in regards to aging – what happens in the cells, the mechanisms at play, and the bioactive substances that facilitate it. We’ll then explain the potential NMN offers in reducing these effects of aging, as well as why it’s a better option than some other alternative solutions!

What is NMN?

Nicotinamide mononucleotide (NMN), a derivative of niacin, is a nucleotide that functions as a precursor to nicotinamide adeninedinucleotide (NAD+)[1]. NAD+ is a molecule that holds a variety of functions within the body, mainly through facilitation of cell-signaling enzymes called sirtuins[2]. These enzymes are crucial for normal functioning, with SIRT1 (there are 7 sirtuins) being particularly unique. Research has shown it to be highly active following caloric restriction, which itself brings multiple benefits, including signs of an extending lifespan[3]. Sure enough, further tests have revealed that elevated levels of SIRT1 can lead to protection from metabolic decline and disease[4].

These sirtuins mainly operate through the mitochondria. They act as “message carriers” of sorts – when cell nuclei send signals to the mitochondria, sirtuins (SIRT1 specifically) help make sure the message gets there[5]. We all know how vital proper mitochondrial function is – they aren’t called the “powerhouse of the cell” for nothing! Because sirtuin activity is directly dependent on NAD+ levels[2], NAD+ becomes incredibly important, too!

But, how exactly does all of this happen?

Calling on the salvage pathway

 Figure1 -De novo pathway

Recycling NAD+ compounds, this pathway typically breaks down precursors through two enzymes, nicotinate phosphoribosyltransferase1 and nicotinamide mononucleotide adenylyl transferase 1,3[7]. However, there seems to be a couple of different ways to reach pure NAD+. In Figure 1, the reactions and paths that can be taken are drawn out. One route, which has been highlighted in Figure 2, turns nicotinamide riboside (NR) into NMN, which ultimately yields NAD+ [7][8]. From there, NAD+ enters cellular barriers where it gives the mitochondria the fuel they need to operate.

Now that we’ve covered the biomechanics involved, what happens once NAD+ is working within our bodies? In other words, why is it important?

Figure 2-Salvage pathway

Functions of NAD+ (via NMN)

Once NMN is broken down into NAD+,our bodies utilize it to help do virtually everything. Being the fuel source ofour cells, our bodies would have a rather difficult time working properly. The mitochondria carry various functions throughout the body, most notably the production of ATP (adenosine triphosphate), which facilitates muscle movement. Here are some other important benefits that stem from sufficient NAD+ levels, from supplementation with NMN:

In the salvage pathway, Nicotinamide (NAM) and Nicotinamide Riboside (NR) are first converted to NMN, which is then further converted to NAD+ . NMN is more correctly referred to as a NAD+ intermediate because NMN is the last step before conversion to NAD+.

Facilitates blood flow and heart health

Research has shown that NMN helps protect from ischemia[9], a result of insufficient blood flow in anyarea of the body. Typically, the body defends itself from ischemia via ischemic preconditioning (IPC)[10]. IPC stimulates SIRT1, which is a NAD+ dependent sirtuin[9], which helps move blood throughout the body. Because NMN activates SIRT1, then, it has the ability to mimic IPC, and thus is capable of protecting the heart from ischemia and reperfusion[9]!

Promotes proper brain functioning and protects from neurological disease

Efficient circulation is, obviously, crucial to overall well-being. Specifically, having adequate blood flow is imperative in brain health. Without enough oxygenated blood reaching our brain, serious issues can arise.

Luckily, NMN helps ensure that this essential organ gets all the oxygen it needs. Improper mitochondrial functioning is a known precursor of neurodegenerative diseases, such as Alzheimer’s. Having hard-working, healthy mitochondria can help fend off these kinds of diseases. Research shows that because NMN increases NAD+, which increases the degree of healthy mitochondria functioning, it has the potential to be aprotective agent against neurodegenerative disease[11].

Fends off obesity and diabetes

Despite how diligent one is in their eating habits, the risks of obesity and diabetes have never been higher than they are in today’s society. Calorically-dense processed foods, in addition to foods and industrialized seed oils with negative nutritional value, are more common than healthy alternatives anymore! Just as consistently-elevated blood sugar and Hypoglycemic hormone levels lead to diabetes, continuous overeating will eventually lead to weight gain. Our metabolisms are well-oiled machines, but unless we ensure they are functioning properly, bad habits can ultimately cause them to falter.

With multiple metabolic pathways operating throughout the body, a lot of different components are involved in keeping adequate metabolic health. One of which is facilitated by nicotinamide phosphoribosyltransferase (NAMPT), which we mentioned earlier is an enzyme dependent on NAD+. In 2011, the ability of NMN supplementation to fix NAMPT deficiencies in diabetic mice was tested. Researchers found that NMN stimulated NAD+ biosynthesis, raising NAD+levels in the pancreas, liver, and white adipose tissue[12].With the pancreas being directly responsible for the secretion of insulin, which keeps blood sugar levels regulated, one can hypothesize that this would help protect from diabetes. Sure enough, that’s what this study found! NMN was found to decrease the effect of underlying causes of diabetes and significantly improve glucose tolerance[12], both of which help protect from diabetes and obesity.

Why not intake NAD+ directly?

As NAD+ molecules are relatively large, so It’s difficult for NAD+ intaken from supplements to penetrate the cell membrane and then enter the cell interior. While NMN molecules can easily cross the cell membrane and enter the cell interior. Once entering the cell interior, two of NMN molecules will be combined spontaneously to form an NAD+ molecule, so that NAD+ can take effect in human body.

Aging and NMN

Most of what we’ve discussed is tied to the mitochondria, sirtuins, and NAD+. This directly-dependent relationship is present virtually everywhere inthe body. It has a role in your vital organs, your brain, and even your ability to keep a healthy weight!

Notice, though, how we tend to discover problems with these things aswe age. As we get older, our bodies begin to break down – we become more susceptible to disease, pains, and weight gain. As unfortunate as this may be, it turns out that these issues are directly linked to NAD+ !

Mitochondrial function and its relation to ageing has been of interest to a number of researchers in recent years. There’s a large amount of studies available that discuss their relationship, but most of them acknowledge the same thing -that mitochondrial function deteriorates as we age! Some even posit that mitochondrial function may even be a key determinant of life span[13]!

All of this makes complete sense, as the things the mitochondria are responsible for regulating seem to slowly degrade as we get older. Furthermore,research has found most of these issues, like metabolic complications from hypoxia[14], are responses of declining mitochondrial functioning. Indeed, as we age, our NAD+ levels reduce drastically[15], which explains why our mitochondria deteriorate! If only there were a way to slow this down…

NMN to the rescue!

But, as we’ve shown, the body can create NAD+ from derivative compounds, such as NMN. Modern research is beginning to tackle the effects of supplemental NMN and its effects on NAD+ protection within the body, and whether it’s a viable resource in defending against mitochondrial deterioration. The theory suggests that more NMN will lead to both more sirtuin stimulation and enzymatic activity, which yields multiple benefits. The most obvious outcome, perhaps, is more NAD+ production. The ancillary benefit would be increased activity of other bodily mechanisms reliant on those sirtuins and enzymes. Both of these outcomes bring anti-aging potential!

In 2016, researchers administered NMN to regularly-fed mice for 12 months. They were given 100mg/kg or 300mg/kg, and final results were compared to a placebo group. After treatment, a variety of measurements pertaining to many different age-related changes were taken.They found that orally-dosed NMNboosted tissue NAD+ levels, suppression of age-related weight gain,increased energy metabolism,andimproved insulin sensitivity[15]! Truly cementing NMN as the cause for these effects, the supplemented mice experienced are versal in age-related gene expression[15].

Another study from 2012 found that an orally-administered NAD+ precursor protected from obesity in mice given a high-fat diet[16]. Suffice to say, these results speak volumes to the potential we’re talking about here.

Results in tests with mice, but in humans…

It’s important we note that almostall research tests conducted have used mice as subjects as opposed to humans. While the cellular mechanisms in play should be virtually the same, these cited benefits have not necessarily been shown in clinical human research.

There is, however, one study that has found some evidence. Research from 2017 found that an NAD+ precursor increased NAD+ levels in a dose-dependent, time-dependent manner[17]. Additional research is on the way too, most notably a comprehensive human trial currently being studied in Japan[18].

While these conclusions are exciting, we are still vying for more proof that NMN can be of benefit for you. That being said, we wouldn’t be formulating our own version if we didn’t believe in its ability!

Why EffePharm’s NMN over NR?

As you may have deduced from Figure 1 above, there are multiple different ways one could supplement for increased NAD+ levels. One of the most popular is through taking nicotinamide riboside (NR). We at EffePharm, however, don’t believe this is the most efficient way to boost NAD+ production.

While NR eventually does degrade into NAD+, it first becomes NMN through phosphorylation[19]. We at EffePharm ask – why use NR, which requires a two-step process, when you could use NMN, which only requires one?

Additionally, while no adverse effects have been cited in NMN, the same cannot be said for other NAD+ precursors, which have brought about nausea and hepatotoxicity[20]. Not only that, buttheir effects weren’t as long-lasting as NMN, either!

If there was a better way of enhancing NAD+ production within the body, we would’ve decided to use it. But, research has continuously supported the claim that NMN is the best way to protect against many age-related changes. In ourhigh-grade,high-quality NMN, we are delivering the most efficient and most effective form of NAD+ supplementation on the market.

Conclusion – Get Your Spring Back with EffePharm’s NMN

The extra baggage that comes along with getting older, quite plainly, is pretty heavy. Being more susceptible to pains and aches and having less energy, all while your metabolism is screeching to a stop, is something that no one looks forward to. But, as current science stands, it remains an inevitability. However, that doesn’t mean there isn’t a way to slow this deterioration down!

Most of the symptoms of aging are directly related to how well our mitochondria are working. These powerhouses run on a specific fuel called NAD+, and this energy source seems to grow harder to find as we get older. Without it, we produce less ATP, and our bodies start to become liable to a variety of diseases and undesirable symptoms.

In EffePharm’s NMN, we are providing you the best way to keep NAD+ production in high-gear. Using NMN boosts both NAD+ production and cellular activity, both of which are needed to keep you feeling like a well-oiled machine.

How often have you watched your children, or your grandchildren, run around tirelessly for hours and thought,“Wow, I wish I had that kind of energy?” Well, with our natural anti-aging energy enhancer, you may just be able to get up and run around with them… at least for a little bit!

 

References:

  1. Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and diseasehttp://web.mit.edu/biology/guarente/references/15.pdf– Overview of the NAD process
  2. Gomes·Ana P·et al. “Declining NAD+Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging.”;Cell; U.S. National Library of Medicine; 19 Dec. 2013;https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076149/– Sirtuins
  3. Cohen· Haim Y·et al. “Calorie Restriction Promotes Mammalian Cell Survival by Inducing the SIRT1 Deacetylase.”;Science (New York, N.Y.); U.S. National Library of Medicine; 16 July 2004;https://www.ncbi.nlm.nih.gov/pubmed/15205477/
  4. Haigis· Marcia C ·David A Sinclair.“Mammalian Sirtuins: Biological Insights and Disease Relevance.”;Annual Review of Pathology; U.S. National Library of Medicine; 2010;https://www.ncbi.nlm.nih.gov/pubmed/20078221/
  5. Sinclair·David A·Leonard Guarente.“Small-molecule allosteric activators of sirtuins.”;Annual review of pharmacology and toxicology;vol. 54; 2014; 363-80 ;https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018738/
  6. Grubmeyer CT· Gross JW·Rajavel M.Energy coupling through molecular discrimination: nicotinate phosphoribosyltransferase. Methods Enzymol 1999; 308:28-48.
  7. Belenky·Peter·et al.“Nicotinamide Riboside Promotes Sir2 Silencing and Extends Lifespan via Nrk and Urh1/Pnp1/Meu1 Pathways to NAD .”;Cell; U.S. National Library of Medicine; 4 May 2007;https://www.ncbi.nlm.nih.gov/pubmed/17482543/
  8. Poddar·Saikat Kumar·et al.“Nicotinamide Mononucleotide: Exploration of Diverse Therapeutic Applications of a Potential Molecule.”;Biomolecules;vol. 9,1 34; 21 Jan. 2019;https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359187/
  9. Yamamoto·Takanobu·et al.“Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and reperfusion.”;PloS one; vol. 9,6 e98972; 6 Jun. 2014;https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048236/
  10. Yellon·Derek M·Derek J Hausenloy.“Myocardial Reperfusion Injury.”;The New England Journal of Medicine; U.S. National Library of Medicine; 13 Sept. 2007;https://www.ncbi.nlm.nih.gov/pubmed/17855673/
  11. Long·Aaron N·et al.“Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer’s disease-relevant murine model.”;BMC neurology;vol. 15 19; 1 Mar. 2015;https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358858/
  12. Yoshino·Jun et al.“Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice.”;Cell metabolism;vol. 14,4; 2011; 528-36;https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204926/
  13. Lanza·Ian R·K Sreekumaran Nair.“Mitochondrial function as a determinant of life span.”;Pflugers Archiv : European journal of physiology;vol. 459,2; 2010; 277-89;https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2801852/
  14. Kluckova·Katarina·Daniel A Tennant.“Metabolic implications of hypoxia and pseudohypoxia in pheochromocytoma and paraganglioma.”;Cell and tissue research;vol. 372,2; 2018; 367-378;https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915505/
  15. Mills·Kathryn F et al.“Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice.”;Cell metabolism;vol. 24,6; 2016; 795-806;https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668137/
  16. Cantó·Carles·et al.“The NAD( ) Precursor Nicotinamide Riboside Enhances Oxidative Metabolism and Protects against High-Fat Diet-Induced Obesity.”;Cell Metabolism; U.S. National Library of Medicine; 6 June 2012;https://www.ncbi.nlm.nih.gov/pubmed/22682224
  17. Dellinger·Ryan W.·et al.“Repeat Dose NRPT (Nicotinamide Riboside and Pterostilbene) Increases NAD Levels in Humans Safely and Sustainably: a Randomized, Double-Blind, Placebo-Controlled Study.”;Nature News; Nature Publishing Group; 24 Nov. 2017;https://www.nature.com/articles/s41514-017-0016-9
  18. Tsubota·Kazuo. “The first human clinical study for NMN has started in Japan.”; NPJ aging and mechanisms of disease; vol. 2 16021; 27 Oct. 2016;https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515004/
  19. Bieganowski·Pawel·Charles Brenner.“Discoveries of Nicotinamide Riboside as a Nutrient and Conserved NRK Genes Establish a Preiss-Handler Independent Route to NAD in Fungi and Humans.”;Cell; U.S. National Library of Medicine; 14 May 2004;https://www.ncbi.nlm.nih.gov/pubmed/15137942/
  20. Kawamura·Tomoyo·et al.“β-Nicotinamide Mononucleotide, an Anti-Aging Candidate Compound, Is Retained in the Body for Longer than Nicotinamide in Rats.”;Journal of Nutritional Science and Vitaminology; U.S. National Library of Medicine; 2016;https://www.ncbi.nlm.nih.gov/pubmed/27725413


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