How does NMN work in the body?

What

is

nicotinamide

mononucleotide

(NMN)?

NMN stands for nicotinamide mononucleotide, a molecule naturally occurring in all life forms.

NMN is the direct precursor of the essential molecule nicotinamide adenine dinucleotide (NAD+) and is considered a key component to increase NAD+ levels in cells. Nicotinamide adenine dinucleotide, or NAD+, a coenzyme that participates in the production of cellular energy and DNA repair.

What is NAD+ NAD+ is an essential coenzyme required for life and cellular functions. Enzymes are catalysts that make biochemical reactions possible. Coenzymes are ‘helper’ molecules that enzymes need in order to function.

Nicotinamide adenine dinucleotide (NAD+) is a cofactor, it plays an essential role in multiple physiological processes such as energy metabolism, DNA repair, and immune activation. It is essential for the activity of sirtuins, a class of enzymes involved in longevity, and poly ADP-ribose polymerase (PARP), a family of DNA-repair enzymes. Cellular NAD+ production declines with age, however, and its depletion has been implicated in the onset and progression of multiple age-related conditions such as metabolic dysregulation and neurodegenerative disease.

What Does NAD+ Do? NAD+ is the most abundant molecule in the body besides water, and without it, an organism would die. NAD+ is used by many proteins throughout the body, such as the sirtuins, which repair damaged DNA. It is also important for mitochondria, which are the powerhouses of the cell and generate the chemical energy that our bodies use.

NAD+ Functions as a Coenzyme in Mitochondria

NAD+ plays an especially active role in metabolic processes, such as glycolysis, the TCA Cycle (AKA Krebs Cycle or Citric Acid cycle), and the electron transport chain, which occurs in our mitochondria and is how we obtain cellular energy.

In its role as a ligand, NAD+ binds to enzymes and transfers electrons between molecules.

Electrons are the atomic basis for cellular energy and by transferring them from one molecule to the next, NAD+ acts through a cellular mechanism similar to recharging a battery. A battery is depleted when electrons are expended to provide energy. Those electrons can’t return to their starting point without a boost. In cells, NAD+ serves as that booster. In this way, NAD+ can decrease or increase enzyme activity, gene expression, and cell signaling.

NAD+ Helps Control DNA Damage As organisms grow older, they accrue DNA damage due to environmental factors such as radiation, pollution, and imprecise DNA replication. According to the current aging theory, the accumulation of DNA damage is the main cause of aging. Almost all cells contain the ‘molecular machinery ’ to repair this damage. This machinery consumes NAD+ and energy molecules.

Therefore, excessive DNA damage can drain valuable cellular resources.

One important DNA repair protein, PARP (Poly (ADP-ribose) polymerase), depends on NAD+ to function. Older individuals experience decreased levels of NAD+. The accumulation of DNA damage as a result of the normal aging process leads to increased PARP, which causes decreased NAD+ concentration. This depletion is exacerbated by any further DNA damage in the mitochondria.

What is NAD+ booster?

While the importance of NAD+ to the body’s is clear, it appears that simply supplying the body with more NAD via oral supplement or the bloodstream should be the first step – not the final one. With the understanding that, over time, these supplies of NAD are depleted in the same manner as the naturally occurring NAD, supplementation options become a crucial component to gradually increasing NAD. NAD+ can also be synthesized from other precursors including nicotinamide (NAM, also called niacinamide), nicotinic acid (NA), and nicotinamide riboside (NR) chloride, which are often collectively referred to as niacin (vitamin B3) or niacin equivalents. These precursors are not equally allocated throughout the body; rather, they exhibit preferential distribution among the blood, brain, gut, and other organs. Tryptophan, an amino acid obtained from the diet, can also be converted into NAD+.

NAD+ acts as a cellular "sensor" to mediate energy-generating pathways and activate

NAD+-consuming enzymes such as sirtuins and poly ADP-ribose polymerases (PARP). NAD+ depletion, which occurs with age, has been implicated in the progression of multiple age-related conditions such as metabolic dysregulation and neurodegenerative diseases. Nicotinamide mononucleotide, as well as other precursors such as NR, help maintain cellular levels of NAD+.

Boosting NAD+ levels through precursors has proven to have therapeutic potential in treating aging and age-related diseases across multiple animal models. The first human phase 1 clinical trial is now underway to determine the safety and bioavailability of nicotinamide mononucleotide supplementation.

Why Should We Care About NAD+ ?

Since the discovery of NAD+ in 1906, the molecule has been on scientists’ radar for its abundance in the body and its crucial role in molecular pathways that keep our body running. In animal studies, raising NAD+ levels in the body has shown promising results in research fields like metabolics and age-related disease and has even shown some anti-aging properties. Age-related illnesses such as diabetes, cardiovascular diseases, neurodegeneration and general decreases in the immune system.

Low NAD+ is a hallmark of aging, but NAD+ supplements may help.

So, in an effort to stave off these age-related changes, can we boost NAD+ levels by taking NAD+ supplements? Not quite. NAD+ in supplemental form has very poor bioavailability, meaning it doesn't have much of an effect when introduced to the body. But, NAD+ has several precursors or intermediates—molecules that transform into NAD+ through enzymatic reactions. Scientists have studied two such intermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), more extensively than others, and the research is encouraging. Several studies indicate that supplementing with these precursors can increase NAD+ levels and prolong the lifespan of yeast, worms, and mice. Furthermore, other animal studies show that boosting NAD+ can also improve muscle generation, cardiovascular function, and glucose metabolism.

The first question researchers asked themselves was “ Is nicotinamide riboside the same as NMN?” They found that NMN actually transforms into NR, which enters human cells first, and is then converted back into NMN and eventually NAD. Thus, the question regarding which precursor makes the better NAD booster has long been subject to debate.

What Is NMN Good For? One way that we might sustain healthy levels of NAD+ is by supplementing our bodies with its precursor, nicotinamide mononucleotide (NMN).

Current research shows that this transformation between NR and NMN must take place for entry to a few cell types. This leads researchers to believe that NMN is, in fact, one of the quickest means of stimulating NAD production. However, NMN supplements are also proving to have their own anti-aging benefits beyond those of NAD production alone.

In addition to the NAD metabolic pathway, NMN can be added directly to cells without converting to NAD. This phenomenon is made possible by newly discovered transport proteins that increase in number after NAD levels drop off. In this form, NMN contributes to cell energy and allows each of the previously mentioned anti-aging properties promoted by cells with adequate ability to grow and regenerate.

Choosing to supplement with NMN along with NAD provides a much more direct path to promoting cell metabolism and is thus a much quicker means of doing the same. In addition, NMN has been found to improve insulin activity and production, resulting in additional metabolic benefits as well as glucose tolerance. In particular, NMN supplements can help work to alleviate metabolic conditions like diabetes, fatty liver disease, and obesity.

Other Potential Benefits of NMN      

Promotes Vascular Health and Blood Flow Improves Muscle Endurance and Strength Protects Against Heart Disease Lowers Risk of Obesity Enhances Maintenance of DNA Repair Increases Mitochondrial Function

Reference: [1] 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.

[2] Katalin Sas, Elza Szabó, László Vécsei. Mitochondria, Oxidative Stress and the Kynurenine

System, with a Focus on 10.3390/molecules23010191.

Ageing

and

Neuroprotection.

Molecules,

2018;

DOI:

[3] Nicotinamide mononucleotide (NMN) supplementation ameliorates the impact of maternal obesity in mice: comparison with exercise.Uddin GM, Youngson NA, Doyle BM, Sinclair DA, Morris MJ. [4] Nicotinamide mononucleotide (NMN) supplementation ameliorates the impact of maternal obesity in mice: comparison with exercise. Uddin GM, Youngson NA, Doyle BM, Sinclair DA, Morris MJ.