NMN is a NAD+ precursor which supports healthy aging.
- Passed initial safety study in first clinical trial in humans 11/2019 (ref)*
Nicotinamide Mononucleotide (NMN) is emerging as a subject of interest in the medical community, but thus far, there has not been research or trials conducted with humans, except for the studies referenced above.*
The following are examples of dynamics associated with NMN through the animal model and may not be representative of the effects in the human body:
- Protects the brain’s blood vessels during aging (in mice)(ref)* Cerebromicrovascular circulation is associated with healthy cognition during aging.
- Increases telomere length (in mouse liver cells)(ref)* Telomeres are the ends of chromosomes which shorten with age.
- Increases sirtuin1 gene activity (in mice)(ref)* Sirtuins are molecules which reduces cellular damage and aging.
Mechanism of Action
Nicotinamide Mononucleotide (NMN) is a nucleotide which is a precursor to NAD (Nicotinamide adenine dinucleotide). NAD is a cofactor found in all living cells and is necessary for cellular reactions. NAD carries electrons between reactions and exists in an oxidized form (NAD+) or a reduced form (NADH) (1).
Maintaining higher levels of NAD increases levels of the energy molecule, ATP, and is vital to DNA repair, gene expression, and signaling between cells. Lower levels of NAD are associated with aging and age-related degeneration (2).
Many NAD precursors are available as supplements to increase levels of NAD in the body. Each precursor has a unique pathway which usually involves breaking down into Nicotinamide Riboside (NR). NR is a type of Vitamin B3 (3). Like NR, Nicotinamide Mononucleotide can be found in some food sources, but only in trace amounts. These food sources include broccoli, cabbage, cucumbers, tomatoes, avocados, and edamame (4).
It was previously believed that NR was the only NAD precursor that could enter the cell, and that supplementing with NR was a more direct way to synthesize NAD. Generally, NMN requires an extra step which converts NMN into NR before entering the cell and then is converted back into NMN through another phosphorylation process (5).
However, scientists recently discovered that a membrane protein (Slc12a8) is specific for NMN transport directly across the cell membrane and into the cell. This protein requires sodium in order to transport the NMN (5).
The majority of the cells which NMN enters can be found in the pancreas, small intestine, liver, and adipose tissue (fat tissue). NMN can be found in the bloodstream as quickly as 5 minutes after being absorbed from the small intestine in mice, and it is distributed into the body tissues quickly thereafter and converted into NAD (6).
NMN has advantages over other NAD precursors, specifically regarding Sirtuin interactions (7).
NMN is currently being studied for its effects in humans, though most of the studies on NAD precursors in humans have been conducted with NR. The scientific research for NMN that is plentiful involves animal studies; however, NMN’s safety profile in humans was recently released in November, 2019 and appears to be a feasible supplement for humans (8).
Side Effects & Toxicity
As stated above, NMN’s complete safety profile in humans is being investigated.
In mice, administering a very high dosage (that is much higher than the recommended human dosage) over a period of a year did not cause any side effects or toxicity. Due to the short lifespan of mice (approximately 2 years), the administration of NMN over 1 year has been likened to administration equal to half their lives (4).
For more information, please see our references tab.