NAD+ Precursor

NAD+ precursors are molecules that can be converted into NAD+, a vital coenzyme found in all living cells, crucial for energy production, cellular repair, and longevity. Taking NAD+ directly is generally considered inefficient due to its inability to enter cells directly due to its large size and polar nature, making it unable to cross the cell membrane effectively. Thus, NAD+ precursors like NMN, NR, and NA, which are smaller and can enter cells more easily, are used to increase cellular NAD+ levels, as they can be converted into NAD+ once inside the cells. These precursors are therefore preferred for supplementation to boost NAD+ levels efficiently within the body.

• Nicotinamide Mononucleotide (NMN): A prominent NAD+ precursor, NMN, is involved in the biosynthesis of NAD+. NMN enters cells via specific transporters and is converted to NAD+ through a series of enzymatic reactions.
• Nicotinamide Riboside (NR): Another significant precursor, NR, is converted into NMN before participating in NAD+ synthesis. NR can enter cells through unique transporters and is phosphorylated to NMN by the enzyme NR kinase.
• Nicotinamide (NAM): NAM, a form of vitamin B3, is also a precursor of NAD+, contributing to its synthesis through the salvage pathway. NAM is converted to NMN by the enzyme nicotinamide phosphoribosyltransferase (NAMPT).
• Nicotinic Acid (NA): NA, another form of vitamin B3, serves as a precursor of NAD+ through the Preiss-Handler pathway. NA is converted to NAD+ via a series of enzymatic reactions, first to nicotinic acid mononucleotide (NAMN), then to nicotinic acid adenine dinucleotide (NAAD), and finally to NAD+.
• Reduced Nicotinamide Mononucleotide (NMNH): A new and efficient NAD+ precursor, NMNH operates via a novel metabolic pathway that is independent of the enzymes NRK (Nicotinamide Riboside Kinase) and NAMPT (Nicotinamide Phosphoribosyltransferase).

Comparision

NAD+ Precursors

Precursor	Nicotinamide Mononucleotide (NMN)	Nicotinamide Riboside (NR)	Nicotinamide (NAM)	Nicotinic Acid (NA)
Structure
Description	A vital NAD+ precursor involved in the biosynthesis of NAD+. NMN enters cells via specific transporters.	A significant precursor that is converted into NMN before participating in NAD+ synthesis. NR can enter cells through unique transporters.	A form of vitamin B3 and a precursor of NAD+, contributing to its synthesis through the salvage pathway.	Another form of vitamin B3 serving as a precursor of NAD+.
Pathway	NAD+ salvage pathway	NAD+ salvage pathway	Salvage Pathway	Preiss-Handler Pathway
Conversion Process	Converted directly to NAD+ through a series of enzymatic reactions.	Phosphorylated to NMN by the enzyme NR kinase, then converted to NAD+.	Converted to NMN by the enzyme nicotinamide phosphoribosyltransferase (NAMPT), then to NAD+.	Converted to NAD+ via a series of enzymatic reactions: NA → NAMN → NAAD → NAD+.
Molecular Weight	334.22 g/mol	255.25 g/mol	122.13 g/mol	123.11 g/mol
Bioavailability	Currently under investigation, but shows promise in preliminary studies	Good bioavailability when taken orally	Lower bioavailability compared to NMN and NR	Well-established bioavailability
Safety and Toxicity	Considered safe at moderate doses; long-term effects still under investigation	Generally regarded as safe; high doses may cause mild side effects	Generally safe; excessive amounts may cause flushing and other side effects	Safe at recommended doses; high doses may cause flushing
Natural Sources	Not found in significant amounts in food	Found in trace amounts in milk	Found in meat, fish, and grains	Found in meat, fish, and grains
Research Status	Extensively studied in animals; human research is ongoing	Well-studied in both animals and humans	Extensively researched	Extensively researched
Cost and Accessibility	Relatively expensive; widely available as a supplement	Moderate cost; widely available as a supplement	Less expensive; widely available in both food and supplement form	Least expensive; widely available in both food and supplement form
Half-Life	Not well-established; more research needed	Short, around 2.7 hours in humans	Longer than NMN and NR	Long, around 5.6 hours in humans
Clinical Trials	Several ongoing to determine efficacy and safety in humans	Numerous completed and ongoing, showing promising results for various health conditions	Extensively studied, with numerous trials completed	Extensively studied, with numerous trials completed

See also

• Nicotinamide Adenine Dinucleotide (NAD)
• NAD+ Booster

Todo

• 2023, The acute effect of different NAD⁺ precursors included in the combined metabolic activators