Nicotinamide mononucleotide ("NMN" and "β-NMN") is a

nucleotide Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...

derived from

ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally occurring form, , is a component of the ribonucleotides from which RNA is built, and so this comp ...

nicotinamide Nicotinamide (International nonproprietary name, INN, British Approved Name, BAN ) or niacinamide (United States Adopted Name, USAN ) is a form of vitamin B3, vitamin B3 found in food and used as a dietary supplement and medication. As a suppl ...

nicotinamide riboside Nicotinamide riboside (NR, SR647) is a pyridine-nucleoside and a form of vitamin B3. It functions as a precursor to nicotinamide adenine dinucleotide, or NAD+, through a two-step and a three-step pathway. Chemistry While the molecular weight of ...

and

niacin Nicotinic acid, or niacin, is an organic compound and a vitamer of vitamin B3, an essential human nutrient. It is produced by plants and animals from the amino acid tryptophan. Nicotinic acid is also a prescription medication. Amounts f ...

. In humans, several enzymes use NMN to generate

nicotinamide adenine dinucleotide Nicotinamide adenine dinucleotide (NAD) is a Cofactor (biochemistry), coenzyme central to metabolism. Found in all living cell (biology), cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphat ...

(NADH). In mice, it has been proposed that NMN is absorbed via the small intestine within 10 minutes of oral uptake and converted to nicotinamide adenine dinucleotide (

NAD+ Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an ade ...

) through the Slc12a8 transporter. However, this observation has been challenged, and the matter remains unsettled. Because NADH is a cofactor for processes inside

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

, for

sirtuin Sirtuins are a family of signaling proteins involved in metabolic regulation. They are ancient in animal evolution and appear to possess a highly conserved structure throughout all kingdoms of life. Chemically, sirtuins are a class of proteins ...

s and PARP, NMN has been studied in

animal model An animal model (short for animal disease model) is a living, non-human, often genetic-engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of ha ...

s as a potential neuroprotective and

anti-aging The anti-aging movement is a social movement devoted to eliminating or reversing aging, or reducing the effects of it. A substantial portion of the attention of the movement is on the possibilities for life extension, but there is also interest i ...

agent. The alleged anti-aging effect at the cellular level by inhibiting mitochondrial decay in presence of increased levels of NAD+ makes it popular among anti-aging products. Dietary supplement companies have aggressively marketed NMN products, claiming those benefits. However, no human studies to date have properly proven its anti-aging effects with proposed health benefits only suggested through research done

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

or through

animal models A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. Mod ...

. Single-dose administration of up to 500 mg was shown safe in men in a study at

Keio University , abbreviated as or , is a private university, private research university located in Minato, Tokyo, Japan. It was originally established as a school for Rangaku, Western studies in 1858 in Edo. It was granted university status in 1920, becomi ...

. One 2021 clinical trial found that NMN improved muscular insulin sensitivity in prediabetic women, while another found that it improved aerobic capacity in amateur runners. A 2023 clinical trial showed that NMN improves performance on a six-minute walking test and a subjective general health assessment. NMN is vulnerable to extracellular degradation by

CD38 CD38 (cluster of differentiation 38), also known as cyclic ADP ribose hydrolase, is a glycoprotein found on the surface of many immune cells (white blood cells), including CD4+, CD8+, B lymphocytes and natural killer cells. CD38 also functions in ...

enzyme, which can be inhibited by compounds such as

CD38-IN-78c CD38-IN-78c is a drug which acts as a potent and selective inhibitor of the glycoprotein enzyme CD38. In animal studies it boosts levels of nicotinamide adenine dinucleotide Nicotinamide adenine dinucleotide (NAD) is a Cofactor (biochemist ...

Dietary sources

NMN is found in fruits and vegetables such as

edamame is an East Asian dish prepared with immature soybeans in their pods, which are boiled or steamed, and may be served with salt or other condiments. The dish has become popular across the world because it is rich in vitamins, dietary fiber, and i ...

broccoli Broccoli (''Brassica oleracea'' var. ''italica'') is an edible green plant in the Brassicaceae, cabbage family (family Brassicaceae, genus ''Brassica'') whose large Pseudanthium, flowering head, plant stem, stalk and small associated leafy gre ...

cabbage Cabbage, comprising several cultivars of '' Brassica oleracea'', is a leafy green, red (purple), or white (pale green) biennial plant grown as an annual vegetable crop for its dense-leaved heads. It is descended from the wild cabbage ( ''B.& ...

cucumber The cucumber (''Cucumis sativus'') is a widely-cultivated creeping vine plant in the family Cucurbitaceae that bears cylindrical to spherical fruits, which are used as culinary vegetables.avocado The avocado, alligator pear or avocado pear (''Persea americana'') is an evergreen tree in the laurel family (Lauraceae). It is native to Americas, the Americas and was first domesticated in Mesoamerica more than 5,000 years ago. It was priz ...

at a concentration of about 1 mg per 100g, making these natural sources impractical to acquire the quantities needed to accomplish the dosing currently being investigated for NMN as a pharmaceutical.

Production

Production of nicotinamide mononucleotide has been redacted since the latter half of 2022 by the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

because it is under investigation as a pharmaceutical drug.

Different expressions of NMN across human organs

The synthesizing enzymes and consumption enzymes of NMN also exhibit tissue specificity: NMN is widely distributed in tissues and organs throughout the body and has been present in various cells since embryonic development.

Potential benefits and risks

NMN is a precursor for NAD⁺ biosynthesis, and NMN dietary supplementation has been demonstrated to increase NAD⁺ concentration and thus has the potential to mitigate aging-related disorders such as

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified ...

neurodegeneration A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their cell death, death. Neurodegenerative diseases include amyotrophic lateral sc ...

and inflammatory responses. The potential benefits and risks of NMN supplementation, as of 2023, are currently under investigation. Certain enzymes are sensitive to the intracellular NMN/ NAD⁺ ratio, such as

SARM1 Sterile alpha and TIR motif containing 1 Is an enzyme that in humans is encoded by the ''SARM1'' gene. It is the most Conserved sequence, evolutionarily conserved member of the Toll-Interleukin receptor, Toll/Interleukin receptor-1 (TIR) family. ...

, a protein responsible for initiating cellular degeneration pathways such as

MAP kinase A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of serine/threonine-specific protein kinases involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflammato ...

and inducing

axon An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...

al loss and neuronal death. NMNAT is an enzyme with neurorescuing properties that functions to deplete NMN and produce NAD⁺, attenuating SARM1 activity and aiding neuronal survival ''in vitro'', an effect that is reversed by applying exogenous NMN which promptly resumed axon destruction. The similar molecule nicotinic acid mononucleotide (NaMN) opposes the activating effect of NMN on

, and is a neuroprotector.

References

{{reflist Nucleotides Ribosides Nicotinamides Anti-aging substances