4 NAD+ Precursors You Need to Know --- NA,NAM,NR,NMN
This is a form of vitamin B3 and is also known as niacin, a word sometimes used as an umbrella term for all vitamin B3s. Nicotinic acid was discovered by a chemist studying nicotine, and the name was changed to niacin in order to differentiate it from tobacco. NA is commonly known to cause flushing. Since the 1940s, NA has been used to fortify flours and rice all over the world because of its benefits. NA makes its way to NAD+ via the Preiss-Handler pathway, which also consolidates the chemically transformed tryptophan (an amino acid NAD+ precursor) to become NAD+.
This is a form of vitamin B3 and is sometimes referred to as niacinamide (again, renamed to disassociate it from the tobacco family of nicotine). Nam goes through the same salvage pathway as NR but has to stop at the rate-limiting step that NR can bypass before it becomes NAD+. Nam is also involved in the salvaging part of the pathway. When NAD+-consuming enzymes, like sirtuins (a family of proteins that regulate cellular health) use NAD+, they split it into parts, using what they need then sending the Nam back through the pathway to create more NAD+.
Nicotinamide riboside, or niagen, is an alternative form of vitamin B3, also called niacin. Like other forms of vitamin B3, nicotinamide riboside is converted by your body into nicotinamide adenine dinucleotide (NAD+), a coenzyme or helper molecule.
NAD+ acts as fuel for many key biological processes, such as
Converting food into energy
Repairing damaged DNA
Fortifying cells’ defense systems
Setting your body’s internal clock or circadian rhythm
However, the amount of NAD+ in your body naturally falls with age. Low NAD+ levels have been linked to health concerns like aging and chronic illnesses, such as diabetes, heart disease, Alzheimer’s disease and vision loss. Interestingly, animal research has found that raising NAD+ levels may help reverse signs of aging and lower the risk of many chronic diseases. Nicotinamide riboside supplements — such as niagen — have quickly become popular because they appear to be especially effective at raising NAD+ levels.
NMN belongs to the family of nucleotides, organic molecules found in most of the foods we eat. As with all nucleotides, NMN is composed of 3 parts: a nitrogenous base, a sugar, and a phosphate group. While most nucleotides are used to build DNA, NMN is used to make nicotinamide adenine dinucleotide (NAD) and fine-tune energy balance. The body creates NMN as an intermediate step or “precursor” to NAD. Put simply: higher NMN levels mean higher NAD levels. NAD increases the body’s main energy currency (ATP), balances the circadian rhythm, and enables hundreds of enzymatic reactions – many of which delay aging. Levels of NAD, especially its NAD+ form, naturally decrease with age in many tissues.
The reason we are talking about NAD "precursors" is because although NAD is abundant in the food we eat, "it has been shown that NAD is unable to cross the mitochondrial membrane," which means that consuming NAD directly does not replenish mitochondrial NAD. Instead, we must ingest precurors to NAD, which are small enough to enter the cell and can then be assembled into NAD inside the cells.
That means expensive products like this one, which offer pure NAD directly, probably cannot replenish mitochondrial NAD and probably are a waste of money.
Pure NAD probably won't help you much. Instead, you need an NAD precursor, like Nicotinamide Riboside or NMN. It may be "the EXACT NAD+ enzyme that your cells need more of" and it may be "absorbed directly to the bloodstream," like it says on the listing, but unless it can also enter the mitochondria, it won't do what you are hoping for.
All tissues produce NAD+ from nicotinamide (NAM) or the recently identified NAD+ precursor, nicotinamide riboside (NR) Some tissues can produce NAD+ from tryptophan de novo and nicotinic acid (NA), although the generation of NAD+ from tryptophan is much less efficient than from the vitamin precursors of NA, NAM, or NR, which are collectively termed vitamin B3. NAD+ can also be supported by dietary precursors. For example, pellagra, a disease of deficiency of NAD+ precursors, can be prevented or treated with approximately 15 mg/day of NA or NAM or with 60-times as much tryptophan. Importantly, despite homeostatic systems and dietary intake of NAD+ precursors, it is now known that the levels of NAD+ co-enzymes are continuously challenged by metabolic stress. In the overfed and type 2 diabetic mouse livers, levels of NADPH are strikingly depressed, whereas in noise-induced hearing loss, heart failure, peripheral nerve damage, central brain injury and the liver of a lactating mouse, NAD+ levels are compromised. Moreover, NAD+ levels have been reported to decline in response to DNA damage, alcohol metabolism, and aging, and the expression of nicotinamide phosphoribosyltransferase (NAMPT), the enzyme required for NAM salvage, declines with aging and chronic inflammation. Thus, considering the relationships between NAD+, metabolic stress and aging, nutritional scientists are now investigating whether the ingestion of higher levels of a B3 vitamin should be part of an evidence-based approach to optimize health.
Although NA, NAM, and NR all produce NAD+ and NADP+, it is important to note that each precursor has unique effects physiologically. NA can lower blood lipids and is used to treat dyslipidemia. At doses of greater than 50 mg/day, NA can also induce flushing. In contrast, NAM does not lower blood lipids or cause flushing, has been reported be a sirtuin inhibitor at high doses, and appears to have a greater effect at elevating blood levels of homocysteine (HCY) in humans than NA via its metabolism to 1-methylnicotinamide (MeNAM). In yeast, NR activates SIR2 and extends replicative lifespan. In mouse models, NR prevents high-fat diet-induced weight gain, fatty liver and diabetic peripheral neuropathy, noise-induced hearing loss, heart failure, and central brain injury. In addition, oral NR greatly improves survival and hematopoietic stem cell regeneration after irradiation of mice—an activity that was not seen in NA or NAM supplemented mice. In rats, oral NR promotes resistance to and reversal of chemotherapeutic neuropathy. In mice, oral NR increases the hepatic levels of the NAD+ metabolome with pharmacokinetics that are superior to that of NA and NAM. In addition, postpartum female mice and rats who were administered NR exhibited increased lactation and produced offspring that are stronger, less anxious, have better memory, and have enhanced adult hippocampal neurogenesis and body composition as adults. Because NR does not cause flushing or inhibit sirtuins and the genes (NRK1 and NRK2) required for the metabolism of NR to NAD+ are upregulated in conditions of metabolic stress, NR has a particularly strong potential as a distinct vitamin B3 to support human wellness during metabolic stress and aging.
In a variety of animal models, nicotinamide mononucleotide (NMN), the 5′-phosphorylated form of NR, has also shown promise in conditions of metabolic stress and aging. Moreover, the gut-expressed multispanning membrane protein Slc12a8, previously annotated as a Na+/K+ Cl− transporter, has been proposed to be a specific transporter of nicotinamide mononucleotide (NMN).
If you are looking to buy Nicotinamide Mononucleotide(NMN) powder in bulk, the best place to buy NMN powder is cofttek.com. Cofttek is a high-tech pharmaceutical enterprise that has been providing innovative and high-quality products since 2008. The company boasts of an impressive R&D team with experienced individuals committed to the development of competitive products. Cofttek has partners and supplies its products to pharmaceutical companies in China, Europe, India, and North America. The β-Nicotinamide Mononucleotide supplied by Cofttek is of very high-quality and completely safe for human consumption. More importantly, the company supplies this powder in bulk, i.e. in units of 25kgs. Thus, if you are looking to buy this powder in bulk, Cofttek is the company you should contact — they are the best Nicotinamide Mononucleotide (NMN) powder supplier in the market.
References
4. Artegiani B., Calegari F. (2012). Age-related cognitive decline: can neural stem cells help us? Aging 4 176–186. 10.18632/aging.100446
5. Assiri M. A., Ali H. R., Marentette J. O., Yun Y., Liu J., Hirschey M. D., et al. (2019). Investigating RNA expression profiles altered by nicotinamide mononucleotide therapy in a chronic model of alcoholic liver disease. Hum. Genomics 13:65. 10.1186/s40246-019-0251-1