What are the differences between nicotinamide riboside and nicotinamide mononucleotide

What

is

nicotinamide

mononucleotide

(NMN)?

Nicotinamide mononucleotide (NMN) belongs to the family of B3 vitamins. The molecule is the immediate precursor of NAD + and is involved in the biosynthesis of NAD + in all living things.

NMN helps maintain cellular levels of NAD+, thereby facilitating NAD+-dependent cellular activities, such as mitochondrial metabolism, regulation of sirtuins, and PARP activity. Animal studies have demonstrated that NMN administration is effective in increasing NAD+ levels across multiple tissues while improving the outcome of a variety of age-related diseases. Although NMN administration has proven to be safe and to effectively increase NAD+ levels in rodents, the safety and efficacy of NMN supplementation in humans remain unknown. NMN is available in supplement form and is present in various types of food, including broccoli, avocado, and beef. It is also an intermediate compound in the NAD+ salvage pathway, the recycling of nicotinamide into NAD+

What

is

nicotinamide

riboside

(NR)

chlorine?

Nicotinamide Riboside (NR) chloride (NIAGEN) is a derivative of NR and chlorine. The compound augments the levels of NAD+ and activates SIRT1 and SIRT3. It reverses aging by enhancing oxidative metabolism and countering diet-related metabolic comorbidities.

How NMN and NR become NAD+ in cells Nicotinamide riboside (NR) chloride and nicotinamide mononucleotide (NMN)

supplements are both support the production of NAD+, there are differences in how they work and the science behind them.

Scientists have studied two such intermediates, nicotinamide riboside (NR) chloride and Beta-Nicotinamide mononucleotide, 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(NR) 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.

Differences between NMN and NR

Similarites

Differences

NMN and NR utilize the salvage pathway of NAD+ biosynthesis to boost NAD+ in cells

NMN is a larger molecule than NR

studies indicate NMN and NR are safe for human consumption

NMN is the immediate precursor to NAD+; NR requires conversion to NMN via an enzyme (NRK) before converting to NAD+

NMN and NR need to be kept in the cold to avoid degradation

NMN has a specific transporter in mice

NAD+ precursor of NR and NMN NAD+ precursor of NR NR is first converted to nicotinamide mononucleotide (NMN), which is then converted to NAD+.

NAD+ precursor of NMN NMN is a direct precursor of NAD+. NMN can be made from either NR or nicotinamide.

Safety of NMN and NR Whenever an individual starts consuming a supplement, safety is a primary concern.

According to studies performed thus far, no safety concerns exist for NMN or NR consumption. The following will review a few studies of safety of NMN and NR. Studies of NMN safety One study in people showed that a single dose of up to 500 mg NMN didn't cause any serious side effects. Scientists in this study find no changes in heart rate, blood pressure, oxygen saturation, or body temperature. As the authors of the study state, “The single oral administration of NMN was safe and effectively metabolized in healthy men without causing any significant deleterious effects.”

Studies of NR safety Oral NR up to 1,000 milligrams a day is well tolerated, with no flushing or serious side effects, even after several weeks. Higher amounts, such as 1,000 milligrams twice a

day, may cause side effects such as itchiness, sweating, bloating, and temporary changes in stools.

Bioavailability of NMN and NR Bioavailability relates to the proportion of a substance entering blood circulation when administered to the body which has an active effect. Indicators of bioavailability include levels of NMN or NR in the blood following NMN or NR administration. One can also use levels of NAD+ in blood following NMN or NR administration as an indicator of bioavailability.

The majority of research on bioavailability of NAD+ precursors has been conducted on NR. In fact, only studies conducted on NR and bioavailability include human subjects. Scientists have conducted studies of NMN bioavailability in rodents.

Studies of NMN bioavailability NMN supplements can support NAD+ levels in various tissues, including the brain; these studies were done in rodents. No studies have looked at its effect on NAD+ levels in people.

A study using mice finds blood plasma NMN levels increase substantially with oral NMN administration of 300 mg/kg. Peak levels of NMN in blood plasma occur around 10 minutes after NMN administration. Following NMN administration, NAD+ levels rise significantly within 30 minutes.

Studies of NR bioavailability A study on the bioavailability of NR finds human blood NAD+ can increase up to 2.7-fold with a single, oral dose of NR in one individual evaluated. The same study reveals a dose-dependent increase in blood NAD+ levels with 100, 300, and 1000 mg single doses of NR. A more recent study on longer-term effects of NR indicates NAD+ levels increase dose-dependently at 100, 300, and 1000 mg NR doses. The increases in NAD+ levels are approximately 22%, 51%, and 142% for each dose, respectively, within two weeks of supplementation.

Oral NR supplements can support NAD+ levels in human blood and skeletal tissue.

Clinical trials of NR and NMN Clinical trials of NR Several clinical trials of NR have been completed, including "gold standard" randomized placebo-controlled trials (RCTs).

Clinical trials of NMN The results of only one NMN clinical trial in people have been published. Other clinical trials of NMN in the United States and other countries are currently underway or have recently been completed.

Commercial supplements of NR and NMN Commercial supplements of NR Several NR supplement products are available, including in powder and capsule form.

Commercial supplements of NMN A small number of NMN supplement products are available in powder and capsule form.

Stability and storage of NMN and NR After an individual decides to consume NMN or NR as a safe and effective method for boosting NAD+ levels, he/she must know how to store it.

A stability analysis demonstrates NR is stable (does not undergo degradation) for up to six hours at room temperature and seven days at two to eight degrees Celsius.

Regarding stability of NMN and NR, David Sinclair, PhD, A.O. of Harvard University says, “Make sure your NR and NMN is kept in the cold. If it’s just on the shelf and it’s not in a stabilized form, then it will degrade to nicotinamide, which is something you don’t want to take high doses of because we’ve shown in my lab many years ago that nicotinamide will inhibit the sirtuins, and PARP as well, and interfere with DNA repair.”

Why We Need NR and NMN?

NR and NMN are both beneficial because they elevate levels of NAD+, which decline with age.

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.

Conclusion/Summary Research indicates nicotinamide mononucleotide (NMN) and Nicotinamide riboside (NR) chloride consumption can increase NAD+ levels safely and effectively through aging.

As the results of the NMN clinical trials that are currently underway are published, it will become clearer whether NMN will work as a supplement for healthy aging.

To demonstrate this, scientists have conducted human safety and bioavailability studies for NR; and scientists have performed a safety study in humans along with bioavailability studies of NMN primarily on rodents. Future bioavailability studies of these two biosynthetic precursors to NAD+ will reveal which of them is better for increasing concentrations of NAD+ in cells.

Reference: [1] Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ Metabolism. Hong W, Mo F, Zhang Z, Huang M, Wei X. [2] Subacute Toxicity Study of Nicotinamide Mononucleotide via Oral Administration.

You Y, Gao Y, Wang H, Li J, Zhang X, Zhu Z, Liu N. [3] Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Irie J,

Inagaki E, Fujita M, Nakaya H, Mitsuishi M, Yamaguchi S, Yamashita K, Shigaki S, Ono T, Yukioka H, Okano H, Nabeshima YI, Imai SI, Yasui M, Tsubota K, Itoh H. [4] Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Conze D, Brenner C, Kruger CL. [5] Safety of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283 and bioavailability of nicotinamide from this source, in the context of Directive 2002/46/EC. EFSA Panel on Nutrition, Novel foods and Food allergens (NDA), Turck D, Castenmiller J, de Henauw S, Hirsch-Ernst KI, Kearney J, Maciuk A, Mangelsdorf I, McArdle HJ, Naska A, Pelaez C, Pentieva K, Siani A, Thies F, Tsabouri S, Vinceti M, Cubadda F, Engel KH, Frenzel T, Heinonen M, Marchelli R, Neuhäuser-Berthold M, Pöting A, Poulsen M, Sanz Y, Schlatter JR, van Loveren Agnès de Sesmaisons-Lecarré H, Germini A, Knutsen HK. [6] Safety assessment of nicotinamide riboside, a form of vitamin B(3). Conze DB, Crespo-Barreto J, Kruger CL. [7] NAD(+) Intermediates: The Biology and Therapeutic Potential of NMN and NR. Yoshino J, Baur JA, Imai SI. [8] Reversal of endothelial dysfunction by nicotinamide mononucleotide via extracellular conversion to nicotinamide riboside. Mateuszuk Ł, Campagna R, Kutryb-Zając B, Kuś K, Słominska EM, Smolenski RT, Chlopicki S. [9] NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. Ratajczak J, Joffraud M, Trammell SA, Ras R, Canela N, Boutant M, Kulkarni SS, Rodrigues M, Redpath P, Migaud ME, Auwerx J, Yanes O, Brenner C, Cantó C.