A Look at NMN: The Basics, Benefits, and Recent Research

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NMN is important for overall health and promoting longevity.

Nicotinamide mononucleotide, or NMN, is an important compound for promoting longevity and overall health. One of the most well-known functions of NMN is its ability to be rapidly converted into NAD (nicotinamide adenine dinucleotide). 

NAD (also known as NAD+ when in its oxidized form) is a coenzyme found in every cell in the body. However, it is known to decline with age. Keeping NAD+ levels elevated, especially in later life, can lead to healthier cells, anti-aging benefits, and reductions in the risk of developing various diseases. 

NMN: The Basics

As NMN is a precursor to NAD+, providing the body with ample amounts of NMN is an effective way to boost the age-related decline seen with NAD+. 

Maintaining NAD+ levels can reduce cellular aging and reduce the risk of chronic diseases. The coenzyme is also involved with regulating sirtuins, which are a family of proteins that play a crucial role in longevity. 

It was previously thought that NMN had to be converted first into NR (nicotinamide riboside). However, it was discovered in 2019 that a specific NMN transporter called Slc12a8 allows for NMN to directly enter cells and convert into NAD+ rapidly. 

NR is also a precursor to NAD+. Both NMN and NR are able to effectively boost the levels of NAD+. As these molecules are relatives of vitamin B3 (niacin), they are found in some foods, although the concentrations are very small compared to supplemental form.

Benefits of NMN and Recent Research 

Other than directly boosting levels of NAD+, NMN has also been studied for its effects on reducing various diseases and improving health markers. So far, all of the studies on health outcomes have been done with animals, as human clinical trials are still in their infancy. 

1. Promoting Longevity 

The most well-known benefit of NMN involves its effects on promoting longevity. As we age, energy production and mitochondrial function decrease, which is in large part due to the parallel decline in NAD+ in various cells and organs in the body.

Aging cells are eventually forced into cellular senescence, which means the cells stop dividing and lose function; senescence plays a major role in the aging and disease process. The effects of cellular senescence can be mitigated through increasing NAD+ levels with supplemental NMN. 

As NMN is a primary precursor to NAD+, supplementing with it can be a beneficial way to reduce the cellular and mitochondrial decline and dysfunction that occurs with age.

NMN can increase longevity and reduce the risk of disease

2. Improved Cognitive Function

NMN has been shown to improve markers of cognition and underlying causes of Alzheimer’s disease (AD). In neurodegenerative disorders like AD, a reduction in NAD+ in the brain leads to impaired mitochondrial function. Replenishing NAD+ stores through NMN can help to prevent this. 

NMN has also been found to inhibit amyloid growth in a study published in Brain Research in April 2016; the buildup of amyloid plaques is a hallmark characteristic of AD pathology. 

In a study published in June 2019 in Redox Biology, older mice who received supplemental NMN had improvements in neurovascular health, spatial working memory, and gait coordination. 

As microvascular dysfunction plays a large role in the development and progression of cognitive decline, improving neurovascular health through NMN may have both preventive and therapeutic potential for conditions like dementia and AD. 

3. Obesity Reduction

Although obesity can occur at any age, older adults are particularly susceptible to age-related weight gain as metabolism slows down, and body composition is altered to favor fat over lean muscle. 

Obese individuals have reductions in both NAD+ levels and ATP production; replenishing NAD+ through NMN can help to reverse this while improving metabolic pathways to maintain a healthy weight. 

In a December 2016 study published in Cell Metabolism, mice who received either 100 or 300 mg/kg dose of NMN for 12 months had reductions in body weight by 4% and 9%, respectively. NMN did not decrease appetite. Rather, it  worked by increasing energy expenditure and oxygen consumption.  

As obesity is a major risk factor for several other chronic diseases, including diabetes, heart disease, dementia, and cancer, NMN may be a helpful way to reduce that risk. 

4. Improved Metabolic Markers

NMN may improve metabolic markers of diabetes.

Metabolic markers that tend to be altered with age include glucose and insulin control and lipid profiles, which are risk factors for diabetes and heart disease. 

In the previously mentioned 2016 study in Cell Metabolism, the mice who were NMN-supplemented for 12 months had significantly improved insulin sensitivity compared to controls that matched their body weight. 

A similar study found that supplementing diabetic mice with NMN led to significantly improved glucose tolerance, enhanced NAD+ concentrations, and improved insulin sensitivity. 

However, short-term NMN supplementation did not result in improvements in fasting glucose, indicating that a longer supplementation period may be needed to see the benefits. 

5. Improved Reproductive Health 

A recent study, published in Cell Reports in February 2020, found that reproductively-aged female mice who received a low dose of NMN had increased birth rates and a reduction in time to get pregnant, as well as improvements in IVF outcomes. Read more about the results from that study here

As obesity is a risk factor for infertility, some of the benefits of NMN supplementation on reproductive health could be tied to its obesity-reducing properties. 

The Different Supplemental Forms of NMN

There are four main methods in which NMN can be taken:

1. Powder

You can take NMN powder by mixing it into water or another liquid. This method allows you to self-administer whichever dose of NMN you prefer. A recommended direction is to allow the powder to dissolve directly under the tongue for optimal absorption. 

2. Sustained-Release Tablets

The acid-resistant tablets allow for a slower release of NMN, which could lead to NAD+ levels being elevated for a longer period of time. The slower release would also allow for NMN to be in the small intestine for longer; the NMN transporter Slc12a8 is mainly found in this area. 

3. Capsules

Capsules are your typical supplement form; this method also allows for a slower release of NMN into the bloodstream.

4. Lozenges

Lozenges avoid the gastrointestinal tract, being fully dissolved under the tongue. This leads to NMN being quickly absorbed into the blood vessels in the mouth.

Safety and Side Effects of NMN

As all of the studies on NMN and health outcomes have been studied with animals, you may be wondering, is the compound safe for humans? 

A study published in Endocrine Journal in February 2020 concluded that, yes, NMN is safe for humans. Single doses of 100, 250, and 500 mg of NMN were all found to be effectively metabolized and safe in a clinical trial.

NMN has not been found to show any major side effects, unlike some of its relatives. Niacin, or nicotinic acid, commonly results in a “niacin flush,” with red, warm, and itchy skin being a common side effect of high doses. 

Although adverse effects have not been found, more clinical trials with humans are needed to fully understand the benefits of NMN on health and disease outcomes.

Key Takeaways:

  • NMN is a precursor to NAD+, which is a necessary coenzyme in all cells of the body that decreases with age and is responsible for many age-related diseases. 
  • The main benefits of supplemental NMN include promoting longevity, reducing obesity, and improving metabolic markers, cognitive function, and reproductive health. 
  • NMN can be taken in several ways, including powder, lozenges, and capsules, and has been shown to be safe for humans to take.

Show references

Bertoldo MJ, Listijono DR, Ho WJ, et al. NAD+ Repletion Rescues Female Fertility during Reproductive Aging. Cell Rep. 2020;30(6):1670–1681.e7. doi:10.1016/j.celrep.2020.01.058

Irie J, Inagaki E, Fujita M, et al. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocr J. 2020;67(2):153–160. doi:10.1507/endocrj.EJ19-0313

Mills KF, Yoshida S, Stein LR, et al. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab. 2016;24(6):795–806. doi:10.1016/j.cmet.2016.09.013

Poddar SK, Sifat AE, Haque S, Nahid NA, Chowdhury S, Mehedi I. Nicotinamide Mononucleotide: Exploration of Diverse Therapeutic Applications of a Potential Molecule. Biomolecules. 2019;9(1):34. doi:10.3390/biom9010034

Tarantini S, Valcarcel-Ares MN, Toth P, et al. Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice. Redox Biol. 2019;24:101192. doi:10.1016/j.redox.2019.101192

Wang X, Hu X, Yang Y, Takata T, Sakurai T. Nicotinamide mononucleotide protects against β-amyloid oligomer-induced cognitive impairment and neuronal death. Brain Res. 2016;1643:1–9. doi:10.1016/j.brainres.2016.04.060

Yoshino J, Baur JA, Imai SI. NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. 2018;27(3):513–528. doi:10.1016/j.cmet.2017.11.002

Yoshino J, Mills KF, Yoon MJ, Imai S. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab2011;14(4):528–536. doi:10.1016/j.cmet.2011.08.014

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