Longevity Articles

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

NMN is important for overall health and promoting longevity.

Updated on 1/26/23 by Cambria Glosz, MS, RD

Nicotinamide mononucleotide, or NMN, is a promising compound that is rising in popularity for its role in supporting longevity and overall health with age. One of the most well-known NMN benefits is its ability to be rapidly converted into NAD+ (nicotinamide adenine dinucleotide) — a vital coenzyme needed by every cell in our bodies.

Despite its essentiality, NAD+ levels are known to decline with age, which increases the risk of accelerated aging and the development or progression of age-related disorders. Keeping NAD+ levels elevated, especially in later life, may help to slow down aspects of the aging process and keep our cells and organs healthy with each passing year.

The Leading Benefits of NMN

Other than directly boosting levels of NAD+, NMN has also been studied for its effects on improving health markers that commonly deteriorate with age. Although most of the studies on NMN have been done with animals or cell-based cultures, some recent trials have tested the compound’s effects in humans — and with beneficial results. 

1. Supporting Longevity 

As we age, the function of our mitochondria — our cells’ energy production centers — decreases, which is in large part due to the corresponding decline in NAD+ levels. Aging cells are eventually forced into a state called cellular senescence, which means the cells stop dividing and lose function. But senescent cells don’t leave the body — they remain in a “zombie-like” state that creates a damaging cascade of inflammatory compounds, playing a significant role in the aging process. 

As NMN is a primary precursor to NAD+, supplementing with it could be a beneficial way to reduce the cellular and mitochondrial decline and dysfunction that occurs with age. While human longevity studies take decades — and millions — to complete, we do have some research with animals to back up these claims. 

Studies have demonstrated that boosting NAD+ synthesis in the body extends the lifespan of yeast, worms, and flies. In rodents, some research has found that supplemental NMN can mitigate both the drop in NAD+ levels and the concurrent physiological decline of these organs that leads to age-related disorders. However, we will need clinical trials before we can state definitively if NMN can extend lifespan in humans.

NMN can increase longevity and reduce the risk of disease

2. Supports Cognitive Function

A reduction in brain NAD+ levels can lead to impaired mitochondrial function, which is thought to be a cause of declining cognitive function with age. Replenishing NAD+ stores through NMN benefits cognition and so may be able to prevent this dysfunction.

NMN has been found to inhibit the buildup of beta-amyloid plaques that are indicative of some neurological conditions, a study published in Brain Research shows. A study published in June 2019 in Redox Biology found that older mice who received supplemental NMN had improvements in spatial working memory, gait coordination, and neurovascular health — another important component of brain function. 

The brain constantly receives nutrients and oxygen through its network of blood vessels called the neurovascular system — and the function of this system markedly declines with age and leads to cognitive decline. In an April 2020 study, researchers found that NMN benefits the health and integrity of both the cerebral blood flow system and the brain as a whole, leading to neurovascular rejuvenation in a group of aged mice. Therefore, improving neurovascular health through NMN may have great potential for supporting neurological conditions. 

3. Healthy Weight Management

Although excessive body weight can develop 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. As obese individuals have reductions in both NAD+ levels and ATP (energy) production, replenishing NAD+ through NMN can help to reverse this while improving metabolic pathways to maintain a healthy weight. 

In a 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 reduce weight by causing an appetite decrease — rather, it worked by increasing energy expenditure and oxygen consumption.  

As excess body weight is a major risk factor for several other chronic conditions, NMN may be a helpful way to support weight management and overall health.

NMN is linked to healthier aging; older adults rollerblading

4. Improved Metabolic Markers and Physical Health 

Metabolic markers that tend to be altered with age include glucose and insulin control and lipid profiles, which are prominent risk factors for disrupted metabolic health.

Notably, the first human trial of its kind — published in April 2021 in the journal Science — demonstrated that an NMN supplement benefits several markers of skeletal muscle glucose metabolism that are commonly dysregulated in people with metabolic disorders. While there are a couple of limitations to this study, including the small sample size and specific subset of postmenopausal, prediabetic, and overweight or obese women, this trial is groundbreaking in that it was the first one of its kind to study the metabolic NMN supplement benefits in humans. 

Similarly, a January 2022 study published in the journal Nutrients looked at the effects of 250 mg of NMN per day on elderly adults’ sleep quality, fatigue, and physical performance. They were divided into four groups: NMN morning intake and afternoon intake; placebo morning and afternoon intake.  They found that adults taking NMN in the afternoon intake showed the greatest improvement in lower limb motor function and sleepiness. These findings suggest that afternoon NMN intake may be more effective in improving lower limb function and reducing sleepiness in the elderly and may be beneficial for mental and physical health.

Animal studies have also proved NMN benefits metabolic health. In the previously mentioned 2016 study in Cell Metabolism, 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 mice with NMN led to significantly improved glucose tolerance, enhanced NAD+ concentrations, and better insulin sensitivity. 

5. Supports Reproductive Health 

A 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, a reduction in time to get pregnant, and improvements in IVF outcomes. As excess body weight is a risk factor for infertility, some of the benefits of NMN supplementation on reproductive health could be tied to its weight-managing properties. 

A similar study found that supplementing aged female mice with a lower dose of 200 mg/kg NMN, as opposed to 1000 mg/kg, restored NAD+ levels in their oocytes (immature egg cells). This lower dose of NMN benefits oocyte quality and maturation, increased birth rates, recovered mitochondrial function, and reduced the accumulation of damaging free radical compounds — all of which support fertilization and healthy pregnancy.

If these results were to translate to humans, it would suggest that NMN supplement benefits could translate to helping women well into their 50s maintain viable pregnancies. In the future, we may see that low-dose NMN supplements could be a non-invasive and low-risk way to increase fertility and support pregnancies with increasing age. While promising, we’ll have to wait for the human clinical trials to see if NMN supplement benefits do indeed improve fertility in the middle-aged and beyond. 

Safety, Efficacy, and Side Effects of NMN

Although most of the research on NMN has been done with animals or cells, a few studies in recent years have verified its safety in humans. 

The first was a study published in Endocrine Journal in February 2020, which concluded that acute NMN administration was safe for human consumption. Single doses of 100, 250, and 500 mg of NMN were all found to be effectively metabolized and safe in a clinical trial with healthy adult males.

A more recent study from April 2022 showed that healthy volunteers who received 250 mg/day of NMN for 12 weeks caused no abnormalities in physiological and laboratory tests and no obvious adverse effects. NAD+ levels in whole blood were significantly increased after NMN administration. They also found that the increased amount of NAD+ was strongly correlated with pulse rate before the administration of NMN. These results suggest that oral administration of NMN is a safe and practical strategy to boost NAD+ levels in humans.

In May 2022, research from Effepharm, a company out of Shanghai, China, came out with clinical results from 66 healthy subjects between the ages of 40 and 65 who took two capsules containing 150 mg of NMN daily after breakfast for 60 days. The study reported results suggesting a rise in the levels of available NAD+ at day 30 and day 60, which they suggest illustrated the potential of NMN to raise the levels of NAD+ in humans. 

Lastly, the latest findings come from a June 2022 study that showed postmenopausal women who consumed NMN 300 mg/day orally for eight weeks had no safety issues. Plus, the researchers found that NMN supplementation led to favorable changes in various biomarkers (i.e., blood biochemistry, glucose metabolism, lipid metabolism, hormones, and immunity) measured as clinical tests.

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

How to Take NMN: Is Liposomal Best? 

While there are several ways to take NMN, including capsules, powders, lozenges, and tablets, supplementing with liposomal NMN may be the most effective. Liposomes are nano-sized bubbles with a unique molecular structure that acts as a delivery vehicle to facilitate the transport of drugs, nutrients, or compounds into the body. 

Liposomes consist of a double layer of phospholipids surrounding a liquid center. These structures have a water-based center, so the second layer of phospholipid heads lines up to face the inside of the bubble. The double-layered bubble safely protects the compound inside, allowing it to travel through the harsh digestive tract and bloodstream until it meets our cells. From there, the liposome merges with our cell membranes and releases the inner nutrient contents into the cell.

The body recognizes and accepts liposomal structures because they are phospholipid-based, mimicking our own cell membranes. This means that compounds can be directly delivered into cells without fearing degradation or excretion in the urine before utilization.

While we don’t have research yet looking at the absorption rates of liposomal NMN, studies on vitamin C have found that liposomal vitamin C increased bioavailability by 75% compared to non-liposomal vitamin C supplements. 

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 conditions. 
  • The main benefits of supplemental NMN include supporting longevity, healthy body weight, metabolic markers, cognitive function, and reproductive health. 
  • NMN has been shown to effectively raise NAD+ levels in the blood and has not exhibited significant adverse effects in humans. 

     


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    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

    Fang EF, Kassahun H, Croteau DL, et al. NAD+ Replenishment Improves Lifespan and Healthspan via Mitophagy and DNA Repair. Cell Metab. 2016;24(4):566-581. doi:10.1016/j.cmet.2016.09.004

    Gopi S, Balakrishnan P. Evaluation and clinical comparison studies on liposomal and non-liposomal ascorbic acid (vitamin C) and their enhanced bioavailability. J Liposome Res. 2021;31(4):356-364. doi:10.1080/08982104.2020.1820521

    Huang H. A Multicentre, Randomised, Double Blind, Parallel Design, Placebo Controlled Study to Evaluate the Efficacy and Safety of Uthever (NMN Supplement), an Orally Administered Supplementation in Middle Aged and Older Adults. Front Aging. 2022;3:851698. Published 2022 May 5. doi:10.3389/fragi.2022.851698

    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

    Kim M, Seol J, Sato T, Fukamizu Y, Sakurai T, Okura T. Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study. Nutrients. 2022;14(4):755. Published 2022 Feb 11. doi:10.3390/nu14040755

    Miao Y, Cui Z, Gao Q, Rui R, Xiong B. Nicotinamide Mononucleotide Supplementation Reverses the Declining Quality of Maternally Aged Oocytes. Cell Rep. 2020;32(5):107987. doi:10.1016/j.celrep.2020.107987

    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

    Okabe K, Yaku K, Uchida Y, et al. Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects. Front Nutr. 2022;9:868640. Published 2022 Apr 11. doi:10.3389/fnut.2022.868640

    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 Metab. 2011;14(4):528–536. doi:10.1016/j.cmet.2011.08.014

    Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;eabe9985. doi:10.1126/science.abe9985



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