Nicotinamide mononucleotide (NMN) has gained a lot of attention both in the scientific community and among anti-aging enthusiasts over the last years. Now, it’s considered to be one of the most promising anti-aging compounds known to science, but what exactly do we know so far?
What does the available evidence say? Is NMN safe to take? What’s the best dosage for anti-aging? What benefits can you expect from it?
Before we dig into the exciting details (with references to all the best studies) on the potential of NMN for anti-aging, let’s take a moment to check the fundamentals of what is aging, to begin with.
Latest update: July 13 – we added a link to our newest article on amazing NMN combinations with resveratrol and ginsenosides!
Molecular Mechanisms of Aging
Aging is a complex biological process characterized by a progressive decline in all functions of the body, along with a gradual rise in susceptibility to all sorts of diseases.
But what are the underlying molecular mechanisms of growing old?
One of the best overviews was proposed by López-Otín and colleagues, who identified 12 molecular hallmarks of aging: (1)
- Genomic instability, meaning an increased risk of DNA mutations
- Shortening of the telomeres (DNA sequences at the end of the chromosomes)
- Epigenetic alterations (changes in DNA structure that don’t affect the DNA coding sequence)
- Loss of protein homeostasis (accumulation of misfolded, damaged proteins)
- Impaired macroautophagy (removal of unnecessary or dysfunctional components within the cell)
- Deregulated sensitivity to nutrients
- Worsening of mitochondrial function
- Cellular senescence (aging)
- Exhaustion of stem cells
- Altered communication and interaction between cells
- Chronic, persistent inflammation
- Dysbiosis (imbalance in the species of microorganisms in the body)
Of course, NMN isn’t a be-all and end-all solution to all the mechanisms of aging at once. It’s not a magic pill of eternal youth. But so far it seems that NMN for anti-aging purposes could be fairly effective for improving DNA repair and supporting healthy energy metabolism within the cells.
The potential benefits of NMN for anti-aging are based on the function of nicotinamide adenine dinucleotide (NAD+) in the body, along with its dramatic decline over the years.
The Link Between NAD+ Decline and Aging
NAD+ is an essential coenzyme for energy metabolism, DNA repair, and gene expression. All living cells in all organisms have NAD+.
Basically, life as we know it is pretty much impossible without NAD+.
The bad news is that NAD+ levels plummet with age. This process has been linked to a wide range of diseases including cancer, cognitive decline, and various metabolic issues. Restoring NAD+ levels can often slow down or even reverse these conditions. (2) NMN is a precursor to NAD+, so it could be useful for supporting or restoring NAD+ levels and counteracting aging.
But how severe is this NAD+ decline to begin with?
By the time a human reaches their middle age, their NAD+ levels have dropped to half (or even lower) of what they had in their youthful years. (3) The worst part is that the downfall doesn’t stop at that. At age 60 and older, NAD+ concentrations in the liver have been shown to be about 30% lower compared to samples from younger subjects, aged below 45. (4)
That’s exactly why scientists all around the world are so excited about the potential of NAD+ and its precursors like NMN for anti-aging. So far, the findings are extremely promising.
NMN for Anti-Aging: What Is It and How Does It Work?
In a nutshell, nicotinamide mononucleotide (NMN) is a precursor for NAD+.
Effective NAD+ supplements don’t exist, so the only way to increase your levels of NAD+ is to take a NAD+ precursor like NMN.
In your body, NMN is transported into the cells through specific transporters, like the SLC12A8, an NMN transporter found in abundance within the small intestine and pancreas. (5)
Once inside the cell, NMN is transformed into NAD+ by several enzymes called nicotinamide nucleotide adenylyltransferases (NMNAT1, NMNAT2, and NMNAT3).
And that’s it! Once NMN is transformed into NAD+ in your cells, it starts taking part in a wide range of metabolic processes, energy exchange, and even DNA repair pathways.
Here are some of the most important functions of NAD+ in the human body:
- Helps regulate interactions between proteins.
- Maintains proper communication between cells (for example, between nerve cells and smooth muscle tissue).
- Ensures proper energy production in all cells of the body.
- Maintains optimal activity levels of sirtuins, signaling proteins that regulate metabolism.
- Regulates inflammatory and anti-inflammatory reactions in the body.
And this is just the tip of the iceberg.
NAD+ is extremely versatile because at its core, it serves as an electron transporter, temporarily storing energy during cellular respiration and a wide range of chemical reactions.
That’s why if there’s any kind of process going on in your body, you can be absolutely sure that NAD+ plays a role there at some point. In other words, ensuring that you have optimal levels of NAD+ is one of the most universal ways to promote general health and slow down aging.
Anti-Aging Effects of NMN
The research of NMN supplementation for anti-aging purposes is still very young, but here are some of the most interesting findings on the rejuvenating properties of NMN and its metabolite NAD+.
One study on mice reported that increasing the animals’ NAD+ levels significantly improved their energy metabolism and stem cell function, resulting in an enhanced lifespan. (6) One other study reported that restoring NAD+ levels in old mice brought back their mitochondrial function to the level of young mice and significantly improved their overall health! (7)
Another interesting study by Massudi and colleagues reported a link between NAD+ decline in humans and the accumulation of DNA damage in the tissues, which seems to be a vicious cycle. (8) DNA damage leads to increased NAD+ catabolism (destruction), which limits the body’s ability to repair DNA, which leads to further DNA damage accumulation, which results in even lower NAD+ levels.
What about humans, though?
Do we have any credible data on the effects of NMN for anti-aging, through the action of its metabolite NAD+?
Emerging data reports that increasing NAD+ levels in older adults may contribute to a lower cardiovascular risk, improved arterial elasticity, and healthier blood pressure levels. (9)
Other potential benefits NMN for anti-aging include: (10)
– Suppressing age-related inflammation of adipose (fatty) tissue
– Enhancing insulin production and action, thus improving glucose metabolism
– Improved function of nerve cells in the brain, possibly resulting in better cognitive function and prevention of neurodegenerative are-related disorders
However, it’s important to emphasize that more long-term clinical trials are needed to pinpoint the exact magnitude of benefits that we can expect from consistent NMN supplementation.
NMN Supplementation: Safety and Side Effects
Since NMN is a supplement that’s supposed to be taken long-term for years or even decades, the matter of its safety is critical.
Luckily, the data that we have so far is highly encouraging.
Clinical trials have confirmed that daily supplementation with up to 900 mg of NMN for 30-60 days is absolutely safe and well-tolerated, with no side effects reported whatsoever. (11)
Another study looked into the safety profile of an even higher daily dose of NMN, namely 1250 mg once daily for 4 weeks. No side effects were reported by any of the participants of the study. (12)
To be 100% sure of the safety profile of long-term NMN supplementation, more studies are needed, with more participants, and preferably running for at least a few years straight. However, the data that we have so far speaks in favor of long-term NMN supplementation being harmless for all adults at a daily dose of about 1 g.
However, keep in mind that even though this supplement seems to be well-tolerated, it’s always better to consult with your doctor before embarking on your NMN anti-aging journey. This is especially true if you have any kind of chronic, recurrent, or severe health condition.
The logic here isn’t to be ”better safe than sorry,” but just to keep your primary healthcare provider up to date on everything related to your health. After all, they will be the ones taking care of you in the long run, so make sure to update them about any new supplement you decide to take, even the safest ones.
How to Choose the Best NMN Supplement for Anti-Aging
Just like with any other supplement, picking the best NMN product for long-term rejuvenating supplementation boils down to five core principles.
Purity and Quality
Make sure that the NMN supplement of your choice comes with a laboratory certificate from a reputable source, confirming the purity and quality of the product. Make sure it doesn’t contain arsenic, lead, cadmium, mercury, or nickel. Low-quality supplements will often be contaminated by any of these heavy metals, putting your health at serious risk.
Some NMN supplement brands recommend you to take well over 1 g of NMN daily, but the efficacy or safety of this dose hasn’t been confirmed by clinical studies. As a result, this may be just a marketing tactic to make you finish the pack sooner and buy the next one, maximizing the profits of the company without really giving you anything in return. Trust only those brands that recommend a daily dose between 0.5 and 1 g of NMN daily for the best results.
NMN supplements come in many shapes and forms, including capsules, tablets, and powders. This is mostly a matter of personal preference, but be aware that pure NMN powder taken under the tongue (sublingually) has much higher absorption and bioavailability rates compared to capsules and tablets.
Country of Production
Ideally, the NMN product of your choice should be developed, manufactured, and tested in a country with a strictly regulated pharmaceutical industry. This is an almost direct guarantee that your product will meet the highest standards and give you the best results possible. The USA, Canada, Japan, and Australia are some of the most trusted NMN manufacturers.
The Exciting Future of NMN Research
The domain of anti-aging supplementation, including NMN and resveratrol, is just starting to make waves across the scientific and medical community. There’s so much to be studied yet, so much to be discovered!
Here are some of the most exciting directions and topics related to NMN that will be explored in the following years and decades.
Long-Term Clinical Trials
Although we already have some data on the safety and effectiveness of NMN in humans, we’re yet to see truly long-term studies running for at least a few years or maybe even a full decade. Ideally, these studies would also be able to determine the optimal dosage of NMN for different purposes (e.g. for cardiovascular health, DNA repair, general anti-aging, and so on).
Potential Synergistic Combinations
Taking NMN combinations, like NMN with resveratrol or ginsenosides, seems to be a powerful anti-aging strategy. But do other supplements work well with NMN? What about resistance training or aerobic exercise? Is there an optimal diet that would help NMN truly shine? Who knows what other anti-aging combos are yet to be discovered?
For example, an extremely promising direction of research is the usage of NMN with methyl donors like trimethylglycine (TMG). In a nutshell, methyl donors are compounds that give methyl groups to other active compounds through a process called the methylation cycle. So… Why is this important? The body uses methyl groups in the process of DNA replication, as well as to turn different genes on and off as needed. Since both NAD+ and methyl groups are essential for DNA replication and repair, it’s easy to see how NMN and methyl donors could be an amazing combination for anti-aging!
Alleviating Age-Related Diseases
We can be quite confident on the matter of NMN preventing various age-related issues but what about already existing age-related disorders? It’s hard to say for sure if NMN supplementation could alleviate neurodegenerative diseases, cardiovascular issues, and chronic metabolic conditions. Long-term clinical studies are needed to shed light on the matter.
NMN for anti-aging seems to be one of the most effective and safest supplements ever discovered by science. However, we still have a very long way to go before we can be absolutely sure about the optimal strategies of supplementation, proper dosages for different goals, and even the best combinations to further increase the potential benefits of NMN.
We’ll be expanding and updating this article as more studies are published and more data becomes available to the general public.
Stay tuned and come back to this post every once in a while! At the top of the page, we’ll include a block highlighting the latest updates.
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- López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-1217. doi:10.1016/j.cell.2013.05.039
- Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021;22(2):119-141. doi:10.1038/s41580-020-00313-x
- Schultz MB, Sinclair DA. Why NAD + Declines during Aging: It’s Destroyed. Cell Metabolism. 2016;23(6):965-966. doi.org/10.1016/j.cmet.2016.05.022
- McReynolds MR, Chellappa K, Baur JA. Age-related NAD+ decline. Experimental Gerontology. 2020;134:110888. doi.org/10.1016/j.exger.2020.110888
- Grozio A, Mills KF, Yoshino J, et al. Slc12a8 is a nicotinamide mononucleotide transporter. Nature Metabolism. 2019;1(1):47-57. doi.org/10.1038/s42255-018-0009-4
- Zhang H, Ryu D, Wu Y, et al. NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science. 2016;352(6292):1436-1443. doi:10.1126/science.aaf2693
- Gomes Ana P, Price Nathan L, Ling Alvin JY, et al. Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging. Cell. 2013;155(7):1624-1638. doi.org/10.1016/j.cell.2013.11.037
- Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012;7(7):e42357. doi:10.1371/journal.pone.0042357
- Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature Communications. 2018;9(1). doi.org/10.1038/s41467-018-03421-7
- Shade C. The Science Behind NMN–A Stable, Reliable NAD+Activator and Anti-Aging Molecule. Integrative Medicine: A Clinician’s Journal. 2020;19(1):12-14. PMID: 32549859
- Yi L, Maier AB, Tao R, et al. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. Geroscience. 2023;45(1):29-43. doi:10.1007/s11357-022-00705-1
- Fukamizu Y, Uchida Y, Shigekawa A, Sato T, Kosaka H, Sakurai T. Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women. Sci Rep. 2022;12(1):14442. Published 2022 Aug 24. doi:10.1038/s41598-022-18272-y