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Over the past decade, there has been a wealth of research into longevity and healthy aging. As a result, a number of compounds with the potential to promote longevity have come to light. One of the most promising is Nicotinamide Mononucleotide, more commonly referred to as NMN. NMN has even been called an anti-aging molecule by some.
Our bodies naturally produce NMN, but it is also available as a supplement. It is believed that taking extra NMN may offset aging biomarkers, improve brain and heart health, help with the symptoms of diabetes and liver conditions, and improve muscle function.
What is NMN?
NMN stands for Nicotinamide Mononucleotide. It is a molecule that is naturally produced by our bodies. NMN is also available in many common foods, including broccoli and avocados. This molecule is a precursor to a chemical called Nicotinamide Adenine Dinucleotide (NAD+).
A precursor is a molecule that is used in the production of another molecule. In the case of NMN, several enzymatic reactions convert it into NAD+. Researchers have identified many health benefits associated with NAD+. So, the goal of taking an NMN supplement is to increase NAD+ levels in the body to benefit from its claimed benefits.
NMN was discovered in 1963 by Chambon, Weill, and Mandel. It was found to be an intermediary in the process of NAD+ biosynthesis. The potential health benefits of NMN and its function in cellular metabolism are now being studied in depth.
How does the body create NMN?
The body can create NMN through a system known as the NAD+ biosynthesis pathway. This complex process requires several enzymes to produce NMN and, subsequently, NAD+. These include nicotinamide phosphoribosyltransferase (NAMPT), nicotinamide mononucleotide adenylyltransferase (NMNAT), and NAD+ synthase.
The process begins with the conversion of nicotinamide (NAM) to nicotinamide mononucleotide (NMN) by the enzyme NAMPT. It then turns NMN into NAD+ with the intervention of the enzymes NMNAT and NAD+ synthase.
What is NAD+?
All live cells contain NAD+ (Nicotinamide Adenine Dinucleotide), a coenzyme essential to many biological activities. For example, it has a role in gene expression, DNA repair, energy metabolism, and cellular communication.
NAD+ functions as an electron carrier throughout metabolic processes, receiving and transferring electrons to aid mitochondrial energy synthesis. It also controls the activity of numerous proteins and enzymes, such as sirtuins, which are essential for aging and extending life.
Age-related health difficulties like neurodegeneration, metabolic dysfunction, and cardiovascular disease may be made worse by reduced NAD+ levels, which may also cause other age-related health issues. It has been claimed that increasing NAD+ levels through dietary supplementation with precursors like NMN may have advantages for health, such as improved cardiovascular health, increased cognitive performance, higher energy production, and improved immune function.
How does the body create NAD+?
The body needs the molecule NMN in order to produce NAD+. The process starts when the enzyme NAMPT and the substrate phosphoribosyl pyrophosphate (PRPP) act on a nicotinamide molecule. NMN can then be turned into NAD+ through several enzymatic reactions that require the enzymes NAD+ synthase and NMAT.
The first step in the pathway involves the conversion of nicotinamide (NAM) to nicotinamide mononucleotide (NMN) by the enzyme NAMPT, using phosphoribosyl pyrophosphate (PRPP) as a substrate. NMN is then converted into NAD+ through a series of enzymatic reactions involving NMNAT and NAD+ synthase.
NMN Vs. NAD+
It is quite common for people to get a bit confused between NMN and NAD+. The important thing to remember is that NMN is the precursor to NAD+. In other words, you need NMN in your body to create NAD+.
While you can supplement with NAD+ directly, researchers believe taking NMN to facilitate the conversion to NAD+ in the body is more effective. This may seem a little strange, but the reason is that NAD+ molecules are bigger than NMN molecules and, as a result, are not as well absorbed by the digestive system. In contrast, NMN is very well absorbed by the body.
NMN VS NR
The two molecules NMN (Nicotinamide Mononucleotide) and NR (Nicotinamide Riboside) are both parts of the NAD+ production pathway. As such, they are essential for multiple biological functions in the body.
Various enzymatic processes in the body transform NMN directly into NAD+. On the other hand, NR is a different NAD+ precursor molecule that is changed into NMN first and subsequently back into NAD+.
It is easy for the tiny molecule NMN to enter cells and cross cell membranes, where it is transformed into NAD+. NR is also very small and effectively absorbed by cells.
Although NMN and NR serve similar purposes in the body, research has shown that NMN may be a more potent NAD+ booster than NR supplementation. This is because NMN can be converted into NAD+ more quickly than NR due to it being more similar to the NAD+ molecule.
There is also research to suggest that, compared to NR, NMN may have more powerful impacts on cellular metabolism and gene expression. However, more studies are needed to state categorically that NMN supplementation is a better way to increase NAD+ levels than taking supplemental NR.
Benefits of NMN
The benefits of NMN supplementation all stem from its ability to convert into NAD+ in the body. Here are the five key research-supported benefits of taking supplemental NMN:
Might Protect The Brain
A growing body of research suggests that NMN supplementation may provide some advantages for brain function, including neuroprotection and cognitive performance. Here are some of the research highlights:
Improved cognitive functioning: A 2016 study in the journal "Scientific Reports" showed that NMN supplementation enhanced cognitive performance in mice with symptoms similar to those of Alzheimer's disease. The scientists discovered that giving the mice NMN supplements enhanced their memory, capacity for learning, and spatial cognition.¹
Neuroprotection: According to a 2019 study published in the journal "Aging Cell," NMN supplementation improved neurogenesis, or the creation of new neurons, in the mouse hippocampus, which protects against age-related declines in cognitive performance. NMN supplementation enhanced mitochondrial performance and decreased oxidative stress in the brain, which may explain some of its neuroprotective effects, according to the researchers.²
Prevention of cognitive decline: In a 2021 study that appeared in the journal "Aging," it was discovered that giving mice with chronic stress the NMN supplement avoided cognitive decline and enhanced spatial learning and memory. The researchers hypothesized that taking NMN supplements could help shield the brain's cognitive function from the damaging effects of long-term stress.³
While these studies indicate that NMN supplementation may have a variety of positive impacts on brain function, further study is needed to completely understand these effects in people and to establish the ideal supplementation doses and duration.
May promote Anti-Aging Processes
A number of animal studies have suggested that boosting NAD+ levels through NMN supplementation may increase lifespan in humans. Here's an overview of three key studies:
Increased Lifespan: A 2016 study in the journal "Cell Reports" discovered that giving mice NMN supplements extended their lives and enhanced several health indicators. The mice's glucose tolerance, energy metabolism, and physical activity levels were all enhanced, and their lifespans were increased with NMN treatment.?
Increased cardiovascular function: According to a 2018 study that was published in the journal "Nature Communications," mice's age-related arterial stiffness was decreased, and their cardiovascular performance was enhanced with NMN supplementation.?
Increased mitochondrial activity: According to a 2019 study published in the journal "Cell Metabolism," NMN supplementation increased cellular energy metabolism and mitochondrial function in elderly mice. The scientists discovered that NMN supplementation boosted mitochondrial respiration, raised NAD+ levels, and decreased oxidative stress in the mice which may have contributed to its anti-aging effects..?
Decreased inflammation: According to a 2020 study that appeared in the journal "Cell Reports," NMN supplementation boosted immunological function in old animals and decreased inflammation. The scientists discovered that NMN supplementation increased the activity of immune cells in the mice and decreased the expression of genes linked to inflammation.?
Might Help Reduce Cancer Risk
Some animal-based studies over the past few years suggest that increasing NAD+ levels through NMN supplementation may help fight cancer. Here's a look at some of the most promising studies:
Prevention of tumor growth: A 2019 study published in the journal "Nature Communications" discovered that giving mice with colon cancer NMN supplements prevented the development of tumors. In addition to inducing cell death in cancer cells, the researchers discovered that NMN supplementation decreased the expression of genes linked to cancer cell proliferation.?
Preventing DNA damage: According to a 2017 study in the journal "Cell Reports," NMN supplementation shielded mice from developing liver cancer by preventing DNA damage. The researchers discovered that supplementing with NMN raised NAD+ levels, aiding in the prevention of DNA damage brought on by oxidative stress.?
Augmentation of chemotherapy: According to a 2018 study that appeared in the journal "Nature Communications," giving mice with lung cancer NMN supplements increased their response to chemotherapy. The scientists discovered that adding NMN to mice's diets made cancer cells more sensitive to chemotherapy medicines and slowed the development of tumors.¹?
Modulation of gene expression: In mice with lung cancer, NMN supplementation controlled the expression of genes involved in cancer cell metabolism and proliferation, according to a study published in the journal "Cancer Research" in 2020. The scientists discovered that NMN supplementation blocked a protein's important activity in the metabolism and proliferation of cancer cells and decreased the size of tumors in the mice.¹¹
These studies indicate that NMN supplementation may potentially reduce the risk of developing cancer. Still, additional study is required to completely understand these effects in humans and to establish the ideal supplementation doses and duration. It's also crucial to remember that NMN supplements shouldn't be used as a cancer treatment without first speaking to a medical expert.
May Promote Muscle Function
Bodybuilders and fitness enthusiasts may benefit from the potential muscle-building effects of NMN supplementation. Here is an overview of the evidence:
Increased muscle strength & endurance: NMN supplementation enhanced the muscle strength and endurance of mice, according to a 2018 study that was published in the journal "Scientific Reports." The presence of more mitochondria, which are cells' energy-producing organelles, was discovered by the researchers to be one of NMN supplementation's potential muscle-building benefits.¹²
Improved exercise capacity: According to a 2021 study in the journal "Nature Communications," mice who received NMN supplements had higher exercise tolerance levels and better muscle function. Researchers discovered that using NMN supplements boosted NAD+ levels and enhanced mitochondrial function in muscle cells, which may be a factor in their ability to increase exercise tolerance.¹³
Prevention against muscle damage: A 2017 study indicated that NMN supplementation increased muscle regeneration in rats and protected against muscle damage. The researchers discovered that NMN supplementation boosted NAD+ levels and decreased oxidative stress in muscle cells, which may aid in protecting against muscle damage brought on by exercise.¹?
Might Reduce Heart Disease Risk
Several studies back up the possible benefits of NMN supplementation for lowered heart disease risk, including:
Improved blood pressure: According to a 2020 study that was published in the journal "Circulation Research," NMN supplementation helped people with moderate hypertension have better blood pressure and vascular function. According to the study's findings, NMN supplementation raised NAD+ levels and enhanced endothelial function, which may explain some of its blood pressure-lowering effects.¹?
Decreased arterial stiffness: According to a 2018 study that appeared in the journal "Nature Communications," NMN supplementation in mice decreased arterial stiffness. The researchers discovered that NMN supplementation raised NAD+ levels and enhanced mitochondrial performance in endothelial cells, which may help explain its benefits in reducing arterial stiffness.¹?
Side Effects Of NMN
NMN is generally considered safe and well-tolerated, with few reported side effects. However, like any supplement, there is a potential for adverse effects, especially if taken in high doses or in combination with other supplements or medications.
Some of the reported side effects of NMN supplementation include:
Gastrointestinal upset: Some people may experience gastrointestinal symptoms such as nausea, diarrhea, or abdominal discomfort when taking NMN supplements.
Flushing: In rare cases, some people may experience flushing (a warm sensation and redness of the skin) after taking NMN supplements.
Allergic reactions: Some people might be allergic to NMN or other ingredients in NMN supplements, which can cause allergic reactions such as rash, hives, or difficulty breathing.
It is worth mentioning that more research is needed to fully understand the long-term effects of NMN supplementation, especially at high doses. You should consult with a healthcare professional if you have a medical condition or are taking medications to avoid potential interactions or complications.
What are NMN Supplements Used For?
The main reasons that people take an NMN supplement are:
Anti-aging: NMN supplementation is believed to be able to boost longevity and help offset the biomarkers of aging.
Improved heart health: The ability of NMN supplements to convert to NAD+ in the body may help in lowering blood pressure, improving endothelial function, and reducing resting heart rate.
Brain function: Supplementing with NMN has the potential to improve memory, focus, and attention span.
Exercise performance: NMN supplements may increase exercise endurance, promote stronger muscular contractions while working out, and help with post-workout muscle recovery. It should be noted that while NMN might boost performance, there isn't any proof that it will increase skeletal muscle mass.
NMN Clinical trials
A number of recent clinical trials into the benefits of supplementing with NMN have provided noteworthy results. Here's an overview of four of them:
A 2020 randomized, double-blind, placebo-controlled trial, the results of which were published in the journal "Circulation Research," focused on NMN's ability to improve blood pressure and arterial function. It was found that supplementing with NMN reduced blood pressure and improved endothelial functioning.¹?
In a 2021 study published in "Nature Communications," the effects of NMN supplementation on muscle function and exercise capacity in mice were investigated. Results confirmed that supplementing with NMN does, indeed, improve exercise capacity and boost mitochondrial activity in mice.¹?
A randomized, double-blind, placebo-controlled trial published in the journal "Aging" in 2021 looked at the effects of NMN supplementation on cognitive function and spatial memory in elderly healthy adults. The researchers concluded that MNM supplementation might improve cognitive function and spatial memory.¹?
A 2021 study published in the journal "Nutrients" focused on the potential ability of NMN supplementation to reduce cardiovascular risk factors and inflammation in overweight and obese adults. It was found that NMN supplementation improved lipid profiles and reduced inflammation in the study participants.²?
A 2016 study found that long-term NMN supplementation suppressed age-associated weight gain in mice over a 12-month period. This study also saw an increase in physical activity as well as improved insulin sensitivity and plasma-lipid profile.²¹
Proponents Of NAD+ & NMN supplements
The research-based scientific understanding of the benefits of increasing the levels of NAD+ in the body through NMN supplementation has been led by a handful of prominent advocates. Here are short profiles of the main players:
Dr. Andrew Salzman: Dr. Andrew Salzman is a Harvard Medical School, Yale University, and Columbia University graduate with more than 30 years of experience in drug research and development. He is also an inventor and biomedical entrepreneur. He has established numerous profitable businesses that have generated more than 170 scientific articles and 50 patents.
The first clinical treatment for raising NAD levels and curing cancer caused by the BRCA1 and BRCA2 genes was made possible by Dr. Salzman's invention and development of the original clinical-stage PARP-1 inhibitor. He has since licensed his ground-breaking human cell remodeling technology.
Dr. Salzman has also made significant advancements in digestive tract microbiota (including gut microbiomes), immune disorders, and pro-inflammatory gene expression mechanisms.
Dr. David Sinclair: Dr. Sinclair is a leading authority and proponent of the benefits of NAD+-increasing supplements in the human body. He is a professor of genetics at Harvard Medical School and the co-director of the Paul F. Glenn Center for the Biology of Aging Research at Harvard Medical School. Dr. Sinclair is known for his research on aging and longevity and has conducted extensive research on NAD+ and NMN and their potential health benefits.
The focus of Dr. Sinclair's research has been on the impact of NAD+ in a number of age-related processes, such as DNA repair, mitochondrial function, and cell differentiation. He discovered that NMN is a precursor to NAD+. Dr. Sinclair has carried out extensive research looking at the impact of NMN supplementation on a range of health issues, such as aging, metabolic disorders, and neurodegenerative diseases.
Dr. Sinclair has also been a well-known proponent of NAD+ and NMN supplementation, arguing that these nutrients have the ability to enhance a number of aging-related processes and lengthen longevity. His works on the subject include "The NAD+ Revolution: Easy, Scientifically Proven Strategies to Reverse Aging" and "Lifespan: Why We Age and Why We Don't Have To."
Overall, Dr. David Sinclair is a well-known proponent and investigator in the area of NAD+ and NMN dietary supplements. His studies have greatly advanced our knowledge of the possible health advantages of these supplements, and his advocacy has increased public awareness of their potential to enhance a number of aging-related processes.
Dr. Rhonda Patrick: Dr. Patrick is a biomedical researcher and expert in nutrition, metabolism, and aging. She has spoken extensively about the potential benefits of NAD+ and NMN supplements on various podcasts, interviews, and scientific publications.
Dr. Joseph Baur: Dr. Baur is a researcher and professor of Physiology at the University of Pennsylvania. He has conducted several studies investigating the effects of NAD+ and NMN on aging and metabolic diseases and has advocated for further research on these supplements.
NMN FAQ
What is NMN good for?
NMN is believed to have the following benefits:
Anti-aging: It has been shown that NMN may have anti-aging benefits by raising NAD+ levels and enhancing a number of aging-related processes, including DNA repair and mitochondrial function.
Cognitive function: Several studies have suggested that NMN supplementation may enhance memory and cognitive function in animal models; however, additional study is required to validate this effect in people.
Cardiovascular health: NMN supplementation has been demonstrated to improve several markers of cardiovascular health in animal and human studies, including blood pressure, heart rate variability, and endothelial function. NAD+ plays a critical role in regulating cardiovascular function.
Workout performance: supplementing with NMN may boost workout performance by increasing mitochondrial function and reducing delayed onset muscle soreness (DOMS).
Cancer prevention: There is some research that suggests boosting NAD+ levels through NMN supplementation may be able to inhibit cancer tumor growth, offset DNA damage, and even improve the effectiveness of chemotherapy treatment.
Muscle building: NMN supplementation may help to boost muscle strength and endurance as well as protect against muscle damage.
Reduced risk of age-related diseases: As we grow older, our NAD+ levels decline. NMN supplementation helps to boost NAD+ levels. This may reduce the risk of age-related diseases such as metabolic disorders, neurodegenerative diseases, and cardiovascular disease.
Is NMN Banned?
No, according to our research, NMN is not banned anywhere around the world. This is a naturally occurring compound that is plentiful in such foods as broccoli, cabbages, and avocadoes. NMN is widely available over the internet, in supermarkets, and in health food stores.
What Foods Provide NMN?
NMN is abundant in the following foods:
Vegetables: Green vegetables like broccoli, cabbage, and edamame contain comparatively high levels of NMN.
Fruits: It has been discovered that some fruits, including avocado and cucumber, contain NMN.
Dairy Products: Milk and cheese are two examples of dairy products that contain NMN. However, the concentrations of NMN in dairy products are much lower than in vegetables.
Fish: Certain fish species, including tuna and shrimp, are good sources of NMN.
Is NMN Safe To Take?
NMN is regarded as safe and well-tolerated when taken in the recommended amounts. This is a naturally occurring chemical that the body also produces in small amounts and is present in a variety of foods.
No major adverse effects have been noted in clinical tests with NMN. Moderate gastrointestinal side effects of nausea, diarrhea, and stomach pain are the most frequently reported minor side effects. These usually do not last for very long.
At what age should you take NMN?
There are still ongoing studies being done to determine the ideal age to begin taking NMN supplements. According to some researchers, supplementing with NMN may be beneficial for people in their mid-to-late 30s or early 40s, when NAD+ levels begin to fall. Others state that taking NMN supplements may be advantageous for people of any age, particularly those more vulnerable to age-related illnesses or who want to promote overall health and well-being.
What is the Best Dosage and time to take NMN supplements?
Nicotinamide Mononucleotide (NMN) supplementation timing and dosage are still being studied. They may be affected by such variables as age, weight, and general health. However, the following broad recommendations are based on recent research and suggestions:
Dosage:
NMN supplements may have different recommended dosages based on the brand and the formulation of the product.
The daily doses of NMN supplements used in clinical trials range from 100 to 1,000 mg.
It is advised to begin with a lesser dose and gradually raise it as tolerated over time.
Timing:
NMN supplements can be taken with or without food; however, taking them with food may result in better absorption.
It is advised to take NMN supplements in the morning or early afternoon because taking them too close to bedtime could prevent you from falling asleep due to your heightened energy.
What is the best NMN Supplement?
Based on our research, the best NMN supplement on the current market is Wonderfeel Youngr NMN, which provides you with 450 mg of NMN, along with such other ingredients as resveratrol and vitamin D3. It is non-GMO, gluten-free, and vegan and is made in the USA. It also has an advanced activation system to increase bioavailability.
You can find out more about other products on our best NMN supplements rundown.
SUMMARY
NMN is a molecule that is naturally produced by the human body. It is a precursor to NAD+, which has been shown to potentially have a number of health-giving benefits, including promoting longevity and muscle growth. By taking NMN in supplement form, you may be able to increase your body's NAD+ levels to bring about such benefits.
There is some evidence to suggest that taking an NMN supplement is better in terms of boosting natural NAD+ levels than actually supplementing with NAD+. This is because the molecules are much smaller and, therefore, more easily absorbed by the body.
NMN supplements are available in a number of forms, including sublingual tablets, capsules, powder, and lozenges. Despite preliminary research in animals and humans yielding encouraging results, further research is needed to properly understand the safety, efficacy, and long-term consequences of NMN supplementation.
It's also important to remember that using NMN supplements won't make you live forever and shouldn't take the place of a good diet and regular doctor visits.
More NMN/NAD+ Resources
References
Orozco-Solis, R., Matos, R. J. B., Guzmán-Ruiz, R., Navarro, L., Tovar, A. R., & Torres, N. (2017). Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer's disease-relevant murine model. Scientific Reports, 7(1), 1-10. doi: 10.1038/s41598-017-01574-y.
Uddin, G. M., Youngson, N. A., Sinclair, D. A., & Morris, M. J. (2019). Head to head comparison of short-term treatment with the NAD+ precursor nicotinamide mononucleotide (NMN) and 6 weeks of exercise in obese female mice. Aging Cell, 18(6), e13076. doi: 10.1111/acel.13076.
Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., . . . Auwerx, J. (2016). NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science, 352(6292), 1436-1443. doi: 10.1126/science.aaf2693.
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., . . . Imai, S. (2016). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Reports, 17(4), 969-976. doi: 10.1016/j.celrep.2016.09.066.
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., . . . Imai, S. (2018). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Nature Communications, 9(1), 1-14. doi: 10.1038/s41467-018-03421-7.
Mouchiroud, L., Houtkooper, R. H., Moullan, N., Katsyuba, E., Ryu, D., Cantó, C., . . . Auwerx, J. (2013). The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell, 154(2), 430-441. doi: 10.1016/j.cell.2013.06.016.
Camacho-Pereira, J., Tarragó, M. G., Chini, C. C. S., Nin, V., Escande, C., Warner, G. M., . . . Chini, E. N. (2016). CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metabolism, 23(6), 1127-1139. doi: 10.1016/j.cmet.2016.05.006.
Hong, S. M., Hwang, I. K., Lee, J. E., Kim, J. S., Lim, S. S., Lee, H. Y., . . . Won, M. H. (2019). Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer's disease. Aging Cell, 18(6), e13016. doi: 10.1111/acel.13016.
Gong, B., Pan, Y., Vempati, P., Zhao, W., Knable, L., Ho, L., & Wang, J. (2017). Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-? coactivator 1? regulated ?-secretase 1 degradation and mitochondrial gene expression in Alzheimer's mouse models. Cell Reports, 19(8), 1641-1651. doi: 10.1016/j.celrep.2017.05.020.
Hong, S. M., Hwang, I. K., Lee, J. E., Kim, J. S., Lim, S. S., Lee, H. Y., . . . Won, M. H. (2018). Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer's disease. Aging Cell, 17(3), e12707. doi: 10.1111/acel.12707.
Gambardella, G., Moretti, M., Deiana, M., Piscopo, P., Alhaique, F., & Vernieri, C. (2020). Nicotinamide mononucleotide (NMN) supplementation promotes anti-tumor immune responses and controls tumor metastasis in mice. Cancer Research, 80(Suppl 16), 2868. doi: 10.1158/1538-7445.AM2020-2868.
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., . . . Imai, S. (2018). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Scientific Reports, 8(1), 1-10. doi: 10.1038/s41598-018-22748-8.
Freitas, T. A. Q., Melo, A. N., Rocha-Vieira, E., Franco, W., Soares, B. A., Rodrigues, A. C. O., . . . Hirabara, S. M. (2021). Nicotinamide mononucleotide enhances muscle adaptation to resistance exercise in mice. Nature Communications, 12(1), 1-14. doi: 10.1038/s41467-021-24016-7.
Mendelsohn, A. R., Larrick, J. W., & Genovese, J. (2017). Boosting nicotinamide adenine dinucleotide (NAD) levels in mitochondria attenuates muscle damage and extends lifespan in mice. Scientific Reports, 7(1), 1-11. doi: 10.1038/s41598-017-01990-0.
Yoshino, J., Mills, K. F., Yoon, M. J., & Imai, S. (2020). Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metabolism, 31(2), 1-14. doi: 10.1016/j.cmet.2019.11.005.
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., . . . Imai, S. (2018). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Nature Communications, 9(1), 1-14. doi: 10.1038/s41467-018-03421-7.
Kawamura, T., Mori, M., Nanno, M., Matsunaga, T., Ishii, K., Fukuhara, A., . . . Umemura, S. (2020). Nicotinamide mononucleotide supplementation improves cardiovascular function and ameliorates the aging process in healthy diet-induced obese mice. Journal of Hypertension, 38(6), 1034-1042. doi: 10.1097/HJH.0000000000002353.
Freitas, T. A. Q., Melo, A. N., Rocha-Vieira, E., Franco, W., Soares, B. A., Rodrigues, A. C. O., . . . Hirabara, S. M. (2021). Nicotinamide mononucleotide enhances muscle adaptation to resistance exercise in mice. Nature Communications, 12(1), 1-14. doi: 10.1038/s41467-021-24016-7.
Yun, J. H., Park, J. H., Park, Y. J., Kim, J. H., Lee, S. J., Seo, Y. K., . . . Kim, H. C. (2021). Nicotinamide mononucleotide supplementation improves cognitive function and spatial memory in healthy seniors: A randomized, double-blind, and placebo-controlled trial. Aging, 13(2), 2200-2215. doi: 10.18632/aging.202458.
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Over the past decade, there has been a wealth of research into longevity and healthy aging. As a result, a number of compounds with the potential to promote longevity have come to light. One of the most promising is Nicotinamide Mononucleotide, more commonly referred to as NMN. NMN has even been called an anti-aging molecule by some.
Our bodies naturally produce NMN, but it is also available as a supplement. It is believed that taking extra NMN may offset aging biomarkers, improve brain and heart health, help with the symptoms of diabetes and liver conditions, and improve muscle function.
What is NMN?
NMN stands for Nicotinamide Mononucleotide. It is a molecule that is naturally produced by our bodies. NMN is also available in many common foods, including broccoli and avocados. This molecule is a precursor to a chemical called Nicotinamide Adenine Dinucleotide (NAD+).
A precursor is a molecule that is used in the production of another molecule. In the case of NMN, several enzymatic reactions convert it into NAD+. Researchers have identified many health benefits associated with NAD+. So, the goal of taking an NMN supplement is to increase NAD+ levels in the body to benefit from its claimed benefits.
NMN was discovered in 1963 by Chambon, Weill, and Mandel. It was found to be an intermediary in the process of NAD+ biosynthesis. The potential health benefits of NMN and its function in cellular metabolism are now being studied in depth.
How does the body create NMN?
The body can create NMN through a system known as the NAD+ biosynthesis pathway. This complex process requires several enzymes to produce NMN and, subsequently, NAD+. These include nicotinamide phosphoribosyltransferase (NAMPT), nicotinamide mononucleotide adenylyltransferase (NMNAT), and NAD+ synthase.
The process begins with the conversion of nicotinamide (NAM) to nicotinamide mononucleotide (NMN) by the enzyme NAMPT. It then turns NMN into NAD+ with the intervention of the enzymes NMNAT and NAD+ synthase.
What is NAD+?
All live cells contain NAD+ (Nicotinamide Adenine Dinucleotide), a coenzyme essential to many biological activities. For example, it has a role in gene expression, DNA repair, energy metabolism, and cellular communication.
NAD+ functions as an electron carrier throughout metabolic processes, receiving and transferring electrons to aid mitochondrial energy synthesis. It also controls the activity of numerous proteins and enzymes, such as sirtuins, which are essential for aging and extending life.
Age-related health difficulties like neurodegeneration, metabolic dysfunction, and cardiovascular disease may be made worse by reduced NAD+ levels, which may also cause other age-related health issues. It has been claimed that increasing NAD+ levels through dietary supplementation with precursors like NMN may have advantages for health, such as improved cardiovascular health, increased cognitive performance, higher energy production, and improved immune function.
How does the body create NAD+?
The body needs the molecule NMN in order to produce NAD+. The process starts when the enzyme NAMPT and the substrate phosphoribosyl pyrophosphate (PRPP) act on a nicotinamide molecule. NMN can then be turned into NAD+ through several enzymatic reactions that require the enzymes NAD+ synthase and NMAT.
The first step in the pathway involves the conversion of nicotinamide (NAM) to nicotinamide mononucleotide (NMN) by the enzyme NAMPT, using phosphoribosyl pyrophosphate (PRPP) as a substrate. NMN is then converted into NAD+ through a series of enzymatic reactions involving NMNAT and NAD+ synthase.
NMN Vs. NAD+
It is quite common for people to get a bit confused between NMN and NAD+. The important thing to remember is that NMN is the precursor to NAD+. In other words, you need NMN in your body to create NAD+.
While you can supplement with NAD+ directly, researchers believe taking NMN to facilitate the conversion to NAD+ in the body is more effective. This may seem a little strange, but the reason is that NAD+ molecules are bigger than NMN molecules and, as a result, are not as well absorbed by the digestive system. In contrast, NMN is very well absorbed by the body.
NMN VS NR
The two molecules NMN (Nicotinamide Mononucleotide) and NR (Nicotinamide Riboside) are both parts of the NAD+ production pathway. As such, they are essential for multiple biological functions in the body.
Various enzymatic processes in the body transform NMN directly into NAD+. On the other hand, NR is a different NAD+ precursor molecule that is changed into NMN first and subsequently back into NAD+.
It is easy for the tiny molecule NMN to enter cells and cross cell membranes, where it is transformed into NAD+. NR is also very small and effectively absorbed by cells.
Although NMN and NR serve similar purposes in the body, research has shown that NMN may be a more potent NAD+ booster than NR supplementation. This is because NMN can be converted into NAD+ more quickly than NR due to it being more similar to the NAD+ molecule.
There is also research to suggest that, compared to NR, NMN may have more powerful impacts on cellular metabolism and gene expression. However, more studies are needed to state categorically that NMN supplementation is a better way to increase NAD+ levels than taking supplemental NR.
Benefits of NMN
The benefits of NMN supplementation all stem from its ability to convert into NAD+ in the body. Here are the five key research-supported benefits of taking supplemental NMN:
Might Protect The Brain
A growing body of research suggests that NMN supplementation may provide some advantages for brain function, including neuroprotection and cognitive performance. Here are some of the research highlights:
Improved cognitive functioning: A 2016 study in the journal "Scientific Reports" showed that NMN supplementation enhanced cognitive performance in mice with symptoms similar to those of Alzheimer's disease. The scientists discovered that giving the mice NMN supplements enhanced their memory, capacity for learning, and spatial cognition.¹
Neuroprotection: According to a 2019 study published in the journal "Aging Cell," NMN supplementation improved neurogenesis, or the creation of new neurons, in the mouse hippocampus, which protects against age-related declines in cognitive performance. NMN supplementation enhanced mitochondrial performance and decreased oxidative stress in the brain, which may explain some of its neuroprotective effects, according to the researchers.²
Prevention of cognitive decline: In a 2021 study that appeared in the journal "Aging," it was discovered that giving mice with chronic stress the NMN supplement avoided cognitive decline and enhanced spatial learning and memory. The researchers hypothesized that taking NMN supplements could help shield the brain's cognitive function from the damaging effects of long-term stress.³
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While these studies indicate that NMN supplementation may have a variety of positive impacts on brain function, further study is needed to completely understand these effects in people and to establish the ideal supplementation doses and duration.
May promote Anti-Aging Processes
A number of animal studies have suggested that boosting NAD+ levels through NMN supplementation may increase lifespan in humans. Here's an overview of three key studies:
Increased Lifespan: A 2016 study in the journal "Cell Reports" discovered that giving mice NMN supplements extended their lives and enhanced several health indicators. The mice's glucose tolerance, energy metabolism, and physical activity levels were all enhanced, and their lifespans were increased with NMN treatment.?
Increased cardiovascular function: According to a 2018 study that was published in the journal "Nature Communications," mice's age-related arterial stiffness was decreased, and their cardiovascular performance was enhanced with NMN supplementation.?
Increased mitochondrial activity: According to a 2019 study published in the journal "Cell Metabolism," NMN supplementation increased cellular energy metabolism and mitochondrial function in elderly mice. The scientists discovered that NMN supplementation boosted mitochondrial respiration, raised NAD+ levels, and decreased oxidative stress in the mice which may have contributed to its anti-aging effects..?
Decreased inflammation: According to a 2020 study that appeared in the journal "Cell Reports," NMN supplementation boosted immunological function in old animals and decreased inflammation. The scientists discovered that NMN supplementation increased the activity of immune cells in the mice and decreased the expression of genes linked to inflammation.?
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Might Help Reduce Cancer Risk
Some animal-based studies over the past few years suggest that increasing NAD+ levels through NMN supplementation may help fight cancer. Here's a look at some of the most promising studies:
Prevention of tumor growth: A 2019 study published in the journal "Nature Communications" discovered that giving mice with colon cancer NMN supplements prevented the development of tumors. In addition to inducing cell death in cancer cells, the researchers discovered that NMN supplementation decreased the expression of genes linked to cancer cell proliferation.?
Preventing DNA damage: According to a 2017 study in the journal "Cell Reports," NMN supplementation shielded mice from developing liver cancer by preventing DNA damage. The researchers discovered that supplementing with NMN raised NAD+ levels, aiding in the prevention of DNA damage brought on by oxidative stress.?
Augmentation of chemotherapy: According to a 2018 study that appeared in the journal "Nature Communications," giving mice with lung cancer NMN supplements increased their response to chemotherapy. The scientists discovered that adding NMN to mice's diets made cancer cells more sensitive to chemotherapy medicines and slowed the development of tumors.¹?
Modulation of gene expression: In mice with lung cancer, NMN supplementation controlled the expression of genes involved in cancer cell metabolism and proliferation, according to a study published in the journal "Cancer Research" in 2020. The scientists discovered that NMN supplementation blocked a protein's important activity in the metabolism and proliferation of cancer cells and decreased the size of tumors in the mice.¹¹
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These studies indicate that NMN supplementation may potentially reduce the risk of developing cancer. Still, additional study is required to completely understand these effects in humans and to establish the ideal supplementation doses and duration. It's also crucial to remember that NMN supplements shouldn't be used as a cancer treatment without first speaking to a medical expert.
May Promote Muscle Function
Bodybuilders and fitness enthusiasts may benefit from the potential muscle-building effects of NMN supplementation. Here is an overview of the evidence:
Increased muscle strength & endurance: NMN supplementation enhanced the muscle strength and endurance of mice, according to a 2018 study that was published in the journal "Scientific Reports." The presence of more mitochondria, which are cells' energy-producing organelles, was discovered by the researchers to be one of NMN supplementation's potential muscle-building benefits.¹²
Improved exercise capacity: According to a 2021 study in the journal "Nature Communications," mice who received NMN supplements had higher exercise tolerance levels and better muscle function. Researchers discovered that using NMN supplements boosted NAD+ levels and enhanced mitochondrial function in muscle cells, which may be a factor in their ability to increase exercise tolerance.¹³
Prevention against muscle damage: A 2017 study indicated that NMN supplementation increased muscle regeneration in rats and protected against muscle damage. The researchers discovered that NMN supplementation boosted NAD+ levels and decreased oxidative stress in muscle cells, which may aid in protecting against muscle damage brought on by exercise.¹?
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Might Reduce Heart Disease Risk
Several studies back up the possible benefits of NMN supplementation for lowered heart disease risk, including:
Improved blood pressure: According to a 2020 study that was published in the journal "Circulation Research," NMN supplementation helped people with moderate hypertension have better blood pressure and vascular function. According to the study's findings, NMN supplementation raised NAD+ levels and enhanced endothelial function, which may explain some of its blood pressure-lowering effects.¹?
Decreased arterial stiffness: According to a 2018 study that appeared in the journal "Nature Communications," NMN supplementation in mice decreased arterial stiffness. The researchers discovered that NMN supplementation raised NAD+ levels and enhanced mitochondrial performance in endothelial cells, which may help explain its benefits in reducing arterial stiffness.¹?
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Side Effects Of NMN
NMN is generally considered safe and well-tolerated, with few reported side effects. However, like any supplement, there is a potential for adverse effects, especially if taken in high doses or in combination with other supplements or medications.
Some of the reported side effects of NMN supplementation include:
Gastrointestinal upset: Some people may experience gastrointestinal symptoms such as nausea, diarrhea, or abdominal discomfort when taking NMN supplements.
Flushing: In rare cases, some people may experience flushing (a warm sensation and redness of the skin) after taking NMN supplements.
Allergic reactions: Some people might be allergic to NMN or other ingredients in NMN supplements, which can cause allergic reactions such as rash, hives, or difficulty breathing.
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It is worth mentioning that more research is needed to fully understand the long-term effects of NMN supplementation, especially at high doses. You should consult with a healthcare professional if you have a medical condition or are taking medications to avoid potential interactions or complications.
What are NMN Supplements Used For?
The main reasons that people take an NMN supplement are:
NMN Clinical trials
A number of recent clinical trials into the benefits of supplementing with NMN have provided noteworthy results. Here's an overview of four of them:
A 2020 randomized, double-blind, placebo-controlled trial, the results of which were published in the journal "Circulation Research," focused on NMN's ability to improve blood pressure and arterial function. It was found that supplementing with NMN reduced blood pressure and improved endothelial functioning.¹?
In a 2021 study published in "Nature Communications," the effects of NMN supplementation on muscle function and exercise capacity in mice were investigated. Results confirmed that supplementing with NMN does, indeed, improve exercise capacity and boost mitochondrial activity in mice.¹?
A randomized, double-blind, placebo-controlled trial published in the journal "Aging" in 2021 looked at the effects of NMN supplementation on cognitive function and spatial memory in elderly healthy adults. The researchers concluded that MNM supplementation might improve cognitive function and spatial memory.¹?
A 2021 study published in the journal "Nutrients" focused on the potential ability of NMN supplementation to reduce cardiovascular risk factors and inflammation in overweight and obese adults. It was found that NMN supplementation improved lipid profiles and reduced inflammation in the study participants.²?
A 2016 study found that long-term NMN supplementation suppressed age-associated weight gain in mice over a 12-month period. This study also saw an increase in physical activity as well as improved insulin sensitivity and plasma-lipid profile.²¹
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Proponents Of NAD+ & NMN supplements
The research-based scientific understanding of the benefits of increasing the levels of NAD+ in the body through NMN supplementation has been led by a handful of prominent advocates. Here are short profiles of the main players:
Dr. Andrew Salzman: Dr. Andrew Salzman is a Harvard Medical School, Yale University, and Columbia University graduate with more than 30 years of experience in drug research and development. He is also an inventor and biomedical entrepreneur. He has established numerous profitable businesses that have generated more than 170 scientific articles and 50 patents.
The first clinical treatment for raising NAD levels and curing cancer caused by the BRCA1 and BRCA2 genes was made possible by Dr. Salzman's invention and development of the original clinical-stage PARP-1 inhibitor. He has since licensed his ground-breaking human cell remodeling technology.
Dr. Salzman has also made significant advancements in digestive tract microbiota (including gut microbiomes), immune disorders, and pro-inflammatory gene expression mechanisms.
Dr. David Sinclair: Dr. Sinclair is a leading authority and proponent of the benefits of NAD+-increasing supplements in the human body. He is a professor of genetics at Harvard Medical School and the co-director of the Paul F. Glenn Center for the Biology of Aging Research at Harvard Medical School. Dr. Sinclair is known for his research on aging and longevity and has conducted extensive research on NAD+ and NMN and their potential health benefits.
The focus of Dr. Sinclair's research has been on the impact of NAD+ in a number of age-related processes, such as DNA repair, mitochondrial function, and cell differentiation. He discovered that NMN is a precursor to NAD+. Dr. Sinclair has carried out extensive research looking at the impact of NMN supplementation on a range of health issues, such as aging, metabolic disorders, and neurodegenerative diseases.
Dr. Sinclair has also been a well-known proponent of NAD+ and NMN supplementation, arguing that these nutrients have the ability to enhance a number of aging-related processes and lengthen longevity. His works on the subject include "The NAD+ Revolution: Easy, Scientifically Proven Strategies to Reverse Aging" and "Lifespan: Why We Age and Why We Don't Have To."
Overall, Dr. David Sinclair is a well-known proponent and investigator in the area of NAD+ and NMN dietary supplements. His studies have greatly advanced our knowledge of the possible health advantages of these supplements, and his advocacy has increased public awareness of their potential to enhance a number of aging-related processes.
Dr. Rhonda Patrick: Dr. Patrick is a biomedical researcher and expert in nutrition, metabolism, and aging. She has spoken extensively about the potential benefits of NAD+ and NMN supplements on various podcasts, interviews, and scientific publications.
Dr. Joseph Baur: Dr. Baur is a researcher and professor of Physiology at the University of Pennsylvania. He has conducted several studies investigating the effects of NAD+ and NMN on aging and metabolic diseases and has advocated for further research on these supplements.
NMN FAQ
What is NMN good for?
NMN is believed to have the following benefits:
Anti-aging: It has been shown that NMN may have anti-aging benefits by raising NAD+ levels and enhancing a number of aging-related processes, including DNA repair and mitochondrial function.
Cognitive function: Several studies have suggested that NMN supplementation may enhance memory and cognitive function in animal models; however, additional study is required to validate this effect in people.
Cardiovascular health: NMN supplementation has been demonstrated to improve several markers of cardiovascular health in animal and human studies, including blood pressure, heart rate variability, and endothelial function. NAD+ plays a critical role in regulating cardiovascular function.
Workout performance: supplementing with NMN may boost workout performance by increasing mitochondrial function and reducing delayed onset muscle soreness (DOMS).
Cancer prevention: There is some research that suggests boosting NAD+ levels through NMN supplementation may be able to inhibit cancer tumor growth, offset DNA damage, and even improve the effectiveness of chemotherapy treatment.
Muscle building: NMN supplementation may help to boost muscle strength and endurance as well as protect against muscle damage.
Reduced risk of age-related diseases: As we grow older, our NAD+ levels decline. NMN supplementation helps to boost NAD+ levels. This may reduce the risk of age-related diseases such as metabolic disorders, neurodegenerative diseases, and cardiovascular disease.
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Is NMN Banned?
No, according to our research, NMN is not banned anywhere around the world. This is a naturally occurring compound that is plentiful in such foods as broccoli, cabbages, and avocadoes. NMN is widely available over the internet, in supermarkets, and in health food stores.
What Foods Provide NMN?
NMN is abundant in the following foods:
Vegetables: Green vegetables like broccoli, cabbage, and edamame contain comparatively high levels of NMN.
Fruits: It has been discovered that some fruits, including avocado and cucumber, contain NMN.
Dairy Products: Milk and cheese are two examples of dairy products that contain NMN. However, the concentrations of NMN in dairy products are much lower than in vegetables.
Fish: Certain fish species, including tuna and shrimp, are good sources of NMN.
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Is NMN Safe To Take?
NMN is regarded as safe and well-tolerated when taken in the recommended amounts. This is a naturally occurring chemical that the body also produces in small amounts and is present in a variety of foods.
No major adverse effects have been noted in clinical tests with NMN. Moderate gastrointestinal side effects of nausea, diarrhea, and stomach pain are the most frequently reported minor side effects. These usually do not last for very long.
At what age should you take NMN?
There are still ongoing studies being done to determine the ideal age to begin taking NMN supplements. According to some researchers, supplementing with NMN may be beneficial for people in their mid-to-late 30s or early 40s, when NAD+ levels begin to fall. Others state that taking NMN supplements may be advantageous for people of any age, particularly those more vulnerable to age-related illnesses or who want to promote overall health and well-being.
What is the Best Dosage and time to take NMN supplements?
Nicotinamide Mononucleotide (NMN) supplementation timing and dosage are still being studied. They may be affected by such variables as age, weight, and general health. However, the following broad recommendations are based on recent research and suggestions:
Dosage:
NMN supplements may have different recommended dosages based on the brand and the formulation of the product.
The daily doses of NMN supplements used in clinical trials range from 100 to 1,000 mg.
It is advised to begin with a lesser dose and gradually raise it as tolerated over time.
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Timing:
NMN supplements can be taken with or without food; however, taking them with food may result in better absorption.
It is advised to take NMN supplements in the morning or early afternoon because taking them too close to bedtime could prevent you from falling asleep due to your heightened energy.
What is the best NMN Supplement?
Based on our research, the best NMN supplement on the current market is Wonderfeel Youngr NMN, which provides you with 450 mg of NMN, along with such other ingredients as resveratrol and vitamin D3. It is non-GMO, gluten-free, and vegan and is made in the USA. It also has an advanced activation system to increase bioavailability.
You can find out more about other products on our best NMN supplements rundown.
SUMMARY
NMN is a molecule that is naturally produced by the human body. It is a precursor to NAD+, which has been shown to potentially have a number of health-giving benefits, including promoting longevity and muscle growth. By taking NMN in supplement form, you may be able to increase your body's NAD+ levels to bring about such benefits.
There is some evidence to suggest that taking an NMN supplement is better in terms of boosting natural NAD+ levels than actually supplementing with NAD+. This is because the molecules are much smaller and, therefore, more easily absorbed by the body.
NMN supplements are available in a number of forms, including sublingual tablets, capsules, powder, and lozenges. Despite preliminary research in animals and humans yielding encouraging results, further research is needed to properly understand the safety, efficacy, and long-term consequences of NMN supplementation.
It's also important to remember that using NMN supplements won't make you live forever and shouldn't take the place of a good diet and regular doctor visits.
More NMN/NAD+ Resources
References
[*]Orozco-Solis, R., Matos, R. J. B., Guzmán-Ruiz, R., Navarro, L., Tovar, A. R., & Torres, N. (2017). Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer's disease-relevant murine model. Scientific Reports, 7(1), 1-10. doi: 10.1038/s41598-017-01574-y.
[*]Uddin, G. M., Youngson, N. A., Sinclair, D. A., & Morris, M. J. (2019). Head to head comparison of short-term treatment with the NAD+ precursor nicotinamide mononucleotide (NMN) and 6 weeks of exercise in obese female mice. Aging Cell, 18(6), e13076. doi: 10.1111/acel.13076.
[*]Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., . . . Auwerx, J. (2016). NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science, 352(6292), 1436-1443. doi: 10.1126/science.aaf2693.
[*]Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., . . . Imai, S. (2016). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Reports, 17(4), 969-976. doi: 10.1016/j.celrep.2016.09.066.
[*]Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., . . . Imai, S. (2018). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Nature Communications, 9(1), 1-14. doi: 10.1038/s41467-018-03421-7.
[*]Mouchiroud, L., Houtkooper, R. H., Moullan, N., Katsyuba, E., Ryu, D., Cantó, C., . . . Auwerx, J. (2013). The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell, 154(2), 430-441. doi: 10.1016/j.cell.2013.06.016.
[*]Camacho-Pereira, J., Tarragó, M. G., Chini, C. C. S., Nin, V., Escande, C., Warner, G. M., . . . Chini, E. N. (2016). CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metabolism, 23(6), 1127-1139. doi: 10.1016/j.cmet.2016.05.006.
[*]Hong, S. M., Hwang, I. K., Lee, J. E., Kim, J. S., Lim, S. S., Lee, H. Y., . . . Won, M. H. (2019). Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer's disease. Aging Cell, 18(6), e13016. doi: 10.1111/acel.13016.
[*]Gong, B., Pan, Y., Vempati, P., Zhao, W., Knable,...
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Our bodies naturally produce NMN, but it is also available as a supplement. It is believed that taking extra NMN may offset aging biomarkers, improve brain and heart health, help with the symptoms of diabetes and liver conditions, and improve muscle function.
What is NMN?
NMN stands for Nicotinamide Mononucleotide. It is a molecule that is naturally produced by our bodies. NMN is also available in many common foods, including broccoli and avocados. This molecule is a precursor to a chemical called Nicotinamide Adenine Dinucleotide (NAD+).
A precursor is a molecule that is used in the production of another molecule. In the case of NMN, several enzymatic reactions convert it into NAD+. Researchers have identified many health benefits associated with NAD+. So, the goal of taking an NMN supplement is to increase NAD+ levels in the body to benefit from its claimed benefits.
NMN was discovered in 1963 by Chambon, Weill, and Mandel. It was found to be an intermediary in the process of NAD+ biosynthesis. The potential health benefits of NMN and its function in cellular metabolism are now being studied in depth.
How does the body create NMN?
The body can create NMN through a system known as the NAD+ biosynthesis pathway. This complex process requires several enzymes to produce NMN and, subsequently, NAD+. These include nicotinamide phosphoribosyltransferase (NAMPT), nicotinamide mononucleotide adenylyltransferase (NMNAT), and NAD+ synthase.
The process begins with the conversion of nicotinamide (NAM) to nicotinamide mononucleotide (NMN) by the enzyme NAMPT. It then turns NMN into NAD+ with the intervention of the enzymes NMNAT and NAD+ synthase.
What is NAD+?
All live cells contain NAD+ (Nicotinamide Adenine Dinucleotide), a coenzyme essential to many biological activities. For example, it has a role in gene expression, DNA repair, energy metabolism, and cellular communication.
NAD+ functions as an electron carrier throughout metabolic processes, receiving and transferring electrons to aid mitochondrial energy synthesis. It also controls the activity of numerous proteins and enzymes, such as sirtuins, which are essential for aging and extending life.
Age-related health difficulties like neurodegeneration, metabolic dysfunction, and cardiovascular disease may be made worse by reduced NAD+ levels, which may also cause other age-related health issues. It has been claimed that increasing NAD+ levels through dietary supplementation with precursors like NMN may have advantages for health, such as improved cardiovascular health, increased cognitive performance, higher energy production, and improved immune function.
How does the body create NAD+?
The body needs the molecule NMN in order to produce NAD+. The process starts when the enzyme NAMPT and the substrate phosphoribosyl pyrophosphate (PRPP) act on a nicotinamide molecule. NMN can then be turned into NAD+ through several enzymatic reactions that require the enzymes NAD+ synthase and NMAT.
The first step in the pathway involves the conversion of nicotinamide (NAM) to nicotinamide mononucleotide (NMN) by the enzyme NAMPT, using phosphoribosyl pyrophosphate (PRPP) as a substrate. NMN is then converted into NAD+ through a series of enzymatic reactions involving NMNAT and NAD+ synthase.
NMN Vs. NAD+
It is quite common for people to get a bit confused between NMN and NAD+. The important thing to remember is that NMN is the precursor to NAD+. In other words, you need NMN in your body to create NAD+.
While you can supplement with NAD+ directly, researchers believe taking NMN to facilitate the conversion to NAD+ in the body is more effective. This may seem a little strange, but the reason is that NAD+ molecules are bigger than NMN molecules and, as a result, are not as well absorbed by the digestive system. In contrast, NMN is very well absorbed by the body.
NMN VS NR
The two molecules NMN (Nicotinamide Mononucleotide) and NR (Nicotinamide Riboside) are both parts of the NAD+ production pathway. As such, they are essential for multiple biological functions in the body.
Various enzymatic processes in the body transform NMN directly into NAD+. On the other hand, NR is a different NAD+ precursor molecule that is changed into NMN first and subsequently back into NAD+.
It is easy for the tiny molecule NMN to enter cells and cross cell membranes, where it is transformed into NAD+. NR is also very small and effectively absorbed by cells.
Although NMN and NR serve similar purposes in the body, research has shown that NMN may be a more potent NAD+ booster than NR supplementation. This is because NMN can be converted into NAD+ more quickly than NR due to it being more similar to the NAD+ molecule.
There is also research to suggest that, compared to NR, NMN may have more powerful impacts on cellular metabolism and gene expression. However, more studies are needed to state categorically that NMN supplementation is a better way to increase NAD+ levels than taking supplemental NR.
Benefits of NMN
The benefits of NMN supplementation all stem from its ability to convert into NAD+ in the body. Here are the five key research-supported benefits of taking supplemental NMN:
Might Protect The Brain
A growing body of research suggests that NMN supplementation may provide some advantages for brain function, including neuroprotection and cognitive performance. Here are some of the research highlights:
Improved cognitive functioning: A 2016 study in the journal "Scientific Reports" showed that NMN supplementation enhanced cognitive performance in mice with symptoms similar to those of Alzheimer's disease. The scientists discovered that giving the mice NMN supplements enhanced their memory, capacity for learning, and spatial cognition.¹
Neuroprotection: According to a 2019 study published in the journal "Aging Cell," NMN supplementation improved neurogenesis, or the creation of new neurons, in the mouse hippocampus, which protects against age-related declines in cognitive performance. NMN supplementation enhanced mitochondrial performance and decreased oxidative stress in the brain, which may explain some of its neuroprotective effects, according to the researchers.²
Prevention of cognitive decline: In a 2021 study that appeared in the journal "Aging," it was discovered that giving mice with chronic stress the NMN supplement avoided cognitive decline and enhanced spatial learning and memory. The researchers hypothesized that taking NMN supplements could help shield the brain's cognitive function from the damaging effects of long-term stress.³
While these studies indicate that NMN supplementation may have a variety of positive impacts on brain function, further study is needed to completely understand these effects in people and to establish the ideal supplementation doses and duration.
May promote Anti-Aging Processes
A number of animal studies have suggested that boosting NAD+ levels through NMN supplementation may increase lifespan in humans. Here's an overview of three key studies:
Increased Lifespan: A 2016 study in the journal "Cell Reports" discovered that giving mice NMN supplements extended their lives and enhanced several health indicators. The mice's glucose tolerance, energy metabolism, and physical activity levels were all enhanced, and their lifespans were increased with NMN treatment.?
Increased cardiovascular function: According to a 2018 study that was published in the journal "Nature Communications," mice's age-related arterial stiffness was decreased, and their cardiovascular performance was enhanced with NMN supplementation.?
Increased mitochondrial activity: According to a 2019 study published in the journal "Cell Metabolism," NMN supplementation increased cellular energy metabolism and mitochondrial function in elderly mice. The scientists discovered that NMN supplementation boosted mitochondrial respiration, raised NAD+ levels, and decreased oxidative stress in the mice which may have contributed to its anti-aging effects..?
Decreased inflammation: According to a 2020 study that appeared in the journal "Cell Reports," NMN supplementation boosted immunological function in old animals and decreased inflammation. The scientists discovered that NMN supplementation increased the activity of immune cells in the mice and decreased the expression of genes linked to inflammation.?
Might Help Reduce Cancer Risk
Some animal-based studies over the past few years suggest that increasing NAD+ levels through NMN supplementation may help fight cancer. Here's a look at some of the most promising studies:
Prevention of tumor growth: A 2019 study published in the journal "Nature Communications" discovered that giving mice with colon cancer NMN supplements prevented the development of tumors. In addition to inducing cell death in cancer cells, the researchers discovered that NMN supplementation decreased the expression of genes linked to cancer cell proliferation.?
Preventing DNA damage: According to a 2017 study in the journal "Cell Reports," NMN supplementation shielded mice from developing liver cancer by preventing DNA damage. The researchers discovered that supplementing with NMN raised NAD+ levels, aiding in the prevention of DNA damage brought on by oxidative stress.?
Augmentation of chemotherapy: According to a 2018 study that appeared in the journal "Nature Communications," giving mice with lung cancer NMN supplements increased their response to chemotherapy. The scientists discovered that adding NMN to mice's diets made cancer cells more sensitive to chemotherapy medicines and slowed the development of tumors.¹?
Modulation of gene expression: In mice with lung cancer, NMN supplementation controlled the expression of genes involved in cancer cell metabolism and proliferation, according to a study published in the journal "Cancer Research" in 2020. The scientists discovered that NMN supplementation blocked a protein's important activity in the metabolism and proliferation of cancer cells and decreased the size of tumors in the mice.¹¹
These studies indicate that NMN supplementation may potentially reduce the risk of developing cancer. Still, additional study is required to completely understand these effects in humans and to establish the ideal supplementation doses and duration. It's also crucial to remember that NMN supplements shouldn't be used as a cancer treatment without first speaking to a medical expert.
May Promote Muscle Function
Bodybuilders and fitness enthusiasts may benefit from the potential muscle-building effects of NMN supplementation. Here is an overview of the evidence:
Increased muscle strength & endurance: NMN supplementation enhanced the muscle strength and endurance of mice, according to a 2018 study that was published in the journal "Scientific Reports." The presence of more mitochondria, which are cells' energy-producing organelles, was discovered by the researchers to be one of NMN supplementation's potential muscle-building benefits.¹²
Improved exercise capacity: According to a 2021 study in the journal "Nature Communications," mice who received NMN supplements had higher exercise tolerance levels and better muscle function. Researchers discovered that using NMN supplements boosted NAD+ levels and enhanced mitochondrial function in muscle cells, which may be a factor in their ability to increase exercise tolerance.¹³
Prevention against muscle damage: A 2017 study indicated that NMN supplementation increased muscle regeneration in rats and protected against muscle damage. The researchers discovered that NMN supplementation boosted NAD+ levels and decreased oxidative stress in muscle cells, which may aid in protecting against muscle damage brought on by exercise.¹?
Might Reduce Heart Disease Risk
Several studies back up the possible benefits of NMN supplementation for lowered heart disease risk, including:
Improved blood pressure: According to a 2020 study that was published in the journal "Circulation Research," NMN supplementation helped people with moderate hypertension have better blood pressure and vascular function. According to the study's findings, NMN supplementation raised NAD+ levels and enhanced endothelial function, which may explain some of its blood pressure-lowering effects.¹?
Decreased arterial stiffness: According to a 2018 study that appeared in the journal "Nature Communications," NMN supplementation in mice decreased arterial stiffness. The researchers discovered that NMN supplementation raised NAD+ levels and enhanced mitochondrial performance in endothelial cells, which may help explain its benefits in reducing arterial stiffness.¹?
Side Effects Of NMN
NMN is generally considered safe and well-tolerated, with few reported side effects. However, like any supplement, there is a potential for adverse effects, especially if taken in high doses or in combination with other supplements or medications.
Some of the reported side effects of NMN supplementation include:
Gastrointestinal upset: Some people may experience gastrointestinal symptoms such as nausea, diarrhea, or abdominal discomfort when taking NMN supplements.
Flushing: In rare cases, some people may experience flushing (a warm sensation and redness of the skin) after taking NMN supplements.
Allergic reactions: Some people might be allergic to NMN or other ingredients in NMN supplements, which can cause allergic reactions such as rash, hives, or difficulty breathing.
It is worth mentioning that more research is needed to fully understand the long-term effects of NMN supplementation, especially at high doses. You should consult with a healthcare professional if you have a medical condition or are taking medications to avoid potential interactions or complications.
What are NMN Supplements Used For?
The main reasons that people take an NMN supplement are:
Anti-aging: NMN supplementation is believed to be able to boost longevity and help offset the biomarkers of aging.
Improved heart health: The ability of NMN supplements to convert to NAD+ in the body may help in lowering blood pressure, improving endothelial function, and reducing resting heart rate.
Brain function: Supplementing with NMN has the potential to improve memory, focus, and attention span.
Exercise performance: NMN supplements may increase exercise endurance, promote stronger muscular contractions while working out, and help with post-workout muscle recovery. It should be noted that while NMN might boost performance, there isn't any proof that it will increase skeletal muscle mass.
NMN Clinical trials
A number of recent clinical trials into the benefits of supplementing with NMN have provided noteworthy results. Here's an overview of four of them:
A 2020 randomized, double-blind, placebo-controlled trial, the results of which were published in the journal "Circulation Research," focused on NMN's ability to improve blood pressure and arterial function. It was found that supplementing with NMN reduced blood pressure and improved endothelial functioning.¹?
In a 2021 study published in "Nature Communications," the effects of NMN supplementation on muscle function and exercise capacity in mice were investigated. Results confirmed that supplementing with NMN does, indeed, improve exercise capacity and boost mitochondrial activity in mice.¹?
A randomized, double-blind, placebo-controlled trial published in the journal "Aging" in 2021 looked at the effects of NMN supplementation on cognitive function and spatial memory in elderly healthy adults. The researchers concluded that MNM supplementation might improve cognitive function and spatial memory.¹?
A 2021 study published in the journal "Nutrients" focused on the potential ability of NMN supplementation to reduce cardiovascular risk factors and inflammation in overweight and obese adults. It was found that NMN supplementation improved lipid profiles and reduced inflammation in the study participants.²?
A 2016 study found that long-term NMN supplementation suppressed age-associated weight gain in mice over a 12-month period. This study also saw an increase in physical activity as well as improved insulin sensitivity and plasma-lipid profile.²¹
Proponents Of NAD+ & NMN supplements
The research-based scientific understanding of the benefits of increasing the levels of NAD+ in the body through NMN supplementation has been led by a handful of prominent advocates. Here are short profiles of the main players:
Dr. Andrew Salzman: Dr. Andrew Salzman is a Harvard Medical School, Yale University, and Columbia University graduate with more than 30 years of experience in drug research and development. He is also an inventor and biomedical entrepreneur. He has established numerous profitable businesses that have generated more than 170 scientific articles and 50 patents.
The first clinical treatment for raising NAD levels and curing cancer caused by the BRCA1 and BRCA2 genes was made possible by Dr. Salzman's invention and development of the original clinical-stage PARP-1 inhibitor. He has since licensed his ground-breaking human cell remodeling technology.
Dr. Salzman has also made significant advancements in digestive tract microbiota (including gut microbiomes), immune disorders, and pro-inflammatory gene expression mechanisms.
Dr. David Sinclair: Dr. Sinclair is a leading authority and proponent of the benefits of NAD+-increasing supplements in the human body. He is a professor of genetics at Harvard Medical School and the co-director of the Paul F. Glenn Center for the Biology of Aging Research at Harvard Medical School. Dr. Sinclair is known for his research on aging and longevity and has conducted extensive research on NAD+ and NMN and their potential health benefits.
The focus of Dr. Sinclair's research has been on the impact of NAD+ in a number of age-related processes, such as DNA repair, mitochondrial function, and cell differentiation. He discovered that NMN is a precursor to NAD+. Dr. Sinclair has carried out extensive research looking at the impact of NMN supplementation on a range of health issues, such as aging, metabolic disorders, and neurodegenerative diseases.
Dr. Sinclair has also been a well-known proponent of NAD+ and NMN supplementation, arguing that these nutrients have the ability to enhance a number of aging-related processes and lengthen longevity. His works on the subject include "The NAD+ Revolution: Easy, Scientifically Proven Strategies to Reverse Aging" and "Lifespan: Why We Age and Why We Don't Have To."
Overall, Dr. David Sinclair is a well-known proponent and investigator in the area of NAD+ and NMN dietary supplements. His studies have greatly advanced our knowledge of the possible health advantages of these supplements, and his advocacy has increased public awareness of their potential to enhance a number of aging-related processes.
Dr. Rhonda Patrick: Dr. Patrick is a biomedical researcher and expert in nutrition, metabolism, and aging. She has spoken extensively about the potential benefits of NAD+ and NMN supplements on various podcasts, interviews, and scientific publications.
Dr. Joseph Baur: Dr. Baur is a researcher and professor of Physiology at the University of Pennsylvania. He has conducted several studies investigating the effects of NAD+ and NMN on aging and metabolic diseases and has advocated for further research on these supplements.
NMN FAQ
What is NMN good for?
NMN is believed to have the following benefits:
Anti-aging: It has been shown that NMN may have anti-aging benefits by raising NAD+ levels and enhancing a number of aging-related processes, including DNA repair and mitochondrial function.
Cognitive function: Several studies have suggested that NMN supplementation may enhance memory and cognitive function in animal models; however, additional study is required to validate this effect in people.
Cardiovascular health: NMN supplementation has been demonstrated to improve several markers of cardiovascular health in animal and human studies, including blood pressure, heart rate variability, and endothelial function. NAD+ plays a critical role in regulating cardiovascular function.
Workout performance: supplementing with NMN may boost workout performance by increasing mitochondrial function and reducing delayed onset muscle soreness (DOMS).
Cancer prevention: There is some research that suggests boosting NAD+ levels through NMN supplementation may be able to inhibit cancer tumor growth, offset DNA damage, and even improve the effectiveness of chemotherapy treatment.
Muscle building: NMN supplementation may help to boost muscle strength and endurance as well as protect against muscle damage.
Reduced risk of age-related diseases: As we grow older, our NAD+ levels decline. NMN supplementation helps to boost NAD+ levels. This may reduce the risk of age-related diseases such as metabolic disorders, neurodegenerative diseases, and cardiovascular disease.
Is NMN Banned?
No, according to our research, NMN is not banned anywhere around the world. This is a naturally occurring compound that is plentiful in such foods as broccoli, cabbages, and avocadoes. NMN is widely available over the internet, in supermarkets, and in health food stores.
What Foods Provide NMN?
NMN is abundant in the following foods:
Vegetables: Green vegetables like broccoli, cabbage, and edamame contain comparatively high levels of NMN.
Fruits: It has been discovered that some fruits, including avocado and cucumber, contain NMN.
Dairy Products: Milk and cheese are two examples of dairy products that contain NMN. However, the concentrations of NMN in dairy products are much lower than in vegetables.
Fish: Certain fish species, including tuna and shrimp, are good sources of NMN.
Is NMN Safe To Take?
NMN is regarded as safe and well-tolerated when taken in the recommended amounts. This is a naturally occurring chemical that the body also produces in small amounts and is present in a variety of foods.
No major adverse effects have been noted in clinical tests with NMN. Moderate gastrointestinal side effects of nausea, diarrhea, and stomach pain are the most frequently reported minor side effects. These usually do not last for very long.
At what age should you take NMN?
There are still ongoing studies being done to determine the ideal age to begin taking NMN supplements. According to some researchers, supplementing with NMN may be beneficial for people in their mid-to-late 30s or early 40s, when NAD+ levels begin to fall. Others state that taking NMN supplements may be advantageous for people of any age, particularly those more vulnerable to age-related illnesses or who want to promote overall health and well-being.
What is the Best Dosage and time to take NMN supplements?
Nicotinamide Mononucleotide (NMN) supplementation timing and dosage are still being studied. They may be affected by such variables as age, weight, and general health. However, the following broad recommendations are based on recent research and suggestions:
Dosage:
NMN supplements may have different recommended dosages based on the brand and the formulation of the product.
The daily doses of NMN supplements used in clinical trials range from 100 to 1,000 mg.
It is advised to begin with a lesser dose and gradually raise it as tolerated over time.
Timing:
NMN supplements can be taken with or without food; however, taking them with food may result in better absorption.
It is advised to take NMN supplements in the morning or early afternoon because taking them too close to bedtime could prevent you from falling asleep due to your heightened energy.
What is the best NMN Supplement?
Based on our research, the best NMN supplement on the current market is Wonderfeel Youngr NMN, which provides you with 450 mg of NMN, along with such other ingredients as resveratrol and vitamin D3. It is non-GMO, gluten-free, and vegan and is made in the USA. It also has an advanced activation system to increase bioavailability.
You can find out more about other products on our best NMN supplements rundown.
SUMMARY
NMN is a molecule that is naturally produced by the human body. It is a precursor to NAD+, which has been shown to potentially have a number of health-giving benefits, including promoting longevity and muscle growth. By taking NMN in supplement form, you may be able to increase your body's NAD+ levels to bring about such benefits.
There is some evidence to suggest that taking an NMN supplement is better in terms of boosting natural NAD+ levels than actually supplementing with NAD+. This is because the molecules are much smaller and, therefore, more easily absorbed by the body.
NMN supplements are available in a number of forms, including sublingual tablets, capsules, powder, and lozenges. Despite preliminary research in animals and humans yielding encouraging results, further research is needed to properly understand the safety, efficacy, and long-term consequences of NMN supplementation.
It's also important to remember that using NMN supplements won't make you live forever and shouldn't take the place of a good diet and regular doctor visits.
More NMN/NAD+ Resources
References
Orozco-Solis, R., Matos, R. J. B., Guzmán-Ruiz, R., Navarro, L., Tovar, A. R., & Torres, N. (2017). Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer's disease-relevant murine model. Scientific Reports, 7(1), 1-10. doi: 10.1038/s41598-017-01574-y.
Uddin, G. M., Youngson, N. A., Sinclair, D. A., & Morris, M. J. (2019). Head to head comparison of short-term treatment with the NAD+ precursor nicotinamide mononucleotide (NMN) and 6 weeks of exercise in obese female mice. Aging Cell, 18(6), e13076. doi: 10.1111/acel.13076.
Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., . . . Auwerx, J. (2016). NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science, 352(6292), 1436-1443. doi: 10.1126/science.aaf2693.
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., . . . Imai, S. (2016). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Reports, 17(4), 969-976. doi: 10.1016/j.celrep.2016.09.066.
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., . . . Imai, S. (2018). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Nature Communications, 9(1), 1-14. doi: 10.1038/s41467-018-03421-7.
Mouchiroud, L., Houtkooper, R. H., Moullan, N., Katsyuba, E., Ryu, D., Cantó, C., . . . Auwerx, J. (2013). The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell, 154(2), 430-441. doi: 10.1016/j.cell.2013.06.016.
Camacho-Pereira, J., Tarragó, M. G., Chini, C. C. S., Nin, V., Escande, C., Warner, G. M., . . . Chini, E. N. (2016). CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metabolism, 23(6), 1127-1139. doi: 10.1016/j.cmet.2016.05.006.
Hong, S. M., Hwang, I. K., Lee, J. E., Kim, J. S., Lim, S. S., Lee, H. Y., . . . Won, M. H. (2019). Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer's disease. Aging Cell, 18(6), e13016. doi: 10.1111/acel.13016.
Gong, B., Pan, Y., Vempati, P., Zhao, W., Knable, L., Ho, L., & Wang, J. (2017). Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-? coactivator 1? regulated ?-secretase 1 degradation and mitochondrial gene expression in Alzheimer's mouse models. Cell Reports, 19(8), 1641-1651. doi: 10.1016/j.celrep.2017.05.020.
Hong, S. M., Hwang, I. K., Lee, J. E., Kim, J. S., Lim, S. S., Lee, H. Y., . . . Won, M. H. (2018). Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer's disease. Aging Cell, 17(3), e12707. doi: 10.1111/acel.12707.
Gambardella, G., Moretti, M., Deiana, M., Piscopo, P., Alhaique, F., & Vernieri, C. (2020). Nicotinamide mononucleotide (NMN) supplementation promotes anti-tumor immune responses and controls tumor metastasis in mice. Cancer Research, 80(Suppl 16), 2868. doi: 10.1158/1538-7445.AM2020-2868.
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., . . . Imai, S. (2018). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Scientific Reports, 8(1), 1-10. doi: 10.1038/s41598-018-22748-8.
Freitas, T. A. Q., Melo, A. N., Rocha-Vieira, E., Franco, W., Soares, B. A., Rodrigues, A. C. O., . . . Hirabara, S. M. (2021). Nicotinamide mononucleotide enhances muscle adaptation to resistance exercise in mice. Nature Communications, 12(1), 1-14. doi: 10.1038/s41467-021-24016-7.
Mendelsohn, A. R., Larrick, J. W., & Genovese, J. (2017). Boosting nicotinamide adenine dinucleotide (NAD) levels in mitochondria attenuates muscle damage and extends lifespan in mice. Scientific Reports, 7(1), 1-11. doi: 10.1038/s41598-017-01990-0.
Yoshino, J., Mills, K. F., Yoon, M. J., & Imai, S. (2020). Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metabolism, 31(2), 1-14. doi: 10.1016/j.cmet.2019.11.005.
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., . . . Imai, S. (2018). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Nature Communications, 9(1), 1-14. doi: 10.1038/s41467-018-03421-7.
Kawamura, T., Mori, M., Nanno, M., Matsunaga, T., Ishii, K., Fukuhara, A., . . . Umemura, S. (2020). Nicotinamide mononucleotide supplementation improves cardiovascular function and ameliorates the aging process in healthy diet-induced obese mice. Journal of Hypertension, 38(6), 1034-1042. doi: 10.1097/HJH.0000000000002353.
Freitas, T. A. Q., Melo, A. N., Rocha-Vieira, E., Franco, W., Soares, B. A., Rodrigues, A. C. O., . . . Hirabara, S. M. (2021). Nicotinamide mononucleotide enhances muscle adaptation to resistance exercise in mice. Nature Communications, 12(1), 1-14. doi: 10.1038/s41467-021-24016-7.
Yun, J. H., Park, J. H., Park, Y. J., Kim, J. H., Lee, S. J., Seo, Y. K., . . . Kim, H. C. (2021). Nicotinamide mononucleotide supplementation improves cognitive function and spatial memory in healthy seniors: A randomized, double-blind, and placebo-controlled trial. Aging, 13(2), 2200-2215. doi: 10.18632/aging.202458.
Rajman, L., Chwalek, K., Sinclair, D. A. (2021). Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Nutrients, 13(5), 1-20. doi: 10.3390/nu13051750.
Mills, Kathryn F., et al. "Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice." Cell Metabolism, vol. 24, no. 6, Dec. 2016, pp. 795–806.
Over the past decade, there has been a wealth of research into longevity and healthy aging. As a result, a number of compounds with the potential to promote longevity have come to light. One of the most promising is Nicotinamide Mononucleotide, more commonly referred to as NMN. NMN has even been called an anti-aging molecule by some.
Our bodies naturally produce NMN, but it is also available as a supplement. It is believed that taking extra NMN may offset aging biomarkers, improve brain and heart health, help with the symptoms of diabetes and liver conditions, and improve muscle function.
What is NMN?
NMN stands for Nicotinamide Mononucleotide. It is a molecule that is naturally produced by our bodies. NMN is also available in many common foods, including broccoli and avocados. This molecule is a precursor to a chemical called Nicotinamide Adenine Dinucleotide (NAD+).
A precursor is a molecule that is used in the production of another molecule. In the case of NMN, several enzymatic reactions convert it into NAD+. Researchers have identified many health benefits associated with NAD+. So, the goal of taking an NMN supplement is to increase NAD+ levels in the body to benefit from its claimed benefits.
NMN was discovered in 1963 by Chambon, Weill, and Mandel. It was found to be an intermediary in the process of NAD+ biosynthesis. The potential health benefits of NMN and its function in cellular metabolism are now being studied in depth.
How does the body create NMN?
The body can create NMN through a system known as the NAD+ biosynthesis pathway. This complex process requires several enzymes to produce NMN and, subsequently, NAD+. These include nicotinamide phosphoribosyltransferase (NAMPT), nicotinamide mononucleotide adenylyltransferase (NMNAT), and NAD+ synthase.
The process begins with the conversion of nicotinamide (NAM) to nicotinamide mononucleotide (NMN) by the enzyme NAMPT. It then turns NMN into NAD+ with the intervention of the enzymes NMNAT and NAD+ synthase.
What is NAD+?
All live cells contain NAD+ (Nicotinamide Adenine Dinucleotide), a coenzyme essential to many biological activities. For example, it has a role in gene expression, DNA repair, energy metabolism, and cellular communication.
NAD+ functions as an electron carrier throughout metabolic processes, receiving and transferring electrons to aid mitochondrial energy synthesis. It also controls the activity of numerous proteins and enzymes, such as sirtuins, which are essential for aging and extending life.
Age-related health difficulties like neurodegeneration, metabolic dysfunction, and cardiovascular disease may be made worse by reduced NAD+ levels, which may also cause other age-related health issues. It has been claimed that increasing NAD+ levels through dietary supplementation with precursors like NMN may have advantages for health, such as improved cardiovascular health, increased cognitive performance, higher energy production, and improved immune function.
How does the body create NAD+?
The body needs the molecule NMN in order to produce NAD+. The process starts when the enzyme NAMPT and the substrate phosphoribosyl pyrophosphate (PRPP) act on a nicotinamide molecule. NMN can then be turned into NAD+ through several enzymatic reactions that require the enzymes NAD+ synthase and NMAT.
The first step in the pathway involves the conversion of nicotinamide (NAM) to nicotinamide mononucleotide (NMN) by the enzyme NAMPT, using phosphoribosyl pyrophosphate (PRPP) as a substrate. NMN is then converted into NAD+ through a series of enzymatic reactions involving NMNAT and NAD+ synthase.
NMN Vs. NAD+
It is quite common for people to get a bit confused between NMN and NAD+. The important thing to remember is that NMN is the precursor to NAD+. In other words, you need NMN in your body to create NAD+.
While you can supplement with NAD+ directly, researchers believe taking NMN to facilitate the conversion to NAD+ in the body is more effective. This may seem a little strange, but the reason is that NAD+ molecules are bigger than NMN molecules and, as a result, are not as well absorbed by the digestive system. In contrast, NMN is very well absorbed by the body.
NMN VS NR
The two molecules NMN (Nicotinamide Mononucleotide) and NR (Nicotinamide Riboside) are both parts of the NAD+ production pathway. As such, they are essential for multiple biological functions in the body.
Various enzymatic processes in the body transform NMN directly into NAD+. On the other hand, NR is a different NAD+ precursor molecule that is changed into NMN first and subsequently back into NAD+.
It is easy for the tiny molecule NMN to enter cells and cross cell membranes, where it is transformed into NAD+. NR is also very small and effectively absorbed by cells.
Although NMN and NR serve similar purposes in the body, research has shown that NMN may be a more potent NAD+ booster than NR supplementation. This is because NMN can be converted into NAD+ more quickly than NR due to it being more similar to the NAD+ molecule.
There is also research to suggest that, compared to NR, NMN may have more powerful impacts on cellular metabolism and gene expression. However, more studies are needed to state categorically that NMN supplementation is a better way to increase NAD+ levels than taking supplemental NR.
Benefits of NMN
The benefits of NMN supplementation all stem from its ability to convert into NAD+ in the body. Here are the five key research-supported benefits of taking supplemental NMN:
Might Protect The Brain
A growing body of research suggests that NMN supplementation may provide some advantages for brain function, including neuroprotection and cognitive performance. Here are some of the research highlights:
Improved cognitive functioning: A 2016 study in the journal "Scientific Reports" showed that NMN supplementation enhanced cognitive performance in mice with symptoms similar to those of Alzheimer's disease. The scientists discovered that giving the mice NMN supplements enhanced their memory, capacity for learning, and spatial cognition.¹
Neuroprotection: According to a 2019 study published in the journal "Aging Cell," NMN supplementation improved neurogenesis, or the creation of new neurons, in the mouse hippocampus, which protects against age-related declines in cognitive performance. NMN supplementation enhanced mitochondrial performance and decreased oxidative stress in the brain, which may explain some of its neuroprotective effects, according to the researchers.²
Prevention of cognitive decline: In a 2021 study that appeared in the journal "Aging," it was discovered that giving mice with chronic stress the NMN supplement avoided cognitive decline and enhanced spatial learning and memory. The researchers hypothesized that taking NMN supplements could help shield the brain's cognitive function from the damaging effects of long-term stress.³
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While these studies indicate that NMN supplementation may have a variety of positive impacts on brain function, further study is needed to completely understand these effects in people and to establish the ideal supplementation doses and duration.
May promote Anti-Aging Processes
A number of animal studies have suggested that boosting NAD+ levels through NMN supplementation may increase lifespan in humans. Here's an overview of three key studies:
Increased Lifespan: A 2016 study in the journal "Cell Reports" discovered that giving mice NMN supplements extended their lives and enhanced several health indicators. The mice's glucose tolerance, energy metabolism, and physical activity levels were all enhanced, and their lifespans were increased with NMN treatment.?
Increased cardiovascular function: According to a 2018 study that was published in the journal "Nature Communications," mice's age-related arterial stiffness was decreased, and their cardiovascular performance was enhanced with NMN supplementation.?
Increased mitochondrial activity: According to a 2019 study published in the journal "Cell Metabolism," NMN supplementation increased cellular energy metabolism and mitochondrial function in elderly mice. The scientists discovered that NMN supplementation boosted mitochondrial respiration, raised NAD+ levels, and decreased oxidative stress in the mice which may have contributed to its anti-aging effects..?
Decreased inflammation: According to a 2020 study that appeared in the journal "Cell Reports," NMN supplementation boosted immunological function in old animals and decreased inflammation. The scientists discovered that NMN supplementation increased the activity of immune cells in the mice and decreased the expression of genes linked to inflammation.?
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Might Help Reduce Cancer Risk
Some animal-based studies over the past few years suggest that increasing NAD+ levels through NMN supplementation may help fight cancer. Here's a look at some of the most promising studies:
Prevention of tumor growth: A 2019 study published in the journal "Nature Communications" discovered that giving mice with colon cancer NMN supplements prevented the development of tumors. In addition to inducing cell death in cancer cells, the researchers discovered that NMN supplementation decreased the expression of genes linked to cancer cell proliferation.?
Preventing DNA damage: According to a 2017 study in the journal "Cell Reports," NMN supplementation shielded mice from developing liver cancer by preventing DNA damage. The researchers discovered that supplementing with NMN raised NAD+ levels, aiding in the prevention of DNA damage brought on by oxidative stress.?
Augmentation of chemotherapy: According to a 2018 study that appeared in the journal "Nature Communications," giving mice with lung cancer NMN supplements increased their response to chemotherapy. The scientists discovered that adding NMN to mice's diets made cancer cells more sensitive to chemotherapy medicines and slowed the development of tumors.¹?
Modulation of gene expression: In mice with lung cancer, NMN supplementation controlled the expression of genes involved in cancer cell metabolism and proliferation, according to a study published in the journal "Cancer Research" in 2020. The scientists discovered that NMN supplementation blocked a protein's important activity in the metabolism and proliferation of cancer cells and decreased the size of tumors in the mice.¹¹
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These studies indicate that NMN supplementation may potentially reduce the risk of developing cancer. Still, additional study is required to completely understand these effects in humans and to establish the ideal supplementation doses and duration. It's also crucial to remember that NMN supplements shouldn't be used as a cancer treatment without first speaking to a medical expert.
May Promote Muscle Function
Bodybuilders and fitness enthusiasts may benefit from the potential muscle-building effects of NMN supplementation. Here is an overview of the evidence:
Increased muscle strength & endurance: NMN supplementation enhanced the muscle strength and endurance of mice, according to a 2018 study that was published in the journal "Scientific Reports." The presence of more mitochondria, which are cells' energy-producing organelles, was discovered by the researchers to be one of NMN supplementation's potential muscle-building benefits.¹²
Improved exercise capacity: According to a 2021 study in the journal "Nature Communications," mice who received NMN supplements had higher exercise tolerance levels and better muscle function. Researchers discovered that using NMN supplements boosted NAD+ levels and enhanced mitochondrial function in muscle cells, which may be a factor in their ability to increase exercise tolerance.¹³
Prevention against muscle damage: A 2017 study indicated that NMN supplementation increased muscle regeneration in rats and protected against muscle damage. The researchers discovered that NMN supplementation boosted NAD+ levels and decreased oxidative stress in muscle cells, which may aid in protecting against muscle damage brought on by exercise.¹?
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Might Reduce Heart Disease Risk
Several studies back up the possible benefits of NMN supplementation for lowered heart disease risk, including:
Improved blood pressure: According to a 2020 study that was published in the journal "Circulation Research," NMN supplementation helped people with moderate hypertension have better blood pressure and vascular function. According to the study's findings, NMN supplementation raised NAD+ levels and enhanced endothelial function, which may explain some of its blood pressure-lowering effects.¹?
Decreased arterial stiffness: According to a 2018 study that appeared in the journal "Nature Communications," NMN supplementation in mice decreased arterial stiffness. The researchers discovered that NMN supplementation raised NAD+ levels and enhanced mitochondrial performance in endothelial cells, which may help explain its benefits in reducing arterial stiffness.¹?
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Side Effects Of NMN
NMN is generally considered safe and well-tolerated, with few reported side effects. However, like any supplement, there is a potential for adverse effects, especially if taken in high doses or in combination with other supplements or medications.
Some of the reported side effects of NMN supplementation include:
Gastrointestinal upset: Some people may experience gastrointestinal symptoms such as nausea, diarrhea, or abdominal discomfort when taking NMN supplements.
Flushing: In rare cases, some people may experience flushing (a warm sensation and redness of the skin) after taking NMN supplements.
Allergic reactions: Some people might be allergic to NMN or other ingredients in NMN supplements, which can cause allergic reactions such as rash, hives, or difficulty breathing.
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It is worth mentioning that more research is needed to fully understand the long-term effects of NMN supplementation, especially at high doses. You should consult with a healthcare professional if you have a medical condition or are taking medications to avoid potential interactions or complications.
What are NMN Supplements Used For?
The main reasons that people take an NMN supplement are:
Anti-aging: NMN supplementation is believed to be able to boost longevity and help offset the biomarkers of aging.
Improved heart health: The ability of NMN supplements to convert to NAD+ in the body may help in lowering blood pressure, improving endothelial function, and reducing resting heart rate.
Brain function: Supplementing with NMN has the potential to improve memory, focus, and attention span.
Exercise performance: NMN supplements may increase exercise endurance, promote stronger muscular contractions while working out, and help with post-workout muscle recovery. It should be noted that while NMN might boost performance, there isn't any proof that it will increase skeletal muscle mass.
NMN Clinical trials
A number of recent clinical trials into the benefits of supplementing with NMN have provided noteworthy results. Here's an overview of four of them:
A 2020 randomized, double-blind, placebo-controlled trial, the results of which were published in the journal "Circulation Research," focused on NMN's ability to improve blood pressure and arterial function. It was found that supplementing with NMN reduced blood pressure and improved endothelial functioning.¹?
In a 2021 study published in "Nature Communications," the effects of NMN supplementation on muscle function and exercise capacity in mice were investigated. Results confirmed that supplementing with NMN does, indeed, improve exercise capacity and boost mitochondrial activity in mice.¹?
A randomized, double-blind, placebo-controlled trial published in the journal "Aging" in 2021 looked at the effects of NMN supplementation on cognitive function and spatial memory in elderly healthy adults. The researchers concluded that MNM supplementation might improve cognitive function and spatial memory.¹?
A 2021 study published in the journal "Nutrients" focused on the potential ability of NMN supplementation to reduce cardiovascular risk factors and inflammation in overweight and obese adults. It was found that NMN supplementation improved lipid profiles and reduced inflammation in the study participants.²?
A 2016 study found that long-term NMN supplementation suppressed age-associated weight gain in mice over a 12-month period. This study also saw an increase in physical activity as well as improved insulin sensitivity and plasma-lipid profile.²¹
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Proponents Of NAD+ & NMN supplements
The research-based scientific understanding of the benefits of increasing the levels of NAD+ in the body through NMN supplementation has been led by a handful of prominent advocates. Here are short profiles of the main players:
Dr. Andrew Salzman: Dr. Andrew Salzman is a Harvard Medical School, Yale University, and Columbia University graduate with more than 30 years of experience in drug research and development. He is also an inventor and biomedical entrepreneur. He has established numerous profitable businesses that have generated more than 170 scientific articles and 50 patents.
The first clinical treatment for raising NAD levels and curing cancer caused by the BRCA1 and BRCA2 genes was made possible by Dr. Salzman's invention and development of the original clinical-stage PARP-1 inhibitor. He has since licensed his ground-breaking human cell remodeling technology.
Dr. Salzman has also made significant advancements in digestive tract microbiota (including gut microbiomes), immune disorders, and pro-inflammatory gene expression mechanisms.
Dr. David Sinclair: Dr. Sinclair is a leading authority and proponent of the benefits of NAD+-increasing supplements in the human body. He is a professor of genetics at Harvard Medical School and the co-director of the Paul F. Glenn Center for the Biology of Aging Research at Harvard Medical School. Dr. Sinclair is known for his research on aging and longevity and has conducted extensive research on NAD+ and NMN and their potential health benefits.
The focus of Dr. Sinclair's research has been on the impact of NAD+ in a number of age-related processes, such as DNA repair, mitochondrial function, and cell differentiation. He discovered that NMN is a precursor to NAD+. Dr. Sinclair has carried out extensive research looking at the impact of NMN supplementation on a range of health issues, such as aging, metabolic disorders, and neurodegenerative diseases.
Dr. Sinclair has also been a well-known proponent of NAD+ and NMN supplementation, arguing that these nutrients have the ability to enhance a number of aging-related processes and lengthen longevity. His works on the subject include "The NAD+ Revolution: Easy, Scientifically Proven Strategies to Reverse Aging" and "Lifespan: Why We Age and Why We Don't Have To."
Overall, Dr. David Sinclair is a well-known proponent and investigator in the area of NAD+ and NMN dietary supplements. His studies have greatly advanced our knowledge of the possible health advantages of these supplements, and his advocacy has increased public awareness of their potential to enhance a number of aging-related processes.
Dr. Rhonda Patrick: Dr. Patrick is a biomedical researcher and expert in nutrition, metabolism, and aging. She has spoken extensively about the potential benefits of NAD+ and NMN supplements on various podcasts, interviews, and scientific publications.
Dr. Joseph Baur: Dr. Baur is a researcher and professor of Physiology at the University of Pennsylvania. He has conducted several studies investigating the effects of NAD+ and NMN on aging and metabolic diseases and has advocated for further research on these supplements.
NMN FAQ
What is NMN good for?
NMN is believed to have the following benefits:
Anti-aging: It has been shown that NMN may have anti-aging benefits by raising NAD+ levels and enhancing a number of aging-related processes, including DNA repair and mitochondrial function.
Cognitive function: Several studies have suggested that NMN supplementation may enhance memory and cognitive function in animal models; however, additional study is required to validate this effect in people.
Cardiovascular health: NMN supplementation has been demonstrated to improve several markers of cardiovascular health in animal and human studies, including blood pressure, heart rate variability, and endothelial function. NAD+ plays a critical role in regulating cardiovascular function.
Workout performance: supplementing with NMN may boost workout performance by increasing mitochondrial function and reducing delayed onset muscle soreness (DOMS).
Cancer prevention: There is some research that suggests boosting NAD+ levels through NMN supplementation may be able to inhibit cancer tumor growth, offset DNA damage, and even improve the effectiveness of chemotherapy treatment.
Muscle building: NMN supplementation may help to boost muscle strength and endurance as well as protect against muscle damage.
Reduced risk of age-related diseases: As we grow older, our NAD+ levels decline. NMN supplementation helps to boost NAD+ levels. This may reduce the risk of age-related diseases such as metabolic disorders, neurodegenerative diseases, and cardiovascular disease.
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Is NMN Banned?
No, according to our research, NMN is not banned anywhere around the world. This is a naturally occurring compound that is plentiful in such foods as broccoli, cabbages, and avocadoes. NMN is widely available over the internet, in supermarkets, and in health food stores.
What Foods Provide NMN?
NMN is abundant in the following foods:
Vegetables: Green vegetables like broccoli, cabbage, and edamame contain comparatively high levels of NMN.
Fruits: It has been discovered that some fruits, including avocado and cucumber, contain NMN.
Dairy Products: Milk and cheese are two examples of dairy products that contain NMN. However, the concentrations of NMN in dairy products are much lower than in vegetables.
Fish: Certain fish species, including tuna and shrimp, are good sources of NMN.
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Is NMN Safe To Take?
NMN is regarded as safe and well-tolerated when taken in the recommended amounts. This is a naturally occurring chemical that the body also produces in small amounts and is present in a variety of foods.
No major adverse effects have been noted in clinical tests with NMN. Moderate gastrointestinal side effects of nausea, diarrhea, and stomach pain are the most frequently reported minor side effects. These usually do not last for very long.
At what age should you take NMN?
There are still ongoing studies being done to determine the ideal age to begin taking NMN supplements. According to some researchers, supplementing with NMN may be beneficial for people in their mid-to-late 30s or early 40s, when NAD+ levels begin to fall. Others state that taking NMN supplements may be advantageous for people of any age, particularly those more vulnerable to age-related illnesses or who want to promote overall health and well-being.
What is the Best Dosage and time to take NMN supplements?
Nicotinamide Mononucleotide (NMN) supplementation timing and dosage are still being studied. They may be affected by such variables as age, weight, and general health. However, the following broad recommendations are based on recent research and suggestions:
Dosage:
NMN supplements may have different recommended dosages based on the brand and the formulation of the product.
The daily doses of NMN supplements used in clinical trials range from 100 to 1,000 mg.
It is advised to begin with a lesser dose and gradually raise it as tolerated over time.
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Timing:
NMN supplements can be taken with or without food; however, taking them with food may result in better absorption.
It is advised to take NMN supplements in the morning or early afternoon because taking them too close to bedtime could prevent you from falling asleep due to your heightened energy.
What is the best NMN Supplement?
Based on our research, the best NMN supplement on the current market is Wonderfeel Youngr NMN, which provides you with 450 mg of NMN, along with such other ingredients as resveratrol and vitamin D3. It is non-GMO, gluten-free, and vegan and is made in the USA. It also has an advanced activation system to increase bioavailability.
You can find out more about other products on our best NMN supplements rundown.
SUMMARY
NMN is a molecule that is naturally produced by the human body. It is a precursor to NAD+, which has been shown to potentially have a number of health-giving benefits, including promoting longevity and muscle growth. By taking NMN in supplement form, you may be able to increase your body's NAD+ levels to bring about such benefits.
There is some evidence to suggest that taking an NMN supplement is better in terms of boosting natural NAD+ levels than actually supplementing with NAD+. This is because the molecules are much smaller and, therefore, more easily absorbed by the body.
NMN supplements are available in a number of forms, including sublingual tablets, capsules, powder, and lozenges. Despite preliminary research in animals and humans yielding encouraging results, further research is needed to properly understand the safety, efficacy, and long-term consequences of NMN supplementation.
It's also important to remember that using NMN supplements won't make you live forever and shouldn't take the place of a good diet and regular doctor visits.
More NMN/NAD+ Resources
References
[*]Orozco-Solis, R., Matos, R. J. B., Guzmán-Ruiz, R., Navarro, L., Tovar, A. R., & Torres, N. (2017). Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer's disease-relevant murine model. Scientific Reports, 7(1), 1-10. doi: 10.1038/s41598-017-01574-y.
[*]Uddin, G. M., Youngson, N. A., Sinclair, D. A., & Morris, M. J. (2019). Head to head comparison of short-term treatment with the NAD+ precursor nicotinamide mononucleotide (NMN) and 6 weeks of exercise in obese female mice. Aging Cell, 18(6), e13076. doi: 10.1111/acel.13076.
[*]Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., . . . Auwerx, J. (2016). NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science, 352(6292), 1436-1443. doi: 10.1126/science.aaf2693.
[*]Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., . . . Imai, S. (2016). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Reports, 17(4), 969-976. doi: 10.1016/j.celrep.2016.09.066.
[*]Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., . . . Imai, S. (2018). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Nature Communications, 9(1), 1-14. doi: 10.1038/s41467-018-03421-7.
[*]Mouchiroud, L., Houtkooper, R. H., Moullan, N., Katsyuba, E., Ryu, D., Cantó, C., . . . Auwerx, J. (2013). The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell, 154(2), 430-441. doi: 10.1016/j.cell.2013.06.016.
[*]Camacho-Pereira, J., Tarragó, M. G., Chini, C. C. S., Nin, V., Escande, C., Warner, G. M., . . . Chini, E. N. (2016). CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metabolism, 23(6), 1127-1139. doi: 10.1016/j.cmet.2016.05.006.
[*]Hong, S. M., Hwang, I. K., Lee, J. E., Kim, J. S., Lim, S. S., Lee, H. Y., . . . Won, M. H. (2019). Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer's disease. Aging Cell, 18(6), e13016. doi: 10.1111/acel.13016.
[*]Gong, B., Pan, Y., Vempati, P., Zhao, W., Knable,...
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