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What is NMN
Published: 3:55 p.m. PST May 5, 2020 | Updated: 3:05 p.m. PST Jul 6, 2023
What’s NMN?
Nicotinamide mononucleotide (NMN) is a naturally occurring molecule found in every living cell of all life forms. At the molecular level, it belongs to a class of molecules called nucleotides, the building blocks of RNA and DNA. Structurally, NMN is composed of three main chemical groups: a phosphate group, a ribose sugar, and a nicotinamide base (see image above). NMN is directly converted to nicotinamide adenine dinucleotide (NAD+), thereby elevating NAD+ levels, which is why NMN is somtimes referred to as an NAD+ booster.
The Importance of Boosting NAD+ with NMN
After water, NAD+ is the most abundant molecule in the body and is necessary for life. NAD+ is a coenzyme — a “helper” molecule that enzymes need to function. Enzymes are a specialized type of protein that make chemical reactions much faster. For example, without enzymes some biological reactions would take 2.3 billion years to finish. Thus, life would likely not exist without enzymes.
Importantly, with age, and in cases of chronic diseases like obesity, cardiovascular disease, neurodegenerative disease, and sarcopenia (age-related muscle wasting), NAD+ declines. Thus restoring NAD+ levels under these circumstances with NAD+ precursors like NMN can potentially mitigate the ill effects of aging and even prevent or reverse chronic diseases. The anti-aging and pro-longevity effects of boosting NAD+ in both animal models and humans is currently supported by a growing body of scientific evidence.
NAD+ Activates Sirtuins
NAD+ fuels a critical class of enzymes called sirtuins. Sirtuins are what some call “guardians of the cell,” as they play an active role in repairing DNA and supporting the health of our mitochondria. Mitochondria are referred to as the powerhouse of the cell because they produce cellular energy called ATP. Unhealthy mitochondria produce less ATP, which leads to cell death. Since excessive DNA damage also leads to cell death, sirtuins promote cell survival by repairing DNA and keeping mitochondria pristine.
As David Sinclair, a Harvard geneticist and NAD+ researcher says we lose NAD+ as we age “and the resulting decline in sirtuin activity, is thought to be a primary reason our bodies develop diseases when we are old but not when we are young.” He believes that increasing NAD+ levels, including with NMN during aging may slow or reverse certain aging processes.
In addition to NMN, polyphenols — longevity-promoting plant-based molecules, exercise and caloric restriction — consuming less calories without malnourishment can also boost NAD+ levels and activate sirtuins. In addition to increasing cell survival and protecting DNA (genomic stability), sirtuins provide a multitude of benefits. Sirtuins protect against diabetes and fatty liver by improving insulin secretion from the pancreas, promoting fat metabolism in the liver, and elevating liver glucose production. Sirtuins also protect against sarcopenia, neurodegenration, and fat (adipose) tissue gain.
NAD+ Functions as a Coenzyme in Mitochondria
NAD+ plays an especially active role in metabolic processes, such as glycolysis, the TCA Cycle (AKA Krebs Cycle or Citric Acid cycle), and the electron transport chain, which occurs in our mitochondria and is how we obtain cellular energy.
In its role as a ligand, NAD+ binds to enzymes and transfers electrons between molecules. Electrons are the atomic basis for cellular energy and by transferring them from one molecule to the next, NAD+ acts through a cellular mechanism similar to recharging a battery. A battery is depleted when electrons are expended to provide energy. Those electrons can’t return to their starting point without a boost. In cells, NAD+ serves as that booster. In this way, NAD+ can decrease or increase enzyme activity, gene expression, and cell signaling.
NAD+ Helps Control DNA Damage
As organisms grow older, they accrue DNA damage due to environmental factors such as radiation, pollution, and imprecise DNA replication. According to the current aging theory, the accumulation of DNA damage is the main cause of aging. Almost all cells contain the ‘molecular machinery’ to repair this damage. This machinery consumes NAD+ and energy molecules. Therefore, excessive DNA damage can drain valuable cellular resources.
One important DNA repair protein, PARP (Poly (ADP-ribose) polymerase), depends on NAD+ to function. Older individuals experience decreased levels of NAD+. The accumulation of DNA damage as a result of the normal aging process leads to increased PARP, which causes decreased NAD+ concentration. This depletion is exacerbated by any further DNA damage in the mitochondria.
Why Should We Care About NAD+
Since the discovery of NAD+ in 1906, the molecule has been on scientists’ radar for its abundance in the body and its crucial role in molecular pathways that keep our body running. In animal studies, raising NAD+ levels in the body has shown promising results in research fields like metabolics and age-related disease and has even shown some anti-aging properties. Age-related illnesses such as diabetes, cardiovascular diseases, neurodegeneration and general decreases in the immune system.
Can NMN Help Fight COVID-19
As COVID-19 swept the cities with pneumonia-like illness, infecting millions of people worldwide, scientists are on the hunt for a safe and effective cure. Gerontologist, scientists who study the biology of aging, believe that therapeutics that target aging may provide a new angle to tackle the pandemic.
Statistics have shown that COVID-19 disproportionately infects older adults. About 13.4 percent of patients 80 or older die from COVID-19, compared to 1.25 percent and 0.06 percent of those in their 50s and 20s. A recent study from the University of Oxford that analyzed 17.4 million UK adults showed age is the most substantial risk factor associated with COVID-19 death. Other risk factors include being male, uncontrolled diabetes and severe asthma.
Given the gerolavic nature – harmful to the old – of the virus, some gerontologists claim that treating “aging” can be a long term solution to defend older adults from COVID-19 and other future infectious diseases. Although more study needs to be done, a recent study listed NAD+ boosting agents such as NMN and NR as one of the potential treatments. Other scientists also hypothesized that older adults might benefit from NAD+’s longevity effects and prevent the deadly over-activation of immune responses called a cytokine storm, in which the body attacks its cells rather than the virus.
The cell uses up NAD+ during the fight against coronavirus, weakening our body, according to a recent study that has not been peer-reviewed. NAD+ is essential for innate immune defense against viruses. The researchers of the study are trying to assess whether NAD+ boosters can help humans beat the pandemic.
While scientists are in the lab racing time to find a cure for COVID-19, physicians on the front lines running out of options turn to innovative techniques. As a last resort to treat his patients, doctor Robert Huizenga of Cedars Sinai Medical Center administered an NMN cocktail infused with boosters like zinc to the patient to calm the cytokine storm stirred up by COVID-19. The NMN cocktail brought down the patients’ fever and inflammation levels within 12 hours.
During the pandemic, NMN is receiving more and more attention for its role in maintaining the immune system balance, which may be a possible treatment for the coronavirus-caused cytokine storm. With the preliminary studies showing some positive results, although not a guaranteed cure, many scientists and physicians believe the NAD+ booster’s effect on COVID-19 is worth investigating.
Aging
NAD+ is the fuel that helps sirtuins sustain genome integrity and promote DNA repair. Like a car cannot drive without fuel, sirtuins’ activation requires NAD+. Results from animal studies showed that raising NAD+ level in the body activates sirtuins and increases the lifespans of yeast, worms and mice. Although animal studies showed promising results in anti-aging properties, scientists are still studying how these results can translate to humans.
Metabolic Disorders
NAD+ is one of the keys to maintaining healthy mitochondrial functions and steady energy output. Aging and high-fat diet reduces the level of NAD+ in the body. Studies have shown that taking NAD+ boosters can alleviate diet-associated and age-associated weight gain in mice and improve their exercise capacity, even in aged mice. Other studies even reversed the diabetes effect in female mice, showing new strategies to fight metabolic disorders, such as obesity.
Heart Function
Boosting NAD+ levels protects the heart and improves cardiac functions. High blood pressure can cause an enlarged heart and blocked arteries that lead to strokes. In mice, NAD+ boosters have replenished NAD+ levels in the heart and prevented injuries to the heart caused by a lack of blood flow. Other studies have shown that NAD+ boosters can protect mice from abnormal heart enlargement.
Neurodegeneration
In mice with Alzheimer’s, raising the NAD+ level can decrease protein build up that disrupts cell communication in the brain to increase cognitive function. Boosting NAD+ levels also protects brain cells from dying when there’s insufficient blood flow to the brain. Many studies in animal models present new prospects of helping the brain age healthily, defending against neurodegeneration and improving memory.
Immune System
As adults get older the immune system declines, people get ill more easily, and it becomes harder for people to bounce back from illnesses such as the seasonal flu, or even COVID-19. Recent studies have suggested that NAD+ levels play an important role in regulating inflammation and cell survival during the immune response and aging. The study underscored the therapeutic potential of NAD+ for immune dysfunction.
How Does the Body Make Nicotinamide Adenine Dinucleotide (NAD+)?
Our bodies naturally produce NAD+ from smaller components, or precursors. Think of them as the raw materials for NAD+. There are five main precursors that occur in the body: tryptophan, nicotinamide (Nam), nicotinic acid (NA, or niacin), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN). Of these, NMN represents one of the final steps of NAD+ synthesis.
These precursors can all come from diet. Nam, NA and NR are all forms of vitamin B3, an important nutrient. Once in the body, our cells can synthesize NAD+ by several different pathways. A biochemical pathway is equivalent to a factory production line. In the case of NAD+, multiple production lines all lead to the same product.
The first of these pathways is called the de novo pathway. De novo is a Latin expression that equates to “from scratch.” The de novo pathway begins with the earliest of the NAD+ precursors, tryptophan, and builds upwards from there.
The second pathway is called the salvage pathway. The salvage pathway is akin to recycling, in that it creates NAD+ from the products of NAD+ degradation. All proteins within the body need to be regularly degraded to stop them from accumulating to unhealthy degrees. As part of this cycle of production and degradation, enzymes take some of the results of a protein’s degradation and put it right back into that same protein’s production line.
NAD+ Biosynthesis from NMN
How is NMN Synthesized In the Body?
NMN is produced from B vitamins in the body. The enzyme responsible for making NMN in the body is called nicotinamide phosphoribosyltransferase (NAMPT). NAMPT attaches nicotinamide (a vitamin B3) to a sugar phosphate called PRPP (5’-phosphoribosyl-1-pyrophosphate). NMN can also be made from ‘nicotinamide riboside’ (NR) through the addition of a phosphate group.
‘NAMPT’ is the rate-limiting enzyme in the production of NAD+. This means lower levels of NAMPT cause decreased NMN production, resulting in decreased NAD+ levels. Adding precursor molecules like NMN can also speed up NAD+ production.
Methods to Increase NAD+ levels
Fasting or reducing calorie intake, better known as calorie restriction, has been shown to increase NAD+ levels and sirtuin activity. In mice, the increased NAD+ and sirtuin activity from calorie restriction has been shown to slow the aging process. Although NAD+ is present in some foods, the concentrations are too low to affect intracellular concentrations. Taking certain supplements, such as NMN, has been shown to increase NAD+ levels.
NAD Supplement as NMN
Intracellular concentrations of NAD+ decrease from aging as normal cellular functions deplete NAD+ supplies over time. Healthy levels of NAD+ are thought to be restored by supplementation with NAD+ precursors. According to research, precursors such as NMN and nicotinamide riboside (NR) are viewed as supplements of NAD+ production, increasing concentrations of NAD+. David Sinclair, a NAD+ researcher from Harvard, says, “Feeding or administering NAD+ directly to organisms is not a practical option. The NAD+ molecule cannot readily cross cell membranes to enter cells, and therefore would be unavailable to positively affect metabolism. Instead, precursor molecules to NAD+ must be used to increase bioavailable levels of NAD+.” This means NAD+ cannot be used as a direct supplement, because it is not easily absorbed. NAD+ precursors are more easily absorbed than NAD+ and are more effective supplements.
How are NMN Supplements Absorbed and Distributed Throughout the Body?
NMN appears to be absorbed into cells through a molecular transporter embedded in the cell surface. Being smaller than NAD+, the NMN molecule may be absorbed more efficiently into cells. NAD+ cannot easily enter the body because of the barrier presented by the cell membrane. The membrane has a waterless space which prevents ions, polar molecules, and large molecules from entering without the use of transporters. It was once thought that NMN must be altered before entering cells but new evidence suggests that it can enter cells directly via an NMN-specific transporter in the cellular membrane.
Furthermore, injections of NMN result in increased NAD+ in many regions in the body including the pancreas, fat tissue, the heart, skeletal muscle, kidneys, testes, eyes, and blood vessels. Oral administration of NMN in mice increases NAD+ in the liver within 15 minutes.
NMN is Quickly Converted to NAD+
NMN Side Effects and Safety
NMN is considered safe in animals, and the results are promising enough that human clinical trials have started. This molecule is largely considered to be safe and not toxic, even at high concentrations in mice and in a human study. Long-term (one-year) oral administration in mice does not have toxic effects. The very first clinical trial in humans was completed and the evidence supports the idea that it is not toxic in single doses.
Although one study of Japanese men published in November 2019 noted that subjects had increased levels of bilirubin in their blood following NMN administration, these levels remained within the normal range. Future studies should focus on long-term safety and efficacy of usage. NMN is not associated with any other known side effects.
The History of NMN and NAD+
Nicotinamide adenine dinucleotide, or NAD for short, is one of the most important and versatile molecules in the body. Because it is central to providing cells with energy, there is almost no biological process that does not require NAD. As a result of this, NAD is the focus of widespread biological research.
In 1906, Arthur Harden and William John Young discovered a “factor” in liquid extracted from brewer’s yeast enhanced the fermentation of sugar into alcohol. That “factor,” called a “coferment” at the time, turned out to be NAD.
Harden, along with Hans von Euler-Chelpin, continued to peel apart the mysteries of fermentation. They were awarded the Nobel Prize in 1929 for developing a detailed understanding of these processes, including the chemical shape and properties of what would soon be known as NAD.
The story of NAD expanded in the 1930’s, under the guidance of Otto Warburg, another Nobel laureate, who discovered NAD’s central role in facilitating many biochemical reactions. Warburg discovered that NAD serves as a sort of biological relay for electrons.
The transfer of electrons from one molecule to another, serves as the basis for the energy needed to perform all biochemical reactions.
In 1937, Conrad Elvehjem and colleagues at the University of Wisconsin, Madison, discovered that NAD+ supplementation cured dogs of pellagra, or “Black Tongue.” In humans, pellagra causes a host of symptoms, including diarrhea, dementia, and sores in the mouth. It stems from a niacin deficiency and is now regularly treated with nicotinamide, one of the precursors to NMN.
Arthur Kornberg’s research on NAD+ throughout the 40’s and 50’ was instrumental in leading him to discover the principles behind DNA replication and RNA transcription, two processes vital for life.
In 1958, Jack Preiss and Philip Handler uncovered the three biochemical steps, by which nicotinic acid is converted to NAD. This series of steps, called a pathway, is known today as the Preiss-Handler Pathway.
In 1963, Chambon, Weill, and Mandel reported that nicotinamide mononucleotide (NMN) provided the energy needed to activate an important nuclear enzyme. This discovery paved the way for a series of remarkable discoveries on a type of protein called a PARP. PARPs play crucial roles in repairing DNA damage, regulating cell death, and whose activity is associated with changes in lifespan.
In 1976, Rechsteiner and his colleagues found convincing evidence NAD+ seemed likely to have “some other major function” in mammalian cells, beyond its classical biochemical role as an energy transfer molecule.
This discovery made it possible for Leonard Guarente and his colleagues to discover that proteins called sirtuins use NAD to extend lifespan by differentially keeping some genes “silent.”
Since then, interest has grown in NAD and its intermediates, NMN and NR, for their potential to ameliorate a number of age-related health issues.
The Future of Nicotinamide Mononucleotide
With the promising therapeutic properties that NMN showed in animal studies, researchers are aiming to understand how this molecule works in the human body. A recent clinical trial in Japan demonstrated that the molecule is safe and well tolerated at the used dosage. More studies and human trials are on the way. It is a fascinating and versatile molecule, from which we still have much to learn.
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Nicotinamide Mononucleotide (NMN): Benefits, Side Effects & Dosage
Thanks to advances in modern medicine, individuals around the world have been living longer. In addition to lower mortality and increased survival, a sustained drop in fertility has shifted the proportion of older individuals upwards. According to the World Health Organization, the world’s population of older individuals is expected to reach 2.1 billion by 2050, doubling the aged population.
A longer life, however, does not guarantee a healthy life. As we age, our organs accumulate damage and progressively decline, making us susceptible to diseases. This is why many scientists have shifted their attention towards finding ways to slowdown, prevent, or even reverse aging. If successful, so-called anti-aging therapies could reduce the prevalence of age-related disease and help us live longer and healthier lives.
Currently, one of the most promising anti-aging targets under study is a vital molecule called nicotinamide adenine dinucleotide (NAD+). NAD+ mediates the production of the energy our cells need to function and survive, fueling enzymes key in repairing DNA damage. As we age, this indispensable molecule progressively declines.
Many scientists hypothesize that the age-related decline in NAD+ underlies the organ decline that characterizes aging. It follows that, by restoring NAD+, our cells become healthier, our organs become healthier, and we become healthier. If this can be achieved, a lack of high-mortality age-related diseases like cardiovascular disease, neurodegenerative disorders, and cancer will allow us to live longer.
How can we restore our NAD+ levels? Since NAD+ occurs naturally, our cells have the machinery necessary to make it on their own; they just need the necessary biochemical components. Our cells generate molecules like a factory assembly line where each component is the precursor for the next. The biochemical precursor to NAD+ is called nicotinamide mononucleotide (NMN). Unlike NAD+ itself, NMN can be ingested orally and can thus be taken in supplement form to raise NAD+ levels.
Potential Benefits of NMN
NMN feeds into the production of NAD+, providing our cells with the energy needed to function. There are several factors thought to underly the aging process, a lack of cellular energy being one of them. Genetic instability resulting from DNA damage is also one of these factors. NAD+ plays a key role in activating enzymes that maintain DNA integrity, thus promoting genetic stability. Given its central role in these cellular processes, the potential benefits of boosting NAD+ with NMN extend to nearly all body systems. Below are some of the better-known examples.
Improves Brain Function
Perhaps one of the most devastating age-related diseases is Alzheimer’s disease, whereby the afflicted are robbed of their memories. NMN has been shown to improve cognition in rodents with Alzheimer’s and reduce brain plaques and neurodegenration in Alzheimer’s mice. While Alzheimer’s is an end-stage disease, many older adults also suffer from cognitive impairments — inability to learn, remember, and think properly. These age-related cognitive impairments have been prevented by NMN in mice. Cognitive impairments are sometimes associated with depression, which has also been shown to be alleviated by NMN in mice.
Because our blood vessels become dysfunctional as we age, blood flow to our brain becomes impaired, leading to cognitive impairments. NMN has been shown to increases blood flow to the brain and improve cognitive function in mice. When the blood vessels in our brain become clogged, we can have a stroke, whereby our brain tissue becomes damaged. NMN has been shown not only delay stroke onset, but also to prevent stroke damage, and improve cognition and mitochondrial health after stroke in rodents.
Restores Blood Vessel Health
Our blood vessels transport vital nutrients to each of our cells. As we age, our blood vessels become rigid and more susceptible to blockage, which can lead to heart attack or stroke. NMN has been shown to reverse vascular aging by restoring blood vessel elasticity in mice. Senescent cells — growth arrested cells that accumulate with aging — contribute to the aging of many organ systems, including the vascular system. In mice, NMN stops blood vessel aging my reducing senescent cells, leading to alleviation of hypertension. One of the ways senescent cells contribute to aging is by promoting inflammation, which underlies nearly every age-related disease. NMN has been shown to reverse blood vessel dysfunction by reducing blood vessel inflammation in mice.
Improves Muscle Function
We rely on our skeletal muscles for movement, stability, and strength. As we age, our muscles lose their ability to regenerate and grow, leading to the age-related decline in muscle strength and size called sarcopenia. Along with muscle weakness, we also become more fatigued and have less physical endurance. NMN seems to reverse these conditions, as one of its transporters has been shown to increase strength and physical endurance in mice. Furthermore, NMN improves muscle strength and performance in older men, and enhances oxygen utilization and exercise endurance in middle-aged runners. On the other hand, another NAD+ precursor called nicotinamide riboside (NR) does seem to improve muscle function.
Promotes Healthy Heart
Our heart can barley afford to skip a beat before death ensues, leaving little room to wonder why heart disease is the worldwide leading cause of death.
As we age, our heart becomes more susceptible to irregular beats, which have devastating outcomes, such as heart failure. NMN has been shown to protect against heart failure in mice. Our heart tissue is precious, as it is not known to regenerate. Instead, damaged tissue manifest in scarring (fibrosis), leading to heart dysfunction. NMN recovers mouse heart function by reducing scarring. Beating constantly and evermore, the heart requires large quantities of energy. For this, it needs healthy mitochondria. NMN improves heart metabolism and protects against heart failure, in part by rejuvenating mitochondria.
Our heart is part of the cardiovascular system, pumping oxygen-containing blood to the rest of our organs. When the blood vessels surrounding our heart become clogged, the adjacent tissue becomes damaged and dies due to a lack of oxygen. This is called ischemia and commonly leads to heart attacks. In mice, NMN protects the heart from ischemic injury. This protection is synergistically improved with stem cell therapy and melatonin. Enhances Cancer Suppression
Aids in Cancer Therapy
One of the most new and promising therapies against cancer are called immunotherapies. These therapies utilize immune cells to suppress tumor growth. Immunotherapies have not been perfect, but in rodents NMN has been shown to enhance the tumor killing capabilities of several different types, including natural killer cell therapy, CAR-T cell therapy, and PD-1 mediated therapy.
While immunotherapies may be a cancer therapy of the near future, chemotherapies are still used widely but come with many harmful side effects. NMN has been shown to reduce these unwanted side effects, such as heart tissue damage and cognitive impairments in mice.
Protects Against Obesity and Diabetes
Obesity is linked to a wide array of metabolic deficiencies, including insulin resistance — when are cells cannot utilize glucose due to impaired insulin signaling — which can lead to diabetes. Mitochondria are the final cellular destination for the food we eat to be converted into energy, making them of key importance in metabolism and related diseases. NMN has been shown to double the amount mitochondria in the livers of obese mice, which could protect against obesity. Stimulating fat breakdown with NMN could also help obese individuals lose fat. Furthermore, NMN improves the metabolism and health of mice born to obese mothers.
Eating too much and becoming obese wreaks havoc on our metabolism and can lead to diabetes. Aging makes both of these conditions worse. In mice, NMN has been shown to reverse diet and aged induced diabetes and prevent the kidney disease and neuron degeneration associated with diabetes, suggesting that NMN can protect against these metabolic impairments. To support this, NMN has been shown to improve muscle insulin sensitivity in older women. Thus, While lifestyle adjustments like consistent exercise and a healthy diet are of paramount importance, NMN may protect against obesity and diabetes.
Could Treat Eye Aging and Injury
Macular degeneration is an age-related disease involving the degeneration of a region of the retina that allows us to see clearly. Thus, more severe forms of macular degeneration can cause blindness. NMN has been shown to repair the mitochondrial dysfunction associated with macular degeneration in mice.
As we age, our eyes become dry and inflamed. NMN has been shown to reduce inflammation and increase oil secretion, treating dry eye in mice. NMN has also been shown to reduce cell death and wound size after eye injury.
Promotes Organ Health
In addition to slowing down aspects of the aging brain, vasculature, muscle, heart, metabolism, and eye, NMN has also been shown to rejuvenate bone stem cells and promote bone formation in rodents. It also reverses intestinal aging, protects against age-related kidney deterioration, and inhibits the onset of liver fibrosis in rodents. Thus, NMN also slow aspects of aging bone, intestines, kidney and liver.
Revitalizes Reproduction
With age comes fertility problems, especially with women. This stems from problems with oocyte (egg) quality. NMN has been shown to improve the age-related decline in oocyte quality and number, as well as female fertility in mice. NMN also protects oocytes from toxins in pigs.
Enhances Maintenance of DNA Repair
Our DNA codes for the building blocks of our cells but accumulates damage as we age. Repairing DNA damage can prevent age-related diseases. NAD+ fuels enzymes called sirtuins — sometimes thought of as the guardians of our healthspan. Sirtuins play a key role in repairing DNA.
Also, each time our cells divide, the DNA at the ends of our chromosomes (telomeres) grow shorter. At a certain point, this telomere shortening begins to damage our genes and cells. Sirtuins slow this process by stabilizing telomere length.
Since sirtuins rely upon NAD+ to function, there has been an effort to enhance sirtuin activity through NAD+ boosting methods. Along these lines, studies have demonstrated that feeding mice NMN activates sirtuins. NMN also repairs DNA damage resulting from radiation and old age in mice. Furthermore, in both mice and humans, NMN increases telomere length.
NMN studies from institutes like Harvard University and Washington University have shown that supplementing with the molecule or enhancing NMN synthesis promotes longevity and health during aging in rodents. Sinclair and colleagues found that when aged mice drank NMN-infused water, their running endurance almost doubled. Further studies have demonstrated that injecting mice with NMN preserves cognition during aging. Moreover, a study from Imai and colleagues indicates that an upsurge in NMN synthesis more than doubles the remaining lifespan of mice.
Recommended Dose for Human Consumption
Research in animal studies has shown that increasing NAD+ levels can reverse various age-related illnesses such as heart diseases, diabetes, and neurodegeneration. Boosting the molecule even extended the lifespans of yeast, worms, and mice. NMN’s NAD+-boosting ability in animals and its healthspan-promoting properties led scientists to believe in the molecule’s therapeutic potentials. Now, scientists are starting clinical trials to understand whether NMN is safe, how much we should take, and what it does to our body.
Clinical Trials on Safety of NMN
An international team of researchers ran the first human clinical study for NMN in Japan to investigate the safety of the molecule. Although the size of the Phase 1 clinical trial was small, the study showed that dosages up to 500 mg of orally administered NMN are safe in humans, implicating a potential therapeutic strategy. The results appeared in the journal Endocrine, November 2019.
NMN’s safety as a dietary supplement has been proven in a number of FDA-approved clinical trials.
Other clinical trials registered with the World Health Organization (WHO) are also examining the safety and efficacy of NMN. In the US, researchers at Washington University School of Medicine are running a clinical trial to test NMN’s effect on cardiovascular and metabolic health with a daily dosage of 250 mg. Another clinical study at Brigham and Women’s Hospital in Boston is also testing the supplement’s effects on the body and if there are any side effects.
Although researchers still need to conduct more studies to determine the efficient dosage for humans, clinical trials of other NAD boosters have shown that 1 gram of oral supplement every day can stimulate NAD+ metabolism in healthy middle-aged and older adults.
Do Scientists Use NMN?
With clinical studies still underway, some scientists are confident enough in NAD+’s benefits for aging and are already taking supplements themselves.
David Sinclair, a Harvard professor who studies aging, talked about taking NMN to remain healthy and prevent aging on The Joe Rogan Experience podcast. Sinclair takes 1 gram of NMN every day, along with other supplements including resveratrol, metformin, and aspirin. When asked if there are any downsides of the supplements, Sinclair said he hasn’t experienced anything other than stomach upset so far, and to him, “anything’s better than what’s coming” — aging.
Side Effects of NMN Supplementation
Currently, no side effects of nicotinamide mononucleotide have been documented in humans. Researchers have conducted the majority of studies on NMN in rodents, which revealed positive effects on metabolism, brain function, liver, skin, muscle, bone structure, heart health, reproduction, immunity, and lifespan. Long-term mice study also showed no toxicity, serious side effects, or increased mortality rate throughout the 12 month intervention period.
A single study of NMN in humans reveals no safety concerns following single oral doses of 100, 250, and 500 mg of NMN. Five hours following the single oral administration of NMN, scientists found no changes in heart rate, blood pressure, blood oxygen levels, or body temperature. Laboratory analyses of blood did not show significant changes, except with levels of four molecules in the blood, which fell within normal ranges. This study also measured sleep quality and found no differences before and after the NMN consumption.
Scientists need to conduct further studies of NMN administration in humans to determine whether side effects come from consuming it. Scientists could look at doses higher than 500 mg to find whether they induce side effects. Research could also look at whether long-term consumption of NMN causes side effects.
Active NMN Clinical Trials
Since NMN has benefits in various mouse models of human disease, several clinical trials of NMN have been conducted to investigate its clinical applicability
Future NMN Research
Recounted by various nations around the world for thousands of years, emperors and kings alike searched every corner they could reach for the Fountain of Youth. The tale remains a mystery to this day, but instead of explorers, scientists are on the quest.
Studies in animals showed NMN’s promising properties in NAD+-boosting and anti-aging. Now, researchers are moving forward with clinical trials to investigate the safety and efficacy of the molecule in humans. With the research efforts that are pouring into the field of anti-aging by institutions and private entities, researchers will start getting answers soon. To scientists, the ultimate goal is to develop treatments that slow, stop or even reverse aging — for people to live a long and healthy life.
Taking NMN may provide a promising means to combat age-related diseases and ailments. Below is a summary of major studies elucidating the potential benefits of NMN.
Research CategorySummary / ConclusionMouse / RatHumanPigBone Repair
Cancer
- Enhances tumor suppression effect of immunotherapies.3, 38, 46
- Reduces toxic side effects of chemotherapies.37, 39, 92, 100, 105
- Inhibits cancer growth.102
Cardiovascular
- Restores heart and blood vessel function.4, 23, 25, 40, 42, 78, 84, 113, 120
- Protects heart against damage after heart attack.41, 43
- Prevents heart failure by promoting the health of mitochondria.44
DNA Repair
- Enhances DNA repair mechanisms. 18
Eye Protection
- Promotes eye recovery after injury.6, 31, 80, 89, 96
- Improves dry eye by reducing inflammation and increasing oil secretion.17, 45
Immunity
- Promotes recovery from COVID-19.7, 117
- Inhibits COVID-19 infection.91, 115
- Reduces severe allergic reaction.50
- Reduces inflammation by supressing immune cell activation.51
- Reduces fat tissue inflammation.106
- Rescues immune cell function against hepatitis B108
Longevity
- Doubles lifespan.8
- Restores cardiovascular, cognitive, and metabolic decline.20
- Doubles telomere length.5, 52
- Reduces biological age. 93
- Improves sleep quality.98
- Rejuvenates stem cells. 99
Metabolism
- Improves insulin sensitivity and glucose metabolism.9, 27, 48, 49, 87, 111
- Enhances energy production by rejuvenating mitochondria.21, 29, 47
- Reduces fat circulating in blood.85
Neurological
- Protects against cognitive deficits and brain deterioration.10, 53, 55, 56, 57, 59, 60, 61, 62, 63, 64, 65, 104, 110, 112, 122, 126
- Protects against stroke. 12, 33, 58, 118
- Redcues depressive behavior.11
Reproduction
- Improves fertility and age-related decline in oocyte (egg) qaulity.13, 66, 83
- Protects oocytes against environmental toxins.19, 107
Skin and Muscle
- Increases muscle strength and improves exercise endurance.69, 71, 72, 95
- Protects against skin aging.70, 79, 82
- Promotes wound healing.94, 119
Organ Health
- Reduces alcohol-induced liver damage.14
- Reduces liver scarring.16
- Protects against kidney damage.15, 74, 81, 90
- Rejuvenates age-related decline of intestines.75, 76, 86
- Protects against lung injury.97, 101, 114
- Protects against infection of organs.103, 116
- Enhances beneficial gut bacterial growth.125
Mechanism
