NAD, NAD+, NMN, NR, vit. B3

NAD+: A Complete Guide To This Longevity-Boosting Coenzyme

After a certain age, not many of us look forward to our next birthday with the same level of enthusiasm we once did. If there were a switch we could flip to slow down the aging process

(to counter the waning energy, to keep those memories sharp, to stay healthy enough to continue having amazing experiences), then we'd probably all flip it in a heartbeat.

The good news: There is something scientists have identified that may be the key—or at least part of it—to keeping your mind and body aging in a healthy way. It's a coenzyme called nicotinamide adenine dinucleotide (NAD+), and it's starting to generate some buzz.

What is nicotinamide adenine dinucleotide (NAD+)?

NAD+ is a coenzyme, or molecule, found in all living cells, and it plays a vital role in energy metabolism and maintaining proper cell functioning. It is particularly crucial for the functioning of ourmitochondria, the power plants in our cells that turn our food and oxygen into energy. The problem is that our levels of NAD+ decline significantly as we get older (impairing mitochondrial functioning, among other things), and these declining levels drive the aging process. Which makes sense when you consider that underperforming or damaged mitochondria are thought to contribute to a number of age-related health conditions.

One way NAD+ seems to exert its health-promoting properties is by helping sirtuins do their job. Sirtuins are a class of proteins that regulate biological pathways, turn certain genes on and off, and help protect cells from age-related decline. For example, NAD+ increases the activity of one type of sirtuins, SIRT1, which has been found to induce the formation of new mitochondria and extend life span, as well as SIRT6, which helps maintain the length of telomeres (the end caps on DNA)—longer telomeres are associated with longevity.

Potential benefits of maintaining healthy NAD+ levels.

According to Ilene Ruhoy, M.D., Ph.D., an integrative neurologist and mindbodygreen health expert, "Appropriate levels of NAD+ are critical to support the body's response to stress, as NAD+ is used by these enzymes to modulate cellular activity in response to extrinsic and intrinsic assaults, including those triggered by environmental toxins, pro-inflammatory foods, trauma, and even chronic use of medication. NAD+ is essential for continued health, wellness, and strength."

Animal studies have shown that supporting healthy levels of NAD+ can lead to improved memory, resistance to weight gain, a longer life span, and other benefits. As mentioned above, NAD+ is able to do this by activating proteins called sirtuins and optimizing cell metabolism in other ways. Here are some of the most promising ways that maintaining or increasing healthy NAD+ levels can improve health:

1. Combat age-related memory loss.

NAD+ is vital to DNA repair and resistance to neuronal stress. Because of this, it help enhance memory and slow down age-related memory loss. According to a recent animal study, researchers developed a strain of mice with features mimicking human age-related memory decline, then added an NR supplement to their drinking water for three months to increase NAD+ levels. Over this period, researchers found that the NR-treated mice had less DNA damage, higher neuroplasticity, increased production of new neurons, and lower levels of neuronal damage. In the hippocampus area of the brain (where damage and loss of volume is found in people with memory issues), NR seemed to clear existing DNA damage or prevent it from spreading farther. The NR-treated mice also performed better on memory tests.

2. Counter high-fat diets and help manage weight gain.

Animal research suggests that increasing your levels of NAD+ may help support metabolism and weight maintenance, even if your diet is high in fat. One study found that mice on high-fat diets that received an NR supplement gained 60 percent less weight than they did on the same diets without NR. They also had more energy. These positive results, researchers say, were due to increased activation of the sirtuins SIRT1 and SIRT3, which led to improved oxidative metabolism.

3. Enhance strength and endurance.

As we age, muscle function and strength tend to decline. But according to animal studies, increasing NAD+ levels by supplementing with NR seems to help. In one study, researchers used mice whose genes were altered so their muscle tissue contained just 15 percent of the normal amount of NAD+. They then measured muscle strength and endurance, which was quite low. But after giving the mice NR-enriched water to replenish NAD+ levels, their exercise capacity was restored to that of a normal, healthy mouse in just one week. In another study, supplementation with NAD+ precursors led to DNA repair and an improvement in the health of muscle tissue within the first week—to the point where researchers couldn't tell the difference between the tissue of a mouse that was two years old and a mouse that was four months old.

4. Promote longevity.

Several studies have found that replenishing levels of NAD+ with supplements containing NR lengthen the life span of mice by improving mitochondrial function and increasing activation of SIRT1, a specific sirtuin protein. This is the same mechanism by which restricting calories seems to lengthen life span. (Additional compounds that may mimic the life-extending effects of calorie restriction include pterostilbene and resveratrol.) Other studies suggest that NAD+ increases the activation of SIRT6, which helps maintain the length of telomeres—the end caps on DNA that are associated with longevity.

How to maintain healthy NAD+ levels in the body.

Knowing this, we want to try to keep NAD+ levels in a healthy place, especially since we know that they decline naturally as we age. But here's the catch, taking an NAD+ supplement might not actually be the best way increase NAD+ levels in the body. This is because NAD+ is a large molecule, so in order for NAD+ to enter your cells and get to work, your body has to take it apart, transport it piece-by-piece into the cell, and then put it back together again. But if NAD+ is not a nutrient present in food or practical to take by supplement, then why are we even talking about it? Turns out, there are a couple of indirect ways to increase your NAD+ levels, which may have positive results for your health:

1. Calorie Restriction

Restricting calories (20 to 30 percent less than what you normally consume) and fasting have been shown to increase NAD+ levels and increase activation of SIRT1. This SIRT1 activation, scientists say, is why calorie restriction has been associated with increased life span in animal studies. However, drastically cutting your calories or fasting for prolonged periods of time isn't realistic or advisable for most people. There is some speculation that intermittent fasting diets and low-carb ketogenic diets might have a similar impact on NAD+ levelswhile being much more sustainable—but more research needs to be done to confirm this.

2. Supplements containing nicotinamide riboside (NR)

Nicotinamide riboside (NR) is a newly discovered form of vitamin B3, which is found in trace amounts in milk. No one really thought much about NR until scientists discovered that our bodies convert NR into NAD+. Two recent human trials on NR-containing supplements found that they both effectively increased levels of NAD+ in the body, which is promising. More studies are needed, but it looks like NR could be the future of healthy aging research.

3. Preventive measures to maintain healthy NAD+ levels

Additionally, there are some things you can do that can help maintain NAD+ levels—even if they don't necessarily increase them. For example, UV rays damage skin cells and your body uses NAD to repair that damage. Therefore, wearing sunscreen or protective clothing can help minimize that damage and preserve NAD+. A healthy, whole-food-based diet and a regular exercise routine (especially HIIT-type workouts) can't hurt, either—as they both boost the health of your mitochondria and help your body use NAD+ more efficiently or sparingly.

The bottom line on NAD+ and your health.

NAD+ is clearly an important molecule for optimizing a variety of cellular functions that promote overall health and longevity. While restricting calories is a natural way to increase NAD+ levels, it's likely not realistic for most people. Supplementing with an NAD+ precursor supplement such as NR, on the other hand, may be easier, and seem to be the next promising thing in healthy aging supplementation.

Source: NAD+ 101: What It Does And How To Get More Naturally (

NAD is a critical regulator of aging and Longevity, and is considered a promising target for the treatment of aging and aging-associated diseases. Numerous studies using mouse models have demonstrated the beneficial effects of NAD precursors against metabolic disorders, cancer, and neurological disorders.

NAD metabolism: Implications in aging and longevity


NAD levels decline with age due to an imbalance between its synthesis and destruction.

Decreased NAD metabolism is associated with various physiological aging processes.
NAD precursors protect against various aging-associated diseases.
Boosting NAD metabolism can extend the lifespan of diverse organisms.


Nicotinamide adenine dinucleotide (NAD) is an important co-factor involved in numerous physiological processes, including metabolism, post-translational protein modification, and DNA repair. In living organisms, a careful balance between NAD production and degradation serves to regulate NAD levels. Recently, a number of studies have demonstrated that NAD levels decrease with age, and the deterioration of NAD metabolism promotes several aging-associated diseases, including metabolic and neurodegenerative diseases and various cancers. Conversely, the upregulation of NAD metabolism, including dietary supplementation with NAD precursors, has been shown to prevent the decline of NAD and exhibits beneficial effects against aging and aging-associated diseases. In addition, many studies have demonstrated that genetic and/or nutritional activation of NAD metabolism can extend the lifespan of diverse organisms. Collectively, it is clear that NAD metabolism plays important roles in aging and longevity. In this review, we summarize the basic functions of the Enzymes involved in NAD synthesis and degradation, as well as the outcomes of their dysregulation in various aging processes. In addition, a particular focus is given on the role of NAD metabolism in the longevity of various organisms, with a discussion of the remaining obstacles in this research field.

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Why should I take anti-aging supplements?

Nicotinamide Adenine Dinucleotide or NAD+, a master regulator of metabolism and a molecule essential for the functionality of all human cells, is being dramatically decreased over time.

Repleted levels of NAD+ are correlated with better mitochondrial function, increased cognitive function and energy levels. Better cellular health = better performance.

The peak of NAD+ and hormonal production in humans happens around the age of 25. As a result, the production of hormones such as testosterone, growth hormone, progesterone and melatonin to name a few is being decreased after 25. That’s the reason most adults start experiencing increased fatigue at this age, sleeping less than they did in their early twenties and their sex drive and focus is on a steady decline. Increased levels of NAD+ are correlated with better mitochondrial function, increased focus and energy.

Few NMN, NAD+, NR (Nicotinamide Riboside or Niagen - niacyn) manufacturers

Imagine taking a vitamin for longevity! Not yet, but a Dartmouth discovery that a cousin of niacin prolongs lifespan in yeast brings the

tantalizing possibility a step closer.

The research, reported in the May 4 issue of Cell, shows how a new vitamin extends lifespan in yeast cells, much like calorie restriction

does in animals. It could pave the way for developing supplements to benefit humans.

Radical calorie reduction can extend life. Dieting or fasting mice live longer and lowering the glucose that yeast grow on extends their

lifespan, according to Dr. Charles Brenner, associate professor of genetics and of biochemistry, who led the research.

"If we could do this in humans give people a drug or vitamin that would mimic effects of calorie restriction without having to skip lunch

-- we would be able to provide some of the benefits of calorie restriction, which are pretty striking in model organisms," said Brenner,

also a member of the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center.

Many benefits, explains Brenner, depend on a family of proteins called sirtuins--dubbed anti-aging gene products for the important roles

they play in longevity and energy expenditure, although the precise mechanisms are still being figured out.

His team found that providing a newly discovered vitamin activates the yeast anti-aging gene product Sir2, which resembles sirtuins

found in humans. The new work builds on Brenner's prior discovery of the vitamin, termed NR (nicotinamide riboside), a natural product

found in milk. Like the B3 vitamin, niacin, NR is a precursor to a versatile cellular factor that is vital for all life.

The factor, called NAD, short for nicotinamide adenine dinucleotide, is elevated by calorie restriction. So the researchers set out to

develop an intervention to elevate NAD, using yeast cells, whose genes are easy to manipulate. "It's surprising that no one was be able

to elevate NAD with a small molecule before," Brenner said.

The team discovered two pathways that allow yeast to raise NAD levels with NR, improve their control of gene expression and live longer

in the presence of high glucose. One of the pathways is new; the other was previously identified by Brenner's lab.

At the molecular level, elevating NAD to turn on Sir2 actually enables the yeast to silence genes that are not supposed to be expressed.

In any organism, not all genes are on at once; in yeast, there are sets of genes that Sir2 normally represses.

"We showed that that we could improve Sir2-dependent gene silencing with NR and increase the longevity of yeast grown in high glucose

conditions," Brenner said.

To test for Sir2 gene repression, the investigators found conditions in which wild-type cells can't accomplish normal gene silencing. Then,

when they take up NR through one of the pathways Brenner's team discovered, Sir2 gene silencing is restored, and yeast are

rejuvenated. Yeast cells formerly capable of dividing 13 times, divided over 23 times when given NR.

Deletion of either pathway makes NR only half as effective as it is when both pathways are intact. So yeast cells seem to use both

pathways equally well to lengthen their lifespan. The first NR pathway, described in 2004, consists of a gene common to yeast and

humans. In fact, that gene is activated in damaged neurons in order to allow NR to protect against loss of axons. The second NR pathway

involves three yeast genes, two of which are found in humans.

Granted that the human anti-aging apparatus is more complex, but animal studies indicate potential. Perhaps the best known sirtuin

activator is the red wine compound resveratrol. Overfed mice on high dose resveratrol have healthier livers, better endurance and

possibly longer lifespan. While resveratrol and NR work through different mechanisms to increase sirtuin activity, Brenner said, "the

two compounds could be complementary or synergistic."

More testing remains for NR in humans, but Brenner foresees intriguing possibilities. "As a natural product found in milk, we expect the

compound to be much safer than most drugs, and to be a more specific remedy than most vitamins."

Though aging itself is not a disease, Brenner anticipates applications in conditions associated with aging including neurodegenerative

diseases, metabolic syndrome, and elevating good cholesterol. There are also indications that NR could be a treatment for one type of

Candida infection.

Team members are Peter Belenky and Katrina L. Bogan, Dartmouth graduate students, and Jeffery S. Smith, Julie M. McClure and

Frances G. Racette of the University of Virginia. The research was supported by the National Institutes of Health


Nicotinamide riboside (NR) and longevity (

NR and NMN: Do These Longevity Supplements Work in Humans?

Could a simple pill be the solution to our aging problems? NAD+ boosters have risen in popularity as laboratory research continues to shed light on their promising effects on longevity and aging. But have we really discovered the fountain of youth? While cell culture and animal research are encouraging, the results of human studies will always trump these laboratory outcomes. And with multiple clinical studies already published or underway, let’s dive into the current research in humans.

Low NAD+ is a hallmark of aging, but NR and NMN supplements may help

To fully understand the science, we must start with the star of the show, nicotinamide adenine dinucleotide or NAD+. NAD+ is a molecule that acts as a coenzyme in many critical processes in our body, including cellular energy production, DNA repair, and sirtuin activity (enzymes involved in aging). Without NAD+ acting as a coenzyme, these processes simply cannot occur and life would not exist. Interestingly, mounting evidence suggests that NAD+ levels decline with age—a change that scientists now consider a hallmark of aging. Lower NAD+ levels are also responsible for many age-related conditions like cardiovascular disease, neurodegenerative diseases, and cancer.

So, in an effort to stave off these age-related changes, can we boost NAD+ levels by taking NAD+ supplements? Not quite. NAD+ in supplemental form has very poor bioavailability, meaning it doesn't have much of an effect when introduced to the body. But, NAD+ has several precursors or intermediatesmolecules that transform into NAD+ through enzymatic reactions. Scientists have studied two such intermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), more extensively than others, and the research is encouraging. Several studies indicate that supplementing with these precursors can increase NAD+ levels and prolong the lifespan of yeast, worms, and mice. Furthermore, other animal studies show that boosting NAD+ can also improve muscle generation, cardiovascular function, and glucose metabolism. But it's critical to remember that findings in animal studies don't necessarily translate to humans. So let’s examine the clinical research currently published.

Of note, in human studies, research is much farther along for NR supplementation compared to NMN. One reason for this could be due to the way the body converts these intermediates to NAD+. Research suggests that cells can uptake NR directly from the blood, where it is then converted to NMN and then NAD+. However, there are two proposed mechanisms for the uptake of NMN in living organisms. One is that NMN must first convert to NR to enter cells where it is then changed back to NMN and subsequently into NAD+. The other is that NMN may enter cells directly through an unknown transporter, More research is needed to fully understand these mechanisms, especially in humans.

Nicotinamide riboside (NR): Results from human studies

2016: Let the clinical trials begin

Clinical research examining the bioavailability of NR in supplemental form began in 2016. ChromaDex, a company that produces the NR supplement NIAGEN, sponsored the first published study conducted in humans. In this small crossover study, twelve healthy individuals were given three single doses of NR. Each subject completed each dose (100mg, 300mg, and 1,000mg) with a 7-day washout period between each one. The results showed that NR was bioavailable in supplement form and increased NAD+ in a dose-dependent manner—higher doses of NR resulted in more NAD+ present in the blood. 

2017: Consistent results continue

More than a year later, two additional studies on humans were published. The first one, released in November 2017, was a self-funded study by supplement company Elysium Health, Inc. examining the safety and sustainability of Basis, its own supplement. Basis is a combination of NR and pterostilbene (PT), a polyphenol found in blueberries linked to anti-aging. The randomized, double-blind trial included 120 healthy subjects between the ages of 60-80 years old. They were assigned to one of three groups in which each completed eight weeks of daily supplementation: (1) a placebo group, (2) a dose of 250 mg NR + 50 mg PT, or (3) a dose of 500 mg NR + 100mg PT. The lower-dose group experienced a 40% increase in NAD+, while the double dose group's levels rose by ~90% . No adverse side effects were noted, and the researchers concluded that NR safely and effectively increases NAD+ levels.
A month later, a much smaller 
study showed similar results. Eight subjects took increasing doses of NR for eight days. Doses started at 250mg of NR on days one and two, then doubled every two days ending with 2,000mg on days seven and eight. Their blood was analyzed at baseline on day nine. Researchers found that NAD+ levels increased in all subjects, ranging from 35-168%.

2018: Disappointing results on metabolic function

In March 2018, a randomized crossover trial examined both the tolerability of NR supplementation in healthy adults and multiple secondary outcomes. ChromaDex also partially funded the study and provided the study pills. The study included 24 lean and healthy men and women between the ages of 55-79 years old. Half of them were placed in Group A, where they received a placebo for six weeks before crossing over to receive 1,000mg of NR capsules for the remaining six weeks. Subjects in Group B received the NR supplementation first, followed by the placebo. NR supplementation raised levels of NAD+ by ~60% compared to the placebo. Furthermore, people with lower blood cellular levels experienced a greater increase in NAD+ levels. The researchers also found that NR generally lowered blood pressure and reduced aortic stiffness, but these findings were not significant. Several other secondary outcomes did not improve, including physical activity, body fat, markers of exercise performance, or glucose and insulin regulation.

In August 2018, a study specifically explored NR’s effect on insulin sensitivity and other metabolic parameters in obese, insulin-resistant men. Forty men, between the ages of 40-70, were randomized into two groups. The experimental group received 2,000mg of NR per day for 12 weeks, while the control group received a placebo. The experimental group experienced no changes in insulin sensitivity and glucose metabolism. No differences in secondary outcomes were observed either, including resting energy expenditure, lipid metabolism, or body composition.

2019: Breakthroughs in ALS research and skeletal muscle

Last year, researchers used Elysium Health’s drug EH301 (essentially a clinical name for Basis) to test its efficacy on the progression of ALS. In this randomized control trial, 32 participants with ALS were given 1200mg of EH301 or a placebo for four months and encouraged to follow a Mediterranean-style diet. The group taking EH301 showed significant improvements in ALS symptoms, pulmonary function, muscular strength, and muscle-to-fat weight ratio. The researchers concluded that EH301 significantly slowed the progression of ALS and improved other health outcomes associated with ALS. Elysium Health, Inc. has announced the initiation of several more clinical trials, including the effects of Basis on fatty liver, muscle metabolism and exercise performance, and in preventing Acute Kidney Illness.

In 2019, another group of researchers evaluated NR’s availability in skeletal muscle in older adults. Over 21 days, twelve 70 to 80-year-old men received a total of 1000mg of NR supplementation (NIAGEN) daily in this randomized control crossover trial. The results showed that NR increased NAD+ in muscle and also exerted anti-inflammatory properties.

The conclusion on NR safety and efficacy in humans

Based on this research, we can conclude that NR supplements are generally safe to take and will most likely increase your NAD+ levels, but the effects of increased NAD+ remain unclear. Furthermore, the study periods were short, so we still don't know the long-term effects of NR supplementation. With that said, many more studies with NR are underway—Chromadex alone claims to have over 100 preclinical trials in the works. For more information on current studies, you can search “nicotinamide ribose” at, or click here.

Nicotinamide Mononucleotide (NMN) research is still in its infancy 

NMN has gained a lot of attention lately, especially after the release of David Sinclair’s book Lifespan. In his book, the Ph.D. and longevity scientist discusses his research examining NMN, particularly in mice. He has been very open about taking NMN, but has also made it clear that he has no opinion on whether anyone else should take the supplement. Similar to NR, the research in animal studies looks promising, but the first study in humans was only published this year. Phase I of this study merely assessed the safety of NMN supplementation, and therefore NAD+ levels were not even measured. Ten healthy Japanese men received a single dose of 100mg, 250mg, and 500mg of NMN on separate occasions. All quantities were tolerated without adverse side effects. The authors concluded that up to 500mg of NMN is safe in healthy men. For phase II, researchers will reportedly examine the efficacy of NMN, as well as appropriate dosage and frequency; however, it remains unclear if this study has started.  

Other ongoing human trials (like this one) will examine the safety and effects of NMN in older adults, while this one will investigate NMN’s impact on cardiovascular and metabolic functions. But, similar to NR, research is preliminary and more studies are needed to draw further conclusions. 

A summary of all the research


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