What are NAD+, NMN and NR, and how do they help with aging?

November 21, 2022By JOOSH Inc

Low levels of NAD can cause health problems. Supplementing with NAD precursors can help raise its levels.
Taking supplements to increase NAD levels can support cellular health and healthy aging.
NMN and NR are NAD precursors widely used for restoring cellular NAD+ levels.

An introduction to NAD, NR and NMN

Nicotinamide adenine dinucleotide (NAD), a chemical your body produces, is essential for survival. It's vital for sustaining life and facilitating a wide range of metabolic functions, including the conversion of nutrients in food into energy for cells. Unfortunately, despite its importance for cellular health and healthy aging, NAD levels decline with age. Nutrition alone cannot sufficiently replenish your supply.

NAD precursors can slow down the decline. Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are two of the most widely used precursors for restoring cellular NAD+ levels. So what is the difference between NAD, NMN, and NR? Let's find out.

NAD and NAD+

The oxidized form of NAD, known as NAD+, is essential as a coenzyme in many metabolic cellular processes and vital bodily functions like DNA repair. NAD + is also necessary to convert food into the energy (ATP) the body needs to perform daily activities like eating, walking, and thinking. A lack of it prevents the conversion of food into energy and other crucial cellular and bodily functions.

NAD promotes DNA repair by activating a family of proteins called sirtuins in the cells. The sirtuins are involved in longevity. Conversely, age-related disorders, including Alzheimer's, diabetes, heart disease, etc., are linked to low levels of NAD.

Fortunately, studies have shown that by enhancing NAD, we can mitigate these unfavorable consequences and, in some cases, even reverse them. And here's where NMN and NR come into play.

The role of NAD +

NAD+ within the mitochondria acts as a fuel to produce ATP and Sirtuins.

What Are NR and NMN?

Nicotinamide riboside (NR)

Nicotinamide riboside is a form of vitamin B3. It increases NAD+ levels in the body and is popularly marketed as an anti-aging supplement. NR also has a long history of being branded as a very effective NAD+ precursor. As a result, extensive research has been done on it, including clinical studies in humans. A study published in 2020 showed that NR is safe and successfully boosts NAD+ levels in humans.

Nicotinamide mononucleotide (NMN)

NMN is becoming popular as a dietary supplement after Dr. David Sinclair disclosed he takes it daily because of NMN's ability to increase cellular levels of NAD+. Given that NMN is a precursor to NAD+, it has the potential to revive the cells and delay the deterioration typically associated with aging. In addition, multiple tissues, including the pancreas, skeletal muscle, kidneys, blood vessels, and the heart, have been demonstrated to benefit from NMN's ability to increase NAD+ synthesis.

Supplementing with NR and NMN

Although NR and NMN are in small amounts in many foods, it is impractical to eat enough of any food to significantly increase NAD+ levels. Therefore, taking a supplement containing an NAD+ precursor is an effective way to substantially replenish it. When your body has more cellular NAD+, your brain, heart, and muscles all benefit.

Safety of NR and NMN

To date, there have been no studies that have shown safety concerns about consuming NMN or NR. As far as we currently know, they pose no health risks. However, it is prudent to consult a medical expert before incorporating dietary supplements into your daily routine. Your doctor is best-equipped to assess the risks and benefits that apply to you.

The following are the findings of some NMN and NR safety investigations.

In a trial of 30 healthy volunteers published in April 2022, participants were given doses of 250 mg/day of NMN for 12 weeks. The researchers observed no abnormalities in either physiological or laboratory tests. In addition, NAD+ levels in the blood were significantly increased, indicating NMN is a safe and effective way to boost NAD+ in humans.
In a trial involving 10 healthy Japanese male subjects, researchers found that single oral dosages of NMN (ranging from 100 mg to 500 mg) were well tolerated. Notably, researchers did not observe any variations in the participants' vital signs (such as pulse rate, blood pressure, oxygen saturation, or core body temperature).
In a study, male and female participants received up to 1000 mg of NR daily for eight weeks. The long-term administration of NR in the overweight but healthy men and women involved in the study raised no safety concerns.

Even though more human studies on NMN and NR are still necessary, as far as we know, there are currently no significant concerns about the safety of NMN and NR.

Data to support NMN’s use

Postmenopausal women who were prediabetic and overweight or obese were included in a trial that evaluated the effects of daily NMN dosages of 250 milligrams (mg) for 10 weeks. There was an improvement in insulin sensitivity and signaling among those who took NMN.

Similar results were seen in another study where NMN was given to 5-month-old mice for a year. Again, the animals demonstrated enhanced insulin sensitivity, bone density, mitochondrial and metabolic performance, and immune system strength.

Furthermore, NMN plays a vital role in cellular metabolism as a bridge between NR and NAD+. This indicates that NR first transforms into NMN before it converts to NAD+.

NAD+ supplements

Bioavailability of NMN and NR

The bioavailability of a drug or substance refers to how much of it makes it into the bloodstream and can have an effect. Blood NMN or NR concentrations after NMN or NR ingestion indicate bioavailability. Bioavailability can also be measured with the amount of NAD+ in the blood after taking NMN or NR.

A bioavailability study shows that a single oral dose of NR can boost NAD+ levels in human blood by a remarkable 2.7-fold. The study also indicates that single doses of 100, 300, and 1000 mg of NR all increased blood NAD+ levels in the proportion of each dose.

Similarly, a study in mice showed that NMN taken orally rapidly increased NMN plasma levels in two and a half minutes, with further increases in 5-10 minutes. The plasma levels then declined, suggesting rapid absorption in the gut

Stability of NMN and NR post absorption

NMN exhibits remarkable stability. In a study on mice, oral administration of 300 mg/kg NMN causes a significant elevation in blood plasma NMN levels. At roughly 10 minutes after delivery, plasma concentrations of NMN reach their maximum. In less than half an hour after receiving NMN, NAD+ levels had increased noticeably.

However, NR is particularly unstable in the bloodstream and digestive tract. When taken orally as a supplement, a significant fraction of NR is swiftly metabolized into nicotinamide (NAM) or vitamin B3 before it reaches tissues. As a result, repeated experiments in mice and humans using high doses of NR have failed to detect any NR in the bloodstream at any time.

The conversion of NR to NAM is a drawback. Even though NAM is a NAD precursor, high concentration can block the action of sirtuins and polyadenylate-specific polymerase (PARP), two essential enzymes in repairing DNA damage.

Does NMN convert into NR, or is it the other way around?

First, although having similar molecular structures, NMN and NR differ in that NMN has a phosphate group. Because of the extra phosphate group, the NMN molecule is considerably larger than the NR molecule.

Some researchers think that NMN is too big to pass through cell membranes and must be converted to NR before entering cells, where NAD+ production occurs. However, new research suggests that NMN may have a dedicated transporter protein that facilitates its trafficking across cell membranes. This means that NMN is nearer in the process (or pathway) of creating NAD+ than NR. To become NAD+, NMN does not need to convert to NR.

Conversely, to use NR as a supplement to NAD+, the body must first add phosphate to it (through the enzyme NRK) to convert it to NMN. The next step is for NMN to be changed into NAD+. This means that NMN serves as a bridge between NR and NAD+. Therefore, NMN must be produced from NR before NAD+ can be synthesized. So, the direct precursor to NAD+ is NMN, not NR.

Cost implications

The production of NMN is quite costly. Even if prices have decreased dramatically due to new production techniques, NMN is still an expensive dietary supplement, especially if you want to produce it with high quality and purity.

JOOSH PURE NMN capsules and powder are produced using only the purest NMN (99 percent). In addition, a third-party lab puts the supplements through rigorous purity and safety testing.

Therefore, be wary of prices that are substantially lower than usual. A warning signal should sound if the price is significantly less than the competition. It is best to get value for your money.

Conclusion

Both nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) increase levels of NAD+, which is perhaps the most critical chemical in terms of cellular health, longevity, and anti-aging. We cannot say which is superior between NMN or NR until more clinical trials directly compare their impacts on health and longevity.

However, studies continue to show that NMN is a safe and effective supplement for raising cellular NAD levels and facilitating a wide range of health advantages. Thus, with the proper NMN supplementation, you can reverse the effects of premature aging and bring your body's NAD+ levels back to normal.