Longevity Articles

What Is the Next Big NAD+ Supplement?

What Is the Next Big NAD+ Supplement?

It is difficult to predict what the next popular supplement will be, as trends in the industry can change rapidly. Some things that can make or break a supplement's popularity are scientific research on how well it works, marketing and advertising efforts, and consumer demand.  

A lot of aging and longevity research has focused on NAD+, a molecule that is found naturally in the body and plays a key role in various biological processes, including energy production, DNA repair, and the regulation of metabolism. Studies show that NAD+ levels drop with age, and taking NAD+ precursors (or precursors of NAD+ precursors) as a supplement may help people age in a healthy way. 

This imbalance can be fixed by taking nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), which are precursors of NAD+. However, the effect on the cellular NAD+ pool is not very strong, and high doses are needed.

The latest research shows that, in the world of NAD+ precursors, there are a couple of new players on the scene to keep an eye out for.

Dihydronicotinamide riboside (NRH)

Dihydronicotinamide riboside (NRH) is a chemical that has the same structure as NR. The only difference is that NRH is what’s called a “reduced” form of NR. NRH has been shown to greatly increase levels of NAD+, both in cultured cells, animals, and humans. In a 2019 study, comparisons with NR and NMN show that in every instance, NRH provides greater NAD+ increases at equivalent concentrations. Similarly, a 2022 study that looked at the effects of NMN, NR, NAM, and NRH on NAD+ levels in immune cells made from bone marrow found that only NRH had a strong effect.

Several animal studies have looked at how NRH affects different parts of health and metabolism. For example, some studies have found that NRH may have beneficial effects on insulin sensitivity, blood pressure, and heart function in animals. Other studies have found that NRH may be able to make mitochondria work better and increase the amount of energy that cells make. But it's important to remember that the results of studies on animals don't always apply to people. More research is needed to find out if NRH is safe and if it works for people.

There have only been a few small studies on the effects of NRH on people. But the results of these studies have been mixed, and more research is needed to figure out whether or not NRH is safe and effective for people. One study found that NRH increased the levels of a molecule called NAD+ in the blood of healthy older individuals, which is thought to be important for energy metabolism and mitochondrial function. Another study found that NRH improved insulin sensitivity in individuals with poor sugar processing (glucose metabolism).

But there’s also a study that showed NRH didn't have any big effects on how healthy people's bodies worked or how much energy they made. Overall, more research is needed to determine what the possible benefits and risks of NRH are for people.

The safe dose of NRH in humans is not well established, as there have been very few studies on the safety of this compound in humans. In the studies that have been done, NRH has been given in doses ranging from 250 mg to 1,000 mg per day. In general, NRH is well tolerated at these doses. But more research is needed to find out if NRH is safe in the long run and to figure out how much to give.

What Is the Next Big NAD+ Supplement?

Reduced Nicotinamide Mononucleotide (NMNH)

Similar to NR and NRH, there is a “reduced” form of NMN known as NMNH. A 2021 study reported that NMNH administration in mice causes a rapid and sustained NAD+ surge in whole blood, which is accompanied by increased NAD+ levels in the liver, kidney, muscle, brain, brown adipose tissue, and heart, but not in white adipose tissue. 

Another study in 2021 showed that NMNH is a better NAD+ enhancer than NMN, both in the lab and in the body. Research has shown that rapid increase of blood NAD+ levels was recorded for both NMN and NMNH, with NMNH showing a higher fold increase than that of NMN after 60 min of administration. More strikingly, while NMN only managed to increase blood NAD+ levels for 4 hours before returning to basal level, NMNH was found to be able to sustain a 2-fold higher level of NAD+ for at least 20 hours. There did seem to be health benefits from the higher levels of NMNH. For example, one study showed that NMNH supplementation supported kidney health in rodents. 

No one knows what the best dose of reduced nicotinamide mononucleotide (NMNH) is for any use. In the studies that have been done on the NMNH so far, animals were given doses that ranged from 50 mg to 1,000 mg per day. While there have been studies on NMNH in cultured human cells, it's important to keep in mind that the safety and effectiveness of NMNH at these doses have not been fully tested in humans, and more research is needed to figure out how much to give.

The Take Home Message

While NR and NMN are popular NAD+ precursors, the reduced forms of these NAD+ precursors appear to be even more potent. Along these lines, NRH and NMNH may be the best choices for raising NAD+ levels because they are better absorbed, more stable, and less likely to break down. There is evidence pointing to the potential of both NRH and NMNH as a dietary supplement that supports health because it may affect how energy is used and improve the function of the mitochondria. However, more research is needed to understand how these compounds affect human wellbeing and if they support healthy aging and longevity.

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