NAD+ vs NMN vs NR - A Closer Look.

30 Sep 2025

This series of articles explores the differences between NAD+, NMN & NR, the relationship between each other, and the role they play in different mechanisms in the body. Initially, this first article will explore the roles of NMN and NR and their functions with regards to NAD+.

Firstly, when looking at NAD+, NMN and NR we can observe that NMN or 'nicotinamide mononucleotide' and NR 'nicotinamide riboside' are actually biosynthetic precursors to NAD+, also known as 'nicotinamide adenine dinucleotide, which is an essential molecule for metabolism.

Multiple studies show that NAD+ levels decline substantially with age. Restoring NAD+ levels in older animals has been linked to improved health and extended lifespan. Research into these two key precursor molecules suggests that supplementation with either can raise NAD+ levels during aging. But what distinguishes these NAD+ precursors from one another?

NMN and NR differ somewhat in not only molecular structure (as seen in Figure 1) but also in how they are biosynthesised by cells to form NAD+. Here is a breakdown of some of the similarities and differences between NMN and NR:

Figure 1 - Comparison of NMN & NR molecular structures.

Differences

NMN is a LARGER molecule than NR.
NMN is the immediate precursor to NAD+ whereas NR requires conversion to NMN via an enzyme known as NRK before converting to NAD+.
NMN has a specific transport in mice.

Similarities

NMN and NR utilise the salvage pathway of NAD+ biosynthesis to boost NAD+ in cells.
Studies indicate NMN and NR are safe for human consumption.
NMN and NR need to be kept in the cold to avoid degradation.

Figure 2 - Central to cellular health, NAD+ impacts the whole body.

The molecular structures of NMN and NR are very similar, with the key difference being that NMN carries an additional phosphate group. This extra group makes NMN a larger molecule than NR. Because of its size, some researchers suggest that NMN cannot easily cross cell membranes and must first be converted into NR before entering cells, where NAD+ is produced. Alternatively, NMN may enter cells through a dedicated transporter, such as Slc12a8.

Once inside the cell, nicotinamide riboside (NR) is converted into nicotinamide mononucleotide (NMN) by enzymes known as NRKs. From there, NMN enters the nicotinamide salvage pathway, the primary route for NAD+ biosynthesis.

Within this pathway, the enzyme NMNAT transforms NMN into NAD+, a vital coenzyme. Sirtuins, a family of proteins that help regulate cellular health, consume NAD+ during their activity, generating nicotinamide (NAM) as a byproduct. NAM is then recycled back into NMN by the enzyme NAMPT, completing the cycle.

The human diet naturally provides vitamin B3 compounds - namely nicotinamide (NAM), nicotinic acid (NA), and nicotinamide riboside (NR) - all of which serve as precursors for NAD+ production. NAD+ can also be synthesized from the amino acid tryptophan. Without vitamin B3 sources, tryptophan, or supplementation with NMN, humans cannot maintain sufficient NAD+ levels.

Research highlights the potential of NR as an NAD+ booster. A 2007 study showed that NR substantially increased NAD+ levels in yeast, and subsequent work revealed boosts of up to 270% in mammalian cells. These findings suggest that the salvage pathway, driven by NR and NMN, plays a particularly important role in sustaining NAD+ availability, though the precise mechanisms are still under investigation.

Debate continues among scientists as to whether NMN or NR is the superior precursor in terms of effectiveness and safety. One argument holds that because NMN is larger, it may need to be converted into NR before crossing the cell membrane, only then converting back into NMN once inside the cell. If this model is correct, NR could be considered the more efficient precursor.

Figure 3. How NMN and NR become NAD+ in cells.

NMN Transporter Discovery

Researchers at Washington University School of Medicine in St. Louis recently identified evidence for a dedicated NMN transporter in the mouse gut, known as Slc12a8. Transporters are proteins that enable molecules to cross biological barriers, such as the cell membrane, allowing efficient uptake into cells.

Genomic analyses suggest that the human genome also encodes the SLC12A8 transporter. According to a human gene expression database, SLC12A8 is present in multiple tissues - including the small intestine, stomach, testis, thyroid, and colon. This raises the possibility that humans, like mice, may express this transporter in the gut, giving NMN a direct absorption pathway. However, confirming this role in humans will require further research. If validated, NMN could represent a more efficient and direct NAD+ precursor compared with NR.

Figure 4: slc12a8 - An NMN transporter found in mice.

Safety of NMN and NR

Safety is a fundamental concern for any supplement. Current research indicates that both NMN and NR are generally well tolerated.

NMN

A clinical study in healthy men in Japan found no adverse effects after a single oral dose of up to 500 mg. The researchers reported no changes in heart rate, blood pressure, oxygen levels, or body temperature, concluding that "oral NMN was safe and effectively metabolized without harmful effects."

NR

Human studies have shown similar results. In one trial, overweight but otherwise healthy adults took up to 1,000mg daily for eight weeks without safety concerns. To date, no major side effects have been reported in human studies of either molecule.

Figure 5 - NMN speak rapidly in plasma before a sustained rise in tissue NAD.

Bioavailability of NMN and NR

Bioavailability refers to how efficiently a compound is absorbed and utilized in the body, often measured by increases in blood levels of the compound itself or NAD+.

NMN

Animal studies show that oral NMN rapidly raises blood NMN and NAD+ levels. In mice, a 300 mg/kg dose produced peak NMN levels in the blood within 10 minutes, and NAD+ levels increased significantly within 30 minutes.

NR

Human studies provide more direct evidence. A single oral dose of NR has been shown to increase blood NAD+ levels by up to 2.7-fold. Additional studies demonstrate clear dose-dependent effects: daily doses of 100, 300, and 1,000mg of NR raised NAD+ levels by approximately 22%, 51%, and 142%, respectively, within two weeks.

Together, these findings confirm that both NMN and NR can enhance NAD+ levels, though the majority of human data currently comes from NR.

Stability and Storage

Proper storage is crucial to maintain the effectiveness of both compounds.

NR - Stable for up to six hours at room temperature and up to seven days when refrigerated (2 - 8°C).
NMN - Like NR, NMN is prone to degradation if not stored properly.

As Dr. David Sinclair of Harvard University advises: "Make sure your NR and NMN are kept cold. If left on a shelf in an unstable form, they degrade into nicotinamide. High doses of nicotinamide can inhibit sirtuins and PARPs, interfering with DNA repair."

Conclusion

Both NMN and NR are safe and effective NAD+ precursors with promising roles in healthy aging. NR has more extensive human bioavailability data, while NMN's potential is supported by strong animal studies and emerging human evidence. Future clinical trials directly comparing the two will help clarify which is the more efficient NAD+ booster.

Legal Disclaimer

This article is intended for educational and informational purposes only. The scientific data and discussion presented here are not meant to diagnose, treat, cure, or prevent any disease. Products mentioned are supplied strictly for laboratory research use only and are not intended for human consumption. Any references to safety, efficacy, or biological effects are drawn from published research studies and do not imply approval for clinical or personal use.

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