Nicotinamide Riboside (NR) vs. Nicotinamide Mononucleotide (NMN): What’s The Difference?

What Are NAD+ Precursors?

Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN are NAD+ precursors, meaning they boost NAD+ levels in the body. The use of oral NAD+ precursors, specifically nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), has gained significant attention for their potential to help restore NAD+ that may be suboptimal. 

Benefits Of NAD+ For Healthy Aging

Nicotinamide adenine dinucleotide (NAD+) is a pivotal coenzyme for cellular metabolism, mitochondrial function, and genomic stability. 

Research indicates that NAD+ levels decline with age, everyday metabolic stress, and suboptimal lifestyle factors. NAD+ supports critical cellular processes, including:

• Energy Metabolism
• Mitochondrial Oxidative Phosphorylation
• DNA Repair
• Redox Balance
• Steroid Hormone Synthesis

Age-related NAD+ decline is linked to mitochondrial dysfunction, increased oxidative stress, and decreased cellular repair capacity, which can impact overall cognitive health and metabolic balance. Therefore, strategies to boost NAD+ are of growing clinical interest.

The Difference Between NR And NMN

Nicotinamide Riboside (NR)

While NR and NMN are structurally similar, only NR can cross cell membranes via equilibrative nucleoside transporters (ENTs) and is considered a bioavailable form of vitamin B3. 

Nicotinamide Mononucleotide (NMN)

NMN, due to its phosphate group, cannot enter cells directly and must be extracellularly converted to NR before NAD+ synthesis can occur. Multiple isotope-labeling and enzymatic studies show that CD73 dephosphorylates dietary NMN to NR, and that once NR is formed, it is transported into cells and converted to NAD+.

Differences In Absorption

In a study published in Nature Metabolism, researchers identified a transport protein, the NMN transporter (Slc12a8), in the small intestine of mice.  However, the NMN transporter Slc12a8 has yet to be identified in other cells and tissues or in humans. The functional relevance or existence of Slc12a8 in humans remains controversial and is largely unsupported by independent analyses. In FEBS Letters 2023 (FEBS Letters is a not-for-profit peer-reviewed scientific journal published on behalf of the Federation of European Biochemical Societies (FEBS), researchers traced the metabolism of isotope-labeled NMN in the intestinal tissue of mice both with and without microbiome ablation (the removal of gut bacteria). They investigated whether the gut microbiome plays a role in NMN metabolism. Treatment with 100% labeled NMN resulted in a striking increase in unlabeled NAD+ metabolites. In fact, a substantial increase was seen in endogenous NR levels in the guts of both antibiotic-treated and untreated mice. Additionally, labeled NMN was found to be overwhelmingly present as NR in the intestinal tissue, which suggests dephosphorylation of NMN is the primary route for its uptake. 

 As a result, the extracellular conversion of NMN to NR is recognized as the predominant physiological pathway for NAD+ biosynthesis from NMN.    

Which Is A Better NAD+ Booster?

Head-to-head preclinical and clinical trials consistently show that NR is more efficient in elevating cellular and systemic NAD+ than NMN. In one in vivo study, oral NR raised liver NAD+ by 220%, compared to only 170% for NMN at equal doses, reflecting approximately 23% greater efficiency.⁷  

However, clinical research has been mixed. A recent study found that, after 8 days of daily supplementation, oral NR raised whole blood NAD+ levels ~2.3-fold higher than NMN at equal doses. A longer study found that after 14 days of supplementation, NR and NMN comparably elevated whole blood NAD+ levels.¹² In contrast, comparing two separate human trials, NR produced a greater increase in whole-blood NAD+ after 2 weeks of supplementation compared with NMN.^13,14

Further, NR provides greater protection against cisplatin-induced DNA damage in cultured cells than NMN, highlighting its benefits for genomic stability and cellular resilience.¹⁵

Dual Mode Of Action: Boosting Synthesis And Inhibiting Consumption

Beyond its ability to increase NAD+ production, NR also inhibits CD38, an NAD+ consuming enzyme whose activity increases with aging and inflammation.  By suppressing CD38, NR helps to preserve NAD+ pools and counter age-related declines. Thus, NR supports increased production and helps conserve existing NAD+ levels. As I share with my patients, it helps prevent loss, much like the adage, "a penny saved is a penny earned." In contrast, NMN does not show comparable CD38 inhibition in vitro, according to recent studies. This inhibitory effect of NR and the lack thereof for NMN were also supported by recent ex vivo analyses of human whole blood.

Head-to-Head Comparison

Concerns regarding NMN purity remain, with 64% of sampled NMN supplements failing to meet label claims in market analyses. Only 14% met the label claim, and 23% were just below it.¹⁸

• NR directly enters cells via ENTs, whereas NMN must be converted to NR. 
• NR has greater NAD+ boosting in some studies, but clinical results are mixed.
• NR supports CD38 Inhibition, which can help conserve NAD+, whereas NMN does not appear to do so

Conclusion

As clinicians, our patients depend on us to provide scientific vetting of the most effective, safest, and evidence-based clinical interventions to support their individual wellness pursuits. NR's dual-mode ability to boost NAD+, inhibit age-related decline mechanisms, and meet stringent regulatory standards underscores its primacy in research-based supplementation. NMN's inconsistent quality control in the marketplace is a concern for us in clinical practice and for our patients.

References:

1. Fletcher, R.S., Ratajczak, J., Doig, C.L., Oakey, L.A., Callingham, R., Xavier, G.D.S. et al. (2017) Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells. Molecular Metabolism, 6, 819–32. https://doi.org/10.1016/j.molmet.2017.05.011
2. Grozio, A., Sociali, G., Sturla, L., Caffa, I., Soncini, D., Salis, A. et al. (6AD) CD73 Protein as a Source of Extracellular Precursors for Sustained NAD+ Biosynthesis in FK866-treated Tumor Cells*. Journal of Biological Chemistry, 288, 25938–49. https://doi.org/10.1074/jbc.m113.470435
3. Kropotov, A., Kulikova, V., Nerinovski, K., Yakimov, A., Svetlova, M., Solovjeva, L. et al. (2021) Equilibrative Nucleoside Transporters Mediate the Import of Nicotinamide Riboside and Nicotinic Acid Riboside into Human Cells. International Journal of Molecular Sciences, 22, 1391.
4. Grozio, A., Mills, K.F., Yoshino, J., Bruzzone, S., Sociali, G., Tokizane, K. et al. (2019) Slc12a8 is a nicotinamide mononucleotide transporter. Nature Metabolim, 1, 47–57. https://doi.org/10.1038/s42255-018-0009-4
5. Kim, L., Chalmers, T.J., Madawala, R., Smith, G.C., Li, C., Das, A. et al. (2023) Host–microbiome interactions in nicotinamide mononucleotide (NMN) deamidation. FEBS Letters,. https://doi.org/10.1002/1873-3468.14698
6. Mateuszuk, Ł., Campagna, R., Kutryb-Zając, B., Kuś, K., Słominska, E.M., Smolenski, R.T. et al. (8AD) Reversal of endothelial dysfunction by nicotinamide mononucleotide via extracellular conversion to nicotinamide riboside. Biochemical Pharmacology, 178, 114019. https://doi.org/10.1016/j.bcp.2020.114019
7. Ratajczak, J., Joffraud, M., Trammell, S.A.J., Ras, R., Canela, N., Boutant, M. et al. (2016) NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. Nature Communications, 7, 13103. https://doi.org/10.1038/ncomms13103
8. Nikiforov, A., Dölle, C., Niere, M. and Ziegler, M. (2011) Pathways and Subcellular Compartmentation of NAD Biosynthesis in Human Cells. Journal of Biological Chemistry, 286, 21767–78. https://doi.org/10.1074/jbc.m110.213298
9. Kulikova, V., Shabalin, K., Nerinovski, K., Yakimov, A., Svetlova, M., Solovjeva, L. et al. (2019) Degradation of Extracellular NAD+ Intermediates in Cultures of Human HEK293 Cells. Metabolites, 9, 293. https://doi.org/10.3390/metabo9120293
10. Sauve, A.A., Wang, Q., Zhang, N., Kang, S., Rathmann, A. and Yang, Y. (2023) Triple-Isotope Tracing for Pathway Discernment of NMN-Induced NAD+ Biosynthesis in Whole Mice. International Journal of Molecular Sciences, 24, 11114. https://doi.org/10.3390/ijms241311114
11. Berven, H., Svensen, M., Eikeland, H., Tvedten, N., Sheard, E. V., Af Geijerstam, S. A., Søgnen, M., McCann, A., Arnsten, L., Årseth, O., Skjeie, V., Hjellbrekke, A., Skeie, G.-O., Torres Cleuren, Y. N., Nido, G. S., Riemer, F., & Tzoulis, C. (2026). The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation. iScience, 114764. https://doi.org/10.1016/j.isci.2026.114764
12. Christen, S., Redeuil, K., Goulet, L., Giner, M.-P., Breton, I., Rota, R., Frézal, A., Nazari, A., Van den Abbeele, P., Godin, J.-P., Nutten, S., & Cuenoud, B. (2026). The differential impact of three different NAD⁺ boosters on circulatory NAD and microbial metabolism in humans. Nature Metabolism, 8, 62–73. https://doi.org/10.1038/s42255-025-01421-8
13. Conze, D., Brenner, C. and Kruger, C.L. (2019) Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Scientific Reports, 9, 9772. https://doi.org/10.1038/s41598-019-46120-z
14. Pencina, K.M., Lavu, S., Santos, M. dos, Beleva, Y.M., Cheng, M., Livingston, D. et al. (2022) MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of β-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-Aged and Older Adults. The Journals of Gerontology: Series A, 78, 90–6. https://doi.org/10.1093/gerona/glac049
15. Qiu, S., Zhang, Y., Shao, S., Zhang, Y., Yin, J., Xu, X. et al. (2023) Nicotinamide Mononucleotide Versus Nicotinamide Riboside in The Protective Effects of Cisplatin-induced DNA Damage in HeLa Cells. https://doi.org/10.21203/rs.3.rs-3177159/v1
16. Covarrubias, A.J., Perrone, R., Grozio, A. and Verdin, E. (2021) NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology, 22, 119–41. https://doi.org/10.1038/s41580-020-00313-x
17. Roboon, J., Hattori, T., Ishii, H., Takarada‐Iemata, M., Nguyen, D.T., Heer, C.D. et al. (2021) Inhibition of CD38 and supplementation of nicotinamide riboside ameliorate lipopolysaccharide‐induced microglial and astrocytic neuroinflammation by increasing NAD+. Journal of Neurochemistry, 158, 311–27. https://doi.org/10.1111/jnc.15367
18. Kao, G., Zhang, X.-N., Nasertorabi, F., Katz, B.B., Li, Z., Dai, Z. et al. (2024) Nicotinamide Riboside and CD38: Covalent Inhibition and Live-Cell Labeling. JACS Au, 4, 4345–60. https://doi.org/10.1021/jacsau.4c00695
19. Tinnevelt, G.H., Engelke, U.F.H., Wevers, R.A., Veenhuis, S., Willemsen, M.A., Coene, K.L.M. et al. (2020) Variable Selection in Untargeted Metabolomics and the Danger of Sparsity. Metabolites, 10, 470. https://doi.org/10.3390/metabo10110470
20. Cooperman T, M.D. NAD Booster Supplements Review (NAD+/NADH, Nicotinamide Riboside, NMN) & Top Picks. ConsumerLab.com. https://www.consumerlab.com/reviews/nmn-nadh-nicotinamide-riboside/nmn-nadh-nicotinamide-riboside/