If you have been browsing products described as „NAD+ supplements”, you may have noticed that many of them do not actually contain NAD+ itself. Instead, they often contain compounds such as NMN or NR. The reason comes down to biochemistry. NMN, NR, niacin and nicotinamide can act as precursors that the body uses to produce NAD+. However, they enter NAD+ metabolism at different stages and should not be treated as interchangeable compounds. Understanding these differences helps to explain why scientists study NAD+ precursors, how NMN and NR are converted into NAD+, and why an increase in measured NAD+ levels does not automatically mean that all of the health effects attributed to it will occur.
What is an NAD+ precursor and how does it differ from NAD+ itself?
An NAD+ precursor is a molecule that the body can use as a starting material to produce NAD+ through one or more enzymatic reactions. The precursor is therefore related to the production of NAD+, but is not NAD+ itself. [1]
This distinction is particularly important in the case of supplements.
NAD+ is a relatively large and charged molecule, and evidence that orally ingested intact NAD+ is efficiently absorbed and directly delivered to cells remains limited. For this reason, research interest has shifted towards smaller precursor molecules that can enter NAD+ biosynthetic pathways and subsequently be converted by the body's enzymes. [1]
Several compounds can contribute to NAD+ synthesis.
These include traditional forms of vitamin B3, such as niacin and nicotinamide, as well as two molecules that have gained particular significance in NAD+ research:
- nicotinamide mononucleotide (NMN);
- nicotinamide riboside (NR).
NMN and NR enter the pathway relatively close to NAD+ itself. This is one of the reasons why they have become an important subject of research into whether precursor supplementation can alter NAD+ availability in humans. [1]
However, describing them as NAD+ precursors does not mean that NMN, NR and NAD+ are chemically or biologically identical.
What is NMN and how is it related to NAD+?
Nicotinamide mononucleotide, usually abbreviated to NMN, is a naturally occurring intermediate compound in the biosynthesis of NAD+.
Simply put, NMN is one of the molecules that cells can directly convert into NAD+.
Structurally, NMN contains a nicotinamide group linked to a ribose sugar, to which a phosphate group is attached. An enzyme known as nicotinamide mononucleotide adenylyltransferase, or NMNAT, then catalyses the step leading to the formation of NAD+. [1]
Because NMN is close to NAD+ in this pathway, researchers are investigating whether providing additional NMN can increase NAD+ concentrations in humans.
In one randomised, multicentre, double-blind, placebo-controlled trial, 80 healthy middle-aged and older adults participated. Participants received 300, 600 or 900 mg of NMN daily for 60 days. [2]
Researchers noted a dose-dependent increase in blood NAD+ concentration in all groups receiving NMN. In the groups taking higher doses, improvements were also observed in the six-minute walk test. [2]
However, not all results have improved.
For example, this study found no significant effect of NMN supplementation on measures of insulin sensitivity. [2]
This is an important distinction. Demonstrating that NMN increases blood NAD+ levels confirms its biological activity, but does not mean that all the proposed metabolic, longevity or performance-related effects will automatically occur.
NMN is also found naturally in small amounts in food, including broccoli, cabbage, cucumbers and edamame. However, the amounts naturally present in food are much smaller than the doses investigated in many supplementation trials.
What is nicotinamide riboside (NR)?
Nicotinamide riboside, commonly referred to as NR, is another NAD+ precursor.
It is chemically related to NMN, but it is not the same molecule.
NR consists of nicotinamide linked to a ribose sugar, without the phosphate group present in NMN. Inside cells, enzymes called nicotinamide riboside kinases, or NRKs, can phosphorylate NR and convert it into NMN. NMN can then be further converted into NAD+. [1]
Therefore, the simplified route looks as follows:
NR → NMN → NAD+
This means that NR is located one enzymatic step upstream of NMN in this particular pathway.
NR has been investigated in several controlled human studies.
In one of the earlier pharmacokinetic studies, single oral doses of 100, 300 and 1000 mg were analysed. The researchers observed dose-dependent changes in NAD+ metabolism and identified nicotinic acid adenine dinucleotide, or NAAD, as a sensitive biomarker associated with NAD+ replenishment. [3]
In another randomised, double-blind, placebo-controlled crossover study involving healthy middle-aged and older adults who received NR for two six-week periods, NR was well tolerated and increased indices related to NAD+ metabolism. However, the researchers noted that further studies are needed to determine potential cardiovascular effects, including the impact on blood pressure and arterial stiffness. [4]
An eight-week randomised, double-blind, placebo-controlled trial evaluated daily doses of NR of 100, 300 and 1,000 mg in healthy, overweight adults. Whole-blood NAD+ levels increased by approximately 22%, 51% and 1,42%, respectively, in the three dose groups, with no significant safety concerns reported during the study. [5]
A further study involved 120 healthy individuals aged 60–80, who were given a preparation containing NR and the polyphenol pterostilbene for eight weeks. In the group receiving the standard dose, NAD+ levels were approximately 40% higher than baseline values in the fourth and eighth weeks, whilst the group receiving the higher dose showed an even greater increase. No similar change was observed in the placebo group. [6]
These studies provide evidence that oral NR can alter NAD+ metabolism in humans.
However, they do not show that merely increasing NAD+ through NR must lead to clinically significant anti-ageing, cardiovascular, metabolic or longevity-related effects.
Are NAD+ and NMN the same thing?
No. NAD+ and NMN are different molecules.
NMN is a precursor used in the biosynthesis of NAD+, whilst NAD+ is a fully formed coenzyme that plays a direct role in numerous metabolic reactions and cellular processes. [1,2]
This distinction is easily blurred because in commercial and informal materials terms such as „NAD+”, „NAD booster” and „NMN” are sometimes used almost interchangeably.
From a biochemical point of view, however, they should be clearly separated.
NMN must undergo a further enzymatic step before it becomes NAD+. In this pathway, NMNAT enzymes catalyse its conversion towards the formation of NAD+.
Formed NAD+ can then directly participate in redox metabolism and act as a substrate for NAD+-dependent enzymes, including sirtuins and PARPs.
NR is even one step earlier.
First it is converted into NMN, and then it can take part in NAD+ synthesis. [1]
Taking a product containing NMN or NR is therefore not the same as directly delivering fully formed NAD+ to the cells.
It supplies precursor material that must enter the organism's existing metabolic pathways.
The efficiency of these pathways can also vary between tissues and depend on physiological conditions. The influence of factors such as age, metabolic state, transporter activity, enzyme expression, and tissue type on the response to individual NAD+ precursors remains a subject of research.
Which precursor is most commonly used in NAD+-boosting products?
Both NMN and NR are widely discussed as precursors that increase NAD+, and current evidence does not indicate that either of them is universally better.
Their research backgrounds are slightly different.
NR acquired a human trials base relatively early, including randomised, placebo-controlled trials on pharmacokinetics, tolerance and changes in NAD+ metabolism. [3–6]
Human studies on NMN developed later, but have also expanded significantly. Controlled trials have shown that oral NMN can increase NAD+ levels in the blood. [2]
However, the mere number of studies does not determine which precursor is „better”.
Direct studies comparing NMN and NR in humans under equivalent conditions are still scarce. Differences in dosages, study populations, duration, biological samples collected, formulations and evaluated endpoints further complicate indirect comparisons.
Products widely referred to as „NAD+ supplements” may also contain other ingredients.
Some contain niacin or nicotinamide, which are traditional forms of vitamin B3 that also participate in NAD+ biosynthesis. Others combine NMN or NR with additional compounds.
Therefore, the term „NAD+ supplement” does not refer to one specific molecule.
The actual active ingredient matters.
An NR-containing product, an NMN product, and a preparation containing nicotinamide can all be advertised in the context of NAD+, even though they utilise different biochemical pathways and have distinct evidence bases.
A more scientific approach therefore involves first identifying a specific precursor and then evaluating the evidence regarding that exact molecule, rather than treating the entire category of NAD+ supplements as a single intervention.
Limitations of current evidence
Most human studies on NMN and NR have been relatively short, typically lasting from a few weeks to a few months. For this reason, long-term, multi-year data on efficacy and safety remain limited. [2,4–6]
Another important limitation is the small number of well-controlled studies directly comparing NMN with NR under the same conditions. Without matching the dose, population, duration, and endpoints, it is difficult to determine whether either precursor is consistently more effective at increasing NAD+ in various human tissues.
Blood levels of NAD+ are also not the same as a demonstrated clinical effect. Human studies show that NMN and NR can alter NAD+ metabolism, but results regarding insulin sensitivity, cardiovascular parameters, physical performance and other proposed effects have not been consistently confirmed across all studies. [2,4]
Another unknown is tissue-specific effects. An increase observed in whole blood does not automatically mean the same increase in the brain, skeletal muscle, liver, heart, or other organs.
When evaluating the literature, funding sources must also be taken into account. Some important research on NR has been funded or supported by companies associated with products containing NAD+ precursors, including studies using Niagen and NR-pterostilbene formulations. [5,6] Industry involvement does not invalidate peer-reviewed randomised controlled trials, but funding sources and potential conflicts of interest are an essential element in evaluating the overall body of evidence.
Disclaimer
This article is for educational and scientific-informational purposes only. It does not constitute medical advice, a diagnosis, treatment guidelines, dosage instructions, or a recommendation for the use of NAD+, NR, NMN, niacin, nicotinamide, or any other NAD+-related compounds.
Research on NAD+ encompasses both well-established biochemical mechanisms and the results of cellular, animal, and human studies with varying levels of evidence. Changes in NAD+ metabolism, sirtuin activity, mitochondrial function, or other cellular pathways should not be interpreted as proof that increasing NAD+ prevents, treats, or reverses ageing, cardiovascular disease, neurological disorders, metabolic diseases, or any other conditions.
Interventions aimed at increasing NAD+ levels and their long-term clinical effects remain the subject of active research. The results of mechanistic studies and an increase in measured NAD+ levels do not necessarily translate into significant health benefits in humans.
References
[1] Yoshino, J., Baur, J. A., & Imai, S. (2018). NAD+ intermediates: The biology and therapeutic potential of NMN and NR. Cell Metabolism, 27(3), 513–528. https://doi.org/10.1016/j.cmet.2017.11.002
[2] Yi, L., Maier, A. B., Tao, R., Lin, Z., Vaidya, A., Pendse, S., Thasma, S., Andhalkar, N., Avhad, G., & Kumbhar, V. (2022). The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: A randomised, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience, 45, 29–43. https://doi.org/10.1007/s11357-022-00705-1
[3] Trammell, S. A. J., Schmidt, M. S., Weidemann, B. J., Redpath, P., Jaksch, F., Dellinger, R. W., Li, Z., Abel, E. D., Migaud, M. E., & Brenner, C. (2016). Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nature Communications, 7, 12948. https://doi.org/10.1038/ncomms12948
[4] Martens, C. R., Denman, B. A., Mazzo, M. R., Armstrong, M. L., Reisdorph, N., McQueen, M. B., Chonchol, M., & Seals, D. R. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature Communications, 9, 1286. https://doi.org/10.1038/s41467-018-03421-7
[5] Conze, D., Brenner, C., & Kruger, C. L. (2019). Safety and metabolism of long-term administration of NIAGEN (nicotinamide riboside chloride) in a randomised, double-blind, placebo-controlled clinical trial of healthy overweight adults. Scientific Reports, 9, 9772. https://doi.org/10.1038/s41598-019-46120-z
[6] Dellinger, R. W., Santos, S. R., Morris, M., Evans, M., Alminana, D., Guarente, L., & Marcotulli, E. (2017). Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: A randomised, double-blind, placebo-controlled study. npj Aging and Mechanisms of Disease, 3, 17. https://doi.org/10.1038/s41514-017-0016-9