Data from a randomized, open-label, placebo-controlled study with healthy adults revealed that NR and NMN were converted by the gut microbiota to produce nicotinic acid (also called niacin, NA), and it is this NA that is raiding NAD+ levels.
In addition, nicotinamide (Nam) is absorbed right away and converted directly to NAD+, giving a transient boost to NAD+ levels, according to findings published in Nature Metabolism.
“This head-to-head comparison of three NAD+ precursors in healthy adults shows that NR and NMN are comparable in their ability to chronically increase baseline whole-blood NAD+ levels, while Nam provides only an acute transient effect,” wrote scientists from Nestlé Research, Nestlé Health Science and Cryptobiotix.
“Furthermore, ex vivo fermentation with human-derived microbiota demonstrated that NR induces metabolic microbial adaptations regardless of donor conditions and, together with NMN, increases SCFA production. This suggests that the oral intake of NR and NMN and their microbially produced metabolite NA may offer dual benefits: a sustained increase in systemic NAD+ levels and enhanced gut health.”
NAD+ and aging
Interest in NAD+ has grown in recent years as awareness and understanding of its links to aging have deepened.
As organisms age, NAD+ levels drop, which leads to a decrease in mitochondrial health; this in turn leads to age-related health issues. NAD+ levels also can be depleted by lifestyle choices such as overeating and lack of exercise. By boosting NAD+, compounds like NR and NMN are reported to improve mitochondrial health and induce the creation of new mitochondria.
The Nestlé scientists noted, however, that while there have been many preclinical studies on the effects of these precursors, a head-to-head comparison in humans had not previously been performed. Additionally, recent data from rodents suggested that the NAD+-boosting effects of NR and NMN was linked to conversion by the gut microbiome to NA, but this mechanism not been confirmed in humans.
Study details
To fill these knowledge gaps, the researchers recruited 65 healthy people (average age of 35) and randomly assigned to one of four groups: placebo, Nam (Pure Encapsulations; 500 mg per day), NR (TRU NIAGEN Pro; 1,000 mg per day), or NMN (UltraHealth; 1,000 mg per day) for 14 days.
Results showed that NR and NMN led to two-fold increases in whole blood NAD+ levels, while Nam only led to short-term changes and did not raise NAD⁺ levels in the same way as NR and NMN.
NR and NMN, but not Nam, produced metabolic adaptations of the gut microbiota and enhancing microbial activity. Both were converted to nicotinic acid which boosts NAD+, the study reported.
“Therefore, the combined increase in NA and SCFA [short chain fatty acids] might uniquely contribute to enhancing the integrity of epithelial tissue, mitigating mucosal inflammation and maintaining intestinal homeostasis,” the researchers wrote, before calling for future studies to explore the potential benefits of NR and NMN on the human gastrointestinal system.
“Ultimately, we propose a gut-dependent model for the modes of action of the three NAD+ precursors with NR and NMN elevating circulatory NAD+ via the Preiss–Handler pathway, while rapidly absorbed Nam acutely affects NAD+ levels via the salvage pathway," they added. “Overall, these results indicate a dual effect of NR and NMN and their microbially produced metabolite NA: a sustained increase in systemic NAD+ levels and a potent modulator of gut health.”
Source: Nature Metabolism. 2026. Volume 8, Pages 62–73. doi: 10.1038/s42255-025-01421-8. “The differential impact of three different NAD+ boosters on circulatory NAD and microbial metabolism in humans”. Authors: S. Christen, et al.
