The differential impact of three different NAD + boosters on circulatory NAD and microbial metabolism in humans.
Level 2 - randomized trial
Individual randomized controlled trial in humans
PubMed 41540253 · doi:10.1038/s42255-025-01421-8
What was done
A randomized, open-label, placebo-controlled trial in 65 healthy adults compared 14 days of supplementation with three NAD+ precursors—nicotinamide (Nam), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN)—against placebo to assess impacts on circulatory NAD+ concentrations. Mechanistic follow-ups included ex vivo human microbiota fermentation assays to measure precursor conversion and bacterial growth, as well as ex vivo whole-blood assays assessing precursor-driven NAD+ synthesis.
What was found
The abstract reports no exact numerical values, effect sizes, or confidence intervals. Directionally, 14 days of supplementation with NR and NMN comparably increased circulatory NAD+ levels, whereas Nam did not show a sustained increase. Nam alone acutely and transiently altered the whole-blood NAD+ metabolome. Ex vivo, NR and NMN were converted by human gut microbiota to nicotinic acid (NA) and enhanced microbial growth and metabolism. In whole blood ex vivo, NA directly boosted NAD+, whereas NMN, NR, and Nam did not.
Why it matters
This trial provides a direct human comparison of common NAD+ boosters, proposing that oral NR and NMN elevate systemic NAD+ through gut microbial conversion to nicotinic acid and the Preiss-Handler pathway rather than direct salvage uptake.
Limits
The study used an open-label design, had a modest sample size (65 participants across multiple groups), tested a brief 14-day duration, and enrolled only healthy adults. Key gut-conversion findings rely on ex vivo models rather than direct in vivo flux tracing, and no numerical effect estimates were provided in the abstract.
Cited by
- supports A clinical study from Nestlé demonstrated that the gut microbiome is involved in converting NR and NMN into NAD in human tissues.
- supports The Nestlé group showed that NR supplementation alters the human microbiome and suggested conversion of NR into nicotinic acid.