Nicotinamide riboside is uniquely and orally bioavailable in mice and humans.
Level 4 - case-series / case-control
Early-phase non-randomized pharmacokinetic study in humans combined with preclinical animal experiments
PubMed 27721479 · doi:10.1038/ncomms12948
What was done
Researchers evaluated the time- and dose-dependent pharmacokinetic effects of oral nicotinamide riboside (NR) on NAD+ metabolism in mice and humans. In mice, hepatic NAD+ accumulation from oral NR was compared against nicotinic acid and nicotinamide. In humans, an initial single-dose pilot evaluation was conducted in one individual, followed by a clinical trial assessing the blood NAD+ metabolome response to single oral doses of 100 mg, 300 mg, and 1,000 mg of NR.
What was found
In the single-participant pilot test, blood NAD+ increased up to 2.7-fold after a single oral NR dose. In mice, oral NR elevated hepatic NAD+ with pharmacokinetics described as distinct and superior to nicotinic acid and nicotinamide. In the human trial, single doses of 100, 300, and 1,000 mg produced dose-dependent increases in the blood NAD+ metabolome. Nicotinic acid adenine dinucleotide (NAAD) was formed from NR, serving as a biomarker of NAD+ repletion. Specific numeric parameters for the multi-dose cohort were not reported in the abstract.
Why it matters
This study provided the first human pharmacokinetic trial data showing that oral nicotinamide riboside increases circulating NAD+ metabolome components in a dose-dependent fashion, establishing NAAD as an in vivo biomarker of supplementation.
Limits
The abstract does not disclose the sample size of the primary human trial beyond the one-person pilot. The evaluation was limited to acute single doses without testing chronic daily dosing, and clinical efficacy or health outcomes were not assessed.
Cited by
- supports Clinical trials show that supplementing with NAD precursors NMN or NR can raise NAD levels approximately twofold in humans.