Pencina et al., 2022 | The Journals of Gerontology
NMN doses of 1,000 mg taken once daily doubles NAD+ levels (middle graph). When taken twice daily, NMN triples NAD+ levels (right graph).
Dr. David Sinclair is a co-founder of Metrobiotech, whose NMN product MIB-626 was used in this research published Feb 19 2022.
32 volunteers were given either placebo, 1000 mg of NMN once per day, or twice per day. Levels of NAD+ metabolites in the blood were tested at baseline, and over 24 hours after supplementation on day 1,7, and 14.
They found their NMN was safe, with no adverse side effects, and was effective at raising levels of NAD+, NMN, NR, and other metabolites in the blood.
Some Notable Findings
- NMN raises NAD+ levels 300%
- NAD+ levels may not increase during the day – no circadian rhythm effect found
- Large dose of NMN more effective than smaller dosages.
- NMN supplement raises levels of NR in blood, NR supplements may not
- Increase of other NAD+ metabolites likely more important than NAD+ itself
NAD+ Levels May Not Increase During the Day – No Circadian Rhythm Effect Found
The chart above shows NAD+ levels over 24 hours after a dose of NMN on day one and day 14.
You can see this research found no peak of NAD+ levels during the day, refuting claims of a circadian rythm with NAD+ levels peaking at noon in humans.
According to the researchers:
Blood NMN and NAD levels were similar on days 8 and 14 and the NMN and NAD concentrations did not vary during the 24-hour period on day 14.
Large Dose of NMN More Effective Than Smaller Dosages
In earlier research, this group found smaller dosages of NMN were not consistently effective at elevating NAD+ levels in the bloodstream, so inreased to 1,000 mg for this study.
The chart above shows that 1,000 mg twice per day were even more effective than a single dose.
According to the researchers:
“1000 mg once-daily regimen was associated with an average 2.7- and 1.7-times increase above baseline and twice-daily treatment resulted in 4.5- and 3.7 times increase in mean Cmax and AUC”
NMN Supplement Raises Levels of NR in blood – NR Supplements Do Not
These charts shows the increased levels of Nicotinamide Riboside (NR) in blood with 1 or 2 daily dosages of NMN.
It is not a huge increase, and relatively little NR is found in the bloodstream compared to other NAD+ metabolites. We only mention it here because the study found NMN supplementation does increase NR levels.
So far, all studies in mice and humans given NR have failed to show an increase of NR in the blood. Dr. Charles Brenner claims that is due to the difficulty in testing the minute quantities of NR, yet this research found otherwise, providing further evidence that the instability and lack of bioavailability of NR as a supplement prevents it from making it past the liver in measurable quantities.
NAD+ Metabolites Increase Likely More Important than NAD+
Testing levels of NAD+ in the bloodstream is the accepted method for measuring effect of NAD+ precursors, but it is most likely not the impactful metabolite for impact on health.
The chart below notes the quantities of different metabolites found in the bloodstream in this research. You can see that N-methyl-2-pyridone- 5-carboxamide (2-PY) is over 100x more prevalent than NAD+ or NAM, and is massively increased with NMN supplementation.
Conclusion
This study shows humans given 1000 mg a day of MIB-626, a patented form of NMN experienced a substantial increase in levels of NAD+ metabolites, with a dose dependent increase for those given 1000 mg twice a day.
The increased NAD+ levels reached their maximum after 1 week, and sustained at 2 weeks.