Restoring NAD+ levels in older animals and humans is at the center of efforts to slow or even stop the effects of aging.
One method being researched is providing supplements such as Nicotinamide Riboside (NR) that the body can use to create NAD+.
The chart above is from this study published in August 2019 by Dr. Charles Brenner which found that NR supplementation for 3 weeks resulted in decreased marker of inflammation in the blood of older humans.
Another study by Dr. Brenner published in January 2019 found NR supplementation of lactating mice resulted in offspring that were smarter, healthier and better adjust socially.
However, both studies agree that NR is never found at more than trace levels in the blood, and was not increased with supplementation.
- NR levels in humans do not increase after 3 weeks of 1,000 mg a day of oral NR supplements
- NR given to lactating mice does not reach the bloodstream
So how does NR supplementation work?
According to Dr. Brenner, the increased NAD+ in the blood made it’s way into the milk of nursing mothers, and that NAD+ provided the benefit to nursing pups.
It seems likely it is also the increased NAD+ in the blood that lowered the inflammation markers in humans, since NR is only found at trace levels in the blood, and doesn’t increase with supplementation.
These studies show NR supplementation resulted in increased levels of NAD+ in the bloodstream, but not NR.
NR supplements do not reach the bloodstream as NR.
Conclusion – NAD+, not NR is transported in the bloodstream to tissues throughout the body where it is needed.
The liver blocks most NR and NMN from circulating in blood
This March 2018 study by Liu/Rabinowitz used radioactive isotopes to trace the pathways used by NR and NMN supplements through the GI tract, into the bloodstream and tissues.
Surprisingly, they found no NR or NMN made it past the liver intact, but were metabolized to nicotinamide (NAM).
Other researchers have questioned the methodology used, but have not yet been able to disprove the main finding.
Humans given 1,000 mg NR a day for 3 weeks – NR in blood not increased
The draft for this research was released June 28, 2019.
12 males aged 70-80 years old were given 1,000 mg of Nicotinamide Riboside (NR) per day for 3 weeks.
NR levels were not increased in blood
- NR was found at trace levels in the blood
- NR levels were unchanged after supplementation
NAD+ levels were greatly increased in blood
- NAD+ was present in the blood at more than 100x the levels of NR in the blood.
- NAD+ levels more than doubled with supplementation of NR.
NR has no effect on levels of NR circulating in the bloodstream.
NR is converted to NAD+, or degraded to NAM when it reaches the bloodstream
NR, but no NMN or NAD+ in urine
Notice that the quantity of NR excreted increases with supplementation. But they found NO NMN or NAD+ is excreted in urine
- NR is found in the urine
- NR supplementation increases levels of NR in urine
- NAD+ is not found in urine before or after supplementation
- NMN is not found in urine before or after supplementation
* BLQ = Below Limits of Quantification (to little to measure)
Increased NAD+ (not NR) in mothers milk a huge benefit for nursing mice
After weaning, the pups were separated from their mothers, so any difference between the 2 groups was strictly due to the difference in milk they received while nursing.
Surprisingly, the pups whose mothers received NR were significantly smarter, stronger, faster, and had less anxiety.
- Higher body weight
- Increased activity
- Larger brain size
- Diminished Anxiety
- improved spatial memory
Dr. Brenner credits increased NAD+ in blood
NAD+ in bloodstream more than doubled
Lactating mothers have much lower levels of NAD+ in the liver, and are able to send more of it to the pups in her milk.
At the 47:00 mark, Dr. Brenner says that during lactation, NAD metabolites in mammary tissue is 20-30x higher than normal, which is totally unprecedented.
He goes on to say the NR led to increased NAD+ in the bloodstream and then the mammary glands and milk.
NAD program is recirculated away from the liver, thru the blood, and into mammary tissue and milk. (47:35)
No NR is found intact in mothers milk
Dr. Brenner says the NR supplement is not making it intact to the bloodstream or into the mothers milk.
Although small quantities of NR are found in the milk of lactating females as shown in charts at left, none was found to be directly from the NR supplements.
A heavy atom was added to the NAM and ribose moieties of NR molecules, and the compound was introduced by gavage to lactating mice at day 13. At 2–24 h post-gavage, mice were milked.
No double-labeled NR was ever detected.
the mother’s oral NR is not directly transmitted to her milk
NR supplementation to nursing mothers increases NAD+ levels in blood which has great benefits to pups.
- The liver blocks most NR (and NMN) supplements from circulating in blood
- NR is found at trace levels in the bloodstream
- NR supplementation does not increase levels of NR in the blood
- NAD+ is present at 100 – 300x higher quantites than NR
- NAD+ levels in the blood do increase with NR supplementation
In both of these studies, increased NAD+ in the bloodstream was found to have significant benefit.
Neither study showed that NR supplementation increased NR in the bloodstream.
NR is either converted to metabolites that are stored in blood like NMN and NAD+, or, is excreted as NR or MeNam.