Natalie and her husband are very enthusiastic about NAD+ since they currently take NMN and want to try NAD+ IVs, as several friends have reported great results from it.
But unfortunately, their technical knowledge about the science is somewhat limited, so Dr Brenner had to generalize quite a bit and it wasn’t nearly as informative as the recent podcasts with Joe Rogan and Dr Sinclair or Dr Chris Masterjohn with Peter Attia
In the podcast Dr Brenner still claims that only NR can enter cells intact, and that NMN or NAD+ must be metabolized to NR to cross the cellular membrane (14:10).
This is may be true of many types of cells, but seems inaccurate to continue making such blanket statements, as several studies have shown NAD+ does enter into hypothalamus, heart and other tissues intact, and most recently, this study shows definitively that the Slc12a8 protein transports NMN (but not NR or NAD+) across the cellular membrane in the smalll intestine.
Increased NAD+ in the bloodstream seems to be the sole reason for benefits from NR supplementation in his latest research.
This is the real takeaway from this podcast.
Increased NAD+ in mothers milk a huge benefit for nursing pups
In this study, they gave lactating mice NR or placebo for 21 days while they were nursing their pups. 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
This was a very impressive result, and Dr Brenner is rightly very excited by the promise it holds to translate to humans, and what it says about the benefits of boosting NAD+ levels.
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. It is very interesting how the mother sacrifices NAD+ levels in the liver, pushing more into the bloodstream and on to the breast milk to aid her pups.
Describing the pathways of how the NR given to the mothers end up benefiting their pups – around the 47:00 mark Dr Brenner says that during lactation, NAD metabolites in mammary tissue is 20-30x higher than normal, which is totally unprecendented.
He goes on to say the NR raised NAD in the liver, which 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
The question of how the NR makes its way to NAD+ comes up and Dr Brenner refers to the Mar 2018 Liu,Rabinowitz study that shows no NR is able to make it past the liver into the bloodstream.
He says they have evidence that some NR can make it past the liver and into muscle intact. But this study also found that 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.
As shown in chart G, very small quantities of NR were found in milk of lactating females.
Single labelled NAM was prevalent for up to 14 hours. However, no double-labeled NR was ever detected.
the mother’s oral NR is not directly transmitted to her milk
Why we point out the pathway from NAD to pups
We know NAD+ levels in the bloodstream drop as we age, so that by age 60, they are about about 1/2 what they are when young. We know that much research measures the increase of NAD+ levels in the blood due to supplementation with NR and NMN.
However, there are questions about how increased levels of NAD+ in the blood may benefit different tissues throughout the body.
In this recent podcast with Dr Peter Attia, Dr. Chris Masterjohn lays out his theory that NAD+ is primarily a signaling molecule in the bloodstream, and isn’t really used as a means to transport NAD+ to other tissues.
That Dr Brenner credits the increased NAD+ in the mothers bloodstream as the sole cause of the incredible benefits conferred to her nursing pups is a strong argument that Dr Masterjohn is mistaken about the role of NAD+ in the blood.
NAD+ drips or clinics
Dr Brenner sounds quite irritated to hear that Natalie and her husband have heard great things about NAD+ IV drips and are very interested in trying it themselves (14:23).
He says he doesn’t recommend NAD+ clinics as he thinks anything with needles is unnecessary, while NR is proven safe and is more convenient.
He also says the science behind NAD+ IVs is unproven, which is technically true – there have not been any clinical studies to prove effectiveness. But NAD+ clinics have been used for decades to treat alcoholism, drug addiction, and mental problems such as depression and anxiety.
It is a bit contradictory of Dr Brenner to claim there is no proof that NAD+ IVs are effective when he clearly says in this podcast that it is elevated levels of NAD+ in the blood which provide the benefit in the research with nursing mothers.
We do agree that IV NAD+ is extremely inconvenient and expensive, and incurs unnecessary risks.
But we are happy to hear Dr Brenner say that it is increased NAD+ in the bloodstream clearly has the great benefit, and believe that provides further justification for using a sublingual NAD+ tablet or powder to bypass the digestive system and deliver NAD+ direct to the bloodstream in a very convenient manner.