NMN ⇒ Bioavailability of Nicotinamide Riboside limited by instability in bloodstream

[ALIVEBYNATURE]

Recent research shows that when added to the bloodstream, NR is mostly degraded to Nicotinamide (NAM) and is no longer found after 1 hour.

Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures (Brenner, August 2019)

12 male humans aged 70-80 years old were given 1,000 mg of Nicotinamide Riboside (NR) per day for 3 weeks.

NR supplementation had no effect on levels of NR circulating in the bloodstream.

• NR was found at trace levels in the blood

• NR levels were unchanged after supplementation

Excess NAM is methylated to MeNAM, Me2PY or Me4PY to enable excretion in the urine.

We review this research, along with 3 other new studies that show NMN is more stable and present in blood at much higher levels than NR.

https://alivebynature.com/nr-limited-by ... oodstream/

[jocko6889]

Very important new research! This would seem to be convincing evidence that oral NR has very little benefit. Nice that this was finally confirmed!

[FitandHealthyinAZ]

Right on ABN team! I often believe that doing research up front often leads to good decisions however confirmation is the best process in terms of supporting a decision. In that spirt here is a short video with Dr. David Sinclair discussing the evidence that NMN and not NR will increase endurance and at least as of this moment in time, how NMN is a better molecule when it comes to increasing cellular levels of NAD+. I've been using ABN's NMN product since last March and my recovery from athletic endeavors has improved markedly allowing me to increase my activity in the gym and compete at higher level on the ball field. https://bit.ly/2F7Jd9h

[ALIVEBYNATURE]

Back in 2016 I began wondering why the research coming out consistently showed NMN having more effect than NR. Of course it is hard to compare as they are never tested head to head, but whenever research was done in similar models, NMN was more effective.

They may have very similar effect in vitro, but now that we know NR is so scarce in blood, it makes perfect since that it is less effective in the body.

I do wonder if NR might show better effect in mice than humans. If it takes 1 hour to degrade in both mouse and human blood, wouldn't it be more effective in that 1 hour in a mouse that has much faster metabolism?

[jocko6889]

I do wonder if NR might show better effect in mice than humans. If it takes 1 hour to degrade in both mouse and human blood, wouldn't it be more effective in that 1 hour in a mouse that has much faster metabolism?

It's quite possible. In fact, a new study identifies a shorter version of the NR molecule called NRH which has been shown to be more stable in the blood plasma of mice than NR. This may not translate to humans, however but it is interesting.

"A reduced form of nicotinamide riboside defines a new path for NAD+ biosynthesis and acts as an orally bioavailable NAD+ precursor

Molecular Metabolism - Volume 30, December 2019, Pages 192-202
Judith Giroud-Gerbetant, Magali Joffraud, Maria PilarGiner et al.

Highlights
• A reduced form of nicotinamide riboside (NRH) is a potent NAD+ precursor in cultured cells and mouse tissues.

• NRH leads to NAD+ synthesis through a new, independent path to that of NR.

• NRH is orally bioavailable and not degraded in plasma.

• NRH alleviates cisplatin-induced acute kidney injury.


Finally, we provide evidence that NRH is orally bioavailable in mice and prevents cisplatin-induced acute kidney injury."

https://www.sciencedirect.com/science/a ... 7819309160

[Newage]

I do wonder if NR might show better effect in mice than humans. If it takes 1 hour to degrade in both mouse and human blood, wouldn't it be more effective in that 1 hour in a mouse that has much faster metabolism?

It's quite possible. In fact, a new study identifies a shorter version of the NR molecule called NRH which has been shown to be more stable in the blood plasma of mice than NR. This may not translate to humans, however but it is interesting.

"A reduced form of nicotinamide riboside defines a new path for NAD+ biosynthesis and acts as an orally bioavailable NAD+ precursor

Molecular Metabolism - Volume 30, December 2019, Pages 192-202
Judith Giroud-Gerbetant, Magali Joffraud, Maria PilarGiner et al.

Highlights
• A reduced form of nicotinamide riboside (NRH) is a potent NAD+ precursor in cultured cells and mouse tissues.

• NRH leads to NAD+ synthesis through a new, independent path to that of NR.

• NRH is orally bioavailable and not degraded in plasma.

• NRH alleviates cisplatin-induced acute kidney injury.


Finally, we provide evidence that NRH is orally bioavailable in mice and prevents cisplatin-induced acute kidney injury."

https://www.sciencedirect.com/science/a ... 7819309160

Thanks Jocko.
The big picture gets more interesting by the day as we work our way through the updated information.