NRNMN IS BIOAVAILABLE AND STABLE IN BLOOD – NR IS NOT

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ALIVEBYNATURE
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NMN IS BIOAVAILABLE AND STABLE IN BLOOD – NR IS NOT

Post by ALIVEBYNATURE » Fri Jan 31, 2020 11:08 am

JUST POSTED THE FOLLOWING ARTICLE THAT EXPLORES RECENT RESEARCH ON BIOAVAILABILTY AND STABILITY OF NR AND NMN IN THE BLOODSTREAM.

NMN IS BIOAVAILABLE AND STABLE IN BLOOD – NR IS NOT

Wikipedia: bioavailability is the fraction of an administered dose of unchanged drug that reaches the systemic circulation

Since the Rabinowitz study in 2018, we have known that both Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN) are mostly digested in the GI tract and liver, before reaching systemic circulation.

The main difference is, if any NR reaches the bloodstream, it is unstable, and is quickly degraded to NAM (3,4).

NR is never found in the bloodstream at more than trace levels, and is not increased with supplementation.

NMN levels in the blood are increased with supplementation.

NMN IS STABLE IN THE BLOODSTREAM, NR IS NOT

Study #1:

Image

The charts above are from the Nikiforov study which examined the stability of NAD+ and its metabolites in blood plasma. They show the degradation of NR to NAM within one hour, while NMN is stable in blood (3).

According to the authors:

NMN exhibits a relatively high chemical stability but is partly dephosphorylated to NR by the cells.

Surprisingly, NR was also rather efficiently hydrolyzed to NAM.



Study #2:
Image
This chart is derived from the Brenner study published in August 2019. NR is found only at trace levels in the bloodstream, and is not increased after supplementation of 1,000 mg of NR per day for 3 weeks.

NR was found at trace levels in the blood
NR levels were unchanged after supplementation
MeNAM and Me2PY are the primary result of NR supplementation, not NR

Study #3:

Image
The chart at left is from the Bauer study and shows the change in NR, NAM and NMN found in blood plasma after oral gavage of NR at 200 mg/kG (7).

NR was found at trace levels and not increased.

Within minutes, NAM was increased 16x, reaching 40x increase by 100 minutes.

This is a short-term increase in NAM following a single dose of NR, which shows it is degraded to NAM. This increased NAM is temporary, as excess NAM will be methylated and excreted in urine.

According to the authors:

Oral NR dosing increased circulating NAM 40-fold while NMN remained unchanged and NR was detected only at trace levels in the blood.

Orally administered NR that reaches the muscle appears to enter in the form of liberated NAM.

Study #4:

Image
The more recent study by Canto measures the degradation of NR to NAM in blood.

This chart shows NAM levels in blood plasma massively increase two hours after oral gavage of 500 mg/kg of NR.

According to the authors:

NR quickly disappears from the bloodstream, and is almost undetectable 1 h after intraperitoneal administration at 500 mg/kg.

Elegant tracer experiments demonstrated that after oral intake, NR was utilized as such by the liver, while it predominantly reached the peripheral tissues as its degradation product, NAM.




NMN QUICKLY RAISES NMN IN LIVER AND BLOOD


Image

The chart at right is from a 2016 study in which mice were given a single dose of NMN in water.

Measurements of NMN levels in blood plasma show the NMN is quickly absorbed from the gut into blood circulation within 2–3 minutes.









NR SUPPLEMENTATION RESULTS IN EXCESS NAM WHICH IS METHYLATED AND EXCRETED IN URINE

Image


When taken as oral supplements, NR is mostly degraded to NAM.

NAM levels increase initially, but excess NAM is methylated to MeNAM or Me2PY and excreted in the urine.





Image




The chart at right is derived from the Brenner study that shows 1,000 mg of NR per day does not increase NR in the blood.

It does greatly increase NAM. When NAM levels are too high, it is methylated to MeNAM, Me2PY or Me4PY to enable excretion in the urine.

According to the authors:

Oral NR dosing increased circulating NAM 40-fold while NMN remained unchanged and NR was detected only at trace levels in the blood.

This study shows that NR is never available in the blood in appreciable quantity.

The majority is excreted in the urine as methylated NAM.







Conclusion
NMN
NMN IS BIOAVAILABLE AND STABLE IN BLOOD

NMN IS FOUND IN BLOOD AT 10X THE QUANTITY AS NR AND IS READILY AVAILABLE TO TISSUES THROUGHOUT THE BODY
NR
NR IS NOT STABLE IN BLOOD AND DEGRADES WITHIN ONE HOUR
NR IS NOT FOUND IN BLOOD AT MORE THAN TRACE LEVELS AND IS NOT AVAILABLE TO TISSUES OUTSIDE THE LIVER
SUPPLEMENTATION WITH NR DOES NOT INCREASE AVAILABILITY OF NR IN THE BLOODSTREAM
DUE TO LIMITED STABILITY, NR IS DEGRADED TO NAM BEFORE REACHING PERIPHERAL TISSUES







1.Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures (Brenner, 2019)
2. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice(Mills, 2013)
3. Degradation of Extracellular NAD+ Intermediates in Cultures of Human HEK293 Cells (Nikiforov, 2019)
4. NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells (Brenner, 2016)
5. Nicotinamide mononucleotide alters mitochondrial dynamics by SIRT3‐dependent mechanism in male mice(Kristian, 2019)
6. Quantitative Analysis of NAD Synthesis-Breakdown Fluxes(Liu, Rabinowitz, 2018)
7. Loss of NAD homeostasis leads to progressive and reversible degeneration of skeletal muscle (Bauer, 2017).
8. A reduced form of nicotinamide riboside defines a new path for NAD+ biosynthesis and acts as an orally bioavailable NAD+ precursor (Canto, december 2019).


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jocko6889
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Re: NMN IS BIOAVAILABLE AND STABLE IN BLOOD – NR IS NOT

Post by jocko6889 » Fri Jan 31, 2020 5:58 pm

These recent studies are important in showing that NR and NMN are not co-equals in boosting levels of NAD+, as has-been assumed for a long time. While NR breaks down into ordinary nicotinamide in the blood, NMN gets to the tissues mostly intact.

Add to this the recent finding that a protein called Slc12a8 is able to escort NMN directly across the cell membrane in the gut and this should settle any further debate that NMN is by far the most efficient way to raise levels of NAD+.
rhett
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Re: NMN IS BIOAVAILABLE AND STABLE IN BLOOD – NR IS NOT

Post by rhett » Fri Jan 31, 2020 10:28 pm

This is extremely interesting and just makes me more confident in my anecdotal experiences with NR and NMN. Thanks for all the good work!
drkris69
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Re: NMN IS BIOAVAILABLE AND STABLE IN BLOOD – NR IS NOT

Post by drkris69 » Sat Feb 01, 2020 9:04 am

This is great news ABN! Another confirmation that NMN is superior to NR, and we here already know ABN's NMN is by far the best product available for public consumption. Rock on Alive By Nature! :D
Newage
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Re: NMN IS BIOAVAILABLE AND STABLE IN BLOOD – NR IS NOT

Post by Newage » Sat Feb 15, 2020 4:36 pm

jocko6889 wrote:
Fri Jan 31, 2020 5:58 pm
These recent studies are important in showing that NR and NMN are not co-equals in boosting levels of NAD+, as has-been assumed for a long time. While NR breaks down into ordinary nicotinamide in the blood, NMN gets to the tissues mostly intact.

Add to this the recent finding that a protein called Slc12a8 is able to escort NMN directly across the cell membrane in the gut and this should settle any further debate that NMN is by far the most efficient way to raise levels of NAD+.
Thanks jocko and ABN.
A great reference to the benefits of NMN over NR. Gives us some definite direction in the ongoing debate over which is better and possibly enlightening for people still taking NR only...
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