Low NAD+ Leads to Disease and Aging
WHAT IS NAD+
is a key co-enzyme that the mitochondria in every cell of our bodies depend on to fuel all basic functions. (3
)NAD+ play a key role in communicating between our cells nucleus and the Mitochondria that power all activity in our cells (5
)Scientists have now confirmed a direct link between falling NAD+ levels and aging in both animal and in human subjects.
NAD+ DECLINES WITH AGE
As we age, our bodies produce less NAD+ and the communication between the Mitochondria and cell nucleus is impaired. (5
).Over time, decreasing NAD+ impairs the cell's ability to make energy, which leads to aging and disease (8
) and perhaps even the key factor in why we age
Restoring NAD+ levels with Supplements
There is no arguing that boosting NAD+ levels brings an array of health benefits like better focus and memory, better sleep, more energy, and a faster metabolism.
Restoring NAD+ levels has been shown in research with mice to be effective at combatting many age related disease such as Parkinson’s, Alzheimers, heart disease diabetes, cancer, and more.
This research published March 2018 gave NMN to old mice for 2 months and found their strength and endurance nearly doubled (r).
Examination of their muscles showed they were indistinguishable from those of young mice. They also grew new blood vessels and vastly increased capillary density.
Does it work as well in humans as in mice?
Dozens of clinical trials are going on now, but it takes years to get approval, conduct and publish research. The first studies with humans demonstrated that the precursors NR and NMN could safely elevate NAD+ levels, but we are waiting for publication of research showing treatment of specific disease.
Metro International Biotech (co-founded by Dr Sinclair) has completed multiple phase 1 studies in humans with their MIB626 (a patented derivative of NMN) but have been keeping the results quiet and are holding off publication for a while longer.
It appears they were successful as they are ready to begin phase 2 testing and file for an IND to treat Freidrichs Ataxia and Mitochondria Myopathy in Mid 2019
Metro International Biotech has conducted multiple IRB-approved human safety and bioavailability trials at a prominent Boston hospital, which demonstrated MIB-626 is well tolerated in healthy human volunteer subjects and raises blood levels of NAD+ and related metabolites.
It has long been known that NAD+ is completely digested in the stomach, so has not been used in oral supplements.
Instead, NAD+ precursors such as Niagen and NMN have been used in research to boost NAD+ and have been available for purchase as a dietary supplement for a few years now.
In February 2018, this thesis by Ling Liu showed that oral supplements of NR and NMN are digested in the stomach and liver, with very little reaching the bloodstream (r).
the main circulating product of the administered NR or NMN was NAM
orally delivered NR and NMN are converted into NAM before reaching the systemic circulation
There is some conflicting research in this January 2019 study that found a dedicated transporter can convert NMN from the small intestine directly to NAD+.
This pathway is upregulated in older animals to compensate for decreased NAD+ levels.
The Slc12a8 pathway is specific for NMN – NR cannot utilize this shortcut to NAD.
the Slc12a8 NMN transporter becomes crucial in aged individuals compared with young ones. In response to significant decreases in NAD+ levels, the aged ileum upregulates Slc12a8 expression and tries to maintain its NAD+ levels
The Slc12a8 shortcut likely explains why research has found NMN can make its way to bloodstream and tissues throughout the body in minutes – far faster than NR.
But it is not yet known how prevalent this transporter is and how much NMN it can process – only that SOME oral supplements of NMN can avoid digestion.
(The Liu thesis research use younger animals, which may explain why they didn’t find any NMN escaped the liver to the bloodstream – Slc12a8 is not “turned on” in healthy, younger animals)
- NAD+ – totally digested in stomach and small intestine
- NR – digested in GI tract and metabolized to NAM in liver
- NMN – mostly digested in GI tract and metabolized to NAM in liver, although some can utilize the Slc12a8 shortcut
Sublingual delivery solves bioavailability issues
Sublingual delivery can bypass the digestive system and deliver NAD+ NR, or NMN directly to the bloodstream.
Improved endurance and muscle growth noted
Using our protocol of frequent doses of NMN taken sublingually, we have seen the same restoration of muscle strength and endurance as the mice in this research, in a very short time. My personal experience has been a return to the strength and fitness of my 20’s in just 3 months.
Alivebynature has been the dominant seller of NMN over the last year. From speaking with customers we have discovered that multiple sublingual dosages throughout the day dramatically increases the effectiveness.