NR, NMN and NAD+ CAPSULES ARE DIGESTED TO NICOTINAMIDE (NAM)
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
SOME NMN IN CAPSULES CAN BYPASS THE GI TRACT
A study published Jan 2019 shows the newly identified Slc12a8 protein can transport NMN to NAD+ in the small intestine, avoiding digestion to NAM for a small quantity of NMN.
It does not quantify HOW MUCH, and the authors imply it is not a significant amount.
It must also be noted that Slc12a8 transporter is most prominent in the small intestine. This NAD+ does not have a direct pathway to the rest of the body.
This means that Slc12a8 might provide a slight increase in effectiveness of NMN over NR, but is not thought to have a dominant impact on NAD+ levels throughout the body. According to the authors:
It is important to note that the discovery of an NMN transporter by no means diminishes the importance of uptake via dephosphorylation
SUBLINGUAL CAN BE MORE BIOAVAILABLE THAN IP INJECTION !
With intraperitoneal injection, the primary route of absorption is via the mesenteric vessels, which drain into the portal vein and pass through the liver before reaching the bloodstream.
This means, IP avoids the GI tract, but is still sent directly to the Liver, where much of it is converted to NAD+.
Elevated NAD+ in the liver is good, but its far better to reach the bloodstream with intact NMN.
The absorption of the different molecules delivered through the sublingual route can be 3 to 10 times greater than oral route and is only surpassed by direct IV injection (r).
Sublingual delivery is not filtered by the Liver and can reach systemic circulation intact, so can actually result in greater bioavailability that direct injection! Some examples are:
- A sublingual formulation of zol… exhibited a faster rate of absorption and higher drug exposure as compared to subcutaneous injection (r)
- sublingually administered epin… results in more rapid absorption and a higher peak plasma concentration compared to injected epin… .(r)
- 40mg of sublingually administered pir.. was found to be as effective as a 75 mg intramuscular injection of dicl… (r)
NAD+ can be synthesized in humans from several different molecules (precursors), thru the De Novo and Salvage Pathways.
Nampt is the rate-limiting step in the salvage process (97).
As we age, Nampt enzyme activity is lower, resulting in less NAM recycling, less NAD+, more disease and aging (97,101).
SUBLINGUAL BYPASSES THE NAMPT BOTTLENECK
Restoring NAD+ in the Liver does not solve NAD+ deficiency throughout the body.
In the Liver, the CD38 enzyme metabolizes NAD+ to NAM, which is excreted to the rest of the body (r).
Sublingual delivery of NMN or NAD+ directly to the bloodstream bypasses the liver and the Nampt bottleneck that is the root cause of NAD+ deficiency in many tissues.
NAD+ and NMN IDEAL FOR SUBLINGUAL DELIVERY
Low molecular weight, low PH, hydrophilic molecules are able to easily enter the tissues under the tongue and throughout the oral mucosa where they are absorbed by capillaries into the bloodstream to quickly make their way throughout the body.
We have partnered with the leading pharmaceutical sublingual products formulator to create the first NMN and NAD+ sublingual powder, tablets, liquid drops and nasal spray that have the ideal characteristics to ensure efficient and rapid uptake.