Research shows NMN and NR are metabolized in the liver to NAM, and only NAM is delivered to the rest of the body. 1, 2
Providing NAD+ or its immediate precursor, NMN, directly to the bloodstream may be much more effective than overloading the liver with large quantities of NR and NAM.
There is research now being conducted to quantify how much NMN and NAD+ are absorbed by sublingual delivery in humans and will be published soon.
We believe sublingual delivery of NMN is a much more efficient delivery method, so in 2017 we stopped selling capsules and 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 (click for more)
It has long been noticed that a small quantity of NMN can reach the bloodstream in minutes. The answer on how this happens was revealed in a study published Jan 2019 that shows the newly identified Slc12a8 protein can transport NMN to NAD+ in the small intestine, avoiding digestion to NAM.
It does not seem to be a significant amount
The study does not publish results showing HOW MUCH NMN the Slc12a8 enzyme can transport, but all previous studies such as the Liu research could not find evidence of any NAD+ at all that was created through this pathway.
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
It must also be noted that Slc12a8 transporter is most prominent in the small intestine, but does not have a pathway to the rest of the body.
There is hope Slc12a8 can be useful in future products
Future products may soon hit the market that target this pathway to help solve the bioavailability problem of NMN capsules. According to the study:
“Dr Imai’s lab already has identified small molecules that can stimulate production of the Slc12a8 NMN transporter, applied for patents, and licensed this technology to a company in Japan”
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.
NAD+ can be synthesized in humans from several different molecules (precursors), thru the De Novo and Salvage Pathways.
In the salvage pathway, Nicotinamide (NAM) and Nicotinamide Riboside (NR) are first converted to NMN, which is then further converted to NAD+ (14).
NMN is more correctly referred to as a NAD+ intermediate because NMN is the last step before conversion to NAD+
The salvage pathway sustains 85% or more of our NAD+ (14), with approximately 3g of NAM metabolized to NMN and then to NAD 2-4 times per day (14).
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).
The NAD+ molecule itself is too large to make it through the digestive system intact when taken as capsules, which is why NR and NMN have been used as supplements to increase NAD+ levels in the body.
Sublingual delivery of NAD+ supplements may bypass digestion in the stomach to provide a direct route for increased NAD+ in the bloodstream.