Why Sublingual: Poor Bioavailability For NAD⁺, NMN, and NR Capsules

This research shows that NMN and NR are metabolized in the liver to NAM, and ONLY NAM is excreted to the rest of the body:

Providing NAD+ or its immediate precursor, NMN, directly to the bloodstream may be much more effective than dropping large quantities of NAM or NR into the liver and trying to force it to produce more NMN and NAD to the bloodstream.

There is research now being conducted to quantify how much NMN and NAD+ are absorbed by sublingual delivery in humans, but none have yet been published.

Only A Small Quantity of NMN Capsules can sometimes bypass the liver

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”

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.

NAD+ CREATION AND USAGE IN HUMANS

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.

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