Sublingual (under the tongue) delivery can provide rapid absorption via the blood vessels under the tongue rather than via the digestive tract. (1,2,3)

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 (3).

Research on sublingual delivery of NMN is not yet published, so the increased efficiency is not yet quantified.

This research published in 2018 confirms that most oral supplements of NMN and NR are digested to NAM in the GI tract or the liver.

Unlike in cell culture where NR and NMN are readily incorporated into NAD, oral administration fails to deliver NR or NMN to tissues (R)

Interestingly, we found that neither compound was able to enter the circulation intact in substantial quantities when delivered orally (R)

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.

 

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 zolmitriptan exhibited a faster rate of absorption and higher drug exposure as compared to subcutaneous injection (4)
• sublingually administered epinephrine results in more rapid absorption and a higher peak plasma concentration compared to injected
• epinephrine (4)
• 40mg of sublingually administered piroxicam was found to be as effective as a 75 mg intramuscular injection of diclofenac (4)

NAD+ METABOLISM IN HUMANS

NAD+ can be synthesized in humans from several different molecules (precursors), thru  the De Novo  and Salvage Pathways.

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.

As we age, Nampt enzyme activity is lower, resulting in less NAM recycling, less NAD+, more disease and aging

SUBLINGUAL NAD+ 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 (6).

Sublingual delivery of NMN or NAD+ directly to the bloodstream partially bypasses the liver and the Nampt bottleneck.