POOR BIOAVAILABILITY FOR NAD+, NMN, AND NR CAPSULES

All NAD+ supplements can restore NAD+ in the Liver but this does not solve NAD+ deficiency throughout the body.

This research shows that ALL NAD+, NMN and NR are metabolized by CD38 in the liver to NAM, and ONLY NAM is excreted to the rest of the body

“orally delivered NR and NMN are converted into NAM before reaching the systemic circulation“

“we found that neither compound was able to enter the circulation intact in substantial quantities when delivered orally“

“IV administration of either compound results in its detection within the circulation, proving that the route of delivery has a profound effect on the ability of these precursors to reach target tissues”

* the above are direct quotes from the research

Quantitative Analysis of NAD Synthesis-Breakdown Fluxes (Liu, 2018)

Providing NAD+ or its immediate precursor, NMN, directly to the bloodstream is 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.

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 is not 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”

SUBLINGUAL CAN BE MORE BIOAVAILABLE THAN 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 (under the tongue) delivery can provide rapid absorption via the blood vessels under the tongue rather than via the digestive tract. (r,r,r)

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+ 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.

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7 thoughts on “SUBLINGUAL NMN and NAD+

  1. mark says:

    How long (without swallowing) should the sublingual be kept under the tongue? As it liquefies, not swallowing becomes difficult…

    • Evelyn says:

      I think most of it gets absorbed into the tissue under the tongue. The rest of the liquid is mainly your saliva,which of course you should swallow when it gets to much to hold in!

    • chuck says:

      I dont know, but it seems to me that as long as you can taste the slight acidic, it probably hasnt yet been absorbed fully.

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