Sublingual administration of NAD+ and NMN can be more effective as it enables delivery of the molecule directly to the bloodstream via the blood vessels under the tongue.
We stopped selling NMN capsules in 2017, even though we were the largest seller in the world. We realized sublingual delivery is so much more effective and didn’t feel good to continue selling what we feel is such an inferior product.
We were proven correct when this study was published in Feb 2018 showing that most oral supplements of NR and NMN are digested to the less effective Nicotinamide (NAM).
THE PROBLEM with CAPSULES – DIGESTED TO NAM
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.
At 50Mg/Kg of body weight, NO NR or NMN made it out of the liver intact.
Future pharmacological and nutraceutical efforts to boost NAD will need to take into account the minimal oral bioavailability of NR and NMN (R)
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)
That question is totally irrelevant if a molecule NEVER REACHES THE BLOODSTREAM.
This study used a small dose – 50 Mg/Kg of bodyweight (equivalent to 250 Mg for a 70 kg human), vs the 300-400 Mg/Kg commonly tested in other research. Perhaps higher dosages allow NAD+ precursors to make it past the Liver to other tissues.
It is clear that for Oral Supplements (Capsules), the bioavailability of any NAD+ precursor is very poor outside of the Liver.
SUBLINGUAL DELIVERY BYPASSES THE STOMACH AND LIVER
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 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 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+ METABOLISM IN HUMANS
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 NMN AND 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 (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.