Why SLC NMN – Bioavailability Problem with Standard Capsules
The 2018 Liu/Rabinowitz study found that very little, if any, NMN or NR make it past the liver into the bloodstream.
The yellow and red bars show NMN and NAD+ in the gastrointestinal tract are many times higher in mice given antibiotics (ABX) or NMN + Antibiotics (NMN + ABX).
This explains why regular NMN capsules perform so poorly compared to sublingual delivery of NMN, that can bypass the stomach and liver to deliver NMN directly to the bloodstream.
The NMN Transporter – SLC12a8
This 2019 study found some NMN (but not NR) can be transported directly through the cell membrane and converted to NAD+ by the newly discovered SLC12a8 enzyme inside the small intestine.
Does the SLC12a8 Transporter mean all NMN capsules are as effective as Sublingual?
No. The quantity that is absorbed utilizing the Slc12a8 enzyme is not thought to be the the majority.
“It is important to note that the discovery of an NMN transporter by no means diminishes the importance of uptake via dephosphorylation.”
There is hope the Slc12a8 Transporter can be useful.
“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.”
There are a some die-hard Nicotinamide Riboside (NR) belivers such as Chromadex chief science advisor, Dr. Brenner, who refuse to accept the reseach on Slc12a8 NMN Transporter, but most accept the science.
However, there is huge variation between individuals and testing to quantify how much NMN is actually transported by SLC12a8 has not yet been published. There is much indirect evidence and researchers generally believe it is less than 10% with standard delivery methods.
The Solution – Stop Digestion of NMN by Bacteria in Stomach and Maximize Uptake by SLC12a8 Transporter in Small Intestine
To maximize uptake by the SLC12a8 enzyme, it is necessary to protect NMN from bacteria in the stomach.
Delayed Release™ Capsules
Reaching the small intestines intact is critical to maximize uptake. Our Delayed Release™ capsules have been engineered to make it through the harsh, acidic environment of the stomach without being degraded. They release their payload only when they reach the alkaline environment of the small intestine. This protects NMN from bacteria in the stomach, greatly increasing the quantity that is available for uptake by SLC12a8 enzymes in the small intestine.
Increasing uptake by SLC12a8 NMN transporter
Researchers like Dr. Sinclair are exploring methods to increase uptake by SLC12a8. Sodium is thought to be required, and making it more available may be key.
Sodium for increased uptake
Dr. Huzienga is a very well-known celebrity doctor who has conducted recent trials treating COVID-19 patients with an NMN cocktail—achieving a 100% success rate so far. (See here and here.) On advice from Dr. Sinclair, he uses Sodium Chloride to increase the uptake of NMN by SLC12a8. He also includes TMG to increase methylation and zinc to increase immunity.
Sodium Bicarbonate instead of Sodium Chloride
While Dr. Huzienga has been using Sodium Chloride (table salt) in his NMN cocktail for treating COVID-19, our team has found Sodium Bicarbonate to be a better alternative for long term usage, as many people are trying to limit their salt intake.
SLC Capsules, Sublingual, Liposomal, Intranasal, or Transdermal?
People often ask us what the “best” delivery method is.
If we thought one was capable of restoring NAD+ in all tissues throughout the body, we wouldn’t bother with multiple methods.
Publication of clinical trials at University NSW to measure the NAD+ increase in blood and tissues from several of our products are delayed by COVID-19, but preliminary results are quite positive.
Regardless of how efficient one delivery method is, we do not think it makes sense to try and overload large dosages of NAD+ precursors through a single limited pathway.
It is like trying to fill Lake Tahoe by pouring water down one of the 33 creeks that feed into it. Rainfall over the entire surface and flowing down all the tributaries is a much better solution.
Sublingual is the fastest and most direct to the bloodstream. The majority of users notice increased energy within minutes, but it is filtered out by the liver within 20-30 minutes.
Liposomal delivers some NMN to the bloodstream quickly, with more being protected through the digestive system before reaching the blood. It may take 2-4 hours before liposomes disintegrate and release the NMN, so it is a more “slow release” method, but seems to have the highest overall efficiency.
Transdermal delivery with our Renue™ face and body serums are less efficient at reaching systemic circulation, with much of the NAD+ and precursors being utilized in the skin. However, many users report some difficulty sleeping after applying too much late at night, which seems to be from a significant amount reaching systemic circulation.
Intranasal likely provides the fastest delivery and highest percentage of active ingredients to the brain and bloodstream.
SLC™ Capsules Although SLC12a8 pathway likely does not provide as much active ingredient as other methods, the benefit comes from its ability to utilize a unique pathway, with some NMN being escorted directly into the cell by the Slc12a8 enzyme in the small intestine and the remainder going through the liver
Providing NAD+ and precursors through multiple pathways is best to avoid bottlenecks and feedback loops.
You do not have to take all of them every day.
Alternating several NAD+ precursors is better than pouring money into a single overflowing creek every day.