Why SLC NMN
Research has increasingly shown that NAD+ and it’s precursors are almost entirely digested in the gastrointestinal tract. So, in 2017 we quit selling capsules to focus on powders and tablets designed for sublingual use, even though we were the biggest seller of NMN capsules on Amazon and through our website.
Then, two research studies were published in 2019 and 2020. The first showed the SLC12a8 enzyme prevalent in the small intestine can transport some NMN directly into cells as NAD+. The second shows that bacteria in the stomach actually consume nearly all NMN BEFORE it reaches the small intestine.
So we designed our SLC NMN with an Acid Resistant capsule that dissolves only when reaching the high pH (base) environment of the small intestine. The NMN can then utilize the SLC12a8 transporter in far greater quantity, along with other ingredients added to maximize uptake by the SLC12a8 enzyme.
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.
Even more striking, this 2020 study found most NMN never makes it to the liver, but is almost completely digested by bacteria in the stomach.
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. Sublingual delivery 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.”
Doubts about SLC12a8
There are a some Nicotinamide Riboside (NR) believers such as Chromadex’s chief science advisor, Dr. Brenner, who refuse to accept the research on the 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, which has not yet been published. 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 – 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, 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.