New research shows that a very large percentage of both NMN and NR is metabolized in the stomach and liver to Nicotinamide when taken as oral supplements (r).
Dr Sinclair has demonstrated remarkable benefits from providing NMN in drinking water, but it is an inefficient delivery method and requires huge dosages.
A better delivery method is needed to bypass the Gastro-Intestinal Tract and deliver smaller dosages of NMN directly to the bloodstream.
So we have decided to no longer offer a capsule version of NMN, and have replaced it with this tablet developed for Sublingual (under the tongue) use.
We believe they bypass the GI tract and deliver some portion of the NMN directly to the bloodstream where it is most effective.
THE PROBLEM with CAPSULES – DIGESTED IN STOMACH
More recently, 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.
Future pharmacological and nutraceutical efforts to boost NAD will need to take into account the minimal oral bioavailability of NR and NMN (R)
We also showed that intravenous, but not oral administration of NR or NMN delivered intact molecules to multiple tissues (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)
The most recent studies showing tremendous health benefits with NMN were accomplished by feeding mice very large dosages of NMN in water (r). However the dosage of 300-400 mg per kg of bodyweight used in many of these studies would equate to approximately 2,000 Mg per day for a 70 kg human. A more effective delivery method is needed !
SUBLINGUAL VS CAPSULES
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 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)
NMN PERFECT FOR SUBLINGUAL
Depending on the molecule, Sublingual delivery can substantially improve the speed and bioavailability. Smaller molecules that are hydrophilic such as NMN are well-suited.
a drug which has been formulated for sublingual should ideally have a molecular weight of less than 500 (r)
SHORT WINDOW FOR MAXIMUM AVAILABILITY
The chart at right is from the 2016 Mills study with mice given 300 mg/kg of bodyweight by oral gavage.
It clearly shows NMN is found in blood plasma within minutes, peaking at around 15 minutes. After that, NMN drops rapidly in blood, and appears as increased NAD+ in the liver.
Of course this is in Mice, and humans have a slower response, but we believe it is during the short time period when NMN is available in the bloodstream and can reach tissues throughout the body that the real benefits occur.
FREQUENCY – HOW OFTEN TO TAKE
Nearly all research on mice and humans using NR and NMN is focused on measuring NAD+ and the various metabolites in the Liver as it is the primary supplier of NAD+ throughout the body (r).
If elevating NAD+ in the liver is the goal, 1-2 larger dosages per day seem to be sufficient to achieve the maximum increase in liver NAD+ (r).
OUTSIDE THE LIVER
However, we believe supplying NMN directly to the bloodstream is more effective at increasing NAD+ not just in the Liver, but throughout the body.
Smaller, More Frequent dosages
Based on the short window that exogenous NMN is available in the bloodstream before being filtered out by the Liver, we believe smaller, more frequent dosages are likely more effective than 1-2 larger dosages.
Using this philosophy, many of our customers have been reporting more perceived benefit from more frequent intake, with many taking 6-12 times per day. We recommend taking 4-8 times per day, with at least 1 hour between dosages.
NOT EVERY DAY
We recommend taking 2-3 days off per week, ideally on days when you will be getting the least exercise. If you relax more on the weekend that is a good time to not take NMN.
CONCLUSION – WHAT WE RECOMMEND
Dr Sinclair takes 500 Mg of NMN CAPSULES per day and prescribes the same for his father, which is in line with dosages used in current and recently completed research on humans.
There is likely an upper limit on the effective dosage of NMN and NR capsules, which seems to be between 500 and 1,000 Mg per day.
We believe that sublingual delivery allows a much greater percentage of NMN to bypass the liver and reach other tissues.
When split between multiple smaller dosages, we believe 1,000-1,500 Mg a day can be taken before reaching the limit on maximum effectiveness.
We recommend taking 1 tablet, 4 to 8 times per day. Ideally, 1 upon waking, 1 immediately before and after exercise, and 1 before bed, with any others spread throughout the day.