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SUBLINGUAL NMN – INCREASED BIOAVAILABILITY

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

It has also long been suspected that most NR is digested to NAM in the Gastro-Intestinal tract intact (r).

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

Sublingual (under the tongue) delivery can provide rapid absorption via the blood vessels under the tongue rather than via the digestive tract. (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 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)

NMN is very hydrophilic, with a molecular weight of 324, making it a perfect fit for sublingual delivery.

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.

7 thoughts on “SUBLINGUAL NMN – INCREASED BIOAVAILABILITY

  1. kumbarillatree says:

    A question.
    I still have 4 bottles of capsules and would hate not to use them. Would they work sublingually if I open them and pour the contents under my tongue?

    • admin says:

      Sure. It’s just a bit inconvenient, and the fillers used in the capsules are a bit slow to dissolve, but that is how we and others discovered that sublingual is so effective.

  2. Wayne Smith says:

    So will this work with your capsules? Would the powder form be more effective? I’ve been taking 5X125mg capsules per day for 3 weeks now. Aches and pains gone. I’m 47 and feel more flexible. Can now touch toes on first try each morning. Stiff neck from old whiplash injury mostly gone. Only negative was a strange taste in the mouth which I assume was niacin but it seems to have gone now or I’ve gotten used to it. My exercise performance is improving. I like doing one armed push ups. Used to regularly do 20. Did 32 on each arm yesterday. Most I’ve ever done is 37 and that was when I was 35 back when I first started doing them. Didn’t exercise for a few years. Got back into it about 5 months ago. Always hated running. Now enjoy it. One thing about getting older that I hate is hairy ears. I run the razor over them. Thickest hairs are on top. I swear they have almost disapeared. My memory has improved and I seem to have more energy. Don’t tire as easy. Can do stair climbing exercise without breaks now. Sometimes eat 4 or 5 times a day but never seem to get fat. Feel great. Will try under the tongue. So glad I visited your site today and read that new article.

    • admin says:

      Great to hear Wayne. I agree that the exercise is synergistic. NMN allows you to exercise a bit more, which builds on the gains, day by day.

  3. admin says:

    Good points. We compare sublingual to IP injection here, because that is what researchers have been using in studies with mice – not IV. So the results from sublingual delivery MAY be as good or better than the research studies using IP injections (which were more effective than in water or supplements)

    You are also correct that many factors influence sublingual effectiveness. But for brevity, and clarity to our readers, we go over what is by far the two most important factors.

  4. admin says:

    Yes, and the University of Colorado study showed NR was NOT FOUND in human blood after oral administration. The Ling Liu thesis findings in this was contrary to all other published research to date.

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