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SUBLINGUAL NMN and NAD+ – INCREASED BIOAVAILABILITY

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)

There is a lot of research and debate about which molecules most easily enter different types of cells.

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

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

The salvage pathway sustains 85% or more of our NAD+ (14), with approximately 3g of NAM metabolized to NMN and then to NAD 2-4 times per day (14).

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.

20 thoughts on “SUBLINGUAL NMN and NAD+ – INCREASED BIOAVAILABILITY

  1. Bill Lanphar says:

    NMN Wow been taking it a month now I’m 67 I have been taking a few other life extension products and do Yoga and martial arts every day . But I have to say this product has helped me cross a threshold that’s very noticeable . I can do 25% more reps weight training and I have been stuck in one place for 3 years . So that’s amazing My mental attitude is what it was like in my 40 when I owned a business had many employees I’m so charged up I am starting a new Business . I realize its time get creative again.. Thanks so Much This stuff rocks

  2. Bill Lanphar says:

    Been taking NMN for about a month 2 times a day under tongue I’m 67 I now am doing 25% more reps on some exercises than possible before I started and have an energetic Mindset I remember in my 40s . I do C 60 also and Ormus this NMN has expanded the rejuvenation of my body very Noticeably . I do yoga and martial arts so I am very in tune with my Body.. I can sense the difference NMN has made very easily

  3. Giles Hammond says:

    What is the best way to take NR sublingually? I have TRU Niagen pills. not easy to spilt the capsules and put the powder under the tonge. Any suggestions?

  4. Shane Kelvin Berthelot says:

    I take NR Sublingual 250mg / day and I can feel it as it takes effect
    usually 5 to 10 minutes after I take it. So I don’t know if NR is in
    the blood but something is and it feels great!

  5. Van says:

    Is there any reason that N+R used subliminally cannot be as effective as NMN? Mix once a week and refrigerate. No chlorine needed. Taste is no problem.

  6. Ali says:

    I would stick with Dr. Sinclair intake method and that is oral, i have been taking NMN 500-750 mg daily and noticed significant increase in energy levels, improved memory and better sleep at night, long term benefits should show after some time, i would want to stick to Dr. Sinclair way rather than following a PHD student dissertation , dont forget that all the experiments that showed positive results on mice used the oral method, which is in direct contradiction with Ling Liu findings.

    • admin says:

      Don’t forget, all the experiments that shows positive results on mice used NMN in the drinking water. Mice lap up water with their tongue, and some NMN is absorbed directly by the tongue and oral mucosa. We don’t know how much, but the delivery method is not the same as a human swallowing a capsule.

  7. John says:

    This is not a paid comment. I received NMN sublingual a few weeks ago and started it just 2x
    day. I am 54 and not an athlete by any measure. In the past 3 days i have noticed a night and day difference in muscle strength. Amhugmincrease. I have changed nothing except adding NMN in addition my focus (memory) is undoubtedly better. I am not sure if this is long term but it is quite impressive. Not sure I need 6x a day so will stick with 2x

  8. Allan Silliphant says:

    I have been taking anti-ageing sups for over 4 years. During that period I have lost & maintained a weight loss of about 43 lbs. I’m 77, & was diagnosed with T2diabetes nearly
    20 years ago. Over that time I have been a Vet Admin. patient as my primary medical care.
    My VA enrollment provides me full panel blood testing. After being legally disabled for
    18 years, I am now able to rejoin the workforce. I have been licensed as California State
    Registered Security Guard, & will pick up my uniforms & badge, & begin patrolling an industrial multi business large complex covering nearly a mile long during several nights a
    week in a patrol vehicle, working alone. To get into the best possible shape for this job I
    sarted on sub-lingual NMN, along with pterostilbene, as well as slow release metformin,
    & sublingual use of liquid Qnol (co- enzymime Q-10) which I swallow after holding under my
    tongue for at least 12 minutes. I have been working out with a 10 lb. arm weight. Where I did
    500 a day over the last year, I am able to do1000 reps, easily. The wrinkles in the skin on the
    bottom of my forearms is almost free of the wrinkle pattern that you could see a week ago. I
    have no doubts that this stuff works. I’ve lost 5 lbs in 5 days by being more active, I’m now
    back to 186 lbs. 6′ 1+” with a 34 inch waist in my patrol uniform. I hope to work until my
    early eighties, based on the way I now feel. Yes….try this NMN, I’m profoundly glad I tried it
    in time to pass muster as a working, highly mobile security officer.

    • admin says:

      Because we just stumbled upon this discovery in the last few months from talking with customers and experimenting with family and friends.

      Dr. Sinclair now says he takes 750 mg per day.

      • Kris says:

        As of January 2019 Dr. Sinclair stated on the Joe Rogan podcast that he takes 1 gram (1000mg) of NMN per day. Along with 500mg resveratrol.

        • JoeT says:

          I listened to the same Joe Rogan podcast and took careful notes and agree with Kris … Dr. Sinclair takes 1 gram of NMN every morning along with 500 mg of resveratrol. To help absorption he mixes the resv powder in yogurt.

          • JoeT says:

            Dr, Sinclair also also stated in the very recent podcast that the two (NMN and resveratrol) work extremely well together — one serves as the gas and the other as the accelerator pedal. I just received my NMN dissolvable tables yesterday, but I’m going to wait until I recv my resveratrol powder in the mail so I can take both together …

          • Beth says:

            Joe Rogan podcast, Dr. Sinclair stated 1gram NMN powder and 500mg of resveratrol powder mixed in a small amount of yogurt. Where do you buy resveratrol powder?

  9. 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.

  10. 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.

  11. 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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