2013 STUDY SHOWS NMN INJECTIONS RESULT IN AGE REVERSAL IN MUSCLES OF MICE
In 2013, Dr David Sinclair published stunning research that showed administration of Nicotinamide Mononucleotide (NMN) not only reversed some aspects of aging, but resulted in the muscles of 2 year old mice being indistinguishable from those of 6 month old mice (r).
Since then there have been dozens of other studies on supplementation with NMN to treat aging (r), and various age related conditions such as obesity (r),brain injury (r),Alzheimers (r,r),neurological impairment (r), and much more.
2018 – OLD MICE GIVEN NMN SUPPLEMENTS HAVE DOUBLE THE ENDURANCE
On March 22 2018, Dr Sinclair published another breakthrough study showing old mice given NMN had nearly double the endurance of mice not given NMN (r).
They fed 400 mg/kg of NMN per day to 20-month-old mice, an age comparable to 70 years in people. After two months, the mice had increased muscular blood flow, enhanced physical performance and endurance and the old mice became as fit and strong as young mice.
For now, Dr Sinclair is so convinced of the safety and effectiveness of NMN for humans that not only has he been taking it himself, so has his 77-year-old father.
The results certainly sound encouraging. Before he started taking a 500mg NMN pill every morning, 47-year-old Professor Sinclair had his blood tested and was told his body had a biological age of 58.
After consuming NMN for three months, he was tested again and his biological age was 32.
As for his father, he’s recently been out-pacing the professor’s younger brother on mountaineering expeditions in their native Australia. According to Dr Sinclair:
‘He’s as vigorous as he was in his 20s and 30s, and he seems to be getting more energetic,’
NAD+ METABOLISM IN HUMANS
In the body, NMN is converted into a related chemical called nicotinamide adenine dinucleotide (NAD), which is found in every cell of living organisms and is essential for life. NAD+ is crucial in fuelling the seven different genes in our body that govern ageing.
NAD DECLINES AS WE AGE
However, our NAD levels decline by about 50 per cent as we age, turning off the body’s defences against ageing and age-related diseases such as cancer, diabetes, heart disease and Alzheimer’s.
NAD+ can be synthesized in humans from several different molecules (precursors), thru the De Novo and Salvage Pathways.
Nampt is the rate-limiting step in the salvage process (r).
BIOAVAILABILITY OF ORAL NMN SUPPLEMENTS – THE PROBLEM
This 2018 doctorate thesis by Ling Liu confirms that most oral supplements of NMN and NR do not make it intact to most tissues throughout the body, but are first digested to NAM or NAD+ in the Gastro-Intestinal tract and Liver.
We also showed that intravenous, but not oral administration of NR or NMN delivered intact molecules to multiple tissues
NAM and NAD+ are beneficial, but elevating NAD+ in the liver is not unique to NMN and NR – many supplements do this.
The real benefit comes from the unique ability of NMN and NR to bypass the NAMPT bottleneck in the salvage pathway and elevate NAD+ in tissues throughout the body – not just the liver.
SUBLINGUAL DELIVERY MORE BIOAVAILABLE THAN ORAL SUPPLEMENTS
As it is such an expensive supplement, it would certainly help if we can get more benefit from less NMN – more “bang for the buck”.
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
NMN is very hydrophilic, with a molecular weight of 324, making it a perfect fit for sublingual delivery.
“sublingual dosage forms not only improve patient compliance, but also reduce the time for onset of therapeutic response, and considerably increase the bioavailability of the drug when compared to conventional orally administered tablets”
INTERPERITONEAL INJECTIONS ARE MORE BIOAVAILALBE THAN ORAL SUPPPLEMENTS, BUT…..
Most of the earlier studies by Dr Sinclair and others used Interperitoneal (IP) injections of NMN, which provides greater bioavailability than oral supplements and made it somewhat simpler to achieve results than from oral supplements.
With intraperitoneal injection, the primary route of absorption is via the mesenteric vessels, which drain into the portal vein and pass through the liver metabolism before reaching the bloodstream.
This means, IP avoids the gastro-intestinal 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.
So even though delivery of NMN by IP is much more bioavailable that oral supplements, IP Injection is still subject to first pass metabolism in the liver.
SUBLINGUAL DELIVERY IS NOT SUBJECT TO GI TRACT OR LIVER FIRST PASS METABOLISM
Smaller molecules are more readily absorbed sublingually. The NMN molecule is small, with a molecular weight of 324, and easily dissolves in water, making NMN a perfect molecule for sublingual delivery.
Sublingual delivery of NMN is NOT subject to first pass metabolism. It can reach systemic circulation intact to reach tissues throughout the body as NMN, not filtered by the Liver.
This is why Sublingual delivery can actually result in greater bioavailability that direct injection ! Some examples are:
- A sublingual formulation of zolmitriptan exhibited a faster rate of absorption and higher drug exposure as compared to subcutaneous injection (r)
- sublingually administered epinephrine results in more rapid absorption and a higher peak plasma concentration compared to injected epinephrine.(r)
- 40mg of sublingually administered piroxicam was found to be as effective as a 75 mg intramuscular injection of diclofenac (r)
ERYTHRITOL AND OTHER SUGAR ALCOHOLS
Alcohol is one substance that can be used to improve absorption in sublingual delivery. (No, that doesn’t mean we suggest taking a glass of wine with NMN).
There are several natural sugar substitutes that are actually “sugar alcohols”. One of the most popular is Erythritol.
Combining Erythritol with NMN which makes it disappear quickly, taste much better, and likely increases absorption substantially.
This makes Erythritol perhaps an ideal catalyst for the sublingual delivery of NMN.
Pure NMN powder has a slightly sour taste that isn’t horrible, but certainly isn’t pleasant.
Many people do not find the taste objectionable, but for those that do, try mixing 2 parts NMN with 1 part Erythritol.
HOW TO TAKE
Put a scoop of powder under the tongue and keep it there until it dissolves (about 10 seconds). Try not to “swish” it around or swallow any.
(Other sugar alcohols such as Xylotil can also provide the same function, but are deadly to dogs so we don’t recommend it)
We believe Sublingual delivery is much more effective, so a smaller dose will provide the same benefit of a much larger dose of oral capsules.
With oral supplements (capsules) 1,000 mg is the most common estimate of the maximum amount that is useful, after which any additional precursor is excreted as NAM in the urine.
What we recommend:
Capsules: 500 – 1000 mg per day
Sublingual: 250 – 2,000 mg per day
We believe 1,000 mg sublingual will be MUCH more effective at reaching tissues throughout the body as opposed to capsules.
However, we don’t believe the same upper limit of 1,000 Mg applies to sublingual NMN, as it is not subject to the GI tract and first pass metabolism in the liver, so doesn’t end up as “expensive urine”
We hear reports from people using higher dosages of 1,500 to 2,000 Mg per day with phenomenal results.
Of course the cost is prohibitive for most people. We just mention it so people are aware of the potential. If you can afford it, we believe you don’t bump into the same ceiling on maximum effective dosage with Sublingual administration.
WHEN TO TAKE
Research studies provide great proof, but we also learn A LOT from chatting with customers.
Many users report increased performance in the gym, but we were surprised to hear that competitive runners and bodybuilders taking very large dosages (1,000 mg or more), before, during or just after training, felt it was much more effective.
We were skeptical ourselves, and didn’t actually try larger dosages until the last 45 days or so, when some of us started taking 375-500 mg SUBLINGUAL, just before exercise.
This is anecdotal evidence, but all reported such a significant effect that we now recommend taking NMN just before and after exercise.
- 50% of your daily dosage immediately before exercise
- 50% of your daily dosage immediately after exercise
- 50% of you daily dosage one hour before exercise
- 50% of your daily dosage immediately after exercise
We recommend taking NMN 5 days a week, with 2 days off.
Ideally, take on days you will exercise, or likely to be more active.
Sublingual delivery of NMN bypasses the digestive system and first pass metabolism of the liver to increase the quantity of NMN that makes it to the bloodstream and reaches tissues throughout the body rather than just the liver.
Sublingual administration can be more Bioavailable than oral supplements and even injections.
If you want to greatly increase the benefits from NMN supplementation at less cost, try our PURE NMN powder for use sublingually.