– Some Amazing Results with NMN –
“After 6 days of NMN, 22 month old mice had the muscle capacity, endurance and metabolism of 6 month old mice” (2013 Sinclair)
“NMN effectively mitigates age-associated physiological decline in mice ” (2016 Sinclair)
“NAD+ and SIRT1 levels were HIGHER in OLD Mice than in YOUNG Mice that did not receive NMN.” (2017 Hao)
“The old mice became as fit and strong as young mice”(2018 Sinclair)
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)
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
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.
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 NMNAND 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 ofNMN or NAD+ directly to the bloodstream bypasses the liver and the Nampt bottleneck that is the root cause of NAD+ deficiency in many tissues.
NMN shows promise for fighting all age related disease
NMN has been shown in research with mice to be effective at combatting nearly all age related disease such as Parkinson’s, Alzheimers, heart disease diabetes, cancer, and more.
Does NMN work as well in humans as it does in mice?
Researchers are hopeful that the same results will apply to humans, but 2 months in mice is equivalent to several years in humans. The longer lifespan and understandable caution in research with humans means it will be years, if not decades, before it is proven.
One area where it has shown the strongest effect in mice is reversing Sarcopenia (muscle wasting), in older subjects. Dr Sinclair’s most recent research gave NMN to old mice for 2 months and found their strength and endurance nearly doubled (r). Examination of their muscles showed they were indistinguishable from those of young mice. They also grew new blood vessels and vastly increased capillary density.
Improved endurance and muscle growth points to YES
Using our protocol of frequent doses of NMN taken sublingually, we have seen the same restoration of muscle strength and endurance as the mice in Dr Sinclair’s research, in a very short time. My personal experience has been a return to the strength and fitness of my 20’s in just 3 months.
Even more shocking, I have experienced muscle growth that is beyond what I EVER had in my 20’s. I am convinced this delivery method and frequency does more than just restore skeletal muscle to youthful levels – it actually increases muscle beyond the “normal” youthful levels.
Sublingual Delivery is the breakthrough
For human usage, it has been available for purchase as a dietary supplement for a few years now. However, recent studies have shown that oral supplements of NMN such as capsules are digested in the stomach and very little of the NMN makes it’s way to the bloodstream (r). Sublingual delivery of NMN can bypass the digestive system and deliver NMN directly to the bloodstream.
Alivebynature has been the dominant seller of NMN over the last year. From speaking with customers we have discovered that multiple sublingual dosages throughout the day dramatically increases the effectiveness of NMN.
Improved muscle growth is great, but just the tip of the iceberg
We have been stunned at the restoration of youthful muscle and endurance, and realized that can be used to demonstrate the effectiveness of NMN using our delivery method.
WE BELIEVE SUBLINGUAL NMN IS THEMOST IMPORTANT HEALTH DISCOVERY IN DECADES
Not for the muscle growth, and what that can mean for seniors to avoid Sarcopenia, but what the vascular growth will do for combatting all age related disease. Greatly increased muscle growth and sports performance are just the fastest and easiest to demonstrate.
That is why we are sponsoring the contest below, to enlist people that have a long history of verifiable performance in sports, so that their improvements during usage of NMN can be documented.
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.
NMN was able to mitigate most age-associated physiological declines in mice Treatment of old mice with NMN reversed all of these biochemical aspects of aging
Raising NAD+ levels in old mice restores mitochondrial function to that of a young mouse
Restore the mitochondrial homeostasis and key biochemical markers of muscle health in a 22-month-old mouse to levels similar to a 6-month-old mouse
This study showed supplementation with NMN was able to repair the DNA in cells damaged by radiation
The cells of old mice were indistinguishable from young mice after just one week of treatment.
NMN was immediately utilized and converted to NAD+ within 15 min, resulting in significant increases in NAD+ levels over 60 min
Administering NMN, a key NAD+ intermediate, can be an effective intervention to treat the pathophysiology of diet- and age-induced T2D
Surprisingly, just one dose of NMN normalized impaired glucose tolerance
NAD(+) levels were increased significantly both in muscle and liver by NMN
NMN-supplementation can induce similar reversal of the glucose intolerance
NMN intervention is likely to be increased catabolism of fats NMN-supplementation does mimic exercise
NMN treatment reduces brain cell death and oxidative stress These results further support the neuroprotection of NMN/NAD+
We now demonstrate that mitochondrial respiratory function was restored
NMN could restore cognition in AD model rats
NMN Treatment Rescues Cognitive impairments
NMN significantly increased the level of NAD+ in the heart
NMN protected the heart from I/R injury
NMN reduces vascular oxidative stress
NMN treatment normalizes aortic stiffness in old mice
NMN represents a novel strategy for combating arterial aging
NMN can reduce myocardial inflammation NMN thus can cut off the initial inflammatory signal, leading to reduced myocardial inflammation
Remarkably, NMN administered to FXN-KO mice restores cardiac function to near-normal levels.
Restoration of cardiac function and energy metabolism upon NMN supplementation
Remarkable decrease in whole-body EE and cardiac energy wasting
Exogenous NMN prevents photoreceptor degeneration and restores vision
NMN rescues retinal dysfunction in light-induced degeneration
Completed and pending publication
- 2016 Keio University Study – UMIN000021309
- 2017 Keio University Study – UMIN000030609 Phase 2, 8 weeks, 30 subjects
- 2017 Hiroshima University Study – UMIN000025739 24 weeks, 20 subjects, 100 & 200mg
- 2017 University of Washington Study – 8 weeks, 50 subjects
- 2017 Sinclair Metrobio study – Phase 1
- 2018 Sinclair Metrobio study – Phase 2
The Phase 1 study by Dr Sinclair has been completed, and they are ready to go forward with the Phase 2 study, so we can conclude there were positive results, and no negative side effects, else they would have to publish those immediately.
In the University of Washington study, participants are 50 healthy women between 55 and 70 years of age with slightly high blood glucose,BMI and triglyceride levels.
Using a dose of 2 capsules of 125mg NMN per day over a period of 8 weeks, researchers are testing for:
- change in beta-cell function
- works to control blood sugar
- blood vessels dilate
- effects of NMN on blood lipids
- effects of NMN on body fat
- markers of cardiovascular and metabolic health
The active supplementation portion of this study has ended, but testing of metabolic parameters will continue for 2 years after supplementation has ended. So researchers know the immediate effects and preliminary results are expected to be announced in 2018, with final results expected in 2020.
WHAT IS NAD+
Scientists have now confirmed a direct link between falling NAD+ levels and aging in both animal and in human subjects.
Read more about NAD+
NAD+ DECLINES WITH AGE
Read more about NAD+
- Whats the difference in ingredients between powder and tablets
- Why 4-8 tablets instead of 2-4 like you used to recommend?
- What happens if I stop taking a NAD+ booster?
Thanks for your interest. We feel the powder is a bit more effective as it absorbed instantly, with none spreading out to other parts of the mouth and being swallowed.
The tablets are more convenient to carry around and take throughout the day.
We believe many doses throughout the day are key to achieving the best/fastest results, so the convenience of the tablets is important for some people.
If you will only take it a few times a day while at home, the convenience isn’t as important and the jars of powder are better.
Actually, for most people the best answer is both. Powder in the morning, before bed, and whenever at home. Carrying the tablets for whenever you will be away from home for several hours.
Sublingual tablets bypass the digestive system so more NMN can be absorbed optimally and deliver a lot more NMN directly to the bloodstream and on to other cells and tissues throughout the body. This delivery method is also more advantageous regarding your investment.
NMN is an expensive product and cost will often be a factor in how much a user chooses to take. There is no required minimum dosage.
2 sublingual tablets a day will provide more benefit than from 2 Capsules that are swallowed and digested in the GI tract, and is a good choice for cost effectiveness.
We recommend what we feel is the maximum useful dosage so people can experience the maximum benefit – not a minimal dosage to make the product seem more affordable.
We previously recommended a lower dosage as we weren’t sure how higher dosages were utilized by the body and did not want to encourage users to incur more expense than necessary for maximum effect.
Now, more experience with sublingual usage has shown that smaller, more frequent dosages are more effective.
Users find 4 dosages are noticeably better than the 2 times a day we previously recommended.
Most users also find even more benefit from 8 times a day.
So we encourage customers to try 4-8 dosages a day, but twice a day is a reasonable choice for cost effectiveness.
As we age, we have increasing damage to our cells. Our bodies constantly repair the damage, but it is a constant battle. One analogy I use is that NAD+ are like the workers that repair roads and structures in a city.
When we are young, we have plenty of NAD+, and the city is new, so there is no problem keeping up with the repairs.
As we age, the roads and buildings deteriorate, and the limited number of workers (NAD+), fall behind in maintenance. Lower priority problems get skipped. More and more problems (disease) develop.
You don’t get old in a day, week, or month. Having insufficient NAD+ levels over years leads to slow deterioration.
Restoring NAD+ levels is like hiring more workers for your city. The most critical needs are addressed first. After that, lower priority tasks get done.
Any repairs your body can make due to having more NAD+ do not disappear overnight, just as you don’t age in one day.
You will probably find the increased energy levels you have from taking a NAD+ booster fade away over some days or weeks. Other benefits will take longer to disappear.