Frequently Asked Questions
What Is NMN?
Nicotinamide Mononucleotide is an intermediate molecule made in the conversion of both nicotinamide and nicotinamide riboside to NAD. It is a type of molecule called a nucleotide, which is very similar to the building blocks of DNA.
NMN is a precursor molecule to NAD+. NMN works synergistically at the cellular level to increase sirtuin and PARP1 activity, optimise mitochondrial function, and restore levels of NAD+.
How much NMN should I take?
Recommended daily dosages of sublingual NMN are at least 400 mg, which equates to 2 scoops of NMN Powder.
The FDA suggests that a 68kg human would require about 560mg per day. Dr David Sinclair has stated he take 1,000mg daily.
How to take NMN?
Humans absorb approximately 20% of nutrients we ingest through digestive system. Sublingual delivery works by avoiding first pass of the digestive system, and NMN and NAD⁺ are absorbed directly into the bloodstream.
Why Sublingual rather than tablet form?
Recent (2018) research has shown NMN and NR are also mostly digested by the stomach and liver.
NMN, NR and NAD+ have low molecular weight and are hydrophilic, meaning they easily interact with water. Thus NMN, NR and NAD+ can be absorbed through the capillaries under the tongue directly into the bloodstream.
The NR molecule is not stable by itself. Therefore, NR manufacturers adds Chloride to make it stable. ALL NR sold is actually Nicotinamide Riboside CHLORIDE A by-product of using Chloride is the taste, making NR unacceptable for sublingual (under the tongue) use.
So NR is only available in capsule form, which much pass through the stomach and liver where it is metabolized to the less effective Nicotinamide (Liu, 2018) .
Sublingual delivery of NAD+ and NMN allows them to bypass the liver and Gastro-Intestinal tract. (Source).
Sublingual delivery of NMN overcomes the bioavailability problem of capsules that get digested in the stomach and greatly improves the effectiveness of NMN.
How to measure NMN powder?
We supply a small, individually wrapped, measuring spoon. Each level scoop holds approximately 250mg of NMN.
To prevent contamination, do not keep the scoop in the bottle. It is best to keep the measuring scoop separate from the product. Wash spoon after each use. Each spoon is individually wrapped and follows pharmaceutical guidelines.
Is NMN Safe?
NMN is found in foods such as broccoli, cabbage, cucumber, edamame and avocado. Studies have shown that NMN is Non-toxic .
NMN is available in vegetables, mushrooms, meat, and shrimp but trying to obtain sufficient through diet alone would be problematic. Studies dosages have been about 50mg – 250mg. The FDA suggests that a 68kg human would require about 560mg per day. The difficulty is that you would have to eat about 45kgs of edamame, 816kgs of broccoli, or similarly impossible amounts of cucumber, cabbage, avocado, tomato, mushrooms, raw beef, or shrimp.
Mice can’t have all the fun, of course, so human studies (conducted in Tokyo’s Keio University School of Medicine and the Washington University School of Medicine) are currently in progress (concluding June 1st, 2020) to determine change in insulin sensitivity, and to determine change in beta-cell function over the course of two years with NMN supplementation.
Researchers also expect to gather results on control of blood sugar, dilation of blood vessels, changes in both blood lipid and body fat levels, and changes in the markers for cardiovascular disease.
As of July 2019, there are the following human studies into NMN:-
- 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 first human trials of NMN commence in Sept 2016 in Japan. Subsequent human studies have been undertaken. Dr David Sinclair complete his phase I study and is now commencing Phase II. If there were safety issue identified in Phase I then Phase II would not go ahead or would be delayed.
Is NMN being tested?
The NMN is tested in a NATA Accredited Australian Laboratory for purity and heavy metals. The product complies with WHO, FDA and EU Standards. The only ingredient in NMN Powder is the NMN molecule itself.
Are there side effects of NMN?
Most human studies are short in duration and have very few participants. For a more accurate idea of its safety, more robust human studies are needed.
Some people have reported mild to moderate side effects, such as nausea, fatigue, headaches, diarrhea, stomach discomfort and indigestion (Source).
It is also clear that high dose supplementation greatly exceeds the body’s requirement for niacin equivalents, and thus will result in substantial elimination through the urine. (Source)
One long-term study in 2016 (1-year) oral administration of NMN (up to 300 mg/kg) is safe and well-tolerated and does not cause any obvious deleterious or toxic effects in normal wild-type mice (Mills et al., 2016). (Source)
From current research there seems no risk is overdosing on NMN or NR.
NR vs NMN?
Comparing NMN and NR at this point in time is more of a moot point at present. The two molecules have not been studied side by side. Yes, there are plenty of studies showing NR and NMN entering cells, circulating around tissues and organs but no study has directly compared the two molecules.
The NAD+ precursor, nicotinamide mononucleotide, NMN, improved cardiac function, while another NAD+ precursor, nicotinamide riboside (NR), improved mitochondrial function in muscle, liver and brown adipose. (Source)
But again, the two have never been matched up against each other in a way that can truly identify one as superior to the other.
NMN appears to enter the cell via a newly discovered transporter
A new study published in Nature Metabolism finally reveals the answer to how NMN enters the cell in order to become NAD+. And that it does not need to convert into NR to do so. The researchers in this new study successfully identify the transporter for NMN, which helps to solve the mystery of how mammals absorb and produce NAD+. (Source)
Prior to this new discovery, it was generally thought that NMN could not enter the cell directly and that it had to convert back into NR in order to do so. This was via a dephosphorylation step taking place on the surface of cells, which converts NMN back into NR prior to entering the cell through equilibrative nucleotide transporters before finally changing back into NMN by being re-phosphorylated by NR kinases.
Nicotinamide mononucleotide (NMN) is a biosynthetic precursor of nicotinamide adenine dinucleotide (NAD+) known to pro-mote cellular NAD+ production and counteract age-associated pathologies associated with a decline in tissue NAD+ levels. How NMN is taken up into cells has not been entirely clear. Here we show that the Slc12a8 gene encodes a specific NMN transporter. We find that Slc12a8 is highly expressed and regulated by NAD+ in the mouse small intestine. Slc12a8 knockdown abrogates the uptake of NMN in vitro and in vivo.
We further show that Slc12a8 specifically transports NMN, but not nicotinamide ribo-side, and that NMN transport depends on the presence of sodium ion. Slc12a8 deficiency significantly decreases NAD+ levels in the jejunum and ileum, which is associated with reduced NMN uptake as traced by doubly labelled isotopic NMN.
Finally, we observe that Slc12a8 expression is upregulated in the aged mouse ileum, which contributes to the maintenance of ileal NAD+levels. Our work identifies a specific NMN transporter and demonstrates that Slc12a8 has a critical role in regulating intestinal NAD+ metabolism.
The new study reveals that a previously characterized membrane protein called Slc12a8 is also an NMN transporter. The Slc12a8 transporter has a variety of unique properties, including requiring sodium, not chloride, to transport NMN. It is also specific to NMN and does not even transport the chemically similar nicotinic acid mononucleotide (NaMN) which is almost the same structurally.
This newly discovered method of NMN transport does not mean that the uptake of NMN via dephosphorylation does not happen or that it is still not important in metabolism. However, it does show that the transport of NAD+ precursors does occur via an alternative and previously unknown mechanism, which builds on our current knowledge of NAD+ biology considerably.
There is also evidence that this mechanism is more prevalent in certain kinds of tissues compared to others, as Slc12a8 expression is around 100-fold times higher in the small intestine of mice than it is in the brain or fat tissue. This suggests that different cells, tissues, and organs may use the various NAD+ precursors in differing amounts and types.
Equally interesting, is that the expression of Slc12a8 actually increases in the gut of aged mice, while NAD+ levels begin to decline. This suggests that this increase of Slc12a8 expression is a compensatory mechanism to try to maintain metabolic homeostasis and resist this aspect of aging.
Remarkably, the function of the Slc12a8 NMN transporter becomes crucial in aged individuals compared with young ones. In response to significant decreases in NAD+ levels, the aged ileum upregulates Slc12a8 expression and tries to maintain its NAD+ levels. When enough NMN is supplied, this feedback system can function adequately to maintain levels of NAD+ comparable to those in young ilea. Therefore, increasing NMN availability or stimulating the function of the NMN transporter could effectively counteract age-associated NAD+ decline in the aged small intestine.
Finally, the authors of this new study speculate that Slc12a8 expression in the gut also facilitates the uptake of NMN, NR, and NAD+ from naturally occurring food sources, including fruits, vegetables, and also milk. However, the amount of NMN required to increase NAD+ in a mouse or human is far beyond the amount found in dietary sources. NMN is found in various foods but at concentrations of less than 1 mg per kg; the dose required to raise NAD+ is hundreds of milligrams.
Our cells can also produce NAD+ through the de novo pathway, which begins with the most basic building block, the amino acid tryptophan (Trp), so it is not clear that dietary NMN can impact NAD+ levels in a significant way or if Slc12a8 expression affects NAD+ levels beyond the liver, where NMN is mostly metabolized..
FAR more increase of NAD+ from NMN
Homeostasis refers to the ability of the body or a cell to seek and maintain a condition of equilibrium or stability within its internal environment when dealing with external changes.
Although NR and NMN are very similar in their effect on NAD+ levels from a single dose, homeostasis appears to impact NR much more quickly than NMN, impacting its ability to maintain increased levels of NAD+.
40-55% NAD+ increase with NR
A single dose of NR has been shown to increase NAD+ by 270%. However, homeostasissoon kicks in and this declines after a few weeks. It was found that increasing the dosage of NR does not provide any further benefit.
Result were an increase of 270% on day 1 and 90% increae on day 30 dropping to only 55% on day 60.
OVER 500% NAD+ increase with NMN ?
The chart at right shows NAD+ increase measured in the liver (and soleus muscle) after 60 days of supplementation with NMN (Sinclair, 2018).
We doubt that other studies will confirm a 500% increase as this study shows, but whatever the true value is, it does seems that the HUGE increase in liver indicates homeostasis is not limiting the NAD+ increase from NMN supplementation in this study.
Does NMN help with Anti-Aging?
Research studies have been published showing benefits of NR and NMN supplementation in various disease and illness, with much overlap in their effects. However, the most dramatic results have been those showing old mice that look and perform the same as young mice.
Below are the three studies that made the biggest splash’s about the potential for reversing aging by restoring NAD+ to youthful levels.
Sinclair 2013 https://www.ncbi.nlm.nih.gov/pubmed/24360282
Mills Long term Study 2016 https://www.ncbi.nlm.nih.gov/pubmed/28068222
Sinclair 2018 https://www.cell.com/cell/pdf/S0092-8674(18)30152-1.pdf
These have ALL been accomplished using NMN.
There have been NO studies with NR showing comparable improvements in strength, endurance, vascularity, and muscle growth, with normal, healthy subjects.
There are successful studies with NR where mice are genetically modified to replicate disease models.
Current belief are that is not a coincidence, but a result of the homeostasis effect with NR that limits its long term effectiveness.
Does NAD+ increase cancers in the body?
There are theories based on research in test tubes that increased NAD⁺ may provide tumors with energy or blood vessels for faster growth.
In reality, there have been no experiments in live animals showing this. In fact, all studies in mice and humans have found no increased incidence, severity, or decreased mortality due to cancer.
In response to this question, Dr. Sinclair states: “Johan Auwerx and I only see health benefits and lifespan extension in mice when we give NR or NMN to old mice. Fasting and exercise raise NAD⁺ and they don’t accelerate aging or cancer.
In a 2017 study demonstrated that targeting the maintenance of healthy mitochondria with increased mitochondrial NAD+levels and SIRT3 activity could be a promising strategy for abolishing the development of tumor-initiating cells as a new therapeutic approach to treating aging-associated tumors. (Source)
What is the pH level of NMN?
NMN need to be slightly acidic, both to maintain stability, and improve sublingual absorption. NMN between 4.0 and 4.5 pH, which is similar to the acidity of tomatoes on the pH scale but less acidic than lemons and oranges.
Prolonged exposure could in theory contribute to loss of enamel, but less so than more acidic foods such as lemons or oranges. The sublingual powder should be placed under the tongue to dissolve. It should not come in contact with the teeth.
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