Nicotinamide Mononucleotide Additional Information
Nicotinamide Mononucleotide (NMN) is a compound that is derived from ribose and a nicotinamide that is a vitamin B₃ metabolite. NMN is not classified as a vitamin as it has the presence of a phosphate.
In the human body NMN is turned into another compound, nicotinamide adenine dinucleotide. Nicotinamide adenine dinucleotide has two forms that both serve important roles in the body. There is the oxidized form (NAD⁺) which acts to accept electrons from other molecules. Another form, a reduced form (NADH) that acts by donating electrons to other molecules. (1)
As a nootropic, NMN works to combat the effects of aging on the body in various manners. (11)
Nicotinamide Mononucleotide vs. Nicotinamide Riboside
Nicotinamide Riboside (NR) is a nucleoside form of vitamin B₃ and like NMN, acts as a precursor to NAD⁺. Although NR can still be an effective precursor to NAD⁺, various studies have found its benefits to be less effective than that of NMN.
Endurance (3,13)
Separate studies were conducted on older mice that found NMN boosted endurance by 100% vs control mice while NR boosted endurance by 20% vs. control mice.
Heart Disease (14,15)
Separates studies to conduct the heart disease Friedreich’s Ataxia were published in 2017, one with NMN and one with NR. The test with NMN showed a restoration of cardiac function while the NR did not improve cardiac function.
Alzheimer’s Disease (17,18)
It’s believed that Alzheimer’s Disease is caused by flaws in production and other various tasks associated with β-amyloid peptide (Aβ). Separates studies conducted with both NMN and NR demonstrated that NMN was able to decrease the build up of Aβ while NR was not.
Nicotinamide Mononucleotide Benefits
NMN works to increase NAD⁺ in the human body. Increasing NAD⁺ fights off many effects of aging. The benefits of NMN are discussed further in the “Research & Scientific Studies” section. These benefits include but are not limited to:
- Decrease weight gain that generally occurs with aging (4,6)
- Helps to decrease effects of brain injuries (7)
- Aids with psychomotor regressive ailments (8)
- Aids with metabolic dysfunction (6,9)
- Combats Alzheimer’s Disease (18)
- Improves endurance (3)
- Improves vision (4,19)
- Assists with DNA repair (5)
How to Use Nicotinamide Mononucleotide
The discovery of Slc12a8 marked a significant change for NMN. It was previously believed that since NMN contained a phosphate that it would not be able to enter cells. The old thought process was that NMN would have to break down and lose the phosphate, essentially turning into NR, before it could enter cells and get to work. This led to thoughts that the only effective method of ingesting NMN was either via a lozenge or sublingually to more effectively permeate cells. (2)
With the discovery of Slc12a8 it was found that the speed at which NMN can take effect was greater than that of NR. (2) When cells are low of NAD, they express the Slc12a8 transporter gene which allows for a more efficient absorption meaning a capsuled form of NMN is more efficient than the previously thought sublingual form. (2)
In this more effective capsuled form, NMN can be found ranging from 100mg to 250mg.
Dosage Instructions
NMN supplied directly to the bloodstream is more effective at supplying NAD⁺ throughout the body but is also available for a shorter time as it is filtered out by the liver. With this in mind, the thought is that NMN is more effective in a greater number of smaller doses. A 125mg dose 4 to 8 times per day, with no more than once an hour, is the general guideline for dosage recommendations.
The first dosage should be taken immediately upon waking up with the remaining doses spread throughout the day. If you plan on exercising during the day, take one dose immediately before and immediately after the exercise. The target being 1,000 to 1,500 total mgs per day.
If an individual’s goal is to only boost NAD⁺ in the liver, then 1 to 2 larger doses would be sufficient. If taking NMN at either level, it is recommended to take 2 to 3 days off a week and only supplement 4 to 5 days per week.
Half-life and Duration of Effects
Oral supplementation of NMN as a capsule shows increased levels of NMN in the bloodstream in as little as 2.5 minutes. (20) With this supplementation an increase of NAD⁺ was seen in the liver in 10 minutes and in muscle tissues at 30 minutes. (20) NMN levels in the bloodstream peak around 15 minutes with a steady decline following. As mentioned, a dosage every hour is recommended to keep peak NAD⁺ levels.
Nicotinamide Mononucleotide Safety and Side Effects
Although testing on humans with NMN was not been completed or published, it is in progress. As an existing supplement, NMN has shown to be very safe and non-toxic. In rodent testing, NMN has shown to be non-toxic when as much as 2.1 to 17 grams have been taken. Please note, this is represented in Human Equivalent Dosages (HED) meaning the rodent experiments usually saw non-toxic levels up to 300mg per kg per day. (4,6)
How Nicotinamide Mononucleotide Works
The primary function on NMN is to increase the levels of NAD⁺ in the body. As we age there is a major decrease in capillary density and blood flow which leads to various health issues, weight gain, and a decrease in energy levels. This correlates to decreasing NAD⁺ levels as the body cannot replenish the compound quickly enough and it is rapidly consumed. (2)
NAD⁺ is responsible for the production of adenosine triphosphate (ATP) which is the chemical that provides energy to cells. Additionally, sirtuins (a class of proteins that influence cellular processes such as aging and inflammation) require NAD⁺ for their enzymatic activity. (12) Generally, inflammation represents a clear connection to metabolism and aging.
NMN works as it is effectively absorbed to the bloodstream, primarily in the gut, via the small intestine. (2) NMN has shown to have a unique transporter gene, Slc12a8, that allows NMN to enter cells directly allowing for the quick and effective absorption. Slc12a8 is abundantly found in the gut.
NMN Research and Studies
Aging (4,5,10)
NAD⁺ levels decline as we age as they are consumed by sirtuins and other enzymes that operate for repair and immune function. A 12-month long study was conducted where mice were orally given NMN. The mice ranged from 5 months to 17 months in age and were either the control group or administered one of two doses on NMN, 100mg or 300mg. The results saw improved metabolic function, reduced weight gain, improved insulin sensitivity, eye function, bone density, and many other health issues that arise due to aging. The results demonstrate the effects NMN can have on age-associated physiological decline and highlights NMN to have potential for anti-aging intervention in humans.
Helps to Reduce Weight Gain (4,6)
In the 12 month study the percent of body weight in mice administered NMN were normalized and shown to be 4% lower in the mice given 100mg and 9% lower in the mice given 300mg. Food and water administration was closely monitored, and the mice showed no significant difference in body length, only fat mass and lean mass. Additionally, the mice who were given NMN were able to maintain higher levels of food and water consumption showing that the weight normalization was not due to a loss of appetite.
A separate study was conducted with 5-week-old female mice. These mice were split into several groups and were varied based on diet and NMN administration. After 6 weeks of diet, exercise on the treadmill began for all groups. During the last 17 days of exercise is when NMN was distributed to half of each group. The groups who were administered NMN closely resembled the groups who were given exercise. However, in the NMN groups NAD⁺ level rose in both the muscle and liver while in the exercise groups, only in the muscle.
Helps with Brain Injuries (7)
Intracerebral hemorrhage (ICH) is when bleeding occurs in brain tissue and causes a stroke (occurs when the brain is deprived of oxygen and blood supply). NAD⁺ has been shown to protect against brain disorders such as amyotrophic lateral sclerosis (ALS) and ischemic strokes, but it is unknown in how it could play a role with ICH.
In collagenase-induced ICH in mice, NMN was administered to determine how well it could replenish NAD⁺. Although NMN was unable to reduce hematoma volume, brain hemoglobin content, or brain water content, it was able to reduce brain edema, brain cell death, oxidative stress, and neuroinflammation. Prolonged treatment of NMN was also able to promote the recovery of neurological function. This demonstrates that NMN can be used to help with brain injuries resulted by inflammation or oxidative stress.
Psychomotor Regressive Ailments (8)
Leigh Syndrome is a severe neurological disorder where an individual progressively looses mental and movement abilities. This disease progresses very quickly and is usually found in the first year of life with death being the result in year two or three.
Mice were given a model of Leigh Syndrome and were found to have significant decrease in NAD⁺ levels and a NAD⁺ imbalance. Mice who were administered NMN were found to have significantly longer lives then the mice who were not. NMN was shown to up-regulate levels of alpha-ketoglutarate (KG) which is a metabolite for HIF1a degradation. Dysregulation and overexpression of HIF1a has been heavily linked to various diseases.
Metabolic Dysfunction (4,6,9)
Maternal overnutrition and general obesity is a well-known cause of several metabolic diseases in offspring as well as the obese individuals. Exercise is able to improve metabolism by increasing NAD⁺ levels. Offspring mice of obese mothers were split into several groups, some given treadmill exercise and some given NMN injections. NMN was shown to improve glucose tolerance at a rate similar to exercise but had stronger effects on liver fat catabolism and synthesis then exercise. The intervention of NMN was most pronounced in the mice who were born to obese mothers.
This research is supported by a 12-month study where mice who were administered NMN showed higher food intake but lower body weight then mice who were not. Additionally, oxygen consumption and energy expenditure were much improved in mice given doses of NMN. Research also suggested that NMN mice were able to switch their main energy source from glucose to fatty acids as their respiratory quotient significantly decreased.
Alzheimer’s Disease (18)
Β-amyloid peptide (Aβ) is believed to by a leading agent of Alzheimer’s Disease. Flaws in the processes that govern production of Aβ, or accumulation or disposal of Aβ are believed to be the cause of Alzheimer’s. Aβ oligomers have been accepted by the scientific community as a therapeutic agent for individuals with Alzheimer’s.
NAD⁺ decline is correlated to Aβ toxicity in individuals with Alzheimer’s. Administration on NMN, the precursor to NAD⁺, help to reduce Aβ production and build up and to decrease synaptic loss on test performed on mice. These mice also saw substantial improvement in behavioral measures of cognitive impairments.
Improves Vision (4,19)
In the 12-month study a type of mouse with a gene mutation that causes light-colored spots in the eye as age progresses were some of the mice that were tested at 100mg and 300mg level of NMN. Half of the mice who were administered the NMN showed a dramatic reduction in these spots suggesting NMN might be able to suppress age related pathological changes. Furthermore, when being tested with electroretinography (ERG) the mice with NMN showed more promise suggesting that NMN is able to prevent decline in rod cell function with age.
A different study focused on photoreceptor death as it is the endpoint of many blinding diseases. Rod or cone photoreceptor-specific deletion of nicotinamide phosphoribosyltransferase (NAMPT), which is the rate-limiting enzyme in NAD⁺, caused retinal decline. It was also shown that NAD⁺ deficiency in the retinal caused dysfunction. By supplementing with NMN, they were able to increase NAD⁺ in both instances.
DNA Repair (4,5)
The 12-month study of mice also revealed some positive effects on NMN for genes. A microarray analysis was completed on the mice that saw certain genes in metabolic organs, skeletal muscle, and the liver were downregulated. This shows promise that NMN is able to prevent age-associated transcriptional changes.
DNA repair efficiency declines as we age. By supplementing NMN, it restores the abundance of NAD⁺ (also decline with age) which is able to regulate the protein-protein interactions. This modulation can in turn then protect against cancer, radiation, and aging.
NMN Frequently Asked Questions
Do you have to take NMN sublingually?
No, with the discovery of the Slc12a8 transporter gene, NMN can now be orally taken as a capsule and permeate cells.
What foods contain NMN?
Some vegetables such as broccoli, cabbage, cucumbers, and edamame contain NMN, but it isn’t a sufficient amount to replenish how much the body loses.
Is NMN the same as Niacin?
No, Niacin is the B₃ vitamin while NMN is a metabolite of Vitamin B₃.
Is NMN more effective if taken sublingually?
With the discovery of the Slc12a8 transporter gene NMN has now been shown to be more effective if taken as a capsule vs. sublingually. The gene is abundant in the gut and has been shown to allow NMN to hit the blood stream in under 10 minutes.
Have there been human studies with NMN?
Human studies have been completed on NMN in Washington and Japan and are currently pending publication.
Cited Sources
- https://www.prohealth.com/library/combat-aging-help-prevent-chronic-disease-nmn-86299
- https://www.nature.com/articles/s42255-018-0009-4
- https://www.cell.com/cell/pdf/S0092-8674(18)30152-1.pdf
- https://www.cell.com/cell-metabolism/pdfExtended/S1550-4131(16)30495-8
- http://science.sciencemag.org/content/355/6331/1312
- https://www.ncbi.nlm.nih.gov/pubmed/27594836
- https://www.nature.com/articles/s41598-017-00851-z
- https://www.ncbi.nlm.nih.gov/pubmed/30816177
- https://www.ncbi.nlm.nih.gov/pubmed/29118320
- https://www.ncbi.nlm.nih.gov/pubmed/24360282
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515290/
- https://www.ncbi.nlm.nih.gov/pubmed/23325925
- http://science.sciencemag.org/content/sci/early/2016/04/27/science.aaf2693.full.pdf
- https://insight.jci.org/articles/view/93885
- https://www.fasebj.org/doi/abs/10.1096/fasebj.31.1_supplement.602.15
- https://www.ncbi.nlm.nih.gov/pubmed/28330719
- https://www.ncbi.nlm.nih.gov/pubmed/29432159
- https://www.ncbi.nlm.nih.gov/pubmed/28330719
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104206/
- https://medicine.wustl.edu/news/natural-compound-nmn-reduces-signs-aging-healthy-mice/
